US 4,246,409 AGrant

Triazinones

Issue Date:1981-01-20

•29 Claims

Abstract

Novel s-triazine compounds are prepared as derivatives of the corresponding amidinourea and amidinothiourea compounds by reacting with an activated form of an acid amide to give substituted s-triazinones and thiones respectively, of the formula ##STR1## The s-triazinones and thiones are useful derivatives in analyzing for the corresponding amidinourea or amidino thiourea precursors and also have useful pharmacological properties which make them suitable for a variety of medicinal purposes including use as antidiarrheal agents.

Metadata

Assignee

William H. Rorer, Inc.

Inventors

George H. Douglas
William L. Studt
Chong M. Won
Stuart A. Dodson
Jerome J. Zalipsky

Application Information

Application Number:US 9596119

Filing Date:1978-11-13

Priority Date:1978-11-13

Art Unit:121

Classifications

IPC:

C07D25142C07D41704C07D41304C07D41314

Field of Search:

544211;212;60;113

Patent Drawings

This patent does not have any drawings.

Description

FIELD OF THE INVENTION

This invention pertains to a novel method for cyclizing amidinoureas and amidino thioureas, to novel heterocyclic compounds produced by the method, and to a novel analytical method.

Amidinourea and amidinothiourea and their derivatives are known in the art and have been previously disclosed as having useful pharmacological properties. Such compounds are disclosed for example in U.S. Pat. Nos. 4,060,635 and 4,058,557 and in co-pending application Ser. No. 671,762 now abandoned all of which are assigned to the assignee of the present application.

In the development of pharmacologically active compounds for drug use in the treatment of human disorders it is well recognized that extensive testing is carried out to define among other things the mode of action, toxicity and ultimate fate of the drug which is administered to the patient. In particular, the amidinoureas continue to be extensively investigated for a variety of pharmacodynamic effects. An important part of such investigations involves the analyses of samples of materials such as body tissue, blood serum, secretions and excretions to determine the qualitative and quantitative presence of the drug in order to establish the characteristics of the drug with respect to absorption, diffusion and transport, biotransformation by decomposition or conjunction and ultimate elimination from the body following administration to humans or animals including test animals. Gas chromatographic analysis has been found to be a useful tool for detecting the presence of a drug in a sample containing a variety of other materials. However, for gas chromatographic detection the drug must be capable of being volatilized without degradation at the temperature of the carrier gas and must be inert to both the carrier gas and the column packing material.

Gas chromatographic analysis of polar organic amides has proved difficult owing to strong interaction between the functional groups and the surface active sites in the stationary materials comprising the chromatographic column. These difficulties can frequently be overcome by first converting the organic amides to less active derivatives such as by forming an alkyl ester of the carboxyl group followed by acylation of the primary amino group. Primary amino groups have also been derivatized by reacting with dimethyl-formamide dimethylacetal (DMF DMA) to form the dimethyl aminomethylene derivative. The same reagent has also been used to esterify carboxyl groups. More recently DMF DMA has been used to simultaneously derivatize carboxylic and amino groups by reacting with amino acids containing only primary amino and carboxyl groups; Analytic Letters, 5(8), 519-529 1972.

Since the use of gas chromatographic techniques to analyze for amidinoureas directly proved difficult, derivatization of the functional groups utilizing DMF DMA as the derivatizing reagent was attempted. The analysis of amidinoureas and amidinothioureas by gas chromatographic techniques was found to be facilitated by such derivatization though unexpectedly the derivatives obtained proved to be a novel class of s-triazinone and thione compounds, more particularly, 1,4-substituted 1,2-dihydro-1,3,5-triazin-2-ones and 1,4-substituted-1,2-dihydro-1,3 -5triazin-2-thiones.

DESCRIPTION OF THE PRIOR ART

As disclosed in co-pending application Ser. No. 671,762, the disclosure of which is hereby incorporated by reference the amidinoureas can exist in various tautomeric or alternative structural forms. The same is true for the amidino thioureas. Among the theoretical forms of the amidinoureas described in said co-pending application are structures having primary amino groups and therefore it might be theorized that the dimethyl amino methylene derivative of such amidinoureas could be prepared by reacting with DMF DMA. Repeated efforts to prepare the derivatives of numerous amidinoureas led instead to the preparation of triazine compounds of novel structure which were nonetheless found to be suitable for gas chromatographic analysis to determine the qualitative and quantitative presence of the corresponding amidinourea. In an analogous way suitable triazine derivatives of the corresponding amidinothioureas are also prepared.

Substituted triazines are well known as are a variety of triazinones and thiones prepared by a number of synthetic routes, for example, as described in U.S. Pat. No. 3,585,197. However, it does not appear that prior disclosures taught that 1,4-disubstituted triazinones especially those having an aryl or aralkyl substituent, can be readily prepared in nearly quantitative yield by cyclizing the corresponding amidinoureas with a derivatizing agent in accordance with the present invention. The preparation of s-triazin-2-ones and s-triazin-2-thiones in accordance with this technique provides a variety of novel triazine derivatives which are biologically active when administered to mammalian species to produce useful pharmacotherapeutic effects. Accordingly, it is an object of this invention to provide a novel process for the preparation of triazines by cyclizing amidinoureas and amidinothioureas thereby to provide derivatives which are useful inter alia as analytical tools to determine the presence of the corresponding amidinoureas or amidinothioureas by gas chromotographic methods which would otherwise not be possible.

Additionally, it is an object of this invention to provide a novel class of compounds possessing useful pharmacological properties which novel compounds and their pharmaceutically acceptable salts can be used for the treatment of a variety of physiological disorders, e.g., diarrhea and other gastrointestinal disorders.

SUMMARY

In accordance with the present invention, there is provided a novel class of 1,4-substituted-1,2-dihydro-1,3,5-triazin-2-ones and thiones of formula I ##STR2## wherein: X is

oxygen or

sulfur;

R.sub.1 is

aryl,

aralkyl,

5 or 6 membered heterocyclic groups or

5 or 6 membered heterocyclic groups attached to the triazine through a lower alkylidene group;

R.sub.2 is

hydrogen or

loweralkyl; and

R.sub.3 and R.sub.4 are each independently selected from the group consisting of

hydrogen,

hydroxyl,

acyl,

an aliphatic or substituted aliphatic group,

an aromatic group,

an aliphatic or aromatic ether group or a heterocyclic group;

or together R.sub.3 and R.sub.4 are alkylene or alkylene interrupted by 0 to 2 hetero atoms which may be N, O or S so that R.sub.3 and R.sub.4 together with the nitrogen to which they are attached form a 3 to 7 membered ring containing 1 to 3 hetero atoms.

The cyclic derivative can be used to assay for the corresponding amidinourea or amidinothiourea by injecting a sample along with a suitable vaporizable carrier into a gas chromatograph. The compounds can also be used for pharmacotherapeutics by administering to animals or humans suitable dosage forms containing an effective amount for the treatment of gastrointestinal irregularities such as diarrhea.

In one aspect this invention pertains to a novel class of triazines which are prepared as derivatives of amidinoureas or amidinothioureas to provide a gas chromatographic method for detecting the presence of the amidinourea or amidinothiourea in a sample containing the amidinourea or amidinothiourea in admixture with unknown materials.

In another aspect this invention provides a novel analytical method to assay for amidinoureas and amidinothioureas in biological samples.

In yet another aspect, this invention provides a novel cyclizing reaction for the preparation of triazines and triazine derivatives.

In still another aspect, this invention provides compounds which are useful in pharmacotherapeutics particularly as antidiarrheals or as antimotility or antisecretory agents or as antispasmodic agents.

Certain of the novel compounds also have effects on nerve tissue indicating use in the control of disorders involving abnormal nerve impulse transmission.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

According to the novel compound aspect of this invention, there is provided a new class of substituted triazines, more particularly a novel class of s-triazinones and s-triazinthiones of the formula: ##STR3## wherein: X is

oxygen or

sulfur;

R.sub.1 is

aryl,

aralkyl,

5 or 6 membered heterocyclic groups or

5 or 6 membered heterocyclic groups attached to the triazine through a lower alkylidene group;

R.sub.2 is

hydrogen or

loweralkyl; and

R.sub.3 and R.sub.4 are each independently selected from the group consisting of

hydrogen,

hydroxyl,

acyl,

an aliphatic or substituted aliphatic group,

an aromatic group,

an aliphatic or aromatic ether group, or

a 5 or 6 membered heterocyclic group; or

together R.sub.3 and R.sub.4 are alkylene or alkylene interrupted by 1 or 2 hetero atoms which may be N, O or S, so that R.sub.3 and R.sub.4 together with the nitrogen to which they are attached form a 3 to 7 membered ring containing 1 to 3 hetero atoms;

and their non-toxic pharmaceutically acceptable salts.

Depending upon the specific substitution, compounds of formula I above may be present in enolized or tautomeric forms. Certain of the compounds can also be obtained as hydrates or in different polymorphic forms. The structures used herein to designate novel compounds are intended to include the compound shown along with its alternatives or transient states. The nomenclature generally employed to identify the novel triazine derivatives as disclosed herein is based upon the ring structure shown in formula I with the triazine ring positions numbered counterclockwise beginning with the nitrogen having the R.sub.1 substitution.

s-triazinones and s-triazinthiones of this invention which form a preferred class of novel compounds, are those represented by the formula I-a. ##STR4## wherein: X is

oxygen or

sulfur;

R.sub.1 is

phenyl,

benzyl or

phenethyl;

or phenyl, benzyl or phenethyl in which one or more of the phenyl hydrogens are substituted by

loweralkyl,

loweralkoxy,

halo,

haloloweralkyl,

amino,

nitro,

acyloxy,

acylamino,

hydroxy,

cyano,

carboxyl, or

loweralkylsulfonyl (especially 2'6'-disubstituted phenyl, benzyl or phenethyl);

pyridyl or substituted pyridyl;

R.sub.2 is

hydrogen or

loweralkyl; and

R.sub.3 and R.sub.4 are each independently selected from the group consisting of

hydrogen,

hydroxyl,

loweralkanoyl,

loweralkyl,

loweralkenyl,

loweralkynyl,

loweralkoxy,

haloloweralkyl,

hydroxyloweralkyl,

loweralkoxyloweralkyl,

phenoxyloweralkyl,

diloweralkylamino,

loweralkyl, or

R.sub.3 and R.sub.4 together with the nitrogen to which they are attached form a 5 or 6 membered nitrogen heterocycle containing 0 to 1 additional hetero atoms which may be

nitrogen,

oxygen or

sulfur;

and their non-toxic salts.

