公开(公告)号：US5214156A

公开(公告)日：1993-05-25

申请号：US866391

申请日：1992-04-10

申请人： Bengt R. Andersson ,  Per Arvid E. Carlsson ,  Kjell A. I. Svensson ,  Hakan V. Wikstrom

发明人： Bengt R. Andersson ,  Per Arvid E. Carlsson ,  Kjell A. I. Svensson ,  Hakan V. Wikstrom

IPC分类号： C07C217/74 ,  C07C323/38 ,  C07D333/20

CPC分类号： C07C323/38 ,  C07C217/74 ,  C07D333/20 ,  C07C2102/10

摘要： This invention is therapeutically useful tetralins and pharmaceutically acceptable acid addition salts thereof of the formula ##STR1## wherein YR.sub.1 is OR.sub.1 at the 8 position where R.sub.1 is --CH.sub.2 --(C.sub.3-8 cycloalkyl);R.sub.2 is hydrogen or C.sub.1-3 alkyl;R.sub.3 is --CH.sub.2 --(C.sub.3-8 cycloalkyl);R.sub.4 is hydrogen, C.sub.1-8 alkyl, --CH.sub.2 --(C.sub.3-4 cycloalkyl), --(CH.sub.2).sub.m --R.sub.5 or --CH.sub.2 --CH.sub.2 --X--(CH.sub.2).sub.n CH.sub.3 ; n is zero to 3 and m is 2 or 3; X is oxygen or sulfur;R.sub.5 is phenyl, C.sub.1-3 alkoxy, C.sub.1-3 alkyl, 2-thiophene, 3-thiophene, or phenyl substituted with one or two substituent groups selected from chlorine, bromine or fluorine; and with the proviso that when R.sub.3 contains more than four carbon atoms and R.sub.4 is alkyl, said alkyl contains from 1 to 3 carbon atoms.Alternatively, --YR.sub.1 is --S--(C.sub.1-3 alkyl) at the 5, 6, 7 or 8 position of the aromatic ring or OR.sub.1 at the 8 position where R.sub.1 is selected from the group consisting of C.sub.1-8 alkyl, C.sub.2-8 alkenyl, --CH.sub.2 --(C.sub.3-8 cycloalkyl) or benzyl;R.sub.2 is hydrogen or (C.sub.1 -C.sub.3) alkyl;R.sub.3 is --CH.sub.2 --(C.sub.3 -C.sub.8) cycloalkyl;R.sub.4 is --(CH.sub.2).sub.m --(2-thiophenyl or 3-thiophenyl); and m is 2 or 3.

摘要翻译： 本发明是治疗上有用的式Ⅰ化合物及其药学上可接受的酸加成盐，其中YR1为OR1，其中R1为-CH2-（C3-8环烷基）; R2是氢或C1-3烷基; R3是-CH2-（C3-8环烷基）; R 4是氢，C 1-8烷基，-CH 2 - （C 3-4环烷基）， - （CH 2）m -R 5或-CH 2 -CH 2 -X-（CH 2）n CH 3; n为0〜3，m为2或3; X是氧或硫; R5是苯基，C1-3烷氧基，C1-3烷基，2-噻吩，3-噻吩或被一个或两个选自氯，溴或氟的取代基取代的苯基; 并且条件是当R 3含有多于4个碳原子且R 4是烷基时，所述烷基含有1至3个碳原子。 或者，-YR1是芳环的5,6,7或8位的-S-（C1-3烷基）或在8位的OR1，其中R1选自C1-8烷基，C2- 8链烯基，-CH 2 - （C 3-8环烷基）或苄基; R2是氢或（C1-C3）烷基; R3是-CH2-（C3-C8）环烷基; R4是 - （CH2）m-（2-噻吩基或3-噻吩基）; m为2或3。

公开(公告)号：US5288748A

公开(公告)日：1994-02-22

申请号：US907932

申请日：1992-07-01

申请人： Hakan V. Wikstrom ,  Per A. E. Carlsson ,  Bengt R. Andersson ,  Kjell A. I. Svensson ,  Stig T. Elebring ,  Nils P. Stjernlof ,  Arthur G. Romero ,  Susanne R. Haadsma-Svensson ,  Chiu-Hong Lin ,  Michael D. Ennis

