公开(公告)号：US5462947A

公开(公告)日：1995-10-31

申请号：US133606

申请日：1993-10-12

申请人： Kjell A. I. Svensson ,  Hakan V. Wikstrom ,  Per A. E. Carlsson ,  Anna M. P. Boije ,  R. Nicholas Waters ,  Clas A. Sonesson ,  Nils P. Stjernlof ,  Bengt R. Andersson ,  Lars O. Hansson

发明人： Kjell A. I. Svensson ,  Hakan V. Wikstrom ,  Per A. E. Carlsson ,  Anna M. P. Boije ,  R. Nicholas Waters ,  Clas A. Sonesson ,  Nils P. Stjernlof ,  Bengt R. Andersson ,  Lars O. Hansson

IPC分类号： 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

CPC分类号： 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

摘要： A compound of Formula I ##STR1## or a pharmaceutically acceptable salt thereof wherein n is 1 or 2; R.sup.1 and R.sup.2 are independently H (provided only one is H at the same time), --OH, CN, CH.sub.2 CN, 2-- or 4--CF.sub.3, CH.sub.2 CF.sub.3, CH.sub.2 CHF.sub.2, CH.dbd.CF.sub.2, (CH.sub.2).sub.2 CF.sub.3, ethenyl, 2-propenyl, OSO.sub.2 CH.sub.3, OSO.sub.2 CF.sub.3, SSO.sub.2 CF.sub.3, COR, COOR, CON(R).sub.2, SO.sub.x CH.sub.3 (where, x is 0-2), SO.sub.x CF.sub.3, O(CH.sub.2).sub.x CF.sub.3, SO.sub.2 N(R).sub.2, CH.dbd.NOR, COCOOR, COCOON(R).sub.2, C.sub.1-8 alkyls, C.sub.3-8 cycloalkyls, CH.sub.2 OR, CH.sub.2 (R).sub.2, NRSO.sub.2 CF.sub.3, NO.sub.2, halogen, a phenyl at positions 2, 3 or 4, thienyl, furyl, pyrrole, oxazole, thiazole, N-pyrroline, triazole, tetrazole or pyridine; R.sup.3 is hydrogen, CF.sub.3, CH.sub.2 CF.sub.3, C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.4 -C.sub.9 cycloalkyl-methyl, C.sub. 2 -C.sub.8 alkenyl, C.sub.2 -C.sub.8 alkynyl, 3,3,3-trifluoropropyl, 4,4,4-trifluorobutyl, --(CH.sub.2).sub.m --R.sup.5 (where m is 1-8), CH.sub.2 SCH.sub.3 or a C.sub.4 -C.sub.8 alkylene bonded to said nitrogen and one of its adjacent carbon atoms inclusive whereby a heterocyclic structure is formed; R.sup.4 and R are independently selected from hydrogen, CF.sub.3, CH.sub.2 CF.sub.3, C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.4 -C.sub.9 cycloalkyl-methyl, C.sub.2 -C.sub.8 alkenyl, C.sub.2 -C.sub.8 alkynyl, 3,3,3-trifluoropropyl, 4,4,4-trifluorobutyl, --(CH.sub.2).sub.m --R.sup.5 where m is 1-8; R.sup.5 is phenyl, phenyl (substituted with a CN, CF.sub.3, CH.sub.2 CF.sub.3, C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.4 -C.sub.9 cycloalkyl-methyl, C.sub.2 -C.sub.8 alkenyl, C.sub.2 -C.sub.8 alkynyl), 2-thiophenyl, 3-thiophenyl, --NR.sup.6 CONR.sup.6 R.sup.7, or --CONR.sup.6 R.sup.7 ; R.sup.6 and R.sup.7 are independently hydrogen, C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.4 -C.sub.9 cycloalkylmethyl, C.sub.2 -C.sub.8 alkenyl or C.sub.2 -C.sub.8 alkynyl; and with the proviso that when R.sup.1 is CN, R.sup.2 and R.sup.4 are H, R.sup.3 is n-Pr and n is 1, then such compound is a pure enantiomer, and when R.sup.1 or R.sup.2 is OH, halogen, CONH.sub.2 or alkyl, then R.sup.4 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.

