1,3-THIAZOL-2-YL SUBSTITUTED BENZAMIDES

• US 20200131169A1
• Filed: 10/01/2019
• Published: 04/30/2020
• Est. Priority Date: 12/09/2014
• Status: Active Grant

• Current Assignee: Evotec AG
• Original Assignee: Bayer AG
• Inventors: DAVENPORT, Adam James, BRAUER, Nico, FISCHER, Oliver Martin, ROTGERI, Andrea, ROTTMANN, Antje, NEAGOE, Ioana, NAGEL, Jens, GODINHO-COELHO, Anne-Marie, KLAR, Jurgen
• Granted Patent: US 11,142,523 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• 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 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/18 for HIV
• 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: C07D 471/08 Bridged systems
• CPC Class Codes: C07D 498/08 Bridged systems
• CPC Class Codes: Y02P 20/582 Recycling of unreacted starting or intermediate materials

Abstract

The present invention relates to 1,3-thiazol-2-yl substituted benzamide compounds of general formula (I) as described and defined herein, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of neurogenic disorder, as a sole agent or in combination with other active ingredients.

Claims

1-38. -38. (canceled)

39. A compound of formula (I):

40. The compound according to claim 39, wherein q is the integer 0.

41. The compound according to claim 40, which is of formula (Ia):

42. The compound according to claim 40, wherein R¹ is methyl or ethyl.

43. The compound according to claim 40, wherein R³ is methyl or ethyl.

44. The compound according to claim 40, wherein:

R² is —

C₃-C₄-cycloalkyl or unsubstituted —

(CH₂)_q-(4- to 6-membered heterocycloalkyl); and

q is the integer 0.

45. The compound according to claim 40, wherein A is optionally substituted pyrimidinyl or pyridazinyl.

46. The compound according to claim 45, wherein A is CF₃-pyrimidinyl or 2-CF₃-pyrimidin-5-yl.

47. The compound according to claim 40, wherein R² is unsubstituted tetrahydrofuran-3-yl or unsubstituted oxetan-3-yl.

48. A method of treating a disease, condition, or disorder in a patient in need thereof, comprising administering an effective amount of the compound according to claim 40 to the patient, wherein the disease, condition, or disorder is associated with a pain syndrome.

49. The method of claim 48, wherein the disease, condition, or disorder associated with a pain syndrome is acute, chronic, inflammatory or neuropathic pain.

50. The method of claim 48, wherein the disease, condition, or disorder associated with a pain syndrome is inflammatory pain, surgical pain, visceral pain, dental pain, premenstrual pain, endometriosis-associated pain, central pain, pain due to burning mouth syndrome, pain due to burns, pain due to migraine, cluster headaches, pain due to nerve injury, pain due to neuritis, neuralgias, pain due to poisoning, pain due to ischemic injury, pain due to interstitial cystitis, cancer pain, pain due to viral, parasitic or bacterial infections, pain due to traumatic nerve-injury, pain due to post-traumatic injuries, pain due to factures and sport injuries, pain due to trigeminal neuralgia, pain associated with small fiber neuropathy, pain associated with diabetic neuropathy, chronic lower back pain, phantom limb pain, pelvic pain syndrome, chronic pelvic pain, neuroma pain, complex regional pain syndrome, pain associated with gastrointestinal distension, chronic arthritic pain and related neuralgias, pain associated with cancer, pain associated with chemotherapy, HIV and HIV treatment-induced neuropathy, hyperalgesia, allodynia, functional bowel disorders, irritable bowel syndrome, arthritis, osteoarthritis, or rheumatoid arthritis

51. The method of claim 48, wherein the compound is:

3-(5-Methyl-1,3-thiazol-2-yl)-5-[(3R)-tetrahydrofuran-3-yloxy]-N-{(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}benzamide;

3-(5-Methyl-1,3-thiazol-2-yl)-5-[(3S)-tetrahydrofuran-3-yloxy]-N-{(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}benzamide;

3-(5-Methyl-1,3-thiazol-2-yl)-5-(oxetan-3-yloxy)-N-{(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}benzamide;

3-(5-Ethyl-1,3-thiazol-2-yl)-5-[(3R)-tetrahydrofuran-3-yloxy]-N-{(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}benzamide;

3-(5-Ethyl-1,3-thiazol-2-yl)-5-[(3S)-tetrahydrofuran-3-yloxy]-N-{(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}benzamide;

3-(5-Ethyl-1,3-thiazol-2-yl)-5-(oxetan-3-yloxy)-N-{(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}benzamide;

3-(5-Methyl-1,3-thiazol-2-yl)-5-[(3R)-tetrahydrofuran-3-yloxy]-N-{(1R)-1-[6-(trifluoromethyl)pyridazin-3-yl]ethyl}benzamide;

or

3-(5-Methyl-1,3-thiazo1-2-yl)-5-[(3S)-tetrahydrofuran-3-yloxy]-N-{(1R)-1-[6-(trifluoromethyl)pyridazin-3-yl]ethyl}benzamide.

52. The method according to claim 51, wherein the compound is:

3-(5-methyl-1,3-thiazol-2-yl)-5-[(3R)-tetrahydrofuran-3-yloxy]-N-{(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}benzamide;

or

3-(5-methyl-1,3-thiazol-2-yl)-5-[(3S)-tetrahydrofuran-3-yloxy]-N-{(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}benzamide.

53. The method according to claim 51, wherein the compound is:

3-(5-methyl-1,3-thiazol-2-yl)-5-[(3R)-tetrahydrofuran-3-yloxy]-N-{(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}benzamide.