发明人： Hakan V. Wikstrom ,  Per A. E. Carlsson ,  Bengt R. Andersson ,  Kjell A. I. Svensson ,  Stig T. Elebring ,  Nils P. Stjernlof ,  Arthur G. Romero ,  Susanne R. Haadsma-Svensson ,  Chiu-Hong Lin ,  Michael D. Ennis

IPC分类号： 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分类号： C07D401/12 ,  C07D209/66 ,  C07D409/12 ,  C07D491/04

摘要： A compound of Formula I ##STR1## or pharmaceutically acceptable salts of Formula I, where R.sup.1 is H, C.sub.1 -C.sub.3 alkyl, --(CH.sub.2).sub.n CONH.sub.2 where n is 2 to 6, (CH2).sub.n -1-(4,4-dimethylpiperidine-2,6-dione-yl), or cyclopropylmethyl;R.sup.2 is hydrogen, C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 cycloalkyl or combined with R.sup.1 to form a C.sub.3 -C.sub.8 cycloalkyl, C.sub.2 -C.sub.8 alkenyl, C.sub.2 -C.sub.8 akynyl, (CH.sub.2).sub.n --R"--Ar where R" is O, S, or NH, 3,3,3-trifluoropropyl, --(CH.sub.2).sub.m --R.sup.9 where m is 2 or 3 and R.sup.9 is phenyl, 2-thienyl or 3-thienyl; R.sup.3 is hydrogen, C.sub.1 -C.sub.3 alkyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, formyl, CN, halogen, CH.sub.2 OR.sup.2, C(O)C(O)OR.sup.1, C(O)CO NR.sup.1 R.sup.2, --(CH.sub.2).sub.q --NR.sup.1 R.sup.2 where q is 0 to 5, C.dbd.NOR.sup.2, 2(4,5-dihydro)oxazolyl, or COR.sup.10 where R.sup.10 is H, R.sup.1, NR.sup.1 R.sup.2 or CF.sub.3 ; R.sup.4 is hydrogen, C.sub.1 -C.sub.3 alkyl, cyclopropylmethyl, CF.sub.3, 2,2,2-trifluoroethyl, CN, CONR.sup.1 R.sup.2, .dbd.O, 2(4,5-dihydro)imidazolyl, 2(4,5-dihydro)oxazolyl, 2-oxazolyl, 3-oxadiazolyl, or 3,3,3-trifluoropropyl; R.sup.5 is hydrogen, R.sup.1, OCH.sub.3, C(O)CH.sub.3 or C(O)OR.sup.1 ; X is (a) a valence bond, (b) CH.sub.2, or (c) O, S or NR.sup.5 where R.sup.5 is H, C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 cycloalkyl, benzyl, COR.sup.6 where R.sup.6 is a C.sub.1 -C.sub.3 alkyl, phenyl, or CONR.sup.7 R.sup.8 where R.sup.7 and R.sup.8 are independently H or C.sub.1 -C.sub.3 alkyl; andZ is a hydrogen or halogen;provided that when X is CH.sub.2, at least one of R.sub.3 and R.sub.4 is other than hydrogen or C.sub.1 -C.sub.3 alkyl. The compounds of Formula I are suitable for treating disorders of the central nervous system, particularly as 5-HT.sub.1A receptor agonists.

