公开(公告)号：US08580981B2

公开(公告)日：2013-11-12

申请号：US13060942

申请日：2009-09-01

申请人： Piet Tom Bert Paul Wigerinck ,  Dominique Louis Nestor Ghislain Surleraux ,  Wim Gaston Verschueren ,  Herman Augustinus De Kock ,  Wim Albert Alex Aelterman

发明人： Piet Tom Bert Paul Wigerinck ,  Dominique Louis Nestor Ghislain Surleraux ,  Wim Gaston Verschueren ,  Herman Augustinus De Kock ,  Wim Albert Alex Aelterman

IPC分类号： C07D493/04

CPC分类号： C07D493/04

摘要： The present invention relates to a process for the preparation of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl(1S,2R)-3-[[(4-aminophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropylcarbamate as well as novel intermediates for use in said process. (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl(1S,2R)-3-[[(4-aminophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropylcarbamate is particularly useful as an HIV protease inhibitor.

摘要翻译： 本发明涉及制备（3R，3aS，6aR） - 六氢呋喃并[2,3-b]呋喃-3-基（1S，2R）-3 - [[（4-氨基苯基）磺酰基] 异丁基）氨基] -1-苄基-2-羟基丙基氨基甲酸酯以及用于所述方法的新型中间体。 （3R，3aS，6aR） - 六氢呋喃并[2,3-b]呋喃-3-基（1S，2R）-3 - [[（4-氨基苯基）磺酰基]（异丁基）氨基] -1-苄基-2- 羟丙基氨基甲酸酯特别可用作HIV蛋白酶抑制剂。

公开(公告)号：US20100280268A1

公开(公告)日：2010-11-04

申请号：US12293589

申请日：2007-04-06

申请人： Géry Karel Julia Dams ,  Inge Vereycken ,  Koenraad Lodewijk August Van Acker ,  Emmanuel Marie Paul Ernest Gustin ,  Wim Gaston Verschueren ,  Asa Catrine Ohagen

发明人： Géry Karel Julia Dams ,  Inge Vereycken ,  Koenraad Lodewijk August Van Acker ,  Emmanuel Marie Paul Ernest Gustin ,  Wim Gaston Verschueren ,  Asa Catrine Ohagen

IPC分类号： C07C69/76 ,  G01N21/64 ,  C07C63/00 ,  C07C229/54

CPC分类号： G01N33/56988 ,  G01N33/542

摘要： The present invention concerns a fluorescence resonance energy transfer based high throughput test system to measure the formation of the HIV gp41 six-helix bundle. In a first embodiment the current invention relates to a homogeneous time resolved fluorescence-based test system comprising a first helical polypeptide consisting essentially of the sequence of IQN36 (SEQ ID NO:1); a second helical polypeptide consisting essentially of the sequence of C34 (SEQ ID NO: 2) wherein said IQN36 is labeled with a light emitting fluorophore and said C34 is labeled with an ultra-violet excitable fluorophore.

摘要翻译： 本发明涉及基于荧光共振能量转移的高通量测试系统来测量HIV gp41六螺旋束的形成。 在第一个实施方案中，本发明涉及基于均匀时间分辨荧光的测试系统，其包含基本上由IQN36（SEQ ID NO：1）序列组成的第一螺旋多肽; 基本上由C34（SEQ ID NO：2）的序列组成的第二螺旋多肽，其中所述IQN36用发光荧光团标记，所述C34用紫外线可激发荧光团标记。

公开(公告)号：US07763641B2

公开(公告)日：2010-07-27

申请号：US10499221

申请日：2002-12-20

申请人： Sandrine Marie Helene Vendeville ,  Wim Gaston Verschueren ,  Abdellah Tahri ,  Samuel Leo Christiaan Moors ,  Montserrat Erra Sola

发明人： Sandrine Marie Helene Vendeville ,  Wim Gaston Verschueren ,  Abdellah Tahri ,  Samuel Leo Christiaan Moors ,  Montserrat Erra Sola

