SUBSTITUTED PIPERAZINES OF AZEPINES, OXAZEPINES, AND THIAZEPINES

摘要

Described herein are antipyschotic 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, O, and S; RSUP1 /SUPis hydrogen, (CSUB1-6/SUB) fluoroalkyl, (CSUB3-6/SUB) cycloalkyl, or (CSUB1-4/SUB) alkyl, wherein the (CSUB1-4/SUB) alkyl is unsubstituted or substituted with hydroxy, methoxy, ethoxy, OCHSUB2/SUBCHSUB2/SUBOH, -CN, imidazolidin-2-one, phenyl, or tetrazole wherein tetrazole is unsubstituted or substituted with (CSUB1-4/SUB) alkyl; RSUP2 /SUPis H, halogen, (CSUB1-6/SUB) fluoroalkyl, (CSUB3-6/SUB) cycloalkyl, ORSUP6/SUP, SRSUP6/SUP, NOSUB2/SUB, CN, CORSUP6/SUP, C(O)ORSUP6/SUP, C(OH)RSUP6/SUP, CONRSUP7/SUPRSUP8/SUP, phenyl or (CSUB1-6/SUB) alkyl, wherein the (CSUB1-6/SUB) alkyl is unsubstituted or substituted with a hydroxy; RSUP3 /SUPis hydrogen, (CSUB1-6/SUB)fluoroalkyl , (CSUB3-6/SUB) cycloalkyl, (CSUB2-6/SUB) alkenyl, phenyl, monocyclic heteroaromatic, bicyclic heteroaromatic, or (CSUB1-4/SUB)alkyl wherein (CSUB1-4/SUB) alkyl is unsubstituted or substituted with a phenyl; RSUP4 /SUPand RSUP5 /SUPare independently selected from hydrogen, halogen, (CSUB1-6/SUB) alkyl, (CSUB1-6/SUB) fluoroalkyl, ORSUP9/SUP, SRSUP9/SUP, NOSUB2/SUB, CN, or CORSUP9/SUP; RSUP6 /SUPis hydrogen, (CSUB1-6/SUB) fluoroalkyl, or (CSUB1-6/SUB) alkyl; RSUP7 /SUPand RSUP8 /SUPare independently hydrogen, or (CSUB1-6/SUB) alkyl; RSUP9 /SUPis hydrogen, (CSUB1-6/SUB) fluoroalkyl, (CSUB1-6/SUB) alkyl; Alk is (CSUB1-4/SUB) alkylene unsubstituted or substituted with a hydroxy; Y is oxygen, sulfur, SOSUB2/SUB, or a bond; X is CHSUB2/SUB, C-O, S, O, or SOSUB2/SUB; Z is hydrogen, halogen, (CSUB1-6/SUB) alkyl, (CSUB1-6/SUB)fluoroalkyl, -OH, (CSUB1-6/SUB) alkoxy, (CSUB1-6/SUB) fluoroalkoxy, (CSUB1-6/SUB) alkylthio, (CSUB1-6/SUB) acyl, (CSUB1-4/SUB)alkylsulfonyl, -OCFSUB3/SUB, -NOSUB2/SUB, -CN, carboxamido which may be substituted on the nitrogen by one or two (CSUB1-4/SUB) alkyl groups, and -NHSUB2 /SUBin which one of the hydrogens may be replaced by a (CSUB1-4/SUB) alkyl group and the other hydrogen may be replaced by either a (CSUB1-4/SUB) alkyl group, a (CSUB1-6/SUB) acyl group, or a (CSUB1-4/SUB) alkylsulfonyl group; the phenyl of RSUP1/SUP, RSUP2 /SUPor RSUP3 /SUPis independently unsubstituted or substituted with one to three substituents independently selected from Z; the monocyclic heteroaromatic of RSUP3 /SUPis unsubstituted or substituted with one to three substituents independently selected from Z; the bicyclic heteroaromatic of RSUP3 /SUPis unsubstituted or substituted with one to three substituents independently selected from Z; 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 disorders, and pharmaceutical formulations of the compounds of formula (I).