HETEROCYCLE AND CARBOCYCLE DERIVATIVES HAVING TRKA INHIBITORY ACTIVITY

• US 20170240512A1
• Filed: 08/05/2015
• Published: 08/24/2017
• Est. Priority Date: 08/06/2014
• Status: Active Grant

• Current Assignee: Shionogi & Co., Ltd.
• Original Assignee: Shionogi & Co., Ltd.
• Inventors: YUKIMASA, Akira, KOZONO, Iori, NAKAMURA, Kenichiroh, HORIGUCHI, Tohru, KANO, Kazuya, INOUE, Takatsugu
• Granted Patent: US 10,160,727 B2
• Time in Patent Office: Days
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• 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 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 213/72 Nitrogen atoms nitro radicals C07D213/61
• CPC Class Codes: C07D 213/75 Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
• CPC Class Codes: C07D 231/40 Acylated on said nitrogen atom
• CPC Class Codes: C07D 231/54 condensed with carbocyclic rings or ring systems
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 403/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 403/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 403/14 : containing three or more hetero rings
• CPC Class Codes: C07D 405/14 : containing three or more hetero rings
• CPC Class Codes: C07D 409/14 : containing three or more hetero rings
• CPC Class Codes: C07D 413/14 : containing three or more hetero rings
• CPC Class Codes: C07D 417/14 : containing three or more hetero rings
• CPC Class Codes: C07D 471/04 : Ortho-condensed systems
• CPC Class Codes: C07D 487/04 : Ortho-condensed systems
• CPC Class Codes: C07D 487/08 : Bridged systems

Abstract

The present invention relates to a compound represented by Formula (I):

wherein -L- is —C(═X)—, or the like, —Z— is —NR⁵—, or the like, —Z^A— is —NR^5A—, or the like, —W— is —C(R⁸R⁹)n-, —W^A— is —C(R³R⁴)m-, B is substituted or unsubstituted aromatic carbocyclyl, or the like, Y is a bond, or the like, the ring C is a substituted or unsubstituted aromatic heterocycle, or the like, R² is a hydrogen atom, or the like, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising thereof.

Claims

1. A compound represented by Formula (I):

2. The compound according to claim 1,

wherein -L- is —

C(═

X)—

,

═

X is ═

O or ═

S,

Y is a bond,

R^1D is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted acyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted aromatic carbocyclyloxy, substituted or unsubstituted non-aromatic carbocyclyloxy, substituted or unsubstituted aromatic heterocyclyloxy, substituted or unsubstituted non-aromatic heterocyclyloxy, substituted or unsubstituted amino, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted alkenylsulfonyl, substituted or unsubstituted alkynylsulfonyl, substituted or unsubstituted aromatic carbocyclylsulfonyl, substituted or unsubstituted non-aromatic carbocyclylsulfonyl, substituted or unsubstituted aromatic heterocyclylsulfonyl, substituted or unsubstituted non-aromatic heterocyclylsulfonyl, carboxy, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, or substituted or unsubstituted non-aromatic heterocyclyl,

B is substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, or substituted or unsubstituted non-aromatic heterocyclyl,

or its pharmaceutically acceptable salt.

3. The compound according to claim 2,

wherein m=1 and n=1,

or its pharmaceutically acceptable salt.

4. The compound according to claim 3,

wherein -A- is —

N⁺(O⁻

)(R^1A)—

or —

CR^1DR^1E,

or its pharmaceutically acceptable salt.

5. The compound according to claim 3,

wherein -A- is —

NR¹—

,

R¹ is

alkyl substituted with

halogenoethyloxy,

substituted or unsubstituted aromatic carbocyclyloxy,

substituted or unsubstituted non-aromatic carbocyclyloxy,

substituted or unsubstituted non-aromatic heterocyclyl,

substituted or unsubstituted alkyloxycarbonylamino,

substituted or unsubstituted alkylcarbonylamino,

substituted or unsubstituted alkylsulfonylamino,

substituted or unsubstituted alkylsulfonyl,

substituted or unsubstituted non-aromatic carbocyclyl,

carboxy,

substituted or unsubstituted alkyloxyalkyloxy, or

acyl;

alkyl substituted with furyl substituted with

carboxy,

halogen,

cyano,

alkyl or

hydroxylalkyl;

alkyl substituted with

substituted or unsubstituted alkyloxy and substituted or unsubstituted amino,

substituted or unsubstituted alkyloxy and cyano,

substituted or unsubstituted alkyloxy and halogen,

substituted or unsubstituted alkyloxy and substituted or unsubstituted aromatic heterocyclyl,

substituted or unsubstituted alkyloxy and hydroxy,

substituted or unsubstituted alkyloxy and substituted or unsubstituted non-aromatic heterocyclyl,

