AHPBA 43a

• 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: AHPBA 43a
• 英文别名: (2S)-2-(1,2-benzoxazole-3-carbonylamino)-N-[(2S,3S)-4-[(2S,4S)-2-(tert-butylcarbamoyl)-4-chloropyrrolidin-1-yl]-3-hydroxy-4-oxo-1-phenylbutan-2-yl]butanediamide
• 化学式: C₃₁H₃₇ClN₆O₇
• 分子量: 641.124
• InChiKey: GAKQRBFTMHFFTE-BPKYXHNXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  45
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  197
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  Boc-L-羟脯氨酸 在 palladium on activated charcoal N-甲基吗啉 、 盐酸 、 四氯化碳 、 氢气 、 三乙胺 、 三苯基膦 、 焦碳酸二乙酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 38.0h， 生成 AHPBA 43a
  参考文献：
  名称：

  Structure-activity relationships of HIV-1 PR inhibitors containing AHPBA—II. Modification of pyrrolidine ring at P1′ proline

  摘要：

  Systematic replacement in the 3- or 4-position of the pyrrolidine ring at P1' proline was carried out. Compound 26, which has a C1 atom in the 4(S)-position was the most active among inhibitors substituted with other halogen atoms or other substituents. Furthermore, the replacement of the Z group in compound 26 with five- or six-membered fused aromatic heterocycle carbonyl groups produced more potent inhibitors. 7-Methoxybenzofuran-2-carbonyl derivative (44) was the best of these and showed K-i = 4.5 nM against HIV PR and IC(50)s 0.58 mu M and 0.06 mu M in chronic and acute infections, respectively. These results suggest that the combination of the 4(S)-Cl atom and fused bicyclic heterocycles may be effective in improving their cellular penetration. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0968-0896(96)00130-7

文献信息

• Structure-activity relationships of HIV-1 PR inhibitors containing AHPBA—II. Modification of pyrrolidine ring at P1′ proline
  作者：Tomoaki Komai、Susumu Higashida、Mitsuya Sakurai、Tamayo Nitta、Atsushi Kasuya、Shuichi Miyamaoto、Ryuichi Yagi、Yuji Ozawa、Hiroshi Handa、Hiroshi Mohri、Akira Yasuoka、Shinichi Oka、Takashi Nishigaki、Satoshi Kimura、Kaoru Shimada、Yuichiro Yabe

  DOI：10.1016/0968-0896(96)00130-7

  日期：1996.8

  Systematic replacement in the 3- or 4-position of the pyrrolidine ring at P1' proline was carried out. Compound 26, which has a C1 atom in the 4(S)-position was the most active among inhibitors substituted with other halogen atoms or other substituents. Furthermore, the replacement of the Z group in compound 26 with five- or six-membered fused aromatic heterocycle carbonyl groups produced more potent inhibitors. 7-Methoxybenzofuran-2-carbonyl derivative (44) was the best of these and showed K-i = 4.5 nM against HIV PR and IC(50)s 0.58 mu M and 0.06 mu M in chronic and acute infections, respectively. These results suggest that the combination of the 4(S)-Cl atom and fused bicyclic heterocycles may be effective in improving their cellular penetration. Copyright (C) 1996 Elsevier Science Ltd