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1. 发明申请

US20050267156A1 Broadspectrum 2-amino-benzothiazole sulfonamide hiv protease inhibitors 审中-公开
标题翻译： Broadspectrum 2-氨基 - 苯并噻唑磺酰胺hiv蛋白酶抑制剂
公开(公告)号：US20050267156A1
公开(公告)日：2005-12-01
申请号：US10523445
申请日：2003-08-04
申请人： Dominique Louis Surleraux , Piet Tom Wigerinck , Daniel Getman
发明人： Dominique Louis Surleraux , Piet Tom Wigerinck , Daniel Getman
IPC分类号： A61K31/425 , A61K31/428 , A61K31/4439 , A61P31/18 , C07D277/82 , C07D417/12 , C07D493/04
CPC分类号： C07D417/12 , A61K31/425 , C07D277/82 , C07D493/04
摘要： The present invention relates to the use of 2-amino-benzothiazoles, having the formula wherein R1 is hexahydrofuro[2,3-b]furanyl, tetrahydrofuranyl, oxazolyl, thiazolyl, pyridinyl, or phenyl optionally substituted with one or more substituents independently selected from C1-6alkyl, hydroxy, amino, halogen, aminoC1-4alkyl and mono- or di(C1-4alkyl)amino; R2 is hydrogen or C1-6alkyl; L is a direct bond, —O—, C1-6alkanediyl-O— or —O—C1-6alkanediyl; R3 is phenylC1-4alkyl; R4 is C1-6alkyl; R5 is hydrogen or C1-6alkyl; R6 is hydrogen or C1-6alkyl; in the manufacture of a medicament useful for inhibiting mutant HIV protease in a mammal infected with said mutant HIV protease. It also relates to novel compounds of formula (I).
摘要翻译：本发明涉及2-氨基 - 苯并噻唑的用途，其具有下式：其中R 1是六氢呋喃并[2,3-b]呋喃基，四氢呋喃基，恶唑基，噻唑基，吡啶基或任选取代的苯基其中一个或多个取代基独立地选自C 1-6烷基，羟基，氨基，卤素，氨基C 1-4烷基和单或二（C 1） -4个烷基）氨基; R 2是氢或C 1-6烷基; L是直链，-O - ， - C 1-6烷二基-O-或-O-C 1-6烷二基; R 3是苯基C 1-4烷基; R 4是C 1-6烷基; R 5是氢或C 1-6烷基; R 6是氢或C 1-6烷基; 在制备用于抑制感染了所述突变HIV蛋白酶的哺乳动物中的突变HIV蛋白酶的药物中。它还涉及新的式（I）化合物。

