{1-benzyl-2-hydroxy-3-[isobutyl-(2-methanesulfonyl-benzothiazole-6-sulfonyl)-amino]-propyl}-carbamic acid hexahydro-furo[2,3-b]furan-3-yl ester | 1000287-01-3

• 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: {1-benzyl-2-hydroxy-3-[isobutyl-(2-methanesulfonyl-benzothiazole-6-sulfonyl)-amino]-propyl}-carbamic acid hexahydro-furo[2,3-b]furan-3-yl ester
• 英文别名: [(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-methylsulfonyl-1,3-benzothiazol-6-yl)sulfonyl]amino]-1-phenylbutan-2-yl]carbamate
• CAS: 1000287-01-3
• 化学式: C₂₉H₃₇N₃O₉S₃
• 分子量: 667.825
• InChiKey: XCKFDBHXFVIHEF-HHJUPYMQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  44
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  206
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  {1-benzyl-2-hydroxy-3-[isobutyl-(2-methanesulfonyl-benzothiazole-6-sulfonyl)-amino]-propyl}-carbamic acid hexahydro-furo[2,3-b]furan-3-yl ester 、 1-cyclopentyl-piperidin-4-yl-ammonium chloride 在 sodium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 48.0h， 以39%的产率得到(1-benzyl-3-{[2-(1-cyclopentyl-piperidin-4-ylamino)-benzothiazole-6-sulfonyl]-isobutyl-amino}-2-hydroxy-propyl)-carbamic acid hexahydro-furo[2,3-b]furan-3-yl ester
  参考文献：
  名称：

  WO2007/147884

  摘要：

  公开号：
• 作为产物：
  描述：

  2-甲硫基苯并噻唑 在 氯磺酸 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 生成 {1-benzyl-2-hydroxy-3-[isobutyl-(2-methanesulfonyl-benzothiazole-6-sulfonyl)-amino]-propyl}-carbamic acid hexahydro-furo[2,3-b]furan-3-yl ester
  参考文献：
  名称：

  Design of HIV-1 Protease Inhibitors Active on Multidrug-Resistant Virus

  摘要：

  On the basis of structural data gathered during our ongoing HIV-1 protease inhibitors program, from which our clinical candidate TMC114 9 was selected, we have discovered new series of fused heteroaromatic sulfonamides. The further extension into the P2' region was aimed at identifying new classes of compounds with an improved broad spectrum activity and acceptable pharmacokinetic properties. Several of these compounds display an exceptional broad spectrum activity against a panel of highly cross-resistant mutants. Certain members of these series exhibit favorable pharmacokinetic profiles in rat and dog. Crystal structures and molecular modeling were used to rationalize the broad spectrum profile resulting from the extension into the P2' pocket of the HIV-1 protease.

  DOI：

  10.1021/jm049454n

文献信息

• 2-(SUBSTITUTED-AMINO)-BENZOTHIAZOLE SULFONAMIDE HIV PROTEASE INHIBITORS
  申请人：De Kock Herman

  公开号：US20090209583A1

  公开（公告）日：2009-08-20

  The present invention relates to 2-(substituted-amino)-benzothiazole sulfonamide compounds and derivatives, 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 2-(substituted-amino)-benzothiazole sulfonamide compounds and derivatives with another anti-retroviral agent. It further relates to their use in assays as reference compounds or as reagents.

  本发明涉及2-(取代氨基)-苯并噻唑磺酰胺化合物及其衍生物，它们的用途是蛋白酶抑制剂，特别是广谱HIV蛋白酶抑制剂，以及它们的制备方法、制药组合物和诊断试剂盒。本发明还涉及将本发明的2-(取代氨基)-苯并噻唑磺酰胺化合物和衍生物与另一种抗逆转录病毒药物组合使用。此外，本发明还涉及将其用作参考化合物或试剂的检测方法。
• US8202887B2
  申请人：——

  公开号：US8202887B2

  公开（公告）日：2012-06-19
• Design of HIV-1 Protease Inhibitors Active on Multidrug-Resistant Virus
  作者：Dominique L. N. G. Surleraux、Herman A. de Kock、Wim G. Verschueren、Geert M. E. Pille、Louis J. R. Maes、Anik Peeters、Sandrine Vendeville、Sandra De Meyer、Hilde Azijn、Rudi Pauwels、Marie-Pierre de Bethune、Nancy M. King、Moses Prabu-Jeyabalan、Celia A. Schiffer、Piet B. T. P. Wigerinck

  DOI：10.1021/jm049454n

  日期：2005.3.1

  On the basis of structural data gathered during our ongoing HIV-1 protease inhibitors program, from which our clinical candidate TMC114 9 was selected, we have discovered new series of fused heteroaromatic sulfonamides. The further extension into the P2' region was aimed at identifying new classes of compounds with an improved broad spectrum activity and acceptable pharmacokinetic properties. Several of these compounds display an exceptional broad spectrum activity against a panel of highly cross-resistant mutants. Certain members of these series exhibit favorable pharmacokinetic profiles in rat and dog. Crystal structures and molecular modeling were used to rationalize the broad spectrum profile resulting from the extension into the P2' pocket of the HIV-1 protease.
• WO2007/147884
  申请人：——

  公开号：——

  公开（公告）日：——