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 (CSUB1-4/SUB) alkylene optionally substituted with OH, methoxy, ethoxy, or F; Ar is optionally substituted phenyl, naphthyl, monocyclic heteroaromatic, or bicyclic heteroaromatic; RSUP1 /SUPis hydrogen or (CSUB1-4/SUB) alkyl optionally substituted with OH, ORSUP3/SUP, or OCHSUB2/SUBCHSUB2/SUBOH, wherein RSUP3 /SUPis (CSUB1-2/SUB) alkyl; RSUP2 /SUPis H, (CSUB1-6/SUB) alkyl, halogen, fluorinated (CSUB1-6/SUB) alkyl, ORSUP4/SUP, SRSUP4/SUP, NOSUB2/SUB, CN, CORSUP4/SUP, CONRSUP5/SUPRSUP6/SUP, SOSUB2/SUBNRSUP5/SUPRSUP6/SUP, NRSUP5/SUPRSUP6/SUP, NRSUP5/SUPCORSUP4/SUP, NRSUP5/SUPSOSUB2/SUBRSUP4/SUP, or optionally substituted phenyl, wherein RSUP4 /SUPis hydrogen, (CSUB1-6/SUB) alkyl, fluorinated (CSUB1-6/SUB) alkyl, or optionally substituted phenyl, RSUP5 /SUPand RSUP6 /SUPare independently hydrogen, (CSUB1-6/SUB) alkyl, or optionally substituted phenyl; Z is one or two substituents independently selected from hydrogen, halogen, (CSUB1-6/SUB) alkyl, fluorinated (CSUB1-6/SUB) alkyl, ORSUP7/SUP, SRSUP7/SUP, NOSUB2/SUB, CN, CORSUP7/SUP, CONRSUP8/SUPRSUP9/SUP, SOSUB2/SUBNRSUP8/SUPRSUP9/SUP, NRSUP8/SUPSOSUB2/SUBRSUP7/SUP, NRSUP8/SUPRSUP9/SUP, or optionally substituted phenyl, wherein RSUP7 /SUPis hydrogen, (CSUB1-6/SUB) alkyl, fluorinated alkyl, or optionally substituted phenyl, RSUP8 /SUPand RSUP9 /SUPare independently hydrogen, (CSUB1-6/SUB) alkyl, or optionally substituted phenyl; and salts, solvates, and crystal forms thereof. Also described are the use of the compounds of formula (I) as antagonists of the dopamine DSUB2 /SUBreceptor and as agents for the treatment of psychosis and bipolar disorder, and pharmaceutical formulations of the compounds of formula (I).