[(1S,2R)-2-hydroxy-3-[(2-methylpropyl)amino]-1-(phenylmethyl)propyl]carbamic acid (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl ester | 664344-42-7

• 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)-2-hydroxy-3-[(2-methylpropyl)amino]-1-(phenylmethyl)propyl]carbamic acid (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl ester
• 英文别名: (1-benzyl-2-hydroxy-3-isobutylamino-propyl)-carbamic acid hexahydro-furo[2,3-b]furan-3-yl ester；(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl N-[(1S,2R)-1-benzyl-3-isobutylamino-2-hydroxypropyl]carbamate；(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl ((2S,3R)-3-hydroxy-4-(isobutylamino)-1-phenylbutan-2-yl)carbamate；[(3aS,4R,6aR)-2,3,3a,4,5,6a-hexahydrofuro[2,3-b]furan-4-yl] N-[(2S,3R)-3-hydroxy-4-(2-methylpropylamino)-1-phenylbutan-2-yl]carbamate
• CAS: 664344-42-7
• 化学式: C₂₁H₃₂N₂O₅
• 分子量: 392.495
• InChiKey: MPNCFAAXPSBGDJ-UHZRXMQZSA-N

物化性质

• 沸点：
  580.5±50.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  28
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  89
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [(1S,2R)-2-hydroxy-3-[(2-methylpropyl)amino]-1-(phenylmethyl)propyl]carbamic acid (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl ester 在 碳酸氢钠 、 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 23.0h， 生成 [(3aS,4R,6aR)-2,3,3a,4,5,6a-hexahydrofuro[2,3-b]furan-4-yl] N-[(2S,3R)-4-[[3-[(2,2-dimethylpropylamino)methylidene]-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 、 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)-2-hydroxy-3-[(2-methylpropyl)amino]-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

• [EN] PROCESS FOR THE PREPARATION OF DARUNAVIR AND DARUNAVIR INTERMEDIATES<br/>[FR] PROCÉDÉ POUR LA PRÉPARATION DE DARUNAVIR ET D'INTERMÉDIAIRES DE DARUNAVIR
  申请人：MAPI PHARMA HK LTD

  公开号：WO2011092687A1

  公开（公告）日：2011-08-04

  The present invention relates to a process for the preparation of darunavir, a nonpeptide protease inhibitor (PI), useful for the treatment of HIV/AIDS patients harboring multidrug-resistant HIV-1 variants that do not respond to previously existing HAART regimens. The present invention further relates to processes for the stereo-directed preparation of darunavir intermediates, in particular (3R,3aS,6aR)-hexahydrofuro [2,3-b] furan-3-ol and to certain novel intermediates obtained by such processes.

  本发明涉及一种用于制备达芦那韦的方法，达芦那韦是一种非肽类蛋白酶抑制剂（PI），用于治疗患有多药耐药HIV-1变异株的HIV/AIDS患者，这些变异株对先前存在的HAART方案没有反应。本发明还涉及用于立体定向制备达芦那韦中间体的方法，特别是(3R,3aS,6aR)-六氢呋喃[2,3-b]呋喃-3-醇，以及通过这些方法获得的某些新型中间体。
• Resistance-repellent retroviral protease inhibitors
  申请人：Eissenstat Michael

  公开号：US20050267074A1

  公开（公告）日：2005-12-01

  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来治疗哺乳动物HIV感染的方法。
• [EN] 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<br/>[FR] PROCÉDÉ DE PRÉPARATION DU COMPOSÉ (3R,3AS,6AR)-HEXAHYDROFURO[2,3-B]FURAN-3-YL(1S,2R)-3-[[(4-AMINOPHÉNYL) SULFONYL](ISOBUTYL)AMINO]-1-BENZYL-2-HYDROXYPROPYLCARBAMATE
  申请人：TIBOTEC PHARM LTD

  公开号：WO2010023322A1

  公开（公告）日：2010-03-04

  The present invention relates to a process for the preparation of (3R,3a S,6aR)-hexa-hydrofuro [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,3a S,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.

  本发明涉及一种制备(3R,3a S,6aR)-六氢呋喃[2,3-b]呋喃-3-基(1S,2R)-3-[[（4-氨基苯基）磺酰](异丁基)氨基]-1-苄基-2-羟基丙基氨基甲酸酯的方法，以及用于该方法的新型中间体。(3R,3a S,6aR)-六氢呋喃[2,3-b]呋喃-3-基(1S,2R)-3-[[（4-氨基苯基）磺酰](异丁基)氨基]-1-苄基-2-羟基丙基氨基甲酸酯特别适用作为HIV蛋白酶抑制剂。
• PROCESS FOR THE PREPARATION OF DARUNAVIR AND DARUNAVIR INTERMEDIATES
  申请人：Mizhiritskii Michael

  公开号：US20120296101A1

  公开（公告）日：2012-11-22

  The present invention relates to a process for the preparation of darunavir, a nonpeptide protease inhibitor (PI), useful for the treatment of HIV/AIDS patients harboring multidrug-resistant HIV-1 variants that do not respond to previously existing HAART regimens. The present invention further relates to processes for the stereo-directed preparation of darunavir intermediates, in particular (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol and to certain novel intermediates obtained by such processes.

  本发明涉及一种制备达芦那韦的方法，达芦那韦是一种非肽类蛋白酶抑制剂（PI），用于治疗携带多药耐药HIV-1变异体且不对先前存在的HAART方案产生反应的HIV/AIDS患者。本发明还涉及一种立体定向制备达芦那韦中间体的方法，特别是（3R，3aS，6aR）-六氢呋喃[2,3-b]呋喃-3-醇，以及通过这些方法获得的某些新型中间体。
• Substituted Aminophenylsulfonamide Compounds as Hiv Protease Inhibitor
  申请人：De Kock Herman Augustinus

  公开号：US20080269322A1

  公开（公告）日：2008-10-30

  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.

  本发明涉及取代氨基苯磺酰胺化合物，其作为蛋白酶抑制剂的用途，特别是作为广谱HIV蛋白酶抑制剂的用途，以及它们的制备过程、包含它们的制药组合物和诊断试剂盒。本发明还涉及将本发明的取代氨基苯磺酰胺化合物与另一种抗逆转录病毒药物组合使用。此外，本发明还涉及其作为参考化合物或试剂在测定中的使用。