When R.sub.1 is pyridyl in formula I-a above, the preferred groups are those wherein the pyridyl nitrogen is adjacent to the ring carbon attached to the triazinone ring, i.e. a 2-pyridyl and substituted pyridyls in which one or both pyridyl ring carbons adjacent to the carbon attached to the triazinone ring are substituted by loweralkyl, loweralkoxy, or haloloweralkyl.

Where R.sub.1 is substituted phenyl, benzyl or phenethyl, the preferred substituents on the phenyl moiety are the loweralkyl, halo, and loweralkoxyphenyl groups in the ortho positions. The substituents may be the same or different.

A more specific group of preferred compounds according to this invention are the s-triazinones of formula I-b. ##STR5## wherein: R.sub.2 is

hydrogen or

loweralkyl;

R.sub.3 and R.sub.4 are each

hydrogen,

loweralkyl,

hydroxy,

loweralkoxy,

phenoxy,

diloweralkylaminoloweralkyl,

loweralkanoyl,

loweralkenyl and

loweralkynyl or

R.sub.3 and R.sub.4 together with the nitrogen to which they are attached form a 5 or 6 membered heterocyclic ring preferably

pyrrolidinyl,

oxazolidinyl,

thiazolidinyl,

pyrazolidinyl,

imidazolidinyl,

piperidyl,

piperazinyl,

thiamorpholinyl, or

morpholinyl.

R.sub.5 is

hydrogen,

halo,

loweralkyl or

loweralkoxy; and

R.sub.9 is

halo,

loweralkyl, or

loweralkoxy.

Another more specific preferred group are the s-triazinones of the formula I-c. ##STR6## wherein: R.sub.3 is

hydrogen,

hydroxy,

loweralkyl,

loweralkoxy, or

diloweralkylaminoloweralkyl; and

R.sub.5 and R.sub.9 are each

loweralkyl,

halo,

haloloweralkyl, or

loweralkoxy; and

R.sub.5 and R.sub.9 may be the same or different.

As employed above and throughout the disclosure, the following terms, unless otherwise indicated, shall be understood to have the following meanings:

"alkyl" means a saturated aliphatic hydrocarbon which may be either straight or branched chain preferably having no more than about 20 carbon atoms; loweralkyl being preferred; also included are the cycloalkyl groups such as cyclohexyl, cyclopropyl etc. and the cycloalkylalkyl groups such as cyclopropylmethyl and the like.

"loweralkyl" means an alkyl group as above, having 1 to 6 carbon atoms, suitable loweralkyl groups are methyl, ethyl propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl and isopentyl.

"cycloalkyl" means an aliphatic monocyclic saturated carbocyclic group having 3 to 6 carbon atoms preferably cyclopropyl, cyclopentyl, and cyclohexyl.

"alkenyl" means an unsaturated aliphatic hydrocarbon having no more than about 20 carbon atoms and which contains one or more double bonds and which may be straight or branched chain with loweralkenyl, i.e. alkenyl of 2 to 6 carbons, being preferred.

"loweralkenyl" means alkenyl of 2 to 6 carbon atoms such as ethylene, propylene, butylene, isobutylene, etc.

"alkynyl" means an unsaturated aliphatic hydrocarbon having no more than about 20 carbon atoms and containing one or more triple bonds with lower alkynyl, i.e. alkynyl of 2 to 6 carbons, being preferred.

"loweralkynyl" means alkynyl of 2 to 6 carbon atoms such as propargyl, butynyl, pentynyl, etc.

"aryl" means phenyl and substituted phenyl.

"substituted phenyl" means a phenyl group in which one or more of the hydrogens has been replaced by the same or different substituents including halo, loweralkyl, haloloweralkyl, nitro, amino, acylamino, hydroxy, loweralkoxy, aryl-loweralkoxy acyloxy, cyano, halo-loweralkoxy or loweralkylsulfonyl.

"aralkyl" means an alkyl (preferably a loweralkyl) in which one or more hydrogens is substituted by an aryl moiety (preferably phenyl or substituted phenyl), e.g. benzyl, phenethyl, etc.

"5 and 6 membered heterocyclic group" means a 5 or 6 membered ring having 1 to 3 hetero atoms which may be nitrogen, oxygen or sulfur including pyridyl, 2-pyridyl or 3-pyridyl; pyrimidyl, pyrazolyl, imidazolyl, furyl, thienyl, oxazoneyl, thiazolyl, piperidyl, morpholinyl etc. with the pyridyl groups being preferred.

"substituted pyridyl" means a pyridyl in which one or more of the hydrogens on the ring carbons have been replaced by substituents as given above with respect to substituted phenyl.

The terms "halo" and "halogen" include all four halogens; namely, fluorine, chlorine, bromine and iodine. The halo alkyls, halophenyl and halosubstituted pyridyl include groups having more than one halo substituent which may be the same or different such as trifluoromethyl, 1-chloro-2-bromo ethyl, chlorophenyl, 4-chloropyridyl, etc.

The term "acyloxy" is intended to mean an organic acid radical such as acetoxy, propionoxy, and the like.

The term "loweralkanoyl" is intended to include the acid radical of a loweralkanoic acid such as acetyl, propionyl and the like.

Among the compounds of formula I, a particularly preferred group of novel compounds are those in which the R.sub.1 substituent is a substituted phenyl and particularly a phenyl having substituents in the 2 and 6 positions (i.e., ortho to the carbon attached to the triazine nitrogen). The preferred phenyl substituents are loweralkyl, loweralkoxy and halo. The preferred R.sub.3 and R.sub.4 substituents are those where R.sub.3 and R.sub.4 are the same and both are loweralkyl, halo-loweralkyl or loweralkoxy-loweralkyl. The preferred loweralkyl substituents are methyl, ethyl, propyl and isopropyl. The preferred halo substituents are chlorine and bromine. The preferred halo-lower alkyl are chloromethyl and trifluoromethyl.

The pyridyl substituents may be either 2-, 3-, or 4-pyridyls; preferred substituted pyridyls are those having substituents on the carbon or carbon atoms vicinal to the carbon attached to the triazine nitrogen.

According to the cyclizing process aspect of this invention, it has been found that an amidinourea can be cyclized to the corresponding s-triazinone by condensing the amidinourea with an organic reagent having an activated methylidene group or capable of forming an activated methylidene for example, a methylidene group having at least one available hydrogen atom and a leaving group such as a di-substituted amino group attached to the methylidene carbon. As organic reagent for condensing an amidinourea or thiourea starting material to form an s-triazinone or s-triazinthiones there is suitably used an activated form of an acid amine or an ortho ester or acyl derivative such as a Vilsmeir reagent which will bring about acylation and ring closure of the amidinourea or thiourea to give s-triazinones and s-triazinthiones of formula I above. The cyclizing process can be used in the same manner to prepare s-triazinthiones from the corresponding amidinothioureas and it will be understood that in referring to the preparation of triazinones it is intended to include also the thiones. The reagent may be the dialkylacetal of a di-alkyl-lowercarboxylic acid amide or the reaction product of a di-alkyl-lowercarboxylic acid amide and an alkylating agent. The reagent can be prepared in situ or in advance depending upon its stability. While this reaction finds applicability generally for cyclizing amidinoureas it is especially useful in preparing the novel s-triazinones of this invention. The synthesis of triazinones according to this invention can employ as starting material known amidinoureas or similar starting materials also known in the art, or the materials employed as precursors for cyclizing to form s-triazinones can be readily prepared by analogy to the preparation of the known starting materials. Suitable amidinourea starting materials are those disclosed in U.S. Pat. Nos. 4,060,635 and 4,058,557 and in copending application Ser. No. 671,762 the disclosures of which, as previously noted, are incorporated here by reference. Thus, the novel cyclizing process of this invention can be used to derivatize amidinoureas and thioureas of formula II below. ##STR7## wherein X, R.sub.1, R.sub.3 and R.sub.4 have the same meanings as above.

It should be understood that whereas the structure of the starting materials are shown here in a particular configuration for the purposes of illustration it is intended to include the various structural isomers as previously noted. By way of illustration, an alternative structure is shown by formula II-a. Where reference is made to that terminal nitrogens, it is intended to denote the urea nitrogen designated as position 1 in formula II and the unsubstituted amidino nitrogen.

Thus, there can be prepared in accordance with the process of this invention 1,3,5-triazin-2-ones and 1,3,5-triazin-2-thiones utilizing as starting materials any of the prior art amidinoureas or amidinothioureas including the 1-arylamidinoureas and thioureas of Formula III below which constitute a preferred group of starting materials. ##STR8## wherein X and the R.sub.3 and R.sub.4 substituents have the same meanings as the corresponding substituents on the novel triazines of formula I described hereinabove and wherein the substituents on the phenyl ring are as follows: R.sub.5, R.sub.6, R.sub.7, R.sub.8 and R.sub.9 may be the same or different and are:

hydrogen,

halo,

loweralkyl,

haloloweralkyl,

nitro,

loweralkoxy,

hydroxy,

arylloweralkoxy,

acyloxy,

cyano,

haloloweralkoxy or

loweralkylsulfonyl.

Amidinourea starting materials which can be used to prepare a more preferred group of triazine derivatives are those wherein

R.sub.3 and R.sub.4 are

hydrogen,

hydroxy,

loweralkyl,

loweralkoxy,

haloloweralkyl, or

aralkyl; or

R.sub.3 and R.sub.4 together may form with the nitrogen to which they are attached a 5-7 atom ring which may include 0-2 hetero atoms of N, O or S.

An even more preferred group of starting materials include those where:

R.sub.5, R.sub.6, R.sub.7, R.sub.8 and R.sub.9 are

hydrogen,

halo,

loweralkyl,

haloloweralkyl,

nitro,

hydroxy or

loweralkoxy.