2. 发明申请

US20070213320A1 4-SUBSTITUTED-1,5-DIHYDRO-PYRIDO[3,2-B]INDOL-2-ONES 失效
公开(公告)号：US20070213320A1
公开(公告)日：2007-09-13
申请号：US11569108
申请日：2005-05-17
申请人： Bart Kesteleyn , Wim Van De Vreken , Dominique Louis Surleraux , Sandrine Vendeville , Pierre Jean-Marie Raboisson , Piet Tom Wigerinck , Annick Peeters
发明人： Bart Kesteleyn , Wim Van De Vreken , Dominique Louis Surleraux , Sandrine Vendeville , Pierre Jean-Marie Raboisson , Piet Tom Wigerinck , Annick Peeters
IPC分类号： A61K31/55 , A61K31/541 , A61K31/5377 , A61K31/506 , A61K31/501 , A61K31/497 , A61K31/496 , A61K31/4745 , C07D498/02 , C07D491/02 , C07D471/02
CPC分类号： C07D471/04 , C07D491/04 , C07D491/14
摘要： 4-substituted 1,5-dihydro-pyrido[3,2-b]indol-2-ones of formula (I): the N-oxides, salts, stereoisomeric forms, racemic mixtures, prodrugs, esters and metabolites thereof, wherein n is 1, 2 or 3; R1 is hydrogen, cyano, halo, substituted carbonyl, methanimidamidyl, N-hydroxy-methanimidamidyl, mono- or di(C1-4alkyl)methanimidamidyl, Het1 or Het2; X is NR2, O, S, SO, SO2; R2 is hydrogen, C1-10alkyl, C2-10alkenyl, C3-7cycloalkyl, which are optionally substituted; R2 is aryl substituted with —COOR4; or R2 is: —CpH2p—CH(OR14)—CqH2q—R15 (b-3); —CH2—CH2—(O—CH2—CH2)m—OR14 (b-4); —CH2—CH2—(O—CH2—CH2)m—NR5aR5b (b-5); -a1=a2-a3=a4- is —CH═CH—CH═CH—; —N═CH—CH═CH—; —CH═N—CH═CH—; —CH═CH—N═CH—; —CH═CH—CH═N—; wherein hydrogen atoms in (c-1)-(c-5) may be replaced by certain radicals; R3 is optionally substituted phenyl or a monocyclic or bicyclic aromatic heterocyclic ring system that can be substituted; R21 is halo, hydroxy, amino, carboxyl, C1-6alkyl, C3-7cycloalkyl, arylC1-6alkyl, formyl, C1-6alkylcarbonyl, C1-6alkyloxycarbonyl, C1-6alkylcarbonyloxy, —C(═O)—NR13R14; C1-6alkyloxy, arylC1-6alkyloxy, polyhaloC1-6alkyloxy, amino, mono or di(C1-6alkyl)amino, formylamino, C1-6alkylcarbonylamino, C1-6alkylsulfonylamino, mercapto, C1-6alkylthio, arylthio, aryloxy, arylC1-6alkylthio, C1-6alkylsulfynyl, C1-6alkylsulfonyl, aryl, arylamino, Het1, Het2.

3. 发明申请

US20070238727A1 5-Substituted 1-Phenyl-1,5-Dihydro-Pyrido[3,2-B]Indol-2-Ones and Analogs as Anti-Virals 审中-公开
公开(公告)号：US20070238727A1
公开(公告)日：2007-10-11
申请号：US11568838
申请日：2005-05-17
申请人： Bart Kesteleyn , Maxime Francis Canard , Wim Van De Vreken , Pierre Jean-Marie Raboisson , Dominique Louis Surleraux , Piet Tom Wigerinck
发明人： Bart Kesteleyn , Maxime Francis Canard , Wim Van De Vreken , Pierre Jean-Marie Raboisson , Dominique Louis Surleraux , Piet Tom Wigerinck
IPC分类号： A61K31/4355 , A61K31/496 , A61K31/5377 , A61K31/541 , A61P31/12 , C07D401/14 , C07D413/14 , C07D417/14 , C07D491/044
CPC分类号： C07D471/04
摘要： Compounds of formula (I) the N-oxides, salts, stereoisomeric forms, prodrugs, esters and metabolites thereof, wherein X is NR2, O, S, SO, SO2; R1 is hydrogen, cyano, halo, a carbonyl derivative, methanimidamidyl, N-hydroxy-methanimidamidyl, mono- or di(C1-4alkyl)-methanimidamidyl, Het1 or Het2; n is 1, 2 or 3; R2 is (i) aryl substituted with a radical —COOR4; (ii) C1-10alkyl, C2-10alkenyl, C3-7cycloalkyl, substituted with aryl which is substituted with a radical —COOR4; (iii) C1-10alkyl, C2-10alkenyl, C3-7cycloalkyl, substituted with —NR5a—C(═NR5b)—NR5cR5d, —O—NR5a—C(═NR5b)—NR5cR5d, -sulfonyl-R6, —NR7R8, —NR9R10, a radical (a-1), (a-2), (a-3), (a-4), (a-5); or (iv) a radical of formula: (a-6), (b-2), —CpH2p—CH(OR14)—CqH2q—R15; —CH2—CH2—(O—CH2—CH2)m—OR14; —CH2—CH2—(O—CH2—CH2)m—NR17aR17b; R3 is nitro, cyano, amino, halo, hydroxy, C1-4alkyloxy, a carbonyl derivative, methanimidamidyl, mono- or di(C1-4alkyl)methanimidamidyl, N-hydroxy-methanimidamidyl or Het1.

