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：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：US07863306B2

公开(公告)日：2011-01-04

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： A61K31/423

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） - ， - O-C（= O） - ， - NR8-C（= O） - ， - O-C1-6烷二基-C（= O） - ，-NR8-C1-6烷二基 -C（= O） - ， - S（= O）2 - ， - O-S（= 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：US07622490B2

公开(公告)日：2009-11-24

申请号：US10474485

申请日：2002-05-10

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： A61K31/423 ,  C07D263/58

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, C3-7 cycloalkyl, 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)—, —C1-6alkanediyl-C(═O)—, —NR8—C1-6alkanediyl-C(═O)—, —S(═O)2—, —O—S(═O)2—, —NR9-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), C3-7 cycloalkyl, 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） - ， - NR 8 -C（-O） - ， - C 1-6烷二基-C（ - ） - ， - NR 8 -C 1-6烷二基-C （-O）2 - ， - S（-O）2 - ， - NR 9 -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; R 4是H，C 1-4烷基OC（-O），羧基，氨基C（-O），单或二（C 1-4烷基）氨基C（-O），C 3-7环烷基，C 2-6烯基，C 2-6炔基或任选取代 C 1-6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：US08012939B2

公开(公告)日：2011-09-06

申请号：US11995714

申请日：2006-07-28

申请人： Kenneth Alan Simmen ,  Herman Augustinus De Kock ,  Pierre Jean-Marie Bernard Raboisson ,  Sandrine Marie Helene Vendeville ,  Lili Hu ,  Abdellah Tahri ,  Dominique Louis Nestor Ghislain Surleraux ,  Wim Van De Vreken ,  Ismet Dorange ,  Yvan Simonnet ,  Karl Magnus Nilsson ,  Bengt Bertil Samuelsson ,  Asa Annica Kristina Rosenquist ,  Hans Kristian Wallberg

发明人： Kenneth Alan Simmen ,  Herman Augustinus De Kock ,  Pierre Jean-Marie Bernard Raboisson ,  Sandrine Marie Helene Vendeville ,  Lili Hu ,  Abdellah Tahri ,  Dominique Louis Nestor Ghislain Surleraux ,  Wim Van De Vreken ,  Ismet Dorange ,  Yvan Simonnet ,  Karl Magnus Nilsson ,  Bengt Bertil Samuelsson ,  Asa Annica Kristina Rosenquist ,  Hans Kristian Wallberg

IPC分类号： A61K38/05 ,  C07D245/00

CPC分类号： C07D401/14 ,  C07D401/12 ,  C07D417/14 ,  C07D487/04 ,  C07K5/06191

摘要： Inhibitors of HCV replication of formula (I) and the N-oxides, salts, and stereoisomers thereof, wherein each variable has specific definitions. Pharmaceutical compositions containing compounds (I) and process for preparing compounds (I) are also provided. Bioavailable combinations of the inhibitors of HCV of Formula (I) with ritonavir are also provided.

摘要翻译： 式（I）的HCV复制抑制剂及其N-氧化物，盐和立体异构体，其中每个变量具有特定定义。 还提供了含有化合物（I）的药物组合物和制备化合物（I）的方法。 还提供了式（I）的HCV抑制剂与利托那韦的生物可利用组合。

公开(公告)号：US07989471B2

公开(公告)日：2011-08-02

申请号：US11995573

申请日：2006-07-28

申请人： Kenneth Alan Simmen ,  Herman Augustinus De Kock ,  Pierre Jean-Marie Bernard Raboisson ,  Sandrine Marie Helene Vendeville ,  Lili Hu ,  Wim Van De Vreken ,  David Craig McGowan ,  Abdellah Tahri ,  Dominique Louis Nestor Ghislain Surleraux

发明人： Kenneth Alan Simmen ,  Herman Augustinus De Kock ,  Pierre Jean-Marie Bernard Raboisson ,  Sandrine Marie Helene Vendeville ,  Lili Hu ,  Wim Van De Vreken ,  David Craig McGowan ,  Abdellah Tahri ,  Dominique Louis Nestor Ghislain Surleraux

IPC分类号： A61K31/47 ,  C07D245/00

CPC分类号： C07D487/04 ,  C07K5/06165

摘要： Inhibitors of HCV of formula (I) and the N-oxides, salts, and stereochemically isomeric forms thereof, wherein the terms R1, L, R2, R3, R4, and n have specific definitions; pharmaceutical compositions containing compounds of formula (I), and processes for preparing compounds of formula (I). Bioavailable combinations of the inhibitors of HCV of formula (I) with ritonavir are also provided.

