발생일자 2015.04.27 

사건번호 1:15-cv-03695 

법원국가 UNITED STATES OF AMERICA 

관할법원명 D.C.N.D.Illinois(지방법원) 

침해권리 특허 

원고명 Apotex, Inc. ( 캐나다 / 외국기업 )  

피고명 Daiichi Sankyo, Inc./ Daiichi Sankyo Co., Ltd. ( 미국 / 외국기업 )  

소송유형 Declaratory Judgement 

[Apotex, Inc. v. Daiichi Sankyo, Inc. et al] 사건번호 1:15-cv-03695에 따르면 원고 Apotex, Inc.는 피고 Daiichi Sankyo, Inc./ Daiichi Sankyo Co., Ltd.을 상대로 특허 US5616599|US6878703에 대한 비침해 확인을 구하는 소송을 미국 일리노이 북부 지방법원에 제기하였다. 

분쟁결과 분쟁중 

산업분류 화학∙바이오 > 의약품 

계쟁제품 Generic 20/12.5 mg, 40/12.5 mg, or 40/25 mg olmesartan medoxomil/hydrochlorothiazide product, generic version of Benicar HCT and Benicar (Declaratory Judgment) 

지재권번호/명칭

US5616599   Angiotensin II antagosist 1-biphenylmethylimidazole compounds and their therapeutic use 

 US6878703   Pharmaceutical composition 

Compounds of the following formula (I) or the formula (I).sub.p : ##STR1## wherein R.sup.1 is alkyl or alkenyl; R.sup.2 and R.sup.3 are hydrogen, alkyl, alkenyl, cycloalkyl, aralkyl, aryl, or aryl fused to cycloalkyl; R.sup.4 is hydrogen, alkyl, alkanoyl, alkenoyl, arylcarbonyl, alkoxycarbonyl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydrothienyl, tetrahydrofuryl, a group of formula --SiR.sup.a R.sup.b R.sup.c, in which R.sup.a, R.sup.b and R.sup.c are alkyl or aryl, alkoxymethyl, (alkoxyalkoxy)methyl, haloalkoxymethyl, aralkyl, aryl or alkanoyloxymethoxycarbonyl; R.sup.5 is carboxy or --CONR.sup.8 R.sup.9, wherein R.sup.8 and R.sup.9 hydrogens or alkyl, or R.sup.8 and R.sup.9 together form alkylene; R.sup.6 is hydrogen, alkyl, alkoxy or halogen; R.sup.7 is carboxy or tetrazol-5-yl; R.sub.p.sup.1 is hydrogen, alkyl, cycloalkyl or alkanoyl; R.sub.p.sup.2 is a single bond, alkylene or alkylidene; R.sub.p.sup.3 and R.sub.p.sup.4 are each hydrogen or alkyl; R.sub.p.sup.6 is carboxy or tetrazol-5-yl; and X.sub.p is oxygen or sulfur; and pharmaceutically acceptable salts and esters thereof. The compounds are AII receptor antagonists and thus have hypotensive activity and can be used for the treatment and prophylaxis of hypertension. The compounds may be prepared by reacting a biphenylmethyl compound with an imidazole compound. 

1. A compound of formula (I): ##STR24## wherein: R.sup.1 represents an alkyl group having from 2 to 5 carbon atoms or an alkenyl group having from 3 to 5 carbon atoms; 

R.sup.2 and R.sup.3 are independently selected from the group consisting of: 

alkyl groups having from 1 to 4 carbon atoms; 

R.sup.4 represents: 

a hydrogen atom; a methyl group; an ethyl group; or 

an alkanoyl group having from 1 to 5 carbon atoms; 

R.sup.5 represents a group of formula --COOR.sup.5a or a group of formula --CONR.sup.8 R.sup.9, 

R.sup.5a 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 is a methyl or ethyl group, 

a cycloalkanoyloxyalkyl group, in which the cycloalkanoyl part has 6 or 7 carbon atoms, and the alkyl part is a methyl or ethyl group, 

an alkoxycarbonyloxyalkyl group, in which the alkoxy part has from 1 to 4 carbon atoms, and the alkyl part is a methyl or ethyl group, 

a cycloalkoxycarbonyloxyalkyl group, in which the cycloalkoxy part has 5 or 6 carbon atoms, and the alkyl part is a methyl or ethyl group, 

a (5-phenyl-2-oxo-1,3-dioxolen-4-yl)methyl group, a (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl group, a (5-ethyl-2-oxo-1,3dioxolen-4-yl)methyl group or a phthalidyl group; 

