公开(公告)号：WO9218475A3

公开(公告)日：1993-02-04

申请号：PCT/US9202227

申请日：1992-03-26

Applicant: UPJOHN CO

Inventor： SVENSSON KJELL ANDERS IVAN ,  WIKSTROEM HAAKAN VILHEM ,  CARLSSON PER ARVID EMIL ,  BOIJE ANNA MARIA PERSDOTTER ,  WATERS ROSS NICHOLAS ,  SONESSON CLAS AKE ,  STJERULOF NILS PETER ,  ANDERSSON BENGT RONNY ,  HANSSON LARS OLOR

IPC: A61K31/44 ,  A61K31/40 ,  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 ,  C07D

CPC classification number: C07D207/08 ,  C07D207/09 ,  C07D211/14 ,  C07D211/18 ,  C07D211/22 ,  C07D211/24 ,  C07D211/28 ,  C07D211/34 ,  C07D211/76 ,  C07D223/04 ,  C07D409/06 ,  C07D409/10 ,  C07D455/02 ,  C07D487/04

Abstract: A compound of formula (I), or a pharmaceutically acceptable salt thereof wherein n is 0-3; R?1 and R2¿ are independently H (provided only one is H at the same time), -OH (provided R4 is other than hydrogen), CN, CH¿2?CN, 2- or 4-CF3, CH2CF3, CH2CHF2, CH=CF2, (CH2)2CF3, ethenyl, 2-propenyl, OSO2CH3, OSO2CF3, SSO2CF3, COR?4, COOR4, CON(R4)¿2, SOxCH3 (where, x is 0-2), SOxCF3, O(CH2)xCF3, SO2N(R4)2, CH=NOR4, COCOOR4, COCOON(R4)2, C1-8 alkyls, C3-8 cycloalkyls, CH2OR4, CH2(R4)2, NR4SO2CF3, NO2, halogen, a phenyl at positions 2, 3 or 4, thienyl, furyl, pyrrole, oxazole, thiazole, N-pyrroline, triazole, tetrazole or pyridine; R3 is hydrogen, CF¿3?, 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?5¿ (where m is 1-8), CH¿2?SCH3 or a C4-C8 alkyl bonded to said nitrogen and one of its adjacent carbon atoms inclusive to form a cyclic structure; R?4¿ is independently hydrogen, CF¿3?, 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?5¿ where m is 1-8; R5 is phenyl, phenyl (substituted with a CN, CF¿3?, CH2CF3, C1-C8 alkyl, C3-C8 cycloalkyl, C4-C9 cycloalkyl-methyl, C2-C8 alkenyl, C2-C8 alkynyl), 2-thiophenyl, 3-thiophenyl, -NR?6CONR6R7¿, or -CONR?6R7; R6 and R7¿ are independently hydrogen, C¿1?-C8 alkyl, C3-C8 cycloalkyl, C4-C9 cycloalkylmethyl, C2-C8 alkenyl or C2-C8 alkynyl; and with the proviso that when R?1¿ is 2-CN or 4-CN, R2 is H, R3 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.

公开(公告)号：WO9111435A3

公开(公告)日：1991-09-05

申请号：PCT/US9100018

申请日：1991-01-08

Applicant: UPJOHN CO

Inventor： WIKSTROM HAKAN VILHELM ,  CARLSSON PER ARVID EMIL ,  ANDERSSON BENGT RONNY ,  SVENSSON KJELL ANDERS IVAN ,  ELEBRING STIG THOMAS ,  STJERNLOF NILS PETER ,  ROMERO ARTHUR GLENN ,  HAADSMA SUSANNE RENEE ,  LIN CHIU-HONG ,  ENNIS MICHAEL DALTON

