- 专利标题: Piperazine substituted aryl benzodiazepines and their use as dopamine receptor antagonists for the treatment of psychotic disorders
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申请号: US10505805申请日: 2003-03-17
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公开(公告)号: US07214673B2公开(公告)日: 2007-05-08
- 发明人: Thomas Daniel Aicher , Zhaogen Chen , Joseph Herman Krushinski, Jr. , Yvan Le Huerou , Marta Maria Pineiro-Nunez , Kevin Michael Ruley , John Mehnert Schaus , Dennis Charles Thompson , David Edward Tupper , Ying Chen , Margaret Mary Faul , Vincent Patrick Rocco
- 申请人: Thomas Daniel Aicher , Zhaogen Chen , Joseph Herman Krushinski, Jr. , Yvan Le Huerou , Marta Maria Pineiro-Nunez , Kevin Michael Ruley , John Mehnert Schaus , Dennis Charles Thompson , David Edward Tupper , Ying Chen , Margaret Mary Faul , Vincent Patrick Rocco
- 申请人地址: US IN Indianapolis
- 专利权人: Eli Lilly and Company
- 当前专利权人: Eli Lilly and Company
- 当前专利权人地址: US IN Indianapolis
- 代理商 Robert D. Titus; John A. Cleveland, Jr.
- 国际申请: PCT/US03/06708 WO 20030317
- 国际公布: WO03/082877 WO 20031009
- 主分类号: A61P25/00
- IPC分类号: A61P25/00 ; A61K31/55 ; C07D243/10
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, 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, 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 (I) as antagonists of the dopamine D2 receptor and as agents for the treatment of psychosis and bipolar disorder, and pharmaceutical formulations of the compounds of formula (I).
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