R.sup.8 and R.sup.9 are independently selected from the group consisting of hydrogen atoms, 

methyl groups, ethyl groups, methoxycarbonylmethyl groups, ethoxycarbonylmethyl groups and carboxymethyl groups; or R.sup.8 and R.sup.9 together represent 

a tetramethylene, pentamethylene, 1-carboxytetramethylene or 1-carboxypentamethylene group; 

R.sup.6 represents a hydrogen atom, 

a methyl group, a methoxy group or a fluorine atom or a chlorine atom at the 6-position of the benzene ring; R.sup.7 represents a carboxy group or a tetrazol-5-yl group at the 2-position of the benzene ring; 

the benzyl ring which bears the substituents represented by R.sup.6 and R.sup.7 is at the 4-position of the benzyl group to which it is attached; 

and pharmaceutically acceptable salts and esters thereof. 

2. The compound of claim 1, wherein R.sup.5a represents a pivaloyloxymethyl, ethoxycarbonyloxymethyl, 1-(ethoxycarbonyloxy)ethyl, isopropoxycarbonyloxymethyl, (1-isopropoxycarbonyloxy)ethyl, (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl or phthalidyl group. 

3. The compound of claim 1, wherein: 

R.sup.1 represents an ethyl, propyl or butyl group; 

R.sup.2 and R.sup.3 are methyl groups; 

R.sup.4 represents a hydrogen atom or a methyl group; 

R.sup.5 represents a group of formula --COOR.sup.5a, in which R.sup.5a 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; and 

R.sup.6 represents a hydrogen atom. 

4. The compound of claim 1, selected from the group consisting of 2-butyl-1-[(2'-carboxybiphenyl-4-yl)methyl]-4-(1-hydroxy-1-methylethyl)imi dazole-5-carboxylic acid and pharmaceutically acceptable salts thereof. 

5. The compound of claim 1, selected from the group consisting of pivaloyloxymethyl 2-butyl-1-[(2'-carboxybiphenyl-4-yl)methyl]-4-(1-hydroxy-1-methylethyl)imi dazole-5-carboxylate and pharmaceutically acceptable salts thereof. 

6. The compound of claim 1, selected from the group consisting of (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 2-butyl-1-[(2'-carboxybiphenyl-4-yl)methyl]-4-(1-hydroxy-1-methylethyl)imi dazole-5-carboxylate and pharmaceutically acceptable salts thereof. 

7. The compound of claim 1, selected from the group consisting of 1-[(2'-carboxybiphenyl-4-yl)methyl]-4-(1-hydroxy-1-methylethyl)-2-propylim idazole-5-carboxylic acid and pharmaceutically acceptable salts thereof. 

8. The compound of claim 1, selected from the group consisting of 1-[(2'-carboxybiphenyl-4-yl)methyl]-2-ethyl-4-(1-hydroxy-1-methylethyl)imi dazole-5-carboxylic acid and pharmaceutically acceptable salts thereof. 

9. The compound of claim 1, selected from the group consisting of 4-(1-hydroxy-1-methylethyl)-2-propyl-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl} methylimidazole-5-carboxylic acid and pharmaceutically acceptable salts thereof. 

10. The compound of claim 1, selected from the group consisting of 2-butyl-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl}m ethylimidazole-5-carboxylic acid and pharmaceutically acceptable salts thereof. 

11. The compound of claim 1, selected from the group consisting of pivaloyloxymethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl} -methylimidazole-5-carboxylate and pharmaceutically acceptable salts thereof. 

12. The compound of claim 1, selected from the group consisting of pivaloyloxymethyl 2-butyl-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl}- methylimidazole-5-carboxylate and pharmaceutically acceptable salts thereof. 

13. 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-propyl-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl} methylimidazole-5-carboxylate and pharmaceutically acceptable salts thereof. 

14. The compound of claim 1, selected from the group consisting of (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 2-butyl-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl}m ethylimidazole-5-carboxylate and pharmaceutically acceptable salts thereof. 

15. The compound of claim 1, selected from the group consisting of ethoxycarbonyloxymethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl} methylimidazole-5-carboxylate and pharmaceutically acceptable salts thereof. 

16. The compound of claim 1, selected from the group consisting of isopropoxycarbonyloxymethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl} methylimidazole-5-carboxylate and pharmaceutically acceptable salts thereof. 

17. The compound of claim 1, selected from the group consisting of 1-(ethoxycarbonyloxy)ethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-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 1-(isopropoxycarbonyloxy)ethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl} methylimidazole-5-carboxylate and pharmaceutically acceptable salts thereof. 

