{(S)-1-[(4R,5R)-2,2-Dimethyl-5-((R)-3-methyl-1-{(1S,2S)-2-methyl-1-[(pyridin-2-ylmethyl)-carbamoyl]-butylcarbamoyl}-butyl)-[1,3]dioxolan-4-yl]-3-methyl-butyl}-carbamic acid tert-butyl ester | 134458-62-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: {(S)-1-[(4R,5R)-2,2-Dimethyl-5-((R)-3-methyl-1-{(1S,2S)-2-methyl-1-[(pyridin-2-ylmethyl)-carbamoyl]-butylcarbamoyl}-butyl)-[1,3]dioxolan-4-yl]-3-methyl-butyl}-carbamic acid tert-butyl ester
• 英文别名: N--3-methylbutyl>-2,2-dimethyl-4(R)-dioxolanyl>-4-methylpentanoyl>-L-isoleucyl>-2-pyridylmethylamine
• CAS: 134458-62-1
• 化学式: C₃₃H₅₆N₄O₆
• 分子量: 604.831
• InChiKey: UUMPKDGTYHEOPV-LOBYWDITSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.35
• 重原子数：
  43.0
• 可旋转键数：
  14.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  127.88
• 氢给体数：
  3.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  {(S)-1-[(4R,5R)-2,2-Dimethyl-5-((R)-3-methyl-1-{(1S,2S)-2-methyl-1-[(pyridin-2-ylmethyl)-carbamoyl]-butylcarbamoyl}-butyl)-[1,3]dioxolan-4-yl]-3-methyl-butyl}-carbamic acid tert-butyl ester 在 ethandithiol 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 乙酰氯 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 19.0h， 生成 N-im-(tert-butyloxycarbonyl)-L-histidyl>-5(S)-amino-3(R),4(R)-dihydroxy-2-(S)-isobutyl-7-methyloctanoyl>-L-isoleucyl>-2-pyridylmethylamine
  参考文献：
  名称：

  Inhibitors of the protease from human immunodeficiency virus: design and modeling of a compound containing a dihydroxyethylene isostere insert with high binding affinity and effective antiviral activity

  摘要：

  The peptidomimetic template and the dihydroxyethylene isostere insert that were applied successfully to the design of renin inhibitors have been extended to the related protease from human immunodeficiency virus (HIV). The present report describes the structure-activity study leading to the identification of an inhibitor with a K(i) of < 1 nM for the HIV type-1 protease (compound II). This compound, containing a diol insert, is highly effective in blocking polyprotein processing in in vitro cell culture assays. Results obtained from kinetic analysis, studies of the stereochemistry of the insert, and modeling have led to insights as to the requisites involved in the active site-inhibitor interaction.

  DOI：

  10.1021/jm00112a005
• 作为产物：
  描述：

  1(R)-<3-(tert-butyloxycarbonyl)-2,2-dimethyl-4(S)-isobutyl-5(R)-oxazolidinyl>-2(R)-isobutyl-1,3-propanediol 在 ruthenium trichloride 、 diethylphosphoryl cyanide 、 camphor-10-sulfonic acid 、 过碘酸 、 N,N-二异丙基乙胺 、 丙酮 作用下， 以 四氯化碳 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 30.75h， 生成 {(S)-1-[(4R,5R)-2,2-Dimethyl-5-((R)-3-methyl-1-{(1S,2S)-2-methyl-1-[(pyridin-2-ylmethyl)-carbamoyl]-butylcarbamoyl}-butyl)-[1,3]dioxolan-4-yl]-3-methyl-butyl}-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Inhibitors of the protease from human immunodeficiency virus: design and modeling of a compound containing a dihydroxyethylene isostere insert with high binding affinity and effective antiviral activity

  摘要：

  The peptidomimetic template and the dihydroxyethylene isostere insert that were applied successfully to the design of renin inhibitors have been extended to the related protease from human immunodeficiency virus (HIV). The present report describes the structure-activity study leading to the identification of an inhibitor with a K(i) of < 1 nM for the HIV type-1 protease (compound II). This compound, containing a diol insert, is highly effective in blocking polyprotein processing in in vitro cell culture assays. Results obtained from kinetic analysis, studies of the stereochemistry of the insert, and modeling have led to insights as to the requisites involved in the active site-inhibitor interaction.

  DOI：

  10.1021/jm00112a005