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：US08084494B2

公开(公告)日：2011-12-27

申请号：US12094799

申请日：2006-11-28

申请人： Herman Augustinus De Kock ,  Tim Hugo Maria Jonckers ,  Stefaan Julien Last ,  Paul Jozef Gabriel Maria Boonants ,  Dominique Louis Nestor Ghislain Surleraux ,  Piet Tom Bert Paul Wigerinck

发明人： Herman Augustinus De Kock ,  Tim Hugo Maria Jonckers ,  Stefaan Julien Last ,  Paul Jozef Gabriel Maria Boonants ,  Dominique Louis Nestor Ghislain Surleraux ,  Piet Tom Bert Paul Wigerinck

IPC分类号： A61K31/343 ,  C07D493/04

CPC分类号： C07D493/04

摘要： The present invention concerns substituted aminophenylsulfonamide compounds, their use as protease inhibitors, in particular as broad-spectrum HIV protease inhibitors, processes for their preparation as well as pharmaceutical compositions and diagnostic kits comprising them. The present invention also concerns combinations of the present substituted aminophenylsulfonamide compounds with another anti-retroviral agent. It further relates to their use in assays as reference compounds or as reagents.

摘要翻译： 本发明涉及取代的氨基苯基磺酰胺化合物，它们作为蛋白酶抑制剂的用途，特别是广谱的HIV蛋白酶抑制剂，其制备方法以及包含它们的药物组合物和诊断试剂盒。 本发明还涉及本发明的取代氨基苯基磺酰胺化合物与另一种抗逆转录病毒剂的组合。 它还涉及它们在测定中作为参考化合物或作为试剂的用途。

公开(公告)号：US07968581B2

公开(公告)日：2011-06-28

申请号：US12557368

申请日：2009-09-10

申请人： François Nique ,  Catherine Jagerschmidt ,  Florence Sylvie Namour ,  Roland Blanqué ,  Jean-Michel Lefrançois ,  Christophe Peixoto ,  Pierre Deprez ,  Nicolas Triballeau ,  Piet Tom Bert Paul Wigerinck

发明人： François Nique ,  Catherine Jagerschmidt ,  Florence Sylvie Namour ,  Roland Blanqué ,  Jean-Michel Lefrançois ,  Christophe Peixoto ,  Pierre Deprez ,  Nicolas Triballeau ,  Piet Tom Bert Paul Wigerinck

IPC分类号： A61K31/4166 ,  C07D233/40 ,  A61P35/00

CPC分类号： C07D233/60 ,  C07D233/66

摘要： Novel compounds are disclosed that have a Formula represented by the following: wherein X, R1, R2a, R2b, R2c, R3a R3b, R4a, R4b, R4c, and m1 are as described herein. The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, cachexia, osteoporosis, sarcopenia, a decline in libido and/or sexual dysfunction.

摘要翻译： 公开了具有由下式表示的式的新化合物：其中X，R1，R2a，R2b，R2c，R3a R3b，R4a，R4b，R4c和m1如本文所述。 化合物可以制备成药物组合物，并且可以用于预防和治疗包括人在内的哺乳动物中的各种病症，包括非限制性实例，恶病质，骨质疏松症，肌肉减少症，性欲下降和/或 性功能障碍。

公开(公告)号：US07803836B2

公开(公告)日：2010-09-28

申请号：US12094697

申请日：2006-11-28

申请人： Herman Augustinus De Kock ,  Tim Hugo Maria Jonckers ,  Stefaan Julien Last ,  Paul Jozef Gabriel Maria Boonants ,  Dominique Louis Nestor Ghislain Surleraux ,  Piet Tom Bert Paul Wigerinck

发明人： Herman Augustinus De Kock ,  Tim Hugo Maria Jonckers ,  Stefaan Julien Last ,  Paul Jozef Gabriel Maria Boonants ,  Dominique Louis Nestor Ghislain Surleraux ,  Piet Tom Bert Paul Wigerinck

IPC分类号： C07D405/02 ,  A61K31/4025

CPC分类号： C07D493/04

摘要： The present invention concerns substituted aminophenylsulfonamide compounds and derivatives, their use as protease inhibitors, in particular as broadspectrum HIV protease inhibitors, processes for their preparation as well as pharmaceutical compositions and diagnostic kits comprising them. The present invention also concerns combinations of the present substituted aminophenylsulfonamide compounds and derivatives with another anti-retroviral agent. It further relates to their use in assays as reference compounds or as reagents.

摘要翻译： 本发明涉及取代的氨基苯基磺酰胺化合物及其衍生物，它们作为蛋白酶抑制剂的用途，特别是作为广谱的HIV蛋白酶抑制剂，其制备方法以及包含它们的药物组合物和诊断试剂盒。 本发明还涉及本发明的取代氨基苯基磺酰胺化合物和其衍生物与另一种抗逆转录病毒剂的组合。 它还涉及它们在测定中作为参考化合物或作为试剂的用途。

公开(公告)号：US07745432B2

公开(公告)日：2010-06-29

申请号：US12241317

申请日：2008-09-30

申请人： Abdellah Tahri ,  Lili Hu ,  Dominique Louis Nestor Ghislain Surleraux ,  Piet Tom Bert Paul Wigerinck

发明人： Abdellah Tahri ,  Lili Hu ,  Dominique Louis Nestor Ghislain Surleraux ,  Piet Tom Bert Paul Wigerinck

IPC分类号： A61K31/5386

CPC分类号： C07D498/04

摘要： The present invention relates to 5H-pyrazolo[1,5-c][1,3]benzoxazin-5-yl)phenyl methanone derivatives as inhibitors of the viral replication of the HIV virus, processes for their preparation as well as pharmaceutical compositions, their use as medicines, and diagnostic kits comprising them. The present invention also concerns combinations of the present HIV inhibitors with other anti-retroviral agents. It further relates to their use in assays as reference compounds or as reagents. The compounds of the present invention are useful for preventing or treating infection by HIV and for treating AIDS.

