Substituted polycyclic aryl and heteroaryl tertiary-heteroalkylamines useful for inhibiting cholesteryl ester transfer protein activity

[0001] This invention is in the field of treating cardiovascular disease, and specifically relates to compounds, compositions and methods for treating atherosclerosis and other coronary artery disease. More particularly, the invention relates to substituted polycyclic aryl and heteroaryl tertiary-heteroalkylamine compounds that inhibit cholesteryl ester transfer protein (CETP), also known as plasma lipid transfer protein-I.

[0002] Numerous studies have demonstrated that a low plasma concentration of high density lipoprotein (HDL) cholesterol is a powerful risk factor for the development of atherosclerosis (Barter and Rye, Atherosclerosis, 121, 1-12 (1996)). HDL is one of the major classes of lipoproteins that function in the transport of lipids through the blood. The major lipids found associated with HDL include cholesterol, cholesteryl ester, triglycerides, phospholipids and fatty acids. The other classes of lipoproteins found in the blood are low density lipoprotein (LDL) and very low density lipoprotein (VLDL). Since low levels of HDL cholesterol increase the risk of atherosclerosis, methods for elevating plasma HDL cholesterol would be therapeutically beneficial for the treatment of atherosclerosis and other diseases associated with accumulation of lipid in the blood vessels. These diseases include, but are not limited to, coronary heart disease, peripheral vascular disease, and stroke.

[0003] Atherosclerosis underlies most coronary artery disease (CAD), a major cause of morbidity and mortality in modern society. High LDL cholesterol (above 180 mg/dl) and low HDL cholesterol (below 35 mg/dl) have been shown to be important contributors to the development of atherosclerosis. Other diseases, such as peripheral vascular disease, stroke, and hypercholesterolaemia are negatively affected by adverse HDL/LDL ratios. Inhibition of CETP by the subject compounds is shown to effectively modify plasma HDL/LDL ratios, and to check the progress and/or formation of these diseases.

[0004] CETP is a plasma protein that facilitates the movement of cholesteryl esters and triglycerides between the various lipoproteins in the blood (Tall, J. Lipid Res., 34, 1255-74 (1993)). The movement of cholesteryl ester from HDL to LDL by CETP has the effect of lowering HDL cholesterol. It therefore follows that inhibition of CETP should lead to elevation of plasma HDL cholesterol and lowering of plasma LDL cholesterol, thereby providing a therapeutically beneficial plasma lipid profile (McCarthy, Medicinal Res. Revs., 13, 139-59 (1993); Sitori, Pharmac. Ther., 67,443-47 (1995)). This exact phenomenon was first demonstrated by Swenson et al., (J. Biol. Chem., 264, 14318 (1989)) with the use of a monoclonal antibody that specifically inhibited CETP. In rabbits, the antibody caused an elevation of the plasma HDL cholesterol and a decrease in LDL cholesterol. Son et al. (Biochim. Biophys. Acta 795, 743-480 (1984)), Morton et al. (J. Lipid Res. 35, 836-847 (1994)) and Tollefson et al. (Am. J. Physiol., 255, (Endocrinol. Metab. 18, E894-E902 (1988))) describe proteins from human plasma that inhibit CETP. U.S. Pat. No. 5,519,001, issued to Kushwaha et al., describes a 36 amino acid peptide derived from baboon apo C-1 that inhibits CETP activity. Cho et al. (Biochim. Biophys. Acta 1391, 133-144 (1998)) describe a peptide from hog plasma that inhibits human CETP. Bonin et al. (J. Peptide Res., 51, 216-225 (1998)) disclose a decapeptide inhibitor of CETP. A depsipeptide fungal metabolite is disclosed as a CETP inhibitor by Hedge et al. in Bioorg. Med. Chem. Lett., 8, 1277-80 (1998).

[0005] There have been several reports of non-peptidic compounds that act as CETP inhibitors. Barrett et al. (J. Am. Chem. Soc., 188, 7863-63 (1996)) and Kuo et al. (J. Am. Chem. Soc., 117, 10629-34 (1995)) describe cyclopropane-containing CETP inhibitors. Pietzonka et al. (Bioorg. Med. Chem. Lett, 6, 1951-54 (1996)) describe phosphonate-containing analogs of cholesteryl ester as CETP inhibitors. Coval et al. (Bioorg. Med. Chem. Lett., 5, 605-610 (1995)) describe Wiedendiol-A and -B, and related sesquiterpene compounds as CETP inhibitors. Japanese Patent Application No. 10287662-A describes polycyclic, non-amine containing, polyhydroxylic natural compounds possessing CETP inhibition properties. Lee et al. (J. Antibiotics, 49, 693-96 (1996)) describe CETP inhibitors derived from an insect fungus. Busch et al. (Lipids, 25, 216-220, (1990)) describe cholesteryl acetyl bromide as a CETP inhibitor. Morton and Zilversmit (J. Lipid Res., 35, 836-47 (1982)) describe that p-chloromercuriphenyl sulfonate, p-hydroxymercuribenzoate and ethyl mercurithiosalicylate inhibit CETP. Connolly et al. (Biochem. Biophys. Res. Comm. 223, 42-47 (1996)) describe other cysteine modification reagents as CETP inhibitors. Xia et al. describe 1,3,5-triazines as CETP inhibitors (Bioorg. Med. Chem. Lett., 6, 919-22 (1996)). Bisgaier et al. (Lipids, 29, 811-8 (1994)) describe 4-phenyl-5-tridecyl-4H-1,2,4-triazole-thiol as a CETP inhibitor. Oomura et al. disclose non-peptidic tetracyclic and hexacyclic phenols as CETP inhibitors in Japanese Patent Application No. 10287662. In WO Patent Application No. 09914204, Sikorski describes 1,2,4-triazolylthiols useful as chlolesteryl ester transfer protein inhibitors.

[0006] Some substituted heteroalkylamine compounds are known. In European Patent Application No. 796846, Schmidt et al. describe 2-aryl-substituted pyridines as cholesteryl ester transfer protein inhibitors useful as cardiovascular agents. One substitutent at C3 of the pyridine ring can be an hydroxyalkyl group. In European Patent Application No. 801060, Dow and Wright describe heterocyclic derivatives substituted with an aldehyde addition product of an alkylamine to afford 1-hydroxy-1-amines. These are reported to be 3-adrenergic receptor agonists useful for treating diabetes and other disorders. In Great Britain Patent Application No. 2305665, Fisher et al. disclose 3-agonist secondary amino alcohol substituted pyridine derivatives useful for treating several disorders including cholesterol levels and artherosclerotic diseases. In European Patent Application No. 818448, Schmidt et al. describe tetrahydroquinoline derivatives as chlolesteryl ester transfer protein inhibitors. European Patent Application No. 818197, Schmek et al. describe pyridines with fused heterocycles as cholesteryl ester transfer protein inhibitors. Brandes et al. in German Patent Application No. 19627430 describe bicyclic condensed pyridine derivatives as cholesteryl ester transfer protein inhibitors. In WO Patent Application No. 09839299, Muller-Gliemann et al. describe quinoline derivatives as cholesteryl ester transfer protein inhibitors. U.S. Pat. No. 2,700,686, issued to Dickey and Towne, describes N-(2-haloalkyl-2-hydroxyethyl)amines in which the amine is further substituted with either 1 to 2 aliphatic groups or one aromatic group and one aliphatic group. U.S. Pat. No. 2,700,686 further describes a process to prepare the N-(2-haloalkyl-2-hydroxyethyl)amines by reacting halogenated-1,2-epoxyalkanes with the corresponding aliphatic amines and N-alkylanilines and their use as dye intermediates.

[0007] The present invention provides compounds that can be used to inhibit cholesteryl ester transfer protein (CETP) activity and that have the general structure:

[0008] In another aspect, the present invention includes pharmaceutical compositions comprising a pharmaceutically effective amount of the compounds of this invention and a pharmaceutically acceptable carrier.

[0009] In another aspect, this invention relates to methods of using these inhibitors as therapeutic agents in humans to inhibit cholesteryl ester transfer protein (CETP) activity, thereby decreasing the concentrations of low density lipoprotein (LDL) and raising the level of high density lipoprotein (HDL), resulting in a therapeutically beneficial plasma lipid profile. The compounds and methods of this invention can also be used to treat dyslipidemia (hypoalphalipoproteinemia), hyperlipoproteinaemia (chylornicronemia and hyperapobet alipoproteinemia), peripheral vascular disease, hypercholesterolaemia, atherosclerosis, coronary artery disease and other CETP-mediated disorders. The compounds can also be used in prophylactic treatment of subjects who are at risk of developing such disorders. The compounds can be used to lower the risk of atherosclerosis. The compounds of this invention would be also useful in prevention of cerebral vascular accident (CVA) or stroke. Besides being useful for human treatment, these compounds are also useful for veterinary treatment of companion animals, exotic animals and farm animals such as primates, rabbits, pigs, horses, and the like.

[0010] The present invention relates to a class of compounds comprising substituted polycyclic aryl and heteroaryl tertiary-heteroalkylamines which are beneficial in the therapeutic and prophylactic treatment of coronary artery disease as given in Formula V-H (also referred to herein as generic substituted polycyclic aryl and heteroaryl tertiary omegaheteroalkylamines):

[0011] or a pharmaceutically acceptable salt thereof, wherein;

[0012] m is an integer selected from 0 through 5;

[0013] n is an integer selected from 0 through 5;

[0014] m plus n is an integer selected from 0 through 6;

[0015] R₁ is selected from the group consisting of haloalkyl, haloalkenyl, haloalkoxyalkyl, and haloalkenyloxyalkyl;

[0016] X is selected from the group consisting of O, H, F, S, S(O), NH, N(OH), N(alkyl), and N(alkoxy);

[0017] R₁₆ is selected from the group consisting of hydrido, alkyl, alkenyl, alkynyl, aryl, aralkyl, aryloxyalkyl, alkoxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, aralkoxyalkyl, heteroaralkoxyalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl, heteroaryl, heteroarylalkyl, monocarboalkoxyalkyl, monocarboalkoxy, dicarboalkoxyalkyl, monocarboxamido, monocyanoalkyl, dicyanoalkyl, carboalkoxycyanoalkyl, acyl, aroyl, heteroaroyl, heteroaryloxyalkyl, dialkoxyphosphonoalkyl, trialkylsilyl, and a spacer selected from the group consisting of a covalent single bond and a linear spacer moiety having from 1 through 4 contiguous atoms linked to the point of bonding of an aromatic substituent selected from the group consisting of R₄, R₈, R₉, R₁₃, R₁₄, and R₁₅ to form a heterocyclyl ring having from 5 through 10 contiguous members with the provisos that said spacer moiety is other than a covalent single bond when R₂ is alkyl and there is no R₁₆ wherein X is H or F;

[0018] D₁, D₂, J₁, J₂ and K₁ are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more than one of D₁, D₂, J₁, J₂ and K₁ can be a covalent bond, no more than one of D₁, D₂, J₁, J₂ and K₁ can be O, no more than one of D₁, D₂, J₁, J₂ and K₁ can be S, one of D₁, D₂, J₁, J₂ and K₁ must be a covalent bond when two of D₁, D₂, J₁, J₂ and K₁ are O and S, and no more than four of D₁, D₂, J₁, J₂ and K₁ can be N;

[0019] D₃, D₄, J₃, J₄ and K₂ are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more than one of D₃, D₄, J₃, J₄ and K₂ can be a covalent bond, no more than one of D₃, D₄, J₃, J₄ and K₂ can be O, no more than one of D₃, D₄, J₃, J₄ and K₂ can be S, one of D₃, D₄, J₃, J₄ and K₂ must be a covalent bond when two of D₃, D₄, J₃, J₄ and K₂ are O and S, and no more than four of D₃, D₄, J₃, J₄ and K₂ can be N;

[0020] R₂ is independently selected from the group consisting of hydrido, hydroxy, hydroxyalkyl, amino, aminoalkyl, alkylamino, dialkylamino, alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkoxyalkyl, aryloxyalkyl, alkoxyalkyl, heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl, aralkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl, heteroaryl, heteroarylalkyl, heteroarylthioalkyl, heteroaralkylthioalkyl, monocarboalkoxyalkyl, dicarboalkoxyalkyl, monocyanoalkyl, dicyanoalkyl, carboalkoxycyanoalkyl, alkylsulfinyl, alkylsulfonyl, alkylsulfinylalkyl, alkylsulfonylalkyl, haloalkylsulfinyl, haloalkylsulfonyl, arylsulfinyl, arylsulfinylalkyl, arylsulfonyl, arylsulfonylalkyl, aralkylsulfinyl, aralkylsulfonyl, cycloalkylsulfinyl, cycloalkylsulfonyl, cycloalkylsulfinylalkyl, cycloalkylsufonylalkyl, heteroarylsulfonylalkyl, heteroarylsulfinyl, heteroarylsulfonyl, heteroarylsulfinylalkyl, aralkylsulfinylalkyl, aralkylsulfonylalkyl, carboxy, carboxyalkyl, carboalkoxy, carboxamide, carboxamidoalkyl, carboaralkoxy, dialkoxyphosphono, diaralkoxyphosphono, dialkoxyphosphonoalkyl, and diaralkoxyphosphonoalkyl;

[0021] R₂ and R₃ can be taken together to form a linear spacer moiety selected from the group consisting of a covalent single bond and a moiety having from 1 through 6 contiguous atoms to form a ring selected from the group consisting of a cycloalkyl having from 3 through 8 contiguous members, a cycloalkenyl having from 5 through 8 contiguous members, and a heterocyclyl having from 4 through 8 contiguous members;

[0022] R₂ and R₁₄ can be taken together to form a linear spacer moiety selected from the group consisting of a covalent bond and a linear spacer moiety having from 1 through 5 contiguous atoms to form a heterocyclyl ring having from 5 through 8 contiguous members with the proviso that said spacer group is other than N;

[0023] R₂ and R₁₅ can be taken together to form a linear spacer moiety selected from the group consisting of a covalent bond and a linear spacer moiety having from 1 through 5 contiguous atoms to form a heterocyclyl ring having from 5 through 8 contiguous members with the proviso that said spacer group is other than N;

[0024] R₂ and R₁₉ can be taken together to form a linear spacer moiety selected from the group consisting of a covalent single bond and a linear moiety having from 1 through 5 contiguous atoms to form a ring selected from the group consisting of a cycloalkyl having from 3 through 8 contiguous members, a cycloalkylenyl having from 5 through 8 contiguous members, and a heterocyclyl having from 4 through 8 contiguous members;

[0025] R₂ and R₄, R₂ and R₈, R₂ and R₉, and R₂ and R₁₃ can be independently selected to form spacer pairs wherein a spacer pair is taken together to form a linear spacer moiety wherein said linear spacer moiety is selected to form a heterocyclyl ring having from 5 through 10 contiguous members;

[0026] R₃ is selected from the group consisting of hydrido, hydroxy, halo, cyano, aryloxy, hydroxyalkyl, amino, alkylamino, dialkylamino, acyl, sulfhydryl, acylamido, alkoxy, alkylthio, arylthio, alkyl, alkenyl, alkynyl, aryl, aralkyl, aryloxyalkyl, alkoxyalkyl, heteroarylthio, aralkylthio, aralkoxyalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, aroyl, heteroaroyl, aralkylthioalkyl, heteroaralkylthioalkyl, heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl, heteroaryl, heteroarylalkyl, heteroarylthioalkyl, monocarboalkoxyalkyl, dicarboalkoxyalkyl, monocyanoalkyl, dicyanoalkyl, carboalkoxycyanoalkyl, alkylsulfinyl, alkylsulfonyl, haloalkylsulfinyl, haloalkylsulfonyl, arylsulfinyl, arylsulfinylalkyl, arylsulfonyl, arylsulfonylalkyl, aralkylsulfinyl, aralkylsulfonyl, cycloalkylsulfinyl, cycloalkylsulfonyl, cycloalkylsulfinylalkyl, cycloalkylsufonylalkyl, heteroarylsulfonylalkyl, heteroarylsulfinyl, heteroarylsulfonyl, heteroarylsulfinylalkyl, aralkylsulfinylalkyl, aralkylsulfonylalkyl, carboxy, carboxyalkyl, carboalkoxy, carboxamide, carboxamidoalkyl, carboaralkoxy, dialkoxyphosphono, diaralkoxyphosphono, dialkoxyphosphonoalkyl, and diaralkoxyphosphonoalkyl;

[0027] R₃ and R₁₄ can be taken together to form a linear spacer moiety selected from the group consisting of a covalent bond and a linear moiety having from 1 through 5 atoms to form a heterocyclyl ring having from 5 through 8 contiguous members;

[0028] R₃ and R₁₅ can be taken together to form a linear spacer moiety selected from the group consisting of a covalent bond and a linear moiety having from 1 through 5 atoms to form a heterocyclyl ring having from 5 through 8 contiguous members;

[0029] R₃ and R₁₉ can be taken together to form a linear spacer moiety selected from the group consisting of a covalent single bond and a linear moiety having a chain length of 1 to 5 atoms to form a ring selected from the group consisting of a cycloalkyl having from 3 through 8 contiguous members, a cycloalkylenyl having from 5 through 8 contiguous members, and a heterocyclyl having from 4 through 8 contiguous members;

[0030] R₃ and R₄, R₃ and R₈, R₃ and R₉, and R₃ and R₁₃ can be independently selected to form spacer pairs wherein a spacer pair is taken together to form a linear spacer moiety wherein said linear spacer moiety is selected to form a heterocyclyl ring having from 5 through 10 contiguous members;

[0031] Y is selected from a group consisting of a covalent single bond, (C(R₁₄)₂)_q wherein q is an integer selected from 1 through 4 and (CH(R₁₄))_gW(CH(R₁₄))_p wherein g and p are integers independently selected from 0 through 2;

[0032] R₁₄ is independently selected from the group consisting of hydrido, hydroxy, halo, cyano, aryloxy, amino, alkylamino, dialkylamino, hydroxyalkyl, acyl, aroyl, heteroaroyl, heteroaryloxyalkyl, sulfhydryl, acylamido, alkoxy, alkylthio, arylthio, alkyl, alkenyl, alkynyl, aryl, aralkyl, aryloxyalkyl, aralkoxyalkylalkoxy, alkylsulfinylalkyl, alkylsulfonylalkyl, aralkylthioalkyl, heteroaralkoxythioalkyl, alkoxyalkyl, heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl, heteroaryl, heteroarylalkyl, heteroarylthioalkyl, heteroaralkylthioalkyl, monocarboalkoxyalkyl, dicarboalkoxyalkyl, monocyanoalkyl, dicyanoalkyl, carboalkoxycyanoalkyl, alkylsulfinyl, alkylsulfonyl, haloalkylsulfinyl, haloalkylsulfonyl, arylsulfinyl, arylsulfinylalkyl, arylsulfonyl, arylsulfonylalkyl, aralkylsulfinyl, aralkylsulfonyl, cycloalkylsulfinyl, cycloalkylsulfonyl, cycloalkylsulfinylalkyl, cycloalkylsufonylalkyl, heteroarylsulfonylalkyl, heteroarylsulfinyl, heteroarylsulfonyl, heteroarylsulfinylalkyl, aralkylsulfinylalkyl, aralkylsulfonylalkyl, carboxy, carboxyalkyl, carboalkoxy, carboxamide, carboxamidoalkyl, carboaralkoxy, dialkoxyphosphono, diaralkoxyphosphono, dialkoxyphosphonoalkyl, diaralkoxyphosphonoalkyl, a spacer selected from a moiety having a chain length of 3 to 6 atoms connected to the point of bonding selected from the group consisting of R₉ and R₁₃ to form a ring selected from the group consisting of a cycloalkenyl ring having from 5 through 8 contiguous members and a heterocyclyl ring having from 5 through 8 contiguous members, and a spacer selected from a moiety having a chain length of 2 to 5 atoms connected to the point of bonding selected from the group consisting of R₄ and R₈ to form a heterocyclyl having from 5 through 8 contiguous members with the proviso that, when Y is a covalent bond, an R₁₄ substituent is not attached to Y;

[0033] R₁₄ and R₁₅ can be taken together to form a spacer selected from a moiety having a chain length of 2 to 5 atoms to form a heterocyclyl ring having from 5 through 8 contiguous members;

[0034] R₁₄ and R₁₉ can be taken together to form a spacer selected from a moiety having a chain length of 2 to 5 atoms to form a heterocyclyl ring having from 5 through 8 contiguous members;

[0035] R₁₄ and R₁₄, when bonded to the different atoms, can be taken together to form a group selected from the group consisting of a covalent bond, alkylene, haloalkylene, and a spacer selected from a group consisting of a moiety having a chain length of 2 to 5 atoms connected to form a ring selected from the group of a saturated cycloalkyl having from 5 through 8 contiguous members, a cycloalkenyl having from 5 through 8 contiguous members, and a heterocyclyl having from 5 through 8 contiguous members;

[0036] R₁₄ and R₁₄, when bonded to the same atom can be taken together to form a group selected from the group consisting of oxo, thiono, alkylene, haloalkylene, and a spacer selected from the group consisting of a moiety having a chain length of 3 to 7 atoms connected to form a ring selected from the group consisting of a cycloalkyl having from 4 through 8 contiguous members, a cycloalkenyl having from 4 through 8 contiguous members, and a heterocyclyl having from 4 through 8 contiguous members;

[0037] W is selected from the group consisting of O, C(O), C(S), C(O)N(R₁₄), C(S)N(R₁₄), (R₁₄)NC(O), (R₁₄)NC(S), S, S(O), S(O)₂, S(O)₂N(R₁₄), (R₁₄)NS(O)₂, and N(R₁₄) with the proviso that R₁₄ is selected from other than halo and cyano;

[0038] Z is independently selected from a group consisting of a covalent single bond, (C(R₁₅)₂)_q wherein q is an integer selected from 1 through 4, (CH(R₁₅))_jW(CH(R₁₅))_k wherein j and k are integers independently selected from 0 through 2 with the proviso that, when Z is a covalent single bond, an R₁₅ substituent is not attached to Z;

[0039] R₁₅ is independently selected, when Z is (C(R₁₅)₂)_q wherein q is an integer selected from 1 through 4, from the group consisting of hydrido, hydroxy, halo, cyano, aryloxy, amino, alkylamino, dialkylamino, hydroxyalkyl, acyl, aroyl, heteroaroyl, heteroaryloxyalkyl, sulfhydryl, acylamido, alkoxy, alkylthio, arylthio, alkyl, alkenyl, alkynyl, aryl, aralkyl, aryloxyalkyl, aralkoxyalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, aralkylthioalkyl, heteroaralkylthioalkyl, alkoxyalkyl, heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl, heteroaryl, heteroarylalkyl, heteroarylthioalkyl, heteroaralkylthioalkyl, monocarboalkoxyalkyl, dicarboalkoxyalkyl, monocyanoalkyl, dicyanoalkyl, carboalkoxycyanoalkyl, alkylsulfinyl, alkylsulfonyl, haloalkylsulfinyl, haloalkylsulfonyl, arylsulfinyl, arylsulfinylalkyl, arylsulfonyl, arylsulfonylalkyl, aralkylsulfinyl, aralkylsulfonyl, cycloalkylsulfinyl, cycloalkylsulfonyl, cycloalkylsulfinylalkyl, cycloalkylsufonylalkyl, heteroarylsulfonylalkyl, heteroarylsulfinyl, heteroarylsulfonyl, heteroarylsulfinylalkyl, aralkylsulfinylalkyl, aralkylsulfonylalkyl, carboxy, carboxyalkyl, carboalkoxy, carboxamide, carboxamidoalkyl, carboaralkoxy, dialkoxyphosphono, diaralkoxyphosphono, dialkoxyphosphonoalkyl, diaralkoxyphosphonoalkyl, a spacer selected from a moiety having a chain length of 3 to 6 atoms connected to the point of bonding selected from the group consisting of R₄ and R₈ to form a ring selected from the group consisting of a cycloalkenyl ring having from 5 through 8 contiguous members and a heterocyclyl ring having from 5 through 8 contiguous members, and a spacer selected from a moiety having a chain length of 2 to 5 atoms connected to the point of bonding selected from the group consisting of R₉ and R₁₃ to form a heterocyclyl having from 5 through 8 contiguous members;

[0040] R₁₅ and R₁₉ can be taken together to form a spacer selected from the group consisting of a covalent single bond and a linear moiety having a chain length of 2 to 5 atoms to form a heterocyclyl ring having from 5 through 8 contiguous members;

[0041] R₁₅ and R₁₅, when bonded to the different atoms, can be taken together to form a group selected from the group consisting of a covalent bond, alkylene, haloalkylene, and a spacer selected from a group consisting of a moiety having a chain length of 2 to 5 atoms connected to form a ring selected from the group of a saturated cycloalkyl having from 5 through 8 contiguous members, a cycloalkenyl having from 5 through 8 contiguous members, and a heterocyclyl having from 5 through 8 contiguous members;

[0042] R₁₅ and R₁₅, when bonded to the same atom can be taken together to form a group selected from the group consisting of oxo, thiono, alkylene, haloalkylene, and a spacer selected from the group consisting of a moiety having a chain length of 3 to 7 atoms connected to form a ring selected from the group consisting of a cycloalkyl having from 4 through 8 contiguous members, a cycloalkenyl having from 4 through 8 contiguous members, and a heterocyclyl having from 4 through 8 contiguous members;

[0043] R₁₅ is independently selected, when Z is (CH(R₁₅))_jW(CH(R₁₅))_k wherein j and k are integers independently selected from 0 through 2, from the group consisting of hydrido, halo, cyano, aryloxy, carboxyl, acyl, aroyl, heteroaroyl, hydroxyalkyl, heteroaryloxyalkyl, acylamido, alkoxy, alkylthio, arylthio, alkyl, alkenyl, alkynyl, aryl, aralkyl, aryloxyalkyl, alkoxyalkyl, heteroaryloxyalkyl, aralkoxyalkyl, heteroaralkoxyalkyl, alkylsulfonylalkyl, alkylsulfinylalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl, heteroaryl, heteroarylalkyl, heteroarylthioalkyl, heteroaralkylthioalkyl, monocarboalkoxyalkyl, dicarboalkoxyalkyl, monocyanoalkyl, dicyanoalkyl, carboalkoxycyanoalkyl, alkylsulfinyl, alkylsulfonyl, haloalkylsulfinyl, haloalkylsulfonyl, arylsulfinyl, arylsulfinylalkyl, arylsulfonyl, arylsulfonylalkyl, aralkylsulfinyl, aralkylsulfonyl, cycloalkylsulfinyl, cycloalkylsulfonyl, cycloalkylsulfinylalkyl, cycloalkylsufonylalkyl, heteroarylsulfonylalkyl, heteroarylsulfinyl, heteroarylsulfonyl, heteroarylsulfinylalkyl, aralkylsulfinylalkyl, aralkylsulfonylalkyl, carboxyalkyl, carboalkoxy, carboxamide, carboxamidoalkyl, carboaralkoxy, dialkoxyphosphonoalkyl, diaralkoxyphosphonoalkyl, a spacer selected from a linear moiety having a chain length of 3 to 6 atoms connected to the point of bonding selected from the group consisting of R₄ and R₈ to form a ring selected from the group consisting of a cycloalkenyl ring having from 5 through 8 contiguous members and a heterocyclyl ring having from 5 through 8 contiguous members, and a spacer selected from a linear moiety having a chain length of 2 to 5 atoms connected to the point of bonding selected from the group consisting of R₉ and R₁₃ to form a heterocyclyl ring having from 5 through 8 contiguous members;