IPC分类号： A61K31/42 ,  A61K31/44 ,  A61K31/425 ,  C07D277/54

CPC分类号： C07D231/12 ,  C07C311/18 ,  C07C2603/18 ,  C07D233/64 ,  C07D233/88 ,  C07D263/32 ,  C07D277/40 ,  C07D277/42 ,  C07D277/46 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14 ,  C07D493/04 ,  C07D513/04

摘要： The present invention concerns the compounds having the formula (I), N-oxides, salt, stereoisomeric forms, racemic mixtures, prodrugs, esters and metabolites thereof, wherein Haryl is an aromatic monocyclic, bicyclic or tricyclic heterocycle having 3 to 14 ring members which contains one or more heteroatom ring members selected from nitrogen, oxygen and sulfur and which may optionally be substituted on (i) one or more carbon atoms by C1-6alkyl, halogen, hydroxy, optionally mono- or disubstituted amino, nitro, cyano, haloC1-6alkyl, carboxyl, C3-7cycloalkyl, optionally mono- or disubstituted aminocarbonyl, methylthio, methylsulfonyl, aryl, —(R7a)n—M—R7b, Het1 and Het2; whereby the optional substituents on any amino function are independently selected from R5 and —A—R6; and on (ii) a nitrogen atom if present by hydroxy or —A—R6. It further relates to their use as broadspectrum HIV protease inhibitors, processes for their preparation as well as pharmaceutical compositions and diagnostic kits comprising them. It also concerns combinations thereof with another anti-retroviral agent, and to their use in assays as reference compounds or as reagents.

摘要翻译： 本发明涉及具有式（I）的化合物，N-氧化物，盐，立体异构形式，外消旋混合物，前药，酯和代谢物，其中Haryl是具有3至14个环成员的芳族单环，双环或三环杂环， 含有一个或多个选自氮，氧和硫的杂原子环成员，并且其可任选地在（i）一个或多个碳原子上被C 1-6烷基，卤素，羟基，任选单或二取代的氨基，硝基，氰基，卤代 烷基，羧基，C 3-7环烷基，任选的单或二取代的氨基羰基，甲硫基，甲基磺酰基，芳基， - （R 7a）n-M-R 7b，Het 1和Het 2; 其中任何氨基官能团上的任选取代基独立地选自R5和-A-R6; 和（ii）如果存在羟基或-A-R 6的氮原子。 它还涉及它们作为广谱的HIV蛋白酶抑制剂，其制备方法以及药物组合物和包含它们的诊断试剂盒的用途。 它还涉及与另一种抗逆转录病毒剂的组合，以及它们在测定中用作参考化合物或作为试剂。

公开(公告)号：US07595334B2

公开(公告)日：2009-09-29

申请号：US11626183

申请日：2007-01-23

申请人： Dominique Louis Nestor Ghislain Surleraux ,  Sandrine Marie Helene Vendeville ,  Wim Gaston Verschueren ,  Marie-Pierre T. M. M. G. De Bethune ,  Herman Augustinus De Kock ,  Abdellah Tahri ,  Montserrat Erra Solà

发明人： Dominique Louis Nestor Ghislain Surleraux ,  Sandrine Marie Helene Vendeville ,  Wim Gaston Verschueren ,  Marie-Pierre T. M. M. G. De Bethune ,  Herman Augustinus De Kock ,  Abdellah Tahri ,  Montserrat Erra Solà