substituted or unsubstituted aromatic heterocyclyl and hydroxy,

substituted or unsubstituted alkyloxy and substituted or unsubstituted carbamoyl,

substituted or unsubstituted alkyloxy and substituted or unsubstituted alkyloxycarbonyl,

substituted or unsubstituted alkyloxy and substituted or unsubstituted alkylthio, or

substituted or unsubstituted alkyloxycarbonyl and substituted or unsubstituted aromatic heterocyclyl;

substituted or unsubstituted alkyloxycarbonyl;

substituted or unsubstituted acyl;

substituted or unsubstituted non-aromatic heterocyclyl, or

substituted or unsubstituted non-aromatic carbocyclyl,

or its pharmaceutically acceptable salt.

6. The compound according to claim 2,

wherein B is phenyl substituted with substituted or unsubstituted alkyloxycarbonyl, phenyl substituted with substituted or unsubstituted carbamoyl, phenyl substituted with substituted or unsubstituted aromatic carbocyclyl, phenyl substituted with substituted or unsubstituted aromatic heterocyclyl, phenyl substituted with substituted or unsubstituted alkenyl, phenyl substituted with substituted or unsubstituted non-aromatic carbocyclyl, phenyl substituted with carboxy, phenyl substituted with alkylamino, phenyl substituted with substituted or unsubstituted acyl, substituted or unsubstituted naphthyl, substituted or unsubstituted non-aromatic heterocyclyl, or substituted or unsubstituted bicyclic aromatic heterocyclyl,

or its pharmaceutically acceptable salt.

7. The compound according to claim 2,

wherein m=2 and n=0,

or its pharmaceutically acceptable salt.

9. The compound according to claim 7,

wherein -A- is —

NR¹—

,

or a pharmaceutically acceptable salt thereof.

10. The compound according to claim 5 or 6,

wherein —

Z—

is —

NH—

, ═

X is ═

O and —

Z^A—

is —

NH—

,

or a pharmaceutically acceptable salt thereof.

11. The compound according to claim 7,

wherein —

Z—

is —

NR⁵—

, ═

X is ═

O and —

Z^A—

is —

NR^5A—

,

or its pharmaceutically acceptable salt.

12. The compound according to claim 11,

wherein R⁵ and R^5A are hydrogen atoms,

or its pharmaceutically acceptable salt.

19. The compound according to claim 2,

wherein R⁸ and R⁹ are hydrogen atoms, or R⁸ and R⁹ are taken together to form oxo,

or its pharmaceutically acceptable salt.

20. The compound according to claim 2,

wherein R³ and R⁴ are hydrogen atoms,

or its pharmaceutically acceptable salt.

21. The compound according to claim 2,

wherein Ring C is a substituted or unsubstituted aromatic heterocycle,

or its pharmaceutically acceptable salt.

22. The compound according to claim 21,

wherein Ring C is substituted or unsubstituted pyrazole,

or its pharmaceutically acceptable salt.

23. The compound according to claim 22,

wherein Ring C is a group represented by Formula:

24. The compound according to claim 23,

wherein R¹³ is a hydrogen atom, or substituted or unsubstituted aromatic carbocyclyl, R¹⁴ is substituted or unsubstituted aromatic heterocyclyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted aromatic carbocyclyl, or substituted or unsubstituted non-aromatic heterocyclyl, and R¹⁵ is substituted or unsubstituted alkyl,

or its pharmaceutically acceptable salt.

25. The compound according to claim 6,

wherein R¹ is substituted or unsubstituted alkyl,

or its pharmaceutically acceptable salt.

26. The compound according to claim 4,

wherein R^1A is substituted or unsubstituted alkyl,

or its pharmaceutically acceptable salt.

27. The compound according to claim 4,

wherein R^1E is a hydrogen atom,

or its pharmaceutically acceptable salt.

28. The compound according to claim 2,

wherein R² is a hydrogen atom, or substituted or unsubstituted alkyl,

or its pharmaceutically acceptable salt.

29. The compound according to claim 1,

wherein the compound is represented by Formula (I′

);

30. The compound according to claim 1,

wherein the compound is represented by Formula (I″

);

31. The compound according to claim 1,

wherein the compound is represented by Formula (I′

″

);

32. A pharmaceutical composition comprising the compound according to claim 1, or its pharmaceutically acceptable salt.

33. The pharmaceutical composition according to claim 32, wherein the composition has a TrkA inhibitory activity.

34. A method for treating or preventing a disease related to TrkA comprising administering the compound according to claim 1, or its pharmaceutically acceptable salt.

8. (canceled)

13-18. -18. (canceled)

35. (canceled)