A still more preferred group of starting materials include those where:

R.sub.5 and R.sub.9 are each

hydrogen,

halo,

loweralkyl,

nitro or

loweralkoxy;

R.sub.6, R.sub.7 and R.sub.8 are each

hydrogen,

hydroxy,

halo,

loweralkyl, or

loweralkoxy; and

R.sub.3 and R.sub.4 are each

hydrogen,

loweralkyl,

hydroxy,

loweralkoxy,

haloloweralkyl, or

acyl.

The most preferred starting materials are those where:

R.sub.5 is

methyl,

ethyl,

chloro or

bromo;

R.sub.6 is hydrogen;

R.sub.7 is hydrogen;

R.sub.8 is hydrogen;

R.sub.9 is

methyl,

ethyl,

nitro,

methoxy,

ethoxy,

chloro,

bromo or

fluoro; and

R.sub.3 and R.sub.4 are each

hydrogen alkyl of C.sub.1 to C.sub.4,

hydroxy,

methoxy,

ethoxy,

chloromethyl,

trifluoromethyl 2,3,2-trifluoroethyl, or

acetyl.

A special embodiment of this invention comprises compounds where the starting materials have:

X is oxygen; and the phenyl group has

R.sub.5, R.sub.9 loweralkyl, loweralkoxy or halo substitution independently of each other;

and one of R.sub.3 and R.sub.4 is hydrogen and the other is

loweralkyl,

haloloweralkyl,

hydroxy,

loweralkoxy or

acyl.

Throughout this disclosure, where reference is made to amidinoureas or triazinones, it will be understood that the same applies also to the corresponding amidinothioureas or triazinthiones; and that in all instances the triazinones and thiones are the 1,2-dihydro-1,3,5-triazin-2-ones and 1,2-dihydro-1,3,5-triazin-2-thiones whatever the abbreviated form of nomenclature that may be used.

The preparation of s-triazinone compounds according to this invention is achieved in general by reacting an appropriate amidinourea or amidinothiourea starting material with an activated form of an acid amide or ortho ester or acyl derivative such as a Vilsmeir reagent which will bring about acylation and ring closure of the amidinourea or thiourea to give the corresponding s-triazinone or thiones of the type described above. The reaction can be carried out by simply combining the reactants in a suitable solvent at room temperature with stirring. The reaction time can be shortened by heating the reaction mixture or by using elevated pressure or both. The solvent selected should have a relatively high boiling point and low vapor pressure in order to permit the reaction mixture to be heated above 100.degree. C. Dimethylformamide is a convenient solvent to use particularly where the cyclizing reagent is a dimethylformamide derivative though other organic solvents can also be used. The solvents that can be used include saturated and unsaturated hydrocarbons, aromatic solvents, alcohols such as methanol and ethanol, halogenated hydrocarbons such as chloroform, carbon tetrachloride, ethylene chloride, or others such as methyl acetate, ethyl acetate, acetonitrile, acetone, ether, acetamide, tetrahydrofuran and the like. Suitable mixtures of solvents can also be used. The reaction is preferably carried out under substantially anhydrous conditions though the presence of water can be tolerated. If small amounts of water are present, the effect can be offset by using an excess of the cyclizing reagent.

The conversion of most amidinoureas to the corresponding s-triazine derivative can be achieved in about 20 minutes or less at temperatures in the order of 100.degree. C. to 120.degree. C. Higher or lower temperatures can be used if desired and the reaction can be carried out at room temperature. In those cases where the reaction proceeds slowly it can be shortened by heat or pressure or both. The reaction can be readily carried out at atmospheric pressure though if desired, the reaction can be facilitated by increased pressure. A convenient method for carrying out the cyclizing reaction is by heating the reaction mixture in a sealed vessel and allowing the reaction to proceed under autogenous pressure. An alternative process is by refluxing the reaction mixture for about an hour or more. Where the starting material utilized is the acid addition salt of an appropriate amidinourea the reaction proceeds almost instantaneously at room temperature in most cases. However, if the amidinourea starting material is used in the form of the free base, a small amount of acid preferably a mineral acid particularly hydrochloric acid is desirably added to the reaction mixture. As mentioned above, the reaction is suitably carried out in the presence of a solvent. The choice of solvent will in general depend upon the cyclizing reagent used. When using a DMF reagent, the preferred solvents are DMF, DMF-dimethylsulfate complex, or a complex with an alcohol (preferably iso-propanol) the particular alcohol will depend on the solubility of the product obtained.

In most cases the cyclized end product can be recovered by filtering after direct crystallization from the reaction mixture particularly where the solvent has been chosen to facilitate recovery of the end product. Where the product does not readily crystallize, the novel s-triazinone derivatives can be conveniently isolated in the pure form by solvent extraction using any of the usual organic solvents which are not miscible with water such as the hydrocarbons, for example, hexane; the chlorinated hydrocarbons, for example, chloroform or carbon tetrafluoride; the aromatic solvents such as benzene, xylene, toluene, o-chloro-toluene and the like; ethers such as dioxane; ketones such as 2 pentanone etc. The s-triazinone product is extracted into the solvent layer generally after stripping the solvent or concentrating the reaction mixture then shaking with an extracting composition of water and solvent and removing the solvent component, leaving the by-product in the aqueous layer. The product is recovered by evaporating off the solvent. If desired, the product can be further purified by recrystallizing from a suitable organic solvent such as those noted above. The selection of solvent is not critical and generally those solvents which are most readily available will be employed.

The amidinourea starting materials which are derivatized in accordance with the process aspect of this invention are known materials prepared as previously noted by known methods such as described in U.S. Pat. Nos. 4,060,635 and 4,058,557.

The cyclizing reagent employed in the reaction can be any cationic reagent system capable of generating in the reaction mixture a stabilized carbonium ion having the oxidation state of an acid or acid amine, preferably an immonium ion. The preferred reagents are the dialkyl carboxylic acid amide dialkyl acetals such as dialkyl formamide dialkyl acetal preferably dimethyl formamide dimethyl acetal; dialkyl acetamide dialkyl acetals preferably dimethyl acetamide dimethyl acetal; dialkyl propionamide dialkyl acetal preferably dimethyl propionamide dimethyl acetal. Other carboxylic acid amide derivatives can also be used including substituted derivatives. Since the carboxyl carbon is incorporated into the ring the choice of reagent will determine the R.sub.2 substitution in the products of formula I above. Thus, in the case of the formamide derivative, R.sub.2 is hydrogen and the resulting triazine is unsubstituted in the 6-position; in the case where the acetamide derivative is used as the cyclizing reagent, R.sub.2 is methyl and the resulting triazine is substituted in the 6-position, and so on. The preferred substituents are lower alkyl for which the cyclizing reagents used are the lower alkanoic acid amide derivatives. Other substituents within the meaning of R.sub.2 are obtained by selection of the correspondingly substituted alkanoic acid amide in preparing the cyclizing reagent.

In general, the preferred cyclizing reagents are the alkanoic acid amide diacetals of the formula: ##STR9## wherein: R.sub.2 is hydrogen or loweralkyl; and each of R.sub.10 through R.sub.13 are loweralkyl or haloloweralkyl.

Other methylidene derivatives that can be used as the cyclizing reagent include the combination of an N,N-disubstituted alkanoic acid amide and any strong alkylating agent preferably a strong methylating agent. Any of the strong alkylating agents known in the art such as methyliodide, methylfluorosulfonate, alkylmethane sulfonates, e.g., methylmethanesulfonate, and alkyl or dialkyl sulfates, e.g., dimethylsulfate can be suitably employed though dimethylsulfate is preferred owing to its ready availability. A preferred cyclizing reagent is a DMF-dimethylsulfate complex particularly DMF-methane methyl-sulfonate or DMF-methylbenzenesulfonate.

Reagents of the type shown in formula IV above are staple products which are commercially available or can be prepared in advance. In carrying out the cyclizing reaction, the cyclizing reagent is preferably used in slight excess of the amount required as the stoichiomeric equivalent of the amidinourea or amidinothiourea starting material. The preferred reagent is dimethyl formamide dimethylacetal in which case dimethylformamide is a convenient solvent. A particularly preferred reagent system is a mixture of dimethyl formamide and dimethyl sulfate utilizing excess dimethyl formamide as a solvent. Such reagent systems employing dimethyl sulfate are prepared as necessary for the cyclization or can be formed in situ in the reaction mixture by adding the reagent components to the reaction vessel in a suitable solvent or solvent mixture. When carrying out the cyclizing reaction with a reagent of the type shown in formula IV, it is preferred to use as starting material an acid addition salt of the amidinourea or amidinothiourea or alternatively, if the free base is used, then an acid preferably a mineral acid such as hydrochloric acid can be added to the reaction mixture. When a reagent system comprising an alkanoic acid amide and a strong alkylating agent is employed, the reagent is itself acidic and the reaction proceeds readily with the free base as starting material. In such instances it may be advantageous to add a proton scavenging solvent such as a tertiary amine, e.g., triethylamine or cyclic amines such as pyridine. Other miscible solvents can be used along with the preferred amines e.g., solvents such as triethanolamine, acrylonitrile, ethanol, etc. though dimethyl formamide is preferred. As in the case of cyclizing with dimethylformamide dimethylacetal the reaction can be carried out at room temperature or at elevated temperatures up to the boiling point of the solvent employed. Preferably, the reaction is carried out at room temperature i.e., at about 18.degree. to 25.degree. C. Elevated pressure may also be used. Suitably, the reaction is carried out by refluxing at the boiling temperature of the solvent. The reaction product is easily recovered from the reaction mixture by solvent extraction as described above. The reaction proceeds nearly quantitatively based upon the amidinourea starting material and the product can be recovered in nearly quantitative yield, the product can be further purified by recrystallizing if desired.

Alternatively, some of the triazinones can be prepared by using other cyclizing reagents such as triethyl orthoformate catalyzed with either base or acid though generally such processes are less suitable and conventional cyclizing agents such as phosphonyl chloride and thionyl chloride have been found to be unsuited for cyclizing amidinoureas.

