Details for Patent: 5,646,171

Title:	Angiotensin II antagonist 1-biphenylmethylimidazole compounds and their therapeutic use
Abstract:	An angiotensin II antagonist of the formula: ##STR1## in which: R.sub.p.sup.1 represents hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 cycloalkyl or C.sub.1 -C.sub.6 alkanoyl; R.sub.p.sup.2 represents a single bond, C.sub.1 -C.sub.4 alkylene or C.sub.1 -C.sub.4 alkylidene; R.sub.p.sup.3 and R.sub.p.sup.4 are independently selected from the group consisting of hydrogen and C.sub.1 -C.sub.6 alkyl; R.sub.p.sup.5 represents hydrogen, C.sub.1 -C.sub.4 alkyl, phenyl, naphthyl, benzyl, diphenylmethyl, naphthylmethyl, alkanoyloxyalkyl, cycloalkanecarbonyloxyalkyl, alkoxycarbonyloxyalkyl, cycloalkyloxycarbonyloxyalkyl, (5-phenyl-2-oxo-1,3-dioxolen-4-yl)methyl, (5-alkyl-2-oxo-1,3-dioxolen-4-yl)methyl or phthalaidyl; R.sub.p.sup.6 represents a carboxy or a tetrazol-5-yl; and X.sub.p represents an oxygen or sulfur, and pharmaceutically acceptable salts thereof. The compounds have hypotensive activity and can thus be used for the treatment and prophylaxis of hypertension.
Inventor(s):	Yanagisawa; Hiroaki (Tokyo, JP), Amemiya; Yoshiya (Tokyo, JP), Shimoji; Yasuo (Tokyo, JP), Kanazaki; Takuro (Tokyo, JP), Koike; Hiroyuki (Tokyo, JP), Sada; Toshio (Tokyo, JP)
Assignee:	Sankyo Company, Limited (Tokyo, JP)
Filing Date:	Jun 05, 1995
Application Number:	08/465,369
Claims:	1. A compound of formula (Ia).sub.p ##STR24## in which: R.sub.p.sup.1 represents a hydrogen atom, an alkyl group having from 1 to 6 carbon atoms, a cycloalkyl group having from 3 to 6 ring carbon atoms or an alkanoyl group having from 1 to 6 carbon atoms; R.sub.p.sup.2 represents a single bond or an alkylene or alkylidene group having from 1 to 4 carbon atoms; R.sub.p.sup.3 and R.sub.p.sup.4 are independently selected from the group consisting of hydrogen atoms and alkyl groups having from 1 to 6 carbon atoms; R.sub.p.sup.5 represents a hydrogen atom, an alkyl group having from 1 to 4 carbon atoms, an unsubstituted phenyl group, a phenyl group substituted by at least one substituent selected from the group consisting of methyl groups, ethyl groups, methoxy groups, ethoxy groups, fluorine atoms and chlorine atoms, a naphthyl group, an unsubstituted benzyl group, a benzyl group substituted by at least one substituent selected from the group consisting of methyl groups, ethyl groups, methoxy groups, ethoxy groups, fluorine atoms and chlorine atoms, a diphenylmethyl group, a naphthylmethyl group, an alkanoyloxyalkyl group in which the alkanoyl part has from 1 to 5 carbon atoms and the alkyl part has from 1 to 4 carbon atoms, a cycloalkanecarbonyloxyalkyl group in which the cycloalkane part has 5 or 6 carbon atoms and the alkyl part has from 1 to 4 carbon atoms, an alkoxycarbonyloxyalkyl group in which the alkoxy and alkyl parts each have from 1 to 4 carbon atoms, a cycloalkyloxycarbonyloxyalkyl group in which the cycloalkyl part has 5 or 6 carbon atoms and the alkyl part has from 1 to 4 carbon atoms, a (5-phenyl-2-oxo-1,3-dioxolen-4-yl)methyl group, a (5-alkyl-2-oxo-1,3-dioxolen-4-yl)methyl group, in which the alkyl part has from 1 to 4 carbon atoms, or a phthalidyl group; R.sub.p.sup.6 represents a carboxy group or a tetrazol-5-yl group; and X.sub.p represents an oxygen or sulfur atom; and pharmaceutically acceptable salts thereof. 2. The compound of claim 1, wherein R.sub.p.sup.1 represents a hydrogen atom, a methyl group, an ethyl group, a cyclopropyl group or an acetyl group. 