2-(2-Pyrrolidin-1-yl-ethylamino)-benzothiazole-6-sulfonic acid ((2R,3S)-3-amino-2-hydroxy-4-phenyl-butyl)-isobutyl-amide | 473739-14-9

• 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: 2-(2-Pyrrolidin-1-yl-ethylamino)-benzothiazole-6-sulfonic acid ((2R,3S)-3-amino-2-hydroxy-4-phenyl-butyl)-isobutyl-amide
• CAS: 473739-14-9
• 化学式: C₂₇H₃₉N₅O₃S₂
• 分子量: 545.77
• InChiKey: CLKLFWDBFTYXBH-UKILVPOCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.38
• 重原子数：
  37.0
• 可旋转键数：
  13.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  111.79
• 氢给体数：
  3.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  2-(2-Pyrrolidin-1-yl-ethylamino)-benzothiazole-6-sulfonic acid ((2R,3S)-3-amino-2-hydroxy-4-phenyl-butyl)-isobutyl-amide 、 地瑞那韦中间体1 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以76%的产率得到(3R,3aS,6aR)-Hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(2-{[2-(1-pyrrolidinyl)ethyl]amino}-1,3-benzothiazol-6-yl)sulfonyl]amino}propylcarbamate
  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
• 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 4.5h， 生成 2-(2-Pyrrolidin-1-yl-ethylamino)-benzothiazole-6-sulfonic acid ((2R,3S)-3-amino-2-hydroxy-4-phenyl-butyl)-isobutyl-amide
  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