19. The compound of claim 1, selected from the group consisting of pivaloyloxymethyl 2-ethyl-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl}- 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 2-ethyl-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl}m ethylimidazole-5-carboxylate and pharmaceutically acceptable salts thereof. 

21. The compound of claim 1, selected from the group consisting of pivaloyloxymethyl 1-[(2'-carboxybiphenyl-4-yl)methyl]-4-(1-hydroxy-1-methylethyl)-2-propylim idazole-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 1-[(2'-carboxybiphenyl-4-yl)methyl]-4-(1-hydroxy-1-methylethyl)-2-propylim idazole-5-carboxylate and pharmaceutically acceptable salts thereof. 

23. The compound of claim 1, selected from the group consisting of phthalidyl 1-[(2'-carboxybiphenyl-4-yl)methyl]-4-(1-hydroxy-1-methylethyl)-2-propylim idazole-5-carboxylate and pharmaceutically acceptable salts thereof. 

24. A pharmaceutical composition for the treatment or prophylaxis of hypertension, 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 (I) and pharmaceutically acceptable salts thereof, as claimed in claim 1. 

25. The composition of claim 24, wherein said anti-hypertensive agent is selected from the group consisting of: 

2-butyl-1-[(2'-carboxybiphenyl-4-yl)methyl]-4-(1-hydroxy-1-methylethyl)imid azole-5-carboxylic acid; 

pivaloyloxymethyl 2-butyl-1-[(2'-carboxybiphenyl-4-yl)methyl]-4-(1-hydroxy-1-methylethyl)imi dazole-5-carboxylate; 

(5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 2-butyl-1-[(2'-carboxybiphenyl-4-yl)methyl]-4-(1-hydroxy-1-methylethyl)imi dazole-5-carboxylate; 

1-[(2'-carboxybiphenyl-4-yl)methyl]-4-(1-hydroxy-1-methylethyl)-2-propylimi dazole-5-carboxylic acid; 

1-[(2'-carboxybiphenyl-4-yl)methyl]-2-ethyl-4-(1-hydroxy-1-methylethyl)imid azole-5-carboxylic acid; 

4-(1-hydroxy-1-methylethyl)-2-propyl-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl}m ethylimidazole-5-carboxylic acid; 

2-butyl-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl}me thylimidazole-5-carboxylic acid; 

pivaloyloxymethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl} methylimidazole-5-carboxylate; 

pivaloyloxymethyl 2-butyl-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl}m ethylimidazole-5-carboxylate; 

(5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 4-(1-hydroxy-1-methylethyl)-2propyl-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl}m ethylimidazole-5-carboxylate; 

(5-methyl-2-oxo-1,3-idoxolen-4-yl)methyl 2-butyl-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl}m ethylimidazole-5-carboxylate; 

ethoxycarbonyloxymethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl} methylimidazole-5-carboxylate; 

isopropoxycarbonyloxymethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl} methylimidazole-5-carboxylate; 

1-(ethoxycarbonyloxy)ethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl} methylimidazole-5-carboxylate; 

1-(isopropoxycarbonyloxy)ethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl} methylimidazole-5-carboxylate; 

pivaloyloxymethyl 2-ethyl-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl}m ethylimidazole-5-carboxylate; 

(5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 2-ethyl-4-(-1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl-phenyl]phenyl} methylimidazole-5-carboxylate; 

pivaloyloxymethyl 1-[(2'-carboxybiphenyl-4-yl)methyl]-4-(1-hydroxy-1-methylethyl)-2-propylim idazole-5-carboxylate; 

(5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 1-[(2'-carboxybiphenyl-4-yl)methyl]-4-(1-hydroxy-1-methylethyl)-2-propylim idazole-5-carboxylate; 

phthalidyl 1-[(2'-carboxybiphenyl-4-yl)methyl]-4-(1-hydroxy-1-methylethyl)-2-propylim idazole-5-carboxylate; 

and pharmaceutically acceptable salts thereof. 

26. A method for the treatment of prophylaxis of hypertension 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) and pharmaceutically acceptable salts thereof, as claimed in claim 1. 