IPC分类号： A61K31/421 ,  A61K31/426 ,  C07D263/54 ,  C07D277/02 ,  C07D413/02

CPC分类号： C07D413/04 ,  C07D263/58 ,  C07D417/12 ,  C07D417/14 ,  C07D493/04

摘要： The present invention concerns the compounds having the formula N-oxides, salts, stereoisomeric forms, racemic mixtures, prodrugs, esters and metabolites thereof, wherein R1 and R8 each are H, optionally substituted C1-6alkyl, C2-6alkenyl, C3-7cycloalkyl, aryl, Het1, Het2; R1 may also be a radical of formula (R11aR11b)NC(R10aR10b)CR9—; t is 0, 1 or 2; R2 is H or C1-6alkyl; L is —C(═O)—, —O—C(═O)—, —NR8—C(═O)—, —O—C1-6alkanediyl-C(═O)—, —NR8—C1-6alkanediyl-C(═O)—, —S(═O)2—, —O—S(═O)2—, —NR8—S(═O)2; R3 is C1-6alkyl, aryl, C3-7cycloalkyl, C3-7cycloalkylC1-4alkyl, or arylC1-4alkyl; R4 is H, C1-4alkylOC(═O), carboxyl, aminoC(═O), mono- or di(C1-4alkyl)aminoC(═O), C3-7cycloalkyl, C2-6alkenyl, C2-6alkynyl or optionally substituted C1-6alkyl; A is C1-6alkanediyl, —C(═O)—, —C(═S)—, —S(═O)2—, C1-6alkanediyl-C(═O)—, C1-6alkanediyl-C(═S)— or C1-6alkanediyl-S(═O)2—; R5 is H, OH, C1-6alkyl, Het1C1-6alkyl, Het2C1-6alkyl, optionally substituted aminoC1-6alkyl; R6 is C1-6alkylO, Het1, Het1O, Het2, Het2O, aryl, arylO, C1-6alkyloxycarbonylamino or amino; and in case -A- is other than C1-6alkanediyl then R6 may also be C1-6alkyl, Het1C1-4alkyl, Het1OC1-4alkyl, Het2C1-4alkyl, Het2OC1-4alkyl, arylC1-4alkyl, arylOC1-4alkyl or aminoC1-4alkyl; whereby each of the amino groups in the definition of R6 may optionally be substituted; -A-R6 is hydroxyC1-6alkyl; R5 and -A-R6 taken together with the nitrogen atom to which they are attached may also form Het1 or Het2. It further relates to their use as broadspectrum HIV protease inhibitors, processes for their preparation as well as pharmaceutical compositions and diagnostic kits comprising them. It also concerns combinations thereof with another anti-retroviral agent, and to their use in assays as reference compounds or as reagents.

公开(公告)号：US07244752B2

公开(公告)日：2007-07-17

申请号：US10474162

申请日：2002-04-09

申请人： Dominique Louis Nestor Ghislain Surleraux ,  Sandrine Marie Helene Vendeville ,  Wim Gaston Verschueren ,  Marie-Pierre T. M. M. G. De Bethune ,  Herman Augustinus De Kock ,  Abdellah Tahri ,  Montserrat Erra Solà

发明人： Dominique Louis Nestor Ghislain Surleraux ,  Sandrine Marie Helene Vendeville ,  Wim Gaston Verschueren ,  Marie-Pierre T. M. M. G. De Bethune ,  Herman Augustinus De Kock ,  Abdellah Tahri ,  Montserrat Erra Solà