4. 发明申请

US20050171173A1 Broadspectrum substituted benzisoxazole sulfonamide hiv protease inhibitors 失效
公开(公告)号：US20050171173A1
公开(公告)日：2005-08-04
申请号：US10514539
申请日：2003-05-16
申请人： Dominique Louis Surleraux , Bernhard Joanna Vergouwen , Herman De Kock
发明人： Dominique Louis Surleraux , Bernhard Joanna Vergouwen , Herman De Kock
IPC分类号： A61K31/423 , A61K31/427 , A61P31/18 , A61P43/00 , C07D261/20 , C07D413/12 , C07D417/12 , C07D493/04 , A61K31/42
CPC分类号： C07D413/12 , C07D261/20 , C07D417/12 , 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 amino-C1-6alkyl; R6 is C1-6alkylO, Het1, Het1O, Het2, Het2O, aryl, arylO, C1-6alkyloxy-carbonylamino 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.

5. 发明申请

US20090203743A1 SMALL MOLECULE ENTRY INHIBITORS 有权
公开(公告)号：US20090203743A1
公开(公告)日：2009-08-13
申请号：US12430547
申请日：2009-04-27
申请人： Dominique Louis Surleraux , Piet Tom Wigernick , Markieke Christiane Voets , Sandrine Marie Vendeville , Herman Augustinus De Kock , Bernhard Joanna Vergouwen
发明人： Dominique Louis Surleraux , Piet Tom Wigernick , Markieke Christiane Voets , Sandrine Marie Vendeville , Herman Augustinus De Kock , Bernhard Joanna Vergouwen
IPC分类号： A61K31/4184 , C07D405/14 , C07D401/14 , A61K31/4439 , A61P31/18
CPC分类号： C07D401/12 , A61K31/415 , C07D235/30 , C07D235/32 , C07D405/12 , C07D413/12 , C07D417/12 , 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 amino-C1-6alkyl; R6 is C1-6alkylO, Het1, Het1O, Het2, Het2O, aryl, arylO, C1-6alkyloxy-carbonylamino 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′ R12 is H, —NH2, —NR5AR6, —C1-6alkyl or alkyl-W—R14, wherein said alkyl is optionally substituted with halogen, hydroxy, aryl, heteroaryl, Het1, Het2, or amino wherein said amino is optionally mono- or di-substituted with C1-4alkyl and R13 is H, C1-6-alkyl, optionally substituted by aryl, Het1, Het2, hydroxy, halogen, amino whereby the amino group may be optionally be mono- or di-substituted with C1-4alkyl.

6. 发明申请

US20070155716A1 HCV INHIBITING BI-CYCLIC PYRIMIDINES 有权
标题翻译： HCV抑制双循环嘧啶
公开(公告)号：US20070155716A1
公开(公告)日：2007-07-05
申请号：US11684288
申请日：2007-03-09
申请人： Kenneth SIMMEN , Tse-I Lin , Oliver Lenz , Dominique Louis Surleraux , Pierre Jean-Marie Raboisson
发明人： Kenneth SIMMEN , Tse-I Lin , Oliver Lenz , Dominique Louis Surleraux , Pierre Jean-Marie Raboisson
IPC分类号： A61K31/55 , A61K31/519 , A61K31/541 , A61K31/5377
CPC分类号： A61K31/517 , A61K31/519 , A61K31/52 , A61K31/53 , A61K31/5377 , Y02A50/385 , Y02A50/387
摘要： The present invention relates to the use of bi-cyclic pyrimidines as inhibitors of HCV replication as well as their use in pharmaceutical compositions aimed to treat or combat HCV infections. In addition, the present invention relates to processes for preparation of such pharmaceutical compositions. The present invention also concerns combinations of the present bi-cyclic pyrimidines with other anti-HCV agents.
摘要翻译：本发明涉及双环嘧啶作为HCV复制抑制剂的用途，以及它们在旨在治疗或对抗HCV感染的药物组合物中的用途。此外，本发明涉及这种药物组合物的制备方法。本发明还涉及本发明的双环嘧啶与其它抗HCV药物的组合。