Pharmaceutically acceptable salts of the compounds can be obtained as acid addition salts prepared from the corresponding free base by recrystallizing from a solution of a non-toxic pharmaceutically acceptable organic or inorganic acid including strong Lewis acids. Other salts for example quarternary ammonium salts are prepared by known methods for quarternizing organic nitrogen compounds. The non-toxic acid addition salts that can be conveniently prepared from the novel triazine derivatives of this invention are preferably those prepared from strong acids of low volatility. Among the suitable acids that can be named are the following:

hydrochloric acid,

hydrobromic acid,

sulfuric acid,

nitric acid,

phosphoric acid,

methane sulfonic acid,

benzene sulfonic acid,

toluene sulfonic acid, etc.

The synthesis of the novel amidinourea and amidinothiourea derivatives of this invention is accomplished in accordance with the novel cyclizing method of this invention which in its broad process aspect consists of cyclizing amidinoureas and amidinothioureas and the like by bridging the terminal nitrogens with a methylidene or substituted methylidene group derived from a suitable derivatizing reagent.

The novel cyclizing reaction can be illustrated schematically as follows: ##STR10## wherein X is sulfur or oxygen indicating that the reaction can employ as starting material either an amidinourea or amidinothiourea. The dangling bonds may be substituted by any appropriate substituent determined by available amidinourea or amidinothourea starting material.

It will be readily apparent that the dangling bonds on the end product 1,3,5-triazin-2-one or 1,3,5-triazine-2-thione will be substituted by groups corresponding to similar substituents on the starting materials.

In accordance with this invention, the process is particularly useful in preparing compounds of formula I by cyclizing the corresponding starting materials and also to prepare compounds of the type shown in formula I where R.sub.1 is an aliphatic group preferably alkyl provided one of R.sub.3 and R.sub.4 is other than hydrogen.

The numerical designations indicate the nomenclature used herein. It will be readily understood that alternative naming systems for these compounds can be employed.

The novel triazine derivatives prepared in accordance with the method of this invention for derivitizing the corresponding amidinourea or thiourea are those in which the substituent in the one position of the amidinourea or amidinothiourea shown schematically above has an aryl or heterocyclic group, preferably compounds of the following formula: ##STR11## wherein: X is

oxygen or

sulfur;

R.sub.1 is

aryl,

aralkyl or

a 5 or 6 membered heterocyclic ring attached directly to the triazine nitrogen or attached through an alkylidene bridge preferably having 1 to 4 carbon atoms;

R.sub.2 is

hydrogen or

loweralkyl;

R.sub.3 and R.sub.4 are each independently selected from the group consisting of

hydrogen,

hydroxyl,

an aliphatic radical which can be alkyl,

alkenyl,

alkynyl,

cycloalkyl or

any of said aliphatic radicals wherein one or more hydrogen atoms has been replaced by hydroxyl,

alkoxy,

phenoxy,

substituted phenoxy,

cycloalkyl,

haloloweralkyl,

amino,

loweralkylamino or

diloweralkylamino,

phenyl or

substituted phenyl or

a 5 or 6 membered heterocyclic group containing 1 to 3 hetero atoms which may be nitrogen,

oxygen or sulfur,

loweralkoxy,

phenoxy,

substituted phenoxy,

phenyl,

substituted phenyl or

acyl preferably loweralkanoyl; or

R.sub.3 and R.sub.4 taken together with the nitrogen to which they are attached may form a 5 or 6 membered heterocyclic ring containing 1 or 2 additional hetero atoms which may be

nitrogen,

oxygen or

sulfur

and the ring may contain 1 or more double bonds; together with their pharmaceutically acceptable salts.

A preferred group of novel triazines prepared by derivetizing amidinoureas are the compounds of the formula: ##STR12## wherein: R.sub.1 is

phenyl,

substituted phenyl,

pyridyl,

substituted pyridyl or

phenyl-loweralkyl; and

R.sub.3 and R.sub.4 are each separately

hydrogen,

loweralkyl,

haloloweralkyl,

hydroxy,

alkoxy,

alkoxyloweralkyl, or loweralkanoyl; and

their non-toxic pharmaceutically acceptable salts.

A particularly preferred group of novel triazinones are the compounds of the formula: ##STR13## wherein: the ortho- substituents on the phenyl moiety designated by R.sub.5 and R.sub.9 are the same or different and are

C.sub.1 to C.sub.4 alkyl,

bromo,

chloro, or

C.sub.1 to C.sub.4 alkoxy; and

the R.sub.3 and R.sub.4 substituents are each

hydrogen,

hydroxyl,

loweralkyl,

haloloweralkyl,

loweralkoxy or

loweralkanoyl.

And those compounds of formula V-b wherein one of R.sub.3 or R.sub.4 is hydrogen are a most preferred group.

Using the general method for cyclizing amidinoureas described above and employing by way of illustration as the starting material any of the amidinoureas in Tables I, Ia and Ib below, there can be obtained the corresponding illustrative triazinone of Tables II, II-a and II-b. The thione analogs and their salts are prepared in the same manner using the corresponding amidinothiourea as starting material. Examples of amidinothiourea starting materials and the corresponding thiones obtained by cyclizing in accordance with the method of this invention are given in Tables III and IV respectively. IV-a, respectively.

