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.

公开(公告)号：US20050214744A1

公开(公告)日：2005-09-29

申请号：US10519436

申请日：2003-06-30

申请人： Hilde Azjin ,  Marie-Pierre De Bethune ,  Johan Henrika Vingerhoets

发明人： Hilde Azjin ,  Marie-Pierre De Bethune ,  Johan Henrika Vingerhoets

IPC分类号： C12Q1/70 ,  G01N33/48 ,  G01N33/50 ,  G06F19/00

CPC分类号： C12Q1/703

摘要： The present invention is directed to the field of nucleic acid diagnostics and the identification of base variation in target nucleic acid sequences. More particularly, the present invention relates to the use of such genotypic characterization of a target population of HIV and the subsequent association, i.e., correlation, of this information to phenotypic interpretation in order to correlate virus mutational profiles with drug resistance. The invention also relates to methods of utilizing the mutational profiles of the invention in drug development, i.e., drug design, drug modification, and therapy, treatment design, clinical management and diagnostic analysis.

摘要翻译： 本发明涉及核酸诊断领域和鉴定靶核酸序列的碱基变异。 更具体地，本发明涉及HIV的目标群体的这种基因型表征的使用以及随后的关联，即该信息与表型解释的相关性，以便将病毒突变特征与耐药性相关联。 本发明还涉及在药物开发中，即药物设计，药物改性和治疗，治疗设计，临床管理和诊断分析中利用本发明的突变特征的方法。

公开(公告)号：US20070269816A1

公开(公告)日：2007-11-22

申请号：US11613584

申请日：2006-12-20

申请人： Sandra Meyer ,  Hilde Azijn ,  Marie-Pierre De Bethune

发明人： Sandra Meyer ,  Hilde Azijn ,  Marie-Pierre De Bethune

IPC分类号： C12Q1/68 ,  G01N33/00

CPC分类号： C12Q1/37 ,  C12N9/506 ,  C12Q1/703 ,  C12Q2600/156 ,  G01N2500/00 ,  G06F19/18

摘要： The present invention is directed to the field of nucleic acid diagnostics and the identification of base variation in target nucleic acid sequences. More particularly, the present invention relates to the use of such genotypic characterization of a target population of HIV and the subsequent association, i.e., correlation, of this information to phenotypic interpretation in order to correlate virus mutational profiles with drug resistance. The invention also relates to methods of utilizing the mutational profiles of the invention in drug development, i.e., drug discovery, drug design, drug modification, and therapy, treatment design, clinical management and diagnostic analysis.

摘要翻译： 本发明涉及核酸诊断领域和鉴定靶核酸序列的碱基变异。 更具体地，本发明涉及HIV的目标群体的这种基因型表征的使用以及随后的关联，即该信息与表型解释的相关性，以便将病毒突变特征与耐药性相关联。 本发明还涉及在药物开发，即药物发现，药物设计，药物修饰和治疗，治疗设计，临床管理和诊断分析中利用本发明的突变特征的方法。

公开(公告)号：US20060166943A1

公开(公告)日：2006-07-27

申请号：US10514361

申请日：2003-05-13

申请人： Jens Van Roey ,  Marie-Pierre De Bethune ,  Paul Stoffels

发明人： Jens Van Roey ,  Marie-Pierre De Bethune ,  Paul Stoffels

IPC分类号： A61K31/655 ,  A61K31/53 ,  A61K31/506 ,  A61K31/505

CPC分类号： A61K31/505 ,  A61K9/0014 ,  A61K9/0034 ,  A61K9/0036 ,  A61K9/06 ,  A61K31/506 ,  A61K31/535 ,  A61K45/06 ,  A61K47/02 ,  A61K47/10 ,  A61K47/12 ,  A61K47/14 ,  A61K47/38

摘要： A present invention concerns the microbicidal activity of certain pyrimidine or triazine containing non-nucleoside reverse transcriptase inhibitors. The compounds of the present invention inhibit the systemic infection of a human being with HIV, in particular, the present compounds prevent sexual HIV transmission in humans.

摘要翻译： 本发明涉及含有非核苷逆转录酶抑制剂的某些嘧啶或三嗪的杀微生物活性。 本发明的化合物抑制HIV患者的全身感染，特别是本发明化合物可预防人的性HIV传播。

公开(公告)号：US20060025594A1

公开(公告)日：2006-02-02

申请号：US10507180

申请日：2003-03-11

申请人： Marie-Pierre De Bethune ,  Sandra De Meyer ,  Kurt Hertogs ,  Rong Lu ,  Lieve Michiels ,  Abdellah Tahri ,  Dong Xie ,  Michael Eissenstat

发明人： Marie-Pierre De Bethune ,  Sandra De Meyer ,  Kurt Hertogs ,  Rong Lu ,  Lieve Michiels ,  Abdellah Tahri ,  Dong Xie ,  Michael Eissenstat

IPC分类号： C07D213/24 ,  C07F7/02

CPC分类号： C07D209/48 ,  C07C229/58 ,  C07C233/55 ,  C07C233/81 ,  C07C235/24 ,  C07C235/56 ,  C07C237/42 ,  C07C255/57 ,  C07C311/21 ,  C07C311/29 ,  C07C311/46 ,  C07C317/14 ,  C07D209/76 ,  C07D213/82 ,  C07D295/26 ,  C07D307/68 ,  C07D333/38

