Heterocycle derivatives having TrkA inhibitory activity

• US 10,640,495 B2
• Filed: 07/06/2016
• Issued: 05/05/2020
• Est. Priority Date: 07/07/2015
• Status: Active Grant

• Current Assignee: Shionogi & Co., Ltd.
• Original Assignee: Shionogi & Co., Ltd.
• Inventors: Yukimasa, Akira, Nakamura, Kenichiroh, Inagaki, Masanao, Kano, Kazuya, Fujiu, Motohiro, Yamaguchi, Hiroki, Hata, Kayoko, Inoue, Takatsugu
• Primary Examiner(s): Rozof, Timothy R
• Application Number:
  US15/741,875
• Publication Number:
  US 20180201607A1
• Time in Patent Office: 1,399 Days
• CPC Class Codes: A61K 31/4155 non condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/422 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/433 Thidiazoles
• CPC Class Codes: A61K 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/454 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• 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 25/00 Drugs for disorders of the nervous system
• 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 35/00 Antineoplastic agents
• 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 231/38 : Nitrogen atoms nitro radicals C07D231/16
• CPC Class Codes: C07D 403/14 : containing three or more hetero rings
• CPC Class Codes: C07D 405/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/14 : 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
• CPC Class Codes: C07D 491/048 : the oxygen-containing ring being five-membered
• CPC Class Codes: C07D 491/056 : with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
• CPC Class Codes: C07D 491/08 : Bridged systems
• CPC Class Codes: C07D 491/107 : with only one oxygen atom as ring hetero atom in the oxygen-containing ring
• CPC Class Codes: C07D 498/04 : Ortho-condensed systems
• CPC Class Codes: C07F 7/1804 : Compounds having Si-O-C linkages Si-O-acyl linkages C07F7/1896

Abstract

The present invention provides a compound having a TrkA inhibitory activity or a pharmaceutically acceptable salt thereof.

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, B is substituted or unsubstituted aromatic carbocyclyl, or the like, Y is a single 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, and the group represented by

is a group represented by Formula:

or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising the same.

Claims

1. A compound represented by Formula (I):

2. The compound according to claim 1,

wherein —

Y—

is a single bond, -L- is —

C(═

X)—

, and R¹ is cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted acyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted alkenyl sulfonyl, 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, 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,

or a pharmaceutically acceptable salt thereof.

3. The compound according to claim 2,

wherein —

Z—

is —

NR⁵—

or —

CR⁶R⁷—

,

or a pharmaceutically acceptable salt thereof.

4. The compound according to claim 3,

wherein —

Z—

is —

NR⁵—

, -L- is —

C(═

O)—

, and —

Z^A—

is —

NR^5A—

,

or a pharmaceutically acceptable salt thereof.

5. The compound according to claim 4,

wherein each of R⁵ and R^5A is a hydrogen atom,

or a pharmaceutically acceptable salt thereof.

6. The compound according to claim 2,

wherein B is substituted or unsubstituted aromatic carbocyclyl or substituted or unsubstituted aromatic heterocyclyl,

or a pharmaceutically acceptable salt thereof.

7. The compound according to claim 2,

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

or a pharmaceutically acceptable salt thereof.

8. The compound according to claim 2,

wherein the group represented by Formula:

9. The compound according to claim 2,

wherein R¹ is substituted or unsubstituted alkyl, R^1A is substituted or unsubstituted alkyl, and R^1B is a hydrogen atom,

or a pharmaceutically acceptable salt.

10. The compound according to claim 2,

wherein each of R³ and R⁴ is a hydrogen atom,

or a pharmaceutically acceptable salt.

11. The compound according to claim 2,

wherein the ring C is a substituted or unsubstituted aromatic heterocycle,

or a pharmaceutically acceptable salt thereof.

12. The compound according to claim 2,

wherein the ring C is substituted or unsubstituted pyrazole,

or a pharmaceutically acceptable salt thereof.

13. The compound according to claim 12,

wherein the ring C is a ring represented by Formula:

14. The compound according to claim 13,

wherein R¹³ is substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted alkyl, or substituted or unsubstituted non-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 a hydrogen atom or substituted or unsubstituted alkyl,

or a pharmaceutically acceptable salt thereof.

15. The compound according to claim 1, wherein

the compound is selected from the group consisting of,

16. A pharmaceutical composition comprising the compound according claim 1, or a pharmaceutically acceptable salt thereof.

17. A method for treating a disease related to TrkA comprising administering the compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein the disease related to TrkA is one or more of pain associated with osteoarthritis, rheumatoid arthritis, fracture, interstitial cystitis, chronic pancreatitis and prostate inflammation;

nociceptive pain as typified by chronic low back pain, diabetic peripheral neuropathy pain, postoperative pain, pelvic pain and cancer pain;

neuropathic pain;

acute pain;

chronic pain;

cancer;

an inflammatory disease;

an allergic disease;

or a dermatological disease.

18. The compound according to claim 2, wherein the group represented by Formula:

19. The compound according to claim 13,

wherein the group represented by Formula:

20. The compound according to claim 14,

wherein the group represented by Formula: