2,2-Dimethyl-succinic acid 4-{(1S,2S)-1-((R)-4-tert-butylcarbamoyl-5,5-dimethyl-thiazolidine-3-carbonyl)-2-[2-(2,6-dimethyl-phenoxy)-acetylamino]-3-phenyl-propyl} ester | 343330-26-7

• 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: 2,2-Dimethyl-succinic acid 4-{(1S,2S)-1-((R)-4-tert-butylcarbamoyl-5,5-dimethyl-thiazolidine-3-carbonyl)-2-[2-(2,6-dimethyl-phenoxy)-acetylamino]-3-phenyl-propyl} ester
• 英文别名: 4-[(2S,3S)-1-[(4R)-4-(tert-butylcarbamoyl)-5,5-dimethyl-1,3-thiazolidin-3-yl]-3-[[2-(2,6-dimethylphenoxy)acetyl]amino]-1-oxo-4-phenylbutan-2-yl]oxy-2,2-dimethyl-4-oxobutanoic acid
• CAS: 343330-26-7
• 化学式: C₃₆H₄₉N₃O₈S
• 分子量: 683.866
• InChiKey: UAGCOBGRDIWDLN-JPHFWNGBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  48
• 可旋转键数：
  15
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  177
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2,2-Dimethyl-succinic acid 4-{(1S,2S)-1-((R)-4-tert-butylcarbamoyl-5,5-dimethyl-thiazolidine-3-carbonyl)-2-[2-(2,6-dimethyl-phenoxy)-acetylamino]-3-phenyl-propyl} ester 在 盐酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-(2-Amino-ethyl)-3,3-dimethyl-succinamic acid (1S,2S)-1-((R)-4-tert-butylcarbamoyl-5,5-dimethyl-thiazolidine-3-carbonyl)-2-[2-(2,6-dimethyl-phenoxy)-acetylamino]-3-phenyl-propyl ester; hydrochloride
  参考文献：
  名称：

  Controlled drug release

  摘要：

  We designed and synthesized a series of highly water-soluble prodrugs of an HIV protease inhibitor, KNI-727 (1), containing tandem-linked two auxiliary units, a solubilizing moiety and a self-cleavable spacer. Prodrugs with an ionized amino group at the solubilizing moiety exhibited a remarkable increase of water-solubility (>10(4) fold) compared to the parent drug 1. These prodrugs released 1 not enzymatically, but chemically via an intramolecular cyclization-elimination reaction through an imide formation in physiological conditions. Diversified rates of parent drug release were observed when the chemical structure of both the solubilizing and the spacer moieties were modified. This new approach for water-soluble prodrugs will enable to control chemically the release of parent drug as well as to maintain high water-solubility. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00007-5
• 作为产物：
  描述：

  2,2-二甲基琥珀酸酐 、 KNI-727 在 二环己胺 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 生成 2,2-Dimethyl-succinic acid 4-{(1S,2S)-1-((R)-4-tert-butylcarbamoyl-5,5-dimethyl-thiazolidine-3-carbonyl)-2-[2-(2,6-dimethyl-phenoxy)-acetylamino]-3-phenyl-propyl} ester
  参考文献：
  名称：

  Controlled drug release

  摘要：

  We designed and synthesized a series of highly water-soluble prodrugs of an HIV protease inhibitor, KNI-727 (1), containing tandem-linked two auxiliary units, a solubilizing moiety and a self-cleavable spacer. Prodrugs with an ionized amino group at the solubilizing moiety exhibited a remarkable increase of water-solubility (>10(4) fold) compared to the parent drug 1. These prodrugs released 1 not enzymatically, but chemically via an intramolecular cyclization-elimination reaction through an imide formation in physiological conditions. Diversified rates of parent drug release were observed when the chemical structure of both the solubilizing and the spacer moieties were modified. This new approach for water-soluble prodrugs will enable to control chemically the release of parent drug as well as to maintain high water-solubility. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00007-5