摘要翻译： 式（I）的HCV抑制剂及其N-氧化物，盐和立体化学异构形式，其中术语R1，L，R2，R3，R4和n具有特定的定义; 含有式（I）化合物的药物组合物，以及制备式（I）化合物的方法。 还提供了式（I）的HCV抑制剂与利托那韦的生物可利用组合。

公开(公告)号：US20090281141A1

公开(公告)日：2009-11-12

申请号：US11995714

申请日：2006-07-28

申请人： Kenneth Alan Simmen ,  Herman Augustinus De Kock ,  Pierre Jean-Marie Bernard Raboisson ,  Sandrine Marie Helene Vendeville ,  Lili Hu ,  Abdellah Tahri ,  Dominique Louis nestor Ghislain Surleraux ,  Wim Van De Vreken ,  Ismet Dorange ,  Yvan Simonnet ,  Karl Magnus Nilsson ,  Bengt Bertil Samuelsson ,  Åsa Annica Kristina Rosenquist ,  Hans Kristian Wallberg

发明人： Kenneth Alan Simmen ,  Herman Augustinus De Kock ,  Pierre Jean-Marie Bernard Raboisson ,  Sandrine Marie Helene Vendeville ,  Lili Hu ,  Abdellah Tahri ,  Dominique Louis nestor Ghislain Surleraux ,  Wim Van De Vreken ,  Ismet Dorange ,  Yvan Simonnet ,  Karl Magnus Nilsson ,  Bengt Bertil Samuelsson ,  Åsa Annica Kristina Rosenquist ,  Hans Kristian Wallberg

IPC分类号： A61K31/4709 ,  C07D245/00 ,  A61P31/12

CPC分类号： C07D401/14 ,  C07D401/12 ,  C07D417/14 ,  C07D487/04 ,  C07K5/06191

摘要： Inhibitors of HCV replication of formula (I) and the N-oxides, salts, and stereoisomers thereof, wherein X is N, CH and where X bears a double bond it is C; R1 is —OR1, —NH—SO2R6; R2 is hydrogen, and where X is C or CH, R2 may also be C1-6alkyl; R3 is hydrogen, C1-6alkyl, C1-6alkoxyC1-6alkyl, or C3-7cycloalkyl; R4 is isoquinolinyl optionally substituted with one, two or three substituents each independently selected from C1-6alkyl, C1-6alkoxy, hydroxy, halo, polyhaloC1-6alkyl, polyhaloC1-6alkoxy, amino, mono- or diC1-6alkylamino, mono- or diC1-6alkylaminocarbonyl, C1-6alkylcarbonyl-amino, aryl, and Het; n is 3, 4, 5, or 6; each dashed line (represented by - - - - - ) represents an optional double bond; R5 is hydrogen; aryl; Het; C3-7cycloalkyl optionally substituted with C1-6alkyl; or C1-6alkyl optionally substituted with C3-7cycloalkyl, aryl or with Het; R6 is aryl; Het; C3-7cycloalkyl optionally substituted with C1-6alkyl; or C1-6alkyl optionally substituted with C3-7cycloalkyl, aryl or with Het; each aryl is phenyl optionally substituted with one, two or three substituents; and each Het is a 5 or 6 membered saturated, partially unsaturated or completely unsaturated heterocyclic ring containing 1 to 4 heteroatoms each independently selected from nitrogen, oxygen and sulfur, and being optionally substituted with one, two or three substituents; pharmaceutical compositions containing compounds (I) and processes for preparing compounds (I). Bioavailable combinations of the inhibitors of HCV of formula (I) with ritonavir are also provided.

摘要翻译： 式（I）的HCV复制抑制剂及其N-氧化物，盐和立体异构体，其中X为N，CH，X为双键时为C; R1为-OR1，-NH-SO2R6; R2是氢，并且其中X是C或CH，R2也可以是C1-6烷基; R 3是氢，C 1-6烷基，C 1-6烷氧基C 1-6烷基或C 3-7环烷基; R 4是任选被一个，两个或三个独立地选自C 1-6烷基，C 1-6烷氧基，羟基，卤素，多卤代C 1-6烷基，多卤代C 1-6烷氧基，氨基，单或二C 1-6烷基氨基，单或二-C 1-6烷基， C 1-6烷基氨基羰基，C 1-6烷基羰基 - 氨基，芳基和Het; n为3,4,5或6; 每个虚线（由 - - - - 表示）表示可选的双键; R5是氢; 芳基; Het; 任选被C 1-6烷基取代的C 3-7环烷基; 或任选被C 3-7环烷基，芳基或与Het取代的C 1-6烷基; R6是芳基; Het; 任选被C 1-6烷基取代的C 3-7环烷基; 或任选被C 3-7环烷基，芳基或与Het取代的C 1-6烷基; 每个芳基是任选被一个，两个或三个取代基取代的苯基; 并且每个Het是含有1至4个各自独立地选自氮，氧和硫的杂原子的5或6元饱和，部分不饱和或完全不饱和的杂环，并且任选地被一个，两个或三个取代基取代; 含有化合物（I）的药物组合物和制备化合物（I）的方法。 还提供了式（I）的HCV抑制剂与利托那韦的生物可利用组合。