摘要翻译： 其中R1为H，C1-C3烷基， - （CH2）nCONH2，其中n为2-6，（CH2）n-1-（4,4-二甲氧基苯基） 二甲基哌啶-2,6-二酮基）或环丙基甲基; R2是氢，C1-C8烷基，C3-C8环烷基或与R1结合以形成C 3 -C 8环烷基，C 2 -C 8烯基，C 2 -C 8炔基，（CH 2）n -R“'Ar，其中R” 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; R3是氢，C1-C3烷基，2,2,2-三氟乙基，3,3,3-三氟丙基，甲酰基，CN，卤素，CH2OR2，C（O）C（O）OR1，C（O） - （CH2）q-NR1R2其中q为0至5，C = NOR2,2（4,5-二氢）恶唑基或COR 10，其中R 10为H，R 1，NR 1 R 2或CF 3; R4是氢，C1-C3烷基，环丙基甲基，CF3,2,2,2-三氟乙基，CN，CONR1R2，= 2,2（4,5-二氢）咪唑基，2（4,5-二氢）恶唑基， 恶唑基，3-恶二唑基或3,3,3-三氟丙基; R5是氢，R1，OCH3，C（O）CH3或C（O）OR1; X是（a）价键，（b）CH 2或（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，其中R 6是C 1 -C 3烷基， 苯基或CONR 7 R 8，其中R 7和R 8独立地为H或C 1 -C 3烷基; Z为氢或卤素; 条件是当X是CH 2时，R 3和R 4中的至少一个不是氢或C 1 -C 3烷基。 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。

公开(公告)号：US5225596A

公开(公告)日：1993-07-06

申请号：US721532

申请日：1991-07-08

申请人： Per A. E. Carlsson ,  Hakan V. Wikstrom ,  Kjell A. I. Svensson ,  Bengt R. Andersson ,  Barbro A. Ekman ,  Nils P. Stjernlof ,  Nils A. Svensson

发明人： Per A. E. Carlsson ,  Hakan V. Wikstrom ,  Kjell A. I. Svensson ,  Bengt R. Andersson ,  Barbro A. Ekman ,  Nils P. Stjernlof ,  Nils A. Svensson

IPC分类号： C07C211/42 ,  C07C217/74

CPC分类号： C07C211/42 ,  C07C217/74 ,  C07C2101/02 ,  C07C2102/10

摘要： This invention is therapeutically useful tetralins and pharmaceutically acceptable acid addition salts thereof of the formula ##STR1## wherein X.sub.1 is halogen, CF.sub.3, --OR.sub.3, or --SR.sub.4 ; wherein R.sub.3 is alkyl(C.sub.1 -C.sub.8); alkenyl(C.sub.1 -C.sub.8); --CH.sub.2 -cycloalkyl(C.sub.3 -C.sub.8) or benzyl; wherein R.sub.4 is alkyl(C.sub.1 -C.sub.3); wherein X.sub.2 is hydrogen, CF.sub.3 or halogen; wherein R.sub.7 is hydrogen or methyl; wherein R.sub.1 is hydrogen, alkyl(C.sub.1 -C.sub.3), or cyclopropylmethyl; wherein R.sub.2 is --CH.sub.2 -cycloalkyl(C.sub.3 -C.sub.8), alkyl(C.sub.1 -C.sub.8), --(CH.sub.2).sub.q --R.sub.5 or --CH.sub.2 CH.sub.2 --Z--(CH.sub.2).sub.r CH.sub.3 ; wherein R.sub.5 is phenyl, 2-thiophene or 3-thiophene; wherein Z is oxygen or sulfur; and wherein p is one or 2, q is 2 or 3, and r is zero to 3; with the provisos that (1) when X.sub.1 is --OR.sub.3, X.sub.2 is halogen or CF.sub.3 ; and (2) when X.sub.1 is halogen, X.sub.2 is hydrogen, and p is 2, X.sub.1 is in a position other than the 8-position. These compounds are useful to treat central nervous system disorders.

摘要翻译： 本发明是治疗上有用的式Ⅰ化合物及其药学上可接受的酸式加成盐，其中X 1是卤素，CF 3，-OR 3或-SR 4; 其中R3是烷基（C1-C8）; 烯基（C1-C8）; -CH 2 - 环烷基（C 3 -C 8）或苄基; 其中R4是烷基（C1-C3）; 其中X 2是氢，CF 3或卤素; 其中R7是氢或甲基; 其中R1是氢，烷基（C1-C3）或环丙基甲基; 其中R2是-CH2-环烷基（C3-C8），（C1-C8）烷基， - （CH2）q-R5或-CH2CH2-Z-（CH2）rCH3; 其中R5是苯基，2-噻吩或3-噻吩; 其中Z是氧或硫; 并且其中p是1或2，q是2或3，并且r是0-3; 条件是（1）当X1为-OR3时，X2为卤素或CF3; 和（2）当X1为卤素时，X2为氢，p为2，X1为8位以外的位置。 这些化合物可用于治疗中枢神经系统疾病。