3. The compound of claim 1, wherein R.sub.p.sup.2 represents a single bond, a methylene group, an ethylene group or an ethylidene group. 4. The compound of claim 1, wherein R.sub.p.sup.3 and R.sub.p.sup.4 are the same or different and each represents a hydrogen atom, a methyl group or an ethyl group. 5. The compound of claim 1, wherein: R.sub.p.sup.1 represents a hydrogen atom, a methyl group, an ethyl group, a cyclopropyl group or an acetyl group; R.sub.p.sup.2 represents a single bond, a methylene group, an ethylene group or an ethylidene group; R.sub.p.sup.3 and R.sub.p.sup.4 are the same or different and each represents a hydrogen atom, a methyl group or an ethyl group. 6. The compound of claim 1, wherein the group of formula R.sub.p.sup.1 --X.sub.p --R.sub.p.sup.2 -- represents a methoxymethyl group, an ethoxymethyl group, a 1-methoxyethyl group, a 2-methoxyethyl group, a 2-ethoxyethyl group, a methylthiomethyl group, an ethylthiomethyl group, a 1-methylthioethyl group, 2-methylthioethyl, a 2-ethylthioethyl group, a methylthio group or an ethylthio group. 7. The compound of claim 1, wherein R.sub.p.sup.3 and R.sub.p.sup.4 are the same or different and each represents a methyl or ethyl group. 8. The compound of claim 1, wherein R.sub.p.sup.5 represents a hydrogen atom, an alkyl group having from 1 to 4 carbon atoms, a benzyl group, an alkanoyloxyalkyl group in which the alkanoyl part has from 1 to 5 carbon atoms and the alkyl part has 1 or 2 carbon atoms, a cycloalkane-carbonyloxyalkyl group in which the cycloalkane part has 5 or 6 carbon atoms and the alkyl part has 1 or 2 carbon atoms, an alkoxycarbonyloxyalkyl group in which the alkoxy part has from 1 to 4 carbon atoms and the alkyl part has 1 or 2 carbon atoms, a cycloalkyloxycarbonyloxyalkyl group in which the cycloalkyl part has 5 or 6 carbon atoms and the alkyl part has 1 or 2 carbon atoms, a (5-phenyl-, 5-methyl- or 5-ethyl-2-oxo-1,3-dioxolen-4-yl)methyl group, or a phthalidyl group. 9. The compound of claim 1, wherein: the group of formula R.sub.p.sup.1 --X.sub.p --R.sub.p.sup.2 -- represents a methoxymethyl group, an ethoxymethyl group, a 1-methoxyethyl group, a 2-methoxyethyl group, a 2-ethoxyethyl group, a methylthiomethyl group, an ethylthiomethyl group, a 1-methylthioethyl group, 2-methylthioethyl, a 2-ethylthioethyl group, a methylthio group or an ethylthio group; R.sub.p.sup.3 and R.sub.p.sup.4 are the same or different and each represents a methyl or ethyl group; R.sub.p.sup.5 represents a hydrogen atom, an alkyl group having from 1 to 4 carbon atoms, a benzyl group, an alkanoyloxyalkyl group in which the alkanoyl part has from 1 to 5 carbon atoms and the alkyl part has 1 or 2 carbon atoms, a cycloalkanecarbonyloxyalkyl group in which the cycloalkane part has 5 or 6 carbon atoms and the alkyl part has 1 or 2 carbon atoms, an alkoxycarbonyloxyalkyl group in which the alkoxy part has from 1 to 4 carbon atoms and the alkyl part has 1 or 2 carbon atom, a cycloalkyloxycarbonyloxyalkyl group in which the cycloalkyl part has 5 or 6 carbon atoms and the alkyl part has 1 or 2 carbon atoms, a (5-phenyl-, 5-methyl- or 5-ethyl-2-oxo-1,3-dioxolen-4-yl)methyl group, or a phthalidyl group. 10. The compound of claim 1, wherein the group of formula R.sub.p.sup.1 --X.sub.p --R.sub.p.sup.2 -- represents a methoxymethyl group an ethoxymethyl group, a methylthiomethyl group, a methylthio group or an ethylthio group. 11. The compound of claim 1 wherein R.sub.p.sup.3 and R.sub.p.sup.4 both represent methyl groups. 