(2R,3S)-3-{(S)-2-[(S)-2-Acetylamino-3-(1H-indol-3-yl)-propionylamino]-3-methyl-butyrylamino}-2-hydroxy-N-((8S,11S)-8-isopropyl-7,10-dioxo-2-oxa-6,9-diaza-bicyclo[11.2.2]heptadeca-1(16),13(17),14-trien-11-yl)-4-phenyl-butyramide

• 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: (2R,3S)-3-{(S)-2-[(S)-2-Acetylamino-3-(1H-indol-3-yl)-propionylamino]-3-methyl-butyrylamino}-2-hydroxy-N-((8S,11S)-8-isopropyl-7,10-dioxo-2-oxa-6,9-diaza-bicyclo[11.2.2]heptadeca-1(16),13(17),14-trien-11-yl)-4-phenyl-butyramide
• 英文别名: (2S)-2-[[(2S)-2-acetamido-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2S,3R)-4-[[(8S,11S)-7,10-dioxo-8-propan-2-yl-2-oxa-6,9-diazabicyclo[11.2.2]heptadeca-1(15),13,16-trien-11-yl]amino]-3-hydroxy-4-oxo-1-phenylbutan-2-yl]-3-methylbutanamide
• 化学式: C₄₅H₅₇N₇O₈
• 分子量: 823.99
• InChiKey: NEFLBYBCIDVAIQ-BYAJYZPISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  60
• 可旋转键数：
  14
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  220
• 氢给体数：
  8
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  N-乙酰-L-色氨酸 在 lithium hydroxide 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 生成 (2R,3S)-3-{(S)-2-[(S)-2-Acetylamino-3-(1H-indol-3-yl)-propionylamino]-3-methyl-butyrylamino}-2-hydroxy-N-((8S,11S)-8-isopropyl-7,10-dioxo-2-oxa-6,9-diaza-bicyclo[11.2.2]heptadeca-1(16),13(17),14-trien-11-yl)-4-phenyl-butyramide
  参考文献：
  名称：

  Design and synthesis of broad-Based mono- and bi- cyclic inhibitors of FIV and HIV proteases

  摘要：

  Based on the substrate transition state and our strategy to tackle the problem of drug resistance, a series of HIV/FIV protease (HIV/FIV PR) monocyclic inhibitors incorporating a 15- or 17-membered macrocycle with an equivalent P3 or P3' group and a unique unnatural amino acid, (2R, 3S)-3-amino-2-hydroxy-4-phenylbutyric acid, have been designed and synthesized. In addition, based on the structure of TL3 with small P3/P3' group, we have synthesized two conformationally restricted bicyclic inhibitors containing the macrocycle, which mimic the P1/P1'-P3/P3' tripeptide [Phe-Val-Ala] of TL3. We have found that the contribution of the macrocycle in our monocyclic inhibitors is important to the overall activity, but the ring size does not affect the activity to a significant extent. Several inhibitors that were developed in this work, exhibit low nanomolar inhibitory activity against the wild-type HIV/FIV PR and found to be highly effective against some drug-resistant as well as TL3-resistant mutants of HIV PRs. Compound 15, in particular, is the most effective cyclic inhibitor in hand to inhibit FIV replication in tissue culture at a concentration of 1.0 mug/mL (1.2 muM). (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00054-3

文献信息

• Design, synthesis, and biological evaluation of HIV/FIV protease inhibitors incorporating a conformationally constrained macrocycle with a small P3′ residue
  作者：Chi Ching Mak、Van-Duc Le、Ying-Chuan Lin、John H Elder、Chi-Huey Wong

  DOI：10.1016/s0960-894x(00)00641-7

  日期：2001.1

  A series of norstatine-based HIV/FIV protease inhibitors incorporating a 15-membered macrocycle as a mimic of the tripeptide (Ala-Val-Phe), a motif with a small P3' residue effective against the FIV protease and the drug-resistant HIV proteases, has been synthesized. It was found that the macrocycle is important to the overall activity of the inhibitors. Certain inhibitors were developed expressing low nanomolar inhibitory activity against the HIV/FIV proteases and they are also effective against some drug-resistant as well as TL3-resistant HIV proteases. (C) 2001 Elsevier Science Ltd. All rights reserved.