公开(公告)号：US5594024A

公开(公告)日：1997-01-14

申请号：US455474

申请日：1995-05-31

申请人： Kjell A. I. Svensson ,  Hakan V. Wikstrom ,  Per A. E. Carlsson ,  Anna M. P. Boije ,  R. Nicholas Waters ,  Clas A. Sonesson ,  Nils P. Stjernlof ,  Bengt R. Andersson ,  Lars O. Hansson

发明人： Kjell A. I. Svensson ,  Hakan V. Wikstrom ,  Per A. E. Carlsson ,  Anna M. P. Boije ,  R. Nicholas Waters ,  Clas A. Sonesson ,  Nils P. Stjernlof ,  Bengt R. Andersson ,  Lars O. Hansson

IPC分类号： 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 ,  C07D207/04

CPC分类号： 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

摘要： A compound or Formula I ##STR1## or a pharmaceutically acceptable salt thereof wherein n is 1 or 2; R.sup.1 and R.sup.2 are independently H (provided only one is H at the same time), --OH, CN, CH.sub.2 CN, 2- or 4-CF.sub.3, CH.sub.2 CF.sub.3, CH.sub.2 CHF.sub.2, CH.dbd.CF.sub.2, (CH.sub.2).sub.2 CF.sub.3, ethenyl, 2-propenyl, OSO.sub.2 CH.sub.3, OSO.sub.2 CF.sub.3, SSO.sub.2 CF.sub.3, COR, COOR, CON(R).sub.2, SO.sub.x CH.sub.3 (where, x is 0-2), SO.sub.x CF.sub.3, O(CH.sub.2).sub.x CF.sub.3, SO.sub.2 N(R).sub.2, CH.dbd.NOR, COCOOR, COCOON(R).sub.2, C.sub.1-8 alkyls, C.sub.3-8 cycloalkyls, CH.sub.2 OR, CH.sub.2 (R).sub.2, NRSO.sub.2 CF.sub.3, NO.sub.2, halogen, a phenyl at positions 2, 3 or 4, thienyl, furyl, pyrrole, oxazole, thiazole, N-pyrroline, triazole, tetrazole or pyridine; R.sup.3 is hydrogen, CF.sub.3, CH.sub.2 CF.sub.3, C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.4 -C.sub.9 cycloalkyl-methyl, C.sub.2 -C.sub.8 alkenyl, C.sub.2 -C.sub.8 alkynyl, 3,3,3-trifluoropropyl, 4,4,4-trifluorobutyl, --(CH.sub.2).sub.m --R.sup.5 (where m is 1-8), CH.sub.2 SCH.sub.3 or a C.sub.4 -C.sub.8 alkylene bonded to said nitrogen and one of its adjacent carbon atoms inclusive whereby a heterocyclic structure is formed; R.sup.4 and R are independently selected from hydrogen, CF.sub.3, CH.sub.2 CF.sub.3, C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.4 -C.sub.9 cycloalkyl-methyl, C.sub.2 -C.sub.8 alkenyl, C.sub.2 -C.sub.8 alkynyl, 3,3,3-trifluoropropyl, 4,4,4-trifluorobutyl, --(CH.sub.2).sub.m --R.sup.5 where m is 1-8; R.sup.5 is phenyl, phenyl (substituted with a CN, CF.sub.3, CH.sub.2 CF.sub.3, C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.4 -C.sub.9 cycloalkyl-methyl, C.sub.2 -C.sub.8 alkenyl, C.sub.2 -C.sub.8 alkynyl), 2-thiophenyl, 3-thiophenyl, --NR.sup.6 CONR.sup.6 R.sup.7, or --CONR.sup.6 R.sup.7 ; R.sup.6 and R.sup.7 are independently hydrogen, C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.4 -C.sub.9 cycloalkylmethyl, C.sub.2 -C.sub.8 alkenyl or C.sub.2 -C.sub.8 alkynyl; and with the proviso that when R.sup.1 is CN, R.sup.2 and R.sup.4 are H, R.sup.3 is n-Pr and n is 1, then such compound is a pure enantiomer, and when R.sup.1 or R.sup.2 is OH, halogen, CONH.sub.2 or alkyl, then R.sup.4 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.