[0044] R₄, R₅, R₆, R₇, R₈, R₉, R₁₀, R₁₁, R₁₂, and R₁₃ are independently selected from the group consisting of perhaloaryloxy, alkanoylalkyl, alkanoylalkoxy, alkanoyloxy, N-aryl-N-alkylamino, heterocyclylalkoxy, heterocyclylthio, hydroxyalkoxy, carboxamidoalkoxy, alkoxycarbonylalkoxy, alkoxycarbonylalkenyloxy, aralkanoylalkoxy, aralkenoyl, N-alkylcarboxamido, N-haloalkylcarboxamido, N-cycloalkylcarboxamido, N-arylcarboxarnidoalkoxy, cycloalkylcarbonyl, cyanoalkoxy, heterocyclylcarbonyl, hydrido, carboxy, heteroaralkylthio, heteroaralkoxy, cycloalkylamino, acylalkyl, acylalkoxy, aroylalkoxy, heterocyclyloxy, aralkylaryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl, perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl, aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl, cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, heteroarylamino, N-heteroarylarnino-N-alkylamino, heteroarylaminoalkyl, haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl, heteroaralkoxy, cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxy, halocycloalkenyloxyalkyl, hydroxy, arnino, thio, nitro, lower alkylamino, alkylthio, alkylthioalkyl, arylarnino, aralkylamino, arylthio, arylthioalkyl, heteroaralkoxyalkyl, alkylsulfinyl, alkylsulfinylalkyl, arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl, haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkyl amnidosulfonyl, dialkyl amidosulfonyl, monoarylamidosulfonyl, arylsulfonamido, diarylamidosulfonyl, monoalkyl monoaryl arnidosulfonyl, arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, heterocyclylsulfonyl, heterocyclylthio, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl, alkenyloxy, alkenyloxyalky, alkylenedioxy, haloalkylenedioxy, cycloalkyl, cycloalkylalkanoyl, cycloalkenyl, lower cycloalkylalkyl, lower cycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, heteroaralkynyl, aryloxy, aralkoxy, aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroaryloxy, heteroaryloxyalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl, carboalkoxy, alkoxycarboxarnido, alkylamidocarbonylamido, arylamidocarbonylamido, carboalkoxyalkyl, carboalkoxyalkenyl, carboaralkoxy, carboxamido, carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono, phosphonoalkyl, diaralkoxyphosphono, and diaralkoxyphosphonoalkyl with the proviso that there are one to five non-hydrido ring substituents R₄, R₅, R₆, R₇, and R₈ present, that there are one to five non-hydrido ring substituents R₉, R₁₀, R₁₁, R₁₂, and R₁₃ present, and R₄, R₅, R₆, R₇, R₈, R₉, R₁₀, R₁₁, R₁₂, and R₁₃ are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;

[0045] R₄ and R₅, R₅ and R₆, R₆ and R₇, R₇ and R₈, R₉ and R₁₀, R₁₀ and R₁₁, R₁₁ and R₁₂, and R₁₂ and R₁₃ can be independently selected to form spacer pairs wherein a spacer pair is taken together to form a linear moiety having from 3 through 6 contiguous atoms connecting the points of bonding of said spacer pair members to form a ring selected from the group consisting of a cycloalkenyl ring having 5 through 8 contiguous members, a partially saturated heterocyclyl ring having 5 through 8 contiguous members, a heteroaryl ring having 5 through 6 contiguous members, and an aryl with the provisos that no more than one of the group consisting of spacer pairs R₄ and R₅, R₅ and R₆, R₆ and R₇, and R₇ and R₈, can be used at the same time and that no more than one of the group consisting of spacer pairs R₉ and R₁₀, R₁₀ and R₁₁, R₁₁ and R₁₂, and R₁₂ and R₁₃ can be used at the same time;

[0046] R₄ and R₉, R₄ and R₁₃, R₈ and R₉, and R₈ and R₁₃ can be independently selected to form a spacer pair wherein said spacer pair is taken together to form a linear moiety wherein said linear moiety forms a ring selected from the group consisting of a partially saturated heterocyclyl ring having from 5 through 8 contiguous members and a heteroaryl ring having from 5 through 6 contiguous members with the proviso that no more than one of the group consisting of spacer pairs R₄ and R₉, R₄ and R₁₃, R₈ and R₉, and R₈ and R₁₃ can be used at the same time;

[0047] R₅ and R₁₀, R₅ and R₁₂, R₇ and R₁₀, and R₇ and R₁₂ can be independently selected to form a spacer pair wherein said spacer pair is taken together to form a linear moiety wherein said linear moiety forms a C8 to C13 heterocyclyl ring having from 8 through 13 contiguous members with the proviso that no more than one of the group consisting of spacer pairs R₅ and R₁₀, R₅ and R₁₂, R₇ and R₁₀, and R₇ and R₁₂ can be used at the same time;

[0048] R₁₉ is selected from the group consisting of hydrido, hydroxyalkyl, acyl, sulfhydryl, acylamido, alkoxy, alkylthio, arylthio, alkyl, alkenyl, alkynyl, aryl, aralkyl, aryloxyalkyl, aralkanoyl, heteroarylthio, aralkylthio, aroyl, heteroaroyl, aralkoxyalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, aralkylthioalkyl, heteroaralkylthioalkyl, alkoxyalkyl, heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl, heteroaryl, heteroarylalkyl, heteroarylthioalkyl, heteroaralkylthioalkyl, monocarboalkoxyalkyl, dicarboalkoxyalkyl, monocyanoalkyl, dicyanoalkyl, carboalkoxycyanoalkyl, alkylsulfinyl, alkylsulfonyl, haloalkylsulfinyl, haloalkylsulfonyl, arylsulfinyl, arylsulfinylalkyl, arylsulfonyl, arylsulfonylalkyl, aralkylsulfinyl, aralkylsulfonyl, cycloalkylsulfinyl, cycloalkylsulfonyl, cycloalkylsulfinylalkyl, cycloalkylsufonylalkyl, heteroarylsulfonylalkyl, heteroarylsulfinyl, heteroarylsulfonyl, heteroarylsulfinylalkyl, aralkylsulfinylalkyl, aralkylsulfonylalkyl, carboxyalkyl, carboalkoxy, carboxamide, carboxamidoalkyl, carboaralkoxy, dialkoxyphosphono, diaralkoxyphosphono, dialkoxyphosphonoalkyl, diaralkoxyphosphonoalkyl, and a spacer group selected from the group consisting of a covalent single bond and a linear moiety having a chain length of 2 to 5 atoms connected to a point of bonding selected from the group consisting of R₄, R₈, R₉, and R₁₃ to form a heterocyclyl ring having from 5 through 8 contiguous members.

[0049] In another embodiment, the compounds correspond to Formula V-H wherein m is an integer selected from 0 through 5; n is an integer selected from 0 through 5; the sum of m plus n is an integer selected from 0 through 6; D₁, D₂, D₃, D₄, J₁, J₂, J₃, J₄, K₁, and K₂ are each a carbon atom; and a terminal carbon atom of the CH(R₃) moiety is directly connected by a covalent single bond to the nitrogen when m0. Compounds of Formula V-H wherein m is an integer selected from 0 through 5, n is an integer selected from 0 through 5, the sum of m plus n is an integer selected from 0 through 6, and D₁, D₂, D₃, D₄, J₁, J₂, J₃, J₄, K₁, and K₂ are each a carbon atom, have the CH(R₃) moiety directly connected by a covalent single bond to the nitrogen when m0 and correspond to Formula V (also referred to herein as generic phenyl tertiary omegaheteroalkylamines):

[0050] or a pharmaceutically acceptable salt thereof, wherein;

[0051] R₁, R₂, R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₁₄, R₁₅, R₁₆, R₁₉, X, Y, and Z are as defined for the compounds of Formula V-H;

[0052] D₁, D₂, D₃, D₄, J₁, J₂, J₃, J₄, K₁, and K₂ are each carbon;

[0053] R₁₆ and R₄, R₁₆ and R₈, R₁₆ and R₉, R₁₆ and R₁₃, R₂ and R₃, R₉ and R₁₄, R₁₃ and R₁₄, R₄ and R₁₄, R₈ and R₁₄, R₁₄ and R₁₄, R₄ and R₁₅, R₈ and R₁₅, R₉ and R₁₅, R₁₃ and R₁₅, R₁₅ and R₁₅, R₄ and R₅, R₅ and R₆, R₆ and R₇, R₇ and R₈, R₉ and R₁₀, R₁₀ and R₁₁, R₁₁ and R₁₂, R₁₂ and R₁₃, R₄ and R₉, R₄ and R₁₃, R₈ and R₉, R₈ and R₁₃, R₁₆ and R₁₄, R₁₆ and R₁₅, R₂ and R₁₄, R₂ and R₁₅, R₂ and R₁₉, R₂ and R₄, R₂ and R₈, R₂ and R₉, R₂ and R₁₃, R₃ and R₁₄, R₃ and R₁₅, R₃ and R₁₉, R₃ and R₄, R₃ and R₈, R₃ and R₉, R₃ and R₁₃, R₁₄ and R₁₉, R₁₄ and R₁₅, R₁₅ and R₁₉, R₅ and R₁₀, R₅ and R₁₂, R₇ and R₁₀, and R₇ and R₁₂ spacer pairs are as defined for the compounds of Formula V-H.

[0054] In another embodiment, the compounds correspond to Formula V-H wherein m is an integer selected from 0 through 5; n is an integer selected from 0 through 5; the sum of m plus n is an integer selected from 0 through 6; and a terminal carbon atom of the CH(R₃) moiety is directly connected by a covalent single bond to the nitrogen when m0. Compounds of Formula V-H wherein wherein m is the integer zero, and n is an integer selected from 0 through 5, have the CH(R₃) moiety directly connected by a covalent single bond to the nitrogen when m0 and correspond to Formula VII-H (also referred to herein as generic substituted polycyclic heteroaryl tertiary 2-heteroalkylamines):

[0055] or a pharmaceutically acceptable salt thereof, wherein;

[0056] R₁, R₂, R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₁₄, R₁₅, R₁₆, D₁, D₂, D₃, D₄, J₁, J₂, J₃, J₄, K₁, K₂, X, Y, and Z are defined for the compounds of Formula V-H;

[0057] R₁₆ and R₄, R₁₆ and R₈, R₁₆ and R₉, R₁₆ and R₁₃, R₂ and R₃, R₉ and R₁₄, R₁₃ and R₁₄, R₄ and R₁₄, R₈ and R₁₄, R₁₄ and R₁₄, R₄ and R₁₅, R₈ and R₁₅, R₉ and R₁₅, R₁₃ and R₁₅, R₁₅ and R₁₅, R₄ and R₅, R₅ and R₆, R₆ and R₇, R₇ and R₈, R₉ and R₁₀, R₁₀ and R₁₁, R₁₁ and R₁₂, R₁₂ and R₁₃, R₄ and R₉, R₄ and R₁₃, R₈ and R₉, and R₈ and R₁₃ spacer pairs are as defined for the compounds of Formula V-H;

[0058] R₁₉ and spacer pairs R₁₆ and R₁₄, R₁₆ and R₁₅, R₂ and R₁₄, R₂ and R₁₅, R₂ and R₁₉, R₂ and R₄, R₂ and R₈, R₂ and R₉, R₂ and R₁₃, R₃ and R₁₄, R₃ and R₁₅, R₃ and R₁₉, R₃ and R₄, R₃ and R₈, R₃ and R₉, R₃ and R₁₃, R₁₄ and R₁₉, R₁₄ and R₁₅, R₁₅ and R₁₉, R₅ and R₁₀, R₅ and R₁₂, R₇ and R₁₀, and R₇ and R₁₂ are not present.

[0059] In another embodiment of compounds of Formula VII-H,

[0060] D₁, D₂, J₁, J₂ and K₁ are each carbon with the proviso that at least one of D₃, D₄, J₃, J₄ and K₂ is selected from the group consisting of O, S, and N, wherein D₃, D₄, J₃, J₄ and K₂ are independently selected from the group consisting of C, N, O, S and covalent bond with the provisos that no more than one of D₃, D₄, J₃, J₄ and K₂ can be a covalent bond, no more than one of D₃, D₄, J₃, J₄ and K₂ can be O, no more than one of D₃, D₄, J₃, J₄ and K₂ can be S, one of D₃, D₄, J₃, J₄ and K₂ must be a covalent bond when two of D₃, D₄, J₃, J₄ and K₂ are O and S, and no more than four of D₃, D₄, J₃, J₄ and K₂ can be N;

[0061] D₁, D₂, J₁, J₂ and K₁ can be selected from the group consisting of C, O, S, N and covalent bond with the provisos that D₃, D₄, J₃, J₄ and K₂ are each carbon and at least one of D₁, D₂, J₁, J₂ and K₁ is selected from the group consisting of O, S, and N wherein, when D₁, D₂, J₁, J₂ and K₁ are selected from the group consisting of C, O, S, covalent bond, and N, no more than one of D₁, D₂, J₁, J₂ and K₁ can be a covalent bond, no more than one of D₁, D₂, J₁, J₂ and K₁ can be O, no more than one of D₁, D₂, J₁, J₂ and K₁ can be S, one of D₁, D₂, J₁, J₂ and K₁ must be a covalent bond when two of D₁, D₂, J₁, J₂ and K₁ are O and S, and no more than four of D₁, D₂, J₁, J₂ and K₁ can be N;

[0062] n is an integer selected from 1 through 4;

[0063] X is oxy;

[0064] R₁₆ is selected from the group consisting of hydrido, acyl, aroyl, and trialkylsilyl;

[0065] R₁ is selected from the group consisting of haloalkyl, haloalkenyl, haloalkoxyalkyl, and haloalkenyloxyalkyl;

[0066] R₂ is selected from the group consisting of hydrido, hydroxy, aryl, aralkyl, alkyl, alkenyl, alkenyloxyalkyl, haloalkyl, haloalkenyl, halocycloalkyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl, perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl, heteroaryl, dicyanoalkyl, and carboalkoxycyanoalkyl;

[0067] R₃ is selected from the group consisting of hydrido, hydroxy, cyano, aryl, aralkyl, acyl, alkoxy, alkyl, alkenyl, alkoxyalkyl, heteroaryl, alkenyloxyalkyl, haloalkyl, haloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, monocyanoalkyl, dicyanoalkyl, carboxamide, and carboxamidoalkyl;

[0068] Y is selected from the group consisting of covalent single bond and (C(R₁₄)₂)_q wherein q is an integer selected from 1 through 2;

[0069] R₁₄ is selected from the group consisting of hydrido, cyano, hydroxyalkyl, acyl, alkoxy, alkyl, alkenyl, alkoxyalkyl, haloalkyl, haloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, monocyanoalkyl, dicyanoalkyl, carboxamide, and carboxamidoalkyl;

[0070] Z is selected from the group consisting of covalent single bond, (C(R₁₅)₂)_q wherein q is an integer selected from 1 through 2, and (CH(R₁₅))_jW(CH(R₁₅))_k wherein j and k are integers independently selected from 0 through 2;

[0071] W is oxy;

[0072] R₁₅ is selected from the group consisting of hydrido, cyano, hydroxyalkyl, acyl, alkoxy, alkyl, alkenyl, alkoxyalkyl, haloalkyl, haloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, monocyanoalkyl, dicyanoalkyl, carboxamide, and carboxamidoalkyl;

[0073] R₄, R₈, R₉, and R₁₃ are independently selected from the group consisting of hydrido, halo, haloalkyl, and alkyl;

[0074] R₅, R₆, R₇, R₁₀, R₁₁, and R₁₂ are independently selected from the group consisting of perhaloaryloxy, alkanoylalkyl, alkanoylalkoxy, alkanoyloxy, N-aryl-N-alkylamino, heterocyclylalkoxy, heterocyclylthio, hydroxyalkoxy, carboxamidoalkoxy, alkoxycarbonylalkoxy, alkoxycarbonylalkenyloxy, aralkanoylalkoxy, aralkenoyl, N-alkylcarboxamido, N-haloalkylcarboxamido, N-cycloalkylcarboxamnido, N-arylcarboxamidoalkoxy, cycloalkylcarbonyl, cyanoalkoxy, heterocyclylcarbonyl, hydrido, carboxy, heteroaralkylthio, heteroarylsulfonyl, heteroaralkoxy, cycloalkylamino, acylalkyl, acylalkoxy, aroylalkoxy, heterocyclyloxy, aralkylaryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl, haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, cycloalkoxy, cycloalkylalkoxy, hydroxy, amino, thio, nitro, lower alkylamino, alkylthio, arylamino, aralkylamino, arylthio, arylthioalkyl, alkylsulfonyl, alkylsulfonamido, monoarylamidosulfonyl, arylsulfonyl, heteroarylthio, heterocyclylsulfonyl, heterocyclylthio, alkanoyl, alkenoyl, aroyl, alkyl, alkenyl, alkynyl, alkenyloxy, alkylenedioxy, haloalkylenedioxy, cycloalkyl, cycloalkylalkanoyl, halo, haloalkyl, haloalkoxy, hydroxyhaloalkyl, hydroxyalkyl, aryl, aralkyl, aryloxy, aralkoxy, saturated heterocyclyl, heteroaryl, heteroaryloxy, heteroaryloxyalkyl, arylalkyl, heteroarylalkyl, arylalkenyl, carboalkoxy, alkoxycarboxamido, alkylamidocarbonylamido, arylamidocarbonylamido, carboalkoxyalkyl, carboalkoxyalkenyl, carboxamido, carboxamidoalkyl, and cyano;

[0075] R₄ and R₅, R₅ and R₆, R₆ and R₇, R₇ and R₈, R₉ and R₁₀, R₁₀ and R₁₁, R₁₁ and R₁₂, and R₁₂ and R₁₃ spacer pairs can be independently selected from the group consisting of alkylene, alkenylene, alkylenedioxy, aralkylene, diacyl, haloalkylene, and aryloxylene with the provisos that no more than one of the group consisting of spacer pairs R₄ and R₅, R₅ and R₆, R₆ and R₇, and R₇ and R₈ can be used at the same time and that no more than one of the group consisting of spacer pairs R₉ and R₁₀, R₁₀ and R₁₁, R₁₁ and R₁₂, and R₁₂ and R₁₃ can be used at the same time.

[0076] In a more specific embodiment of compounds of Formula VII-H,

[0077] D₁, D₂, J₁, J₂ and K₁ are each carbon;

[0078] D₃, D₄, J₃, J₄ and K₂ are independently selected from the group consisting of C, N, O, S and covalent bond with the provisos that at least one of D₃, D₄, J₃, J₄ and K₂ is selected from the group consisting of O, S, and N, wherein no more than one of D₃, D₄, J₃, J₄ and K₂ can be a covalent bond, no more than one of D₃, D₄, J₃, J₄ and K₂ can be O, no more than one of D₃, D₄, J₃, J₄ and K₂ can be S, one of D₃, D₄, J₃, J₄ and K₂ must be a covalent bond when two of D₃, D₄, J₃, J₄ and K₂ are O and S, and no more than four of D₃, D₄, J₃, J₄ and K₂ can be N;

[0079] n is an integer selected from 1 through 3;

[0080] X is oxy;

[0081] R₁ is selected from the group consisting of trifluoromethyl, 1,1,2,2-tetrafluoroethoxymethyl, trifluoromethoxymethyl, chloromethyl, fluoromethyl, difluoromethyl, chlorodifluoromethyl, pentafluoroethyl, 2,2,3,3,3-pentafluoropropyl, and heptafluoropropyl;

[0082] R₁₆ is selected from the group consisting of acetyl, benzoyl, dimethyl tert-butylsilyl, hydrido, and trimethylsilyl;

[0083] R₂ is selected from the group consisting of hydrido, hydroxy, methyl, ethyl, propyl, butyl, isopropyl, isobutyl, vinyl, phenyl, trifluoromethyl, 4-trifluoromethylphenyl, 1,1,2,2-tetrafluoroethoxymethyl, chloromethyl, trifluoromethoxymethyl, fluoromethyl, difluoromethyl, chlorodifluoromethyl, pentafluoroethyl, 2,2,3,3,3-pentafluoropropyl, and heptafluoropropyl, pentafluorophenyl, and pentafluorophenoxymethyl;

[0084] R₃ is selected from the group consisting of hydrido, hydroxy, cyano, acetyl, methoxy, ethoxy, methyl, ethyl, propyl, vinyl, phenyl, methoxymethyl, 4-trifluoromethylphenyl, trifluoromethyl, 1,1,2,2-tetrafluoroethoxymethyl, trifluoromethoxymethyl, chloromethyl, fluoromethyl, difluoromethyl, chlorodifluoromethyl, pentafluoroethyl, 2,2,3,3,3-pentafluoropropyl, heptafluoropropyl, pentafluorophenyl, and pentafluorophenoxymethyl.

[0085] In a more specific embodiment of compounds of Formula VII-H,

[0086] D₃, D₄, J₃, J₄ and K₂ are each carbon;

[0087] D₁, D₂, J₁, J₂ and K₁ are independently selected from the group consisting of C, N, O, S and covalent bond with the provisos that at least one of D₁, D₂, J₁, J₂ and K₁ is selected from the group consisting of O, S, and N, wherein no more than one of D₁, D₂, J₁, J₂ and K₁ can be a covalent bond, no more than one of D₁, D₂, J₁, J₂ and K₁ can be O, no more than one of D₁, D₂, J₁, J₂ and K₁ can be S, one of D₁, D₂, J₁, J₂ and K₁ must be a covalent bond when two of D₁, D₂, J₁, J₂ and K₁ are O and S, and no more than four of D₁, D₂, J₁, J₂ and K₁ can be N;

[0088] n is an integer selected from 1 through 3;

[0089] X is oxy;

[0090] R₁ is selected from the group consisting of trifluoromethyl, 1,1,2,2-tetrafluoroethoxymethyl, trifluoromethoxymethyl, chloromethyl, fluoromethyl, difluoromethyl, chlorodifluoromethyl, pentafluoroethyl, 2,2,3,3,3-pentafluoropropyl, and heptafluoropropyl;

[0091] R₁₆ is selected from the group consisting of acetyl, benzoyl, dimethyl tert-butylsilyl, hydrido, and trimethylsilyl;

[0092] R₂ is selected from the group consisting of hydrido, hydroxy, methyl, ethyl, propyl, butyl, isopropyl, isobutyl, vinyl, phenyl, trifluoromethyl, 4-trifluoromethylphenyl, 1,1,2,2-tetrafluoroethoxymethyl, chloromethyl, trifluoromethoxymethyl, fluoromethyl, difluoromethyl, chlorodifluoromethyl, pentafluoroethyl, 2,2,3,3,3-pentafluoropropyl, and heptafluoropropyl, pentafluorophenyl, and pentafluorophenoxymethyl;

[0093] R₃ is selected from the group consisting of hydrido, hydroxy, cyano, acetyl, methoxy, ethoxy, methyl, ethyl, propyl, vinyl, phenyl, methoxymethyl, 4-trifluoromethylphenyl, trifluoromethyl, 1,1,2,2-tetrafluoroethoxymethyl, trifluoromethoxymethyl, chloromethyl, fluoromethyl, difluoromethyl, chlorodifluoromethyl, pentafluoroethyl, 2,2,3,3,3-pentafluoropropyl, heptafluoropropyl, pentafluorophenyl, and pentafluorophenoxymethyl.

