[(1S,2R)-3-[[(2,3-dihydro-2-oxo-1H-indol-5-yl)sulfonyl](2-methylpropyl)amino]-2-hydroxy-1-(phenylmethyl)propyl]carbamic acid (3R,3aS,6aR)-hexahydrofuro[2,3-b] furan-3-yl ester | 664344-17-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [(1S,2R)-3-[[(2,3-dihydro-2-oxo-1H-indol-5-yl)sulfonyl](2-methylpropyl)amino]-2-hydroxy-1-(phenylmethyl)propyl]carbamic acid (3R,3aS,6aR)-hexahydrofuro[2,3-b] furan-3-yl ester
• 英文别名: hexahydrofuro[2,3-b]furan-3-yl N-(1-benzyl-2-hydroxy-3-{isobutyl[(2-oxo-2,3-dihydro-1H-indol-5-yl)sulfonyl]amino}propyl} carbamate；{1-benzyl-2-hydroxy-3-[isobutyl-(2-oxo-2,3-dihydro-1H-indole-5-sulfonyl)-amino]-propyl}-carbamic acid hexahydro-furo[2,3-b]furan-3-yl ester；[(3aS,4R,6aR)-2,3,3a,4,5,6a-hexahydrofuro[2,3-b]furan-4-yl] N-[(2S,3R)-3-hydroxy-4-[2-methylpropyl-[(2-oxo-1,3-dihydroindol-5-yl)sulfonyl]amino]-1-phenylbutan-2-yl]carbamate
• CAS: 664344-17-6
• 化学式: C₂₉H₃₇N₃O₈S
• 分子量: 587.694
• InChiKey: NRIZDWOOHSSWFV-FKAUUQQGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  41
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  152
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  [(1S,2R)-3-[[(2,3-dihydro-2-oxo-1H-indol-5-yl)sulfonyl](2-methylpropyl)amino]-2-hydroxy-1-(phenylmethyl)propyl]carbamic acid (3R,3aS,6aR)-hexahydrofuro[2,3-b] furan-3-yl ester 在 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 [(3aS,4R,6aR)-2,3,3a,4,5,6a-hexahydrofuro[2,3-b]furan-4-yl] N-[(2S,3R)-4-[[3-(ethylaminomethylidene)-2-oxo-1H-indol-5-yl]sulfonyl-(2-methylpropyl)amino]-3-hydroxy-1-phenylbutan-2-yl]carbamate
  参考文献：
  名称：

  Enamino-oxindole HIV protease inhibitors

  摘要：

  We have designed and synthesized a series of HIV protease inhibitors (PIs) with enamino-oxindole substituents optimized to interact with the S2' subsite of the HIV protease binding pocket. Several of these inhibitors have sub-nanomolar K-i and antiviral IC50 in the low nM range against WT HIV and against a panel of multi-drug resistant (MDR) strains. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.05.120
• 作为产物：
  描述：

  [(1S,2R)-2-羟基-3-[(2-甲基丙基)氨基]-1-(苯基甲基)丙基]-1,1,-二甲基乙酯 在 盐酸 、 palladium 10% on activated carbon 、 氢气 、 碳酸氢钠 、 sodium carbonate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 4.0h， 生成 [(1S,2R)-3-[[(2,3-dihydro-2-oxo-1H-indol-5-yl)sulfonyl](2-methylpropyl)amino]-2-hydroxy-1-(phenylmethyl)propyl]carbamic acid (3R,3aS,6aR)-hexahydrofuro[2,3-b] furan-3-yl ester
  参考文献：
  名称：

  Enamino-oxindole HIV protease inhibitors

  摘要：

  We have designed and synthesized a series of HIV protease inhibitors (PIs) with enamino-oxindole substituents optimized to interact with the S2' subsite of the HIV protease binding pocket. Several of these inhibitors have sub-nanomolar K-i and antiviral IC50 in the low nM range against WT HIV and against a panel of multi-drug resistant (MDR) strains. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.05.120

文献信息

• Resistance-repellent retroviral protease inhibitors
  申请人：Eissenstat Michael

  公开号：US20050209301A1

  公开（公告）日：2005-09-22

  Resistance-repellent and multidrug resistant retroviral protease inhibitors are provided. Pharmaceutical composition comprising such compounds, and methods of using such compounds to treat HIV infections in mammals, are also provided.