TABLE I

1-(2',6'-diethylphenyl)-3-methylamidinourea

1-(2',6'-diethylphenyl)-3-ethylamidinourea

1-(2',6'-diethylphenyl)-3-propylamidinourea

1-(2',6'-diethylphenyl)-3-i-propylamidinourea

1-(2',6'-diethylphenyl)-3-butylamidinourea

1-(2',6'-diethylphenyl)-3-i-butylamidinourea

1-(2',6'-diethylphenyl)-3-pentylamidinourea

1-(2',6'-diethylphenyl)-3-allylamidinourea

1-(2',6'-diethylphenyl)-3-propargylamidinourea

1-(2',6'-diethylphenyl)-3-cyclopropylamidinourea

1-(2',6'-diethylphenyl)-3-methoxyethylamidinourea

1-(2',6'-diethylphenyl)-3-benzyloxyethylamidinourea

1-(2',6'-diethylphenyl)-3-phenethoxyethylamidinuourea

1-(2',6'-diethylphenyl)-3-benzylamidinourea

1-(2',6'-diethylphenyl)-3-(N,N-dimethylamidino)urea

1-(2',6'-diethylphenyl)-3-(N,N-diethylamidino)urea

1-(2',6'-diethylphenyl)-3-(N,N-tetramethyleneamidino)urea

1-(2',6'-diethylphenyl)-3-(N,N-pentamethyleneamidino)urea

1-(2'-methyl-6'-ethylphenyl)-3-methylamidinourea

1-(2'-methyl-6'-ethylphenyl)-3-ethylamidinourea

1-(2'-methyl-6'-ethylphenyl)-3-propylamidinourea

1-(2'-methyl-6'-ethylphenyl)3-i-propylamidinourea

1-(2'-methyl-6'-ethylphenyl)-3-butylamidinourea

1-(2'-methyl-6'-ethylphenyl)3-i-butylamidinourea

1-(2'-methyl-6'-ethylphenyl)3-t-butylamidinourea

1-(2'-methyl-6'-ethylphenyl)-3-pentylamidinourea

1-(2'-methyl-6'-ethylphenyl)-3-allylamidinourea

1-(2'-methyl-6'-ethylphenyl)-3-propargylamidinourea

1-(2'-methyl-6'-ethylphenyl)-3-cyclopropylamidinourea

1-(2'-methyl-6'-ethylphenyl)-3-cyclobutylamidinourea

1-(2'-methyl-6'-ethylphenyl)-3-[N-(3'-cyclopentenyl)amidino]urea

1-(2'-methyl-6'-ethylphenyl)-3-cyclopropylmethylamidinourea

1-(2'-methyl'6'-ethylphenyl)-3-methoxyethylamidinourea

1-(2'-methyl-6'-ethylphenyl)-3-benzyloxyethylamidinourea

1-(2'-methyl-6'-ethylphenyl)-3-phenethoxyethylamidinourea

1-(2'-methyl-6'-ethylphenyl)-3-benzylamidinourea

1-(2'-methyl-6'-ethylphenyl)-3-(N,N-dimethylamidino)urea

1-(2'-methyl-6'-ethylphenyl)-3-(N,N-diethylamidino)urea

1-(2'-methyl-6'-ethylphenyl)-3-(N,N-tetramethyleneamidino)urea

1-(2'-methyl-6'-ethylphenyl)-3-[N,N(3'-methyl-3'-azapentamethylene)amidino] urea

1-(2'-methyl-6'-ethylphenyl)-3-[N,N-(3'-oxapentamethylene)amidino]urea

1-(2'-methyl-6'-chlorophenyl)-3-methylamidinourea

1-(2'-methyl-6'-chlorophenyl)-3-ethylamidinourea

1-(2'methyl-6'-chlorophenyl)-3-propylamidinourea

1-(2'-methyl-6'-chlorophenyl)3-i-propylamidinourea

1-(2'-methyl-6'-chlorophenyl)-3-butylamidinourea

1-(2'-methyl-6'-chlorophenyl)-3-i-butylamidinourea

1-(2'-methyl-6'-chlorophenyl)-3-t-butylamidinourea

1-(2'-methyl-6'-chlorophenyl)-3-pentylamidinourea

1-(2'-methyl-6'-chlorophenyl)-3-allylamidinourea

1-(2'-methyl-6'-chlorophenyl)-3-propargylamidinourea

1-(2'-methyl-6'-chlorophenyl)-3-cyclobutylamidinourea

1-(2'-methyl-6'-chlorophenyl)-3-cyclohexylamidinourea

1-(2'-methyl-6'-chlorophenyl)-3-benzylamidinourea

1-(2'-methyl-6'-chlorophenyl)-3-methoxyethylamidinourea

1-(2'-methyl-6'-chlorophenyl)-3-benzyloxyethylamidinourea

1-(2'-methyl-6'-chlorophenyl)-3-phenethoxyethylamidinourea

1-(2'-methyl-6'-chlorophenyl)-3-(N,N-diethylamidino)urea

1-(2'-methyl-6'-chlorophenyl)-3-(N,N-pentamethyleneamidino)urea

1-(2'-methyl-6'-bromophenyl)-3-methylamidinourea

1-(2'-methyl-6'-bromophenyl)-3-ethylamidinourea

1-(2'-methyl-6'-bromophenyl)-3-propylamidinourea

1-(2''-methyl-6'-bromophenyl)-3-i-propylamidinourea

1-(2-methyl-6'-bromophenyl)-3-butylamidinourea

1-(2'-methyl-6'-bromophenyl)-3-t-butylamidinourea

1-(2'-methyl-6'-bromophenyl)-3-pentylamidinourea

1-(2'-methyl-6'-bromophenyl)-3-hexylamidinourea

1-(2'-methyl-6'-bromophenyl)-3-propargylamidinourea

1-(2'-methyl-6'-bromophenyl)-3-allylamidinourea

1-(2'-methyl-6'-bromophenyl)-3-methoxyethylamidinourea

1-(2'-methyl-6'-bromophenyl)-3-benzyloxyethylamidinourea

1-(2'-methyl-6'-bromophenyl)-3-phenethoxyethylamidinourea

1-(2'-methyl-6'-bromophenyl)-3-(N,N-dimethylamidino)urea

1-(2'-methyl-6'-bromophenyl)-3-(N,N-diethylamidino)urea

1-(2'-methyl-6'-bromophenyl)-3-(N-methyl-N-ethylamidino)urea

1-(2'-methyl-6'-bromophenyl)-3-(N,N-tetramethyleneamidino)urea

1-(2'-methyl-6'-bromophenyl)-3-(N,N-pentamethyleneamidino)urea

1-(2'-methyl-6'-bromophenyl)-3-(N,N-hexamethyleneamidino)urea

1-(2'-ethyl-6'-chlorophenyl)-3-methylamidinourea

1-(2'-ethyl-6'-chlorophenyl)-3-ethylamidinourea

1-(2'-ethyl-6'-chlorophenyl)-3-propylamidinourea

1-(2'-ethyl-6'-chlorophenyl)-3-butylamidinourea

1-(2'-ethyl-6'-chlorophenyl)-3-i-butylamidinourea

1-(2'-ethyl-6'-chlorophenyl)-3-pentylamidinourea

1-(2'-ethyl-6'-chlorophenyl)-3-allylamidinourea

1-(2'-ethyl-6'-chlorophenyl)-3-propargylamidinourea

1-(2'-ethyl-6'-chlorophenyl)-3-methoxyethylamidinourea

1-(2'-ethyl-6'-chlorophenyl)-3-benzyloxyethylamidinourea

1-(2'-ethyl-6'-chlorophenyl)-3-(N,N-dimethylamidino)urea

1-(2'-ethyl-6'-chlorophenyl)-3-(N,N-diethylamidino)urea

1-(2'-ethyl-6'-chlorophenyl)-3-(N,N-tetramethyleneamidino)urea

1-(2'-methyl-6'-fluorophenyl)-3-methylamidinourea

1-(2',6'-dimethyl-4'-hydroxyphenyl)-3-methylamidinourea

1-(2',6'-diethyl-4'-hydroxyphenyl)-3-methylamidinourea

1-(2'-methyl-6'-chloro-4'-hydroxyphenyl)-3-methylamidinourea

1-(2'-methyl-6'-bromo-4'-hydroxyphenyl)-3-methylamidinourea

1-(2'-methyl-6'-fluoro-4'-hydroxyphenyl)-3-methylamidinourea

1-(2'-methyl-6'-ethyl-4'-hydroxyphenyl)-3-methylamidinourea

1-(2'-ethyl-6'-chloro-4'-hydroxyphenyl)-3-methylamidinourea

1-(2'-ethyl-6'-bromo-4'-hydroxyphenyl)-3-methylamidinourea

1-(2'-ethyl-6'-fluoro-4'-hydroxyphenyl)-3-methylamidinourea

1-(2',6'-dimethyl-4'-aminophenyl)-3-methylamidinourea

1-(2',6'-diethyl-4'-aminophenyl)-3-methylamidinourea

1-(2'-methyl-6'-ethyl-4'-aminophenyl)-3-methylamidinourea

1-(2'-methyl-6'-chloro-4'-aminophenyl)-3-methylamidinourea

1-(2'-methyl-6'-bromo-4'-aminophenyl)-3-methylamidinourea

1-(2'-methyl-6'-fluoro-4'-aminophenyl)-3-methylamidinourea

1-(2'-ethyl-6'-chloro-4'-aminophenyl)-3-methylamidinourea

1-(2'-ethyl-6'-bromo-4'-aminophenyl)-3-methylamidinourea

1-(2'-ethyl-6'-fluoro-4'-aminophenyl)-3-methylamidinourea

1-(2',6'-dimethyl-4'-acetylamino)-3-methylamidinourea

1-(2',6'-diethyl-4'-acetylamino)-3-methylamidinourea

1-(2'-methyl-6'-ethyl-4'-acetylamino)-3-methylamidinourea

1-(2'-methyl-6'-chloro-4'-acetylamino)-3-methylamidinourea

1-(2'-methyl-6'-bromo-4'-acetylamino)-3-methylamidinourea

1-(2'-methyl-6'-fluoro-4'-acetylamino)-3-methylamidinourea

1-(2'-ethyl-6'-chloro-4'-acetylamino)-3-methylamidinourea

1-(2'-ethyl-6'-bromo-4'-acetylamino)-3-methylamidinourea

1-(2'-ethyl-6'-fluoro-4'-acetylamino)-3-methylamidinourea

1-(2',6'-diethyl-4'-nitrophenyl)-3-methylamidinourea hydrochloride

1-(4'-amino-2',6'-diethylphenyl)-3-methylamidinourea dihydrochloride

1-(2',6'-dimethyl-4'-aminophenyl-3-methylamidinourea hydrochloride

1-(2',6'-dimethylphenyl)-3-(N,N-diethylamidino)urea hydrochloride

1-(2',6'-dimethylphenyl)-3-(N-ethyl-N-methylamidino)urea hydrochloride

1-(2',6'-dimethylphenyl)-3-(N-methyl-N-propylamidino)urea hydrochloride

1-(2',6'-dimethylphenyl)-3-(N-methyl-N-butylamidino)urea hydrochloride

1-(2',6'-dimethylphenyl)-3-(N,N-dipropylamidino)urea hydrochloride

1-(2',6'-dimethylphenyl)-3-(N-ethyl-N-propylamidino)urea hydrochloride

1-(2',6'-dimethylphenyl)-3-(N-methyl-N-benzyloxypropylamidino)urea hydrochloride

1-(2',6'-dimethylphenyl)-3-(N-methyl-N-phenethoxyethylamidino)urea hydrochloride

1-(2',6'-dimethylphenyl)-3-(N-methyl-N-benzyloxyethylamidino)urea hydrochloride

1-(2',6'-dimethylphenyl)-3-(N,N-tetrametnyleneamidino)urea hydrochloride

1-(2',6'-dimethylphenyl)-3-(N,N-pentamethyleneamidino)urea hydrochloride

1-(2',6'-dimethylphenyl)-3-(N,N-hexamethyleneamidino)urea hydrochloride

1-(2',6'-dimethylphenyl)-3-[N,N-(3'-oxapentamethylene)amidino]urea hydrochloride

1-(2',6'-dimethylphenyl)-3-[N,N-(3'-methyl-3'-azapentamethylene)amidino]ure a hydrochloride

1-(2',6'-dimethylphenyl)-3-[N,N-(3'-methyl-3'-azahexemethylene)amidino]urea hydrochloride

1-(2',6'-dimethylphenyl)-3-[N,N-(3'-thiapentamethylene)amidino]urea hydrochloride

1-(2',6'-dimethylphenyl)-3-[N,N-(2'-thiatetramethylene)amidino]urea hydrochloride