IPC分类号： A61K31/421 ,  A61K31/426 ,  C07D263/54 ,  C07D277/02 ,  C07D413/02 ,  C07D417/02

CPC分类号： C07D413/04 ,  C07D263/58 ,  C07D417/12 ,  C07D417/14 ,  C07D493/04

摘要： The present invention concerns the compounds having the formula N-oxides, salts, stereoisomeric forms, racemic mixtures, prodrugs, esters and metabolites thereof, wherein R1 and R8 each are H, optionally substituted C1-6alkyl, C2-6alkenyl, C3-7cycloalkyl, aryl, Het1, Het2; R1 may also be a radical of formula (R11aR11b)NC(R10aR10b)CR9—; t is 0, 1 or 2; R2 is H or C1-6alkyl; L is —C(═O)—, —O—C(═O)—, —NR8—C(═O)—, —O—C1-6alkanediyl-C(═O)—, —NR8—C1-6alkanediyl-C(═O)—, —S(═O)2—, —O—S(═O)2—, —NR8—S(═O)2; R3 is C1-6alkyl, aryl, C3-7cycloalkyl, C3-7cycloalkylC1-4alkyl, or arylC1-4alkyl; R4 is H, C1-4alkylOC(═O), carboxyl, aminoC(═O), mono- or di(C1-4alkyl)aminoC(═O), C3-7cycloalkyl, C2-6alkenyl, C2-6alkynyl or optionally substituted C1-6alkyl; A is C1-6alkanediyl, —C(═O)—, —C(═S)—, —S(═O)2—, C1-6alkanediyl-C(═O)—, C1-6alkanediyl-C(═S)— or C1-6alkanediyl-S(═O)2—; R5 is H, OH, C1-6alkyl, Het1C1-6alkyl, Het2C1-6alkyl, optionally substituted aminoC1-6alkyl; R6 is C1-6alkylO, Het1, Het1O, Het2, Het2O, aryl, arylO, C1-6alkyloxycarbonylamino or amino; and in case -A- is other than C1-6alkanediyl then R6 may also be C1-6alkyl, Het1C1-4alkyl, Het1OC1-4alkyl, Het2C1-4alkyl, Het2OC1-4alkyl, arylC1-4alkyl, arylOC1-4alkyl or aminoC1-4alkyl; whereby each of the amino groups in the definition of R6 may optionally be substituted; -A-R6 is hydroxyC1-6alkyl; R5 and -A-R6 taken together with the nitrogen atom to which they are attached may also form Het1 or Het2. It further relates to their use as broadspectrum HIV protease inhibitors, processes for their preparation as well as pharmaceutical compositions and diagnostic kits comprising them. It also concerns combinations thereof with another anti-retroviral agent, and to their use in assays as reference compounds or as reagents.

公开(公告)号：US20100029632A1

公开(公告)日：2010-02-04

申请号：US12575216

申请日：2009-10-07

申请人： Dominique Louis Nestor Ghislain SURLERAUX ,  Sandrine Marie Helene Vendeville ,  Wim Gaston Verschueren ,  Marie-Pierre T.M.M.G. De Bethune ,  Herman Augustinus De Kock ,  Abdellah Tahri

发明人： Dominique Louis Nestor Ghislain SURLERAUX ,  Sandrine Marie Helene Vendeville ,  Wim Gaston Verschueren ,  Marie-Pierre T.M.M.G. De Bethune ,  Herman Augustinus De Kock ,  Abdellah Tahri

IPC分类号： A61K31/5383 ,  A61K31/421 ,  C12N7/04 ,  A61K31/426 ,  A61K31/436 ,  A61K31/4439 ,  A61K31/505 ,  A61P31/12

CPC分类号： C07D263/58 ,  C07D413/12 ,  C07D417/12 ,  C07D491/04 ,  C07D493/04 ,  C07D513/04

摘要： The present invention concerns the compounds having the formula N-oxides, salts, stereoisomeric forms, racemic mixtures, prodrugs, esters and metabolites thereof, wherein R1 and R8 each are H, optionally substituted C1-6alkyl, C2-6alkenyl, C3-7cycloalkyl, aryl, Het1, Het2; R1 may also be a radical of formula (R11aR11b)NC(R10aR10b)CR9—; t is 0, 1 or 2; R2 is H or C1-6alkyl; L is —C(═O)—, —O—C(═O)—, —NR8—C(═O)—, —O—C1-6alkanediyl-C(═O)—, —NR8—C1-6alkanediyl-C(═O)—, —S(═O)2—, —O—S(═O)2—, —NR8—S(═O)2; R3 is C1-6alkyl, aryl, C3-7cycloalkyl, C3-7cycloalkylC1-4alkyl, or arylC1-4alkyl; R4 is H, C1-4alkylOC(═O), carboxyl, aminoC(═O), mono- or di(C1-4alkyl)aminoC(═O), C3-7cycloalkyl, C2-6alkenyl, C2-6alkynyl or optionally substituted C1-6alkyl; R5 and R6 are H or C1-6alkyl. It further relates to their use as broadspectrum HIV protease inhibitors, processes for their preparation as well as pharmaceutical compositions and diagnostic kits comprising them. It also concerns combinations thereof with another anti-retroviral agent, and to their use in assays as reference compounds or as reagents.

