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.

公开(公告)号：US5708018A

公开(公告)日：1998-01-13

申请号：US592318

申请日：1996-02-02

申请人： Susanne R. Haadsma-Svensson ,  Bengt R. Andersson ,  Clas A. Sonesson ,  Chiu-Hong Lin ,  R. Nicholas Waters ,  Kjell A. I. Svensson ,  Per A. E. Carlsson ,  Lars O. Hansson ,  N. Peter Stjernlof

发明人： Susanne R. Haadsma-Svensson ,  Bengt R. Andersson ,  Clas A. Sonesson ,  Chiu-Hong Lin ,  R. Nicholas Waters ,  Kjell A. I. Svensson ,  Per A. E. Carlsson ,  Lars O. Hansson ,  N. Peter Stjernlof

IPC分类号： C07D295/08 ,  A61K31/135 ,  A61K31/335 ,  A61K31/357 ,  A61K31/36 ,  A61K31/40 ,  A61K31/42 ,  A61K31/421 ,  A61P25/00 ,  A61P25/18 ,  A61P25/20 ,  A61P25/28 ,  A61P25/30 ,  A61P43/00 ,  C07C211/42 ,  C07C215/42 ,  C07C217/52 ,  C07C217/74 ,  C07C219/26 ,  C07C223/04 ,  C07C225/20 ,  C07C225/22 ,  C07C229/50 ,  C07C233/43 ,  C07C233/44 ,  C07C237/30 ,  C07C237/48 ,  C07C255/54 ,  C07C255/58 ,  C07C309/56 ,  C07C309/65 ,  C07C309/66 ,  C07C309/73 ,  C07C309/76 ,  C07C311/08 ,  C07C311/21 ,  C07C311/37 ,  C07C311/39 ,  C07C317/32 ,  C07C317/36 ,  C07C323/30 ,  C07C323/36 ,  C07D207/32 ,  C07D207/325 ,  C07D209/48 ,  C07D263/32 ,  C07D295/096 ,  C07D295/12 ,  C07D295/135 ,  C07D317/58 ,  C07D317/70 ,  C07D319/14 ,  C07D319/18 ,  C07D333/20 ,  A61K31/165

CPC分类号： C07D207/325 ,  C07C211/42 ,  C07C215/42 ,  C07C217/52 ,  C07C217/74 ,  C07C219/26 ,  C07C223/04 ,  C07C225/20 ,  C07C229/50 ,  C07C233/43 ,  C07C233/44 ,  C07C237/48 ,  C07C255/54 ,  C07C255/58 ,  C07C309/65 ,  C07C309/66 ,  C07C309/73 ,  C07C311/08 ,  C07C311/21 ,  C07C311/39 ,  C07C317/36 ,  C07D209/48 ,  C07D295/096 ,  C07D295/135 ,  C07D317/70 ,  C07D319/14 ,  C07D333/20 ,  C07C2102/08

摘要： Compounds and their pharmaceutically acceptable salts suitable for treating central nervous system disorders associated with the dopamine D3 receptor activity of Formula I: ##STR1## wherein R.sub.1 and R.sub.2 are independently chosen from hydrogen, C.sub.1 -C.sub.8 alkyl, OCH.sub.3, OH, OSO.sub.2 CF.sub.3, OSO.sub.2 CH.sub.3, SOR.sub.5, CO.sub.2 R.sub.5, CONH.sub.2, CONR.sub.5 R.sub.6, COR.sub.5, CN, SO.sub.2 NH.sub.2, SO.sub.2 NR.sub.5 R.sub.6, SO.sub.2 R.sub.5, --OCO--(C.sub.1 -C.sub.6 alkyl), --NCO--(C.sub.1 -C.sub.6 alkyl), --CH.sub.2 O--(C.sub.1 -C.sub.6 alkyl), --CH.sub.2 OH, --CO-Aryl, --NHSO.sub.2 -Aryl, --NHSO.sub.2 --(C.sub.1 -C.sub.6 alkyl), phthalimide, thiophenyl, pyrrol, pyrrolinyl, oxazolyl, or R.sub.1 and R.sub.2 together form --O(CH.sub.2).sub.1-2 O-- or --(CH.sub.2).sub.3-6 -- (except that only one of R.sub.1 and R.sub.2 can be hydrogen or OH in any such compound); R.sub.3 and R.sub.4 are independently chosen from C.sub.2 -C.sub.4 alkenyl, C.sub.3 -C.sub.8 alkynyl, C.sub.3 -C.sub.8 cycloalkyl, --(CH.sub.2).sub.p -- thienyl (where p is 1-4), or C.sub.1 -C.sub.8 alkyl (except where R.sub.1 or R.sub.2 are hydrogen or OH or where both R.sub.1 and R.sub.2 are OCH.sub.3 or a C.sub.1 -C.sub.8 alkyl); R.sub.5 is hydrogen, C.sub.1 -C.sub.8 alkyl, C.sub.2 -C.sub.4 alkenyl, C.sub.3 -C.sub.8 cycloalkyl; and R.sub.6 is C.sub.1 -C.sub.8 alkyl, C.sub.2 -C.sub.4 alkenyl, C.sub.2 -C.sub.8 alkynyl, C.sub.3 -C.sub.8 cycloalkyl, or Aryl.

