(4R)-3-[(2S,3S)-3-[[2-[4-(2-chloroethylamino)-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 | 1595091-75-0

• 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-chloroethylamino)-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: 1595091-75-0
• 化学式: C₃₇H₄₅ClN₄O₆S
• 分子量: 709.307
• InChiKey: DYYCCBYHJPNEGJ-ZYOXRPPDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  49
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  166
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  氯乙醛 、 (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 、 sodium cyanoborohydride 作用下， 以 甲醇 、 乙腈 为溶剂， 生成 (4R)-3-[(2S,3S)-3-[[2-[4-(2-chloroethylamino)-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