3-Amino-propionic acid (2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-2-ylmethyl ester | 748123-94-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 3-Amino-propionic acid (2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-2-ylmethyl ester
• 英文别名: [(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl 3-aminopropanoate
• CAS: 748123-94-6
• 化学式: C₁₃H₁₈N₆O₅
• 分子量: 338.323
• InChiKey: DYTGENHMRAAUFU-IVZWLZJFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  125
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3-Amino-propionic acid (2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-2-ylmethyl ester 、 (R)-N-tert-butyl-3-[(2S,3S)-3-(2,6-dimethylphenoxyacetyl)amino-2-glutaryloxy-4-phenylbutanoyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxamide 在 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 N,N-二甲基甲酰胺 为溶剂， 生成 KNI-1047
  参考文献：
  名称：

  ‘Double-drugs’— A new class of prodrug form of an HIV protease inhibitor conjugated with a reverse transcriptase inhibitor by a spontaneously cleavable linker

  摘要：

  We designed and synthesized a new series of prodrug-type anti-HIV agents consisting of a peptidomimetic HIV protease inhibitor conjugated with a nucleoside reverse transcriptase inhibitor in an effort to enhance the antiviral activity. For the conjugation, a series of linkers that conjoin the two different classes of inhibitors have been investigated. Conjugates using a succinyl amino acid linker were shown to release the parent components via the spontaneous imide formation at a faster rate compared to conjugates using a glutaryl amino acid linker, as expected from the energetically favorable cyclization to the five-membered ring. Herein, we report a new 'double-drug' 4b (KNI-1039) with a glutarylglycine linker, which exhibited extremely potent anti-HIV activity compared with that of the individual components. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00202-x
• 作为产物：
  描述：

  齐多夫定 在 盐酸 、 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-Amino-propionic acid (2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-2-ylmethyl ester
  参考文献：
  名称：

  ‘Double-drugs’— A new class of prodrug form of an HIV protease inhibitor conjugated with a reverse transcriptase inhibitor by a spontaneously cleavable linker

  摘要：

  We designed and synthesized a new series of prodrug-type anti-HIV agents consisting of a peptidomimetic HIV protease inhibitor conjugated with a nucleoside reverse transcriptase inhibitor in an effort to enhance the antiviral activity. For the conjugation, a series of linkers that conjoin the two different classes of inhibitors have been investigated. Conjugates using a succinyl amino acid linker were shown to release the parent components via the spontaneous imide formation at a faster rate compared to conjugates using a glutaryl amino acid linker, as expected from the energetically favorable cyclization to the five-membered ring. Herein, we report a new 'double-drug' 4b (KNI-1039) with a glutarylglycine linker, which exhibited extremely potent anti-HIV activity compared with that of the individual components. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00202-x

文献信息

• ‘Double-drugs’— A new class of prodrug form of an HIV protease inhibitor conjugated with a reverse transcriptase inhibitor by a spontaneously cleavable linker
  作者：Hikaru Matsumoto、Tomonori Hamawaki、Hisashi Ota、Tooru Kimura、Toshiyuki Goto、Kouichi Sano、Yoshio Hayashi、Yoshiaki Kiso

  DOI：10.1016/s0960-894x(00)00202-x

  日期：2000.6

  We designed and synthesized a new series of prodrug-type anti-HIV agents consisting of a peptidomimetic HIV protease inhibitor conjugated with a nucleoside reverse transcriptase inhibitor in an effort to enhance the antiviral activity. For the conjugation, a series of linkers that conjoin the two different classes of inhibitors have been investigated. Conjugates using a succinyl amino acid linker were shown to release the parent components via the spontaneous imide formation at a faster rate compared to conjugates using a glutaryl amino acid linker, as expected from the energetically favorable cyclization to the five-membered ring. Herein, we report a new 'double-drug' 4b (KNI-1039) with a glutarylglycine linker, which exhibited extremely potent anti-HIV activity compared with that of the individual components. (C) 2000 Elsevier Science Ltd. All rights reserved.