KNI-1976 | 1029146-57-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: KNI-1976
• 英文别名: (R)-N-(2-methylbenzyl)-3-[(2S,3S)-3-((2S)-2-acetylamino-3-(benzylthio)propanoyl)amino-2-hydroxy-4-phenylbutanoyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxamide；(4R)-3-[(2S,3S)-3-[[(2S)-2-acetamido-3-benzylsulfanylpropanoyl]amino]-2-hydroxy-4-phenylbutanoyl]-5,5-dimethyl-N-[(2-methylphenyl)methyl]-1,3-thiazolidine-4-carboxamide
• CAS: 1029146-57-3
• 化学式: C₃₆H₄₄N₄O₅S₂
• 分子量: 676.901
• InChiKey: MZMAOWBMFRRUOG-MLMSKLGMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  47
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  178
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  、 乙酸酐 在 N-甲基吗啉 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 KNI-1976
  参考文献：
  名称：

  Combination of Non-natural d-Amino Acid Derivatives and Allophenylnorstatine−Dimethylthioproline Scaffold in HIV Protease Inhibitors Have High Efficacy in Mutant HIV

  摘要：

  Several non-natural D-amino acid derivatives were introduced as P(2)/P(3) residues in allophenylnorstatine-containing (Apns; (2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid) HIV protease inhibitors. The synthetic analogues exhibited potent inhibitory activity against HIV-1 protease enzyme and HIV-1 replication in MT-4 cells. Structure-activity relationships revealed that D-cysteine or serine derivatives contributed to highly potent anti-HIV activities. Interestingly, anti-HIV activity of all the D-amino acid-introduced inhibitors was remarkably enhanced in their anti-HIV activities against a Nelfinavir-resistant clone, which has a D30N mutation in the protease, over that of the wild-type strain. HIV inhibitory activity of several analogues was moderately affected by an inclusion of alpha(1)-acid glycoprotein in the test medium.

  DOI：

  10.1021/jm701555p