1-(2',6'-dimethylphenyl)-3-[N-(2'-butenyl)amidino]urea hydrochloride

1-(2',6'-dimethylphenyl)-3-[N-(2'-butynyl)amidino]urea hydrochloride

1-(2',6'-dimethylphenyl)-3-[N-(3'-butynyl)amidino]urea hydrochloride

1-(2',6'-dimethylphenyl)-3-(N-methyl-N-allylamidino)urea hydrochloride

1-(2',6'-dimethylphenyl)-3-(N-methyl-N-propargylamidino)urea hydrochloride

1-(2',6'-dimethylphenyl)-3-(N-methyl-N-cyclopropylamidino)urea hydrochloride

1-(2',6'-dimethylphenyl)-3-(N-methylamidino)urea

1-(2',6'-dimethylphenyl)-3-(N,N-dimethylamidino)urea

1-(2'-methyl-6'-methoxyphenyl)-3-(N-methylamidino)urea

1-(2'-methylphenyl)-3-(N-methylamidino)urea

1-(2',4',6'-trimethylphenyl)-3-(N-methylamidino)urea

1-(2'-methyl-4'-bromo-6'-chlorophenyl)-3-(N-methylamidino)urea

1-(2'-chloro-6'-fluorophenyl)-3-(N-methylamidino)urea

1-(2',5'-dichlorophenyl)-3-(N-methylamidino)urea

1-(2'-chloro-6'-bromophenyl)-3-(N-methylamidino)urea

1-(2'-chloro-5'-bromophenyl)-3-(N-methylamidino)urea

1-(2'-chloro-5'-fluorophenyl)-3-(N-methylamidino)urea

1-(2'-fluoro-5'-chlorophenyl)-3-(N-methylamidino)urea

1-(2'-fluoro-5'-bromophenyl)-3-(N-methylamidino)urea

1-(2',4',6'-triethylphenyl)-3-(N-methylamidino)urea

1-(2',4'-dimethyl-6'-ethylphenyl)-3-(N-methylamidino)urea

1-(2',6'-dimethyl-4'-ethylphenyl)-3-(N-methylamidino)urea

1-(2'-ethylphenyl)-3-(N-methylamidino)urea

1-(2'-ethyl-4'-bromo-6'-chlorophenyl)-3-(N-methylamidino)urea

1-(2'-ethyl-6'-methoxyphenyl)-3-(N-methylamidino)urea

1-(2'-methyl-6'-ethoxyphenyl)-3-(N-methylamidino)urea

1-(2',6'-dimethylphenyl)-3-(N-ethylamidino)urea

1-(2',6'-dimethylphenyl)-3-(N-propylamidino)urea

1-(2',6'-dimethylphenyl)-3-(N-i-propylamidino)urea

1-(2',6'-dimethylphenyl)-3-(N-butylamidino)urea

1-(2',6'-dimethylphenyl)-3-(N-i-butylamidino)urea

1-(2',6'-dimethylphenyl)-3-(N-sec-butylamidino)urea

1-(2',6'-dimethylphenyl)-3-(N-t-butylamidino)urea

1-(2',6'-dimethylphenyl)-3-(N-pentylamidino)urea

1-(2',6'-dimethylphenyl)-3-(N-hexylamidino)urea

1-(2',6'-dimethylphenyl)-3-(N-heptylamidino)urea

1-(2',6'-dimethylphenyl)-3-(N-cyclopropylamidino)urea

1-(2',6'-dimethylphenyl)-3-(N-cyclobutylamidino)urea

1-(2',6'-dimethylphenyl)-3-(N-cyclopentylamidino)urea

1-(2',6'-dimethylphenyl)-3-(N-cyclohexylamidino)urea

1-(2',6'-dimethylphenyl)-3-(N-phenylamidino)urea

1-(2',6'-dimethylphenyl)-3-(N-benzylamidino)urea

1-(2',6'-dimethylphenyl)-3-(N-phenethylamidino)urea

1-(2',6'-dimethylphenyl)-3-(N-methyl-N-benzylamidino)urea

1-(2',6'-dimethylphenyl)-3-(N,N-dibenzylamidino)urea

1-(2'-methyl-6'-chlorophenyl)-3-amidinourea

1-(2'-methyl-6'-fluorophenyl)-3-amidinourea

1-(2'-methyl-6'-bromophenyl)-3-amidinourea

1-(2'-methyl-6'-iodophenyl)-3-amidinourea

1-(2'-methyl-6'-methoxyphenyl)-3-amidinourea

1-(2'-methyl-6'-ethoxyphenyl)-3-amidinourea

1-(2'-methyl-6'-ethylphenyl)-3-amidinourea

1-(2'-methyl-6'-propylphenyl)-3-amidinourea

1-(2'-methyl-6'-i-propylphenyl)-3-amidinourea

1-(2'-methyl-6'-butylphenyl)-3-amidinourea

1-(2'-methyl-6'-cyano phenyl)-3-amidinourea

1-(2'-methyl-6'-trifluoromethylphenyl)-3-amidinourea

1-(2'-methyl-6'-nitrophenyl)-3-amidinourea

1-(2'-methyl-6'-methylsulfonylphenyl)-3-amidinourea

1-(2'-ethyl-6'-chlorophenyl)-3-amidinourea

1-(2'-ethyl-6'-fluorophenyl)-3-amidinourea

1-(2'-ethyl-6'-bromophenyl)-3-amidinourea

1-(2'-ethyl-6'-methoxyphenyl)-3-amidinourea

1-(2'-ethyl-6'-ethoxyphenyl)-3-amidinourea

1-(2',6'-diethylphenyl)-3-amidinourea

1-(2'-ethyl-6'-propylphenyl)-3-amidinourea

1-(2'-ethyl-6'-trifluoromethylphenyl)-3-amidinourea

1-(2'-propyl-6'-chlorophenyl)-3-amidinourea

1-(2'-propyl-6'-bromophenyl)-3-amidinourea

1-(2'-propyl-6'-methoxyphenyl)-3-amidinourea

1-(2'-propyl-6'-ethoxyphenyl)-3-amidinourea

1-(2',6'-dipropylphenyl)-3-amidinourea

1-(2'-i-propyl-6'-chlorophenyl)-3-amidinourea

1-(2',6'-dichlorophenyl)-3-amidinourea

1-(2'-chloro-3'-methylphenyl)-3-amidinourea

1-(2'-chloro-4'-methylphenyl)-3-amidinourea

1-(2'-chloro-5'-methylphenyl)-3-amidinourea

1-(2'-chloro-5'-trifluoromethylphenyl)-3-amidinourea

1-(2'-chloro-6'-fluorophenyl)-3-amidinourea

1-(2',6'-difluorophenyl)-3-amidinourea

1-(2'-propylphenyl)-3-amidinourea

1-(4'-trifluoromethylphenyl)-3-amidinourea

1-(3',4'-dimethoxyphenyl)-3-amidinourea

1-(3',4',5'-trimethoxyphenyl)-3-amidinourea

1-(3',4'-diethoxyphenyl)-3-amidinourea

1-(2',4'-dimethylphenyl)-3-amidinourea

1-(2',4'-diethylphenyl)-3-amidinourea

1-(2'-methyl-4'-ethylphenyl)-3-amidinourea

1-(2'-methyl-4'-chlorophenyl)-3-amidinourea

1-(2'-ethyl-4'-chlorophenyl)-3-amidinourea

1-(2',4',6'-trimethylphenyl)-3-amidinourea

1-(2',4'-dimethyl-6'-ethylphenyl)-3-amidinourea

1-(2',4'-dimethyl-6'-trifluoromethylphenyl)-3-amidinourea

1-(2',4'-dimethyl-6'-nitrophenyl)-3-amidinourea

1-(2',4'-dimethyl-6'-methoxyphenyl)-3-amidinourea

1-(2',6'-dimethyl-4'-chlorophenyl)-3-amidinourea

1-(2',6'-dimethyl-4'-bromophenyl)-3-amidinourea

1-(2',6'-dimethyl-4'-methoxyphenyl)-3-amidinourea

1-(2'-methyl-4',6'-dichlorophenyl)-3-amidinourea

1-(2'-methyl-4',6'-difluorophenyl)-3-amidinourea

1-(2'-methyl-4'-fluoro-6'-bromophenyl)-3-amidinourea

1-(2'-methyl-4'-chloro-6'-trifluoromethylphenyl)-3-amidinourea

1-(2'-methyl-4'-trifluoromethyl-6'-chlorophenyl)-3-amidinourea

1-(2'-ethyl-4',6'-dichlorophenyl)-3-amidinourea

1-(2',6'-diethyl-4'-chlorophenyl)-3-amidinourea

1-(2',6'-diethyl-4'-bromophenyl)-3-amidinourea

1-(2',6'-diethyl-4'-fluorophenyl)-3-amidinourea

1-(2'-chloro-6'-methylphenyl)-3-amidinourea

1-(2',6'-dimethylphenyl)-3-amidinourea

1-(2',6'-diethylphenyl)-3-amidinourea

1-(2'-methyl-6'-methoxyphenyl)-3-amidinourea

1-(2'-methyl-6'-chlorophenyl)-3-amidinourea

1-(2'-methylphenyl)-3-amidinourea

1-(2'-chloro-6'-fluorophenyl)-3-amidinourea

1-(2'-methyl-6'-ethylphenyl)-3-amidinourea

1-(2',4',6'-trimethylphenyl)-3-amidinourea

1-(2'-methyl-6'-methoxyphenyl)-3-(N-methylamidino)urea

1-(2'-methylphenyl)-3-(N-methylamidino)urea

1-(2',4',6'-trimethylphenyl)-3-(N-methylamidino)urea

1-(2'-methyl-4'-bromo-6'-chlorophenyl)-3-(N-methylamidino)urea

1-(2'-chloro-6'-fluorophenyl)-3-(N-methylamidino)urea

1-(2',5'-dichlorophenyl)-3-(N-methylamidino)urea

1-(2'-chloro-6'-bromophenyl)-3-(N-methylamidino)urea

1-(2'-chloro-5'-bromophenyl)-3-(N-methylamidino)urea

1-(2'-chloro-5'-fluorophenyl)-3-(N-methylamidino)urea

1-(2'-fluoro-5'-chlorophenyl)-3-N-methylamidino)urea

1-(2'-fluoro-5'-bromophenyl)-3-(N-methylamidino)urea

1-(2',4',6'-triethylphenyl)-3-(N-methylamidino)urea

1-(2',4'-dimethyl-6'-ethylphenyl)-3-(N-methylamidino)urea

1-(2',6'-dimethyl-4'-ethylphenyl)-3-(N-methylamidino)urea

1-(2'-ethylphenyl)-3-(N-methylamidino)urea

1-(2'-ethyl-4'-bromo-6'-chlorophenyl)-3-(N-methylamidino)urea

1-(2'ethyl-6'-methoxyphenyl)-3-(N-methylamidino)urea

1-(2'-methyl-6'-ethoxyphenyl)-3-(N-methylamidino)urea

1-(2',6'-dimethylphenyl)-3-[N-(2',6'-dimethylphenyl)amidino]urea

1-(2',6'-dimethylphenyl)-3-[N-(2'methylpheynl)amidino]yrea

1-(2',6'-dimethylphenyl)-3-[N-(2',6'-diethylphenyl)amidino]urea

1-(2',6'-dimethylphenyl)-3-[N-(2'methyl-6'-chlorophenyl)amidino]urea

1-(2',6'-dimethylphenyl)-3-[N-(2',4',6'-trimethylphenyl)amidino]urea

TABLE II

1-(2',6'-diethylphenyl)-4-methylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'6'-diethylphenyl)-4-ethylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-diethylphenyl)-4-propylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-diethylphenyl)-4-i-propylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-diethylphenyl)-4-butylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-diethylphenyl)-4-i-butylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-diethylphenyl)-4-pentylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-diethylphenyl)-4-allylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-diethylphenyl)-4-propargylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-diethylphenyl)-4-cyclopropylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-diethylphenyl)-4-methoxyethylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-diethylphenyl)-4-benzyloxyethylamino-1,2-dihydro-1,3,5-triazin-2-o ne

1-(2',6'-diethylphenyl)-4-phenethoxyethylamino-1,2-dihydro-1,3,5-triazin-2- one

1-(2',6'-diethylphenyl)-4-benzylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-diethylphenyl)-4-(N,N-dimethylamino)-1,2-dihydro-1,3,5-triazin-2-o ne