摘要： The present invention concerns a compound having the formula (I) a N-oxide form, a stereochemical isomer, racemic mixture, salt, prodrug, ester or metabolite thereof. It further relates to 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 entry inhibitors with 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： 本发明涉及具有式（I）的N-氧化物形式的化合物，立体化学异构体，外消旋混合物，盐，前药，酯或代谢物。 它还涉及其制备方法以及药物组合物，它们作为药物的用途，以及包含它们的诊断试剂盒。 本发明还涉及本入口抑制剂与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：US20050239053A1

公开(公告)日：2005-10-27

申请号：US10518525

申请日：2003-06-30

申请人： Hilde Azijn ,  Marie-Pierre De Bethune ,  Johan Vingerhoets

发明人： Hilde Azijn ,  Marie-Pierre De Bethune ,  Johan Vingerhoets

IPC分类号： C12Q1/48 ,  C12Q1/70 ,  G01N33/48 ,  G01N33/50 ,  G06F19/00

CPC分类号： G01N33/48 ,  C12Q1/48 ,  C12Q1/703 ,  G01N2333/16 ,  G01N2333/91245 ,  G01N2333/9125 ,  G01N2500/04

摘要： The present invention is directed to the field of nucleic acid diagnostics and the identification of base variation in target nucleic acid sequences. More particularly, the present invention relates to the use of such genotypic characterization of a target population of HIV and the subsequent association, i.e., correlation, of this information to phenotypic interpretation in order to correlate virus mutational profiles with drug resistance. The invention also relates to methods of utilizing the mutational profiles of the invention in drug development, i.e., drug discovery, drug design, drug modification, and therapy, treatment design, clinical management and diagnostic analysis

摘要翻译： 本发明涉及核酸诊断领域和鉴定靶核酸序列的碱基变异。 更具体地，本发明涉及HIV的目标群体的这种基因型表征的使用以及随后的关联，即该信息与表型解释的相关性，以便将病毒突变特征与耐药性相关联。 本发明还涉及在药物开发中利用本发明的突变特征的方法，即药物发现，药物设计，药物修饰和治疗，治疗设计，临床管理和诊断分析

公开(公告)号：US20050233312A1

公开(公告)日：2005-10-20

申请号：US10519035

申请日：2003-06-30

申请人： Sandra De Meyer ,  Hilde Azijn ,  Marie-Pierre De Bethune

发明人： Sandra De Meyer ,  Hilde Azijn ,  Marie-Pierre De Bethune

IPC分类号： C12N9/50 ,  C12Q1/37 ,  C12Q1/68 ,  C12Q1/70 ,  G01N33/48 ,  G01N33/50 ,  G06F19/18 ,  G06F19/00

CPC分类号： C12Q1/37 ,  C12N9/506 ,  C12Q1/703 ,  C12Q2600/156 ,  G01N2500/00 ,  G06F19/18

摘要： The present invention is directed to the field of nucleic acid diagnostics and the identification of base variation in target nucleic acid sequences. More particularly, the present invention relates to the use of such genotypic characterization of a target population of HIV and the subsequent association, i.e., correlation, of this information to phenotypic interpretation in order to correlate virus mutational profiles with drug resistance. The invention also relates to methods of utilizing the mutational profiles of the invention in drug development, i.e., drug discovery, drug design, drug modification, and therapy, treatment design, clinical management and diagnostic analysis.

摘要翻译： 本发明涉及核酸诊断领域和鉴定靶核酸序列的碱基变异。 更具体地，本发明涉及HIV的目标群体的这种基因型表征的使用以及随后的关联，即该信息与表型解释的相关性，以便将病毒突变特征与耐药性相关联。 本发明还涉及在药物开发，即药物发现，药物设计，药物修饰和治疗，治疗设计，临床管理和诊断分析中利用本发明的突变特征的方法。

公开(公告)号：US20050158709A1

公开(公告)日：2005-07-21

申请号：US10504675

申请日：2003-02-21

申请人： Hilde Azijn ,  Piet Tom Wigerinck ,  Marie-Pierre De Bethune

发明人： Hilde Azijn ,  Piet Tom Wigerinck ,  Marie-Pierre De Bethune

IPC分类号： G01N33/50 ,  A61K45/00 ,  A61P31/18 ,  A61P43/00 ,  C12Q1/02 ,  C12Q1/18 ,  C12Q1/37 ,  C12Q1/70 ,  G01N33/15 ,  G01N33/569 ,  G01N33/68

CPC分类号： G01N33/56988 ,  C12Q1/025 ,  C12Q1/18 ,  C12Q1/37 ,  G01N33/68 ,  G01N2500/10

摘要： The present invention relates to methods for determining the influence of human plasma or serum protein binding on antiretroviral activity at physiologically achieved conditions, by using specific virus strains in a cell-based antiviral assay.

摘要翻译： 本发明涉及通过在基于细胞的抗病毒测定中使用特异性病毒株来确定人血浆或血清蛋白结合对生理实现条件下抗逆转录病毒活性的影响的方法。