摘要翻译： 本发明涉及作为HIV病毒的病毒复制的抑制剂的5H-吡唑并[1,5-c] [1,3]苯并恶嗪-5-基）苯基甲酮衍生物，其制备方法以及药物组合物， 它们用作药物，以及包括它们的诊断试剂盒。 本发明还涉及本发明的HIV抑制剂与其它抗逆转录病毒剂的组合。 它还涉及它们在测定中作为参考化合物或作为试剂的用途。 本发明的化合物可用于预防或治疗HIV感染和治疗AIDS。

公开(公告)号：US20080214588A1

公开(公告)日：2008-09-04

申请号：US11814982

申请日：2006-03-02

申请人： Herman Augustinus De Kock ,  Piet Tom Bert Paul Wigerinck

发明人： Herman Augustinus De Kock ,  Piet Tom Bert Paul Wigerinck

IPC分类号： A61K31/513 ,  C07D239/48 ,  A61P31/18

CPC分类号： C07D239/48 ,  C07D405/12

摘要： HIV replication inhibitors of formula (I) pharmaceutically acceptable addition salts; or stereochemically isomeric forms thereof, wherein R1 is halo; R2 and R3 each independently are C1-6alkyl; pharmaceutical compositions containing these compounds as active ingredient and processes for preparing these compounds and compositions.

摘要翻译： 式（I）的HIV复制抑制剂药学上可接受的加成盐; 或其立体化学异构体形式，其中R 1是卤素; R 2和R 3各自独立地为C 1-6烷基; 含有这些化合物作为活性成分的药物组合物和制备这些化合物和组合物的方法。

公开(公告)号：US08518987B2

公开(公告)日：2013-08-27

申请号：US12536807

申请日：2009-08-06

申请人： Hans Wim Pieter Vermeersch ,  Daniel Joseph Christiaan Thone ,  Luc Donne Marie-Louise Janssens ,  Piet Tom Bert Paul Wigerinck

发明人： Hans Wim Pieter Vermeersch ,  Daniel Joseph Christiaan Thone ,  Luc Donne Marie-Louise Janssens ,  Piet Tom Bert Paul Wigerinck

IPC分类号： A61K31/353

CPC分类号： C07D493/04

摘要： New pseudopolymorphic forms of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-3-[[(4-aminophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropylcarbamate and processes for producing them are disclosed.

摘要翻译： （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- 公开了苄基-2-羟丙基氨基甲酸酯及其制备方法。

公开(公告)号：US08383608B2

公开(公告)日：2013-02-26

申请号：US13167682

申请日：2011-06-23

申请人： François Nique ,  Catherine Jagerschmidt ,  Florence Sylvie Namour ,  Roland Blanqué ,  Jean-Michel Lefrançois ,  Christophe Peixoto ,  Pierre Deprez ,  Nicolas Triballeau ,  Piet Tom Bert Paul Wigerinck

发明人： François Nique ,  Catherine Jagerschmidt ,  Florence Sylvie Namour ,  Roland Blanqué ,  Jean-Michel Lefrançois ,  Christophe Peixoto ,  Pierre Deprez ,  Nicolas Triballeau ,  Piet Tom Bert Paul Wigerinck

IPC分类号： A61K31/4166 ,  A61K31/675 ,  A61P15/00

CPC分类号： C07D233/60 ,  C07D233/66

摘要： Novel compounds are disclosed that have a Formula represented by the following: wherein X, R1, R2a, R2b, R2c, R3a R3b, R4a, R4b, R4c, and m1 are as described herein. The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, cachexia, osteoporosis, sarcopenia, a decline in libido and/or sexual dysfunction.

摘要翻译： 公开了具有由下式表示的式的新化合物：其中X，R1，R2a，R2b，R2c，R3a R3b，R4a，R4b，R4c和m1如本文所述。 化合物可以制备成药物组合物，并且可以用于预防和治疗包括人在内的哺乳动物中的各种病症，包括非限制性实例，恶病质，骨质疏松症，肌肉减少症，性欲下降和/或 性功能障碍。

公开(公告)号：US07772411B2

公开(公告)日：2010-08-10

申请号：US10596732

申请日：2004-12-23

申请人： Nicolaas Martha Felix Goyvaerts ,  Piet Tom Bert Paul Wigerinck ,  Hartmut Burghard Zinser ,  Birgit M. Ebert

发明人： Nicolaas Martha Felix Goyvaerts ,  Piet Tom Bert Paul Wigerinck ,  Hartmut Burghard Zinser ,  Birgit M. Ebert

IPC分类号： C07D493/04

CPC分类号： C07D493/02 ,  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 intermediates for use in said process. More in particular the invention relates to processes 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 which make use of 4-amino-N-((2R,3S)-3-amino-2-hydroxy-4-phenylbutyl)-N-(isobutyl)benzene sulfonamide intermediate, and to processes amenable to industrial scaling up. (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 HIV protease inhibitors.

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中间体。 更具体地，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] 使用4-氨基-N - （（2R，3S）-3-氨基-2-羟基-4-苯基丁基）-N-（异丁基）苯磺酰胺的（异丁基）氨基] -1-苄基-2-羟基丙基氨基甲酸叔丁酯 中间和适用于工业规模化的流程。 （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：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.