公开(公告)号：US4612316A

公开(公告)日：1986-09-16

申请号：US601981

申请日：1984-04-19

申请人： Bengt R. Andersson ,  Folke L. Arvidsson ,  Per A. E. Carlsson ,  John S. M. Hjort ,  Anette M. Johansson ,  Per L. Lindberg ,  John L. G. Nilsson ,  Domingo Sanchez ,  Kjell A. I. Svensson ,  Hakan V. Wikstrom

发明人： Bengt R. Andersson ,  Folke L. Arvidsson ,  Per A. E. Carlsson ,  John S. M. Hjort ,  Anette M. Johansson ,  Per L. Lindberg ,  John L. G. Nilsson ,  Domingo Sanchez ,  Kjell A. I. Svensson ,  Hakan V. Wikstrom

IPC分类号： A61K31/435 ,  A61P25/00 ,  C07D20060101 ,  C07D221/10 ,  C07D401/12 ,  C07D413/12 ,  C07D417/12 ,  C07D419/12 ,  A61K31/445

CPC分类号： C07D221/10

摘要： Compounds of the formula ##STR1## wherein C.sup.1 and N.sup.4 are in trans configuration to each other, wherein R and Y are defined herein below, as bases and pharmaceutically acceptable acid addition salts thereof, processes for their preparation and pharmaceutical preparations and methods of treatment employing such compounds. The compounds are useful for treatment of disorders in the central nervous system.

摘要翻译： 其中C1和N4彼此反式构型，其中R和Y定义如下的化合物作为碱及其药学上可接受的酸加成盐，其制备方法和药物制剂以及治疗方法 使用这种化合物。 该化合物可用于治疗中枢神经系统疾病。

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：US5461061A

公开(公告)日：1995-10-24

申请号：US144857

申请日：1993-10-28

申请人： Hakan V. Wikstrom ,  Per A. E. Carlsson ,  Bengt R. Andersson ,  Kjell A. I. Svensson ,  Stig T. Elebring ,  Nils P. Stjernlof ,  Arthur G. Romero ,  Susanne R. Haadsma-Svensson ,  Chiu-Hong Lin ,  Michael D. Ennis

发明人： Hakan V. Wikstrom ,  Per A. E. Carlsson ,  Bengt R. Andersson ,  Kjell A. I. Svensson ,  Stig T. Elebring ,  Nils P. Stjernlof ,  Arthur G. Romero ,  Susanne R. Haadsma-Svensson ,  Chiu-Hong Lin ,  Michael D. Ennis

IPC分类号： 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分类号： C07D401/12 ,  C07D209/66 ,  C07D409/12 ,  C07D491/04

