# US 4,396,771 A · Imidazole derivatives and salts thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 4,396,771 A - Document ID: US4396771A - Status: Granted - Kind: A - Application number: 06/067,379 - Filed: 1979-08-17 - Granted: 1983-08-02 - Earliest claimed: 1977-10-19 - Assignees: Burroughs Wellcome Co. - Inventors: Peter B. Thorogood - Web page: https://patentgrep.com/patent/US4396771A ## CPC - C07D 233/56: with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms - A61K 31/415: 1,2-Diazoles - A61K 31/44: Non condensed pyridines; Hydrogenated derivatives thereof - A61K 31/445: Non condensed piperidines, e.g. piperocaine - A61K 31/485: Morphinan derivatives, e.g. morphine, codeine - A61K 31/505: Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim - A61K 31/52: Purines, e.g. adenine - A61K 31/535: having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines - A61K 31/55: having seven-membered rings, e.g. azelastine, pentylenetetrazole - C07D 233/84: Sulfur atoms - C07D 319/20: with substituents attached to the hetero ring - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) ## Abstract 1-Substituted-imidazoles of the formula: ##STR1## in which A is selected from the group consisting of straight or branched, saturated or unsaturated, acyclic hydrocarbon radicals of from 1 to 3 carbon atoms and R is ##STR2## wherein n is an integer which is at least 1, and the or each Q substituent, which when n is greater than 1 may be the same or different, is selected from a saturated alkyl group of from 1 to 4 carbon atoms or an unsaturated alkyl group of from 2 to 4 carbon atoms, with the proviso that when A is unsaturated Q may also be selected from alkoxy of from 1 to 4 carbon atoms; halo; trihalomethyl; hydroxy; carboxyl; a salt of such a carboxyl group; carboalkyloxy; carboaryloxy; carboarylalkyloxy; --NR.sup.6 R.sup.7 or --CONR.sup.6 R.sup.7 ; in which R.sup.6 and R.sup.7 may be the same or different and are hydrogen or alkyl of from 1 to 4 carbon atoms; the 1-substituted-imidazole being the free base or an acid addition salt thereof. Methods of preparing the 1-substituted-imidazoles are also provided. The imidazoles have pharmacological properties that make them of use in the treatment of thromboembolic disorders, shock and angina pectoris. ## Claims ### Claim 1 A 1-substituted-imidazole of the formula ##STR21## in which A is selected from the group consisting of straight or branched, saturated, acyclic hydrocarbon radicals of 1, 2 or 3 carbon atoms, and straight or branched unsaturated acyclic hydrocarbon radicals of 2 or 3 carbon atoms, and R is ##STR22## wherein n is an integer which is at least 1, and the or each Q substituent, which when n is greater than 1 may be the same or different, is selected from a saturated hydrocarbon group of from 1 to 4 carbon atoms and an unsaturated hydrocarbon group of from 2 to 4 carbon atoms, with the provisos that (a) when A is ethylidene, n is at least 2 when each Q is a saturated hydrocarbon group; (b) when A is straight propylidene, n is at least 3 when each Q is a saturated hydrocarbon group; (c) when A is unsaturated Q may also be selected from alkoxy of from 1 to 4 carbon atoms; halo; trihalomethyl; hydroxy; carboxyl; a salt of such carboxyl group; carboalkoxy; carbophenoxy; carbophenalkyloxy; --NR.sup.6 R.sup.7 or --CONR.sup.6 R.sup.7 ; in which R.sup.6 and R.sup.7 may be the same or different and are hydrogen or alkyl of from 1 to 4 carbon atoms, with the further proviso that when n is 1, Q is not a saturated alkyl group nor halo; (d) when A is methylene, ethylene or straight propylene, n is at least 3 when each Q is selected from a saturated hydrocarbon group; and (e) when A is branched propylene, n is at least 4 when each Q is selected from a saturated hydrocarbon group; the substituted-imidazole being the free base or a pharmaceutically acceptable acid addition salt thereof. ### Claim 2 (depends on 1) A compound