(1S-(1R*,2S*(2S,3R*)))-<3-<<3-<<(dimethylethoxy)carbonyl>amino>-2-hydroxy-4-(4-hydroxyphenyl)butyl>amino>-2-hydroxy-1-(2-phenylmethyl)propyl>carbamic acid 1,1-dimethylethyl ester | 162538-18-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (1S-(1R*,2S*(2S,3R*)))-<3-<<3-<<(dimethylethoxy)carbonyl>amino>-2-hydroxy-4-(4-hydroxyphenyl)butyl>amino>-2-hydroxy-1-(2-phenylmethyl)propyl>carbamic acid 1,1-dimethylethyl ester
• 英文别名: 12-Oxa-2,6,10-triazatetradecanoic acid, 4,8-dihydroxy-3-((4-hydroxyphenyl)methyl)-13,13-dimethyl-11-oxo-9-(phenylmethyl)-, 1,1-dimethylethyl ester, (3S-(3R*,4S*,8S*,9R*))-；tert-butyl N-[(2S,3R)-3-hydroxy-4-[[(2R,3S)-2-hydroxy-4-(4-hydroxyphenyl)-3-[(2-methylpropan-2-yl)oxycarbonylamino]butyl]amino]-1-phenylbutan-2-yl]carbamate
• CAS: 162538-18-3
• 化学式: C₃₀H₄₅N₃O₇
• 分子量: 559.703
• InChiKey: QVGOLNUEBCOLGS-QEGGNFSNSA-N

物化性质

• 沸点：
  745.2±60.0 °C(Predicted)
• 密度：
  1.177±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  40
• 可旋转键数：
  16
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  149
• 氢给体数：
  6
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  1-苄基-2,3-环氧正丙基-氨基甲酸叔丁酯 在 palladium dihydroxide ammonium hydroxide 、 氢气 、 lithium perchlorate 、 三乙胺 、 二异丙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 40.0h， 生成 (1S-(1R*,2S*(2S,3R*)))-<3-<<3-<<(dimethylethoxy)carbonyl>amino>-2-hydroxy-4-(4-hydroxyphenyl)butyl>amino>-2-hydroxy-1-(2-phenylmethyl)propyl>carbamic acid 1,1-dimethylethyl ester
  参考文献：
  名称：

  Amino Diol HIV Protease Inhibitors. 1. Design, Synthesis, and Preliminary SAR

  摘要：

  A series of HIV protease inhibitors containing a novel C-2 symmetrical ''aminodiol'' core structure were prepared from amino acid starting materials. The ability of the aminodiols to inhibit HIV replication in cell culture is comparable to their ability to inhibit the isolated enzyme, a result compatible with good cell membrane penetration by this class of compounds. Optimization of the structure-activity in this series led to aminodiol 9a (K-i = 100 nM; ED(50) (HIV-1) = 80 nM) containing P-1/P-1', benzyl and P-2/P-2' Boc substituents. Compound 9a is a selective inhibitor of HIV protease versus other aspartyl proteases such as human renin, human cathepsin D, and porcine pepsin. In addition, 9a is equipotent against HIV-1 and HIV-2 in cell culture and demonstrates similar activity in infected T-lymphocytes and PBMCs. After iv and oral administration in rats, 9a displayed significant oral bioavailability (ca. 40%) and a promising plasma elimination half-life (4 h).

  DOI：

  10.1021/jm00038a005

文献信息

• Amino Diol HIV Protease Inhibitors. 1. Design, Synthesis, and Preliminary SAR
  作者：Joel C. Barrish、Eric Gordon、Masud Alam、Pin-Fang Lin、Gregory S. Bisacchi、Ping Chen、Peter T. W. Cheng、Alan W. Fritz、Jill A. Greytok

  DOI：10.1021/jm00038a005

  日期：1994.6

  A series of HIV protease inhibitors containing a novel C-2 symmetrical ''aminodiol'' core structure were prepared from amino acid starting materials. The ability of the aminodiols to inhibit HIV replication in cell culture is comparable to their ability to inhibit the isolated enzyme, a result compatible with good cell membrane penetration by this class of compounds. Optimization of the structure-activity in this series led to aminodiol 9a (K-i = 100 nM; ED(50) (HIV-1) = 80 nM) containing P-1/P-1', benzyl and P-2/P-2' Boc substituents. Compound 9a is a selective inhibitor of HIV protease versus other aspartyl proteases such as human renin, human cathepsin D, and porcine pepsin. In addition, 9a is equipotent against HIV-1 and HIV-2 in cell culture and demonstrates similar activity in infected T-lymphocytes and PBMCs. After iv and oral administration in rats, 9a displayed significant oral bioavailability (ca. 40%) and a promising plasma elimination half-life (4 h).