2,2-dimethyl-4-oxo-4-{[(1R,2R,5R,10S,13R,14R,17S,19R)-1,2,14,18,18-pentamethyl-7-oxo-5-[oxo({[2-(pyrrolidin-1-yl)propyl]carbamoyl})methyl]-8-(propan-2-yl)pentacyclo[11.8.0.0^2,10.0^5,9.0^14,19]henicos-8-en-17-yl]oxy}butanoic acid | 1326312-55-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 2,2-dimethyl-4-oxo-4-{[(1R,2R,5R,10S,13R,14R,17S,19R)-1,2,14,18,18-pentamethyl-7-oxo-5-[oxo({[2-(pyrrolidin-1-yl)propyl]carbamoyl})methyl]-8-(propan-2-yl)pentacyclo[11.8.0.0^2,10.0^5,9.0^14,19]henicos-8-en-17-yl]oxy}butanoic acid
• 英文别名: 4-[[(3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-5a,5b,8,8,11a-pentamethyl-2-oxo-3a-[2-oxo-2-(3-pyrrolidin-1-ylpropylamino)acetyl]-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3H-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid
• CAS: 1326312-55-3
• 化学式: C₄₄H₆₈N₂O₇
• 分子量: 737.033
• InChiKey: DSRDYKDUIRKDBT-CZNDSZCVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  53
• 可旋转键数：
  12
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  130
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-(hydroxymethyl)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl acetate 在 吡啶 、 4-二甲氨基吡啶 、 草酰氯 、 silica gel 、 戴斯-马丁氧化剂 、 溶剂黄146 、 三乙胺 、 pyridinium chlorochromate 、 sodium nitrite 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 4.67h， 生成 2,2-dimethyl-4-oxo-4-{[(1R,2R,5R,10S,13R,14R,17S,19R)-1,2,14,18,18-pentamethyl-7-oxo-5-[oxo({[2-(pyrrolidin-1-yl)propyl]carbamoyl})methyl]-8-(propan-2-yl)pentacyclo[11.8.0.0^2,10.0^5,9.0^14,19]henicos-8-en-17-yl]oxy}butanoic acid
  参考文献：
  名称：

  Discovery of a novel and potent class of anti-HIV-1 maturation inhibitors with improved virology profile against gag polymorphisms

  摘要：

  A new class of betulin-derived a-keto amides was identified as HIV-1 maturation inhibitors. Through lead optimization, GSK8999 was identified with IC50 values of 17 nM, 23 nM, 25 nM, and 8 nM for wild type, Q369H, V370A, and T371A respectively. When tested in a panel of 62 HIV-1 isolates covering a diversity of CA-SP1 genotypes including A, AE, B, C, and G using a PBMC based assay, GSK8999 was potent against 57 of 62 isolates demonstrating an improvement over the first generation maturation inhibitor BVM. The data disclosed here also demonstrated that the new alpha-keto amide GSK8999 has a mechanism of action consistent with inhibition of the proteolytic cleavage of CA-SP1. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.04.042