  提供了抗药性和多药耐药性的逆转录病毒蛋白酶抑制剂。还提供了包含这些化合物的药物组合物，以及使用这些化合物治疗哺乳动物HIV感染的方法。
• [EN] BROADSPECTRUM SUBSTITUTED OXINDOLE SULFONAMIDE HIV PROTEASE INHIBITORS<br/>[FR] OXINDOLE SULFONAMIDES SUBSTITUES INHIBITEURS A LARGE SPECTRE DE LA PROTEASE DU VIH
  申请人：TIBOTEC PHARM LTD

  公开号：WO2004016619A1

  公开（公告）日：2004-02-26

  The present invention concerns the compounds having the formula (I) N-oxides, salts, stereoisomeric forms, racemic mixtures, prodrugs, esters and metabolites thereof, wherein R1 and R8 each are H, optionally substituted C 1-6alkyl, C2-6alkenyl, C3-7cycloalkyl, aryl, Het1, Het2; R1 may also be a radical of formula (R11aR11b)NC(R10a R10b)CR9-; t is 0, 1 or 2; R2 is H or C1-6alkyl; L is -C(=O)-, -O-C(=O)-, -NR8-C(=O)-, -O-C1-6 alkanediyl-C(=O)-, -NR8-C1-6alkanediyl-C(=O)-, -S(=O)2-, -O-S(=O)2-, -NR8-S(=0)2 ; R3 is C1-6alkyl, aryl, C3-7 cycloalkyl, C3-7cycloalkylC1-4 alkyl, 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; formula (II) is formula (III) or formula (IV) ; R5a and R5b is C2-6alkenyl, C2-6 alkynyl, C3-7cycloalkyl or C1-6alkyl, optionally substituted on one or more atoms; R5a and R5b may also be hydrogen, aryl, Het1, Het2; R6 is hydrogen or C1-6alkyl optionally substituted on one ore more carbon atoms. 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.

  本发明涉及具有以下式（I）的化合物：N-氧化物、盐、立体异构体形式、消旋混合物、前药、酯及其代谢物，其中R1和R8各自为H，可选择地取代的C1-6烷基，C2-6烯基，C3-7环烷基，芳基，Het1，Het2；R1也可以是式（R11aR11b）NC（R10a R10b）CR9-的基团；t为0、1或2；R2为H或C1-6烷基；L为-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-，-NR8-S（=0）2；R3为C1-6烷基，芳基，C3-7环烷基，C3-7环烷烷基，或芳基C1-4烷基；R4为H，C1-4烷基氧基（=O），羧基，氨基（=O），单烷基或二烷基氨基（=O），C3-7环烷基，C2-6烯基，C2-6炔基或可选择地取代的C1-6烷基；式（II）为式（III）或式（IV）；R5a和R5b为C2-6烯基，C2-6炔基，C3-7环烷基或C1-6烷基，可选择地取代一个或多个原子；R5a和R5b也可以是氢，芳基，Het1，Het2；R6为氢或C1-6烷基，可选择地取代一个或多个碳原子。它还涉及它们作为广谱HIV蛋白酶抑制剂的用途，以及它们的制备方法、包括它们的药物组合物和诊断试剂盒。它还涉及与另一种抗逆转录病毒药物的组合物，并将它们用作参考化合物或试剂在测定中的用途。
• Enamino-oxindole HIV protease inhibitors
  作者：Michael Eissenstat、Tanya Guerassina、Sergei Gulnik、Elena Afonina、Abelardo M. Silva、Douglas Ludtke、Hiroko Yokoe、Betty Yu、John Erickson

  DOI：10.1016/j.bmcl.2012.05.120

  日期：2012.8

  We have designed and synthesized a series of HIV protease inhibitors (PIs) with enamino-oxindole substituents optimized to interact with the S2' subsite of the HIV protease binding pocket. Several of these inhibitors have sub-nanomolar K-i and antiviral IC50 in the low nM range against WT HIV and against a panel of multi-drug resistant (MDR) strains. (C) 2012 Elsevier Ltd. All rights reserved.