US 4,404,387 AGrant
Aminoalkyl-Substituted Imidazoles
Issue Date:1983-09-13
•13 Claims
Abstract
The present invention provides certain substituted-piperazinyl-1,2,4-triazoles which are useful for the treatment of sensitized humans for allergies and anaphylactic reactions.
Metadata
Assignee
- The Upjohn Company
Inventor
- Martin Gall
Application Information
Application Number:US 3624463
Filing Date:1982-03-26
Priority Date:1980-09-17
Art Unit:122
Classifications
IPC:
C07D23354C07D40308A61K 31445
Field of Search:
548546336193;210
Patent Drawings
This patent does not have any drawings.
Description
Background of the Invention
The present invention relates to novel substituted imidazoles. Most particularly, the present invention relates to certain aminoalkyl substituted imidazols. The pharmaceutical use and preparation of these compounds is described in U.S. Pat. No. 4,338,453, which is expressly incorporated herein by reference.
Prior Art
Various imidazoles are known. These compounds have been described as useful for a wide range of uses. Known imidazole compounds include 1,2,4,5-tetra-substituted imidazoles useful as antitumor, antiviral, antiinflammatory agent agents, and as protective agents against cerebral anoxia or hypoxia such as are described in British Pat. No. 2,016,011 (abstracted in Derwent Farmdoc CPI No. 68606B/38), French Pat. No. 2,132,632 (abstracted in Derwent Farmdoc CPI No. 10105U-B), U.S. Pat. No. 3,651,080, and Belgian Pat. No. 810,117 (abstracted in Farmdoc CPI No. 41717V/23); 1-substituted imidazoles for use in treating inflammation, hypertension, thrombosis and asthma such as described in Japanese Patent Application No. 109974 (abstracted in Derwent Farmdoc CPI No. 72897B/40); 1,2-di-substituted-4-haloimidazoles-5-acetic acid derivatives for use as diuretics and hypotensives, as described in U.S. Pat. No. 4,207,324; and 1,4,5-trisubstituted imidazoles useful as antiallergic and hypotensive agents such as described in British Pat. No. 1,134,580. U.S. Pat. No. 3,505,350 discloses certain mercapto imidazole derivatives which are useful an antiinflammatory agents.
Summary of the Invention
The present invention particularly provides a compound according to Formula I ##STR1## or a pharmacologically acceptable salt thereof, wherein X.sub.1 is
(a) .dbd.CH--; or
(b) .dbd.C(CH.sub.3)--;
wherein m is zero, one, 2 or 3;
wherein n is zero, one or 2,
wherein R.sub.1 is:
(a) 1-piperidinyl substituted at the 3 or 4 position by R.sub.15, wherein R.sub.15 is defined as below;
(b) --N(CH.sub.3)--(CH.sub.2).sub.p --R.sub.15, wherein R.sub.15 and p are as defined below; or
(c) --NH--(CH.sub.2).sub.p --R.sub.15, wherein p is 1, 2, or 3 and R.sub.15 is as defined below;
wherein R.sub.4 is:
(a) hydrogen;
(b) alkyl of one to three carbon atoms, inclusive;
(c) R.sub.54 OCH.sub.2 --, wherein R.sub.54 is defined below;
(d) --CH(R.sub.35)(OH); or
(e) --R.sub.35 ;
wherein R.sub.5, R.sub.15, R.sub.25 and R.sub.35 are the same or different and are
(i) 2,3, or 4 pyridinyl, or
(ii) phenyl substituted by zero to 2 chloro, fluoro, bromo, alkyl of from one to 3 carbon atoms, or alkoxy of from one to 3 carbon atoms, or
(iii) phenyl substituted by one trifluoromethyl and zero to one of the previous phenyl substituents,
wherein R.sub.6 is:
(a) hydrogen;
(b) --OR.sub.54 ;
(c) alkanoyloxy of from one to 3 carbon atoms; or
(d) alkyl of from one to 3 carbon atoms; with the proviso that when m is zero, R.sub.6 does not contain oxygen;
wherein R.sub.17 is methyl, phenyl, benzyl, or 2-phenylethyl; and
wherein R.sub.54 is hydrogen or alkyl of one to 3 carbon atoms;
or an enantiomer (when R.sub.4 is --CH(R.sub.35)OH or when R.sub.6 is not hydrogen) or diastereomer (when R.sub.4 is --CH(R.sub.35)OH and R.sub.6 is not hydrogen) of such compound.