[0094] In a preferred embodiment of compounds of Formula VII-H, the compounds correspond to the Formula VII (also referred to herein as generic phenyl tertiary 2-heteroalkylamines):

[0095] or a pharmacuetically acceptable salt thereof, wherein;

[0096] n is an integer selected from 0 through 4;

[0097] X is selected from the group consisting of O, H, F, S, S(O), NH N(OH), N(alkyl), and N(alkoxy);

[0098] R₁₆ is selected from the group consisting of hydrido, alkyl, acyl, aroyl, heteroaroyl, trialkylsilyl, and a spacer selected from the group consisting of a covalent single bond and a linear spacer moiety having a chain length of 1 to 4 atoms linked to the point of bonding of any aromatic substituent selected from the group consisting of R₄, R₈, R₉, and R₁₃ to form a heterocyclyl ring having from 5 through 10 contiguous members with the proviso that said linear spacer moiety is other than covalent single bond when R₂ is alkyl;

[0099] R₁ is selected from the group consisting of haloalkyl, haloalkenyl, haloalkoxyalkyl, and haloalkenyloxyalkyl;

[0100] R₂ is selected from the group consisting of hydrido, hydroxy, hydroxyalkyl, aryl, aralkyl, alkyl, alkenyl, aralkoxyalkyl, aryloxyalkyl, alkoxyalkyl, heteroaryloxyalkyl, alkenyloxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl, heteroaryl, heteroarylalkyl, monocyanoalkyl, and dicyanoalkyl, carboalkoxycyanoalkyl;

[0101] R₃ is selected from the group consisting of hydrido, hydroxy, halo, cyano, hydroxyalkyl, aryl, aralkyl, acyl, alkoxy, alkyl, alkenyl, alkoxyalkyl, aroyl, heteroaroyl, alkenyloxyalkyl, haloalkyl, haloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, monocarboalkoxyalkyl, dicarboalkoxyalkyl, monocyanoalkyl, dicyanoalkyl, carboalkoxycyanoalkyl, carboxamide, and carboxamidoalkyl;

[0102] Y is selected from the group consisting of covalent single bond and (C(R₁₄)₂)_q wherein q is an integer selected from 1 through 2;

[0103] R₁₄ is selected from the group consisting of hydrido, hydroxy, cyano, hydroxyalkyl, acyl, alkoxy, alkyl, alkenyl, alkynyl, alkoxyalkyl, haloalkyl, haloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, monocarboalkoxyalkyl, monocyanoalkyl, dicyanoalkyl, carboalkoxycyanoalkyl, carboalkoxy, carboxamide, carboxamidoalkyl;

[0104] Z is selected from the group consisting of covalent single bond, (C(R₁₅)₂)_q wherein q is an integer selected from 1 through 2, and (CH(R₁₅))_jW(CH(R₁₅))_k wherein j and k are integers independently selected from 0 through 2;

[0105] W is selected from the group consisting of O, C(O), C(S), C(O)N(R₁₄), C(S)N(R₁₄), (R₁₄)NC(O), (R₁₄)NC(S), S, S(O), S(O)₂, S(O)₂N(R₁₄), (R₁₄)NS(O)₂, and N(R₁₄) with the proviso that R₁₄ is other than cyano;

[0106] R₁₅ is selected from the group consisting of hydrido, cyano, hydroxyalkyl, acyl, alkoxy, alkyl, alkenyl, alkynyl, alkoxyalkyl, haloalkyl, haloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, monocarboalkoxyalkyl, monocyanoalkyl, dicyanoalkyl, carboalkoxycyanoalkyl, carboalkoxy, carboxamide, and carboxamidoalkyl;

[0107] R₄, R₈, R₉, and R₁₃ are independently selected from the group consisting of hydrido, halo, haloalkyl, and alkyl;

[0108] R₅, R₆, R₇, R₁₀, R₁₁, and R₁₂ are independently selected from the group consisting of perhaloaryloxy, alkanoylalkyl, alkanoylalkoxy, alkanoyloxy, N-aryl-N-alkylamino, heterocyclylalkoxy, heterocyclylthio, hydroxyalkoxy, carboxamidoalkoxy, alkoxycarbonylalkoxy, alkoxycarbonylalkenyloxy, aralkanoylalkoxy, aralkenoyl, N-alkylcarboxamido, N-haloalkylcarboxamido, N-cycloalkylcarboxamido, N-arylcarboxamidoalkoxy, cycloalkylcarbonyl, cyanoalkoxy, heterocyclylcarbonyl, hydrido, carboxy, heteroaralkylthio, heteroaralkoxy, cycloalkylamino, acylalkyl, acylalkoxy, aroylalkoxy, heterocyclyloxy, aralkylaryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl, perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl, aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl, cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, heteroarylamino, N-heteroarylamino-N-alkylarnino, heteroarylaminoalkyl, haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl, heteroaralkoxy, cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxy, halocycloalkenyloxyalkyl, hydroxy, amino, thio, nitro, lower alkylamino, alkylthio, alkylthioalkyl, arylamino, aralkylamino, arylthio, arylthioalkyl, heteroaralkoxyalkyl, alkylsulfinyl, alkylsulfinylalkyl, arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl, haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, monoarylamidosulfonyl, arylsulfonamido, diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl, arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, heterocyclylsulfonyl, heterocyclylthio, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl, alkenyloxy, alkenyloxyalky, alkylenedioxy, haloalkylenedioxy, cycloalkyl, cycloalkylalkanoyl, cycloalkenyl, lower cycloalkylalkyl, lower cycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, heteroaralkynyl, aryloxy, aralkoxy, aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroaryloxy, heteroaryloxyalkyl, heteroaralkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl, carboalkoxy, alkoxycarboxamido, alkylamidocarbonylarido, arylamidocarbonylamido, carboalkoxyalkyl, carboalkoxyalkenyl, carboaralkoxy, carboxamido, carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono, phosphonoalkyl, diaralkoxyphosphono, and diaralkoxyphosphonoalkyl;

[0109] R₄ and R₅, R₅ and R₆, R₆ and R₇, R₇ and R₈, R₉ and R₁₀, R₁₀ and R₁₁, R₁₁ and R₁₂, and R₁₂ and R₁₃ can be independently selected to form spacer pairs wherein a spacer pair is taken together to form a linear moiety having from 3 through 6 contiguous atoms connecting the points of bonding of said spacer pair members to form a ring selected from the group consisting of a cycloalkenyl ring having 5 through 8 contiguous members, a partially saturated heterocyclyl ring having 5 through 8 contiguous members, a heteroaryl ring having 5 through 6 contiguous members, and an aryl with the provisos that no more than one of the group consisting of spacer pairs R₄ and R₅, R₅ and R₆, R₆ and R₇, and R₇ and R₈, can be used at the same time and that no more than one of the group consisting of spacer pairs R₉ and R₁₀, R₁₀ and R₁₁, R₁₁ and R₁₂, and R₁₂ and R₁₃ can be used at the same time.

[0110] In a preferred embodiment of compounds of Formula VII, compounds have the Formula VII-2:

[0111] wherein;

[0112] n is an integer selected from 1 through 4;

[0113] R₁₆ is selected from the group consisting of hydrido, acyl, aroyl, and trialkylsilyl;

[0114] R₁ is selected from the group consisting of haloalkyl, haloalkenyl, haloalkoxyalkyl, and haloalkenyloxyalkyl;

[0115] R₂ is selected from the group consisting of hydrido, hydroxy, aryl, aralkyl, alkyl, alkenyl, alkenyloxyalkyl, haloalkyl, haloalkenyl, halocycloalkyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl, perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl, heteroaryl, dicyanoalkyl, and carboalkoxycyanoalkyl;

[0116] R₃ is selected from the group consisting of hydrido, hydroxy, cyano, aryl, aralkyl, acyl, alkoxy, alkyl, alkenyl, alkoxyalkyl, heteroaryl, alkenyloxyalkyl, haloalkyl, haloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, monocyanoalkyl, dicyanoalkyl, carboxamide, and carboxamidoalkyl;

[0117] Y is selected from the group consisting of covalent single bond and (C(R₁₄)₂)_q wherein q is an integer selected from 1 through 2;

[0118] R₁₄ is selected from the group consisting of hydrido, cyano, hydroxyalkyl, acyl, alkoxy, alkyl, alkenyl, alkoxyalkyl, haloalkyl, haloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, monocyanoalkyl, dicyanoalkyl, carboxamide, and carboxamidoalkyl;

[0119] Z is selected from the group consisting of covalent single bond, (C(R₁₅)₂)_q wherein q is an integer selected from 1 through 2, and (CH(R₁₅))_jW(CH(R₁₅))_k wherein j and k are integers independently selected from 0 through 2;

[0120] W is oxy;

[0121] R₁₅ is selected from the group consisting of hydrido, cyano, hydroxyalkyl, acyl, alkoxy, alkyl, alkenyl, alkoxyalkyl, haloalkyl, haloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, monocyanoalkyl, dicyanoalkyl, carboxamide, and carboxamidoalkyl;

[0122] R₄, R₈, R₉, and R₁₃ are independently selected from the group consisting of hydrido, halo, haloalkyl, and alkyl;

[0123] R₅, R₆, R₇, R₁₀, R₁₁, and R₁₂ are independently selected from the group consisting of perhaloaryloxy, alkanoylalkyl, alkanoylalkoxy, alkanoyloxy, N-aryl-N-alkylamino, heterocyclylalkoxy, heterocyclylthio, hydroxyalkoxy, carboxamidoalkoxy, alkoxycarbonylalkoxy, alkoxycarbonylalkenyloxy, aralkanoylalkoxy, aralkenoyl, N-alkylcarboxamido, N-haloalkylcarboxamido, N-cycloalkylcarboxamido, N-arylcarboxamidoalkoxy, cycloalkylcarbonyl, cyanoalkoxy, heterocyclylcarbonyl, hydrido, carboxy, heteroaralkylthio, heteroarylsulfonyl, heteroaralkoxy, cycloalkylamino, acylalkyl, acylalkoxy, aroylalkoxy, heterocyclyloxy, aralkylaryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl, haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, cycloalkoxy, cycloalkylalkoxy, hydroxy, amino, thio, nitro, lower alkylamino, alkylthio, arylamino, aralkylamino, arylthio, arylthioalkyl,alkylsulfonyl, alkylsulfonamido, monoarylamidosulfonyl, arylsulfonyl, heteroarylthio, heterocyclylsulfonyl, heterocyclylthio, alkanoyl, alkenoyl, aroyl, alkyl, alkenyl, alkynyl, alkenyloxy, alkylenedioxy, haloalkylenedioxy, cycloalkyl, cycloalkylalkanoyl, halo, haloalkyl, haloalkoxy, hydroxyhaloalkyl, hydroxyalkyl, aryl, aralkyl, aryloxy, aralkoxy, saturated heterocyclyl, heteroaryl, heteroaryloxy, heteroaryloxyalkyl, arylalkyl, heteroarylalkyl, arylalkenyl, carboalkoxy, alkoxycarboxamido, alkylamidocarbonylamido, arylamidocarbonylamido, carboalkoxyalkyl, carboalkoxyalkenyl, carboxamido, carboxamidoalkyl, and cyano;

[0124] R₄ and R₅, R₅ and R₆, R₆ and R₇, R₇ and R₈, R₉ and R₁₀, R₁₀ and R₁₁, R₁₁ and R₁₂, and R₁₂ and R₁₃ spacer pairs can be independently selected from the group consisting of alkylene, alkenylene, alkylenedioxy, aralkylene, diacyl, haloalkylene, and aryloxylene with the provisos that no more than one of the group consisting of spacer pairs R₄ and R₅, R₅ and R₆, R₆ and R₇, and R₇ and R₈ can be used at the same time and that no more than one of the group consisting of spacer pairs R₉ and R₁₀, R₁₀ and R₁₁, R₁₁ and R₁₂, and R₁₂ and R₁₃ can be used at the same time.

[0125] In a more preferred embodiment of compounds of Formula VII-2,

[0126] n is an integer selected from 1 through 2;

[0127] R₁ is selected from the group consisting of haloalkyl and haloalkoxyalkyl;

[0128] R₁₆ is hydrido;

[0129] R₂ is selected from the group consisting of hydrido, aryl, alkyl, alkenyl, haloalkyl, haloalkoxy, haloalkoxyalkyl, perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl, and heteroaryl;

[0130] R₃ is selected from the group consisting of hydrido, aryl, alkyl, alkenyl, haloalkyl, and haloalkoxyalkyl;

[0131] Y is selected from the group consisting of a covalent single bond and alkylene;

[0132] Z is selected from the group consisting of a covalent single bond and alkylene;

[0133] R₁₄ is selected from the group consisting of hydrido, alkyl, and haloalkyl;

[0134] R₁₅ is selected from the group consisting of hydrido, alkyl, and haloalkyl;

[0135] R₄, R₈, R₉, and R₁₃ are independently selected from the group consisting of hydrido and halo;

[0136] R₅, R₆, R₇, R₁₀, R₁₁, and R₁₂ are independently selected from the group consisting of perhaloaryloxy, N-aryl-N-alkylamino, heterocyclylalkoxy, heterocyclylthio, hydroxyalkoxy, carboxamidoalkoxy, alkoxycarbonylalkoxy, alkoxycarbonylalkenyloxy, aralkanoylalkoxy, aralkenoyl, N-arylcarboxamidoalkoxy, cycloalkylcarbonyl, cyanoalkoxy, heterocyclylcarbonyl, hydrido, alkyl, halo, haloalkyl, haloalkoxy, aryl, alkylthio, arylamino, arylthio, aroyl, arylsulfonyl, aryloxy, aralkoxy, heteroaryloxy, alkoxy, aralkyl, cycloalkoxy, cycloalkylalkoxy, cycloalkylalkanoyl, heteroaryl, cycloalkyl, haloalkylthio, hydroxyhaloalkyl, heteroaralkoxy, heterocyclyloxy, aralkylaryl, heteroaryloxyalkyl, heteroarylthio, and heteroarylsulfonyl.

[0137] In an even more preferred embodiment of compounds of Formula VII-2,

[0138] n is the integer 1;

[0139] R₁₆ is hydrido;

[0140] R₁ is haloalkyl;

[0141] R₂ is selected from the group consisting of hydrido, alkyl, haloalkyl, aryl, and haloalkoxy;

[0142] R₃ is selected from the group consisting of hydrido, alkyl, and haloalkyl;

[0143] Y is alkylene;

[0144] Z is covalent single bond;

[0145] R₁₄ is hydrido;

[0146] R₄, R₈, R₉, and R₁₃ are independently selected from the group consisting of hydrido and halo;

[0147] R₅, R₆, R₇, R₁₀, R₁₁, and R₁₂ are independently selected from the group consisting of perhaloaryloxy, N-aryl-N-alkylamino, heterocyclylalkoxy, heterocyclylthio, hydroxyalkoxy, aralkanoylalkoxy, aralkenoyl, cycloalkylcarbonyl, cyanoalkoxy, heterocyclylcarbonyl, hydrido, alkyl, halo, haloalkyl, haloalkoxy, aryl, alkylthio, arylamino, arylthio, aroyl, arylsulfonyl, aryloxy, aralkoxy, heteroaryloxy, alkoxy, aralkyl, cycloalkoxy, cycloalkylalkoxy, cycloalkylalkanoyl, heteroaryl, cycloalkyl, haloalkylthio, hydroxyhaloalkyl, heteroaralkoxy, and heteroaryloxyalkyl.

[0148] In an embodiment of compounds of Formula VII-2,

[0149] n is an integer selected from 1 to 3;

[0150] R₁ is selected from the group consisting of trifluoromethyl, 1,1,2,2-tetrafluoroethoxymethyl, trifluoromethoxymethyl, chloromethyl, fluoromethyl, difluoromethyl, chlorodifluoromethyl, pentafluoroethyl, 2,2,3,3,3-pentafluoropropyl, and heptafluoropropyl;

[0151] R₁₆ is selected from the group consisting of acetyl, benzoyl, dimethyl tert-butylsilyl, hydrido, and trimethylsilyl;

[0152] R₂ is selected from the group consisting of hydrido, hydroxy, methyl, ethyl, propyl, butyl, isopropyl, isobutyl, vinyl, phenyl, trifluoromethyl, 4-trifluoromethylphenyl, 1,1,2,2-tetrafluoroethoxymethyl, chloromethyl, trifluoromethoxymethyl, fluoromethyl, difluoromethyl, chlorodifluoromethyl, pentafluoroethyl, 2,2,3,3,3-pentafluoropropyl, and heptafluoropropyl, pentafluorophenyl, and pentafluorophenoxymethyl;

[0153] R₃ is selected from the group consisting of hydrido, hydroxy, cyano, acetyl, methoxy, ethoxy, methyl, ethyl, propyl, vinyl, phenyl, methoxymethyl, 4-trifluoromethylphenyl, trifluoromethyl, 1,1,2,2-tetrafluoroethoxymethyl, trifluoromethoxymethyl, chloromethyl, fluoromethyl, difluoromethyl, chlorodifluoromethyl, pentafluoroethyl, 2,2,3,3,3-pentafluoropropyl, heptafluoropropyl, pentafluorophenyl, and pentafluorophenoxymethyl.

[0154] In a preferred embodiment of compounds of Formula VII-2,

[0155] n is the integer 1;

[0156] R₁₆ is hydrido;

[0157] R₁ is selected from the group consisting of trifluoromethyl, 1,1,2,2-tetrafluoroethoxymethyl, trifluoromethoxymethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl;

[0158] R₂ is selected from the group consisting of hydrido, methyl, ethyl, propyl, butyl, vinyl, phenyl, 4-trifluoromethylphenyl, trifluoromethyl, 1,1,2,2-tetrafluoroethoxymethyl, trifluoromethoxymethyl, difluoromethyl, chlorodifluoromethyl, pentafluoroethyl, 2,2,3,3,3-pentafluoropropyl, and heptafluoropropyl;

[0159] R₃ is selected from the group consisting of hydrido, phenyl, 4-trifluoromethylphenyl, methyl, ethyl, vinyl, methoxymethyl, trifluoromethyl, trifluoromethoxymethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl;

[0160] In a even more preferred embodiment of compounds of Formula VII-2,

[0161] n is the integer 1;

[0162] R₁ is selected from the group consisting of trifluoromethyl, 1,1,2,2-tetrafluoroethoxymethyl, trifluoromethoxymethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl;

[0163] R₁₆ is hydrido;

[0164] R₂ is selected from the group consisting of hydrido, methyl, ethyl, phenyl, 4-trifluoromethylphenyl, trifluoromethyl, trifluoromethoxymethyl, 1,1,2,2-tetrafluoroethoxymethyl, difluoromethyl, chlorodifluoromethyl, pentafluoroethyl, 2,2,3,3,3-pentafluoropropyl, and heptafluoropropyl;

[0165] R₃ is selected from the group consisting of hydrido, phenyl, 4-trifluoromethylphenyl, methyl, trifluoromethyl, difluoromethyl, and chlorodifluoromethyl;

[0166] In a most preferred embodiment of compounds of Formula VII-2,

[0167] n is the integer 1;

[0168] R₁ is selected from the group consisting of trifluoromethyl and pentafluoroethyl;

[0169] R₁₆ is hydrido;

[0170] R₂ is selected from the group consisting of hydrido, phenyl, and trifluoromethyl;

[0171] R₃ is selected from the group consisting of hydrido, methyl, trifluoromethyl, and difluoromethyl;

[0172] In another embodiment of compounds of Formula VII, compounds have the Formula Cyclo-VII:

[0173] wherein:

[0174] R₁₆ is taken together with R₄, R₈, R₉ or R₁₃ to form a spacer selected from the group consisting of a covalent single bond and a linear spacer moiety having a chain length of 1 to 4 atoms to form a heterocyclyl ring having from 5 through 10 contiguous members with the proviso that said linear spacer moiety is other than covalent single bond when R₂ is alkyl;

[0175] n is an integer selected from 1 through 3;

[0176] X is selected from the group consisting of O, S, NH, N(alkyl), and N(alkoxy);

[0177] R₁ is selected from the group consisting of haloalkyl, haloalkenyl, haloalkoxyalkyl, and haloalkenyloxyalkyl;

[0178] R₂ is selected from the group consisting of hydrido, hydroxy, hydroxyalkyl, aryl, aralkyl, alkyl, alkenyl, aralkoxyalkyl, aryloxyalkyl, alkoxyalkyl, heteroaryloxyalkyl, alkenyloxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl, heteroaryl, heteroarylalkyl, monocyanoalkyl, and dicyanoalkyl, carboalkoxycyanoalkyl;

[0179] R₃ is selected from the group consisting of hydrido, hydroxy, halo, cyano, hydroxyalkyl, aryl, aralkyl, acyl, alkoxy, alkyl, alkenyl, alkoxyalkyl, aroyl, heteroaroyl, alkenyloxyalkyl, haloalkyl, haloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, monocarboalkoxyalkyl, dicarboalkoxyalkyl, monocyanoalkyl, dicyanoalkyl, carboalkoxycyanoalkyl, carboxamide, and carboxamidoalkyl;

[0180] Y is selected from the group consisting of covalent single bond and (C(R₁₄)₂)_q wherein q is an integer selected from 1 through 2;

[0181] R₁₄ is selected from the group consisting of hydrido, hydroxy, cyano, hydroxyalkyl, acyl, alkoxy, alkyl, alkenyl, alkynyl, alkoxyalkyl, haloalkyl, haloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, monocarboalkoxyalkyl, monocyanoalkyl, dicyanoalkyl, carboalkoxycyanoalkyl, carboalkoxy, carboxamide, carboxamidoalkyl;

[0182] Z is selected from the group consisting of covalent single bond, (C(R₁₅)₂)_q wherein q is an integer selected from 1 through 2, and (CH(R₁₅))_jW(CH(R₁₅))_k wherein j and k are integers independently selected from 0 through 2;

[0183] W is selected from the group consisting of O, C(O), S, S(O), and S(O)₂;

[0184] R₁₅ is selected from the group consisting of hydrido, cyano, hydroxyalkyl, acyl, alkoxy, alkyl, alkenyl, alkynyl, alkoxyalkyl, haloalkyl, haloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, monocarboalkoxyalkyl, monocyanoalkyl, dicyanoalkyl, carboalkoxycyanoalkyl, carboalkoxy, carboxamide, and carboxamidoalkyl;

[0185] R₄, R₈, R₉, and R₁₃ can be independently selected from the group consisting of hydrido, halo, haloalkyl, and alkyl;

[0186] R₅, R₆, R₇, R₁₀, R₁₁, and R₁₂ are independently selected from the group consisting of perhaloaryloxy, alkanoylalkyl, alkanoylalkoxy, alkanoyloxy, N-aryl-N-alkylamino, heterocyclylalkoxy, heterocyclylthio, hydroxyalkoxy, carboxamidoalkoxy, alkoxycarbonylalkoxy, alkoxycarbonylalkenyloxy, aralkanoylalkoxy, aralkenoyl, N-alkylcarboxamido, N-haloalkylcarboxamido, N-cycloalkylcarboxamido, N-arylcarboxamidoalkoxy, cycloalkylcarbonyl, cyanoalkoxy, heterocyclylcarbonyl, hydrido, carboxy, heteroaralkylthio, heteroaralkoxy, cycloalkylamino, acylalkyl, acylalkoxy, aroylalkoxy, heterocyclyloxy, aralkylaryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl, perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl, aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl, cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, heteroarylamino, N-heteroarylamino-N-alkylamino, heteroarylaminoalkyl, haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl, heteroaralkoxy, cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxy, halocycloalkenyloxyalkyl, hydroxy, amino, thio, nitro, lower alkylamino, alkylthio, alkylthioalkyl, arylamino, aralkylamino, arylthio, arylthioalkyl, heteroaralkoxyalkyl, alkylsulfinyl, alkylsulfinylalkyl, arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl, haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, monoarylamidosulfonyl, arylsulfonamido, diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl, arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, heterocyclylsulfonyl, heterocyclylthio, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl, alkenyloxy, alkenyloxyalky, alkylenedioxy, haloalkylenedioxy, cycloalkyl, cycloalkylalkanoyl, cycloalkenyl, lower cycloalkylalkyl, lower cycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, heteroaralkynyl, aryloxy, aralkoxy, aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroaryloxy, heteroaryloxyalkyl, heteroaralkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl, carboalkoxy, alkoxycarboxamido, alkylamidocarbonylamido, arylamidocarbonylamido, carboalkoxyalkyl, carboalkoxyalkenyl, carboaralkoxy, carboxamido, carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono, phosphonoalkyl, diaralkoxyphosphono, and diaralkoxyphosphonoalkyl;

[0187] R₅ and R₆, R₆ and R₇, R₇ and R₈, R₉ and R₁₀, R₁₀ and R₁₁, R₁₁ and R₁₂, and R₁₂ and R₁₃ can be independently selected to form spacer pairs wherein a spacer pair is taken together to form a linear moiety having from 3 through 6 contiguous atoms connecting the points of bonding of said spacer pair members to form a ring selected from the group consisting of a cycloalkenyl ring having 5 through 8 contiguous members, a partially saturated heterocyclyl ring having 5 through 8 contiguous members, a heteroaryl ring having 5 through 6 contiguous members, and an aryl with the provisos that no more than one of the group consisting of spacer pairs R₅ and R₆, R₆ and R₇, and R₇ and R₈, can be used at the same time and that no more than one of the group consisting of spacer pairs R₉ and R₁₀, R₁₀ and R₁₁, R₁₁ and R₁₂, and R₁₂ and R₁₃ can be used at the same time.

[0188] In an embodiment of compounds of Formula Cyclo-VII,

[0189] n is the integer 1;

[0190] X is selected from the group consisting of O, NH, and S;

[0191] R₁₆ is taken together with R₄, R₈, R₉ or R₁₃ to form a spacer selected from the group consisting of a covalent single bond, CH₂, CH(CH₃), CF₂, C(O), C(S), and SO₂;

[0192] R₁ is selected from the group consisting of trifluoromethyl, 1,1,2,2-tetrafluoroethoxymethyl, trifluoromethoxymethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl;

[0193] R₂ is selected from the group consisting of hydrido, phenyl, 4-trifluoromethylphenyl, vinyl, trifluoromethyl, pentafluoroethyl, 1,1,2,2-tetrafluoroethoxymethyl, trifluoromethoxymethyl, difluoromethyl, chlorodifluoromethyl, 2,2,3,3,3-pentafluoropropyl, and heptafluoropropyl;

[0194] R₃ is selected from the group consisting of hydrido, methyl, ethyl, vinyl, phenyl, 4-trifluoromethylphenyl, methoxymethyl, trifluoromethyl, trifluoromethoxymethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl.

[0195] In another embodiment of compounds of Formula Cyclo-VII, compounds have the formula:

[0196] n is the integer 1;

[0197] X is oxy;

[0198] R₁₆ and R₄ are taken together to form a covalent single bond;

[0199] R₁ is selected from the group consisting of trifluoromethyl, 1,1,2,2-tetrafluoroethoxymethyl, trifluoromethoxymethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl;

[0200] R₂ is selected from the group consisting of hydrido, phenyl, 4-trifluoromethylphenyl, vinyl, trifluoromethyl, pentafluoroethyl, 1,1,2,2-tetrafluoroethoxymethyl, trifluoromethoxymethyl, difluoromethyl, chlorodifluoromethyl, 2,2,3,3,3-pentafluoropropyl, and heptafluoropropyl;

[0201] R₃ is selected from the group consisting of hydrido, methyl, ethyl, vinyl, phenyl, 4-trifluoromethylphenyl, methoxymethyl, trifluoromethyl, trifluoromethoxymethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl.

[0202] In another embodiment of compounds of Formula VII, compounds have the Formula VII-3:

[0203] or a pharmaceutically acceptable salt thereof, wherein:

[0204] R₁ is selected from the group consisting of haloalkyl, haloalkenyl, haloalkoxyalkyl and haloalkenyloxyalkyl;

[0205] R₂ is hydroxyalkyl;

[0206] Y is selected from the group consisting of covalent single bond and (C(R₁₄)₂)_q wherein q is an integer selected from 1 through 2;

[0207] R₁₄ is selected from the group consisting of hydrido, cyano, hydroxyalkyl, acyl, alkoxy, alkyl, alkenyl, alkoxyalkyl, haloalkyl, haloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, monocyanoalkyl, dicyanoalkyl, carboxamide, and carboxamidoalkyl;

[0208] Z is selected from the group consisting of covalent single bond, (C(R₁₅)₂)_q wherein q is an integer selected from 1 through 2, and (CH(R₁₅))_jW(CH(R₁₅))_k wherein j and k are integers independently selected from 0 through 2;

[0209] W is oxy;

[0210] R₁₅ is selected from the group consisting of hydrido, cyano, hydroxyalkyl, acyl, alkoxy, alkyl, alkenyl, alkoxyalkyl, haloalkyl, haloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, monocyanoalkyl, dicyanoalkyl, carboxamide, and carboxamidoalkyl;

[0211] R₄, R₈, R₉, and R₁₃ are independently selected from the group consisting of hydrido, halo, haloalkyl, and alkyl;

[0212] R₅, R₆, R₇, R₁₀, R₁₁, and R₁₂ are independently selected from the group consisting of perhaloaryloxy, alkanoylalkyl, alkanoylalkoxy, alkanoyloxy, N-aryl-N-alkylamino, heterocyclylalkoxy, heterocyclylthio, hydroxyalkoxy, carboxamidoalkoxy, alkoxycarbonylalkoxy, alkoxycarbonylalkenyloxy, aralkanoylalkoxy, aralkenoyl, N-alkylcarboxamido, N-haloalkylcarboxamido, N-cycloalkylcarboxamido, N-arylcarboxamidoalkoxy, cycloalkylcarbonyl, cyanoalkoxy, heterocyclylcarbonyl, hydrido, carboxy, heteroaralkylthio, heteroarylsulfonyl, heteroaralkoxy, cycloalkylamino, acylalkyl, acylalkoxy, aroylalkoxy, heterocyclyloxy, aralkylaryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl, haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, cycloalkoxy, cycloalkylalkoxy, hydroxy, amino, thio, nitro, lower alkylamino, alkylthio, arylamino, aralkylamino, arylthio, arylthioalkyl,alkylsulfonyl, alkylsulfonamido, monoarylamidosulfonyl, arylsulfonyl, heteroarylthio, heterocyclylsulfonyl, heterocyclylthio, alkanoyl, alkenoyl, aroyl, alkyl, alkenyl, alkynyl, alkenyloxy, alkylenedioxy, haloalkylenedioxy, cycloalkyl, cycloalkylalkanoyl, halo, haloalkyl, haloalkoxy, hydroxyhaloalkyl, hydroxyalkyl, aryl, aralkyl, aryloxy, aralkoxy, saturated heterocyclyl, heteroaryl, heteroaryloxy, heteroaryloxyalkyl, arylalkyl, heteroarylalkyl, arylalkenyl, carboalkoxy, alkoxycarboxarido, alkylamidocarbonylamido, arylamidocarbonylamido, carboalkoxyalkyl, carboalkoxyalkenyl, carboxamido, carboxamidoalkyl, and cyano;

[0213] R₄ and R₅, R₅ and R₆, R₆ and R₇, R₇ and R₈, R₉ and R₁₀, R₁₀ and R₁₁, R₁₁ and R₁₂, and R₁₂ and R₁₃ spacer pairs can be independently selected from the group consisting of alkylene, alkenylene, alkylenedioxy, aralkylene, diacyl, haloalkylene, and aryldioxylene with the provisos that no more than one of the group consisting of spacer pairs R₄ and R₅, R₅ and R₆, R₆ and R₇, and R₇ and R₈ can be used at the same time and that no more than one of the group consisting of spacer pairs R₉ and R₁₀, R₁₀ and R₁₁, R₁₁ and R₁₂, and R₁₂ and R₁₃ can be used at the same time.