according to claim 1 wherein n is at least 2. ### Claim 3 (depends on 2) A compound according to claim 2 wherein one of the groups is in the 4-position of the benzene ring, relative to the group A. ### Claim 4 (depends on 1) A compound according to claim 1 wherein A is --CH.sub.2 --. ### Claim 5 (depends on 1) A compound according to claim 1 wherein A is, in the orientation of formula (I), --CH.sub.2 --CH.dbd.CH--. ### Claim 6 (depends on 5) A compound according to claim 5 wherein the group Q is selected from alkyl, chloro or methoxy. ### Claim 7 A 1-substituted-imidazole of the formula: ##STR23## in which A is selected from the group consisting of straight or branched, saturated, acyclic hydrocarbon radicals of 2 carbon atoms, and straight or branched unsaturated acyclic hydrocarbon radicals of 2 or 3 carbon atoms, and R Is ##STR24## wherein n is an integer which is at least 1, and the or each Q substituent, which when n is greater than 1 may be the same or different, is selected from a saturated hydrocarbon group of from 1 to 4 carbon atoms and an unsaturated hydrocarbon group of from 2 to 4 carbon atoms, with the provisos that (a) when A is ethylidene, n is at least 2 when each Q is a saturated hydrocarbon group; (b) when A is unsaturated Q may also be selected from alkoxy of from 1 to 4 carbon atoms; trihalomethyl; hydroxy; carboxyl; a salt of such a carboxyl group; carboalkoxy; --NR.sup.6 R.sup.7 or --CONR.sup.6 R.sup.7 ; in which R.sup.6 and R.sup.7 may be the same or different and are hydrogen or alkyl of from 1 to 4 carbon atoms, with the further proviso that when n is 1, Q is not a saturated alkyl group; and (c) when A is ethylene, n is at least 3 when each Q is a saturated hydrocarbon group; the substituted-imidazole being the free base or a pharmaceutically acceptable acid addition salt thereof. ### Claim 8 (depends on 7) A compound according to claim 7 wherein n is at least 2. ### Claim 9 (depends on 8) A compound according to claim 8 wherein one of the groups is in the 4-position of the benzene ring, relative to the group A. ### Claim 10 1-(3,4-dimethylbenzyl)imidazole or a pharmaceutically acceptable acid addition salt thereof. ### Claim 11 1-(3,4-dimethylbenzyl)imidazole. ### Claim 12 A 1-substituted-imidazole selected from 1-[3-(2,4-dichlorophenyl)prop-2-enyl]imidazole, 1-[3-(2,6-dichlorophenyl)prop-2-enyl]imidazole and pharmaceutically acceptable acid addition salts thereof. ### Claim 13 A 1-substituted imidazole selected from 1-(2,4,6-trimethylbenzyl)imidazole, 1-[3-(3,4-dimethylphenyl)prop-2-enyl]imidazole and pharmaceutically acceptable acid addition salts thereof. ### Claim 14 A 1-substituted-imidazole selected from the group consisting of: 1-[3-(3,4,5-trimethoxyphenyl)prop-2-enyl]imidazole; 1-[3-(3,4-dimethoxyphenyl)prop-2-enyl]imidazole; 1-[3-(2-hydroxyphenyl)prop-2-enyl]imidazole; 1-[3-(3-bromophenyl)prop-2-enyl]imidazole; 1-[3-(4-chlorophenyl)prop-2-enyl]imidazole; 1-[3-(2-methoxyphenyl)prop-2-enyl]imidazole; and pharmaceutically acceptable acid addition salts thereof. ### Claim 15 1-(2,4,6-Trimethylbenzyl)imidazole, or a pharmaceutically acceptable acid addition salt thereof. ### Claim 16 A 1-substituted-imidazole of the formula: ##STR25## in which A is a straight or branched unsaturated acyclic hydrocarbon radical of 2 or 3 carbon atoms, and R is ##STR26## wherein n is an integer which is at least 1, and the Q substituent is selected from alkoxy of from 1 to 4 carbon atoms; trihalomethyl; hydroxy; carboxyl; a salt of such a carboxyl group; carboalkoxy; --NR.sup.6 R.sup.7 or --CONR.sup.6 R.sup.7 ; in which R.sup.6 and R.sup.7 may be the same or different and are hydrogen or alkyl of from 1 to 4 carbon atoms, the substituted-imidazole being the free base or a pharmaceutically acceptable acid addition salt thereof. ### Claim 17 (depends on 16) A compound according to claim 16 wherein A is, in the orientation of formula (I), --CH.sub.2 --CH.dbd.CH--.