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Claims for Patent: 7,572,920

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Claims for Patent: 7,572,920

Title:Benzimidazole derivative and use as a II receptor antagonist
Abstract:The present invention relates to a compound represented by the formula (I) ##STR00001## wherein R.sup.1 is a group represented by the formula ##STR00002## wherein R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7 and R.sup.8 are each independently a hydrogen atom or a C.sub.1-6 alkyl, or a salt thereof. The compound of the present invention is useful as an agent for the prophylaxis or treatment of circulatory diseases such as hypertension and the like and metabolic diseases such as diabetes and the like.
Inventor(s): Kuroita; Takanobu (Katano, JP), Sakamoto; Hiroki (Amagasaki, JP), Ojima; Mami (Amagasaki, JP)
Assignee: Takeda Pharmaceutical Company Limited (Osaka, JP)
Application Number:11/466,633
Patent Claims: 1. A process for producing a compound represented by the formula ##STR00016## wherein R.sup.2 is methyl or a salt thereof, which comprises reacting a reactive derivative of 2-ethoxy-1-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]met- hyl}-1H-benzimidazole-7-oxylic acid or a salt thereof with a compound represented by the formula ##STR00017## wherein R.sup.2 is as defined above, or a salt thereof.

2. A pharmaceutical composition comprising (5-methyl-2-oxo-1, 3-dioxol-4-yl)methyl 2-ethoxy-1-{[2'-(5-oxo-4, 5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-c- arboxylate, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

3. The pharmaceutical composition of claim 2, which is an angiotensin II antagonist.

4. The pharmaceutical composition of 2, which is an agent for the treatment of hypertension.

5. A pharmaceutical composition comprising (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-ethoxy-1- {[2'-(5-oxo-4, 5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-c- arboxylate, or a pharmaceutically acceptable salt thereof in combination with a calcium antagonist.

6. The pharmaceutical composition of claim 5, which is an agent for the treatment of hypertension.

7. A method for antagonizing angiotensin II in a mammal, which comprises administering an effective amount of (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-ethoxy-1-{[2'-(5-oxo-4, 5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-c- arboxylate, or a pharmaceutically acceptable salt thereof to said mammal in need thereof.

8. A method for treating hypertension mediated by angiotensin II in a mammal, which comprises administering an effective amount of (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-ethoxy-1-{[2'-(5-oxo-4, 5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-c- arboxylate, or a pharmaceutically acceptable salt thereof to said mammal in need thereof.

9. A method for treating hypertension mediated by angiotensin II in a mammal, which comprises administering an effective amount of (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-ethoxy-1-{[2'-(5-oxo-4, 5-dihydro- 1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-carboxylate- , or a pharmaceutically acceptable salt thereof in combination with a calcium antagonist to said mammal in need thereof.

10. A pharmaceutical composition comprising (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-ethoxy-1-{[2'-(5-oxo-4, 5 -dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-ca- rboxylate, or a pharmaceutically acceptable salt thereof in combination with a diuretic agent.

11. A method for treating hypertension mediated by angiotensin II in a mammal, which comprises administering an effective amount of (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-ethoxy-1-{[2'-(5-oxo-4, 5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-c- arboxylate, or a pharmaceutically acceptable salt thereof in combination with a diuretic agent to said mammal in need thereof.

12. The pharmaceutical composition of claim 10, which is an agent for the treatment of hypertension.

13. A pharmaceutical composition comprising (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-ethoxy-1-{[2'-(5-oxo-4, 5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-c- arboxylate, or a pharmaceutically acceptable salt thereof in combination with an insulin sensitizer.

14. The pharmaceutical composition of claim 13, which is an agent for the treatment of hypertension.

15. A pharmaceutical composition comprising (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-ethoxy-1-{[2'-(5-oxo-4, 5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-c- arboxylate, or a pharmaceutically acceptable salt thereof in combination with a biguanide.

16. The pharmaceutical composition of claim 15, which is an agent for the treatment of hypertension.

17. A method for treating hypertension mediated by angiotensin II in a mammal which comprises administering an effective amount of (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-ethoxy-1-{[2'-(5-oxo-4, 5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-c- arboxylate, or a pharmaceutically acceptable salt thereof in combination with an insulin sensitizer to said mammal in need thereof.

18. A method for treating hypertension mediated by angiotensin II in a mammal, which comprises administering an effective amount of (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-ethoxy-1-{[2'-(5-oxo-4, 5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl }-1H-benzimidazole-7-carboxylate, or a pharmaceutically acceptable salt thereof in combination with a biguanide to said mammal in need thereof.
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