摘要： A compound of Formula I ##STR1## or pharmaceutically acceptable salts of Formula I, where R.sup.1 is H, C.sub.1 -C.sub.3 alkyl, --(CH.sub.2).sub.n CONH.sub.2 where n is 2 to 6, (CH2).sub.n -1-(4,4-dimethylpiperidine-2,6-dione-yl), or cyclopropylmethyl;R.sup.2 is hydrogen, C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 cycloalkyl or combined with R.sup.1 to form a C.sub.3 -C.sub.8 cycloalkyl, C.sub.2 -C.sub.8 alkenyl, C.sub.2 -C.sub.8 akynyl, (CH.sub.2).sub.n --X--Ar where X is O, S, or NH, 3,3,3-trifluoropropyl, --(CH.sub.2).sub.m --R.sup.9 where m is 2 or 3 and R.sup.9 is phenyl, 2-thiophenyl or 3-thiophenyl; R.sup.3 is hydrogen, C.sub.1 -C.sub.3 alkyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, formyl, CN, halogen, CH.sub.2 OR.sup.2, C(O)C(O)OR.sup.1, C(O)CO NR.sup.1 R.sup.2, --(CH.sub.2).sub.q --NR.sup.1 R.sup.2 where q is 0 to 5, C.dbd.NOR.sup.2, 2(4,5-dihydro)oxazolyl, or COR.sup.10 where R.sup.10 is H, R.sup.1, NR.sup.1 R.sup.2 or CF.sub.3 ; R.sup.4 is hydrogen, C.sub.1 -C.sub.3 alkyl, cyclopropylmethyl, CF.sub.3, 2,2,2-trifluoroethyl, CN, CONR.sup.1 R.sup.2, .dbd.O, 2(4,5-dihydro)imidazolyl, 2(4,5-dihydro)oxazolyl, 2-oxazolyl, 3-oxadiazolyl, or 3,3,3-trifluoropropyl; R.sup.5 is hydrogen, R.sup. 1, OCH.sub.3, C(O)CH.sub.3 or C(O)OR.sup.1 ; X is (a) a valence bond, (b) CH.sub.2, or (c) O, S or NR.sup.5 where R.sup.5 is H, C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 cycloalkyl, benzyl, COR.sup.6 where R.sup.6 is a C.sub.1 -C.sub.3 alkyl, phenyl, or CONR.sup.7 R.sup.8 where R.sup.7 and R.sup.8 are independently H or C.sub.1 -C.sub.3 alkyl; andZ is a hydrogen or halogen;provided that when X is CH.sub.2, at least one of R.sub.3 and R.sub.4 is other than hydrogen or C.sub.1 -C.sub.3 alkyl. The compounds of Formula I are suitable for treating disorders of the central nervous system, particularly as 5-HT.sub.1A receptor agonists.

摘要翻译： 其中R1为H，C1-C3烷基， - （CH2）nCONH2，其中n为2-6，（CH2）n-1-（4,4-二甲氧基苯基） 二甲基哌啶-2,6-二酮基）或环丙基甲基; R2是氢，C1-C8烷基，C3-C8环烷基或与R1结合以形成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是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; R3是氢，C1-C3烷基，2,2,2-三氟乙基，3,3,3-三氟丙基，甲酰基，CN，卤素，CH2OR2，C（O）C（O）OR1，C（O） - （CH2）q-NR1R2其中q为0至5，C = NOR2,2（4,5-二氢）恶唑基或COR 10，其中R 10为H，R 1，NR 1 R 2或CF 3; R4是氢，C1-C3烷基，环丙基甲基，CF3,2,2,2-三氟乙基，CN，CONR1R2，= 2,2（4,5-二氢）咪唑基，2（4,5-二氢）恶唑基， 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或（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，其中R 6是C 1 -C 3烷基， 苯基或CONR 7 R 8，其中R 7和R 8独立地为H或C 1 -C 3烷基; Z为氢或卤素; 条件是当X是CH 2时，R 3和R 4中的至少一个不是氢或C 1 -C 3烷基。 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。

公开(公告)号：US5306830A

公开(公告)日：1994-04-26

申请号：US994073

申请日：1992-12-21

申请人： Bengt R. Andersson ,  Per A. E. Carlsson ,  Kjell A. I. Svensson ,  Hakan V. Wikstrom ,  Anders R. Hallberg

发明人： Bengt R. Andersson ,  Per A. E. Carlsson ,  Kjell A. I. Svensson ,  Hakan V. Wikstrom ,  Anders R. Hallberg

IPC分类号： C07D311/58

CPC分类号： C07D311/58

摘要： The present invention is directed to novel chromane derivatives substituted in the 3-position by a substituted amino moiety and substituted on the aromatic ring with one or two substituents. The novel chromane derivatives have useful CNS properties. ##STR1##

摘要翻译： 本发明涉及通过取代的氨基部分在3-位上取代并在芳环上被一个或两个取代基取代的新的色原烷衍生物。 新的色原衍生物具有有用的CNS性质。 （*化学结构*）

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：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）