7. 发明申请

US20090062311A1 MACROCYLIC INHIBITORS OF HEPATITIS C VIRUS 有权
标题翻译： HEPATITIS C病毒的大肠抑制剂
公开(公告)号：US20090062311A1
公开(公告)日：2009-03-05
申请号：US11995835
申请日：2008-01-16
申请人： Kenneth Alan Simmen , Herman Augustinus De Kock , Pierre Jean-Marie Raboisson , Lili Hu , Dominique Louis Surleraux , Karl Magnus Nilsson , Bengt Bertil Samuelsson , Asa Annica Kristina Rosenquist , Lourdes Salvador Oden
发明人： Kenneth Alan Simmen , Herman Augustinus De Kock , Pierre Jean-Marie Raboisson , Lili Hu , Dominique Louis Surleraux , Karl Magnus Nilsson , Bengt Bertil Samuelsson , Asa Annica Kristina Rosenquist , Lourdes Salvador Oden
IPC分类号： A61K31/517 , C07D255/04 , C07D245/04 , A61P31/12 , A61K31/4709
CPC分类号： C07D487/04 , C07D245/04 , C07K5/06139
摘要： Inhibitors of HCV replication of formula (I) and the N-oxides, salts, and stereoisomers thereof, wherein each dashed line represents an optional double bond; X is N, CH and where X bears a double bond it is C; R1a and R1b are hydrogen, C3-7cycloalkyl, aryl, Het, C1-6alkoxy, C1-6alkyl optionally substituted with halo, C1-6alkoxy, cyano, polyhaloC1-6alkoxy, C3-7cycloalkyl, aryl, or with Het; or R1a and R1b together with the nitrogen to which they are attached form a 4 to 6 membered heterocyclic ring which may be optionally substituted; L is a direct bond, —O—, —O—C1-4alkanediyl-, —O—CO—, —O—C(═O)—NR5a— or —O—C(═O)—NR5a—C1-4alkanediyl-; 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, amino, mono- or diC1-6alkylamino; R4 is aryl or a saturated, a partially unsaturated or completely unsaturated 5 or 6 membered monocyclic or 9 to 12 membered bicyclic heterocyclic ring system wherein said ring system contains one nitrogen, and optionally one to three additional heteroatoms selected from O, S and N, and wherein the remaining ring members are carbon atoms; wherein said ring system may be optionally substituted; n is 3, 4, 5, or 6; p is 1 or 2; aryl is phenyl, naphthyl, indanyl, or 1,2,3,4-tetrahydronaphthyl, each of which may be optionally substituted with one, two or three substituents; and Het is a 5 or 6 membered saturated, partially unsaturated or completely unsaturated heterocyclic ring containing 1 to 4 heteroatoms selected from N, O and S, being optionally condensed with a benzene ring, and wherein Het may be optionally substituted with one, two or three substituents; pharmaceutical compositions containing compounds (I) and processes for preparing compounds (I).
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，其中每个虚线表示任选的双键; X为N，CH，X为双键，为C; R 1a和R 1b是氢，C 3-7环烷基，芳基，Het，C 1-6烷氧基，任选被卤素，C 1-6烷氧基，氰基，多卤代C 1-6烷氧基，C 3-7环烷基，芳基或与Het取代的C 1-6烷基; 或R 1a和R 1b与它们所连接的氮一起形成可任选被取代的4至6元杂环; L是直接键，-O - ， - O-C 1-4烷二基 - ， - O-CO - ， - O-C（-O）-NR 5a - 或-O-C（-O）-NR 5a -C 1-4烷二基 - 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，氨基，单或二C 1-6烷基氨基; R4是芳基或饱和的，部分不饱和的或完全不饱和的5或6元单环或9至12元双环杂环体系，其中所述环体系含有一个氮，以及任选地一至三个选自O，S和N的杂原子，并且其中剩余的环成员是碳原子; 其中所述环系可以任选地被取代; n为3,4,5或6; p为1或2; 芳基是苯基，萘基，茚满基或1,2,3,4-四氢萘基，其各自可以任选地被一个，两个或三个取代基取代; 并且Het是含有1至4个选自N，O和S的杂原子的5或6元饱和的，部分不饱和的或完全不饱和的杂环，任选地与苯环稠合，并且其中Het可以任选被一个，两个或三个取代基; 含有化合物（I）的药物组合物和制备化合物（I）的方法。

