公开(公告)号：US20060270656A1

公开(公告)日：2006-11-30

申请号：US10569244

申请日：2004-09-07

申请人： John He ,  Vincent Rocco ,  John Schaus ,  Fionna Martin ,  William Owton ,  David Tupper

发明人： John He ,  Vincent Rocco ,  John Schaus ,  Fionna Martin ,  William Owton ,  David Tupper

IPC分类号： A61K31/554 ,  A61K31/55 ,  A61K31/553 ,  C07D498/02 ,  C07D491/02

CPC分类号： C07D417/04 ,  C07D495/04 ,  C07D513/04

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; R1 is hydrogen, (C1-6) fluoroalkyl, (C3-6) cycloalkyl, or (C1-4) alkyl, wherein the (C1-4) alkyl is unsubstituted or substituted with hydroxy, methoxy, ethoxy, OCH2CH2OH, —CN, imidazolidin-2-one, phenyl, or tetrazole wherein tetrazole is unsubstituted or substituted with (C1-4) alkyl; R2 is H, halogen, (C1-6) fluoroalkyl, (C3-6) cycloalkyl, OR6, SR6, NO2, CN, COR6, C(O)OR6, C(OH)R6, CONR7R8, phenyl or (C1-6) alkyl, wherein the (C1-6) alkyl is unsubstituted or substituted with a hydroxy; R3 is hydrogen, (C1-6)fluoroalkyl , (C3-6) cycloalkyl, (C2-6) alkenyl, phenyl, monocyclic heteroaromatic, bicyclic heteroaromatic, or (C1-4)alkyl wherein (C1-4) alkyl is unsubstituted or substituted with a phenyl; R4 and R5 are independently selected from hydrogen, halogen, (C1-6) alkyl, (C1-6) fluoroalkyl, OR9, SR9, NO2, CN, or COR9; R6 is hydrogen, (C1-6) fluoroalkyl, or (C1-6) alkyl; R7 and R8 are independently hydrogen, or (C1-6) alkyl; R9 is hydrogen, (C1-6) fluoroalkyl, (C1-6) alkyl; Alk is (C1-4) alkylene unsubstituted or substituted with a hydroxy; Y is oxygen, sulfur, SO2, or a bond; X is CH2, C═O, S, O, or SO2; Z is hydrogen, halogen, (C1-6) alkyl, (C1-6)fluoroalkyl, —OH, (C1-6) alkoxy, (C1-6) fluoroalkoxy, (C1-6) alkylthio, (C1-6) acyl, (C1-4)alkylsulfonyl, —OCF3, —NO2, —CN, carboxamido which may be substituted on the nitrogen by one or two (C1-4) alkyl groups, and —NH2 in which one of the hydrogens may be replaced by a (C1-4) alkyl group and the other hydrogen may be replaced by either a (C1-4) alkyl group, a (C1-6) acyl group, or a (C1-4) alkylsulfonyl group; the phenyl of R1, R2 or R3 is independently unsubstituted or substituted with one to three substituents independently selected from Z; the monocyclic heteroaromatic of R3 is unsubstituted or substituted with one to three substituents independently selected from Z; the bicyclic heteroaromatic of R3 is 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 D2 receptor and as agents for the treatment of psychosis and bipolar disorders, and pharmaceutical formulations of the compounds of formula (I).

公开(公告)号：US20060084643A1

公开(公告)日：2006-04-20

申请号：US10523147

申请日：2003-07-28

申请人： Thomas Aicher ,  Zhaogen Chen ,  Yvan Lehuerou ,  Fionna Martin ,  Marta Pineiro-Nunez ,  Vincent Rocco ,  Kevin Ruley ,  John Schaus ,  Patrick Spinazze ,  David Tupper

发明人： Thomas Aicher ,  Zhaogen Chen ,  Yvan Lehuerou ,  Fionna Martin ,  Marta Pineiro-Nunez ,  Vincent Rocco ,  Kevin Ruley ,  John Schaus ,  Patrick Spinazze ,  David Tupper

IPC分类号： A61K31/551 ,  C07D498/02

CPC分类号： C07D403/04 ,  C07D495/04 ,  C07D513/04

摘要： Described herein are compounds of formula (I) use of the compounds of formula (I) as antagonists of the dopamine D2 receptor and as agents for the treament of psychosis and bipolar disorders, and pharmaceutical formulations of the compounds of formula (I).

摘要翻译： 本文描述的式（I）化合物是式（I）化合物用作多巴胺D2受体的拮抗剂并用作精神病和双相性精神障碍的药剂，以及式（I）化合物的药物制剂。

公开(公告)号：US20050203296A1

公开(公告)日：2005-09-15

申请号：US10505805

申请日：2003-03-17

申请人： Thomas Aicher ,  Zhaogen Chen ,  Joseph Krushinski ,  Yvan Le Huerou ,  Marta Pineiro-Nunez ,  Kevin Ruley ,  John Schaus ,  Dennis Thompson ,  David Tupper ,  Ying Chen ,  Margaret Faul ,  Vincent Rocco

发明人： Thomas Aicher ,  Zhaogen Chen ,  Joseph Krushinski ,  Yvan Le Huerou ,  Marta Pineiro-Nunez ,  Kevin Ruley ,  John Schaus ,  Dennis Thompson ,  David Tupper ,  Ying Chen ,  Margaret Faul ,  Vincent Rocco

IPC分类号： C07D333/62 ,  A61K31/551 ,  A61K31/5517 ,  A61P25/18 ,  A61P43/00 ,  C07D243/38 ,  C07D333/68 ,  C07D403/04 ,  C07D487/04 ,  C07D495/04 ,  C07D498/02 ,  C07D513/04

CPC分类号： C07D487/04 ,  C07D243/38 ,  C07D495/04 ,  C07D513/04

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 (C1-4) alkylene optionally substituted with OH, methoxy, ethoxy, or F; Ar is optionally substituted phenyl, naphthyl, monocyclic heteroaromatic, or bicyclic heteroaromatic; R1 is hydrogen or (C1-4) alkyl optionally substituted with OH, OR3, or OCH2CH2OH, wherein R3 is (C1-2) alkyl; R2 is H, (C1-6) alkyl, halogen, fluorinated (C1-6) alkyl, OR4, SR4, NO2, CN, COR4, CONR5R6, SO2NR5R6, NR5R6, NR5COR4, NR5SO2R4, or optionally substituted phenyl, wherein R4 is hydrogen, (C1-6) alkyl, fluorinated (C1-6) alkyl, benzyl, or optionally substituted phenyl, R5 and R6 are independently hydrogen, (C1-6) alkyl, or optionally substituted phenyl; Z is one or two substituents independently selected from hydrogen, halogen, (C1-6) alkyl, fluorinated (C1-6) alkyl, OR7, SR7, NO2, CN, COR7, CONR8R9, SO2NR8R9, NR8SO2R7, NR8R9, or optionally substituted phenyl, wherein R7 is hydrogen, (C1-6) alkyl, fluorinated alkyl, benzyl, or optionally substituted phenyl, R8 and R9 are independently hydrogen, (C1-6) 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).