IPC: A61K31/40 ,  A61K31/403 ,  A61K31/407 ,  A61K31/435 ,  A61K31/4427 ,  A61K31/4433 ,  A61K31/454 ,  A61K31/475 ,  A61P11/14 ,  A61P25/00 ,  A61P25/20 ,  A61P25/24 ,  A61P25/26 ,  A61P25/28 ,  A61P43/00 ,  C07D209/56 ,  C07D209/60 ,  C07D209/66 ,  C07D401/06 ,  C07D401/12 ,  C07D403/04 ,  C07D409/12 ,  C07D413/04 ,  C07D471/04 ,  C07D491/04 ,  C07D491/052 ,  C07D495/04

CPC classification number: C07D401/12 ,  C07D209/66 ,  C07D409/12 ,  C07D491/04

Abstract: A compound of formula (I) or pharmaceutically acceptable slats of formula (I), where R1 is H, C¿1?-C3 alkyl, -(CH2)nCONH2 where n is 2 to 6, (CH2)n-1-(4,4-dimethylpiperidine-2,6-dione-yl), cyclopropylmethyl; R?2¿ is hydrogen, C¿1?-C8 alkyl, C3-C8 cycloalkyl or combined with R?1¿ to form a C¿3?-C8 cycloalkyl, C2-C8 alkenyl, C2-C8 alkynyl, (CH2)n-X-Ar where X is O, S, or NH, 3,3,3-trifluoropropyl, -(CH2)m-R?9¿ where m is 2 or 3 and R9 is phenyl, 2-thiophenyl or 3-thiophenyl; R3 is C1-C3 alkyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, formyl, CN, halogen, CH2OR2, C(O)C(O)Y where Y is OR?1 or NR1R2¿, -(CH¿2?)q-NR?1R2¿ where q is 0 to 5, C=NOR2,2(4,5-dihydro)oxazolyl, or COR10 where R10 is H, R?1, NR1R2¿ or CF¿3?; R?4 is C¿1-C3 alkyl, cyclopropylmethyl, CF3, 2,2,2-trifluoroethyl, CN, CONR1R2, =O, 2(4,5-dihydro)imidazolyl, 2(4,5-dihydro)oxazolyl, 2-oxazolyl, 3-oxadiazolyl, or 3,3,3-trifluoropropyl; R5 is hydrogen, R1, OCH3, C(O)CH3 or C(O)OR1; X is (a) a valence bond, (b) CH¿2?, (c) O, S or NR?5¿ where R5 is H, C¿1?-C8 alkyl, C3-C8 cycloalkyl, benzyl, COR?6¿ where R6 is a C¿1?-C3 alkyl, phenyl, or CONR?7R8¿ where R?7 and R8¿ are independently H or C¿1?-C3 alkyl; and Z is a hydrogen or halogen. The compounds of formula (I) are suitable for treating disorders of the central nervous system, particularly as 5-HT1A receptor agonists.

公开(公告)号：WO9111435A2

公开(公告)日：1991-08-08

申请号：PCT/US9100018

申请日：1991-01-08

Applicant: UPJOHN CO

Inventor： WIKSTROM HAKAN VILHELM ,  CARLSSON PER ARVID EMIL ,  ANDERSSON BENGT RONNY ,  SVENSSON KJELL ANDERS IVAN ,  ELEBRING STIG THOMAS ,  STJERNLOF NILS PETER ,  ROMERO ARTHUR GLENN ,  HAADSMA SUSANNE RENEE ,  LIN CHIU-HONG ,  ENNIS MICHAEL DALTON

IPC: A61K31/40 ,  A61K31/403 ,  A61K31/407 ,  A61K31/435 ,  A61K31/4427 ,  A61K31/4433 ,  A61K31/454 ,  A61K31/475 ,  A61P11/14 ,  A61P25/00 ,  A61P25/20 ,  A61P25/24 ,  A61P25/26 ,  A61P25/28 ,  A61P43/00 ,  C07D209/56 ,  C07D209/60 ,  C07D209/66 ,  C07D401/06 ,  C07D401/12 ,  C07D403/04 ,  C07D409/12 ,  C07D413/04 ,  C07D471/04 ,  C07D491/04 ,  C07D491/052 ,  C07D495/04