摘要翻译： 本发明涉及具有式N-氧化物，盐，立体异构形式，外消旋混合物，前药，酯和代谢物的化合物，其中R 1和R 8各自为H，任选取代的C 1-6烷基，C 2-6烯基，C 3-7环烷基， 芳基，Het1，Het2; R1也可以是式（R11aR11b）NC（R10aR10b）CR9-的基团; t为0,1或2; R2是H或C1-6烷基; L是-C（-O） - ， - OC（-O） - ， - NR8-C（-O） - ， - O-C1-6烷二基-C（ - ） - ，-NR8-C1-6烷二基-C （-O） - ， - S（-O）2 - ， - O（O）2 - ， - NR 8 -S（-O）2; R 3是C 1-6烷基，芳基，C 3-7环烷基，C 3-7环烷基C 1-4烷基或芳基C 1-4烷基; R4是H，C1-4烷基OC（-O），羧基，氨基C（-O），单或二（C1-4烷基）氨基C（-O），C3-7环烷基，C2-6烯基，C2-6炔基或任选取代的C1 -6-烷基; R5和R6是H或C1-6烷基。 它还涉及它们作为广谱的HIV蛋白酶抑制剂，其制备方法以及药物组合物和包含它们的诊断试剂盒的用途。 它还涉及与另一种抗逆转录病毒剂的组合，以及它们在测定中用作参考化合物或作为试剂。

公开(公告)号：US06900222B1

公开(公告)日：2005-05-31

申请号：US09980451

申请日：2000-05-23

申请人： Marcel Frans Leopold De Bruyn ,  Kristof Van Emelen ,  Piet Tom Bert Paul Wigerinck ,  Wim Gaston Verschueren

发明人： Marcel Frans Leopold De Bruyn ,  Kristof Van Emelen ,  Piet Tom Bert Paul Wigerinck ,  Wim Gaston Verschueren

IPC分类号： A61K31/505 ,  A61K31/513 ,  A61P1/06 ,  A61P1/14 ,  A61P9/00 ,  C07D405/12 ,  C07D405/14

CPC分类号： C07D405/12 ,  C07D405/14

摘要： The present invention concerns compounds of formula (I) a stereochemically isomeric form thereof, an N-oxide form thereof or a pharmaceutically acceptable acid addition salt thereon wherein —Z1—Z2— is a bivalent radical; R1, R2 and R3 are each independently selected from hydrogen, C1-6alkyl, hydroxy, halo and the like; or when R1 and R2 are on adjacent carbon atoms, R1 and R2 taken together may form a bivalent radical of formula; Alk is optionally substituted C1-6alkanediyl; the bivalent radical is a substituted piperidinyl, an optionally substituted pyrrolidinyl, homopiperidinyl, piperazinyl or tropyl; R5 is a radical of formula wherein n is 1 or 2; p1 is 0, and p2 is 1 or 2; or p1 is 1 or 2, and p2 is 0; X is oxygen, sulfur or ═NR9; Y is oxygen or sulfur; R7 is hydrogen, C1-6alkyl, C3-6cycloalkyl, phenyl or phenylmethyl; R8 is C1-6alkyl, C3-6cycloalkyl phenyl or phenylmethyl; R9 is cyano, C1-6alkyl, C3-6cyclo-alkyl, C1-6alkyloxycarbonyl or aminocarbonyl; R10 is hydrogen or C1-6alkyl; and Q is a bivalent radical. Processes for preparing said products, formulations comprising said products and their use as a medicine are disclosed, in particular for treating conditions which are related to impaired fundic relaxation.

