FUSED IMIDAZOLE CARBOXAMIDES AS TRPV3 MODULATORS

摘要

Disclosed herein are fused imidazole carboxamide compounds of formula (I), wherein the substituents are as defined within the specification, processes for their preparation, compositions comprising said compounds and uses thereof. Said compounds are useful as transient receptor potential vanilloid 3 (TRPV3) modulators and as such are useful in the treatment of pain, acute pain, chronic pain, nociceptive pain, neuropathic pain, post-operative pain, dental pain, cancer pain, cardiac pain arising from an ischemic myocardium, pain due to migraine, arthralgia, neuropathies, neuralgia, trigeminal neuralgia nerve injury, diabetic neuropathy, neurodegeneration, retinopathy, neurotic skin disorder, stroke, urinary bladder hypersensitiveness, urinary incontinence, vulvodynia, gastrointestinal disorders such as irritable bowel syndrome. Examples of particularly preferred compounds include: 6-{ (E)-2-[3-Difluoromethoxy-2-(2,2-dimethylpropoxy)phenyl]vinyl} -N-[4-(trifluoro-methyl)-1,3-thiazol-2-yl]imidazo[2,1-b][1,3]thiazole-5-carboxamide, 6-[(E)-2-(2-Cyclopentyloxy-3-methoxyphenyl)vinyl]-N-[4-(trifluoromethyl)-1,3-thiazol-2-yl]imidazo[2,1-b][1,3]thiazole-5-carboxamide; 6-{ (E)-2-[3-(Difluoromethoxy)-2-(2,2-dimethylpropoxy)phenyl]vinyl} -N-(3-trifluoromethylphenyl)imidazo[2,1-b][1,3]thiazole-5-carboxamide; 6-{ (E)-2-[3-(Difluoromethoxy)-2-pentyloxy)phenyl]vinyl} -N-(4-cyclopropyl-1,3-thiazol-2-yl)imidazo[2,1-b][1,3]thiazole-5-carboxamide; 2-{ (E)-2-[3-(Difluoromethoxy)-2-(3-methylbutoxy)phenyl]vinyl} -N-[4-(trifluoromethyl)-1,3-thiazol-2-yl]imidazo[1,2-a]pyridine-3-carboxamide.