基本信息:
- 专利标题: NEW CENTRALLY ACTING SUBSTITUTED PHENYLAZACYCLOALKANES
- 专利标题(中):新的中央行动取代的苯甲酰氯
- 申请号:PCT/US1992002227 申请日:1992-03-26
- 公开(公告)号:WO1992018475A2 公开(公告)日:1992-10-29
- 发明人: THE UPJOHN COMPANY
- 申请人: THE UPJOHN COMPANY , SVENSSON, Kjell, Anders, Ivan , WIKSTRÖM, Håkan, Vilhem , CARLSSON, Per, Arvid, Emil , BOIJE, Anna, Maria, Persdotter , WATERS, Ross, Nicholas , SONESSON, Clas, Ake , STJERULOF, Nils, Peter , ANDERSSON, Bengt, Ronny , HANSSON, Lars, Olor
- 专利权人: THE UPJOHN COMPANY,SVENSSON, Kjell, Anders, Ivan,WIKSTRÖM, Håkan, Vilhem,CARLSSON, Per, Arvid, Emil,BOIJE, Anna, Maria, Persdotter,WATERS, Ross, Nicholas,SONESSON, Clas, Ake,STJERULOF, Nils, Peter,ANDERSSON, Bengt, Ronny,HANSSON, Lars, Olor
- 当前专利权人: THE UPJOHN COMPANY,SVENSSON, Kjell, Anders, Ivan,WIKSTRÖM, Håkan, Vilhem,CARLSSON, Per, Arvid, Emil,BOIJE, Anna, Maria, Persdotter,WATERS, Ross, Nicholas,SONESSON, Clas, Ake,STJERULOF, Nils, Peter,ANDERSSON, Bengt, Ronny,HANSSON, Lars, Olor
- 优先权: US686,799 19910417
- 主分类号: C07D0
- IPC分类号: C07D0
摘要:
A compound of formula (I), or a pharmaceutically acceptable salt thereof wherein n is 0-3; R and R are independently H (provided only one is H at the same time), -OH (provided R is other than hydrogen), CN, CH2CN, 2- or 4-CF3, CH2CF3, CH2CHF2, CH=CF2, (CH2)2CF3, ethenyl, 2-propenyl, OSO2CH3, OSO2CF3, SSO2CF3, COR , COOR , CON(R )2, SOxCH3 (where, x is 0-2), SOxCF3, O(CH2)xCF3, SO2N(R )2, CH=NOR , COCOOR , COCOON(R )2, C1-8 alkyls, C3-8 cycloalkyls, CH2OR , CH2(R )2, NR SO2CF3, NO2, halogen, a phenyl at positions 2, 3 or 4, thienyl, furyl, pyrrole, oxazole, thiazole, N-pyrroline, triazole, tetrazole or pyridine; R is hydrogen, CF3, CH2CF3, C1-C8 alkyl, C3-C8 cycloalkyl, C4-C9 cycloalkyl-methyl, C2-C8 alkenyl, C2-C8 alkynyl, 3,3,3-trifluoropropyl, 4,4,4-trifluorobutyl, -(CH2)m-R (where m is 1-8), CH2SCH3 or a C4-C8 alkyl bonded to said nitrogen and one of its adjacent carbon atoms inclusive to form a cyclic structure; R is independently hydrogen, CF3, CH2CF3, C1-C8 alkyl, C3-C8 cycloalkyl, C4-C9 cycloalkyl-methyl, C2-C8 alkenyl, C2-C8 alkynyl, 3,3,3-trifluoropropyl, 4,4,4-trifluorobutyl, -(CH2)m-R where m is 1-8; R is phenyl, phenyl (substituted with a CN, CF3, CH2CF3, C1-C8 alkyl, C3-C8 cycloalkyl, C4-C9 cycloalkyl-methyl, C2-C8 alkenyl, C2-C8 alkynyl), 2-thiophenyl, 3-thiophenyl, -NR CONR R , or -CONR R ; R and R are independently hydrogen, C1-C8 alkyl, C3-C8 cycloalkyl, C4-C9 cycloalkylmethyl, C2-C8 alkenyl or C2-C8 alkynyl; and with the proviso that when R is 2-CN or 4-CN, R is H, R is n-Pr and n is 1 or 3 then such compound is a pure enantiomer. The formula (I) compounds possess selective pharmacological properties and are useful in treating central nervous system disorders related to dopamine receptor activity including depression symptoms, geriatric disorders in the improvement of mental and motor functions, schizophrenia, narcolepsy, MBD, obesitas, and disturbances of sexual functions and impotence.
摘要(中):
式(I)化合物或其药学上可接受的盐,其中n为0-3; R 1和R 2独立地是H(同时只有一个是H),-OH(提供的R 4不是氢),CN,CH 2 CN,2-或4- CF 3,CH 2 CF 3 ,CH 2 CF 2,(CH 2)2 CF 3,乙烯基,2-丙烯基,OSO 2 CH 3,OSO 2 CF 3,SSO 2 CF 3,COR 4,COOR 4,CON(R 4)2,SO x CH 3(其中,x为0 -2),SO x CF 3,O(CH 2)x CF 3,SO 2 N(R 4)2,CH = NOR 4,COCOOR 4,COCOON(R 4)2,C 1-8烷基, 环烷基,CH 2 OR 4,CH 2(R 4)2,NR 4 SO 2 CF 3,NO 2,卤素,2,3或4位的苯基,噻吩基,呋喃基,吡咯,恶唑,噻唑,N-吡咯啉, 三唑,四唑或吡啶; R 3是氢,CF 3,CH 2 CF 3,C 1 -C 8烷基,C 3 -C 8环烷基,C 4 -C 9环烷基 - 甲基,C 2 -C 8烯基,C 2 -C 8炔基,3,3,3-三氟丙基, (CH 2)m R 5(其中m为1-8),CH 2 SCH 3或与所述氮键合的C 4 -C 8烷基及其相邻碳原子之一,以形成环状结构; R 4独立地是氢,CF 3,CH 2 CF 3,C 1 -C 8烷基,C 3 -C 8环烷基,C 4 -C 9环烷基 - 甲基,C 2 -C 8烯基,C 2 -C 8炔基,3,3,3-三氟丙基, ,4-三氟丁基, - (CH 2)m R 5,其中m为1-8; R 5是苯基(被CN,CF 3,CH 2 CF 3,C 1 -C 8烷基,C 3 -C 8环烷基,C 4 -C 9环烷基 - 甲基,C 2 -C 8烯基,C 2 -C 8炔基),2-噻吩基, 3-噻吩基,-NR 6 CONR 6 R 7或-CONR 6 R 7; R 6和R 7独立地是氢,C 1 -C 8烷基,C 3 -C 8环烷基,C 4 -C 9环烷基甲基,C 2 -C 8烯基或C 2 -C 8炔基; 并且条件是当R 1为2-CN或4-CN时,R 2为H,R 3为n-Pr,n为1或3,则该化合物为纯对映异构体。 式(I)化合物具有选择性药理学性质,并且可用于治疗与多巴胺受体活性相关的中枢神经系统疾病,包括抑郁症状,改善精神和运动功能的老年疾病,精神分裂症,发作性睡病,脑血管疾病,肥胖症和干扰 性功能和阳。。