公开(公告)号：US6133277A

公开(公告)日：2000-10-17

申请号：US192686

申请日：1998-11-16

申请人： Piet Tom Bert Paul Wigerinck ,  Wim Gaston Verschueren ,  Marc Francis Josephine Schroven ,  Marcel Frans Leopold De Bruyn

发明人： Piet Tom Bert Paul Wigerinck ,  Wim Gaston Verschueren ,  Marc Francis Josephine Schroven ,  Marcel Frans Leopold De Bruyn

IPC分类号： A61K31/4166 ,  A61K31/443 ,  A61K31/454 ,  A61K31/495 ,  A61K31/496 ,  A61K31/506 ,  A61P1/00 ,  A61P1/14 ,  A61P43/00 ,  C07D405/12 ,  C07D405/14 ,  C07D417/12 ,  A61K31/54 ,  A01N43/54 ,  A61K31/505 ,  C07D285/16 ,  C07D473/00

CPC分类号： C07D405/12 ,  C07D405/14

摘要： The present invention of compounds of formula (I) a stereochemically isomeric form thereof, an N-oxide form thereof or a pharmaceutically acceptable acid addition salt thereof, wherein Alk.sup.1 is C.sub.1-6 alkanediyl optionally substituted with hydroxy, C.sub.1-4 alkyloxy or C.sub.1-4 alkylcarbonyloxy; --Z.sup.1 --Z.sup.2 -- is a bivalent radical; R.sup.1, R.sup.2 and R.sup.3 are each independently selected from hydrogen, C.sub.1-6 alkyl, hydroxy, halo and the like; or when R.sup.1 and R.sup.2 are on adjacent carbon atoms, R.sup.1 and R.sup.2 taken together may form a bivalent radical; R.sup.4 is hydrogen or C.sub.1-6 alkyl; A is a bivalent radical of formula --NR.sup.6 --Alk.sup.2 -- (b-1), or --Npiperidinyl--(CH.sub.2).sub.m (b-2) wherein m is 0 or 1; R.sup.5 is a radical of formula ##STR1## wherein n is 1 or 2; p.sup.1 is 0, and p.sup.2 is 1 or 2; or p.sup.1 is 1 or 2, and p.sup.2 is 0; X is oxygen, sulfur or .dbd.NR.sup.9 ; Y is oxygen or sulfur; R.sup.7 is hydrogen, C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, phenyl or phenylmethyl; R.sup.8 is C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl phenyl or phenylmethyl; R.sup.9 is cyano, C.sub.1-6 alkyl, C.sub.3-6 cyclo-alkyl, C.sub.1-6 alkyloxycarbonyl or aminocarbonyl; R.sup.10 is hydrogen or C.sub.1-6 alkyl; and Q is a bivalent radical. Processes for preparing said products, formulations comprising said products and their use as a medicine are disclosed, in particular for treating conditions which are related to impaired fundic relaxation.

公开(公告)号：US6100268A

公开(公告)日：2000-08-08

申请号：US123893

申请日：1998-07-28

申请人： Guy Rosalia Eugene Van Lommen ,  Piet Tom Bert Paul Wigerinck ,  Marcel Frans Leopold De Bruyn ,  Wim Gaston Verschueren ,  Marc Francis Josephine Schroven

发明人： Guy Rosalia Eugene Van Lommen ,  Piet Tom Bert Paul Wigerinck ,  Marcel Frans Leopold De Bruyn ,  Wim Gaston Verschueren ,  Marc Francis Josephine Schroven