12. The compound of claim 1, wherein R.sub.p.sup.5 represents a hydrogen atom, a pivaloyloxymethyl group, an ethoxycarbonyloxymethyl group, a 1-(ethoxycarbonyloxy) ethyl group, an isopropoxycarbonyloxymethyl group, a 1-(isopropoxycarbonyloxy)ethyl group, a (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl group or a phthalidyl group. 13. The compound of claim 1, wherein: the group of formula R.sub.p.sup.1 --X.sub.p --R.sub.p.sup.2 -- represents a methoxymethyl group, an ethoxymethyl group, a methylthiomethyl group, a methylthio group or an ethylthio group; R.sub.p.sup.3 and R.sub.p.sup.4 both represent methyl groups; R.sub.p.sup.5 represents a hydrogen atom, a pivaloyloxymethyl group, an ethoxycarbonyloxymethyl group, a 1-(ethoxycarbonyloxy)ethyl group, an isopropoxycarbonyloxymethyl group, a 1-(isopropoxycarbonyloxy)ethyl group, a (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl group or a phthalidyl group. 14. The compound of claim 1, selected from the group consisting of 4-(1-hydroxy-1-methylethyl)-2-methoxymethyl-1-{4-[2-(tetrazol-5-yl)phenyl] phenyl}methylimidazole-5-carboxylic acid and pharmaceutically acceptable salts thereof. 15. The compound of claim 1, selected from the group consisting of 2-ethoxymethyl-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]p henyl}methylimidazole-5-carboxylic acid and pharmaceutically acceptable salts thereof. 16. The compound of claim 1, selected from the group consisting of 2-ethylthio-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]phen yl}methylimidazole-5-carboxylic acid and pharmaceutically acceptable salts thereof. 17. The compound of claim 1, selected from the group consisting of pivaloyloxymethyl 4-(1-hydroxy-1-methylethyl)-2-methoxymethyl-1-{4-[2-(tetrazol-5-yl)phenyl] phenyl}methylimidazole-5-carboxylate and pharmaceutically acceptable salts thereof. 18. The compound of claim 1, selected from the group consisting of pivaloyloxymethyl 2-ethoxymethyl-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]p henyl}methylimidazole-5-carboxylate and pharmaceutically acceptable salts thereof. 19. The compound of claim 1, selected from the group consisting of pivaloyloxymethyl 2-ethylthio-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]phen yl}methylimidazole-5-carboxylate and pharmaceutically acceptable salts thereof. 20. The compound of claim 1, selected from the group consisting of (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 4-(1-hydroxy-1-methylethyl)-2-methoxymethyl-1-{4-[2-(tetrazol-5-yl)phenyl] phenyl}methylimidazole-5-carboxylate and pharmaceutically acceptable salts thereof. 21. The compound of claim 1, selected from the group consisting of (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 2-ethoxymethyl-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]p henyl}methylimidazole-5-carboxylate and pharmaceutically acceptable salts thereof. 22. The compound of claim 1, selected from the group consisting of (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 2-ethylthio-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]phen yl}methylimidazole-5-carboxylate and pharmaceutically acceptable salts thereof. 23. The compound of claim 1, selected from the group consisting of ethoxycarbonyloxymethyl 4-(1-hydroxy-1-methylethyl)-2-methoxymethyl-1-{4-[2-(tetrazol-5-yl) phenyl]phenyl}methylimidazole-5-carboxylate and pharmaceutically acceptable salts thereof. 24. The compound of claim 1, selected from the group consisting of ethoxycarbonyloxymethyl 2-ethoxymethyl-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]p henyl}methylimidazole-5-carboxylate and pharmaceutically acceptable salts thereof. 