27. The method of claim 26, wherein said anti-hypertensive agent is selected from the group consisting of: 

2-butyl-1-[(2'-carboxybiphenyl-4-yl)methyl]-4-(1-hydroxy-1-methylethyl)imid azole-5-carboxylic acid; 

pivaloyloxymethyl 2-butyl-1-[(2'-carboxybiphenyl-4-yl)methyl]-4-(1-hydroxy-1-methylethyl)imi dazole-5-carboxylate; 

(5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 2-butyl-1-[(2'-carboxybiphenyl-4-yl)methyl]-4-(1-hydroxy-1-methylethyl)imi dazole-5-carboxylate; 

1-[(2'-carboxybiphenyl-4-yl)methyl]-4-(1-hydroxy-1-methylethyl)-2-propylimi dazole-5-carboxylic acid; 

1-[(2'-carboxybiphenyl-4-yl)methyl]-2-ethyl-4-(1-hydroxy-1-methylethyl)imid azole-5-carboxylic acid; 

4-(1-hydroxy-1-methylethyl)-2-propyl-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl}m ethylimidazole-5-carboxylic acid; 

2-butyl-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl}me thylimidazole-5-carboxylic acid; 

pivaloyloxymethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl} methylimidazole-5-carboxylate; 

pivaloyloxymethyl 2-butyl-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl}m ethylimidazole-5-carboxylate; 

(5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl} methylimidazole-5-carboxylate; 

(5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 2-butyl-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl}m ethylimidazole-5-carboxylate; 

ethoxycarbonyloxymethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl} methylimidazole-5-carboxylate; 

isopropoxycarbonyloxymethtyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl} methylimidazole-5-carboxylate; 

1-(ethoxycarbonyloxy)ethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl} methylimidazole-5-carboxylate; 

1-(isopropoxycarbonyloxy)ethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl} methylimidazole-5-carboxylate; 

pivaloyloxymethyl 2-ethyl-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl}m ethylimidazole-5-carboxylate; 

(5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 2-ethyl-4-(1-hydroxy-1-methylethyl)-1-{4-[2-(tetrazol-5-yl)phenyl]phenyl}m ethylimidazole-5-carboxylate; 

pivaloyloxymethyl 1-[(2'-carboxybiphenyl-4-yl)methyl]-4-(1-hydroxy-1-methylethyl)-2-propylim idazole-5-carboxylate; 

(5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 1-[(2'-carboxybiphenyl-4-yl)methyl]-4-(1-hydroxy-1-methylethyl)-2-propylim idazole-5-carboxylate; 

phthalidyl 1-[(2'-carboxybiphenyl-4-yl)methyl]-4-(1-hydroxy-1-methylethyl)-2-propylim idazole-5-carboxylate; 

and pharmaceutically acceptable salts thereof. 

28. The compound of claim 1, wherein R.sup.2 and R.sup.3 are both methyl groups. 

29. The compound of claim 1, wherein both of R.sup.2 and R.sup.3 are ethyl groups. 

30. The compound of claim 1, wherein one of R.sup.2 and R.sup.3 is a methyl group and the other of R.sup.2 and R.sup.3 is an ethyl group. 

31. The compound of claim 1, wherein R.sup.5 is ##STR25## 

32. The composition of claim 21, wherein R.sup.2 and R.sup.3 are both methyl groups. 

33. The method of claim 26, wherein R.sup.2 and R.sup.3 are both methyl groups. 

34. A compound of formula (I): ##STR26## wherein: R.sup.1 represents an alkyl group having from 1 to 6 carbon atoms or an alkenyl group having from 3 to 6 carbon atoms; 

R.sup.2 and R.sup.3 are independently alkyl groups having from 1 to 6 carbon atoms; 

R.sup.4 represents: 

a hydrogen atom; 

an alkyl group having from 1 to 6 carbon atoms; 

an alkanoyl group having from 1 to 6 carbon atoms; 

a substituted alkanoyl group having from 2 to 6 carbon atoms and substituted by at least one substituent selected from the group consisting of halogen atoms and alkoxy groups having from 1 to 6 carbon atoms; 

an alkenoyl group having from 3 to 6 carbon atoms; 

an arylcarbonyl group in which the aryl part is as defined below; 

an alkoxycarbonyl group in which the alkyl part has from 1 to 6 carbon atoms; 

a tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydrothienyl or tetrahydrofuryl group; 

a substituted tetrahydropyranyl, tetrahydrofuryl group which is substituted by at least one substituent selected from the group consisting of halogen atoms and alkoxy groups having from 1 to 6 carbon atoms; 

alkoxymethyl groups in which the alkoxy part has from 1 to 6 carbon atoms; 