IPC分类号： C07D491/052 ,  A61K31/35 ,  A61K31/352 ,  A61K31/40 ,  A61K31/4025 ,  A61K31/415 ,  A61K31/425 ,  A61K31/44 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/50 ,  A61K31/501 ,  A61K31/505 ,  A61K31/506 ,  A61K31/53 ,  A61P9/00 ,  A61P9/08 ,  C07D311/58 ,  C07D311/78 ,  C07D311/92 ,  C07D311/94 ,  C07D405/12 ,  C07D405/14 ,  C07D409/14 ,  C07D417/12 ,  C07D493/04

CPC分类号： C07D405/12 ,  C07D311/58 ,  C07D405/14 ,  C07D409/14 ,  C07D417/12 ,  C07D493/04

摘要： The present invention is concerned with compounds of formula ##STR1## the pharmaceutically acceptable acid addition salts thereof, and the stereochemically isomeric forms thereof, wherein R.sup.1 is hydrogen or C.sub.1-6 alkyl; R.sup.2 is hydrogen or C.sub.1-6 alkyl; R.sup.3 is hydrogen or C.sub.1-6 -alkyl; R.sup.4 is hydrogen, halo, C.sub.1-6 alkyl, hydroxy, C.sub.1-6 alkyloxy, aryloxy or arylmethoxy; R.sup.5 and R.sup.6 designate R.sup.5a and R.sup.6a wherein R.sup.5a and R.sup.6a taken together form a bivalent radical; or R.sup.5 and R.sup.6 can designate R.sup.5b and R.sup.6b wherein R.sup.5b is hydrogen and R.sup.6b is a heterocycle or an optionally substituted alkenyl or alkynyl group; or R.sup.5 and R.sup.6 designate R.sup.5c and R.sup.6c, wherein R.sup.5c and R.sup.6c are hydrogen, halo, C.sub.1-6 alkyl, C.sub.3-6 alkenyl, C.sub.3-6 alkynyl, hydroxy, C.sub.1-6 alkyloxy, cyano, aminoC.sub.1-6 alkyl, carboxyl, C.sub.1-6 alkyloxycarbonyl, nitro, amino, aminocarbonyl, C.sub.1-6 alkylcarbonylamino, or mono-di(C.sub.1-6 alkyl)amino; Q is a heterocyclic ring containing at least one nitrogen atom or a radical of formula ##STR2## pharmaceutical compositions, preparations and use as a medicine are also described.

摘要翻译： 本发明涉及式的化合物及其药学上可接受的酸加成盐及其立体化学异构形式，其中R 1是氢或C 1-6烷基; R2是氢或C1-6烷基; R3是氢或C1-6烷基; R4是氢，卤素，C1-6烷基，羟基，C1-6烷氧基，芳氧基或芳基甲氧基; R5和R6表示R5a和R6a，其中R5a和R6a一起形成二价基团; 或R5和R6可以表示R5b和R6b，其中R5b是氢，R6b是杂环或任选取代的烯基或炔基; 或者R5和R6表示R5c和R6c，其中R5c和R6c是氢，卤素，C1-6烷基，C3-6烯基，C3-6炔基，羟基，C1-6烷氧基，氰基，氨基C1-6烷基，羧基，C1-6烷氧基羰基，硝基， 氨基，氨基羰基，C 1-6烷基羰基氨基或单 - 二（C 1-6烷基）氨基; Q是含有至少一个氮原子的杂环或式的药物组合物的基团，作为药物的制剂和用途也被描述。

公开(公告)号：US5824682A

公开(公告)日：1998-10-20

申请号：US586760

申请日：1996-01-30

申请人： Guy Rosalia Eugene Van Lommen ,  Piet Tom Bert Paul Wigerinck ,  Marcel Frans Leopold De Bruyn ,  Wim Gaston Verschueren ,  Marc Francis Josephine Schroven