公开(公告)号：US20090281140A1

公开(公告)日：2009-11-12

申请号：US11632102

申请日：2006-07-28

申请人： Kenneth Alan Simmen ,  Herman Augustinus De Kock ,  Pierre Jean-Marie Bernard Raboisson ,  Lili Hu ,  Abdellah Tahri ,  Dominique Louis Nestor Ghislain Surleraux ,  Karl Magnus Nilsson ,  Bengt Bertil Samuelson ,  Åsa Annica Kristina Rosenquist ,  Vladimir Ivanov ,  Michael Pelcman ,  Anna Karin Gertrud Linnea Belfrage ,  Per-Ola Mikael Johansson ,  Sandrine Marie Helene Vendeville

发明人： Kenneth Alan Simmen ,  Herman Augustinus De Kock ,  Pierre Jean-Marie Bernard Raboisson ,  Lili Hu ,  Abdellah Tahri ,  Dominique Louis Nestor Ghislain Surleraux ,  Karl Magnus Nilsson ,  Bengt Bertil Samuelson ,  Åsa Annica Kristina Rosenquist ,  Vladimir Ivanov ,  Michael Pelcman ,  Anna Karin Gertrud Linnea Belfrage ,  Per-Ola Mikael Johansson ,  Sandrine Marie Helene Vendeville

IPC分类号： A61K31/4709 ,  C07D245/00 ,  A61P31/12

CPC分类号： C07D487/04 ,  A61K31/427 ,  A61K31/4709 ,  A61K31/7056 ,  A61K38/05 ,  A61K38/212 ,  A61K45/06 ,  A61K47/60 ,  C07D245/04 ,  C07D277/56 ,  C07D401/14 ,  C07D417/04 ,  C07D417/14 ,  C07K5/06139 ,  Y02A50/385 ,  Y02A50/387 ,  Y02A50/389 ,  Y02A50/393

摘要： Inhibitors of HCV replication of formula (I) and the N-oxides, salts, and stereoisomers, wherein each dashed line represents an optional double bond; X is N, CH and where X bears a double bond it is C; R1 is —OR7, —NH—SO2R8; R2 is hydrogen, and where X is C or CH, R2 may also be C1-6alkyl; R3 is hydrogen, C1-6alkyl, C1-6alkoxyC1-6alkyl, C3-7cycloalkyl; R4 is aryl or Het; n is 3, 4, 5, or 6; R5 is halo, C1-6alkyl, hydroxy, C1-6alkoxy, phenyl, or Het; R6 is C1-6alkoxy, or dimethylamino; R7 is hydrogen; aryl; Het; C3-7cycloalkyl optionally substituted with C1-6alkyl; or C1-6alkyl optionally substituted with C3-7cycloalkyl, aryl or with Het; R8 is aryl; Het; C3-7cycloalkyl optionally substituted with C1-6alkyl; or C1-6alkyl optionally substituted with C3-7cycloalkyl, aryl or with Het; aryl is phenyl optionally substituted with one, two or three substituents; Het is a 5 or 6 membered saturated, partially unsaturated or completely unsaturated heterocyclic ring containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and being optionally substituted with one, two or three substituents; pharmaceutical compositions containing compounds (I) and processes for preparing compounds (I). Bioavailable combinations of the inhibitors of HCV of formula (I) with ritonavir are also provided.

摘要翻译： 式（I）的HCV复制抑制剂和N-氧化物，盐和立体异构体，其中每个虚线表示任选的双键; X为N，CH，X为双键，C为C; R1是-OR7，-NH-SO2R8; R2是氢，并且其中X是C或CH，R2也可以是C1-6烷基; R 3是氢，C 1-6烷基，C 1-6烷氧基C 1-6烷基，C 3-7环烷基; R4是芳基或Het; n为3,4,5或6; R 5为卤素，C 1-6烷基，羟基，C 1-6烷氧基，苯基或Het; R6是C1-6烷氧基或二甲基氨基; R7是氢; 芳基; Het; 任选被C 1-6烷基取代的C 3-7环烷基; 或任选被C 3-7环烷基，芳基或与Het取代的C 1-6烷基; R8是芳基; Het; 任选被C 1-6烷基取代的C 3-7环烷基; 或任选被C 3-7环烷基，芳基或与Het取代的C 1-6烷基; 芳基是任选被一个，两个或三个取代基取代的苯基; Het是含有1至4个选自氮，氧和硫的杂原子并且任选地被一个，两个或三个取代基取代的5或6元饱和，部分不饱和或完全不饱和的杂环。 含有化合物（I）的药物组合物和制备化合物（I）的方法。 还提供了式（I）的HCV抑制剂与利托那韦的生物可利用组合。