摘要翻译： PCT No.PCT / US94 / 08046 Sec。 371日期：1996年5月14日 102（e）日期1996年5月14日PCT提交1994年7月21日PCT公布。 公开号WO95 / 04713 日期1995年2月16日化合物及其药学上可接受的盐适用于治疗与式I的多巴胺D3受体活性相关的中枢神经系统疾病：其中R1和R2独立地选自氢，C1-C8烷基，OCH3，OH ，（C 1 -C 6烷基），-NCO-（C 1 -C 6烷基），-CH 2 O-（C 1 -C 6烷基）， - （C 1 -C 6）烷氧基羰基， 烷基），-CH 2 OH，-CO-芳基，-NHSO 2 - 芳基，-NHSO 2 - （C 1 -C 6烷基），邻苯二甲酰亚胺，噻吩基，吡咯，吡咯烷基，恶唑基或R 1和R 2一起形成-O（CH 2） - 或 - （CH 2）3-6 - （除了R1和R2中只有一个可以是任何这样的化合物中的氢或OH）; R 3和R 4独立地选自C 2 -C 4烯基，C 3 -C 8炔基，C 3 -C 8环烷基， - （CH 2）p - 噻吩基（其中p为1-4）或C 1 -C 8烷基（除了其中R 1或R 2为 氢或OH或其中R 1和R 2均为OCH 3或C 1 -C 8烷基）; R5是氢，C1-C8烷基，C2-C4烯基，C3-C8环烷基; 并且R 6是C 1 -C 8烷基，C 2 -C 4烯基，C 2 -C 8炔基，C 3 -C 8环烷基或芳基。

公开(公告)号：US5639778A

公开(公告)日：1997-06-17

申请号：US522290

申请日：1995-09-07

申请人： Bengt R. Andersson ,  Per A. E. Carlsson ,  Lars O. Hansson ,  Clas A. Sonesson ,  N. Peter Stjernlof ,  Kjell A. I. Svensson ,  R. Nicholas Waters ,  Susanne R. Haadsma-Svensson

发明人： Bengt R. Andersson ,  Per A. E. Carlsson ,  Lars O. Hansson ,  Clas A. Sonesson ,  N. Peter Stjernlof ,  Kjell A. I. Svensson ,  R. Nicholas Waters ,  Susanne R. Haadsma-Svensson

IPC分类号： A61K31/34 ,  A61K31/343 ,  A61K31/40 ,  A61K31/403 ,  A61P25/00 ,  A61P43/00 ,  C07D209/58 ,  C07D209/60 ,  C07D307/92 ,  C07D307/93 ,  C07D409/12 ,  C07D491/04 ,  C07D491/052 ,  C07D493/04 ,  A61K31/33

CPC分类号： C07D209/58 ,  C07D209/60 ,  C07D307/92 ,  C07D307/93 ,  C07D409/12 ,  C07D491/04

摘要： A compound of formula (I) and pharmaceutically acceptable salts thereof, where Z is R.sub.3 and X and Y form (a), or X is R.sub.3 and Y and Z form (a) or (b); R.sub.1 and R.sub.2 are independently hydrogen, C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, --CH.sub.2 --C.sub.3-7 cycloalkyl, phenyl (optionally substituted with halogen or C.sub.1-6 alkyl), -thiophenyl (optionally substituted with halogen or C.sub.1-6 alkyl), or C.sub.1-6 alkyl phenyl; R.sub.3 are independently hydrogen, halogen, --O--C.sub.1-6 alkyl or C.sub.1-6 alkyl; R.sub.4 is a valence bond, CH.sub.2 or oxygen; R.sub.5 and R.sub.6 are independently hydrogen, sulfur, --S--C.sub.1-6 alkyl, halogen, CON(R.sub.3).sub.2, --COCF.sub.3, --CO--C.sub.1-6 alkyl, --CO phenyl, oxygen, --CHO, CN except that when Y and Z form (b), R.sub.1 and R.sub.2 are hydrogen or a C.sub.1-6 alkyl and R.sub.3 is hydrogen, then at least one of R.sub.5 and R.sub.6 must be other than hydrogen. These compounds and derivatives thereof exhibit dopamine-receptor stimulating activity in mammals. ##STR1##

摘要翻译： PCT No.PCT / US94 / 02800 Sec。 371 1995年9月7日第 102（e）1995年9月7日PCT PCT 1994年3月21日PCT公布。 出版物WO94 / 21608 1994年9月29日一种式（I）化合物及其药学上可接受的盐，其中Z为R 3，X和Y为（a），或X为R 3，Y和Z为（a）或（b）。 R 1和R 2独立地是氢，C 1-6烷基，C 3-7环烷基，-CH 2 -C 3-7环烷基，苯基（任选被卤素或C 1-6烷基取代） - 噻吩基（任选地被卤素或C 1-6烷基 ）或C 1-6烷基苯基; R 3独立地是氢，卤素，-O-C 1-6烷基或C 1-6烷基; R4是价键，CH2或氧; R 5和R 6独立地是氢，硫，-S-C 1-6烷基，卤素，CON（R 3）2，-COCF 3，-CO-C 1-6烷基，-CO苯基，氧，-CHO， 和Z形式（b）中，R 1和R 2是氢或C 1-6烷基，R 3是氢，则R 5和R 6中的至少一个必须不是氢。 这些化合物及其衍生物在哺乳动物中表现出多巴胺受体刺激活性。 （a）（a）（b）

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.