Description of the Preferred Embodiments
The present invention particularly provides:
5-Methyl-1-phenyl-N-(2-phenylethyl)-1H-imidazole-ethaneamine;
N-5-Dimethyl-1-phenyl-N-(2-phenylethyl)-1H-imidazole-ethaneamine; and
1-(4-Fluorophenyl)-5-methyl-N-(2-phenylethyl)-1H-imidazole-2-ethaneamine.
Claims
I claim:
1. A compound according to formula I ##STR2## or a pharmacologically acceptable salt thereof, wherein X.sub.1 is (a) .dbd.CH--; or (b) .dbd.C(CH.sub.3)--; wherein m is zero, one, 2 or 3; wherein n is zero, one or 2, wherein R.sub.1 is: (a) 1-piperidinyl substituted at the 3 or 4 position by R.sub.15, wherein R.sub.15 is defined as below; (b) --N(CH.sub.3)--(CH.sub.2).sub.p --R.sub.15, wherein R.sub.15 and p are as defined below; or (c) --NH--(CH.sub.2).sub.p --R.sub.15, wherein p is 1, 2, or 3 and R.sub.15 is as defined below; wherein R.sub.4 is: (a) hydrogen; (b) alkyl of one to three carbon atoms, inclusive; (c) R.sub.54 OCH.sub.2 --, wherein R.sub.54 is defined below; (d) --CH(R.sub.35)(OH); or (e) --R.sub.35 ; wherein R.sub.5, R.sub.15, R.sub.25 and R.sub.35 are the same or different and are (i) 2,3, or 4 pyridinyl, or (ii) phenyl substituted by zero to 2 chloro, fluoro, bromo, alkyl of from one to 3 carbon atoms, or alkoxy of from one to 3 carbon atoms, or (iii) phenyl substituted by one trifluoromethyl and zero to one of the previous phenyl substituents, wherein R.sub.6 is: (a) hydrogen; (b) --OR.sub.54 ; (c) alkanoyloxy of from one to 3 carbon atoms; or (d) alkyl of from one to 3 cabon atoms; with the proviso that when m is zero, R.sub.6 does not contain oxygen; wherein R.sub.17 is methyl, phenyl, benzyl, or 2-phenylethyl; and wherein R.sub.54 is hydrogen or alkyl of one to 3 carbon atoms; or an enantiomer (when R.sub.4 is --CH(R.sub.35)OH or when R.sub.6 is not hydrogen) or diastereomer (when R.sub.4 is --CH(R.sub.35)OH and R.sub.6 is not hydrogen) of such compound.
2. A compound of claim 1, wherein n is zero and R.sub.6 is hydrogen.
3. A compound of claim 2, wherein m is 2.
4. A compound of claim 2, wherein m is one or 2, and R.sub.4 is hydrogen, methyl, hydroxymethyl, or --CH(R.sub.35)(OH), wherein R.sub.5 and R.sub.35 are phenyl substituted by zero to 2 chloro, fluoro or bromo.
5. 5-Methyl-1-phenyl-N-(2-phenylethyl)-1H-imidazole-ethaneamine, a compound of claim 4.
6. N,5-Dimethyl-1-phenyl-N-(2-phenylethyl)-1H-imidazole-ethaneamine, a compound of claim 4.
7. A compound of claim 4, wherein R.sub.4 is methyl.
8. 1-(4-Fluorophenyl)-5-methyl-N-(2-phenylethyl)-1H- imidazole-2-ethaneamine, a compound of claim 7.
9. A compound of claim 1, wherein X.sub.1 is .dbd.CH--.
10. A compound of claim 1, wherein X.sub.1 is .dbd.C(CH.sub.3)--.
11. A compound of claim 1, wherein R.sub.4 is hydrogen.
12. A compound of claim 4, wherein R.sub.6 is hydrogen.
13. A compound of claim 1, wherein R.sub.4 is methyl or thiomethyl.
Patent Citations (1)
| Patent | Date | Inventor | Cited By |
|---|---|---|---|
| US3927011 | 1975-12-01 | Nakanishi et al. |