benzyl N-[(3S,6S,9S)-3-[(1R,2R)-2-[(3S,6S,9S)-9-(benzyloxycarbonylamino)-6-isopropyl-5,8,12-trioxo-4,7,13-triazabicyclo[12.3.1]octadeca-1(18),14,16-trien-3-yl]-1,2-dihydroxy-ethyl]-6-isopropyl-5,8,12-trioxo-4,7,13-triazabicyclo[12.3.1]octadeca-1(18),14,16-trien-9-yl]carbamate

• 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: benzyl N-[(3S,6S,9S)-3-[(1R,2R)-2-[(3S,6S,9S)-9-(benzyloxycarbonylamino)-6-isopropyl-5,8,12-trioxo-4,7,13-triazabicyclo[12.3.1]octadeca-1(18),14,16-trien-3-yl]-1,2-dihydroxy-ethyl]-6-isopropyl-5,8,12-trioxo-4,7,13-triazabicyclo[12.3.1]octadeca-1(18),14,16-trien-9-yl]carbamate
• 英文别名: benzyl N-[(6S,9S,12S)-12-[(1R,2R)-1,2-dihydroxy-2-[(6S,9S,12S)-3,7,10-trioxo-6-(phenylmethoxycarbonylamino)-9-propan-2-yl-2,8,11-triazabicyclo[12.3.1]octadeca-1(17),14(18),15-trien-12-yl]ethyl]-3,7,10-trioxo-9-propan-2-yl-2,8,11-triazabicyclo[12.3.1]octadeca-1(17),14(18),15-trien-6-yl]carbamate
• 化学式: C₅₄H₆₆N₈O₁₂
• 分子量: 1019.16
• InChiKey: IKQSBEABIWOQNE-PXRJHXIUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  74
• 可旋转键数：
  13
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  292
• 氢给体数：
  10
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  在 三氟乙酸 作用下， 以 水 为溶剂， 反应 2.0h， 以40 mg的产率得到benzyl N-[(3S,6S,9S)-3-[(1R,2R)-2-[(3S,6S,9S)-9-(benzyloxycarbonylamino)-6-isopropyl-5,8,12-trioxo-4,7,13-triazabicyclo[12.3.1]octadeca-1(18),14,16-trien-3-yl]-1,2-dihydroxy-ethyl]-6-isopropyl-5,8,12-trioxo-4,7,13-triazabicyclo[12.3.1]octadeca-1(18),14,16-trien-9-yl]carbamate
  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