Cyclic amide derivative, and its production and use

• US 8,697,865 B2
• Filed: 03/02/2010
• Issued: 04/15/2014
• Est. Priority Date: 05/21/2004
• Status: Expired due to Fees

• Current Assignee: Takeda Pharmaceutical Company Limited
• Original Assignee: Takeda Pharmaceutical Company Limited
• Inventors: Kubo, Keiji, Imaeda, Yasuhiro
• Primary Examiner(s): Chu, Yong
• Assistant Examiner(s): WRIGHT, SONYA N
• Application Number:
  US12/715,930
• Publication Number:
  US 20100160629A1
• Time in Patent Office: 1,505 Days
• Field of Search: 544/224, 514/247
• US Class Current: 544/224
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 211/76 attached in position 2 or 6
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 403/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 413/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 417/04 directly linked by a ring-member-to-ring-member bond

Abstract

The present invention provides a cyclic amide derivative useful as a drug for treating thrombosis, which is represented by the formula (I):

wherein R¹ represents an optionally substituted cyclic hydrocarbon group or an optionally substituted heterocyclic group, W represents a bond or an optionally substituted divalent chain hydrocarbon group, a represents 0, 1, or 2, X¹ represents an optionally substituted lower alkylene or an optionally substituted lower alkenylene, Y¹ represents —C(O)—, —S(O)— or —S(O)₂—, A represents a piperazine ring which may be further substituted or a piperidine ring which may be further substituted, X² represents a bond or an optionally substituted lower alkylene, Y² represents —C(O)—, —S(O)—, —S(O)₂— or —C(═NR⁷)—, X³ represents an optionally substituted C_1-4 alkylene or an optionally substituted C_2-4 alkenylene, Z³ represents —N(R⁴)—, —O— or a bond, Z¹ represents —C(R²) (R^2′)—, —N(R²)—, etc., and Z² represents —C(R³)(R^3′)—, —N(R³)—, etc., or a salt thereof.

Claims

1. A compound represented by the formula (I):

2. The compound according to claim 1, wherein R¹ is an aryl which may be optionally substituted.

3. The compound according to claim 1, wherein R¹ is a naphthyl which may be substituted with a halogen atom.

4. The compound according to claim 1, wherein W is a bond.

5. The compound according to claim 1, wherein Y¹ is —

C(O)—

.

6. The compound according to claim 1, wherein —

X¹—

Y¹—

is represented by the formula;

7. The compound according to claim 1, wherein A is a group represented by the formula:

8. The compound according to claim 1, wherein X² is a bond.

9. The compound according to claim 1, wherein Y² is —

C(O)—

or —

C(═

NR⁷)—

.

10. The compound according to claim 1, wherein is a single bond.

11. The compound according to claim 1, wherein Z³ is a bond.

12. The compound according to claim 1, wherein the group:

13. The compound according to claim 1, wherein the group:

14. The compound according to claim 1, wherein a is 2.

15. The compound according to claim 1, wherein W is a bond, a is 2, —

X¹—

Y¹—

is represented by the formula;

16. The compound according to claim 15, wherein R¹ is an aryl which may be optionally substituted, and A is a group represented by the formula:

17. The compound according to claim 16, wherein R¹ is an aryl which may be substituted with 1 to 3 halogen atom(s), Y² is —

C(O)—

or —

C(═

NR⁷)—

,

is a single bond, and Z³ is a bond.

18. The compound according to claim 17, wherein the group:

19. The compound according to claim 17, wherein the group:

20. A pharmaceutical composition comprising the compound according to claim 1.

21. The pharmaceutical composition according to claim 20, which is an anticoagulant.

22. The pharmaceutical composition according to claim 20, which is an activated blood coagulation factor X inhibitor.