BENZOTHIAZOLE AND BENZOXAZOLE DERIVATIVES AND METHODS OF USE

摘要

Disclosed are 2-(pyrrolidin-1-yl)benzo[d]thiazole derivatives as represented by the general formula (I), wherein Z is sulfur; n is an integer from 0 to 2; p is an integer from 0 to 1; and wherein the remaining substituents are as defined herein; and radiolabelled analogues thereof. Representative compounds include 6-(1-methyl-1H-pyrazol-4-yl)-2-(3-(piperidin-1-yl)azetidin-1-yl)benzo[d]thiazole, (R)-4-(2-(1,3'-bipyrrolidin-1'-yl)benzo[d]thiazol-6-yl)benzonitrile, (R)-6-(1-(11C)methyl-1H-pyrazol-4-yl)-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazole, (R)-6-(1-methyl-1H-pyrazol-4-yl)-2-(3-(4-(18F)fluoro-piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazole, (R)-2-(2-(3-(4-(18F)fluoro-piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazol-6-yl)pyridazin-3(2R)-one; (R)-3-(2-(3-(4-(18F)fluoro-piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazol-6-yl)oxazolidin-2-one, (S)-3-hydroxy-1-(2-((R)-3-(4-(18F)fluoro-piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazol-6-yl)pyrrolidin-2-one and (R)-N-(2-(18F)fluoroethyl)-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazole-6-carboxamide. Further disclosed is a pharmaceutical composition comprising a therapeutically effective amount of a compound as defined above in combination with a pharmaceutically acceptable carrier for treating a condition or disorder modulated by the histamine-3 receptors selected from acute myocardial infarction, Alzheimer's disease, asthma, attention-deficit hyperactivity disorder, bipolar disorder, cognitive dysfunction, cognitive deficits in psychiatric disorders, deficits of memory, deficits of learning, dementia, cutaneous carcinoma, drug abuse, diabetes, type II diabetes, depression, epilepsy, gastrointestinal disorders, inflammation, insulin resistance syndrome, jet lag, medullary thyroid carcinoma, melanoma, Meniere's disease, metabolic syndrome, mild cognitive impairment, migraine, mood and attention alteration, motion sickness, narcolepsy, neurogenic inflammation, obesity, obsessive compulsive disorder, pain, neuropathic pain, osteoarthritis pain, Parkinson's disease, polycystic ovary syndrome, schizophrenia, cognitive deficits of schizophrenia, seizures, septic shock, Syndrome X, Tourette's syndrome, vertigo, and sleep disorders.