Pde10 inhibitors and related compositions and methods

摘要

Disclosed are 1-(5-phenyl-furan-2-yl)-2-alkoxy-2-aryl-ethanone derivatives as represented by the general formula (I), or a pharmaceutically acceptable salt, stereoisomer, solvate or prodrug thereof, wherein: A is a heteroaryl moiety as defined herein and preferably selected from furan-2-yl, R1 is alkyl, haloalkyl, aralkyl, aryl, -(CH2)nO(CH2)mCH3 or -CH2)nN(CH3)2; R2 is (i) substituted or unsubstituted aryl or (ii) substituted or unsubstituted heterocyclyl; R3 is substituted or unsubstituted aryl; n is 1, 2, 3, 4, 5 or 6; and m is 0, 1, 2, 3, 4, 5 or 6; and wherein“alkyl”means a straight chain or branched, noncyclic or cyclic, unsaturated or saturated aliphatic hydrocarbon radical containing from 1 to 6 carbon atoms, and wherein the remaining substituents are as defined herein. Representative compounds include 1-(5-(4-bromo-3,5-dimethoxyphenyl)furan-2-yl)-2-methoxy-2-(4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl)ethanone, 2-methoxy-2-(4-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl)-1-(5-(3,4,5-trimethoxyphenyl)furan-2-yl)ethanone and 1-(5-(4-chloro-3,5-dimethoxyphenyl)furan-2-yl)-2-ethoxy-2-(4-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl)ethanone. Also disclosed is a pharmaceutical composition comprising a compound as defined above, and a pharmaceutically acceptable carrier or diluent, for treating neurological disorders such as psychotic disorders, anxiety disorders, movement disorders and/or neurological disorders such as Parkinson’s disease, Huntington’s disease, Alzheimer’s disease, encephalitis, phobias, epilepsy, aphasia, Bell’s palsy, cerebral palsy, sleep disorders, pain, Tourette’s syndrome, schizophrenia, delusional disorders, bipolar disorders, post-traumatic stress disorders, drug-induced psychosis, panic disorders, obsessive-compulsive disorders, attention deficit disorders, disruptive behavior disorders, autism, depression, dementia, cognitive disorders, epilepsy, insomnias and multiple sclerosis.