[0214] In an embodiment of compounds of Formula VII-3,

[0215] R₁ is selected from the group consisting of trifluoromethyl, 1,1,2,2-tetrafluoroethoxymethyl, chloromethyl, trifluoromethoxymethyl, fluoromethyl, difluoromethyl, chlorodifluoromethyl, pentafluoroethyl, 2,2,3,3,3-pentafluoropropyl, heptafluoropropyl, and pentafluorophenoxymethyl;

[0216] R₂ is hydroxymethyl, 1-hydroxyethyl, and 1,2-dihydroxyethyl.

[0217] In another embodiment of compounds of Formula VII, compounds have the Formula VII4:

[0218] wherein;

[0219] X is oxy;

[0220] R₁ is selected from the group consisting of haloalkyl and haloalkoxyalkyl;

[0221] R₁₆ is hydrido;

[0222] R₂ and R₃ are taken together to form a linear spacer moiety selected from the group consisting of a covalent single bond and a moiety having from 1 through 6 contiguous atoms to form a ring selected from the group consisting of a cycloalkyl having from 3 through 8 contiguous members, a cycloalkenyl having from 5 through 8 contiguous members, and a heterocyclyl having from 4 through 8 contiguous members;

[0223] Y is selected from the group consisting of a covalent single bond and alkylene;

[0224] Z is selected from the group consisting of a covalent single bond and alkylene;

[0225] R₁₄ is selected from the group consisting of hydrido, alkyl, and haloalkyl;

[0226] R₁₅ is selected from the group consisting of hydrido, alkyl, and haloalkyl;

[0227] R₄, R₈, R₉, and R₁₃ are independently selected from the group consisting of hydrido and halo;

[0228] R₅, R₆, R₇, R₁₀, R₁₁, and R₁₂ are independently selected from the group consisting of perhaloaryloxy, N-aryl-N-alkylamino, heterocyclylalkoxy, heterocyclylthio, hydroxyalkoxy, carboxamidoalkoxy, alkoxycarbonylalkoxy, alkoxycarbonylalkenyloxy, aralkanoylalkoxy, aralkenoyl, N-arylcarboxamidoalkoxy, cycloalkylcarbonyl, cyanoalkoxy, heterocyclylcarbonyl, hydrido, alkyl, halo, haloalkyl, haloalkoxy, aryl, alkylthio, arylamino, arylthio, aroyl, arylsulfonyl, aryloxy, aralkoxy, heteroaryloxy, alkoxy, aralkyl, cycloalkoxy, cycloalkylalkoxy, cycloalkylalkanoyl, heteroaryl, cycloalkyl, haloalkylthio, hydroxyhaloalkyl, heteroaralkoxy, heterocyclyloxy, aralkylaryl, heteroaryloxyalkyl, heteroarylthio, and heteroarylsulfonyl.

[0229] In an embodiment of compounds of Formula VII4,

[0230] X is oxy;

[0231] R₁₆ is hydrido;

[0232] R₁ is selected from the group consisting of trifluoromethyl, 1,1,2,2-tetrafluoroethoxymethyl, trifluoromethoxymethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl;

[0233] R₂ and R₃ spacer pair is selected from the group consisting of CH₂SCH₂, CH₂OCH₂, CH₂CH(R₁₇), CHC(R₁₇), CH₂S(O)₂CH₂, CH₂CH₂CH(R₁₇), CH₂CH(R₁₇)CH₂, CH₂CHC(R₁₇), CH(R₁₇)CHCH, CH₂C(R₁₇)CH, CH(R₁₇)C(O)N(R₁₇), C(O)N(R₁₇)CH(R₁₇), CH(R₁₇)C(O)NHCH₂, CH₂C(O)NHCH(R₁₇), CH(R₁₇)CH(R₁₇)C(O)NH, C(O)NHCH(R₁₇)CH(R₁₇), CH₂CH(R₁₇)CH₂CH₂, CH(R₁₇)CH₂CH₂CH₂, CH₂CHCHCH₂, CHCHCH₂CH₂, CHCHCHCH, CH₂CH₂CH₂CH₂CH₂, CH₂CH₂CHCHCH₂, (CH₂)₂O, (CH₂CHR₁₇)O, (CF₂)₂O, SCH₂CH₂, S(O)CH₂CH₂, CH₂S(O)CH₂, CH₂S(O)CH₂CH₂, S(O)₂CH₂, CH₂N(R₁₇)O, CH₂CH₂C(O), CH₂C(O)NR₁₇, and CH₂NR₁₇CH₂ wherein R₁₇ is selected from the group consisting of H, CH₃, OCH₃, CF₃, CH₂CH₃, F, Cl, CH₂OH, and OH.

[0234] In an embodiment of compounds of Formulas VII-H, VII, VII-2, VII-3, VII-4, and Cyclo-VII,

[0235] Y is selected from the group consisting of a covalent single bond, methylene, 2-fluoroethylidene, ethylidene, 2,2-difluoroethylidene, and 2,2,2-trifluoroethylidene;

[0236] Z is group selected from the group consisting of covalent single bond, oxy, methyleneoxy, methylene, ethylene, ethylidene, 2-fluoroethylidene, 2,2-difluoroethylidene, and 2,2,2-trifluoroethylidene;

[0237] R₄, R₈, R₉, and R₁₃ are independently selected from the group consisting of hydrido and fluoro;

[0238] R₅ and R₁₀ are independently selected from the group consisting of acetoxy, 3-acetamidophenoxy, 3-acetylphenoxy, 4-acetylphenylsulfonyl, amino, 4-acetylphenylthio, acetylthio, 3-aminobenzyloxy, 4-aminobenzyloxy, 4-aminophenoxy, 3-aminophenyl, benzoyl, benzoylamido, benzoylmethoxy, benzyl, N-benzylamidocarbonyl, benzylamino, 3-benzylimidazol-4-ylmethoxy, N-benzyl-N-methylamidocarbonyl, benzyloxy, 4-benzyloxybenzyloxy, 4-benzylphenoxy, 4-benzylpiperidinyl, bromo, 5-bromo-2-fluorophenoxy, 4-bromo-3-fluorophenoxy, bromomethyl, 4-bromo-2-nitrophenoxy, 2-bromobenzyloxy, 3-bromobenzyloxy, 4-bromobenzyloxy, 4-bromophenoxy, 5-bromopyrid-2-yloxy, 4-bromothiophen-3-ylthio, butoxy, 4-butoxyphenoxy, N-butylylcarboxamido, N-butyl-N-methylcarboxamido, N-butyl-4-ethoxycarbonylphenylamino, 4-butylphenoxy, carboxy, carboxamidomethoxy, 3-carboxybenzyloxy, 4-carboxybenzyloxy, 4-carboxyphenyl, 5-carboxypyrid-3-yloxy, chloro, 3-chlorobenzyl, 2-chlorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 2-chlorophenoxy, 4_chlorophenoxy, 4-chloro-3-ethylphenoxy, 3-chloro-4-fluorobenzyl, 3-chloro-4-fluorophenyl, 3-chloro-2-fluorobenzyloxy, 3-chloro-2-hydroxypropoxy, 4-chloro-3-methylphenoxy, 4-chloro-3-methylbenzyl, 2-chloro-4-fluorophenoxy, 4-chlorophenoxy, 3-chloro-4-ethylphenoxy, 3-chloro-4-methylphenoxy, 3-chloro-4-fluorophenoxy, 4-chloro-3-fluorophenoxy, 4-chloro-2-fluorophenoxy, 3-chloro-4-fluorophenylsulfonylamido, 4-chlorophenyl, 3-chlorophenylamino, 4-chlorophenylamino, 5-chlorophenylthiophen-3-ylmethoxy, 5-chloropyrid-3-yloxy, 4-chlorothiophen-2-ylmethylthio, cyano, 3-cyanobenzyloxy, 4-cyanobenzyloxy, 4-(2-cyano-2-ethoxycarbonylacetyl)phenylamino, N-(2-cyanoethyl)-4-methylphenylamino, 2-cyanopyrid-3-yloxy, 4-cyanophenoxy, 4-cyanophenyl, 3-cyanophenylamino, 4-cyanophenylamino, 3-cyanopropoxy, cyclobutoxy, cyclobutyl, cyclohexylamidocarbonyl, cyclohexoxy, cyclohexylmethoxy, cyclopentoxy, cyclopentyl, N-cyclopentylamidocarbonyl, cyclopentylcarbonyl, 4-cyclopentylphenxoy, cyclopropyl, cyclopropylmethoxy, cyclopropoxy, 3,5-dichlorobenzyloxy, 3,5-dichloro-4-methylphenoxy, 2,3-dichlorophenoxy, 2,4-dichlorophenoxy, 3,5-dichlorophenoxy, 2,4-dichlorophenyl, 3,5-dichlorophenyl, 3,5-dichloro-4-methoxyphenyl, 3,5-dichlorobenzyl, 3,4-dichlorophenoxy, 3,4-dichlorophenyl, 3,4-difluorophenoxy, 2,4-difluorobenzyloxy, 2,5-difluorobenzyloxy, 3,5-difluorobenzyloxy, 2,6-difluorobenzyloxy, 3,5-difluorophenoxy, 3,4-difluorophenyl, 4-difluoromethoxybenzyloxy, 2,3-difluorophenoxy, 2,4-difluorophenoxy, 2,3-difluorobenzyloxy, 3,4-difluorobenzyloxy, difluoromethoxy, 2,5-difluorophenoxy, 3,5-difluorophenylamino, 3,5-dimethoxyphenoxy, dimethylamino, N,N-dimethylcarboxamido, 2-(N,N-dimethylamino)ethoxy, 3-dimethylaminophenoxy, 3,4-dimethylbenzyloxy, 3,5-dimethylbenzyloxy, 3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 3,5-dimethyl-4-(N,N-dimethylamino)phenyl, 3,4-dimethoxyphenylamino, 3,4-dimethylbenzyl, 3,4-dimethylbenzyloxy, 1,1-dimethylhydroxymethyl, 3,3-dimethyl-2-oxobutoxy, 2,2-dimethylpropoxy, 1,3-dioxan-2-yl, 1,4-dioxan-2-yl, 1,3-dioxolan-2-yl, ethoxy, ethoxycarbonyl, 3-ethoxycarbonylphenylamino, 4-ethoxycarbonylphenylamino, 1-ethoxycarbonylbutoxy, 4-ethoxyphenoxy, ethyl, 4,4ethylenedioxypiperidinyl, N-ethyl-N-methylcarboxamido, 3-ethylphenoxy, 4-ethylaminophenoxy, 4-ethylbenzyloxy, 3-ethyl-5-methylphenoxy, N-ethyl-3-methylphenylamino, N-ethyl-4-methoxyphenylamino, fluoro, 4-fluorobenzylamino, 4-fluoro-3-methylbenzyl, 2-fluoro-3-methylbenzyloxy, 4-fluoro-3-methylphenyl, 4-fluorobenzoyl, 4-fluoro-3-methylbenzoyl, 3-fluorobenzyloxy, 4-fluorobenzyloxy, 2-fluoro-3-methylphenoxy, 3-fluoro-4-methylphenoxy, 3-fluorophenoxy, 3-fluoro-2-nitrophenoxy, 2-fluoro-3-trifluoromethylbenzyloxy, 4-fluoro-2-trifluoromethylbenzyloxy, 4-fluoro-3-trifluoromethylbenzyloxy, 5-fluoro-3-trifluoromethylbenzyloxy, 2-fluorophenoxy, 4-fluorophenoxy, 2-fluoro-3-trifluoromethylphenoxy, 2-fluorobenzyloxy, 4-fluorophenylamidocarbonylamido, 4-fluorophenylamino, 4-fluorobenzoylamido, 4-fluorobenzylamidocarbonyl, 2-fluoro-4-trifluoromethylphenoxy, 4-fluoro-2-trifluoromethylphenoxy, 2-fluoro-4-chloromethylphenoxy, 4-fluoropyrid-2-yloxy, 2-furyl, 3-furyl, N-(2,2,3,3,4,4,4-heptafluorobutyl)amidocarbonyl, heptafluoropropyl, 1,1,1,3,3,3-hexafluoropropyl, hydrazinocarbonyl, hydrido, hydroxy, 2-hydroxyethoxy, 1-hydroxyisobutyl, 3-hydroxy-2,2-dimethylpropoxy, hydroxymethyl, 3-hydroxymethylphenoxy, 4-hydroxyphenoxy, 3-hydroxypropoxy, 2-hydroxy-3,3,3-trifluoropropoxy, 4-imidazol-1-yl-phenoxy, indol-5-yloxy, iodo, 3-iodobenzyloxy, isobutylamino, isobutoxy, N-isobutoxycarbonylamido, isobutyl, isobutyryl, isobutyrylamido, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, isopropoxy, isopropyl, isopropylamidocarbonyl, isopropylamidocarbonylamido, 4-isopropylbenzyloxy, N-isopropyl-N-methylamino, 3-isopropylphenoxy, 4-isopropylphenoxy, isopropylthio, 4-isopropyl-3-methylphenoxy, isopropylsulfonyl, isopropylsulfonylamido, isoquinolin-3-yloxy, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, methoxy, 3-methoxybenzoylamido, 3-methoxybenzyl, methoxycarbonyl, 4-methoxycarbonylbutoxy, 3-methoxycarbonylbenzyloxy, 4-methoxycarbonylbenzyloxy, 2-methoxyethoxy, 3-methoxycarbonylmethoxy, 3-methoxycarbonylprop-2-enyloxy, methoxymethyl, N-methoxy-N-methylcarboxamido, 3-methoxyphenoxy, 4-methoxyphenoxy, 4-methoxy-3-methylphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 3-methoxyphenylamino, 4-methoxyphenylamino, 3-methoxyphenylamidocarbonylamido, 4-methoxyphenylthio, methyl, N-methyl-4-methoxyphenylamino, 4-methylbenzyl, 3-methylbutyl, 3-methylphenoxy, 4-methylsulfonylphenyl, 3-methyl-4-methylthiophenoxy, 3-methylbenzyloxy, 4-methylbenzyloxy, 2-methyl-3-nitrophenoxy, 2-methyl-5-nitrophenoxy, 4-methylphenoxy, 4-methylphenyl, N-methyl-N-phenylamidocarbonyl, N-methyl -N-propylcarboxamido, 4-(5-(4-methylphenyl)-1,3,4-oxadiazol-2-yl)phenylamino, 3-methylphenylsulfonylamido, 4-methylpiperazin-1-ylcarbonyl, 1-methylpropoxy, 3-methylbut-2-enyloxy, 2-methylpyrid-6-yl, 3-methylpyrid-2-yl, 2-methylpyrid-3-yloxy, 2-methylpyrid-5-yloxy, N-methylpyrrol-2-yl, 4-methylsulfonylphenylsulfonyl, 4-methylsulfonylphenylthio, 4-methylthiophenoxy, 4-methylthiophenyl, 4-methylthiobenzyl, morpholin-4-ylcarbonyl, 2-naphthyloxy, N-neopentylamidocarbonyl, nitro, 3-nitrobenzyl, 3-nitrobenzyloxy, 4-nitrobenzyloxy, 2-nitrophenoxy, 3-nitrophenoxy, 4-nitrophenoxy, 3-nitrophenyl, 4-nitrophenylsulfonyl, 3-nitrophenylsulfonylamido, 4-nitrophenylthio, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 2-oxobutoxy, 5-oxohexoxy, N-oxypyrid-3-ylmethylsulfonyl, 2,3,4,5,6-pentafluorobenzyloxy, pentafluoroethyl, pentafluoroethylthio, 4-(2,3,4,5,6-pentafluorophenyl)-2,3,5,6-tetrafluorophenoxy, 2,2,3,3,3-pentafluoropropyl, 1,1,3,3,3-pentafluoropropyl, 1,1,2,2,3-pentafluoropropyl, phenoxy, 3-phenoxybenzyloxy, phenyl, phenylamidocarbonylamido, 1-(N-phenylcarboxamido)ethoxy, phenylamino, 4-phenylbenzyloxy, 1-phenylethoxy, phenylhydroxymethyl, 3-phenylphenoxy, 4-phenylphenoxy, phenylsulfonyl, phenylsulfonylamido, 2-phenylsulfonylethoxy, phenylthio, 1-piperidinyl, piperidin-4-ylcarbonyl, piperidin-4-ylsulfonyl, piperidin-4-ylthio, hexahydropyran-4-yloxy, 4-propanoyl, 4-propanoylphenoxy, propoxy, 4-propylphenoxy, 4-propylphenylamino, 4-propoxyphenoxy, pyrid-2-yl, pyrid-3-yl, pyrid-3-ylcarboxamido, pyrid-2-ylmethoxy, pyrid-3-ylmethoxy, pyrid-4-fylmethoxy, pyrid-2-yloxy, pyrid-3-yloxy, pyrid-2-ylmethylthio, pyrid-4-ylthio, pyrimid-2-yl, pyrimid-2-yloxy, pyrimid-5-yloxy, pyrrolin-1-ylcarbonyl, 2-(pyrrolidin-1-yl)ethoxy, thiophen-3-yl, sec-butyl, 4-sec-butylphenoxy, tert-butoxy, N-tert-butylamidocarbonyl, 4-tert-butylbenzyl, 4-tert-butylbenzyloxy, 3-tert-butylphenoxy, 4-tert-butylphenoxy, 4-tert-butylphenyl, tetrazol-5-yl, 3-(1,1,2,2-tetrafluoroethoxy)benzylamino, 1,1,2,2-tetrafluoroethoxy, 2,3,5,6-tetrafluoro-4-methoxybenzyloxy, 2,3,5,6-tetrafluoro-4-trifluoromethylbenzyloxy, tetrahydrofuran-2-yl, 2-(5,6,7,8-tetrahydronaphthyloxy), thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, thiol, 4-thiophenoxy, thiophen-2-yl, 2,3,5-trifluorobenzyloxy, 2,4,6-trifluorobenzyloxy, N-(4,4,4-trifluorobutyl)-4-methoxyphenylamino, 2,2,2-trifluoroethoxy, 2,2,2-trifluoroethyl, 3,3,3-trifluoro-2-hydroxypropyl, N-(2,2,2-trifluoroethyl)amidocarbonyl, trifluoromethoxy, 3-trifluoromethoxybenzyloxy, 3-trifluoromethoxybenzylamidocarbonyl, 3-trifluoromethoxybenzylamidocarbonylhydrazinocarbonyl, 4-trifluoromethoxybenzyloxy, 3-trifluoromethoxyphenoxy, 4-trifluoromethoxyphenoxy, 4-trifluoromethoxyphenylamino, trifluoromethyl, 3-trifluoromethylbenzylamine, 3-trifluoromethylbenzyloxy, 4-trifluoromethylbenzyloxy, 2,4-bis-trifluoromethylbenzyloxy, 3,4-bis-trifluoromethylbenzyloxy, 1,1-bis-trifluoromethyl-1-hydroxymethyl, 3,5-bis-trifluoromethylphenyl, 3-trifluoromethylbenzyl, 3,5-bis-trifluoromethylbenzyloxy, 4-trifluoromethylphenoxy, 3-trifluoromethylphenoxy, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 3-trifluoromethylphenylamidocarbonylamido, 4-trifluoromethylphenylamino, 3-trifluoromethylphenylsulfonylamido, 3-trifluoromethylthiobenzyloxy, 4-trifluoromethylthiobenzyloxy, 2,3,4-trifluorophenoxy, 2,3,4-trifluorophenyl, 2,3,5-trifluorophenoxy, 3,4,5-trimethylphenoxy, 3,4,5-trimethoxyphenylamino, 3-trifluoromethylpyrid-2-yl, 3-trifluoromethylpyrid-2-yloxy, 5-trifluoromethylpyrid-2-yloxy, 3-difluoromethoxyphenoxy, 3-pentafluoroethylphenoxy, 3-(1,1,2,2-tetrafluoroethoxy)phenoxy, 3-trifluoromethylthiophenoxy, and trifluoromethylthio;

[0239] R₆ and R₁₁ are independently selected from the group consisting of acetoxy, benzyloxy, bromo, butoxy, butoxycarbonyl, chloro, 4-chlorophenyl, 3,4dichlorophenoxy, cyano, 2-cyanophenyl, difluoromethoxy, ethoxy, fluoro, hydrido, hydroxy, methoxy, methoxycarbonyl, methyl, methylsulfonyl, morpholin-4-yl, nitro, octyl, phenoxy, phenyl, phenylethenyl, phenylethynyl, propoxy, thiophen-2-yl, trifluoromethyl, pentafluoroethyl, 1,1,2,2-tetrafluoroethoxy, and trifluoromethoxy;

[0240] R₇ and R₁₂ are independently selected from the group consisting of benzyloxy, hydrido, fluoro, hydroxy, methoxy, and trifluoromethyl;

[0241] R₅ and R₆ can be taken together to form a spacer group selected from the group consisting of benzylidene, 5-bromobenzylidene, ethylene-1,2-dioxy, tetrafluoroethylene-1,2-dioxy, 1,4butadienyl, methylene-1,1-dioxy, phenoxylidene, and propylene-1,3-dioxy;

[0242] R₆ and R₇ can be taken together to form a spacer group selected from the group consisting of benzylidene, 5-bromobenzylidene, ethylene-1,2-dioxy, tetrafluoroethylene-1,2-dioxy, 1,4-butadienyl, methylene-1,1-dioxy, phenoxylidene, and propylene-1,3-dioxy;

[0243] R₁₀ and R₁₁ can be taken together to form a spacer group selected from the group consisting of benzylidene, ethylene-1,2-dioxy, methylene-1,1-dioxy, phthaloyl, and tetrafluoroethylene-1,2-dioxy;

[0244] R₁₁ and R₁₂ can be taken together to form a spacer group selected from the group consisting of benzylidene, ethylene-1,2-dioxy, methylene-1,1-dioxy, phthaloyl, and tetrafluoroethylene-1,2-dioxy;

[0245] R₁₂ and R₁₃ can be the spacer group 1,4-butadienyl.