25. The compound of claim 1, selected from the group consisting of ethoxycarbonyloxymethyl 2-ethylthio-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]phen yl}methylimidazole-5-carboxylate and pharmaceutically acceptable salts thereof. 26. The compound of claim 1, selected from the group consisting of isopropoxycarbonyloxymethyl 4-(1-hydroxy-1-methylethyl)-2-methoxymethyl-1-{4-[2-(tetrazol-5-yl)phenyl] phenyl}methylimidazole-5-carboxylate and pharmaceutically acceptable salts thereof. 27. The compound of claim 1, selected from the group consisting of isopropoxycarbonyloxymethyl 2-ethoxymethyl-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]p henyl}methylimidazole-5-carboxylate and pharmaceutically acceptable salts thereof. 28. The compound of claim 1, selected from the group consisting of isopropoxycarbonyloxymethyl 2-ethylthio-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]phen yl}methylimidazole-5-carboxylate and pharmaceutically acceptable salts thereof. 29. A pharmaceutical composition for the treatment or prophylaxis of hypertension or of a cardiovascular disease, which comprises an effective amount of an anti-hypertensive agent in admixture with a pharmaceutically acceptable carrier or diluent, wherein the anti-hypertensive agent is selected from the group consisting of compounds of formula (Ia).sub.p and pharmaceutically acceptable salts thereof, as claimed in claim 1. 30. The composition of claim 29, wherein: R.sub.p.sup.1 represents a hydrogen atom, a methyl group an ethyl group, a cyclopropyl group or an acetyl group; R.sub.p.sup.2 represents a single bonds, a methylene group, an ethylene group or an ethylidene group; R.sub.p.sup.3 and R.sub.p.sup.4 are the same or different and each represents a hydrogen atom, a methyl group or an ethyl group. 31. The composition of claim 29, wherein: the group of formula R.sub.p.sup.1 --X.sub.p --R.sub.p.sup.2 -- represents a methoxymethyl group, an ethoxymethyl group, a 1-methoxyethyl group, a 2-methoxyethyl group, a 2-ethoxyethyl group, a methylthiomethyl group, an ethylthiomethyl group, a 1-methylthioethyl group, 2-methylthioethyl, a 2-ethylthioethyl group, a methylthio group or an ethylthio group; R.sub.p.sup.3 and R.sub.p.sup.4 are the same or different and each represents a methyl or ethyl group; R.sub.p.sup.5 represents a hydrogen atom, an alkyl group having from 1 to 4 carbon atoms, a benzyl group, an alkanoyloxyalkyl group in which the alkanoyl part has from 1 to 5 carbon atoms and the alkyl part has 1 or 2 carbon atoms, a cycloalkanecarbonyloxyalkyl group in which the cycloalkane part has 5 or 6 carbon atoms and the alkyl part has 1 or 2 carbon atoms, an alkoxycarbonyloxyalkyl group in which the alkoxy part has from 1 to 4 carbon atoms and the alkyl part has 1 or 2 carbon atoms, a cycloalkyloxycarbonyloxyalkyl group in which the cycloalkyl part has 5 or 6 carbon atoms and the alkyl part has 1 or 2 carbon atoms, a (5-phenyl-, 5-methyl- or 5-ethyl-2-oxo-1,3-dioxolen-4-yl)methyl group, or a phthalidyl group. 32. The composition of claim 29, wherein: the group of formula R.sub.p.sup.1 --X.sub.p --R.sub.p.sup.2 -- represents a methoxymethyl group, an ethoxymethyl group, a methylthiomethyl group, a methylthio group or an ethylthio group; R.sub.p.sup.3 and R.sub.p.sup.4 both represent methyl groups; R.sub.p.sup.5 represents a hydrogen atom, a pivaloyloxymethyl group, an ethoxycarbonyloxymethyl group, a 1-(ethoxycarbonyloxy)ethyl group, an isopropoxycarbonyloxymethyl group, a 1-(isopropoxycarbonyloxy)ethyl group, a (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl group or a phthalidyl group. 