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标题翻译：取代的哌嗪，氧化氮和噻唑的哌嗪

公开(公告)号：WO2005026177A1

公开(公告)日：2005-03-24

申请号：PCT/US2004/025610

申请日：2004-09-07

申请人： ELI LILLY AND COMPANY , HE, John, Xiaoqinag , ROCCO, Vincent, Patrick , SCHAUS, John, Mehnert , MARTIN, Fionna, Mitchell , OWTON, William, Martin , TUPPER, David, Edward

发明人： HE, John, Xiaoqinag , ROCCO, Vincent, Patrick , SCHAUS, John, Mehnert , MARTIN, Fionna, Mitchell , OWTON, William, Martin , TUPPER, David, Edward

IPC分类号： C07D513/04

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; R 1 is hydrogen, (C 1-6 ) fluoroalkyl, (C 3-6 ) cycloalkyl, or (C 1-4 ) alkyl, wherein the (C 1-4 ) alkyl is unsubstituted or substituted with hydroxy, methoxy, ethoxy, OCH 2 CH 2 OH, -CN, imidazolidin-2-one, phenyl, or tetrazole wherein tetrazole is unsubstituted or substituted with (C 1-4 ) alkyl; R 2 is H, halogen, (C 1-6 ) fluoroalkyl, (C 3-6 ) cycloalkyl, OR 6 , SR 6 , NO 2 , CN, COR 6 , C(O)OR 6 , C(OH)R 6 , CONR 7 R 8 , phenyl or (C 1-6 ) alkyl, wherein the (C 1-6 ) alkyl is unsubstituted or substituted with a hydroxy; R 3 is hydrogen, (C 1-6 )fluoroalkyl , (C 3-6 ) cycloalkyl, (C 2-6 ) alkenyl, phenyl, monocyclic heteroaromatic, bicyclic heteroaromatic, or (C 1-4 )alkyl wherein (C 1-4 ) alkyl is unsubstituted or substituted with a phenyl; R 4 and R 5 are independently selected from hydrogen, halogen, (C 1-6 ) alkyl, (C 1-6 ) fluoroalkyl, OR 9 , SR 9 , NO 2 , CN, or COR 9 ; R 6 is hydrogen, (C 1-6 ) fluoroalkyl, or (C 1-6 ) alkyl; R 7 and R 8 are independently hydrogen, or (C 1-6 ) alkyl; R 9 is hydrogen, (C 1-6 ) fluoroalkyl, (C 1-6 ) alkyl; Alk is (C 1-4 ) alkylene unsubstituted or substituted with a hydroxy; Y is oxygen, sulfur, SO 2 , or a bond; X is CH 2 , C=O, S, O, or SO 2 ; Z is hydrogen, halogen, (C 1-6 ) alkyl, (C 1-6 )fluoroalkyl, -OH, (C 1-6 ) alkoxy, (C 1-6 ) fluoroalkoxy, (C 1-6 ) alkylthio, (C 1-6 ) acyl, (C 1-4 )alkylsulfonyl, -OCF 3 , -NO 2 , - CN, carboxamido which may be substituted on the nitrogen by one or two (C 1-4 ) alkyl groups, and -NH 2 in which one of the hydrogens may be replaced by a (C 1-4 ) alkyl group and the other hydrogen may be replaced by either a (C 1-4 ) alkyl group, a (C 1-6 ) acyl group, or a (C 1-4 ) alkylsulfonyl group; the phenyl of R 1 , R 2 or R 3 is independently unsubstituted or substituted with one to three substituents independently selected from Z; the monocyclic heteroaromatic of R 3 is unsubstituted or substituted with one to three substituents independently selected from Z; the bicyclic heteroaromatic of R 3 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 D 2 receptor and as agents for the treatment of psychosis and bipolar disorders, and pharmaceutical formulations of the compounds of formula (I).

摘要翻译：本文描述的是式（I）的抗颤动化合物，其中：是具有0至3个独立地选自N，O和S的杂原子的任选苯并稠合的5或6元芳族环; R 1是氢，（C 1-6）氟烷基，（C 3-6）环烷基或（C 1-4）烷基，其中（C 1-4）烷基是未取代的或被羟基，甲氧基，乙氧基，OCH 2 CH 2 OH， -CN，咪唑烷-2-酮，苯基或四唑，其中四唑未被取代或被（C 1-4）烷基取代; R 2是H，卤素，（C 1-6）氟烷基，（C 3-6）环烷基，OR 6，SR 6，NO 2，CN，COR 6，C（O），C（OH）R 6，CONR 7 R 8，苯基或（C 1-6）烷基，其中（C 1-6）烷基未被取代或被羟基取代; R 3是氢，（C 1-6）氟烷基，（C 3-6）环烷基，（C 2-6）烯基，苯基，单环杂芳族，双环杂芳族或（C 1-4）烷基，其中（C 1-4 ）烷基是未取代的或被苯基取代; R 4和R 5独立地选自氢，卤素，（C 1-6）烷基，（C 1-6）氟烷基，OR 9，SR 9，NO 2，CN或COR 9 ; R 6是氢，（C 1-6）氟代烷基或（C 1-6）烷基; R 7和R 8独立地是氢或（C 1-6）烷基; R 9是氢，（C 1-6）氟代烷基，（C 1-6）烷基; Alk是未被取代或被羟基取代的（C 1-4）亚烷基; Y是氧，硫，SO 2或键; X是CH 2，C = O，S，O或SO 2; Z为氢，卤素，（C 1-6）烷基，（C 1-6）氟代烷基，-OH，（C 1-6）烷氧基，（C 1-6）氟烷氧基，（C 1-6）烷硫基，（C 1-6），（C 1-4）烷基磺酰基，-OCF 3，-NO 2，-CN，可以在氮上被一个或两个（C 1-4）烷基取代的甲酰氨基，和-NH 2，其中一个氢可以被（C 1-4）烷基，另一个氢可以被（C 1-4）烷基，（C 1-6）酰基或（C 1-4）烷基磺酰基取代; R 1，R 2或R 3的苯基独立地是未取代的或被一至三个独立地选自Z的取代基取代; R 3的单环杂芳基是未取代的或被一至三个独立地选自Z的取代基取代; R 3的双环杂芳基是未取代的或被一至三个独立地选自Z的取代基取代; 及其盐，溶剂合物和晶体形式。还描述了式（I）化合物作为多巴胺D2受体的拮抗剂和用于治疗精神病和双相性障碍的药物以及式（I）化合物的药物制剂的用途。

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