[0246] In a preferred embodiment of compounds of Formulas VII-H, VII, VII-2, VII-3, VII4, and Cyclo-VII,

[0247] Y is selected from the group consisting of methylene, ethylene, and ethylidene;

[0248] Z is covalent single bond;

[0249] R₄, R₈, R₉, and R₁₃ are independently selected from the group consisting of hydrido and fluoro;

[0250] R₅ and R₁₀ are independently selected from the group consisting of 4-aminophenoxy, benzoyl, benzyl, benzyloxy, 5-bromo-2-fluorophenoxy, 4-bromo-3-fluorophenoxy, 4-bromo-2-nitrophenoxy, 3-bromobenzyloxy, 4-bromobenzyloxy, 4-bromophenoxy, 5-bromopyrid-2-yloxy, 4-butoxyphenoxy, chloro, 3-chlorobenzyl, 2-chlorophenoxy, 4-chlorophenoxy, 4-chloro-3-ethylphenoxy, 3-chloro-4-fluorobenzyl, 3-chloro-4-fluorophenyl, 3-chloro-2-fluorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 4-chloro-3-methylphenoxy, 2-chloro-4-fluorophenoxy, 4-chloro-2-fluorophenoxy, 4-chlorophenoxy, 3-chloro-4-ethylphenoxy, 3-chloro-4-methylphenoxy, 3-chloro-4-fluorophenoxy, 4-chloro-3-fluorophenoxy, 4-chlorophenylamino, 5-chloropyrid-3-yloxy, 2-cyanopyrid-3-yloxy, 4-cyanophenoxy, cyclobutoxy, cyclobutyl, cyclohexoxy, cyclohexylmethoxy, cyclopentoxy, cyclopentyl, cyclopentylcarbonyl, cyclopropyl, cyclopropylmethoxy, cyclopropoxy, 2,3-dichlorophenoxy, 2,4-dichlorophenoxy, 2,4-dichlorophenyl, 3,5-dichlorophenyl, 3,5-dichlorobenzyl, 3,4-dichlorophenoxy, 3,4-difluorophenoxy, 2,3-difluorobenzyloxy, 2,4-difluorobenzyloxy, 3,4-difluorobenzyloxy, 2,5-difluorobenzyloxy, 3,5-difluorophenoxy, 3,4-difluorophenyl, 3,5-difluorobenzyloxy, 4-difluoromethoxybenzyloxy, 2,3-difluorophenoxy, 2,4-difluorophenoxy, 2,5-difluorophenoxy, 3,5-dimethoxyphenoxy, 3-dimethylaminophenoxy, 3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 3,4-dimethylbenzyl, 3,4-dimethylbenzyloxy, 3,5-dimethylbenzyloxy, 2,2-dimethylpropoxy, 1,3-dioxan-2-yl, 1,4-dioxan-2-yl, 1,3-dioxolan-2-yl, ethoxy, 4-ethoxyphenoxy, 4-ethylbenzyloxy, 3-ethylphenoxy, 4-ethylaminophenoxy, 3-ethyl-5-methylphenoxy, fluoro, 4-fluoro-3-methylbenzyl, 4-fluoro-3-methylphenyl, 4-fluoro-3-methylbenzoyl, 4-fluorobenzyloxy, 2-fluoro-3-methylphenoxy, 3-fluoro-4-methylphenoxy, 3-fluorophenoxy, 3-fluoro-2-nitrophenoxy, 2-fluoro-3-trifluoromethylbenzyloxy, 3-fluoro-5-trifluoromethylbenzyloxy, 4-fluoro-2-trifluoromethylbenzyloxy, 4-fluoro-3-trifluoromethylbenzyloxy, 2-fluorophenoxy, 4-fluorophenoxy, 2-fluoro-3-trifluoromethylphenoxy, 2-fluorobenzyloxy, 4-fluorophenylamino, 2-fluoro-4-trifluoromethylphenoxy, 4-fluoropyrid-2-yloxy, 2-furyl, 3-furyl, heptafluoropropyl, 1,1,1,3,3,3-hexafluoropropyl, 2-hydroxy-3,3,3-trifluoropropoxy, 3-iodobenzyloxy, isobutyl, isobutylamino, isobutoxy, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, isopropoxy, isopropyl, 4-isopropylbenzyloxy, 3-isopropylphenoxy, 4-isopropylphenoxy, isopropylthio, 4-isopropyl-3-methylphenoxy, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 3-methoxybenzyl, 4-methoxycarbonylbutoxy, 3-methoxycarbonylprop-2-enyloxy, 4-methoxyphenyl, 3-methoxyphenylamino, 4-methoxyphenylamino, 3-methylbenzyloxy, 4-methylbenzyloxy, 3-methylphenoxy, 3-methyl-4-methylthiophenoxy, 4-methylphenoxy, 1-methylpropoxy, 2-methylpyrid-5-yloxy, 4-methylthiophenoxy, 2-naphthyloxy, 2-nitrophenoxy, 4-nitrophenoxy, 3-nitrophenyl, 4-nitrophenylthio, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, pentafluoroethyl, pentafluoroethylthio, 2,2,3,3,3-pentafluoropropyl, 1,1,3,3,3-pentafluoropropyl, 1,1,2,2,3-pentafluoropropyl, phenoxy, phenylamino, 1-phenylethoxy, phenylsulfonyl, 4-propanoylphenoxy, propoxy, 4-propylphenoxy, 4-propoxyphenoxy, thiophen-3-yl, sec-butyl, 4-sec-butylphenoxy, tert-butoxy, 3-tert-butylphenoxy, 4-tert-butylphenoxy, 1,1,2,2-tetrafluoroethoxy, tetrahydrofuran-2-yl, 2-(5,6,7,8-tetrahydronaphthyloxy), thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, thiophen-2-yl, 2,3,5-trifluorobenzyloxy, 2,2,2-trifluoroethoxy, 2,2,2-trifluoroethyl, 3,3,3-trifluoro-2-hydroxypropyl, trifluoromethoxy, 3-trifluoromethoxybenzyloxy, 4-trifluoromethoxybenzyloxy, 3-trifluoromethoxyphenoxy, 4-trifluoromethoxyphenoxy, trifluoromethyl, 3-trifluoromethylbenzyloxy, 4-trifluoromethylbenzyloxy, 2,4bis-trifluoromethylbenzyloxy, 1,1-bis-trifluoromethyl-1-hydroxymethyl, 3-trifluoromethylbenzyl, 3,5-bis-trifluoromethylbenzyloxy, 4-trifluoromethylphenoxy, 3-trifluoromethylphenoxy, 3-trifluoromethylphenyl, 3-trifluoromethylthiobenzyloxy, 4-trifluoromethylthiobenzyloxy, 2,3,4-trifluorophenoxy, 2,3,4-trifluorophenyl, 2,3,5-trifluorophenoxy, 3,4,5-trimethylphenoxy, 3-difluoromethoxyphenoxy, 3-pentafluoroethylphenoxy, 3-(1,1,2,2-tetrafluoroethoxy)phenoxy, 3-trifluoromethylthiophenoxy, and trifluoromethylthio;

[0251] R₆ and R₁₁ are independently selected from the group consisting of chloro, fluoro, hydrido, pentafluoroethyl, 1,1,2,2-tetrafluoroethoxy, trifluoromethyl, and trifluoromethoxy;

[0252] R₇ and R₁₂ are independently selected from the group consisting of hydrido, fluoro, and trifluoromethyl.

[0253] In an even more preferred embodiment of compounds of Formulas VII-H, VII, VII-2, VII-3, VII4, and Cyclo-VII,

[0254] Y is methylene;

[0255] Z is covalent single bond;

[0256] R₄, R₈, R₉, and R₁₃ are independently selected from the group consisting of hydrido and fluoro;

[0257] R₅ and R₁₀ are independently selected from the group consisting of benzyloxy, 5-bromo-2-fluorophenoxy, 4-bromo-3-fluorophenoxy, 3-bromobenzyloxy, 4-bromophenoxy,4-butoxyphenoxy, 3-chlorobenzyloxy, 2-chlorophenoxy, 4-chloro-3-ethylphenoxy, 4-chloro-3-methylphenoxy, 2-chloro-4-fluorophenoxy, 4-chloro-2-fluorophenoxy, 4-chlorophenoxy, 3-chloro-4-ethylphenoxy, 3-chloro-4-methylphenoxy, 3-chloro-4-fluorophenoxy, 4-chloro-3-fluorophenoxy, 4-chlorophenylamino, 5-chloropyrid-3-yloxy, cyclobutoxy, cyclobutyl, cyclohexylmethoxy, cyclopentoxy, cyclopentyl, cyclopentylcarbonyl, cyclopropylmethoxy, 2,3-dichlorophenoxy, 2,4-dichlorophenoxy, 2,4-dichlorophenyl, 3,5-dichlorophenyl, 3,5-dichlorobenzyl, 3,4-dichlorophenoxy, 3,4-difluorophenoxy, 2,3-difluorobenzyloxy, 3,5-difluorobenzyloxy, difluoromethoxy, 3,5-difluorophenoxy, 3,4-difluorophenyl, 2,3-difluorophenoxy, 2,4-difluorophenoxy, 2,5-difluorophenoxy, 3,5-dimethoxyphenoxy, 3-dimethylaminophenoxy, 3,4-dimethylbenzyloxy, 3,5-dimethylbenzyloxy, 3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 1,3-dioxolan-2-yl, 3-ethylbenzyloxy, 3-ethylphenoxy, 4-ethylaminophenoxy, 3-ethyl-5-methylphenoxy, 4-fluoro-3-methylbenzyl, 4-fluorobenzyloxy, 2-fluoro-3-methylphenoxy, 3-fluoro-methylphenoxy, 3-fluorophenoxy, 3-fluoro-2-nitrophenoxy, 2-fluoro-3-trifluoromethylbenzyloxy, 3-fluoro-5-trifluoromethylbenzyloxy, 2-fluorophenoxy, 4-fluorophenoxy, 2-fluoro-3-trifluoromethylphenoxy, 2-fluorobenzyloxy, 4-fluorophenylamino, 2-fluoro-trifluoromethylphenoxy, 2-furyl, 3-furyl, heptafluoropropyl, 1,1,1,3,3,3-hexafluoropropyl, 2-hydroxy-3,3,3-trifluoropropoxy, isobutoxy, isobutyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, isopropoxy, 3-isopropylbenzyloxy, 3-isopropylphenoxy, isopropylthio, 4-isopropyl-3-methylphenoxy, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 3-methoxybenzyl, 4-methoxyphenylamino, 3-methylbenzyloxy, 4-methylbenzyloxy, 3-methylphenoxy, 3-methyl-4-methylthiophenoxy, 4-methylphenoxy, 1-methylpropoxy, 2-methylpyrid-5-yloxy, 4-methylthiophenoxy, 2-naphthyloxy, 2-nitrophenoxy, 4-nitrophenoxy, 3-nitrophenyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, pentafluoroethyl, pentafluoroethylthio, 2,2,3,3,3-pentafluoropropyl, 1,1,3,3,3-pentafluoropropyl, 1,1,2,2,3-pentafluoropropyl, phenoxy, phenylamino, 1-phenylethoxy, 4-propylphenoxy, 4-propoxyphenoxy, thiophen-3-yl,tert-butoxy, 3-tert-butylphenoxy, 4-tert-butylphenoxy, 1,1,2,2-tetrafluoroethoxy, tetrahydrofuran-2-yl, 2-(5,6,7,8-tetrahydronaphthyloxy), thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, thiophen-2-yl, 2,2,2-trifluoroethoxy, 2,2,2-trifluoroethyl, 3,3,3-trifluoro-2-hydroxypropyl, trifluoromethoxy, 3-trifluoromethoxybenzyloxy, 4-trifluoromethoxybenzyloxy, 4-trifluoromethoxyphenoxy, 3-trifluoromethoxyphenoxy, trifluoromethyl, 3-trifluoromethylbenzyloxy, 1,1-bis-trifluoromethyl-1-hydroxymethyl, 3-trifluoromethylbenzyl, 3,5-bis-trifluoromethylbenzyloxy, 4-trifluoromethylphenoxy, 3-trifluoromethylphenoxy, 3-trifluoromethylphenyl, 2,3,4-trifluorophenoxy, 2,3,5-trifluorophenoxy, 3,4,5-trimethylphenoxy, 3-difluoromethoxyphenoxy, 3-pentafluoroethylphenoxy, 3-(1,1,2,2-tetrafluoroethoxy)phenoxy, 3-trifluoromethylthiophenoxy, 3-trifluoromethylthiobenzyloxy, and trifluoromethylthio;

[0258] R₆ and R₁₁ are independently selected from the group consisting of chloro, fluoro, hydrido, pentafluoroethyl, 1,1,2,2-tetrafluoroethoxy, and trifluoromethyl;

[0259] R₇ and R₁₂ are independently selected from the group consisting of hydrido, fluoro, and trifluoromethyl.

[0260] In a most preferred embodiment of compounds of Formulas VII-H, VII, VII-2, VII-3, VII4, and Cyclo-VII,

[0261] Y is methylene;

[0262] Z is covalent single bond;

[0263] R₄, R₈, R₉, and R₁₃ are independently selected from the group consisting of hydrido and fluoro;

[0264] R₅ is selected from the group consisting of 5-bromo-2-fluorophenoxy, 4-chloro-3-ethylphenoxy, 2,3-dichlorophenoxy, 3,4-dichlorophenoxy, 3-difluoromethoxyphenoxy, 3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 3-ethylphenoxy, 3-ethyl-5-methylphenoxy, 4-fluoro-3-methylphenoxy, 4-fluorophenoxy, 3-isopropylphenoxy, 3-methylphenoxy, 3-pentafluoroethylphenoxy, 3-tert-butylphenoxy, 3-(1,1,2,2-tetrafluoroethoxy)phenoxy, 2-(5,6,7,8-tetrahydronaphthyloxy), 3-trifluoromethoxybenzyloxy,3-trifluoromethoxyphenoxy, 3-trifluoromethylbenzyloxy, and 3-trifluoromethylthiophenoxy;

[0265] R₁₀ is selected from the group consisting of cyclopentyl, 1,1,2,2-tetrafluoroethoxy, 2-furyl, 1,1-bis-trifluoromethyl-1-hydroxymethyl, pentafluoroethyl, trifluoromethoxy, trifluoromethyl, and trifluoromethylthio;

[0266] R₆ and R₁₁ are independently selected from the group consisting of fluoro and hydrido;

[0267] R₇ and R₁₂ are independently selected from the group consisting of hydrido and fluoro.

[0268] The use of generic terms in the description of the compounds are herein defined for clarity.

[0269] Standard single letter elemental symbols are used to represent specific types of atoms unless otherwise defined. The symbol C represents a carbon atom. The symbol O represents an oxygen atom. The symbol N represents a nitrogen atom. The symbol P represents a phosphorus atom. The symbol S represents a sulfur atom. The symbol H represents a hydrogen atom. Double letter elemental symbols are used as defined for the elements of the periodical table (i.e., Cl represents chlorine, Se represents selenium, etc.).

[0270] As utilized herein, the term alkyl, either alone or within other terms such as haloalkyl and alkylthio, means an acyclic alkyl radical containing from 1 to about 10, preferably from 1 to about 8 carbon atoms and more preferably 1 to about 6 carbon atoms. Said alkyl radicals may be optionally substituted with groups as defined below. Examples of such radicals include methyl, ethyl, chloroethyl, hydroxyethyl, n-propyl, oxopropyl, isopropyl, n-butyl, cyanobutyl, isobutyl, sec-butyl, tert-butyl, pentyl, aminopentyl, iso-amyl, hexyl, octyl and the like.

[0271] The term alkenyl refers to an unsaturated, acyclic hydrocarbon radical in so much as it contains at least one double bond. Such alkenyl radicals contain from about 2 to about 10 carbon atoms, preferably from about 2 to about 8 carbon atoms and more preferably 2 to about 6 carbon atoms. Said alkenyl radicals may be optionally substituted with groups as defined below. Examples of suitable alkenyl radicals include propenyl, 2-chloropropenyl, buten-1-yl, isobutenyl, penten-1-yl, 2-2-methylbuten-1-yl, 3-methylbuten-1-yl, hexen-1-yl, 3-hydroxyhexen-1-yl, hepten-1-yl, and octen-1-yl, and the like.

[0272] The term alkynyl refers to an unsaturated, acyclic hydrocarbon radical in so much as it contains one or more triple bonds, such radicals containing about 2 to about 10 carbon atoms, preferably having from about 2 to about 8 carbon atoms and more preferably having 2 to about 6 carbon atoms. Said alkynyl radicals may be optionally substituted with groups as defined below. Examples of suitable alkynyl radicals include ethynyl, propynyl, hydroxypropynyl, butyn-1-yl, butyn-2-yl, pentyn-1-yl, pentyn-2-yl, 4-methoxypentyn-2-yl, 3-methylbutyn-1-yl, hexyn-1-yl, hexyn-2-yl, hexyn-3-yl, 3,3-dimethylbutyn-1-yl radicals and the like.

[0273] The term hydrido denotes a single hydrogen atom (H). This hydrido radical may be attached, for example, to an oxygen atom to form a hydroxyl radical, one hydrido radical may be attached to a carbon atom to form a methine radical (CH), or two hydrido radicals may be attached to a carbon atom to form a methylene (CH₂) radical.

[0274] The term carbon radical denotes a carbon atom without any covalent bonds and capable of forming four covalent bonds.

[0275] The term cyano radical denotes a carbon radical having three of four covalent bonds shared by a nitrogen atom.

[0276] The term hydroxyalkyl embraces radicals wherein any one or more of the alkyl carbon atoms is substituted with a hydroxyl as defined above. Specifically embraced are monohydroxyalkyl, dihydroxyalkyl and polyhydroxyalkyl radicals.

[0277] The term alkanoyl embraces radicals wherein one or more of the terminal alkyl carbon atoms are substituted with one or more carbonyl radicals as defined below. Specifically embraced are monocarbonylalkyl and dicarbonylalkyl radicals. Examples of monocarbonylalkyl radicals include formyl, acetyl, and pentanoyl. Examples of dicarbonylalkyl radicals include oxalyl, malonyl, and succinyl.

[0278] The term alkylene radical denotes linear or branched radicals having from 1 to about 10 carbon atoms and having attachment points for two or more covalent bonds. Examples of such radicals are methylene, ethylene, ethylidene, methylethylene, and isopropylidene.

[0279] The term alkenylene radical denotes linear or branched radicals having from 2 to about 10 carbon atoms, at least one double bond, and having attachment points for two or more covalent bonds. Examples of such radicals are 1,1-vinylidene (CH₂C), 1,2-vinylidene (CHCH), and 1,4-butadienyl (CHCHCHCH).

[0280] The term halo means halogens such as fluorine, chlorine, bromine or iodine atoms.

[0281] The term haloalkyl embraces radicals wherein any one or more of the alkyl carbon atoms is substituted with halo as defined above. Specifically embraced are monohaloalkyl, dihaloalkyl and polyhaloalkyl radicals. A monohaloalkyl radical, for one example, may have either a bromo, chloro or a fluoro atom within the radical. Dihalo radicals may have two or more of the same halo atoms or a combination of different halo radicals and polyhaloalkyl radicals may have more than two of the same halo atoms or a combination of different halo radicals. More preferred haloalkyl radicals are lower haloalkyl radicals having one to about six carbon atoms. Examples of such haloalkyl radicals include fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, trifluoroethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl and dichloropropyl.

[0282] The term hydroxyhaloalkyl embraces radicals wherein any one or more of the haloalkyl carbon atoms is substituted with hydroxy as defined above. Examples of hydroxyhaloalkyl radicals include hexafluorohydoxypropyl.

[0283] The term haloalkylene radical denotes alkylene radicals wherein any one or more of the alkylene carbon atoms is substituted with halo as defined above. Dihalo alkylene radicals may have two or more of the same halo atoms or a combination of different halo radicals and polyhaloalkylene radicals may have more than two of the same halo atoms or a combination of different halo radicals. More preferred haloalkylene radicals are lower haloalkylene radicals having one to about six carbon atoms. Examples of haloalkylene radicals include difluoromethylene, tetrafluoroethylene, tetrachloroethylene, alkyl substituted monofluoromethylene, and aryl substituted trifluoromethylene.

[0284] The term haloalkenyl denotes linear or branched radicals having from 1 to about 10 carbon atoms and having one or more double bonds wherein any one or more of the alkenyl carbon atoms is substituted with halo as defined above. Dihaloalkenyl radicals may have two or more of the same halo atoms or a combination of different halo radicals and polyhaloalkenyl radicals may have more than two of the same halo atoms or a combination of different halo radicals.

[0285] The terms alkoxy and alkoxyalkyl embrace linear or branched oxy-containing radicals each having alkyl portions of one to about ten carbon atoms, such as methoxy radical. The term alkoxyalkyl also embraces alkyl radicals having one or more alkoxy radicals attached to the alkyl radical, that is, to form monoalkoxyalkyl and dialkoxyalkyl radicals. More preferred alkoxy radicals are lower alkoxy radicals having one to six carbon atoms. Examples of such radicals include methoxy, ethoxy, propoxy, butoxy, isopropoxy and tert-butoxy alkyls. The alkoxy radicals may be further substituted with one or more halo atoms, such as fluoro, chloro or bromo, to provide haloalkoxy and haloalkoxyalkyl radicals. Examples of such haloalkoxy radicals include fluoromethoxy, chloromethoxy, trifluoromethoxy, difluoromethoxy, trifluoroethoxy, fluoroethoxy, tetrafluoroethoxy, pentafluoroethoxy, and fluoropropoxy. Examples of such haloalkoxyalkyl radicals include fluoromethoxymethyl, chloromethoxyethyl, trifluoromethoxymethyl, difluoromethoxyethyl, and trifluoroethoxymethyl.

[0286] The terms alkenyloxy and alkenyloxyalkyl embrace linear or branched oxy-containing radicals each having alkenyl portions of two to about ten carbon atoms, such as ethenyloxy or propenyloxy radical. The term alkenyloxyalkyl also embraces alkenyl radicals having one or more alkenyloxy radicals attached to the alkyl radical, that is, to form monoalkenyloxyalkyl and dialkenyloxyalkyl radicals. More preferred alkenyloxy radicals are lower alkenyloxy radicals having two to six carbon atoms. Examples of such radicals include ethenyloxy, propenyloxy, butenyloxy, and isopropenyloxy alkyls. The alkenyloxy radicals may be further substituted with one or more halo atoms, such as fluoro, chloro or bromo, to provide haloalkenyloxy radicals. Examples of such radicals include trifluoroethenyloxy, fluoroethenyloxy, difluoroethenyhloxy, and fluoropropenyloxy.

[0287] The term haloalkoxyalkyl also embraces alkyl radicals having one or more haloalkoxy radicals attached to the alkyl radical, that is, to form monohaloalkoxyalkyl and dihaloalkoxyalkyl radicals. The term haloalkenyloxy also embraces oxygen radicals having one or more haloalkenyloxy radicals attached to the oxygen radical, that is, to form monohaloalkenyloxy and dihaloalkenyloxy radicals. The term haloalkenyloxyalkyl also embraces alkyl radicals having one or more haloalkenyloxy radicals attached to the alkyl radical, that is, to form monohaloalkenyloxyalkyl and dihaloalkenyloxyalkyl radicals.

[0288] The term alkylenedioxy radicals denotes alkylene radicals having at least two oxygens bonded to a single alkylene group. Examples of alkylenedioxy radicals include methylenedioxy, ethylenedioxy, alkylsubstituted methylenedioxy, and arylsubstituted methylenedioxy. The term haloalkylenedioxy radicals denotes haloalkylene radicals having at least two oxy groups bonded to a single haloalkyl group. Examples of haloalkylenedioxy radicals include difluoromethylenedioxy, tetrafluoroethylenedioxy, tetrachloroethylenedioxy, alkylsubstituted monofluoromethylenedioxy, and arylsubstituted monofluoromethylenedioxy.

[0289] The term aryl, alone or in combination, means a carbocyclic aromatic system containing one, two or three rings wherein such rings may be attached together in a pendant manner or may be fused. The term fused means that a second ring is present (ie, attached or formed) by having two adjacent atoms in common (ie, shared) with the first ring. The term fused is equivalent to the term condensed. The term aryl embraces aromatic radicals such as phenyl, naphthyl, tetrahydronaphthyl, indane and biphenyl.

[0290] The term perhaloaryl embraces aromatic radicals such as phenyl, naphthyl, tetrahydronaphthyl, indane and biphenyl wherein the aryl radical is substituted with 3 or more halo radicals as defined below.

[0291] The term heterocyclyl embraces saturated, partially saturated and unsaturated heteroatom-containing ring-shaped radicals having from 5 through 15 ring members selected from carbon, nitrogen, sulfur and oxygen, wherein at least one ring atom is a heteroatom. Heterocyclyl radicals may contain one, two or three rings wherein such rings may be attached in a pendant manner or may be fused. Examples of saturated heterocyclic radicals include saturated 3 to 6-membered heteromonocylic group containing 1 to 4 nitrogen atoms e.g. pyrrolidinyl, imidazolidinyl, piperidino, piperazinyl, etc.; saturated 3 to 6-membered heteromonocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms e.g. morpholinyl, etc.; saturated 3 to 6-membered heteromonocyclic group containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms e.g., thiazolidinyl, etc.. Examples of partially saturated heterocyclyl radicals include dihydrothiophene, dihydropyran, dihydrofuran and dihydrothiazole. Examples of unsaturated heterocyclic radicals, also termed heteroaryl radicals, include unsaturated 5 to 6 membered heteromonocyclyl group containing 1 to 4 nitrogen atoms, for example, pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, triazolyl e.g., 4H-1,2,4-triazolyl, 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, etc. tetrazolyl e.g. 1H-tetrazolyl, 2H-tetrazolyl, etc., etc.; unsaturated condensed heterocyclic group containing 1 to 5 nitrogen atoms, for example, indolyl, isoindolyl, indolizinyl, benzimidazolyl, quinolyl, isoquinolyl, indazolyl, benzotriazolyl, tetrazolopyridazinyl e.g., tetrazolo 1,5-bpyridazinyl, etc., etc.; unsaturated 3 to 6-membered heteromonocyclic group containing an oxygen atom, for example, pyranyl, 2-furyl, 3-furyl, etc.; unsaturated 5 to 6-membered heteromonocyclic group containing a sulfur atom, for example, 2-thienyl, 3-thienyl, etc.; unsaturated 5- to 6-membered heteromonocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, for example, oxazolyl, isoxazolyl, oxadiazolyl e.g., 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,5-oxadiazolyl, etc. etc.; unsaturated condensed heterocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms e.g. benzoxazolyl, benzoxadiazolyl, etc.; unsaturated 5 to 6membered heteromonocyclic group containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms, for example, thiazolyl, thiadiazolyl e.g., 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,5-thiadiazolyl, etc. etc.; unsaturated condensed heterocyclic group containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms e.g., benzothiazolyl, benzothiadiazolyl, etc. and the like. The term also embraces radicals where heterocyclic radicals are fused with aryl radicals. Examples of such fused bicyclic radicals include benzofuran, benzothiophene, and the like. Said heterocyclyl group may have 1 to 3 substituents as defined below. Preferred heterocyclic radicals include five to twelve membered fused or unfused radicals. Non-limiting examples of heterocyclic radicals include pyrrolyl, pyridinyl, pyridyloxy, pyrazolyl, triazolyl, pyrimidinyl, pyridazinyl, oxazolyl, thiazolyl, imidazolyl, indolyl, thiophenyl, furanyl, tetrazolyl, 2-pyrrolinyl, 3-pyrrolinyl, pyrrolindinyl, 1,3-dioxolanyl, 2-imidazolinyl, imidazolidinyl, 2-pyrazolinyl, pyrazolidinyl, isoxazolyl, isothiazolyl, 1,2,3-oxadiazolyl, 1,2,3-triazolyl, 1,3,4-thiadiazolyl, 2H-pyranyl, 4H-pyranyl, piperidinyl, 1,4-dioxanyl, morpholinyl, 1,4-dithianyl, thiomorpholinyl, pyrazinyl, piperazinyl, 1,3,5-triazinyl, 1,3,5-trithianyl, benzo(b)thiophenyl, benzimidazoyl, quinolinyl, tetraazolyl, and the like.

[0292] The term sulfonyl, whether used alone or linked to other terms such as alkylsulfonyl, denotes respectively divalent radicals SO₂. Alkylsulfonyl, embraces alkyl radicals attached to a sulfonyl radical, where alkyl is defined as above. Alkylsulfonylalkyl, embraces alkylsulfonyl radicals attached to an alkyl radical, where alkyl is defined as above. Haloalkylsulfonyl, embraces haloalkyl radicals attached to a sulfonyl radical, where haloalkyl is defined as above. Haloalkylsulfonylalkyl, embraces haloalkylsulfonyl radicals attached to an alkyl radical, where alkyl is defined as above. The term aminosulfonyl denotes an amino radical attached to a sulfonyl radical.

[0293] The term sulfinyl, whether used alone or linked to other terms such as alkylsulfinyl, denotes respectively divalent radicals S(O). Alkylsulfinyl, embraces alkyl radicals attached to a sulfinyl radical, where alkyl is defined as above. Alkylsulfinylalkyl, embraces alkylsulfinyl radicals attached to an alkyl radical, where alkyl is defined as above. Haloalkylsulfinyl, embraces haloalkyl radicals attached to a sulfinyl radical, where haloalkyl is defined as above. Haloalkylsulfinylalkyl, embraces haloalkylsulfinyl radicals attached to an alkyl radical, where alkyl is defined as above.

[0294] The term aralkyl embraces aryl-substituted alkyl radicals. Preferable aralkyl radicals are lower aralkyl radicals having aryl radicals attached to alkyl radicals having one to six carbon atoms. Examples of such radicals include benzyl, diphenylmethyl, triphenylmethyl, phenylethyl and diphenylethyl. The terms benzyl and phenylmethyl are interchangeable.