33. The composition of claim 29, wherein said anti-hypertensive agent is selected from the group consisting of: 4-(1-hydroxy-1-methylethyl)-2-methoxymethyl-1-{4-[2-(tetrazol-5-yl)phenyl]p henyl}methylimidazole-5-carboxylic acid; 2-ethoxymethyl-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]ph enyl}methylimidazole-5-carboxylic acid; 2-ethylthio-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]pheny l}methylimidazole-5-carboxylic acid; pivaloyloxymethyl 4-(1-hydroxy-1-methylethyl)-2-methoxymethyl-1-{4-[2-(tetrazol-5-yl)phenyl] phenyl}methylimidazole-5-carboxylate; pivaloyloxymethyl 2-ethoxymethyl-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]p henyl}methylimidazole-5-carboxylate; pivaloyloxymethyl 2-ethylthio-4-(1-hydroxy-1-methyl ethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl}methylimidazole-5-carboxylate; (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 4-(1-hydroxy-1-methylethyl)-2-methoxymethyl-1-{4-[2-(tetrazol-5-yl)phenyl] phenyl}methylimidazole-5-carboxylate; (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 2-ethoxymethyl-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]p henyl}methylimidazole-5-carboxylate; (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 2-ethylthio-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]phen yl}methylimidazole-5-carboxylate; ethoxycarbonyloxymethyl 4-(1-hydroxy-1-methylethyl)-2- methoxymethyl-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl}methylimidazole-5-carbo xylate; ethoxycarbonyloxymethyl 2-ethoxymethyl-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]p henyl}methylimidazole-5-carboxylate; ethoxycarbonyloxymethyl 2-ethylthio-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]phen yl}methylimidazole-5-carboxylate; isopropoxycarbonyloxymethyl 4-(1-hydroxy-1-methylethyl)-2-methoxymethyl-1-{4-[2-(tetrazol-5-yl)phenyl] phenyl}methylimidazole-5-carboxylate; isopropoxycarbonyloxymethyl 2-ethoxymethyl-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]p henyl}methylimidazole-5-carboxylate; isopropoxycarbonyloxymethyl 2-ethylthio-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]phen yl}methylimidazole-5-carboxylate; and pharmaceutically acceptable salts thereof. 34. A method for the treatment or prophylaxis of hypertension or of a cardiovascular disease in a mammal, which comprises administering an effective amount of an anti-hypertensive agent to said mammal, wherein the anti-hypertensive agent is selected from the group consisting of compounds of formula (I).sub.p and pharmaceutically acceptable salts thereof, as claimed in claim 1. 35. The method of claim 34, wherein: R.sub.p.sup.1 represents a hydrogen atom, a methyl group, an ethyl group, a cyclopropyl group or an acetyl group; R.sub.p.sup.2 represents a single bond, a methylene group, an ethylene group or an ethylidene group; R.sub.p.sup.3 and R.sub.p.sup.4 are the same or different and each represents a hydrogen atom, a methyl group or an ethyl group. 