1-(2',6'-diethylphenyl)-4-(N,N-diethylamino)-1,2-dihydro-1,3,5-triazin-2-on e

1-(2',6'-diethylphenyl)-4-(N-pyrrolidinyl)-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-diethylphenyl)-4-(N-piperidyl)-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-6'-ethyl-phenyl)-4-methylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-6'-ethyl-phenyl)-4-ethylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-6'-ethyl-phenyl)-4-propylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-6'-ethyl-phenyl)-4-i-propylamino-1,2-dihydro-1,3,5-triazin-2-o ne

1-(2'-methyl-6'ethyl-phenyl)-4-butylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'methyl-6'ethyl-phenyl)-4-i-butylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'methyl-6'-ethyl-phenyl)-4-t-butylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-6'-ethyl-phenyl)-4-pentylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'methyl-6'ethyl-phenyl)-4-allylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'methyl-6'-ethyl-phenyl)-4-propargylamino-1,2-dihydro-1,3,5-triazin-2-o ne

1-(2'-methyl-6'-ethylphenyl)-4-cyclopropylamino-1,2-dihydro-1,3,5-triazin-2 -one

1-(2'-methyl-6'ethyl-phenyl)-4-cyclobutylamino-1,2-dihydro-1,3,5-triazin-2- one

1-(2'-methyl-6'-ethyl-phenyl)-4-cyclopenten-3-yl-amino-1,3,5-triazin-2-one

1-(2'methyl-6'ethyl-phenyl)-4-cyclopropylmethylamino-1,2-dihydro-1,3,5-tria zin-2-one

1-(2'methyl-6'-ethyl-phenyl)-4-methoxyethylamino-1,2-dihydro-1,3,5-triazin- 2-one

1-(2'-methyl-6'-ethyl-phenyl)-4-benzyloxyethylamino-1,2-dihydro-1,3,5-triaz in-2-one

1-(2'methyl-6'-ethyl-phenyl)-4-phenethoxyethylamino-1,2-dihydro-1,3,5-triaz in-2-one

1-(2'-methyl-6'-ethyl-phenyl)-4-benzylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'methyl-6'-ethyl-phenyl)-4-(N,N-dimethylamino)-1,2-dihydro-1,3,5-triazi n-2-one

1-(2'methyl-6'-ethyl-phenyl)-4-(N,N-diethylamino)-1,2-dihydro-1,3,5-triazin -2-one

1-(2'methyl-6-ethyl-phenyl)-4-(N-pyrrolidinyl)-1,2-dihydro-1,3,5-triazin-2- one

1-(2'methyl-6'-ethyl-phenyl)-4-[3-(N-methyl-piperidyl)]-1,2-dihydro-1,3,5-t riazin-2-one

1-(2'-methyl-6'-chlorophenyl)-4-methylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'methyl-6'-ethylphenyl)-4-(N-morpholinyl)-1,2-dihydro-1,3,5-triazin-2-o ne

1-(2'-methyl-6'-chlorophenyl)-4-ethylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-6'-chlorophenyl)-4-propylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-6'-chlorophenyl)-4-i-propylamino-1,2-dihydro-1,3,5-triazin-2-o ne

1-(2'-methyl-6'-chlorophenyl-4-butylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-6'-chlorophenyl)-4-i-butylamino-1,2-dihydro-1,3,5-triazin-2-on e

1-(2'-methyl-6'-chlorophenyl)-4-t-butylamino-1,2-dihydro-1,3,5- triazin-2-one

1-(2'-methyl-6'-chlorophenyl)-4-pentylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-6'-chlorophenyl)-4-propargylamino-1,2-dihydro-1,3,5-triazin-2- one

1-(2'-methyl-6'- chlorophenyl)-4-cyclobutylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-6-chlorophenyl)-4-cyclohexylamino-1,2-dihydro-1,3,5-triazin-2- one

1-(2'-methyl-6'-chlorophenyl)-4-benzylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-6'-chlorophenyl)-4-methoxyethylamino-1,2-dihydro-1,3,5-triazin -2-one

1-(2'-methyl-6'-chlorophenyl)-4-benzyloxyethylamino-1,2-dihydro-1,3,5-triaz in-2-one

1-(2'-methyl-6'-chlorophenyl)-4-phenethoxyethylamino-1,2-dihydro-1,3,5-tria zin-2-one

1-(2'-methyl-6'-chlorophenyl)-4-(N,N-diethylamino)-1,2-dihydro-1,3,5-triazi n-2-one

1-(2'-methyl-6'-chlorophenyl)-4-(N-piperidinyl)-1,2-dihydro-1,3,5-triazin-2 -one

1-(2'-methyl-6'-bromophenyl)-4-methylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-6'-bromophenyl)-4-ethylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-6'-bromophenyl-4-propylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-6'-bromophenyl)-4-i-propylamino-1,2-dihydro-1,3,5-triazin-2-on e

1-(2'-methyl-6'-bromophenyl)-4-butylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-6'-bromophenyl-4-t-butylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-6'-bromophenyl)-4-pentylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-6'-bromophenyl)-4-hexylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2-methyl-6'-bromophenyl)-4-propargylamino-1,2-dihydro-1,3,5-triazin-2-on e

1-(2'-methyl-6'-bromophenyl)-4-allylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-6'-bromophenyl)-4-methoxyethylamino-1,2-dihydro-1,3,5-triazin- 2-one

1-(2'-methyl-6'-bromophenyl)-4-benzyloxyethylamino-1,2-dihydro-1,3,5-triazi n-2-one

1-(2'-methyl-6'-bromophenyl)-4-phenethoxyethylamino-1,2-dihydro-1,3,5-triaz in-2-one

1-(2'-methyl-6'-bromophenyl)-4-(N,N-dimethylamino)-1,2-dihydro-1,3,5-triazi ne-2-one

1-(2'-methyl-6'-bromophenyl)-4-(N,N-diethylamino)-1,2-dihydro-1,3,5-triazin -2-one

1-(2'-methyl-6'-bromophenyl)-4-(N-methyl-N-ethylamino)-1,2-dihydro-1,3,5-tr iazin-2-one

1-(2'-methyl-6'-bromophenyl)-4-(N-pyrrolidyl)-1,2-dihydro-1,3,5-triazin-2-o ne

1-(2'-methyl-6'-bromophenyl)-4-(N-piperidyl)-1,2-dihydro-1,3,5-triazin-2-on e

1-(2'-methyl-6'-bromophenyl)-4-(N-azepinyl)-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-ethyl-6'-chlorophenyl)-4-methylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-ethyl-6'-chlorophenyl)-4-ethylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-ethyl-6'-chlorophenyl)-4-propylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-ethyl-6'-chlorophenyl)-4-butylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-ethyl-6'-chlorophenyl)-4-i-butylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-ethyl-6'-chlorophenyl)-4-pentylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-ethyl-6'-chlorophenyl)-4-allylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-ethyl-6'-chlorophenyl)-4-propargylamino-1,2-dihydro-1,3,5-triazin-2-o ne

1-(2'-ethyl-6'-chlorophenyl)-4-methoxyethylamino-1,2-dihydro-1,3,5-triazin- 2-one 1-(2'-ethyl-6'-chlorophenyl)-4-benzyloxyethylamino-1,2-dihydro-1,3,5-triaz in-2-one

1-(2'-ethyl-6'-chlorophenyl)-4-(N,N-dimethylamino)-1,2-dihydro-1,3,5-triazi n-2-one

1-( 2'-ethyl-6'-chlorophenyl)-4-(N,N-diethylamino)-1,2-dihydro-1,3,5-triazin-2 -one

1-(2'-ethyl-6'-chlorophenyl)-4-(N-pyrrolidinyl)-1,2-dihydro-1,3,5-triazin-2 -one

1-(2'-methyl-6'-fluorophenyl)-4-methylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-dimethyl-4'-hydroxyphenyl)-4-methylamino-1,2-dihydro-1,3,5-triazin -2-one

1-(2',6'-diethyl-4'-hydroxyphenyl)-4-methylamino-1,2-dihydro-1,3,5-triazin- 2-one

1-(2'-methyl-6'-chloro-4'-hydroxyphenyl)-4-methylamino-1,2-hydro-1,3,5-tria zin-2-one

1-(2'-methyl-6'-bromo-4'-hydroxyphenyl)-4-methylamino-1,2-dihydro-1,3,5-tri azin-2-one

1-(2'-methyl-6'-fluoro-4'-hydroxyphenyl-4-methylamino-1,2-dihydro-1,3,5-tri azin-2-one

1-(2'-methyl-6'-ethyl-4'-hydroxyphenyl)-4-methylamino-1,2-dihydro-1,3,5-tri azin-2-one

1-(2'-ethyl-6'-chloro-4'-hydroxyphenyl)-4-methylamino-1,2-dihydro-1,3,5-tri azin-2-one 1-(2'-ethyl-6'-bromo-4'-hydroxyphenyl)-4-methylamino-1,2-dihydro-1,3,5-tri azin-2-one

1-(2'-ethyl-6'-fluoro-4'-hydroxyphenyl)-4-methylamino-1,2-dihydro-1,3,5-tri azin-2-one

1-(2',6'-dimethyl-4'-aminophenyl)-4-methylamino-1,2-dihydro-1,3,5-triazin-2 -one

1-(2',6'-diethyl-4'-aminophenyl)-4-methylamino-1,2-dihydro-1,3,5-triazin-2- one

1-(2'-methyl-6'-ethyl-4'-aminophenyl)-4-methylamino-1,2-dihydro-1,3,5-triaz in-2-one

1-(2'-methyl-6'-bromo-4'-aminophenyl)-4-methylamino-1,2-dihydro-1,3,5-triaz in-2-one

1-(2'-methyl-6'-fluoro-4'-aminophenyl)-4-methylamino-1,2-dihydro-1,3,5-tria zin-2-one

1-(2'-ethyl-6'-chloro-4'-aminophenyl)-4-methylamino-1,2-dihydro-1,3,5-triaz in-2-one 1-(2'-ethyl-6'-bromo-4'-aminophenyl)-4-methylamino-1,2-dihydro-1,3,5-triaz in-2-one

