Claims for Patent: 5,958,961

Summary for Patent: 5,958,961

Title:	Pharmaceutical composition for angiotensin II-mediated diseases
Abstract:	This invention relates to a pharmaceutical composition for angiotensin II-mediated diseases, which comprises a compound having angiotensin II antagonistic activity of the formula ##STR1## wherein R1 is H or an optionally substituted hydrocarbon residue; R2 is an optionally esterified carboxyl group; R3 is a group capable of forming an anion or a group convertible thereinto; X is a covalent bond between the 2 phenyl rings or a spacer having a chain length of 1 to 2 atoms as the linear moiety between the adjoining phenylene group and phenyl group; n is 1 or 2; the ring A is a benzene ring having 1 or 2 optional substituents in addition to R2 ; and Y is a bond, --O--, --S(O)m- (wherein m is 0, 1 or 2) or --N(R4)-- (wherein R4 is H or an optionally substituted alkyl group), or a pharmaceutically acceptable salt thereof in combination with a compound having diuretic activity or a compound having calcium antagonistic activity.
Inventor(s):	Yoshiyuki Inada, Keiji Kubo
Assignee:	Takeda Pharmaceutical Co Ltd
Application Number:	US08/883,040
Patent Claims:	1. A pharmaceutical composition for treating angiotensin II-mediated diseases, which comprises a compound having angiotensin II antagonistic activity of the formula ##STR16## wherein R1 is H or an optionally substituted hydrocarbon residue; R2 is an optionally esterified carboxyl group; R3 is a group capable of forming an anion or a group convertible thereinto; X is a covalent bond between the 2 phenyl rings or a spacer having a chain length of 1 to 2 atoms as the linear moiety between the adjoining phenylene group and phenyl group; n is 1 or 2; the ring A is a benzene ring having 1 or 2 optional substituents in addition to R2 ; and Y is a bond, --O--, --S(O)m- (wherein m is 0, 1 or 2) or --N(R4)-- (wherein R4 is H or an optionally substituted alkyl group), or a pharmaceutically acceptable salt thereof in combination with hydrochlorothiazide or manidipine hydrochloride. 2. The composition claimed in claim 1, in which R1 is an optionally substituted lower alkyl or lower cycloalkyl. 3. The composition claimed in claim 2, in which R1 is ethyl. 4. The composition claimed in claim 1, in which R1 is ethyl and Y is --O--. 5. The composition claimed in claim 1, in which R2 is a group represented by the --CO--D" (wherein D" stands for hydroxyl or a lower alkoxy whose alkyl moiety is optionally substituted with hydroxyl, amino, halogen, lower alkanoyloxy, lower cycloalkanoyloxy, lower alkoxycarbonyloxy, lower cycloalkoxycarbonyloxy or lower alkoxy). 6. The composition claimed in claim 5, in which R2 is a lower alkoxycarbonyl optionally substituted with cyclohexyloxycarbonyloxy. 7. The composition of claim 1, in which R3 is an optionally substituted 5-7 membered monocyclic heterocyclic residue having a hydrogen atom capable of leaving as a proton. 8. The composition claimed in claim 7, in which R3 is ##STR17## 9. The composition claimed in claim 8, in which R3 is tetrazolyl. 10. The composition claimed in claim 8, in which R3 is 2,5-dihydro-5-oxo-1,2,4-oxadiazole-3-yl. 11. The composition claimed in claim 1, in which R2 is a lower alkoxycarbonyl substituted with cyclohexyloxycarbonyloxy and R3 is tetrazolyl. 12. The composition of claim 1, in which R1 is a lower alkyl and Y is --O--, R2 is a lower alkoxycarbonyl substituted with cyclohexyloxycarbonyloxy, and R3 is tetrazolyl. 13. The composition of claim 1, in which the compound represented by the formula (I) is 2-ethoxy-1- 2'-(1H-tetrazol-5-yl)biphenyl-4-yl!methyl!-1H-benzimidazole-7-carboxylic acid. 14. The composition of claim 1, in which the compound represented by the formula (I) is pivaloyloxymethyl 2-ethoxy-1- 2'-(1H-tetrazol-5-yl)biphenyt-4-yl!methyl!-1H-benzimidazole-7-carboxylate. 15. A method for the prophylaxis or treatment of hypertension in a mammal in need thereof which comprises administering an effective amount of a compound having angiotensin II antagonistic activity represented by the formula (I) wherein R1 is H or an optionally substituted hydrocarbon residue; R2 is an optionally esterified carboxyl group; R3 is a group capable of forming an anion or a group convertible thereinto; X is a covalent bond between the 2 phenyl rings or a spacer having a chain length of 1 to 2 atoms as the linear moiety between the adjoining phenylene group and phenyl group; n is 1 or 2; the ring A is a benzene ring having 1 or 2 optional substituents in addition to R2 ; and Y is a bond, --O--, --S(O)m- (wherein m is 0, 1 or 2) or --N(R4)-- (wherein R4 is H or an optionally substituted alkyl group), or a pharmaceutically acceptable salt thereof in combination with an effective amount of hydrochlorothiazide or manidipine hydrochloride.