CPC classification number: C07D401/12 ,  C07D209/66 ,  C07D409/12 ,  C07D491/04

Abstract: A compound of formula (I) or pharmaceutically acceptable slats of formula (I), where R is H, C1-C3 alkyl, -(CH2)nCONH2 where n is 2 to 6, (CH2)n-1-(4,4-dimethylpiperidine-2,6-dione-yl), cyclopropylmethyl; R is hydrogen, C1-C8 alkyl, C3-C8 cycloalkyl or combined with R to form a C3-C8 cycloalkyl, C2-C8 alkenyl, C2-C8 alkynyl, (CH2)n-X-Ar where X is O, S, or NH, 3,3,3-trifluoropropyl, -(CH2)m-R where m is 2 or 3 and R is phenyl, 2-thiophenyl or 3-thiophenyl; R is C1-C3 alkyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, formyl, CN, halogen, CH2OR , C(O)C(O)Y where Y is OR or NR R , -(CH2)q-NR R where q is 0 to 5, C=NOR ,2(4,5-dihydro)oxazolyl, or COR where R is H, R , NR R or CF3; R is C1-C3 alkyl, cyclopropylmethyl, CF3, 2,2,2-trifluoroethyl, CN, CONR R , =O, 2(4,5-dihydro)imidazolyl, 2(4,5-dihydro)oxazolyl, 2-oxazolyl, 3-oxadiazolyl, or 3,3,3-trifluoropropyl; R is hydrogen, R , OCH3, C(O)CH3 or C(O)OR ; X is (a) a valence bond, (b) CH2, (c) O, S or NR where R is H, C1-C8 alkyl, C3-C8 cycloalkyl, benzyl, COR where R is a C1-C3 alkyl, phenyl, or CONR R where R and R are independently H or C1-C3 alkyl; and Z is a hydrogen or halogen. The compounds of formula (I) are suitable for treating disorders of the central nervous system, particularly as 5-HT1A receptor agonists.

Abstract translation: 式（I）的化合物或式（I）的药学上可接受的片条，其中R 1是H，C 1 -C 3烷基， - （CH 2）n CONH 2，其中n是2-6，（CH2）n-1- 4,4-二甲基哌啶-2,6-二酮基），环丙基甲基; R 2是氢，C 1 -C 8烷基，C 3 -C 8环烷基或与R 1结合形成C 3 -C 8环烷基，C 2 -C 8烯基，C 2 -C 8炔基，（CH 2）n X-Ar，其中X为 O，S或NH，3,3,3-三氟丙基， - （CH 2）m R 9，其中m为2或3，R 9为苯基，2-噻吩基或3-噻吩基; R 3是C 1 -C 3烷基，2,2,2-三氟乙基，3,3,3-三氟丙基，甲酰基，CN，卤素，CH 2 O 2，C（O）C（O） 其中q为0至5，C = NOR 2，2（4,5-二氢）恶唑基（CH 2）q -NR 2 R 2， 或COR 10，其中R 10是H，R 1，NR 1 R 2或CF 3; R 4是C 1 -C 3烷基，环丙基甲基，CF 3，2,2,2-三氟乙基，CN，CONR 1 R 2，O 2（4,5-二氢）咪唑基，2（4， 5-二氢）恶唑基，2-恶唑基，3-恶二唑基或3,3,3-三氟丙基; R 5是氢，R 1，OCH 3，C（O）CH 3或C（O）OR 1; X是（a）价键，（b）CH 2，（C）O，S或NR 5，其中R 5是H，C 1 -C 8烷基，C 3 -C 8环烷基，苄基，COR 6 R 6是C 1 -C 3烷基，苯基或CONR 7 R 8，其中R 7和R 8独立地是H或C 1 -C 3烷基; Z是氢或卤素。 式（I）化合物适用于治疗中枢神经系统疾病，特别是5-HT 1A受体激动剂。