发明人： Guy Rosalia Eugene Van Lommen ,  Piet Tom Bert Paul Wigerinck ,  Marcel Frans Leopold De Bruyn ,  Wim Gaston Verschueren ,  Marc Francis Josephine Schroven

IPC分类号： C07D491/052 ,  A61K31/35 ,  A61K31/352 ,  A61K31/40 ,  A61K31/4025 ,  A61K31/415 ,  A61K31/425 ,  A61K31/44 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/50 ,  A61K31/501 ,  A61K31/505 ,  A61K31/506 ,  A61K31/53 ,  A61P9/00 ,  A61P9/08 ,  C07D311/58 ,  C07D311/78 ,  C07D311/92 ,  C07D311/94 ,  C07D405/12 ,  C07D405/14 ,  C07D409/14 ,  C07D417/12 ,  C07D493/04

CPC分类号： C07D405/12 ,  C07D311/58 ,  C07D405/14 ,  C07D409/14 ,  C07D417/12 ,  C07D493/04

摘要： The present invention is concerned with compounds of formula ##STR1## the pharmaceutically acceptable acid addition salts thereof, and the stereochemically isomeric forms thereof, wherein R.sup.1 is hydrogen or C.sub.1-6 alkyl; R.sup.2 is hydrogen or C.sub.1-6 alkyl; R.sup.3 is hydrogen or C.sub.1-6 alkyl; R.sup.4 is hydrogen, halo, C.sub.1-6 alkyl, hydroxy, C.sub.1-6 alkyloxy, aryloxy or arylmethoxy; R.sup.5 and R.sup.6 designate R.sup.5a and R.sup.6a wherein R.sup.5a and R.sup.6a taken together form a bivalent radical; or R.sup.5 and R.sup.6 can designate R.sup.5b and R.sup.6b wherein R.sup.5b is hydrogen and R.sup.6b is a heterocycle or an optionally substituted alkenyl or alkynyl group; or R.sup.5 and R.sup.6 designate R.sup.5c and R.sup.6c, wherein R.sup.5c and R.sup.6c are hydrogen, halo, C.sub.1-6 alkyl, C.sub.3-6 alkenyl, C.sub.3-6 alkynyl, hydroxy, C.sub.1-6 alkyloxy, cyano, aminoC.sub.1-6 alkyl, carboxyl, C.sub.1-6 alkyloxycarbonyl, nitro, amino, aminocarbonyl, C.sub.1-6 alkylcarbonylamino, or mono-di(C.sub.1-6 alkyl)amino; Q is a heterocyclic ring containing at least one nitrogen atom or a radical of formula ##STR2## pharmaceutical compositions, preparations and use as a medicine are also described.

摘要翻译： PCT No.PCT / EP94 / 02703 Sec。 371日期1996年1月30日 102（e）日期1996年1月30日PCT 1994年8月12日PCT PCT。 公开号WO95 / 05383 日期：1995年2月23日本发明涉及式（I）化合物及其药学上可接受的酸加成盐及其立体化学异构形式，其中R 1为氢或C 1-6烷基; R2是氢或C1-6烷基; R3是氢或C1-6烷基; R4是氢，卤素，C1-6烷基，羟基，C1-6烷氧基，芳氧基或芳基甲氧基; R5和R6表示R5a和R6a，其中R5a和R6a一起形成二价基团; 或R5和R6可以表示R5b和R6b，其中R5b是氢，R6b是杂环或任选取代的烯基或炔基; 或者R5和R6表示R5c和R6c，其中R5c和R6c是氢，卤素，C1-6烷基，C3-6烯基，C3-6炔基，羟基，C1-6烷氧基，氰基，氨基C1-6烷基，羧基，C1-6烷氧基羰基，硝基， 氨基，氨基羰基，C 1-6烷基羰基氨基或单 - 二（C 1-6烷基）氨基; Q是含有至少一个氮原子的杂环或式（ⅩⅧ）基团的药物组合物，制剂和作为药物的用途。