Trk-INHIBITING COMPOUND

• US 20150111865A1
• Filed: 04/25/2013
• Published: 04/23/2015
• Est. Priority Date: 04/26/2012
• Status: Active Grant

• Current Assignee: ONO Pharmaceutical Company Limited
• Original Assignee: ONO Pharmaceutical Company Limited
• Inventors: Takeuchi, Jun, Iwahashi, Maki, Ikura, Masahiro, Higashino, Masato, Hashimura, Kazuya
• Granted Patent: US 9,242,977 B2
• Time in Patent Office: Days
• US Class Current: 514/210.02
• 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 31/444 containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
• CPC Class Codes: A61K 31/513 having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 17/04 Antipruritics
• 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 33/02 Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• 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 417/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/14 containing three or more hetero rings
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

An object of the present invention is to provide a drug containing a compound having Trk-inhibiting activity as an active ingredient in prophylaxis and/or therapy of diseases such as pain, pruritus, lower urinary tract dysfunction, asthma, allergic rhinitis, inflammatory bowel disease or Chagas disease. A compound represented by the general formula (I):

(wherein all symbols represent the same meanings as described in the specification), a salt thereof, an N-oxide thereof, a solvate thereof or a prodrug thereof is useful as a drug component having Trk-inhibiting activity in prophylaxis and/or therapy of diseases such as pain, pruritus, lower urinary tract dysfunction, asthma, allergic rhinitis, inflammatory bowel disease or Chagas disease.

Claims

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

2. The compound according to claim 1, wherein the general formula (I) is:

3. The compound according to claim 2, wherein the general formula (I-1) is:

4. The compound according to claim 2, wherein the ring Cy₁ is a benzene ring or a 5- to 6-membered monocyclic aromatic heterocycle.

5. The compound according to claim 1, wherein one of A₁ and A₂ is ═

N— and

the other is ═

CH—

or both are ═

N— and

A₃, A₄, A₅ and A₆ are ═

CH—

.

6. The compound according to claim 1, wherein the general formula (I) is:

7. The compound according to claim 6, wherein one of A and A₂ is ═

N— and

the other is ═

CH—

or both are ═

N— and

A, A₄, As and A₆ are ═

CH—

.

8. The compound according to claim 1, wherein the general formula (I) is:

9. The compound according to claim 8, wherein one of A and A₂ is ═

N— and

the other is ═

CH—

or both are ═

N— and

A, A₄, As and A₆ are ═

CH—

.

10. A pharmaceutical composition comprising the compound represented by the general formula (I) according to claim 1, a salt thereof, an N-oxide thereof, a solvate thereof or a prodrug thereof as an active ingredient.

11. The pharmaceutical composition according to claim 10, which is a Trk inhibitor.

12. The pharmaceutical composition according to claim 10, which is a prophylactic and/or therapeutic agent for pain, pruritus, lower urinary tract dysfunction, asthma, allergic rhinitis, inflammatory bowel disease or Chagas disease.

13. The pharmaceutical composition according to claim 12, wherein the pain is pain of osteoarthritis, cancer pain, chronic low back pain, low back pain of osteoporosis, pain of bone fracture, pain of rheumatoid arthritis, neuropathic pain, postherpetic pain, pain of diabetic neuropathy, fibromyalgia, pain of pancreatitis, pain of interstitial cystitis, pain of endometriosis, pain of irritable bowel syndrome, migraine or pain of pulpitis.

14. A medicament which is a combination of the compound represented by the general formula (I) according to claim 1, a salt thereof, an N-oxide thereof, a solvate thereof or a prodrug thereof and at least one selected from acetaminophen, a nonsteroid antiinflammatory drug, an opioid, an antidepressant, an antiepileptic agent, an N-methyl-D-aspartate antagonist, a muscle relaxant, an antiarrhythmic agent, a steroid and a bisphosphonate.

15. A method for prophylaxis and/or therapy of pain, pruritus, lower urinary tract dysfunction, asthma, allergic rhinitis, inflammatory bowel disease or Chagas disease, comprising administering, to a patient, an effective amount of the compound represented by the general formula (I) according to claim 1, a salt thereof, an N-oxide thereof, a solvate thereof or a prodrug thereof.

16. The compound represented by the general formula (I) according to claim 1, a salt thereof, an N-oxide thereof, a solvate thereof or a prodrug thereof for prophylaxis and/or therapy of pain, pruritus, lower urinary tract dysfunction, asthma, allergic rhinitis, inflammatory bowel disease or Chagas disease.

17. A method for inhibiting Trk, comprising administering, to a patient, an effective amount of the compound represented by the general formula (I) according to claim 1, a salt thereof, an N-oxide thereof, a solvate thereof or a prodrug thereof.