Ring-fused heterocyclic derivative

Patent metadata

Field	Value
Publication number	US-9000186-B2
Application number	US-201213983248-A
Country	US
Kind code	B2
Filing date	Feb 1, 2012
Priority date	Feb 1, 2011
Publication date	Apr 7, 2015
Grant date	Apr 7, 2015

Abstract

A ring-fused heterocyclic derivative represented by the following general formula (I) or a pharmaceutically acceptable salt thereof having a T-type calcium channel regulatory effect and useful as a pruritus therapeutic and/or preventive agent, and the like are provided. In the general formula (I), R 1 represents optionally substituted lower alkyl, and the like; R 2 represents an optionally substituted cycloalkyl, and the like; Q represents a hydrogen atom, and the like; R 3 represents —C(═O)NR 8 R 9 (wherein R 8 and R 9 may be the same or different, and each represents a hydrogen atom, and the like), and the like; L 1 represents —CR 11A R 11B — (wherein R 11A and R 11B may be the same or different, and each represents a hydrogen atom, and the like), and the like; and W 1 and W 2 may be the same or different, and each represents C—R 12 (wherein R 12 represents a hydrogen atom, and the like), and the like.

First claim

The invention claimed is:

1. A compound represented by the general formula (IA) or a pharmaceutically acceptable salt thereof,

wherein R 1A represents optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted cycloalkyl, optionally substituted lower alkoxy, an optionally substituted aromatic heterocyclic group, an optionally substituted aliphatic heterocyclic group, optionally substituted aralkyl, —C(═O)R 4 (wherein R 4 represents optionally substituted lower alkyl, optionally substituted aralkyl, optionally substituted cycloalkyl, or an optionally substituted aliphatic heterocyclic group), —C(═O)OR 4 (wherein R 4 has the same definition as described above), —C(═O)NR 5 R 6 (wherein R 5 and R 6 may be the same or different, and each represents a hydrogen atom, optionally substituted lower alkyl, or optionally substituted aralkyl), —NR 7 C(═O)OR 4 (wherein R 4 has the same definition as described above, and R 7 represents a hydrogen atom, or optionally substituted lower alkyl), or —S(O)nR 4 (wherein R 4 has the same definition as described above, and n represents an integer of 0 to 2),
R 2A represents an optionally substituted cycloalkyl, optionally substituted aryl, an optionally substituted aromatic heterocyclic group, or an optionally substituted aliphatic heterocyclic group,
Q A represents a hydrogen atom, halogen, or optionally substituted lower alkyl,
R 3A represents (i) —C(═O)NHR 9A , wherein R 9A represents a hydrogen atom, optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted aralkyl, optionally substituted aryl, an optionally substituted aromatic heterocyclic group, an optionally substituted aliphatic heterocyclic group, or —OR 10 (wherein R 10 represents optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted cycloalkyl, optionally substituted aralkyl, optionally substituted aryl, an optionally substituted aromatic heterocyclic group, or an optionally substituted aliphatic heterocyclic group), (ii) —C(═O)NR 7A —NR 7B C(═O)R 10 (wherein R 7A and R 7B may be the same or different, and each has the same definition as the above R 7 , and R 10 has the same definition as described above), (iii) —NHC(═O)R 10 (wherein R 10 has the same definition as described above), (iv) —NHC(═O)NR 8A R 9A (wherein R 8A and R 9A may be the same or different, and have the same definition as the above R 9A ), (v) —NR 7A C(═O)OR 10 (wherein R 7A and R 10 have the same definitions as described above, respectively), (vi) —SO 2 NR 8A R 9A (wherein R 8A and R 9A may be the same or different, and each has the same definition as the above R 9A ), (vii) —NHSO 2 R 10 (wherein R 10 has the same definition as described above), (viii) —NHSO 2 NR 8A R 9A (wherein R 8A and R 9A may be the same or different, and each has the same definition as the above R 9A ), or (ix) optionally substituted benzimidazol-2-yl,
L 1A represents —CR 11A R 11B — (wherein R 11A and R 11B may be the same or different, and each represents a hydrogen atom, optionally substituted lower alkyl, halogen, optionally substituted lower alkoxy, or hydroxy), or —(CR 11A R 11B )n 1 -L 2 - (wherein R 11A and R 11B may be the same or different, and each represents a hydrogen atom, optionally substituted lower alkyl, halogen, optionally substituted lower alkoxy, or hydroxy, n 1 represents an integer of 0 to 1, and L 2 represents —C(═O)—, —O—, —S(O)n 2 - (wherein n 2 represents an integer of 0 to 1), or —SO 2 NR 7C — (wherein R 7C represents a hydrogen atom, optionally substituted lower alkyl, or optionally substituted cycloalkyl), and
W 1A and W 2A may be the same or different, and each represents C—R 12 (wherein R 12 represents a hydrogen atom, halogen, optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted lower alkoxy, or optionally substituted lower alkenyl).

2. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R 1A is optionally substituted lower alkyl or optionally substituted cycloalkyl.

3. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R 1A is optionally substituted lower alkyl.

4. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R 1A is halogen-substituted lower alkyl.

5. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R 1A is optionally substituted cycloalkyl.

6. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R 2A is optionally substituted cycloalkyl.

7. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R 2A is an optionally substituted aliphatic heterocyclic group.

8. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein L 1A is —CR 11A R 11B — (wherein R 11A and R 11B may be the same or different, and have the same definitions as described above, respectively).

9. The compound or a pharmaceutically acceptable salt thereof according to claim 8 , wherein R 11A and R 11B are hydrogen atoms.

10. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein L 1A is —(CR 11A R 11B )n 1 -L 2 - (wherein R 11A , R 11B , n 1 , and L 2 have the same definitions as described above, respectively).

11. The compound or a pharmaceutically acceptable salt thereof according to claim 10 , wherein n 1 is 0.

12. The compound or a pharmaceutically acceptable salt thereof according to claim 10 , wherein n 1 is 1.

13. The compound or a pharmaceutically acceptable salt thereof according to claim 10 , wherein L 2 is —O—.

14. The compound or a pharmaceutically acceptable salt thereof according to claim 10 , wherein L 2 is —S(O)n 2 - (wherein n 2 has the same definition as described above).

15. The compound or a pharmaceutically acceptable salt thereof according to claim 14 , wherein n 2 is 2.

16. The compound or a pharmaceutically acceptable salt thereof according to claim 10 , wherein L 2 is —SO 2 NR 7C — (wherein R 7c has the same definition as described above).

17. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein Q A is a hydrogen atom.

18. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein Q A is halogen.

19. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein Q A is optionally substituted lower alkyl.

20. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R 3A is —NHC(═O)R 10 (wherein R 10 has the same definition as described above).

21. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R 3A is —C(═O)NHR 9A (wherein R 9A has the same definition as described above).

22. The compound or a pharmaceutically acceptable salt thereof according to claim 21 , wherein R 9A is optionally substituted lower alkyl, optionally substituted aryl, an optionally substituted aromatic heterocyclic group, or an optionally substituted aliphatic heterocyclic group.

23. The compound or a pharmaceutically acceptabl

Assignees

• Sawada Takashi
• Danjo Tomohiro
• Motosawa Keiichi
• Furuta Takayuki
• Ichioka Maki
• Sugawara Masamori
• Uesaka Noriaki
• Kyowa Hakko Kirin Co Ltd

Inventors

• Sawada Takashi
• Danjo Tomohiro
• Motosawa Keiichi
• Furuta Takayuki
• Ichioka Maki
• Sugawara Masamori
• Uesaka Noriaki

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P5/00

  Drugs for disorders of the endocrine system · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title