Piperazine substituted aryl benzodiazepines

摘要

Described herein are compounds of formula (I) wherein: is an optionally benzo-fused five or six member aromatic ring having zero to three hetero atoms independently selected from N, S, and O; Alk is (C_1-4) alkylene or hydroxy substituted (C_1-4) alkylene; X is oxygen or sulfur; R¹ is hydrogen, (C_1-6) fluroalkyl, (C_3-6) cycloalkyl, or (C_1-4) alkyl, wherein the (C_1-4) alkyl is unsubstituted or substituted with hydroxy, methoxy, ethoxy, OCH₂CH₂OH, or -CN; R² is H, halogen, (C_1-6) fluoroalkyl, (C_1-6) cycloalkyl, OR⁴, SR⁴, NO₂, CN, COR⁴, C(O)OR⁴, CONR⁵R⁶, NR⁵R⁶, SO₂NR⁵R⁶, NR⁵COR⁴, NR⁵SO₂R⁴, optionally substituted aromatic, or (C_1-6) alkyl, wherein (C_1-6) alkyl is unsubstituted or substituted with a hydroxy group; R³ is hydrogen (C_1-6) fluoroalkyl, (C_2-6) alkenyl, Ar, (C_1-4)alkyl-Ar, or (C_1-4) alkyl wherein (C_1-4) alkyly is unsubstituted or substituted with a phenyl; R⁴ is hydrogen, (C_1-6) alkyl, (C_1-6) fluoroalkyl, or optionally substituted aromatic; R⁵ and R⁶ are independently hydrogen, (C_1-6) alkyl, or optionally substituted aromatic, R⁷ is hydrogen, (C_1-6) alkyl, (C_1-6) fluoroalkyl, or optionally substituted aromatic; R⁸ and R⁹ are independently hydrogen, (C_1-6) alkyl, or optionally substituted aromatic; Ar is optionally substituted phenyl, napthyl, monocyclic heteroaromatic or bicyclic heteroaromatic; Z¹ and Z² are independently selected from hydrogen, halogen, (C_1-6) alkyl, (C_1-6) fluoroalkyl, OR⁷, SR⁷, NO², CN, COR⁷, CONR⁸R⁹, NR⁸R⁹, and optionally substituted aromatic; and all salts, solvates, optical and geometric isomers, and crystalline forms thereof. Also, described are the use of the compounds of formula (I) as antagonists of the dopamine D2 receptor and as agents for the treatment of psychosis and bipolar disorders, and pharmaceutical formulations of the compounds of formula (I)