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：US07659404B2

公开(公告)日：2010-02-09

申请号：US10467609

申请日：2002-02-14

申请人： Dominique Louis Nestor Ghislain Surleraux ,  Piet Tom Bert Paul Wigerinck ,  Daniel Getman ,  Wim Gaston Verschueren ,  Sandrine Vendeville ,  Marie-Pierre De Bethune ,  Jan Octaaf Antoon De Kerpel ,  Samuel Leo Christiaan Moors ,  Herman Augustinus De Kock ,  Marieke Christiane Johanna Voets

发明人： Dominique Louis Nestor Ghislain Surleraux ,  Piet Tom Bert Paul Wigerinck ,  Daniel Getman ,  Wim Gaston Verschueren ,  Sandrine Vendeville ,  Marie-Pierre De Bethune ,  Jan Octaaf Antoon De Kerpel ,  Samuel Leo Christiaan Moors ,  Herman Augustinus De Kock ,  Marieke Christiane Johanna Voets

IPC分类号： A61K31/428 ,  C07D417/12

CPC分类号： C07D417/12 ,  C07D277/82

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; 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.