36. The method of claim 33, wherein: the group of formula R.sub.p.sup.1 --X.sub.p --R.sub.p.sup.2 -- represents a methoxymethyl group, an ethoxymethyl group, a 1-methoxyethyl group, a 2-methoxyethyl group, a 2-ethoxyethyl group, a methylthiomethyl group, an ethylthiomethyl group, a 1-methylthioethyl group, 2-methylthioethyl, a 2-ethylthioethyl group, a methylthio group or an ethylthio group; R.sub.p.sup.3 and R.sub.p.sup.4 are the same or different and each represents a methyl or ethyl group; R.sub.p.sup.5 represents a hydrogen atom, an alkyl group having from 1 to 4 carbon atoms, a benzyl group, an alkanoyloxyalkyl group in which the alkanoyl part has from 1 to carbon atoms and the alkyl part has 1 or 2 carbon atoms, a cycloalkanecarbonyloxyalkyl group in which the cycloalkane part has 5 or 6 carbon atoms and the alkyl part has 1 or 2 carbon atoms, an alkoxycarbonyloxyalkyl group in which the alkoxy part has from 1 to 4 carbon atoms and the alkyl part has 1 or 2 carbon atoms, a cycloalkyloxycarbonyloxyalkyl group in which the cycloalkyl part has 5 or 6 carbon atoms and the alkyl part has 1 or 2 carbon atoms, a (5-phenyl-, 5-methyl- or 5-ethyl-2-oxo-1,3-dioxolen-4-yl)methyl group, or a phthalidyl group. 37. The method of claim 34, wherein: the group of formula R.sub.p.sup.1 --X.sub.p --R.sub.p.sup.2 -- represents a methoxymethyl group, an ethoxymethyl group, a methylthiomethyl group, a methylthio group or an ethylthio group; R.sub.p.sup.3 and R.sub.p.sup.4 both represent methyl groups; R.sub.p.sup.5 represents a hydrogen atom, a pivaloyloxymethyl group, an ethoxycarbonyloxymethyl group, a 1-(ethoxycarbonyloxy)ethyl group, an isopropoxycarbonyloxymethyl group, a 1-(isopropoxycarbonyloxy)ethyl group, a (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl group or a phthalidyl group. 38. The method of claim 34, wherein said anti-hypertensive agent is selected from the group consisting of: 4-(1-hydroxy-1-methylethyl)-2-methoxymethyl-1-{4-[2-(tetrazol-5-yl)phenyl]p henyl}methylimidazole-5-carboxylic acid; 2-ethoxymethyl-4-(1-hydroxy-1-methylethyl)-1-(4-[2-(tetrazol-5-yl)phenyl]ph enyl}methylimidazole-5-carboxylic acid; 2-ethylthio-4-(1-hydroxy-1-methylethyl)-1-(4-[2-(tetrazol-5-yl)phenyl]pheny l)methylimidazole-5-carboxylic acid; pivaloyloxymethyl 4-(1-hydroxy-1-methylethyl)-2-methoxymethyl-1-{4-[2-(tetrazol-5-yl)phenyl] phenyl}methylimidazole-5-carboxylate; pivaloyloxymethyl 2-ethoxymethyl-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]p henyl}methylimidazole-5-carboxylate; pivaloyloxymethyl 2-ethylthio-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]phen yl}methylimidazole-5-carboxylate; (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 4-(1-hydroxy-1-methylethyl)-2-methoxymethyl-1-{4-[2-(tetrazol-5-yl)phenyl] phenyl}methylimidazole-5-carboxylate; (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 2-ethoxymethyl-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]p henyl}methylimidazole-5-carboxylate; (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 2-ethylthio-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]phen yl}methylimidazole-5-carboxylate; ethoxycarbonyloxymethyl 4-(1-hydroxy-1-methylethyl)-2-methoxymethyl-1-{4-[2-(tetrazol-5-yl)phenyl] phenyl}methylimidazole-5-carboxylate; ethoxycarbonyloxymethyl 2-ethoxymethyl-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]p henyl}methylimidazole-5-carboxylate; ethoxycarbonyloxymethyl 2-ethylthio-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]phen yl}methylimidazole-5-carboxylate; isopropoxycarbonyloxymethyl 4-(1-hydroxy-1-methylethyl)-2-methoxymethyl-1-{4-[2-(tetrazol-5-yl)phenyl] phenyl}methylimidazole-5-carboxylate; isopropoxycarbonyloxymethyl 2-ethoxymethyl-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]p henyl}methylimidazole-5-carboxylate; isopropoxycarbonyloxymethyl 2-ethylthio-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]phen yl}methylimidazole-5-carboxylate; and pharmaceutically acceptable salts thereof.