(R)-N-(2-methylbenzyl)-3-[(2S,3S)-3-amino-2-hydroxy-4-(3,4-methylenedioxyphenyl)butanoyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxamide | 500871-64-7

• 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: (R)-N-(2-methylbenzyl)-3-[(2S,3S)-3-amino-2-hydroxy-4-(3,4-methylenedioxyphenyl)butanoyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxamide
• 英文别名: (4R)-3-[(2S,3S)-3-amino-4-(1,3-benzodioxol-5-yl)-2-hydroxybutanoyl]-5,5-dimethyl-N-[(2-methylphenyl)methyl]-1,3-thiazolidine-4-carboxamide
• CAS: 500871-64-7
• 化学式: C₂₅H₃₁N₃O₅S
• 分子量: 485.604
• InChiKey: AEZCLMBHHGBEQV-YUXAGFNASA-N

物化性质

• 沸点：
  789.6±60.0 °C(Predicted)
• 密度：
  1.302±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  139
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (R)-N-(2-methylbenzyl)-3-[(2S,3S)-3-amino-2-hydroxy-4-(3,4-methylenedioxyphenyl)butanoyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxamide 在 sodium hydroxide 、 三乙胺 、 氯磷酸二苯酯 作用下， 以 甲醇 、 水 、 乙酸乙酯 为溶剂， 生成 (R)-3-[(2S,3S)-4-Benzo[1,3]dioxol-5-yl-2-hydroxy-3-(3-hydroxy-2-methyl-benzoylamino)-butyryl]-5,5-dimethyl-thiazolidine-4-carboxylic acid 2-methyl-benzylamide
  参考文献：
  名称：

  Structure–activity and structure–metabolism relationships of HIV protease inhibitors containing the 3-hydroxy-2-methylbenzoyl-allophenylnorstatine structure

  摘要：

  A series of peptidomimetic human immunodeficiency virus (HIV) protease inhibitors containing substituted allophenyinorstatine [Apns: (2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid] were designed and synthesized. From the structure-metabolism relationship of this type of HIV protease inhibitors, the compounds having para substitution of the phenyl ring of Apris and/or 2,6-disubstitution of the P2' benzylamine were found to be able to avoid the P2 phenol glucuronidation that occurs with SM-319777 (formerly named JE-2147, KNI-764); one of the main metabolic pathways of SM-319777. These new analogues, such as SM-322377, had more desirable pharmacokinetic profiles and more potent antiviral activity against not only wild type HIV-1 but also the multi-drug-resistant HIV-1 than SM-319777. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.10.037
• 作为产物：
  描述：

  (R)-N-(2-methylbenzyl)-5,5-dimethyl-1,3-thiazolidine-4-carboxamide 在 盐酸 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 乙酸乙酯 为溶剂， 生成 (R)-N-(2-methylbenzyl)-3-[(2S,3S)-3-amino-2-hydroxy-4-(3,4-methylenedioxyphenyl)butanoyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxamide
  参考文献：
  名称：

  Structure–activity and structure–metabolism relationships of HIV protease inhibitors containing the 3-hydroxy-2-methylbenzoyl-allophenylnorstatine structure

  摘要：

  A series of peptidomimetic human immunodeficiency virus (HIV) protease inhibitors containing substituted allophenyinorstatine [Apns: (2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid] were designed and synthesized. From the structure-metabolism relationship of this type of HIV protease inhibitors, the compounds having para substitution of the phenyl ring of Apris and/or 2,6-disubstitution of the P2' benzylamine were found to be able to avoid the P2 phenol glucuronidation that occurs with SM-319777 (formerly named JE-2147, KNI-764); one of the main metabolic pathways of SM-319777. These new analogues, such as SM-322377, had more desirable pharmacokinetic profiles and more potent antiviral activity against not only wild type HIV-1 but also the multi-drug-resistant HIV-1 than SM-319777. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.10.037

文献信息

• Structure–activity relationships of novel HIV-1 protease inhibitors containing the 3-amino-2-chlorobenzoyl-allophenylnorstatine structure
  作者：Tsutomu Mimoto、Satoshi Nojima、Keisuke Terashima、Haruo Takaku、Makoto Shintani、Hideya Hayashi

  DOI：10.1016/j.bmc.2007.10.062

  日期：2008.2.1

  A series of peptidomimetic human immunodeficiency virus (HIV) protease inhibitors containing substituted allophenylnorstatine (Apns: (2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid) were designed and synthesized. From the structure-activity relationship of this series of compounds, SM-309515 was found to have potent antiviral activity against wild-type and resistant HIV-1s and to possess a desirable

  设计并合成了一系列含有取代的别苯基去甲他汀（Apns：（2S，3S）-3-氨基-2-羟基-4-羟基丁酸）的拟肽类人免疫缺陷病毒（HIV）蛋白酶抑制剂。从该系列化合物的构效关系，发现SM-309515对野生型和抗性HIV-1具有有效的抗病毒活性，并在犬中具有理想的药代动力学特征。