Title:
NEW CENTRALLY ACTING SUBSTITUTED PHENYLAZACYCLOALKANES
Document Type and Number:
WIPO Patent Application WO1992018475
Kind Code:
A3
Abstract:
A compound of Formula I or a pharmaceutically acceptable salt thereof wherein n is 1 or 2; R1 and R2 are independently H (provided only one is H at the same time), -OH, 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, NRSO2CF3, NO2, halogen, a phenyl at positions 2, 3 or 4, thienyl, furyl, pyrrole, oxazole, thiazole, N-pyrroline, triazole, tetrazole or pyridine; R3 is hydrogen, CF3, CH2CF3, C1-C8 alkyl, C3-C8 cycloalkyl, C4-C9 cycloalkyl-methyl, C 2-C8 alkenyl, C2-C8 alkynyl, 3,3,3-trifluoropropyl, 4,4,4-trifluorobutyl, -(CH2)m-R5 (where m is 1-8), CH2SCH3 or a C4-C8 alkylene bonded to said nitrogen and one of its adjacent carbon atoms inclusive whereby a heterocyclic structure is formed; R4 and R are independently selected from 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-R5 where m is 1-8; R5 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, -NR6CONR6R7, or -CONR6R7; R6 and R7 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 R1 is CN, R2 and R4 are H, R3 is n-Pr and n is 1, then such compound is a pure enantiomer, and when R1 or R2 is OH, halogen, CONH2 or alkyl, then R4 is not hydrogen. 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.
Inventors:
SVENSSON KJELL ANDERS IVAN (SE)
WIKSTROEM HAAKAN VILHEM (SE)
CARLSSON PER ARVID EMIL (SE)
BOIJE ANNA MARIA PERSDOTTER (SE)
WATERS ROSS NICHOLAS (SE)
SONESSON CLAS AKE (SE)
STJERULOF NILS PETER (SE)
ANDERSSON BENGT RONNY (SE)
HANSSON LARS OLOR (SE)
WIKSTROEM HAAKAN VILHEM (SE)
CARLSSON PER ARVID EMIL (SE)
BOIJE ANNA MARIA PERSDOTTER (SE)
WATERS ROSS NICHOLAS (SE)
SONESSON CLAS AKE (SE)
STJERULOF NILS PETER (SE)
ANDERSSON BENGT RONNY (SE)
HANSSON LARS OLOR (SE)
Application Number:
PCT/US1992/002227
Publication Date:
February 04, 1993
Filing Date:
March 26, 1992
Export Citation:
Assignee:
UPJOHN CO (US)
International Classes:
A61K31/40; A61K31/44; A61K31/4025; A61K31/4427; A61K31/443; A61K31/4433; A61K31/445; A61K31/451; A61K31/535; A61K31/55; A61P25/00; A61P25/02; A61P25/16; A61P25/18; A61P25/20; A61P25/24; A61P43/00; C07D207/08; C07D207/09; C07D211/08; C07D211/14; C07D211/18; C07D211/22; C07D211/24; C07D211/26; C07D211/28; C07D211/30; C07D211/34; C07D211/76; C07D223/04; C07D227/04; C07D401/00; C07D401/10; C07D403/00; C07D405/00; C07D405/10; C07D409/06; C07D409/10; C07D411/10; C07D413/00; C07D413/10; C07D417/00; C07D455/02; C07D471/04; C07D487/04; (IPC1-7): C07D/
Foreign References:
| EP0435387A1 | 1991-07-03 | |||
| EP0381235A2 | 1990-08-08 | |||
| EP0372776A2 | 1990-06-13 | |||
| EP0309914A2 | 1989-04-05 | |||
| EP0309913A2 | 1989-04-05 | |||
| EP0244739A2 | 1987-11-11 | |||
| US4263438A | 1981-04-21 | |||
| US4259337A | 1981-03-31 |
Other References:
JOURNAL OF MEDICINAL CHEMISTRY vol. 24, no. 12, December 1981, pages 1475 - 1482; HACKSELL U. ET AL.: '3-Phenylpiperidines. Central dopamine-autoreceptor stimulating activity' cited in the application
IL FARMACO, ED. SCI. vol. 21, no. 2, 1966, pages 131 - 154; BIANCHI G. & MAFFII G.: 'Farmacologia della 3-fenilazetidina e di alcuni suoi derivati'
JOURNAL OF MEDICINAL CHEMISTRY vol. 27, no. 8, August 1984, pages 1030 - 1036; WIKSTRÖM H. ET AL.: 'Resolved 3-(-3-Hydroxyphenyl)-N-n-propylpiperidine and its analogues: Central dopamine receptor stimulating activity' cited in the application
JOURNAL OF MEDICINAL CHEMISTRY vol. 30, no. 1, January 1987, pages 142 - 150; BOGESO K.P. ET AL.: 'Indolizidine and quinolizidine derivatives of the dopamine autoreceptor agonist 3-(-3-Hydroxyphenyl) N-n-propylpiperidine (3-PPP)' cited in the application
IL FARMACO, ED. SCI. vol. 21, no. 2, 1966, pages 131 - 154; BIANCHI G. & MAFFII G.: 'Farmacologia della 3-fenilazetidina e di alcuni suoi derivati'
JOURNAL OF MEDICINAL CHEMISTRY vol. 27, no. 8, August 1984, pages 1030 - 1036; WIKSTRÖM H. ET AL.: 'Resolved 3-(-3-Hydroxyphenyl)-N-n-propylpiperidine and its analogues: Central dopamine receptor stimulating activity' cited in the application
JOURNAL OF MEDICINAL CHEMISTRY vol. 30, no. 1, January 1987, pages 142 - 150; BOGESO K.P. ET AL.: 'Indolizidine and quinolizidine derivatives of the dopamine autoreceptor agonist 3-(-3-Hydroxyphenyl) N-n-propylpiperidine (3-PPP)' cited in the application
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