(-)-(3S,4aS,8aS)-(1H-indol-5-yl)-carbamic acid 3-(3-tert-butylcarbamoyl-octahydro-isoquinolin-2-yl)-(2R)-hydroxy-propyl ester | 1185258-50-7

• 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: (-)-(3S,4aS,8aS)-(1H-indol-5-yl)-carbamic acid 3-(3-tert-butylcarbamoyl-octahydro-isoquinolin-2-yl)-(2R)-hydroxy-propyl ester
• 英文别名: (-)-(R)-3-[(3S,4aS,8aS)-3-(tert-butylcarbamoyl)octahydroisoquinolin-2(1H)-yl]-2-hydroxypropyl-1H-indol-5-ylcarbamate；[(2R)-3-[(3S,4aS,8aS)-3-(tert-butylcarbamoyl)-3,4,4a,5,6,7,8,8a-octahydro-1H-isoquinolin-2-yl]-2-hydroxy-propyl] N-(1H-indol-5-yl)carbamate；[(2R)-3-[(3S,4aS,8aS)-3-(tert-butylcarbamoyl)-3,4,4a,5,6,7,8,8a-octahydro-1H-isoquinolin-2-yl]-2-hydroxypropyl] N-(1H-indol-5-yl)carbamate
• CAS: 1185258-50-7
• 化学式: C₂₆H₃₈N₄O₄
• 分子量: 470.612
• InChiKey: FYTLYMDZLQGTLK-GBPFJNKXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  107
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-氨基吲哚 在 三乙胺 作用下， 以 二氯甲烷 、 异丙醇 为溶剂， 反应 40.0h， 生成 (-)-(3S,4aS,8aS)-(1H-indol-5-yl)-carbamic acid 3-(3-tert-butylcarbamoyl-octahydro-isoquinolin-2-yl)-(2R)-hydroxy-propyl ester
  参考文献：
  名称：

  （S）-缩水甘油的新型吲哚类非肽类HIV蛋白酶抑制剂：合成和初步生物学活性

  摘要：

  从相同的旋光前体（S）-缩水甘油开始合成了一系列非肽类HIV蛋白酶抑制剂。通过区域选择性反应，底物容易转化为不同的吲哚磺酰胺或胺。评价初步抑制活性。

  DOI：

  10.1016/j.tet.2009.05.089

文献信息

• New indolic non-peptidic HIV protease inhibitors from (S)-glycidol: synthesis and preliminary biological activity
  作者：Lucia Chiummiento、Maria Funicello、Paolo Lupattelli、Francesco Tramutola、Pietro Campaner

  DOI：10.1016/j.tet.2009.05.089

  日期：2009.8

  A series of non-peptidic HIV protease inhibitors were synthesized starting from the same optically active precursor, (S)-glycidol. The substrate was easily converted into different indolic sulfonamides or amines by regioselective reactions. The preliminary inhibitory activity was evaluated.

  从相同的旋光前体（S）-缩水甘油开始合成了一系列非肽类HIV蛋白酶抑制剂。通过区域选择性反应，底物容易转化为不同的吲哚磺酰胺或胺。评价初步抑制活性。
• Synthesis and biological evaluation of new simple indolic non peptidic HIV Protease inhibitors: The effect of different substitution patterns
  作者：C. Bonini、L. Chiummiento、N. Di Blasio、M. Funicello、P. Lupattelli、F. Tramutola、F. Berti、A. Ostric、S. Miertus、V. Frecer、D.-X. Kong

  DOI：10.1016/j.bmc.2014.06.055

  日期：2014.9

  New structurally simple indolic non peptidic HIV Protease inhibitors were synthesized from (S)-glycidol by regioselective methods. Following the concept of targeting the protein backbone, different substitution patterns were introduced onto the common stereodefined isopropanolamine core modifying the type of functional group on the indole, the position of the functional group on the indole and the type of the nitrogen containing group (sulfonamides or perhydroisoquinoline), alternatively. The systematic study on in vitro inhibition activity of such compounds confirmed the general beneficial effect of the 5-indolyl substituents in presence of arylsulfonamide moieties, which furnished activities in the micromolar range. Preliminary docking analysis allowed to identify several key features of the binding mode of such compounds to the protease.