Benzene fused heterocyclic derivatives having thromboxane A2 receptor antagonistic activity and prostaglandin I2 Agonistic activity and application thereof

• US 6,407,096 B1
• Filed: 05/04/2000
• Issued: 06/18/2002
• Est. Priority Date: 08/04/1998
• Status: Expired due to Fees

• Current Assignee: Toray Industries Incorporated
• Original Assignee: Toray Industries Incorporated
• Inventors: Ohtake, Atsushi, Hoshi, Kazuhiro, Yamada, Naohiro, Takeda, Takahiro, Ohno, Michihiro
• Primary Examiner(s): Shah, Mukund J.
• Assistant Examiner(s): Patel, Sudhaker B.
• Application Number:
  US09/509,909
• Time in Patent Office: 775 Days
• Field of Search: 514/222.2, 514/231.2, 514/227.5
• US Class Current: 514/222.2
• CPC Class Codes: C07D 215/20 Oxygen atoms

Abstract

Benzene fused derivatives represented by the following formula:

having strong TXA₂ receptor antagonistic action and PGI₂ receptor agonistic action, and effective for treating or preventing diseases concerning TXA₂.

Claims

1. A benzene fused heterocyclic derivative, represented by the following formula (II):

2. A benzene fused heterocyclic derivative according to claim 1, wherein R¹ is —

O—

(CH₂)_n—

COOR⁶.

3. A benzene fused heterocyclic derivative according to claim 1, wherein A³ is alkylene having 1 to 4 carbon atoms.

4. A benzene fused heterocyclic derivative according to claim 3, wherein A⁴ is —

S(O)_p— and

p represents an integer of 0 to 2.

5. A pharmaceutical composition comprising a therapeutically effective amount of a benzene fused heterocyclic derivative according to any one of claims 1, 2, 3, or 4 as an active ingredient and a pharmaceutically acceptable carrier.

6. A thromboxane A₂ receptor antagonist comprising a benzene fused heterocyclic derivative according to any one of claims 1, 2, 3 or 4 as an active ingredient.

7. A thromboxane A₂ receptor antagonist having a PGI₂ receptor agonistic action, comprising a benzene fused heterocyclic derivative according to any of claims 1, 2, 3 or 4 as an active ingredient.

8. A pharmaceutical composition for treating humans having hypertension, thrombosis, ischemic heart diseases, cerebral circulatory disorders, peripheral circulatory disorders, arteriosclerosis, platelet functional disorders, hyperlipidemia, nephritis, asthma, or allergic diseases, comprising a benzene fused heterocyclic derivative according to any one of claims 1, 2, 3 or 4 as an active ingredient.

9. A pharmaceutical composition for preventing diseases in humans at high risk for developing one or more said disease, wherein said diseases comprise hypertension, thrombosis, ischemic heart diseases, cerebral circulatory disorders, peripheral circulatory disorders, arteriosclerosis, platelet functional disorders, hyperlipidemia, nephritis, asthma, or allergic diseases, said medicine comprising a benzene-fused heterocyclic derivative according to any one of claims 1, 2, 3 or 4 as an active ingredient.

10. A pharmaceutical composition according to claim 5, wherein said pharmaceutically acceptable carrier comprises one or more of starch, lactose, sucrose, crystalline cellulose, an excipient, a colorant, a lubricant, a binder, a disintegrant, and a coating agent.

11. A pharmaceutical composition according to claim 5, wherein said composition is in the form of a sterilized solution.

12. A pharmaceutical composition according to claim 11, further comprising one or more of a tonicity agent, glucose, a pH regulator, and solution adjuvant.

13. A pharmaceutical composition according to claim 5, wherein the form of said composition is one selected from the group consisting of tablets, powders, granules, solution, suppositories, ointments, or lotions.

14. A method for treating a disease related to high thromboxane A₂ activity in humans comprising administering a therapeutically effective amount of a benzene-fused heterocyclic derivative according to any one of claims 1, 2, 3 or 4.

15. A method according to claim 14, wherein said benzene-fused heterocyclic.

16. A method according to claim 15, wherein said benzene-fused heterocyclic derivative is administered 1 to 4 times per day.

17. A method according to claim 14, wherein said benzene-fused heterocyclic derivative is administered by a method selected from the group consisting of intravenous injection, intraarterial injection, intramuscular injection, percutaneous administration, subcutaneous administration, oral administration, or rectal administration.