[0295] The term heteroaralkyl embraces heteroaryl-substituted alkyl radicals wherein the heteroaralkyl radical may be additionally substituted with three or more substituents as defined above for aralkyl radicals. The term perhaloaralkyl embraces aryl-substituted alkyl radicals wherein the aralkyl radical is substituted with three or more halo radicals as defined above.

[0296] The term aralkylsulfinyl, embraces aralkyl radicals attached to a sulfinyl radical, where aralkyl is defined as above. Aralkylsulfinylalkyl, embraces aralkylsulfinyl radicals attached to an alkyl radical, where alkyl is defined as above.

[0297] The term aralkylsulfonyl, embraces aralkyl radicals attached to a sulfonyl radical, where aralkyl is defined as above. Aralkylsulfonylalkyl, embraces aralkylsulfonyl radicals attached to an alkyl radical, where alkyl is defined as above.

[0298] The term cycloalkyl embraces radicals having three to ten carbon atoms. More preferred cycloalkyl radicals are lower cycloalkyl radicals having three to seven carbon atoms. Examples include radicals such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl. The term cycloalkylalkyl embraces cycloalkyl-substituted alkyl radicals. Preferable cycloalkylalkyl radicals are lower cycloalkylalkyl radicals having cycloalkyl radicals attached to alkyl radicals having one to six carbon atoms. Examples of such radicals include cyclohexylhexyl. The term cycloalkenyl embraces radicals having three to ten carbon atoms and one or more carbon-carbon double bonds. Preferred cycloalkenyl radicals are lower cycloalkenyl radicals having three to seven carbon atoms. Examples include radicals such as cyclobutenyl, cyclopentenyl, cyclohexenyl and cycloheptenyl. The term halocycloalkyl embraces radicals wherein any one or more of the cycloalkyl carbon atoms is substituted with halo as defined above. Specifically embraced are monohalocycloalkyl, dihalocycloalkyl and polyhalocycloalkyl radicals. A monohalocycloalkyl radical, for one example, may have either a bromo, chloro or a fluoro atom within the radical. Dihalo radicals may have two or more of the same halo atoms or a combination of different halo radicals and polyhalocycloalkyl radicals may have more than two of the same halo atoms or a combination of different halo radicals. More preferred halocycloalkyl radicals are lower halocycloalkyl radicals having three to about eight carbon atoms. Examples of such halocycloalkyl radicals include fluorocyclopropyl, difluorocyclobutyl, trifluorocyclopentyl, tetrafluorocyclohexyl, and dichlorocyclopropyl. The term halocycloalkenyl embraces radicals wherein any one or more of the cycloalkenyl carbon atoms is substituted with halo as defined above. Specifically embraced are monohalocycloalkenyl, dihalocycloalkenyl and polyhalocycloalkenyl radicals.

[0299] The term cycloalkoxy embraces cycloalkyl radicals attached to an oxy radical. Examples of such radicals includes cyclohexoxy and cyclopentoxy. The term cycloalkoxyalkyl also embraces alkyl radicals having one or more cycloalkoxy radicals attached to the alkyl radical, that is, to form monocycloalkoxyalkyl and dicycloalkoxyalkyl radicals. Examples of such radicals include cyclohexoxyethyl. The cycloalkoxy radicals may be further substituted with one or more halo atoms, such as fluoro, chloro or bromo, to provide halocycloalkoxy and halocycloalkoxyalkyl radicals.

[0300] The term cycloalkylalkoxy embraces cycloalkyl radicals attached to an alkoxy radical. Examples of such radicals includes cyclohexylmethoxy and cyclopentylmethoxy.

[0301] The term cycloalkenyloxy embraces cycloalkenyl radicals attached to an oxy radical. Examples of such radicals includes cyclohexenyloxy and cyclopentenyloxy. The term cycloalkenyloxyalkyl also embraces alkyl radicals having one or more cycloalkenyloxy radicals attached to the alkyl radical, that is, to form monocycloalkenyloxyalkyl and dicycloalkenyloxyalkyl radicals. Examples of such radicals include cyclohexenyloxyethyl. The cycloalkenyloxy radicals may be further substituted with one or more halo atoms, such as fluoro, chloro or bromo, to provide halocycloalkenyloxy and halocycloalkenyloxyalkyl radicals.

[0302] The term cycloalkylenedioxy radicals denotes cycloalkylene radicals having at least two oxygens bonded to a single cycloalkylene group. Examples of alkylenedioxy radicals include 1,2-dioxycyclohexylene.

[0303] The term cycloalkylsulfinyl, embraces cycloalkyl radicals attached to a sulfinyl radical, where cycloalkyl is defined as above. Cycloalkylsulfinylalkyl, embraces cycloalkylsulfinyl radicals attached to an alkyl radical, where alkyl is defined as above. The term Cycloalkylsulfonyl, embraces cycloalkyl radicals attached to a sulfonyl radical, where cycloalkyl is defined as above. Cycloalkylsulfonylalkyl, embraces cycloalkylsulfonyl radicals attached to an alkyl radical, where alkyl is defined as above.

[0304] The term cycloalkylalkanoyl embraces radicals wherein one or more of the cycloalkyl carbon atoms are substituted with one or more carbonyl radicals as defined below. Specifically embraced are monocarbonylcycloalkyl and dicarbonylcycloalkyl radicals. Examples of monocarbonylcycloalkyl radicals include cyclohexylcarbonyl, cyclohexylacetyl, and cyclopentylcarbonyl. Examples of dicarbonylcycloalkyl radicals include 1,2-dicarbonylcyclohexane.

[0305] The term alkylthio embraces radicals containing a linear or branched alkyl radical, of one to ten carbon atoms, attached to a divalent sulfur atom. More preferred alkylthio radicals are lower alkylthio radicals having one to six carbon atoms. An example of lower alkylthio is methylthio (CH₃S). The alkylthio radicals may be further substituted with one or more halo atoms, such as fluoro, chloro or bromo, to provide haloalkylthio radicals. Examples of such radicals include fluoromethylthio, chloromethylthio, trifluoromethylthio, difluoromethylthio, trifluoroethylthio, fluoroethylthio, tetrafluoroethylthio, pentafluoroethylthio, and fluoropropylthio.

[0306] The term alkyl aryl amino embraces radicals containing a linear or branched alkyl radical, of one to ten carbon atoms, and one aryl radical both attached to an amino radical. Examples include N-methylmethoxyaniline, N-ethyl-4-methoxyaniline, and N-methyl-4-trifluoromethoxyaniline.

[0307] The terms alkylamino denotes monoalkylamino and dialkylamino containing one or two alkyl radicals, respectively, attached to an amino radical.

[0308] The terms arylamino denotes monoarylamino and diarylamino containing one or two aryl radicals, respectively, attached to an amino radical. Examples of such radicals include N-phenylamino and N-naphthylamino.

[0309] The term aralkylamino, embraces aralkyl radicals attached to an amino radical, where aralkyl is defined as above. The term aralkylamino denotes monoaralkylamino and diaralkylamino containing one or two aralkyl radicals, respectively, attached to an amino radical. The term aralkylamino further denotes monoaralkyl monoalkylamino containing one aralkyl radical and one alkyl radical attached to an amino radical.

[0310] The term arylsulfinyl embraces radicals containing an aryl radical, as defined above, attached to a divalent S(O) atom. The term arylsulfinylalkyl denotes arylsulfinyl radicals attached to a linear or branched alkyl radical, of one to ten carbon atoms.

[0311] The term arylsulfonyl, embraces aryl radicals attached to a sulfonyl radical, where aryl is defined as above. arylsulfonylalkyl, embraces arylsulfonyl radicals attached to an alkyl radical, where alkyl is defined as above. The term heteroarylsulfinyl embraces radicals containing an heteroaryl radical, as defined above, attached to a divalent S(O) atom. The term heteroarylsulfinylalkyl denotes heteroarylsulfinyl radicals attached to a linear or branched alkyl radical, of one to ten carbon atoms. The term Heteroarylsulfonyl, embraces heteroaryl radicals attached to a sulfonyl radical, where heteroaryl is defined as above. Heteroarylsulfonylalkyl, embraces heteroarylsulfonyl radicals attached to an alkyl radical, where alkyl is defined as above.

[0312] The term aryloxy embraces aryl radicals, as defined above, attached to an oxygen atom. Examples of such radicals include phenoxy, 4-chloro-3-ethylphenoxy, 4-chloro-3-methylphenoxy, 3-chloro-4-ethylphenoxy, 3,4-dichlorophenoxy, 4-methylphenoxy, 3-trifluoromethoxyphenoxy, 3-trifluoromethylphenoxy, 4-fluorophenoxy, 3,4-dimethylphenoxy, 5-bromo-2-fluorophenoxy, 4-bromo-3-fluorophenoxy, 4-fluoro-3-methylphenoxy, 5,6,7,8-tetrahydronaphthyloxy, 3-isopropylphenoxy, 3-cyclopropylphenoxy, 3-ethylphenoxy, 4-tert-butylphenoxy, 3-pentafluoroethylphenoxy, and 3-(1,1,2,2-tetrafluoroethoxy)phenoxy.

[0313] The term aroyl embraces aryl radicals, as defined above, attached to an carbonyl radical as defined above. Examples of such radicals include benzoyl and toluoyl.

[0314] The term aralkanoyl embraces aralkyl radicals, as defined herein, attached to an carbonyl radical as defined above. Examples of such radicals include, for example, phenylacetyl.

[0315] The term aralkoxy embraces oxy-containing aralkyl radicals attached through an oxygen atom to other radicals. More preferred aralkoxy radicals are lower aralkoxy radicals having phenyl radicals attached to lower alkoxy radical as described above. Examples of such radicals include benzyloxy, 1-phenylethoxy, 3-trifluoromethoxybenzyloxy, 3-trifluoromethylbenzyloxy, 3,5-difluorobenyloxy, 3-bromobenzyloxy, 4-propylbenzyloxy, 2-fluoro-3-trifluoromethylbenzyloxy, and 2-phenylethoxy.

[0316] The term aryloxyalkyl embraces aryloxy radicals, as defined above, attached to an alkyl group. Examples of such radicals include phenoxymethyl.

[0317] The term haloaryloxyalkyl embraces aryloxyalkyl radicals, as defined above, wherein one to five halo radicals are attached to an aryloxy group.

[0318] The term heteroaroyl embraces heteroaryl radicals, as defined above, attached to an carbonyl radical as defined above. Examples of such radicals include furoyl and nicotinyl.

[0319] The term heteroaralkanoyl embraces heteroaralkyl radicals, as defined herein, attached to an carbonyl radical as defined above. Examples of such radicals include, for example, pyridylacetyl and furylbutyryl.

[0320] The term heteroaralkoxy embraces oxy-containing heteroaralkyl radicals attached through an oxygen atom to other radicals. More preferred heteroaralkoxy radicals are lower heteroaralkoxy radicals having heteroaryl radicals attached to lower alkoxy radical as described above.

[0321] The term haloheteroaryloxyalkyl embraces heteroaryloxyalkyl radicals, as defined above, wherein one to four halo radicals are attached to an heteroaryloxy group.

[0322] The term heteroarylamino embraces heterocyclyl radicals, as defined above, attached to an amino group. Examples of such radicals include pyridylamino.

[0323] The term heteroarylaminoalkyl embraces heteroarylamino radicals, as defined above, attached to an alkyl group. Examples of such radicals include pyridylmethylamino.

[0324] The term heteroaryloxy embraces heterocyclyl radicals, as defined above, attached to an oxy group. Examples of such radicals include 2-thiophenyloxy, 2-pyrimidyloxy, 2-pyridyloxy, 3-pyridyloxy, and 4-pyridyloxy.

[0325] The term heteroaryloxyalkyl embraces heteroaryloxy radicals, as defined above, attached to an alkyl group. Examples of such radicals include 2-pyridyloxymethyl, 3-pyridyloxyethyl, and 4-pyridyloxymethyl.

[0326] The term arylthio embraces aryl radicals, as defined above, attached to an sulfur atom. Examples of such radicals include phenylthio.

[0327] The term arylthioalkyl embraces arylthio radicals, as defined above, attached to an alkyl group. Examples of such radicals include phenylthiomethyl.

[0328] The term alkylthioalkyl embraces alkylthio radicals, as defined above, attached to an alkyl group. Examples of such radicals include methylthiomethyl. The term alkoxyalkyl embraces alkoxy radicals, as defined above, attached to an alkyl group. Examples of such radicals include methoxymethyl.

[0329] The term carbonyl denotes a carbon radical having two of the four covalent bonds shared with an oxygen atom. The term carboxy embraces a hydroxyl radical, as defined above, attached to one of two unshared bonds in a carbonyl group. The term carboxamide embraces amino, monoalkylamino, dialkylamino, monocycloalkylamino, alkylcycloalkylamino, and dicycloalkylamino radicals, attached to one of two unshared bonds in a carbonyl group. The term carboxamidoalkyl embraces carboxamide radicals, as defined above, attached to an alkyl group. The term carboxyalkyl embraces a carboxy radical, as defined above, attached to an alkyl group. The term carboalkoxy embraces alkoxy radicals, as defined above, attached to one of two unshared bonds in a carbonyl group. The term carboaralkoxy embraces aralkoxy radicals, as defined above, attached to one of two unshared bonds in a carbonyl group. The term monocarboalkoxyalkyl embraces one carboalkoxy radical, as defined above, attached to an alkyl group. The term dicarboalkoxyalkyl embraces two carboalkoxy radicals, as defined above, attached to an alkylene group. The term monocyanoalkyl embraces one cyano radical, as defined above, attached to an alkyl group. The term dicyanoalkylene embraces two cyano radicals, as defined above, attached to an alkyl group. The term carboalkoxycyanoalkyl embraces one cyano radical, as defined above, attached to an carboalkoxyalkyl group.

[0330] The term acyl, alone or in combination, means a carbonyl or thionocarbonyl group bonded to a radical selected from, for example, hydrido, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, alkoxyalkyl, haloalkoxy, aryl, heterocyclyl, heteroaryl, alkylsulfinylalkyl, alkylsulfonylalkyl, aralkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, alkylthio, arylthio, amino, alkylamino, dialkylamino, aralkoxy, arylthio, and alkylthioalkyl. Examples of acyl are formyl, acetyl, benzoyl, trifluoroacetyl, phthaloyl, malonyl, nicotinyl, and the like. The term haloalkanoyl embraces one or more halo radicals, as defined herein, attached to an alkanoyl radical as defined above. Examples of such radicals include, for example, chloroacetyl, trifluoroacetyl, bromopropanoyl, and heptafluorobutanoyl. The term diacyl, alone or in combination, means having two or more carbonyl or thionocarbonyl groups bonded to a radical selected from, for example, alkylene, alkenylene, alkynylene, haloalkylene, alkoxyalkylene, aryl, heterocyclyl, heteroaryl, aralkyl, cycloalkyl, cycloalkylalkyl, and cycloalkenyl. Examples of diacyl are phthaloyl, malonyl, succinyl, adipoyl, and the like.

[0331] The term benzylidenyl radical denotes substituted and unsubstituted benzyl groups having attachment points for two covalent bonds. One attachment point is through the methylene of the benzyl group with the other attachment point through an ortho carbon of the phenyl ring. The methylene group is designated for attached to the lowest numbered position. Examples include the base compound benzylidene of structure:

[0332] The term phenoxylidenyl radical denotes substituted and unsubstituted phenoxy groups having attachment points for two covalent bonds. One attachment point is through the oxy of the phenoxy group with the other attachment point through an ortho carbon of the phenyl ring. The oxy group is designated for attached to the lowest numbered position. Examples include the base compound phenoxylidene of structure:

[0333] The term phosphono embraces a pentavalent phosphorus attached with two covalent bonds to an oxygen radical. The term dialkoxyphosphono denotes two alkoxy radicals, as defined above, attached to a phosphono radical with two covalent bonds. The term diaralkoxyphosphono denotes two aralkoxy radicals, as defined above, attached to a phosphono radical with two covalent bonds. The term dialkoxyphosphonoalkyl denotes dialkoxyphosphono radicals, as defined above, attached to an alkyl radical. The term diaralkoxyphosphonoalkyl denotes diaralkoxyphosphono radicals, as defined above, attached to an alkyl radical.

[0334] Said alkyl, alkenyl, alkynyl, alkanoyl, alkylene, alkenylene, benzylidenyl, phenoxylidenyl, hydroxyalkyl, haloalkyl, haloalkylene, haloalkenyl, alkoxy, alkenyloxy, alkenyloxyalkyl, alkoxyalkyl, aryl, perhaloaryl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxy, haloalkenyloxyalkyl, alkylenedioxy, haloalkylenedioxy, heterocyclyl, heteroaryl, hydroxyhaloalkyl, alkylsulfonyl, haloalkylsulfonyl, alkylsulfonylalkyl, haloalkylsulfonylalkyl, alkylsulfinyl, alkylsulfinylalkyl, haloalkylsulfinylalkyl, aralkyl, heteroaralkyl, perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl, aralkylsulfinylalkyl, cycloalkyl, cycloalkylalkanoyl, cycloalkylalkyl, cycloalkenyl, halocycloalkyl, halocycloalkenyl, cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, cycloalkoxy, cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxy, cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxy, halocycloalkenyloxyalkyl, alkylthio, haloalkylthio, alkylsulfinyl, amino, oxy, thio, alkylamino, arylamino, aralkylamino, arylsulfinyl, arylsulfinylalkyl, arylsulfonyl, arylsulfonylalkyl, heteroarylsulfinyl, heteroarylsulfinylalkyl, heteroarylsulfonyl, heteroarylsulfonylalkyl, heteroarylamino, heteroarylaminoalkyl, heteroaryloxy, heteroaryloxylalkyl, aryloxy, aroyl, aralkanoyl, aralkoxy, aryloxyalkyl, haloaryloxyalkyl, heteroaroyl, heteroaralkanoyl, heteroaralkoxy, heteroaralkoxyalkyl, arylthio, arylthioalkyl, alkoxyalkyl, acyl and diacyl groups defined above may optionally have 1 to 5 non-hydrido substituents such as perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl, aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl, cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, heteroarylamino, N-heteroarylamnino-N-alkylamino, heteroarylaminoalkyl, heteroaryloxy, heteroaryloxylalkyl, haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl, heteroaralkoxy, cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxy, halocycloalkenyloxyalkyl, hydroxy, amino, thio, nitro, lower alkylamino, alkylthio, alkylthioalkyl, arylamino, aralkylamino, arylthio, arylthioalkyl, heteroaralkoxyalkyl, alkylsulfinyl, alkylsulfinylalkyl, arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl, haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, monoarylamidosulfonyl, arylsulfonamido, diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl, arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl, alkenyloxy, alkenyloxyalky, alkylenedioxy, haloalkylenedioxy, cycloalkyl, cycloalkylalkanoyl, cycloalkenyl, lower cycloalkylalkyl, lower cycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, aralkyl, aryloxy, aralkoxy, aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroaryloxy, heteroaryloxyalkyl, arylalkyl, heteroarylalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl, carboalkoxy, alkoxycarbonyl, carboaralkoxy, carboxamido, carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono, phosphonoalkyl, diaralkoxyphosphono, and diaralkoxyphosphonoalkyl.

[0335] The term spacer can include a covalent bond and a linear moiety having a backbone of 1 to 7 continous atoms. The spacer may have 1 to 7 atoms of a univalent or multi-valent chain. Univalent chains may be constituted by a radical selected from C(H), C(R₁₇), O, S, S(O), S(O)₂, NH, N(R₁₇), N, CH(OH), C(OH), CH(OR₁₇), C(OR₁₇), and C(O) wherein R₁₇ is selected from alkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl, aryloxyalkyl, alkoxyalkyl, alkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, haloalkenyl, haloalkoxyalkyl, perhaloaralkyl, heteroarylalkyl, heteroaryloxyalkyl, heteroarylthioalkyl, and heteroarylalkenyl. Multi-valent chains may consist of a straight chain of 1 or 2 or 3 or 4 or 5 or 6 or 7 atoms or a straight chain of 1 or 2 or 3 or 4 or 5 or 6 atoms with a side chain. The chain may be constituted of one or more radicals selected from: lower alkylene, lower alkenyl, O, OCH₂, SCH₂, CH₂CH₂, ethenyl, CHCH(OH), OCH₂O, O(CH₂)₂O, NHCH₂, OCH(R₁₇)), O(CH₂CHR₁₇)O, OCF₂O, O(CF₂)₂O, S, S(O), S(O)₂, N(H), N(H)O, N(R₁₇)O, N(R₁₇), C(O), C(O)NH, C(O)NR₁₇, N, OCH₂, SCH₂, S(O)CH₂, CH₂C(O), CH(OH), C(OH), CH(OR₁₇), C(OR₁₇), S(O)₂CH₂, and NR₁₇CH₂ and many other radicals defined above or generally known or ascertained by one of skill-in-the art. Side chains may include substituents such as 1 to 5 non-hydrido substituents such as perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl, aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl, cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, heteroarylamino, N-heteroarylamino-N-alkylamino, heteroarylaminoalkyl, heteroaryloxy, heteroaryloxylalkyl, haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl, heteroaralkoxy, cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxy, halocycloalkenyloxyalkyl, hydroxy, amino, thio, nitro, lower alkylamino, alkylthio, alkylthioalkyl, arylamino, aralkylamino, arylthio, arylthioalkyl, heteroaralkoxyalkyl, alkylsulfinyl, alkylsulfinylalkyl, arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl, haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, monoarylamidosulfonyl, arylsulfonamido, diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl, arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl, alkenyloxy, alkenyloxyalky, alkylenedioxy, haloalkylenedioxy, cycloalkyl, cycloalkenyl, lower cycloalkylalkyl, lower cycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, aralkyl, aryloxy, aralkoxy, aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroaryloxy, heteroaryloxyalkyl, arylalkyl, heteroarylalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl, carboalkoxy, carboaralkoxy, carboxamido, carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono, phosphonoalkyl, diaralkoxyphosphono, and diaralkoxyphosphonoalkyl.

[0336] Compounds of the present invention can exist in tautomeric, geometric or stereoisomeric forms. The present invention contemplates all such compounds, including cis- and trans-geometric isomers, E- and Z-geometric isomers, R- and S-enantiomers, diastereomers, d-isomers, l-isomers, the racemic mixtures thereof and other mixtures thereof, as falling within the scope of the invention.

[0337] Pharmaceutically acceptable sales of such tautomeric, geometric or stereoisomeric. forms are also included within the invention.

[0338] The terms cis and trans denote a form of geometric isomerism in which two carbon atoms connected by a double bond will each have a hydrogen atom on the same side of the double bond (cis) or on opposite sides of the double bond (trans).

[0339] Some of the compounds described contain alkenyl groups, and are meant to include both cis and trans or F and Z geometric forms. Some of the compounds described contain one or more stereocenters and are meant to include R, S, and mixtures of R and S forms for each stereocenter present.

[0340] Some of the compounds described herein may contain one or more ketonic or aldehydic carbonyl groups or combinations thereof alone or as part of a heterocyclic ring system. Such carbonyl groups may exist in part or principally in the keto form and in part or principally as one or more enol forms of each aldehyde and ketone group present. Compounds of the present invention having aldehydic or ketonic carbonyl groups are meant to include both keto and enol tautomeric forms.

[0341] Some of the compounds described herein may contain one or more amide carbonyl groups or combinations thereof alone or as part of a heterocyclic ring system. Such carbonyl groups may exist in part or principally in the keto form and in part or principally as one or more enol forms of each amide group present. Compounds of the present invention having amidic carbonyl groups are meant to include both keto and enol tautomeric forms. Said amide carbonyl groups may be both oxo (CO) and thiono (CS) in type.

[0342] Some of the compounds described herein may contain one or more imine or enamine groups or combinations thereof. Such groups may exist in part or principally in the imine form and in part or principally as one or more enamine forms of each group present. Compounds of the present invention having said imine or enamine groups are meant to include both imine and enamine tautomeric forms.

[0343] The following general synthetic sequences are useful in making the present invention. Abbreviations used in the schemes are as follows: AA represents amino acids, BINAP represents 2,2-bis(diphenylphosphino)-1,1-binaphthyl, Boc represents tert-butyloxycarbonyl, BOP represents benzotriazol-1-yl-oxy-tris-(dimethylamino), bu represents butyl, dba represents dibenzylideneacetone, DCC represents 1,3-dicyclohexylcarbodiimide, DIBAH represents diisobutylaluminum hydride, DIPEA represents diisopropylethylamine, DMF represents dimethylformamide, DMSO represents dimethylsulfoxide, Fmoc represents 9-fluorenylmethoxycarbonyl, LDA represents lithium diisopropylamide, PHTH represents a phthaloyl group, pnZ represents 4-nitrobenzyloxycarbonyl, PTC represents a phase transfer catalyst, p-TsOH represents paratoluenesulfonic acid, TBAF represents tetrabutylammonium fluoride, TBTU represents 2-(1H-benzotriozole-1-yl)-1,1,3,3-tetramethyl uronium tetrafluoroborate, TEA represents triethylamine, TFA represents trifluoroacetic acid, THF represents tetrahydrofuran, TMS represents trimethylsilyl, and Z represents benzyloxycarbonyl.

[0344] The present invention comprises a pharmaceutical composition comprising a therapeutically-effective amount of a compound of Formulas V-H, V, VII-H, VII, VII-2, VII-3, VII4, and Cyclo-VII, in association with at least one pharmaceutically-acceptable carrier, adjuvant or diluent.

[0345] The present invention also comprises a treatment and prophylaxis of coronary artery disease and other CETP-mediated disorders in a subject, comprising administering to the subject having such disorder a therapeutically-effective amount of a compound of Formula V-H:

[0346] wherein R₁, R₂, R₃, R₄, R₅, R_6, R₇, R₈, R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₁₄, R₁₅, R₁₆, R₁₉, X, Y, and Z are as defined above for the compounds of Formula V-H;

[0347] or a pharmaceutically-acceptable salt thereof.

[0348] As a further embodiment, compounds of the present invention of Formulas V-H, V, VII-H, VII, VII-2, VII-3, VII4, and Cyclo-VII, or a pharmaceutically-acceptable salt thereof as defined above and further including those, wherein R₁₆ is a covalent single bond linked to a point of bonding of R₄ or R₈ when R₂ is alkyl, R₂ and R₁₄ are taken together to form a N spacer group, and R₂ and R₁₅ are taken together to form a N spacer group, comprise a treatment and prophylaxis of coronary artery disease and other CETP-mediated disorders in a subject, comprising administering to the subject having such disorder a therapeutically-effective amount of compounds of Formulas V-H, V, VII-H, VII, VII-2, VII-3, VII4, and Cyclo-VII, of the present invention or a pharmaceutically-acceptable salt thereof.