8. 发明申请

US20070249655A1 4-Substituted-1,5-Dihydro-Pyrido[3,2-B]Indol-2-Ones 审中-公开
标题翻译： 4-取代的-1,5-二氢吡啶并[3,2-B]吲哚-2-基
公开(公告)号：US20070249655A1
公开(公告)日：2007-10-25
申请号：US11569111
申请日：2005-05-17
申请人： Bart Kesteleyn , Wim Van De Vreken , Natalie Kindermans , Maxime Francis Canard , Kurt Hertogs , Eva Bettens , Veronique De Vroey , Dirk Jochmans , Piet Wigerinck , Abdellah Tahri , Jing Wang , Dominique Louis Surleraux
发明人： Bart Kesteleyn , Wim Van De Vreken , Natalie Kindermans , Maxime Francis Canard , Kurt Hertogs , Eva Bettens , Veronique De Vroey , Dirk Jochmans , Piet Wigerinck , Abdellah Tahri , Jing Wang , Dominique Louis Surleraux
IPC分类号： A61K31/435 , A61K31/5377 , A61K31/7052 , A61P31/18
CPC分类号： A61K31/475 , A61K31/496 , A61K31/5377 , A61K2300/00
摘要： The present invention concerns combinations comprising a compound of formula (I) the N-oxides, salts, stereoisomeric forms, racemic mixtures, prodrugs, esters or metabolites thereof, wherein n is 1, 2 or 3; R1 is H, CN, halo, aminoC(═O), C(═O)OH, C1-4alkyloxyC(═O), C1-4alkylC(═O), mono- or di(C1-4alkyl)aminoC(═O), arylaminoC(═O), N-(aryl)-N-(C1-4alkyl)aminoC(═O), methanimidamidyl, N-hydroxy-methanimidamidyl, mono- or di(C1-4alkyl)methanimidamidyl, Het1 or Het2; R2 is H, C1-4alkyl, C2-10alkenyl, C3-7cycloalkyl, wherein said C1-10alkyl, C2-10alkenyl and C3-7cycloalkyl may be optionally substituted; R3 is nitro, cyano, amino, halo, hydroxy, C1-4alkyloxy, hydroxyC(═O), aminoC(═O), C1-4alkyloxyC(═O), mono- or di(C1-4alkyl)aminoC(═O), C1-4alkylC(═O), methanimidamidyl, mono- or di(C1-4alkyl)methanimidamidyl, N-hydroxy-methanimidamidyl or Het1; and another HIV inhibitor. The invention also concerns products comprising a compound of formula (I) and another HIV inhibitor, as a combined preparation for simultaneous, separate or sequential use in treatment of retroviral infections such as HIV infection, in particular, in the treatment of infections with multi-drug resistant retroviruses.
摘要翻译：本发明涉及包含式（I）化合物的N-氧化物，盐，立体异构形式，外消旋混合物，前药，酯或代谢物的组合，其中n为1,2或3; R 1是H，CN，卤素，氨基C（-O），C（-O）OH，C 1-4烷氧基C（-O），C 1-4烷基C（-O），单或二（C 1-4烷基）氨基C（-O），芳基氨基C（-O），N-（芳基）-N - （C 1-4烷基）氨基C（-O），甲亚氨基亚氨基，N-羟基 - 甲亚磺酰氨基，一或二（C 1-4烷基）甲酰胺基，Het 1 或Het 2 ; R 2是H，C 1-4烷基，C 2-10链烯基，C 3-7环烷基，其中所述C 1-10烷基，C 2-10链烯基和C 3-7环烷基可以是任选取代的; R 3是硝基，氰基，氨基，卤素，羟基，C 1-4烷氧基，羟基C（-O），氨基C（-O），C 1 -4烷氧基C（-O），单 - 或二（C 1-4烷基）氨基C（-O），C 1-4烷基C（ - 甲氧基亚氨基甲酰胺基或甲基亚氨基甲酰胺基，甲基亚氨基甲酰胺基或甲基亚氨基甲酰胺基; 和另一种HIV抑制剂。本发明还涉及包含式（I）化合物和另一种HIV抑制剂的产品，作为用于同时，分别或顺序用于治疗逆转录病毒感染如HIV感染的组合制剂，特别是用于治疗多发性感染的感染，耐药性逆转录病毒

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