(alkoxyalkoxy)methyl groups in which each alkoxy part has from 1 to 6 carbon atoms; 

haloalkoxymethyl groups in which the alkoxy part has from 1 to 6 carbon atoms; 

aralkyl groups, in which an alkyl group having from 1 to 6 carbon atoms is substituted by at least one aryl group, as defined below; or 

alkanoyloxymethoxycarbonyl groups in which the alkanoyl part has from 1 to 6 carbon atoms; 

R.sup.5 represents a carboxy group or a group of formula --CONR.sup.8 R.sup.9, wherein R.sup.8 and R.sup.9 are independently selected from the group consisting of 

hydrogen atoms, 

unsubstituted alkyl groups having from 1 to 6 carbon atoms, and 

substituted alkyl groups which have from 1 to 6 carbon atoms and which are substituted by at least one substituent selected from the group consisting of substituents (a), defined below, or 

R.sup.8 and R.sup.9 together represent an unsubstituted alkylene group having from 2 to 6 carbon atoms or a substituted alkylene group which has from 2 to 6 carbon atoms and which is substituted by at least one substituent selected from the group consisting of carboxy groups and alkoxycarbonyl groups in which the alkyl part has from 1 to 6 carbon atoms; 

R.sup.6 represents a hydrogen atom, an alkyl group having from 1 to 6 carbon atoms, an alkoxy group having from 1 to 6 carbon atoms or a halogen atom; 

R.sup.7 represents a carboxy group or a tetrazol-5-yl group; said substituents (a) are selected from the group consisting of: 

aryl groups as defined below; 

heterocyclic groups having 5 or 6 ring atoms, of which from 1 to 4 are hetero-atoms selected from the group consisting of nitrogen, oxygen and sulfur atoms; 

halogen atoms; 

hydroxy groups; 

alkoxy groups having from 1 to 6 carbon atoms; 

carboxy groups 

alkoxycarbonyl groups in which the alkyl part has from 1 to 6 carbon atoms; 

amino groups; and 

acylamino groups, in which the acyl part is an alkanoyl group having from 1 to 6 carbon atoms or an arylcarbonyl group, in which the aryl part is as defined below; 

said aryl groups are aromatic carbocyclic groups which have from 6 to 14 ring atoms and which are unsubstituted or are substituted by at least one substituent selected from the group consisting of substituents (b), defined below; and 

said substituents (b) are selected from the group consisting of nitro groups, cyano groups, halogen atoms, unsubstituted carbocyclic aryl groups having from 6 to 10 ring atoms, alkyl groups having from 1 to 6 carbon atoms, alkoxy groups having from 1 to 6 carbon atoms, carboxy groups, alkoxycarbonyl groups in which the alkoxy part has from 1 to 6 carbon atoms and alkylenedioxy and alkylidene-dioxy groups having from 1 to 3 carbon atoms; 

and pharmaceutically acceptable salts thereof. 

35. The compound of claim 1, wherein R.sup.2 and R.sup.3 are methyl and R.sup.4 is hydrogen. 

36. The compound of claim 1, wherein said R.sup.5 is the group of the formula --COOR.sup.5a. 

37. The composition of claim 24, wherein said R.sup.5 is the group of the formula --COOR.sup.5a. 

38. The method of claim 26, wherein said R.sup.5 is the group of the formula --COOR.sup.5a. 

39. The compound of claim 1, wherein: 

R.sup.1 represents an alkyl group having from 2 to 5 carbon atoms; and 

R.sup.5a represents 

a hydrogen atom, 

a methyl, ethyl or benzyl group, 

an alkanoyloxymethyl group, in which the alkanoyl part has from 1 to 5 carbon atoms, 

a 1-(alkanoyloxy)ethyl group, in which the alkanoyl part has from 1 to 5 carbon atoms, 

an alkoxycarbonyloxymethyl group, in which the alkoxy part has from 1 to 4 carbon atoms, 

a 1-(alkoxycarbonyloxy)ethyl group, in which the alkoxy part has from 1 to 4 carbon atoms, 

a (5-phenyl-2-oxo-1,3-dioxolen-4-yl)methyl group, a (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl group or a phthalidyl group. 