[0349] Compounds of Formulas V-H, V, VII-H, VII, VII-2, VII-3, VII4, and Cyclo-VII including those, wherein R₁₆ is a covalent single bond linked to a point of bonding of R₄ or R₈ when R₂ is alkyl, R₂ and R₁₄ are taken together to form a N spacer group, and R₂ and R₁₅ are taken together to form a N spacer group, are capable of inhibiting activity of cholesteryl ester transfer protein (CETP), and thus could be used in the manufacture of a medicament, a method for the prophylactic or therapeutic treatment of diseases mediated by CETP, such as peripheral vascular disease, hyperlipidaemia, hypercholesterolemia, and other diseases attributable to either high LDL and low HDL or a combination of both, or a procedure to study the mechanism of action of the cholesteryl ester transfer protein (CETP) to enable the design of better inhibitors. The compounds of Formulas V-H, V, VII-H, VII, VII-2, VII-3, VII4, and Cyclo-VII would be also useful in prevention of cerebral vascular accident (CVA) or stroke.

[0350] Also included in the family of compounds of Formulas V-H, V, VII-H, VII, VII-2, VII-3, VII4, and Cyclo-VII are the pharmaceutically-acceptable salts thereof. The term pharmaceutically-acceptable salts embraces salts commonly used to form alkali metal salts and to form addition salts of free acids or free bases. The nature of the salt is not critical, provided that it is pharmaceutically acceptable. Suitable pharmaceutically-acceptable acid addition salts of compounds of Formula V-H may be prepared from inorganic acid or from an organic acid. Examples of such inorganic acids are hydrochloric, hydrobromic, hydroiodic, nitric, carbonic, sulfuric and phosphoric acid. Appropriate organic acids may be selected from aliphatic, cycloaliphatic, aromatic, araliphatic, heterocyclic, carboxylic and sulfonic classes of organic acids, examples of which are formic, acetic, propionic, succinic, glycolic, gluconic, lactic, malic, tartaric, citric, ascorbic, glucoronic, maleic, fumaric, pyruvic, aspartic, glutamic, benzoic, anthranilic, mesylic, salicylic, p-hydroxybenzoic, phenylacetic, mandelic, embonic (pamoic), methanesulfonic, ethylsulfonic, benzenesulfonic, sulfanilic, stearic, cyclohexylaminosulfonic, algenic, galacturonic acid. Suitable pharmaceutically-acceptable base addition salts of compounds of Formula V-H include metallic salts made from aluminum, calcium, lithium, magnesium, potassium, sodium and zinc or organic salts made from N,N-dibenzylethyleneldiamine, choline, chloroprocaine, diethanolamine, ethylenediamine, meglumine (N-methylglucamine) and procain. All of these salts may be prepared by conventional means from the corresponding compounds of Formulas V-H, V, VII-H, VII, VII-2, VII-3, VII4, and Cyclo-VII by reacting, for example, the appropriate acid or base with the compounds of Formulas V-H, V, VII-H, VII, VII-2, VII-3, VII4, and Cyclo-VII.

[0351] Also embraced within this invention is a class of pharmaceutical compositions comprising the active compounds of Formula V-H in association with one or more non-toxic, pharmaceutically-acceptable carriers and/or diluents and/or adjuvants (collectively referred to herein as carrier materials) and, if desired, other active ingredients. The active compounds of the present invention may be administered by any suitable route, preferably in the form of a pharmaceutical composition adapted to such a route, and in a dose effective for the treatment intended. The active compounds and composition may, for example, be administered orally, intravascularly, intraperitoneally, subcutaneously, intramuscularly or topically.

[0352] For oral administration, the pharmaceutical composition may be in the form of, for example, a tablet, capsule, suspension or liquid. The pharmaceutical composition is preferably made in the form of a dosage unit containing a particular amount of the active ingredient. Examples of such dosage units are tablets or capsules. The active ingredient may also be administered by injection as a composition wherein, for example, saline, dextrose or water may be used as a suitable carrier.

[0353] The amount of therapeutically active compounds which are administered and the dosage regimen for treating a disease condition with the compounds and/or compositions of this invention depends on a variety of factors, including the age, weight, sex and medical condition of the subject, the severity of the disease, the route and frequency of administration, and the particular compound employed, and thus may vary widely.

[0354] The pharmaceutical compositions may contain active ingredients in the range of about 0.1 to 2000 mg, and preferably in the range of about 0.5 to 500 mg. A daily dose of about 0.01 to 100 mg/kg body weight, and preferably between about 0.5 and about 20 mg/kg body weight, may be appropriate. The daily dose can be administered in one to four doses per day.

[0355] The compounds may be formulated in topical ointment or cream, or as a suppository, containing the active ingredients in a total amount of, for example, 0.075 to 30% w/w, preferably 0.2 to 20% w/w and most preferably 0.4 to 15% w/w. When formulated in an ointment, the active ingredients may be employed with either paraffinic or a water-miscible ointment base. Alternatively, the active ingredients may be formulated in a cream with an oil-in-water cream base. If desired, the aqueous phase of the cream base may include, for example at least 30% w/w of a polyhydric alcohol such as propylene glycol, butane-1,3-diol, mannitol, sorbitol, glycerol, polyethylene glycol and mixtures thereof. The topical formulation may desirably include a compound which enhances absorption or penetration of the active ingredient through the skin or other affected areas. Examples of such dermal penetration enhancers include dimethylsulfoxide and related analogs. The compounds of this invention can also be administered by a transdermal device. Preferably topical administration will be accomplished using a patch either of the reservoir and porous membrane type or of a solid matrix variety. In either case, the active agent is delivered continuously from the reservoir or microcapsules through a membrane into the active agent permeable adhesive, which is in contact with the skin or mucosa of the recipient. If the active agent is absorbed through the skin, a controlled and predetermined flow of the active agent is administered to the recipient. In the case of microcapsules, the encapsulating agent may also function as the membrane.

[0356] The oily phase of the emulsions of this invention may be constituted from known ingredients in a known manner. While the phase may comprise merely an emulsifier, it may comprise a mixture of at least one emulsifier with a fat or an oil or with both a fat and an oil. Preferably, a hydrophilic emulsifier is included together with a lipophilic emulsifier which acts as a stabilizer. It is also preferred to include both an oil and a fat. Together, the emulsifier(s) with or without stabilizer(s) make-up the so-called emulsifying wax, and the wax together with the oil and fat make up the so-called emulsifying ointment base which forms the oily dispersed phase of the cream formulations. Emulsifiers and emulsion stabilizers suitable for use in the formulation of the present invention include Tween 60, Span 80, cetostearyl alcohol, myristyl alcohol, glyceryl monostearate, and sodium lauryl sulfate, among others.

[0357] The choice of suitable oils or fats for the formulation is based on achieving the desired cosmetic properties, since the solubility of the active compound in most oils likely to be used in pharmaceutical emulsion formulations is very low. Thus, the cream should preferably be a non-greasy, non-staining and washable product with suitable consistency to avoid leakage from tubes or other containers. Straight or branched chain, mono- or dibasic alkyl esters such as di-isoadipate, isocetyl stearate, propylene glycol diester of coconut fatty acids, isopropyl myristate, decyl oleate, isopropyl palmitate, butyl stearate, 2-ethylhexyl palmitate or a blend of branched chain esters may be used. These may be used alone or in combination depending on the properties required. Alternatively, high melting point lipids such as white soft paraffin and/or liquid paraffin or other mineral oils can be used.

[0358] For therapeutic purposes, the active compounds of this combination invention are ordinarily combined with one or more adjuvants appropriate to the indicated route of administration. If administered per os, the compounds may be admixed with lactose, sucrose, starch powder, cellulose esters of alkanoic acids, cellulose alkyl esters, talc, stearic acid, magnesium stearate, magnesium oxide, sodium and calcium salts of phosphoric and sulfuric acids, gelatin, acacia gum, sodium alginate, polyvinylpyrrolidone, and/or polyvinyl alcohol, and then tableted or encapsulated for convenient administration. Such capsules or tablets may contain a controlled-release formulation as may be provided in a dispersion of active compound in hydroxypropylmethyl cellulose. Formulations for parenteral administration may be in the form of aqueous or non-aqueous isotonic sterile injection solutions or suspensions. These solutions and suspensions may be prepared from sterile powders or granules having one or more of the carriers or diluents mentioned for use in the formulations for oral administration. The compounds may be dissolved in water, polyethylene glycol, propylene glycol, ethanol, corn oil, cottonseed oil, peanut oil, sesame oil, benzyl alcohol, sodium chloride, and/or various buffers. Other adjuvants and modes of administration are well and widely known in the pharmaceutical art.

[0359] All mentioned references are incorporated by reference as if here written.

[0360] Although this invention has been described with respect to specific embodiments, the details of these embodiments are not to be construed as limitations.

[0361] The compounds of the present invention can be synthesized, for example, according to the following procedures of Schemes 1 through 59 below, wherein the substituents are as defined for Formulas V-H, V, VII-H, VII, VII-2, VII-3, VII-4, and Cyclo-VII above except where further noted.

[0362] Synthetic Schemes 1 and 2 shows the preparation of compounds of formula XIII (Generic Secondary Amines) which are intermediates in the preparation of the compounds of the present invention corresponding to Formula V-H (Generic Substituted Polycyclic Aryl and Heteroaryl tertiary omegahydroxyalkylamines), Formula V (Generic Substituted Polycyclic Aryl tertiary omegahydroxyalkylamines), Formula VII (Generic Substituted Polycyclic Aryl tertiary-2-hydroxyalkylamines), and Formula VII-H (Generic Substituted Polycyclic Heteroaryl tertiary-2-hydroxyalkylamines) wherein A and Q are independently aryl and heteroaryl. Schemes 1 and 2, taken together, prepare tertiary oxyalkylamine compounds of the present invention by addition of a halogenated, oxygen containing precursor to a secondary amine to introduce an oxy containing alkyl group wherein the two groups making up the secondary amine both are made up of aromatic groups or both groups contain aromatic rings wherein said aromatic rings maybe 0 to 2 aryl rings and 0 to 2 heteroaryl rings.

[0363] The Generic Imine corresponding to Formula XII can be prepared through dehydration techniques generally known in the art and the preferred technique depending on the nature of Generic Amine-1 of Formula X by reacting it with the Generic Carbonyl Compound of Formula XI. For example, when Z is a covalent bond, methylene, methine substituted with another subsitutent, ethylene, or another subsituent as defined in Formula V-H, the two reactants (X and XI) react by refluxing them in an aprotic solvent, such as hexane, toluene, cyclohexane, benzene, and the like, using a DeanStark type trap to remove water. After about 2-8 hours or until the removal of water is complete, the aprotic solvent is removed in vacuo to yield the Generic Imine of Formula XII. Alternately, when Z is an oxygen, the Generic Imine is an oxime derivative. Oxime type Generic Imine compounds are readily prepared from the corresponding O-substituted hydroxylamine and the appropriate aldehyde or ketone type Generic Carbonyl Compound. Suitable procedures are described by Shriner, Fuson, and Curtin in The Systematic Indentification of Organic Compounds, 5th Edition, John Wiley & Sons and by Fieser and Fieser in Reagents for Organic Synthesis, Volume 1, John Wiley & Sons, which are incorporated herein by reference. Alternately, when Z is a nitrogen, the Generic Imine is a hydrazone derivative. Hydrazone type Generic Imine compounds are readily prepared from the corresponding hydrazine and the appropriate aldehyde or ketone type Generic Carbonyl Compound. Suitable procedures for formiing the hydrazone imines are also described by Shriner, Fuson, and Curtin in The Systematic Indentification of Organic Compounds, 5th Edition, John Wiley & Sons, and by Fieser and Fieser in Reagents for Organic Synthesis, Volume 1, John Wiley & Sons, which are incorporated herein by reference.

[0364] Scheme 1 shows the preparation of Generic Imine compounds in which the amine functionality is bonded to Z; Z is bonded to A; and Y is bonded to Q. One of skill in the art will recognize that A and Q as defined can be structurally interchanged to prepare Generic Imine compounds with similar, identical or different structures.

[0365] The Generic Secondary Amines of Formula XIII can be prepared from the corresponding Generic Imine of Formula XII in several ways.

[0366] For example, in one synthetic scheme (Reduction Method-1), which is preferred when Z is a nitrogen, the Generic Imine hydrazone of Formula XII is partially or completely dissolved in lower alkanols such as ethanol or like solvent containing sufficient organic acid such as acetic acid or mineral acid such as HCl or sulfuric acid to neutralize the hydrazone as described in WO Patent Application No.9738973, Swiss Patent CH 441366 and U.S. Pat. Nos. 3,359,316 and 3,334,017, which are incorporated herein by reference. The resulting mixture is then hydrogenated at 0-100 C., more preferrably 20-50 C., and most preferrably between 20-30 C. and pressures of 10-200 psi hydrogen or more preferrably between 50-70 psi hydrogen in the presence of a noble metal catalyst such as PtO₂. The mixture is cooled, and a base such as sodium carbonate or sodium hydroxide added until the solution is neutral to just alkaline (pH 6-8).

[0367] Isolation of the desired product can be accomplished, for example, by removing the ethanol, adding water, and extracting the aqueous-organic mixture twice with a solvent, such as diethyl ether or methylene chloride, that is immiscible with water. The combined solvent extract is washed with saturated brine, dried with a drying agent such as anhydrous magnesium sulfate, and concentrated in vacua to yield the Generic Secondary Amines hydrazine of Formula XIII. If needed the Generic Secondary Amines hydrazine can be further purified by crystallization, distillation at reduced pressure, or liquid chromatography.

[0368] In another synthetic scheme (Reduction Method-2), which is preferrred when Z is a single bond or carbon, the Generic Imine of Formula XII is slurried in a lower alcohol such as ethanol, methanol or like solvent at 0-10 C. and solid sodium borohydride is added in batches over 5-10 minutes at 0-10 C. with stirring. The reaction mixture is stirred below 10 C. for 30-90 minutes and then is warmed gradually to 15-30 C. After about 1-10 hours, the mixture is cooled and acid is added until the aqueous layer was just acidic (pH 5-7).

[0369] Isolation of the desired product can be accomplished, for example, by extracting the aqueous layer twice with a solvent, such as diethyl ether or methylene chloride, that is immiscible with water. The combined solvent extract is washed with saturated brine, dried with a drying agent such as anhydrous MgSO4, and concentrated in vacuo to yield the Generic Secondary Amines amine, aniline, or amine of Formula XIII. If needed the Generic Secondary Amines amine, aniline, or amine derivative can be further purified by crystallization, distillation at reduced pressure, or liquid chromatography.

[0370] In yet another synthetic scheme (Reduction Method-3), which is preferrred when Z is an oxygen, the Generic Imine oxime of Formula XII is slurried in a lower alcohol solvent such methanol or like solvent at 0-10 C. and acidified to a pH less than 4. Solid sodium cyanoborohydride is added in batches over 30-90 minutes at 0-20 C. with stirring and addition of a suitable organic or mineral acid to keep the pH at or below 4. The reaction mixture is stirred and warmed gradually to about 20-25 C. After about 1-10 hours, the mixture is cooled and base added until the mixture was just slightly alkaline.

[0371] Isolation of the desired product can be accomplished, for example, by removing the methanol or other low boiling solvent in vacuo. The residue is slurried with water and aqueous-organic mixture is extracted twice with a solvent, such as diethyl ether or methylene chloride, that is immiscible with water. The combined solvent extract is washed with saturated brine, dried with a drying agent such as anhydrous MgSO₄, and concentrated in vacuo to yield the Generic Secondary Amines hydroxylamine of Formula XIII. If needed the Generic Secondary Amines hydroxylamine can be further purified by crystallization, distillation at reduced pressure, or liquid chromatography.

[0372] The Generic Secondary Amines of Formula XIII can also be prepared, according to Scheme 1 by two alkylation procedures based on the nucleophilic substitution of bromides by amines. In one procedure, Generic Amine-1 of Formula X is reacted with Generic Bromide-1 of Formula XXI. In another alkylation procedure, Generic Amine-2 of Formula XXII is reacted together with Generic Bromide-2 of Formula XXIII.

[0373] In one synthetic alkylation scheme (Alkylation Method-1), a Generic Amine-1 of Formula X is reacted with a Generic Bromide-2 of Formula XXIII as described in Vogel's Textbook of Practical Organic Chemistry, Fifth Edition, 1989, pages 902 to 905 and references cited therein all of which are incorporated herein by reference. In this procedure, the Generic Amine-1 is placed in a reaction vessel equipped with a reflux condenser with the capability to either cool or heat the vessel as dictated by the reaction. A suitable Generic Amine-1 will be selected from primary amine and primary aromatic amine classes of compounds. Cooling may be needed and used should the reaction prove strongly exothermic. Heating may be needed and used to drive the reaction to completion. A suitable solvent may also be used to dissolve the Generic Amine-1. Suitable solvents are hydrocarbons such as toluene, hexane, xylene, and cyclohexane, ethers, amides such as dimethylformamide, esters such as ethyl acetate, ketones such as acetone, and nitriles such as acetonitrile or mixtures of two or more of these solvents. A suitable base is also added to the reaction vessel. Suitable bases include cesium carbonate, calcium carbonate, sodium carbonate and sodium bicarbonate. The base will normally be added in at least a stoichmetric quantity compared to the Generic Amine-1 so as to neutralize liberated acid as it forms.

[0374] The Generic Bromide-1 of Formula XXI is then added to the reaction vessel in portions so as to minimize the rate of heat evolution and minimize the concentration of the Generic Bromide-1. The Generic Bromide-1 will be selected from primary and secondary organic alkyl and substituted alkyl halide compounds. The halide will preferrably be a bromide although iodides and chlorides may also be generally used. One of skill in the art will also be able to readily select and utilize organic alkyl and substituted alkyl compounds containing readily displaceable primary and secondary groups such as tosylates, mesylates, triflates, and the like. Alternately, the halides can be generally prepared from the corresponding alcohols by reaction with, for example, concentrated hydrohalic acids such as HBr or by reaction with phosphorus trihalides such as PBr₃ as described in Fieser and Fieser in Reagents for Organic Synthesis, Volume 1, John Wiley & Sons, which are incorporated herein by reference. The appropriate alcohols can be converted to tosylates, mesylates, and triflates using procedures described below.

[0375] Addition of the Generic Bromide-1 is carried out over a period of a few minutes to several hours at temperatures between 0 and 150 C. Preferrably, the addition will take 30-120 minutes at a temperature of 0 to 50 C. The reaction can be stirred until completion. Completion can be monitored, for example, spectroscopically using nuclear magnetic resonance or chromatographically using thin layer, liquid, or gas chromatographic procedures. If the reaction does not proceed to completion, the reactants may be heated until completion is obtained and verified.

[0376] Isolation of the desired product can be accomplished, for example, when a water immiscible solvent was used for the reaction, by adding water to the finished reaction. Additional base such as sodium carbonate can be added to ensure the reaction is basic (pH of 9 to 11). The organic layer containing the Generic Secondary Amine is washed with saturated brine, dried with a drying agent such as anhydrous MgSO₄, and concentrated in vacuo to yield the Generic Secondary Amine amine, aniline, or amine of Formula XIII. If needed the Generic Secondary Amine amine, aniline, or amine derivative can be further purified by crystallization, distillation at reduced pressure, or liquid chromatography.

[0377] In a second synthetic alkylation scheme (Alkylation Method-2), a Generic Amine-2 of Formula XXII is reacted with a Generic Bromide-2 of Formula XXIII in a method employing pallladium catalyzed carbon-nitrogen bond formation. Suitable procedures for this conversion are described in Wagaw and Buchwald, J. Org. Chem.(1996), 61, 7240-7241, Wolfe, Wagaw and Buchwald, J. Am. Chem. Soc. (1996), 118, 7215-7216, and Wolfe and Buchwald, Tetrahedron Letters (1997), 38(36), 6359-6362 and references cited therein all of which are incorporated herein by reference. The preferred Generic Bromide-2 of Formula XXIII are generally aryl bromides, aryl triflates, and heteroaryl bromides.

[0378] The Generic Amine-1 and Generic Amine-2 amines, hydroxylamines, and hydrazines, the Generic Carbonyl Compound aldehydes, ketones, hydrazones, and oximes, and Generic Bromide-1 and Generic Bromide-2 halides, tosylates, mesylates, triflates, and precursor alcohols required to prepare the Generic Secondary Amine compounds are available from commercial sources, can be prepared by one skilled in the art from published procedures, and/or can be obtained using specific procedures shown in Schemes 42, 43, and 44. Commercial sources include but are not limited to Aldrich Chemical, TCI-America, LancasterSynthesis, Oakwood Products, Acros Organics, and Maybridge Chemical. Disclosed procedures for Generic Amine amines, hydroxylamines, and hydrazines include Sheradsky and Nov, J. Chem. Soc., Perkin Trans.1 (1980), (12), 2781-6; Marcoux, Doye, and Buchwald, J. Am. Chem. Soc. (1997), 119, 1053-9; Sternbach and Jamison, Tetrahedron Lett. (1981), 22(35), 33314; U.S. Pat. No. 5,306,718; EP No. 314435; WO No. 9001874; WO No. 9002113; JP No. 05320117; WO No. 9738973; Swiss Patent No. CH 441366; U.S. Pat. Nos. 3,359,316 and 3,334,017; and references cited therein which are incorporated herein by reference. Representative specific Generic Secondary Amine of Formula XIII compounds useful for the preparation of compounds of the present invention are listed in Tables 3, 4, and 5.

[0379] As summarized in the general Scheme 1 and specific descriptions above, Schemes 3, 4, 9, and 10 illustrate the principles of Scheme 1 for the preparation of specifically substituted Secondary Heteroaryl Amines (XIIIA-H) having 0 to 2 aryl groups and 0 to 2 aromatic heterocyclyl groups and Secondary Phenyl Amines (XIII-A) having two aryl groups.

[0380] Synthetic Scheme 2 shows the preparation of the class of compounds of the present invention corresponding to Formula V-H (Generic Substituted Polycyclic Aryl and Heteroaryl tertiary omegahydroxyalkylamines), Formula V (Generic Substituted Polycyclic Aryl tertiary omegahydroxyalkylamines), Formula VII (Generic Substituted Polycyclic Aryl tertiary-2-hydroxyalkylamines), and Formula VII-H (Generic Substituted Polycyclic Heteroaryl tertiary-2-hydroxyalkylamines) wherein A and Q are independently aryl and heteroaryl.

[0381] Derivatives of Generic Substituted Polycyclic Aryl and Heteroaryl tertiary omegahydroxyalkylamines and Generic Substituted Polycyclic Aryl tertiary omegahydroxyalkylamines, wherein A and Q are independently aryl and heteroaryl, in which the hetero atom (O) is attached to an alkyl group removed from the amine by three or more carbons are readily prepared by anion chemistry using Method B of Scheme 2. The anion of Generic Secondary Amine amines, hydroxylamines, and hydrazines of Formula XIII are readily formed by dissolving the specific amine, hydroxylamine, or hydrazine in an aprotic solvent, such as tetrahydrofuran, toluene, ether, dimethylformamide, and dimethylformamide, under anhydrous conditions.

[0382] The solution is cooled to a temperature between 78 and 0 C., preferrably between 78 and 60 C. and the anion formed by the addition of at least one equivalent of a strong, aprotic, non-nucleophillic base such as NaH or n-butyllithium under an inert atmosphere for each acidic group present.

