Piperazine substituted aryl benzodiazepines and their use as dopamine receptor antagonists for the treatment of psychotic disorders

摘要

Described herein are antipyschotic compounds of formula (I) wherein, A is an optionally benzo-fused five or six member aromatic ring having zero to three hetero atoms independently selected from N, O, and S; Alk is (C_1-4) alkylene optionally substituted with OH, methoxy, ethoxy, or F; Ar is optionally substituted phenyl, naphthyl, monocyclic heteroaromatic, or bicyclic heteroaromatic; R¹ is hydrogen or (C_1-4) alkyl optionally substituted with OH, OR³, or OCH₂CH₂OH, wherein R³ is (C_1-2) alkyl; R² is H, (C_1-6) alkyl, halogen, fluorinated (C_1-6) alkyl, OR⁴, SR⁴, NO₂, CN, COR⁴, CONR⁵R⁶, SO₂NR⁵R⁶, NR⁵R⁶, NR⁵COR⁴, NR⁵SO₂R⁴, or optionally substituted phenyl, wherein R⁴ is hydrogen, (C_1-6) alkyl, fluorinated (C_1-6) alkyl, benzyl, or optionally substituted phenyl, R⁵ and R⁶ are independently hydrogen, (C_1-6) alkyl, or optionally substituted phenyl; Z is one or two substituents independently selected from hydrogen, halogen, (C_1-6) alkyl, fluorinated (C_1-6) alkyl, OR⁷, SR⁷, NO₂, CN, COR⁷, CONR⁸R⁹, SO₂NR⁸R⁹, NR⁸SO₂R⁷, NR⁸R⁹, or optionally substituted phenyl, wherein R⁷ is hydrogen, (C_1-6) alkyl, fluorinated alkyl, benzyl, or optionally substituted phenyl, R⁸ and R⁹ are independently hydrogen, (C_1-6) alkyl, or optionally substituted phenyl; and salts, solvates, and crystal forms thereof. Also described are the use of the compounds of formula (a) 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). Also described are compounds useful as intermediates for the synthesis of the compounds of formula (I).