公开(公告)号：US08349869B2

公开(公告)日：2013-01-08

申请号：US13412997

申请日：2012-03-06

申请人： Kenneth Alan Simmen ,  Herman Augustinus De Kock ,  Pierre Jean-Marie Bernard Raboisson ,  Lili Hu ,  Abdellah Tahri ,  Dominique Louis Nestor Ghislain Surleraux ,  Karl Magnus Nilsson ,  Bengt Bertil Samuelsson ,  Åsa Annica Kristina Rosenquist ,  Vladimir Ivanov ,  Mikael Pelcman ,  Anna Karin Gertrud Linea Belfrage ,  Per-Ola Mikael Johansson ,  Sandrine Marie Helene Vendeville

发明人： Kenneth Alan Simmen ,  Herman Augustinus De Kock ,  Pierre Jean-Marie Bernard Raboisson ,  Lili Hu ,  Abdellah Tahri ,  Dominique Louis Nestor Ghislain Surleraux ,  Karl Magnus Nilsson ,  Bengt Bertil Samuelsson ,  Åsa Annica Kristina Rosenquist ,  Vladimir Ivanov ,  Mikael Pelcman ,  Anna Karin Gertrud Linea Belfrage ,  Per-Ola Mikael Johansson ,  Sandrine Marie Helene Vendeville

IPC分类号： C07D487/04 ,  A61K31/33 ,  A61P31/14

CPC分类号： C07D487/04 ,  A61K31/427 ,  A61K31/4709 ,  A61K31/7056 ,  A61K38/05 ,  A61K38/212 ,  A61K45/06 ,  A61K47/60 ,  C07D245/04 ,  C07D277/56 ,  C07D401/14 ,  C07D417/04 ,  C07D417/14 ,  C07K5/06139 ,  Y02A50/385 ,  Y02A50/387 ,  Y02A50/389 ,  Y02A50/393

摘要： Inhibitors of HCV replication of formula (I) and the N-oxides, salts, and stereoisomers, wherein each dashed line represents an optional double bond; X is N, CH and where X bears a double bond it is C; R1 is —OR7, —NH—SO2R8; R2 is hydrogen, and where X is C or CH, R2 may also be C1-6alkyl; R3 is hydrogen, C1-6alkyl, C1-6alkoxyC1-6alkyl, C3-7cycloalkyl; R4 is aryl or Het; n is 3, 4, 5, or 6; R5 is halo, C1-6alkyl, hydroxy, C1-6alkoxy, phenyl, or Het; R6 is C1-6alkoxy, or dimethylamino; R7 is hydrogen; aryl; Het; C3-7cycloalkyl optionally substituted with C1-6alkyl; or C1-6alkyl optionally substituted with C3-7cycloalkyl, aryl or with Het; R8 is aryl; Het; C3-7cycloalkyl optionally substituted with C1-6alkyl; or C1-6alkyl optionally substituted with C3-7cycloalkyl, aryl or with Het; aryl is phenyl optionally substituted with one, two or three substituents; Het is a 5 or 6 membered saturated, partially unsaturated or completely unsaturated heterocyclic ring containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and being optionally substituted with one, two or three substituents; pharmaceutical compositions containing compounds (I) and processes for preparing compounds (I). Bioavailable combinations of the inhibitors of HCV of formula (I) with ritonavir are also provided.

摘要翻译： 式（I）的HCV复制抑制剂和N-氧化物，盐和立体异构体，其中每个虚线表示任选的双键; X为N，CH，X为双键，C为C; R1是-OR7，-NH-SO2R8; R2是氢，并且其中X是C或CH，R2也可以是C1-6烷基; R 3是氢，C 1-6烷基，C 1-6烷氧基C 1-6烷基，C 3-7环烷基; R4是芳基或Het; n为3,4,5或6; R 5为卤素，C 1-6烷基，羟基，C 1-6烷氧基，苯基或Het; R6是C1-6烷氧基或二甲基氨基; R7是氢; 芳基; Het; 任选被C 1-6烷基取代的C 3-7环烷基; 或任选被C 3-7环烷基，芳基或与Het取代的C 1-6烷基; R8是芳基; Het; 任选被C 1-6烷基取代的C 3-7环烷基; 或任选被C 3-7环烷基，芳基或与Het取代的C 1-6烷基; 芳基是任选被一个，两个或三个取代基取代的苯基; Het是含有1至4个选自氮，氧和硫的杂原子并且任选地被一个，两个或三个取代基取代的5或6元饱和，部分不饱和或完全不饱和的杂环。 含有化合物（I）的药物组合物和制备化合物（I）的方法。 还提供了式（I）的HCV抑制剂与利托那韦的生物可利用组合。