1-(2'-ethyl-6'-fluoro-4'-aminophenyl)-4-methylamino-1,2-dihydro-1,3,5-triaz in-2-one

1-(2',6'-dimethyl-4'-acetylamino)-4-methylamino-1,2-dihydro-1,3,5-triazin-2 -one

1-(2',6'-diethyl-4'-acetylamino)-4-methylamino-1,2-dihydro-1,3,5-triazin-2- one

1-(2'-methyl-6'-ethyl-4'-acetylamino)-4-methylamino-1,2-dihydro-1,3,5-triaz in-2-one

1-(2'-methyl-6'-chloro-4'-acetylamino)-4-methylamino-1,2-dihydro-1,3,5-tria zin-2-one

1-(2'-methyl-6'-bromo-4'-acetylamino)-4-methylamino-1,2-dihydro-1,3,5-triaz in-2-one

1-(2'-methyl-6'-fluoro-4'-acetylamino)-4-methylamino-1,2-hydro-1,3,5-triazi n-2-one

1-(2'-ethyl-6'-chloro-4'-acetylamino)-4-methylamino-1,2-hydro-1,3,5-triazin -2-one

1-(2'-ethyl-6'-bromo-4'-acetylamino)-4-methylamino-1,2-dihydro-1,3,5-triazi n-2-one

1-(2'-ethyl-6'-fluoro-4'-acetylamino-4-methylamino-1,2-dihydro-1,3,5-triazi n-2-one

1-(2',6'-diethyl-4'-nitrophenyl)-4-methylamino-1,2-dihydro-1,3,5-triazin-2- one

1-(4'-amino-2',6'-diethylphenyl)-4-methylamino-1,2-dihydro-1,3,5-triazin-2- one

1-(2',6'-dimethyl-4'-aminophenyl-4-methylamino-1,2-dihydro-1,3,5-triazin-2- one

1-(2',6'-dimethylphenyl)-4-(N,N-diethylamino-1,2-dihydro-1,3,5-triazin-2-on e

1-(2',6'-dimethylphenyl)-4-(N-ethyl-N-methylamino)-1,2-dihydro-1,3,5-triazi n-2-one

1-(2',6'-dimethylphenyl)-4-(N-methyl-N-propylamino)-1,2-dihydro-1,3,5-triaz in-2-one

1-(2',6'-dimethylphenyl)-4-(N-methyl-N-butylamino)-1,2-dihydro-1,3,5-triazi n-2-one

1-(2',6'-dimethylphenyl)-4-(N,N-dipropylamino)-1,2-dihydro-1,3,5-triazin-2- one

1-(2',6'-dimethylphenyl)-4-(N-ethyl-N-propylamino)-1,2-dihydro-1,3,5-triazi n-2-one 1-(2',6'-dimethylphenyl)-4-(N-methyl-N-benzyloxypropylamino)-1,2-dihydro-1 ,3,5-triazin-2-one

1-(2',6'-dimethylphenyl)-4-(N-methyl-N-phenethoxyethylamino)-1,2-dihydro-1, 3,5-triazin-2-one

1-(2',6'-dimethylphenyl)-4-(N-methyl-N-benzyloxyethylamino)-1,2-dihydro-1,3 ,5-triazin-2-one

1-(2',6'-dimethylphenyl)-4-(N-pyrrolidinyl)-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-dimethylphenyl)-4-(N-piperidyl)-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-dimethylphenyl)4-(N-azipinyl)-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-dimethylphenyl)-4-(N-morpholinyl)-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-dimethyl)-4-[3-(N-methyl piperidyl]-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-dimethylphenyl)-4-[3-(N-methyl acepinyl]-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-dimethylphenyl)-4-[N-(3-thiomorpholinyl]-1,2-dihydro-1,3,5-triazin -2-one

1-(2',6'-dimethylphenyl)-4-[N(3-thioazolinyl)]-1,2-dihydro-1,3,5-triazin-2- one

1-(2',6'-dimethylphenyl)4-(2-butenylamino)-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-dimethylphenyl)-4-(2-butylnylamino)-1,2-dihydro-1,3,5-triazin-2-on e

1-(2',6'-dimethylphenyl)-4-(3-butynylamino)-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-dimethylphenyl)-4-(N-methyl-N-allylamino)-1,2-dihydro-1,3,5-griazi n-2-one

1-(2',6'-dimethylphenyl)-4-(N-methyl-N-propargylamino)-1,2-dihydro-1,3,5-tr iazin-2-one

1-(2',6'-dimethylphenyl)-4-(N-methyl-N-cyclopropylamino)-1,2-dihydro-1,3,5- triazin-2-one

1-(2',6'-dimethylphenyl)4-methylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-dimethylphenyl)-4-(N,N-dimethylamino)-1,2-dihydro-1,3,5-triazin-2- one

1-(2'-methyl-6'-methoxyphenyl)-4-methylamino-1,2-dihydro-1,3,5-triazin-2-on e

1-(2'-methylphenyl)-4-methylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',4',6'-trimethylphenyl)-4-methylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-4'-bromo-6'-chlorophenyl)-4-methylamino-1,2-dihydro-1,3,5-tria zin-2-one

1-(2'-chloro-6'-fluorophenyl)-4-methylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',5'-dichlorophenyl)-4-methylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-chloro-6'-bromophenyl)-4-methylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-chloro-5'-bromophenyl)-4-methylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-chloro-5'-fluorophenyl)-4-methylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-fluoro-5'-chlorophenyl)-4-methylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-fluoro-5'-bromophenyl)-4-methylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',5',6'-triethylphenyl)-4-methylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',4'-dimethyl-6'-ethylphenyl)-4-methylamino-1,2-dihydro-1,3,5-triazin-2 -one

1-(2',6'-dimethyl-4'-ethylphenyl)-4-methylamino-1,2-dihydro-1,3,5-triazin-2 -one

1-(2'-ethylphenyl)-4-methylamino-1,2-dihydro-1,3,5-triazin-2-one 1-(2'-ethyl-4'-bromo-6'-chlorophenyl)-4-methylamino-1,2-dihydro-1,3,5-tria zin-2-on3

1-(2'-ethyl-6'-methoxyphenyl)-4-methylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-6'-ethoxyphenyl)-4-methylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-dimethylphenyl)-4-ethylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-dimethylphenyl)-4-propylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-dimethylphenyl)-4-(i-propylamino)1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-dimethylphenyl)-4-butylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-dimethylphenyl)-4-(i-butylamino)-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-dimethylphenyl)-4-(sec-butylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-dimethylphenyl)-4-(t-butylamino)-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-dimethylphenyl)-4-pentylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-dimethylphenyl)-4-hexylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-dimethylphenyl)-4-heptylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-dimethylphenyl)-4-cyclopropylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-dimethylphenyl)-4-cyclobutylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-dimethylphenyl)-4-cyclopentylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-dimethylphenyl)-4-cyclohexylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-dimethylphenyl)-4-anilino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-dimethylphenyl)-4-benzylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-dimethylphenyl)-4-phenethylamino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-dimethylphenyl)-4-(N-methyl-N-benzylamino)-1,2-dihydro-1,3,5-triaz in-2-one

1-(2',6'-dimethylphenyl)-4-(N,N-dibenzylamino)-1,2-dihydro-1,3,5-triazin-2- one

1-(2'-methyl-6'-chlorophenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-6'-fluorophenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-6'-bromophenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-6'-indophenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-6'-methoxyphenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-6'-ethoxyphenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-6'-ethylphenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-6'-propylphenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-6'-i-propylphenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-6'-butylphenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-6'-cyano phenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'methyl-6'-trifluoromethylphenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-o ne

1-(2'-methyl-6'-nitrophenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-6'-methylsulfonylphenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-o ne

1-(2'-ethyl-6'-chlorophenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-ethyl-6'-fluorophenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-ethyl-6'-bromophenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-ethyl-6'-methoxyphenyl)-4-amino-1,2-dihydro-1,3,t-triazin-2-one

1-(2'-ethyl-6'-ethoxyphenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-diethylphenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-ethyl-6'-propylphenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-ethyl-6'-trifluoromethylphenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-o ne

1-(2'-propyl-6'-chlorophenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-propyl-6'-bromophenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-propyl-6-methoxyphenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-propyl-6'-ethoxyphenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-dipropylphenyl)4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-i-propyl-6'-chlorophenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-dichlorophenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-chloro-3'-methylphenyl)-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-chloro-4'-methylphenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-chloro-5'-methylphenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-chloro-5'-trifluoromethylphenyl)-4-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-chloro-6'-fluorophenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-difluorophenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-propylphenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-on3

1-(4'-trifluoromethylphenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(3',4'-dimethoxyphenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(3',4',5',-trimethoxyphenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(3',4',diethoxyphenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2

1-(2,4'-dimethylphenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2,4'-diethylphenyl)4-4amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-4'-ethylphenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-4'-chlorophenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-ethyl-4'-chlorophenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',4',6'-trimethylphenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',4'-dimethyl-6'-ethylphenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',4'-dimethyl-6'-trifluoromethylphenyl)-4-amino-1,2-dihydro-1,3,5-triaz in-2-one

1-(2',4'-dimethyl-6'-nitrophenyl-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',4'-dimethyl-6'-methoxyphenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-dimethyl-4'-chlorophenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-dimethyl-4'-bromophenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-dimethyl-4'-methoxyphenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-4',6'-dichlorophenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-4',6'-difluorophenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-4'-fluoro-6'-bromophenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2- one

1-(2'-methyl-4'-chloro-6'-trifluoromethylphenyl)-4-amino-1,2-dihydro-1,3,5- triazin-2-one

1-(2'-methyl-4'-trifluoromethyl-6-chlorophenyl)-4-amino-1,2-dihydro-1,3,5-t riazin-2-one

1-(2'-ethyl-4',6'-dichlorophenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-diethyl-4'-chlorophenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-diethyl-4'-bromophenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-diethyl-4'-fluorophenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-chloro-6'-methylphenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-dimethylphenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2',6'-diethylphenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-6'-methoxyphenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methyl-6'-chlorophenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one

1-(2'-methylphenyl)-4-amino-1,2-dihydro-1,3,5-triazin-2-one