[0383] Maintaining the temperature between 78 and 0 C., preferrably between 78 and 60 C., with suitable cooling, an appropriate alkyl

TABLE 3
Structure of Secondary Phenyl Amine Reagents.
	Secondary Phenyl Amine (XIIIA)
Reagent
Number	R4	R5	R6	R7	R9	R10	R11	Y	R14
1N	H	phenoxy	H	H	H	OCF2CF2H	H	CH	H
2N	H	OCF3	H	H	H	OCF2CF2H	H	CH	H
3N	F	H	H	F	H	OCF2CF2H	H	CH	H
4N	H	F	H	H	H	OCF2CF2H	H	CH	H
5N	H	phenoxy	H	H	H	OCF3	H	CH	H
6N	H	OCF3	H	H	H	OCF3	H	CH	H
7N	H	H	phenyl	H	H	OCF3	H	CH	H
8N	H	phenyl	H	H	H	OCF3	H	CH	H
9N	H	H	H	H	H	OCF3	H	CH	H
10N	H	Br	H	H	H	OCF3	H	CH	H
11N	H	CF3	F	H	H	CF3	H	CH	H
12N	H	CH3	H	H	H	CF3	H	CH	H
13N	H	CF3	H	H	H	CF3	H	CH	H
14N	H	CH3	H	H	H	OCF3	H	CH	H
15N	H	F	F	H	H	OCF3	H	CH	H
16N	H	Br	H	H	H	CF3	H	CH	H
17N	H	CF3	F	H	H	OCF3	H	CH	H
18N	H	F	H	H	H	OCF3	H	CH	H
19N	H	Cl	H	H	H	OCF3	H	CH	H
20N	H	F	H	H	H	CF3	H	CH	H
21N	H	F	F	H	H	CF3	H	CH	H
22N	H	Cl	H	H	H	CF3	H	CH	H
23N	H	F	H	H	H	phenoxy	H	CH	H
24N	H	CF3	Cl	H	H	CH3	H	CH	H
25N	H	CF3	F	H	H	CH3	H	CH	H
26N	H	H	H	H	H	CF3	H	CH	H
27N	F	F	H	H	H	CF3	H	CH	H
28N	H	H	OCH3	H	H	CF3	H	CH	H
29N	H	F	F	H	H	CH3	H	CH	H
30N	H	OCH3	H	H	H	CH3	H	CH	H
31N	H	H	CH3	H	H	H	H	CH	H
32N	H	Cl	H	H	H	H	H	CH	H
33N	H	F	H	H	H	F	H	CH	H
34N	H	H	OCH3	H	H	CH3	H	CH	H
35N	H	H	H	H	H	H	H	CH	H
36N	H	H	CH3	H	H	CH3	H	CH	H
37N	H	H	Cl	H	H	H	H	CH	H
38N	H	F	H	H	H	3-CF3-phenoxy	H	CH	H
39N	H	F	H	H	H	4-CH3O-phenoxy	H	CH	H
40N	H	F	H	H	H	4-Cl-phenoxy	H	CH	H
41N	H	F	H	H	H	H	H	CH	H
42N	H	F	H	H	H	CH3	H	CH	H
43N	H	F	H	F	H	CH3	H	CH	H
44N	F	F	H	H	H	CH3	H	CH	H
45N	H	Cl	H	H	H	CH3	H	CH	H
46N	H	CH3	H	H	H	CH3	H	CH	H
48N	H	H	CH3	H	H	CF3	H	CH	H
51N	H	H	CH3	H	H	F	H	CH	H
52N	H	CF3	H	H	H	F	H	CH	H
53N	H	CF3	H	H	H	CH3	H	CH	H
54N	H	OCH3	H	H	H	CF3	H	CH	H
56N	H	H	CH3	H	H	CF3	H	CH	H
57N	H	phenoxy	H	H	H	H	OCF3	CH	H
58N	H	H	H	H	H	H	OCF3	CH	H
59N	H	OCF3	H	H	H	H	OCF3	CH	H
60N	H	CF3	F	H	H	H	CF3	CH	H
61N	H	H	OCH3	H	H	H	CF3	CH	H
62N	H	CH3	H	H	H	H	CF3	CH	H
63N	H	Cl	H	H	H	H	CF3	CH	H
64N	H	CF3	H	H	H	H	OCF3	CH	H
65N	H	F	H	H	H	H	OCF3	CH	H
66N	H	F	H	F	H	H	OCF3	CH	H
67N	H	Br	H	H	H	H	OCF3	CH	H
68N	H	Cl	H	H	H	H	OCF3	CH	H
69N	H	F	F	H	H	H	OCF3	CH	H
70N	H	F	H	H	H	H	phenyl	CH	H
71N	H	CH3	H	H	H	H	OCF3	CH	H
72N	H	F	F	H	H	H	CF3	CH	H
73N	H	Cl	H	H	H	H	CH3	CH	H
74N	H	OCH3	H	H	H	H	CH3	CH	H
75N	H	F	H	H	H	H	CH3	CH	H
76N	F	F	H	H	H	H	OCF3	CH	H
78N	H	H	OCH3	H	H	H	CH3	CH	H
79N	H	H	CH3	H	H	H	CH3	CH	H
80N	H	CH3	H	H	H	H	CH3	CH	H
82N	H	F	F	H	H	H	CH3	CH	H
83N	H	F	H	F	H	H	CH3	CH	H
84N	F	F	H	H	H	H	CH3	CH	H
85N	F	CF3	H	H	H	H	CH3	CH	H
86N	H	H	CH3	H	H	H	CF3	CH	H
88N	H	CF3	H	H	H	H	CH3	CH	H
90N	H	H	CF3	H	H	H	CH3	CH	H
92N	H	CF3	F	H	H	H	CH3	CH	H

[0384]

TABLE 4
Structure of Secondary Phenyl Amine Reagents (Z is covalent bond; there is no R15 substituent; R4 and R13 equal H).
	Secondary Phenyl Amine (XIII-A)
												Spacer
Rgnt.												Bond
No.	R5	R6	R7	R8	Y	R14	R9	R10	R11	R12	Spacer	Points
93N	Br	H	H		CH	H		H	H	OCF3	O	R8 R9
94N	OCF3	H	H		CH	H		H	H	OCF3		R8 R9
95N	Br	H	H		C		H	OCF3	H	H	CH	R8
												R14
96N	OH	OH	H	H	CH	H	H	C6H5O	H	H	none	none
97N	C6H5O	H	H	H	CH	H	H	OH	OH	H	none	none
98N	3-pyridyl	H	H	H	CH	H	H	CF3	H	H	none	none
99N	SO2N(CH3)2	H	H	H	CH	H	H	OCF3	H	H	none	none
100N	SO2CH3	H	H	H	CH	H	H	OCF3	H	H	none	none
101N	C6H5O	H	H	H	CH	H	H	C6H5O	H	H	none	none
102N	CF3O	H	H	H	CH	H	H	C6H5O	H	H	none	none
103N	C6H5	H	H	H	CH	H	H	C6H5O	H	H	none	none
104N	H	C6H5	H	H	CH	H	H	C6H5O	H	H	none	none
105N	C6H5O	H	H	H	CH	H	H	4-ClC6H4O	H	H	none	none
106N	CF3O	H	H	H	CH	H	H	4-ClC6H4O	H	H	none	none
107N	C6H5O	H	H	H	CH	H	H	3,4-ClC6H3O	H	H	none	none
108N	CF3O	H	H	H	CH	H	H	3,4-ClC6H3O	H	H	none	none
109N	CF3O	H	H	H	CH	H	H	3,5-ClC6H3O	H	H	none	none
110N	CF3O	H	H	H	CH	H	H	3-CH3OC6H4O	H	H	none	none
111N	CF3O	H	H	H	CH	H	H	H	3-CH3OC6H4O	H	none	none
112N	CF3O	H	H	H	CH	H	H	3-CF3C6H4O	H	H	none	none
113N	CF3O	H	H	H	CH	H	H	C6H5CH2O	H	H	none	none
114N	CF3O	H	H	H	CH	H	H	C6H5CH2O	CH3O	H	none	none
115N	CF3O	H	H	H	CH	H	H	C6H5CH2O	C6H5CH2O	H	none	none
116N	CF3O	H	H	H	CH	H	H	ethoxy	H	H	none	none
117N	CF3O	H	H	H	CH	H	H	CH3CO2	H	H	none	none
118N	CF3O	H	H	H	CH	H	H	HOCH2CH2O	H	H	none	none
119N	CF3O	H	H	H	CH	H	H		H	H	none	none
120N	CF3O	H	H	H	CH	H	H	R10 R11 OCH2O	H	none	none
121N	CF3O	H	H	H	CH	H	H	R10 R11 OCH2CH2O	H	none	none
122N	CF3O	H	H	H	CH	H	H	CH3O	CH3O	H	none	none
123N	CF3O	H	H	H	CH	H	H	ethoxy	CH3O	H	none	none
124N	CF3O	H	H	H	CH	H	H	ethoxy	ethoxy	H	none	none
125N	CF3O	H	H	H	CH	H	H	CH3CO2	CH3CO2	H	none	none
126N	CF3O	H	H	H	CH	H	H	CH3O	CH3CO2	H	none	none
127N	CF3O	H	H	H	CH	H	H	n-butoxy	H	H	none	none
128N	CF3O	H	H	H	CH	H	H	CH3O	H	H	none	none
129N	CF3O	H	H	H	CH	H	H	H	CH3O	H	none	none
130N	CF3O	H	H	H	CH	H	H	CH3O	H	H	none	none
131N	CF3O	H	H	H	CH	H	H	H	CF3O	H	none	none
132N	CF3O	H	H	H	CH	H	H	H	ethoxy	H	none	none
133N	CF3O	H	H	H	CH	H	H	H	n-propoxy	H	none	none
134N	C6H5CH2O	H	H	H	CH	H	H	CF3O	H	H	none	none
135N	C6H5CH2O	H	H	H	CH	H	H	C6H5O	H	H	none	none
136N	ethoxy	H	H	H	CH	H	H	CF3O	H	H	none	none
137N	R5 R6 OCH2O	H	H	CH	H	H	CF3O	H	H	none	none
138N	R5 R6 OCH2O	H	H	CH	H	H	C6H5O	H	H	none	none
139N	R5 R6 OCH2CH2O	H	H	CH	H	H	CF3O	H	H	none	none
140N	CH3O	CH3O	H	H	CH	H	H	CF3O	H	H	none	none
141N	R5 R6 OCH2CH2CH2O	H	H	CH	H	H	CF3O	H	H	none	none
142N	cyclopentoxy	CH3O	H	H	CH	H	H	CF3O	H	H	none	none
143N	H	C6H5O	H	H	CH	H	H	CF3O	H	H	none	none
144N	CH3O	CH3O	CH3O	H	CH	H	H	CF3O	H	H	none	none
145N	H	CF3O	H	H	CH	H	H	CF3O	H	H	none	none
146N	H	Benzyl	H	H	CH	H	H	CF3O	H	H	none	none
147N	C6H5O	H	H	CH	H	H	R10 R11 OCH2CH2O	H	none	none
148N	H	CF3O	H	H	CH	H	H	CF3	H	H	none	none
149N	C6H5O	H	H	H	CH	H	H	CF3	H	H	none	none
150N	C6H5	H	H	H	CH	H	H	CF3	H	H	none	none
151N	H	C6H5	H	H	CH	H	H	CF3	H	H	none	none
152N	CN	H	H	H	CH	H	H	CF3	H	H	none	none
153N	H	OCF3	H	H	CH	H	H	CF3	H	H	none	none
154N	OCF3	H	H	H	CH	H	H	H	CF3	H	none	none
155N	C6H5O	H	H	H	CH	H	H	H	CF3	H	none	none
156N	C6H5	H	H	H	CH	H	H	H	CF3	H	none	none
157N	H	C6H5	H	H	CH	H	H	H	CF3	H	none	none
158N	CN	H	H	H	CH	H	H	H	CF3	H	none	none
159N	OCF3	H	H	H	CH	H	H	H	CF3	H	none	none
160N	CF3	H	H	H	CH	H	H	H	C6H5	H	none	none
161N	CF3	H	H	H	CH	H	H	3-CF3C6H5O	H	H	none	none
162N	CF3	H	H	H	CH	H	H	C6H5O	H	H	none	none
163N	CF3	H	H	H	CH	H	H	CF3O	H	H	none	none
164N	H	CF3	H	H	CH	H	H	H	C6H5	H	none	none
165N	H	CF3	H	H	CH	H	H	3-CF3C6H5O	H	H	none	none
166N	H	CF3	H	H	CH	H	H	CF3O	H	H	none	none
167N	H	CF3	H	H	CH	H	H	C6H5O	H	H	none	none
168N	CF3	H	CF3	H	CH	H	H	CF3O	H	H	none	none
169N	CF3	H	CF3	H	CH	H	H	C6H5O	H	H	none	none
170N	CF3O	H	H	H	CH	H	H	CF3	H	CF3	none	none
171N	C6H5O	H	H	H	CH	H	H	CF3	H	CF3	none	none
172N	H	C6H5O	H	H	CH	H	H	C6H5O	H	H	none	none
173N	H	CF3O	H	H	CH	H	H	CF3O	H	H	none	none
174N	H	CF3O	H	H	CH	H	H	H	C6H5O	H	none	none
175N	C6H5O	H	H	H	CH	H	H	H	C6H5O	H	none	none
176N	H	C6H5O	H	H	CH	H	H	H	OCF3	H	none	none
177N	H	C6H5O	H	H	CH	H	H	H	C6H5O	H	none	none
178N	C6H5O	H	H	H	CH	H	H	H	CN	H	none	none
179N	C6H5O	H	H	H	CH	H	H	CN	H	H	none	none
180N	C6H5O	H	H	H	CH	H	H	NO2	H	H	none	none
181N	C6H5O	H	H	H	CH	H	H	H	NO2	H	none	none
182N	C6H5O	H	H	H	CH	H	H	H	SO2CH3	H	none	none
183N	C6H5O	H	H	H	CH	H	H	H	2-NO2-4-ClC6H3O	H	none	none
184N	C6H5O	H	H	H	CH	H	H	4-ClC6H4O	H	H	none	none
185N	C6H5O	H	H	H	CH	H	H	3,4-ClC6H3O	H	H	none	none
186N	C6H5O	H	H	H	CH	H	H	3-CF3C6H3O	H	H	none	none
187N	C6H5O	H	H	H	CH	H	H	3,5-ClC6H3O	H	H	none	none
188N	C6H5O	H	H	H	CH	H	H	H	CH3O	H	none	none
189N	C6H5O	H	H	H	CH	H	H	H	CO2CH3	H	none	none
190N	C6H5O	H	H	H	CH	H	H	3-CH3OC6H5O	H	H	none	none
191N	C6H5O	H	H	H	CH	H	H	4-CH3OC6H5O	H	H	none	none
193N	C6H5O	H	H	H	CH	H	H	CO2CH3	H	H	none	none
194N	CN	H	H	H	CH	H	H	OCF3	H	H	none	none
195N	NO2	H	H	H	CH	H	H	OCF3	H	H	none	none
196N	H	CN	H	H	CH	H	H	OCF3	H	H	none	none
197N	H	NO2	H	H	CH	H	H	OCF3	H	H	none	none
198N	SO2CH3	H	H	H	CH	H	H	OCF3	H	H	none	none
199N	H	SO2CH3	H	H	CH	H	H	OCF3	H	H	none	none
200N	H	4-FC6H5SO2	H	H	CH	H	H	OCF3	H	H	none	none
201N	SO2N(CH3)2	H	H	H	CH	H	H	OCF3	H	H	none	none
202N	H	SO2N(CH3)2	H	H	CH	H	H	OCF3	H	H	none	none
203N	H	CONH2	H	H	CH	H	H	OCF3	H	H	none	none
204N	H	CONHC6H5	H	H	CH	H	H	OCF3	H	H	none	none
205N	H	CO2CH3	H	H	CH	H	H	OCF3	H	H	none	none
206N	H	CO2C4H9	H	H	CH	H	H	OCF3	H	H	none	none
207N	H	4-ClC6H5	H	H	CH	H	H	C6H5O	H	H	none	none
208N	H	4-CF3OC6H5	H	H	CH	H	H	CF3O	H	H	none	none
209N	4-FC6H4O	H	H	H	CH	H	H	CF3O	H	H	none	none
210N	C6F5O	H	H	H	CH	H	H	CF3O	H	H	none	none
211N	H	4-FC6H5	H	H	CH	H	H	CF3O	H	H	none	none
212N	H	4-CNC6H5	H	H	CH	H	H	CF3O	H	H	none	none
213N	H	4-C6H5C6H5	H	H	CH	H	H	CF3O	H	H	none	none
214N	C6H5O	H	H	H	CH	CH3	H	CF3O	H	H	none	none
215N	C6H5O	H	H	H	CH	CH3	H	NO2	H	H	none	none
216N	C6H5O	H	H	H	CH	CH3	H	H	CN	H	none	none
217N	C6H5O	H	H	H	CH	3-CF3C6H5	H	CF3	H	H	none	none
218N	C6H5O	H	H	H	CH	C6H5	H	H	C6H5	H	none	none
219N	C6H5O	H	H	H	CH	C6H5	H	CF3	H	H	none	none
220N	C6H5O	H	H	H	CH	CH3	H	F	H	H	none	none
221N	C6H5O	H	H	H	CH	CF3	H	H	H	H	none	none
222N	bond to Oof R6 aryl group		H	H	CH	H	H	CF3O	H	H	none	none
223N	to CH2 of R5 aryl group		H	H	CH	H	H	CF3O	H	H	none	none
224N	C6H5O	H	H	H	CH	H	H	OCF2CF2H	H	H	none	none
225N	4-ClC6H5O	H	H	H	CH	H	H	OCF2CF2H	H	H	none	none
226N	4-FC6H5O	H	H	H	CH	H	H	OCF2CF2H	H	H	none	none
227N	3,4-ClC6H5O	H	H	H	CH	H	H	OCF2CF2H	H	H	none	none
228N	H	C6H5	H	H	CH	H	H	OCF2CF2H	H	H	none	none
229N	H	4-ClC6H5	H	H	CH	H	H	OCF2CF2H	H	H	none	none
230N	H	4-FC6H5	H	H	CH	H	H	OCF2CF2H	H	H	none	none
231N	H	4-BrC6H5	H	H	CH	H	H	OCF2CF2H	H	H	none	none
232N	4-BrC6H5O	H	H	H	CH	H	H	OCF2CF2H	H	H	none	none
233N	C6H5O	H	H	H	CH	H	H	OCF2CF3	H	H	none	none
234N	4-ClC6H5O	H	H	H	CH	H	H	OCF2CF3	H	H	none	none
235N	4-FC6H5O	H	H	H	CH	H	H	OCF2CF3	H	H	none	none
236N	3,4-ClC6H5O	H	H	H	CH	H	H	OCF2CF3	H	H	none	none
237N	H	C6H5	H	H	CH	H	H	OCF2CF3	H	H	none	none
238N	H	4-ClC6H5	H	H	CH	H	H	OCF2CF3	H	H	none	none
239N	H	4-FC6H5	H	H	CH	H	H	OCF2CF3	H	H	none	none
240N	H	4-BrC6H5	H	H	CH	H	H	OCF2CF3	H	H	none	none
241N	4-BrC6H5O	H	H	H	CH	H	H	OCF2CF3	H	H	none	none
242N	C6H5O	H	H	H	CH	H	H	OCCl2CCl2H	H	H	none	none
243N	4-ClC6H5O	H	H	H	CH	H	H	OCCl2CCl2H	H	H	none	none
244N	4-FC6H5O	H	H	H	CH	H	H	OCCl2CCl2H	H	H	none	none
245N	3,4-ClC6H5O	H	H	H	CH	H	H	OCCl2CCl2H	H	H	none	none
246N	H	C6H5	H	H	CH	H	H	OCCl2CCl2H	H	H	none	none
247N	H	4-ClC6H5	H	H	CH	H	H	OCCl2CCl2H	H	H	none	none
248N	H	4-FC6H5	H	H	CH	H	H	OCCl2CCl2H	H	H	none	none
249N	H	4-BrC6H5	H	H	CH	H	H	OCCl2CCl2H	H	H	none	none
250N	4-BrC6H5O	H	H	H	CH	H	H	OCCl2CCl2H	H	H	none	none
251N	C6H5O	H	H	H	CH	H	H	OCCl2CCl3	H	H	none	none
252N	4-ClC6H5O	H	H	H	CH	H	H	OCCl2CCl3	H	H	none	none
253N	4-FC6H5O	H	H	H	CH	H	H	OCCl2CCl3	H	H	none	none
254N	3,4-ClC6H5O	H	H	H	CH	H	H	OCCl2CCl3	H	H	none	none
255N	H	C6H5	H	H	CH	H	H	OCCl2CCl3	H	H	none	none
256N	H	4-ClC6H5	H	H	CH	H	H	OCCl2CCl3	H	H	none	none
257N	H	4-FC6H5	H	H	CH	H	H	OCCl2CCl3	H	H	none	none
258N	H	4-BrC6H5	H	H	CH	H	H	OCCl2CCl3	H	H	none	none
259N	4-BrC6H5O	H	H	H	CH	H	H	OCCl2CCl3	H	H	none	none
260N	C6H5O	H	H	H	CH	H	H	OCCl2CF3	H	H	none	none
261N	4-ClC6H5O	H	H	H	CH	H	H	OCCl2CF3	H	H	none	none
262N	4-FC6H5O	H	H	H	CH	H	H	OCCl2CF3	H	H	none	none
263N	3,4-ClC6H5O	H	H	H	CH	H	H	OCCl2CF3	H	H	none	none
264N	H	C6H5	H	H	CH	H	H	OCCl2CF3	H	H	none	none
265N	H	4-ClC6H5	H	H	CH	H	H	OCCl2CF3	H	H	none	none
266N	H	4-FC6H5	H	H	CH	H	H	OCCl2CF3	H	H	none	none
267N	H	4-BrC6H5	H	H	CH	H	H	OCCl2CF3	H	H	none	none
268N	4-BrC6H5O	H	H	H	CH	H	H	OCCl2CF3	H	H	none	none
269N	C6H5O	H	H	H	CH	H	H	OCF2CCl3	H	H	none	none
270N	4-ClC6H5O	H	H	H	CH	H	H	OCF2CCl3	H	H	none	none
271N	4-FC6H5O	H	H	H	CH	H	H	OCF2CCl3	H	H	none	none
272N	3,4-ClC6H5O	H	H	H	CH	H	H	OCF2CCl3	H	H	none	none
273N	H	C6H5	H	H	CH	H	H	OCF2CCl3	H	H	none	none
274N	H	4-ClC6H5	H	H	CH	H	H	OCF2CCl3	H	H	none	none
275N	H	4-FC6H5	H	H	CH	H	H	OCF2CCl3	H	H	none	none
276N	H	4-BrC6H5	H	H	CH	H	H	OCF2CCl3	H	H	none	none
277N	4-BrC6H5O	H	H	H	CH	H	H	OCF2CCl3	H	H	none	none
278N	C6H5O	H	H	H	CH	H	H	OCF2CF2H	OCF2CF2H	H	none	none
279N	4-ClC6H5O	H	H	H	CH	H	H	OCF2CF2H	OCF2CF2H	H	none	none
280N	4-FC6H5O	H	H	H	CH	H	H	OCF2CF2H	OCF2CF2H	H	none	none
281N	3,4-ClC6H5O	H	H	H	CH	H	H	OCF2CF2H	OCF2CF2H	H	none	none
282N	H	C6H5	H	H	CH	H	H	OCF2CF2H	OCF2CF2H	H	none	none
283N	H	4-ClC6H5	H	H	CH	H	H	OCF2CF2H	OCF2CF2H	H	none	none
284N	H	4-FC6H5	H	H	CH	H	H	OCF2CF2H	OCF2CF2H	H	none	none
285N	H	4-BrC6H5	H	H	CH	H	H	OCF2CF2H	OCF2CF2H	H	none	none
286N	4-BrC6H5O	H	H	H	CH	H	H	OCF2CF2H	OCF2CF2H	H	none	none
287N	C6H5O	H	H	H	CH	H	H	OCF3	OCF3	H	none	none
288N	4-ClC6H5O	H	H	H	CH	H	H	OCF3	OCF3	H	none	none
289N	4-FC6H5O	H	H	H	CH	H	H	OCF3	OCF3	H	none	none
290N	3,4-ClC6H5O	H	H	H	CH	H	H	OCF3	OCF3	H	none	none
291N	H	C6H5	H	H	CH	H	H	OCF3	OCF3	H	none	none
292N	H	4-ClC6H5	H	H	CH	H	H	OCF3	OCF3	H	none	none
293N	H	4-FC6H5	H	H	CH	H	H	OCF3	OCF3	H	none	none
294N	H	4-BrC6H5	H	H	CH	H	H	OCF3	OCF3	H	none	none
295N	4-BrC6H5O	H	H	H	CH	H	H	OCF3	OCF3	H	none	none
296N	C6H5O	H	H	H	CH	H	H	OCF2H	OCF2H	H	none	none
297N	4-ClC6H5O	H	H	H	CH	H	H	OCF2H	OCF2H	H	none	none
298N	4-FC6H5O	H	H	H	CH	H	H	OCF2H	OCF2H	H	none	none
299N	3,4-ClC6H5O	H	H	H	CH	H	H	OCF2H	OCF2H	H	none	none
300N	H	C6H5	H	H	CH	H	H	OCF2H	OCF2H	H	none	none
301N	H	4-ClC6H5	H	H	CH	H	H	OCF2H	OCF2H	H	none	none
302N	H	4-FC6H5	H	H	CH	H	H	OCF2H	OCF2H	H	none	none
303N	H	4-BrC6H5	H	H	CH	H	H	OCF2H	OCF2H	H	none	none
304N	4-BrC6H5O	H	H	H	CH	H	H	OCF2H	OCF2H	H	none	none
305N	C6H5O	H	H	H	CH	H	H	R10 R11 OCF2CF2O	H	none	none
306N	4-ClC6H5O	H	H	H	CH	H	H	R10 R11 OCF2CF2O	H	none	none
307N	4-FC6H5O	H	H	H	CH	H	H	R10 R11 OCF2CF2O	H	none	none
308N	3,4-ClC6H5O	H	H	H	CH	H	H	R10 R11 OCF2CF2O	H	none	none
309N	H	C6H5	H	H	CH	H	H	R10 R11 OCF2CF2O	H	none	none
310N	H	4-ClC6H5	H	H	CH	H	H	R10 R11 OCF2CF2O	H	none	none
311N	H	4-FC6H5	H	H	CH	H	H	R10 R11 OCF2CF2O	H	none	none
312N	H	4-BrC6H5	H	H	CH	H	H	R10 R11 OCF2CF2O	H	none	none
313N	4-BrC6H5O	H	H	H	CH	H	H	R10 R11 OCF2CF2O	H	none	none
314N	C6H5O	H	H	H	CH	H	H	R10 R11 OCCl2CCl2O	H	none	none
315N	4-ClC6H5O	H	H	H	CH	H	H	R10 R11 OCCl2CCl2O	H	none	none
316N	4-FC6H5O	H	H	H	CH	H	H	R10 R11 OCCl2CCl2O	H	none	none
317N	3,4-ClC6H5O	H	H	H	CH	H	H	R10 R11 OCCl2CCl2O	H	none	none
318N	H	C6H5	H	H	CH	H	H	R10 R11 OCCl2CCl2O	H	none	none
319N	H	4-ClC6H5	H	H	CH	H	H	R10 R11 OCCl2CCl2O	H	none	none
320N	H	4-FC6H5	H	H	CH	H	H	R10 R11 OCCl2CCl2O	H	none	none
321N	H	4-BrC6H5	H	H	CH	H	H	R10 R11 OCCl2CCl2O	H	none	none
322N	4-BrC6H5O	H	H	H	CH	H	H	R10 R11 OCCl2CCl2O	H	none	none
323N	H	H	H	H	CH	H	H	OH	H	H	none	none
324N	H	H	H	H	CH	H	H	OH	OH	H	none	none
325N	H	H	H	H	CH	H	H	H	OH	H	none	none
326N	H	H	H	H	CH	H	H	OCH2CF3	H	H	none	none
327N	H	H	H	H	CH	H	H	H	OCH2CF3	H	none	none
328N	H	H	H	H	CH	H	H	OCH2CF2CF3	H	H	none	none
329N	H	H	H	H	CH	H	H	OCH2CH2CF3	H	H	none	none
330N	H	H	H	H	CH	H	H	OCH(CF3)3	H	H	none	none
331N	H	4-FC6H5O	H	H	CH	H	H	H	H	H	none	none
332N	4-FC6H5O	H	H	H	CH	H	H	H	H	H	none	none
333N	H	cyclohexoxy	H	H	CH	H	H	H	H	H	none	none
334N	cyclo-hexoxy	H	H	H	CH	H	H	H	H	H	none	none
335N	H	C(CH3)3	H	H	CH	H	H	H	H	H	none	none
336N	F	H	H	H	CH	H	H		bond to indicated phenyl carbon of R10 subst.	H	none	none

[0385]

TABLE 5
Structure of Secondary Phenyl Amine Reagents (Y and Z each
equal CH; R7, R8, R12, R13, R14, and R15 each equal H).
	(XIII-A)
	Reagent
	Number	R4	R5	R6	R9	R10	R11
	1DB	H	OCF3	H	H	OCF3	H
	2DB	H	Cl	H	H	H	CF3
	3DB	H	Br	H	H	OCF3	H
	4DB	H	Cl	H	H	OCF3	H
	5DB	H	Cl	H	H	CF3	H
	6DB	H	H	Cl	H	CF3	H
	7DB	H	F	H	H	OCF3	H
	8DB	H	H	Cl	H	H	CF3
	9DB	H	F	H	H	H	CF3
	10DB	H	H	F	H	H	CF3
	11DB	F	H	H	H	H	CF3
	12DB	H	Cl	H	CF3	H	H
	13DB	H	H	Cl	CF3	H	H
	14DB	Cl	H	H	CF3	H	H
	15DB	H	F	H	CH3	H	H
	16DB	H	H	F	H	H	CH3
	17DB	H	F	H	H	CH3	H
	18DB	F	H	H	CH3	H	H
	19DB	H	H	F	H	CH3	H
	20DB	F	H	H	H	H	CH3
	21DB	F	H	H	H	CF3	H
	22DB	Cl	H	H	H	CF3	H
	23DB	H	F	H	CF3	H	H
	24DB	H	H	F	CF3	H	H
	25DB	H	F	H	H	CF3	H
	26DB	H	H	F	H	CF3	H
	27DB	H	OCF3	H	H	H	OCF3