(4R)-3-[(2S,3S)-3-[[2-[4-[(2-aminoacetyl)amino]-2,6-dimethylphenoxy]acetyl]amino]-2-hydroxy-4-phenylbutanoyl]-N-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]-5,5-dimethyl-1,3-thiazolidine-4-carboxamide | 1595091-77-2

• 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: (4R)-3-[(2S,3S)-3-[[2-[4-[(2-aminoacetyl)amino]-2,6-dimethylphenoxy]acetyl]amino]-2-hydroxy-4-phenylbutanoyl]-N-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]-5,5-dimethyl-1,3-thiazolidine-4-carboxamide
• CAS: 1595091-77-2
• 化学式: C₃₇H₄₅N₅O₇S
• 分子量: 703.86
• InChiKey: ZUISNNULZKLLCT-JBSLAQFFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  50
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  209
• 氢给体数：
  6
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  (R)-N-[(1S,2R)-2-hydroxyindan-1-yl]-3-[(2S,3S)-3-((4-amino-2,6-dimethylphenoxyacetyl)amino)-2-hydroxy-4-phenylbutanoyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxamide hydrochloride 在 盐酸 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 苯甲醚 、 三乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 (4R)-3-[(2S,3S)-3-[[2-[4-[(2-aminoacetyl)amino]-2,6-dimethylphenoxy]acetyl]amino]-2-hydroxy-4-phenylbutanoyl]-N-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]-5,5-dimethyl-1,3-thiazolidine-4-carboxamide
  参考文献：
  名称：

  Optimization of plasmepsin inhibitor by focusing on similar structural feature with chloroquine to avoid drug-resistant mechanism of Plasmodium falciparum

  摘要：

  The plasmepsins are specific aspartic proteases of the malaria parasite and a potential target for developing new antimalarial agents. Our previously reported peptidomimetic plasmepsin inhibitor with modified 2-aminoethylamino substituent, KNI-10740, was tested against chloroquine sensitive Plasmodium falciparum, D6, to be highly potent, however, the inhibitor exhibited about 5 times less activity against multi-drug resistant parasite (TM91C235). We hypothesized the potency reduction resulted from structural similarity between 2-aminoethylamino substituent of KNI-10740 and chloroquine. Then, we modified the moiety and finally identified compound 15d (KNI-10823), that could avoid drug-resistant mechanism of TM91C235 strain. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.02.051