40. The compound of claim 39, wherein R.sup.2 and R.sup.3 are both methyl groups. 

41. The composition of claim 24, wherein: 

R.sup.1 represents an alkyl group having from 2 to 5 carbon atoms; and 

R.sup.5a represents 

a hydrogen atom, 

a methyl, ethyl or benzyl group, 

an alkanoyloxymethyl group, in which the alkanoyl part has from 1 to 5 carbon atoms, 

a 1-(alkanoyloxy)ethyl group, in which the alkanoyl part has from 1 to 5 carbon atoms, 

an alkoxycarbonyloxymethyl group, in which the alkoxy part has from 1 to 4 carbon atoms, 

a 1-(alkoxycarbonyloxy)ethyl group, in which the alkoxy part has from 1 to 4 carbon atoms, 

a (5-phenyl-2-oxo-1,3-dioxolen-4-yl)methyl group, a (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl group or a phthalidyl group. 

42. The method of claim 26, wherein: 

R.sup.1 represents an alkyl group having from 2 to 5 carbon atoms; and 

R.sup.5a represents 

a hydrogen atom, 

a methyl, ethyl or benzyl group, 

an alkanoyloxymethyl group, in which the alkanoyl part has from 1 to 5 carbon atoms, 

a 1-(alkanoyloxy)ethyl group, in which the alkanoyl part has from 1 to 5 carbon atoms, 

an alkoxycarbonyloxymethyl group, in which the alkoxy part has from 1 to 4 carbon atoms, 

a 1-(alkoxycarbonyloxy)ethyl group, in which the alkoxy part has from 1 to 4 carbon atoms, 

a (5-phenyl-2-oxo-1,3-dioxolen-4-yl)methyl group, a (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl group or a phthalidyl group. 

A pharmaceutical composition comprises an angiotensin II receptor antagonist selected from among compounds having the following formula (I), a pharmacologically acceptable salt thereof, a pharmacologically acceptable ester thereof and a pharmacologically acceptable salt of such ester, and one or more diuretics: ##STR1## The pharmaceutical composition of the present invention has an excellent hypotensive effect and low toxicity, and therefore is useful as a medicament for preventing or treating hypertension or heart disease. 

1. A method for treating hypertension comprising administering to a warm-blooded animal in need thereof a pharmaceutically effective amount of each of (i) an angiotensin II receptor antagonist selected from the group consisting of a compound having the following formula (I): ##STR10## 

a pharmacologically acceptable salt thereof, a pharmacologically acceptable ester thereof and a pharmacologically acceptable salt of said ester thereof, and (ii) a diuretic which is hydrochlorothiazide. 

2. The method according to claim 1, wherein the warm-blooded animal is a human. 

3. The method according to claim 2, wherein the angiotensin II receptor antagonist is the compound of the formula (I) or a pharmacologically acceptable ester hereof. 

4. The method according to claim 2, wherein the angiotensin II receptor antagonist is a pharmacologically acceptable ester of the compound of the formula (I). 

5. The method according to claim 2, wherein the angiotensin II receptor antagonist is the pivaloyloxymethyl ester, phthalidyl ester, or (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl ester of the compound of the formula (I). 

6. The method according to claim 2, wherein the angiotensin II receptor antagonist is the (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl ester of the compound of th formula (I). 

7. The method according to claim 2, wherein the diuretic further comprises one or more diuretics selected from the group consisting of methylclothiazide, benzyl-hydrochlorothiazide, trichlormethiazide, cyclopenthiazide, polythiazide, ethiazide, cyclothiazide, bendroflumethiazide and hydroflumethiazide. 

8. The method according to claim 2, wherein a weight ratio of amounts of the compound of the formula (I) to the diuretic is 1:200 to 200:1. 

9. The method according to claim 3, wherein a weight ratio of amounts of the compound of the formula (I) to the diuretic is 1:200 to 200:1. 

10. The method according to claim 5, wherein a weight ratio of amounts of the compound of the formula (I) to the diuretic is 1:200 to 200:1. 

11. The method according to claim 2, wherein the compound of the formula (I) is administered at least once a day in an amount of 0.5 to 1,000 mg and the diuretic is administered at least once a day in an amount of 0.05 to 1,500 mg. 

12. The method according to claim 2, wherein the compound of the formula (I) is administered at least once a day in an amount of 1 to 100 mg and the diuretic is administered at least once a day in an amount of 5 to 300 mg. 

13. The method according to claim 6, wherein a weight ratio of amounts of the compound of the formula (I) to the diuretic is 1:200 to 200:1. 

14. The method according to claim 6, wherein the compound of the formula (I) is administered at least once a day in an amount of 0.5 to 1,000 mg and the diuretic is administered at least once a day in an amount of 0.05 to 1,500 mg. 

15. The method according to claim 6, wherein the compound of the formula (I) is administered at least once a day in an amount of 1 to 100 mg and the diuretic is administered at least once a day in an amount of 5 to 300 mg.