2,2-dimethyl-4-oxo-4-{[(1R,2R,5R,10S,13R,14R,17S,19R)-1,2,14,18,18-pentamethyl-7-oxo-5-{oxo[(thiophen-2-ylmethyl)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 | 1326312-43-9

• 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[(thiophen-2-ylmethyl)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: 2,2-dimethyl-4-oxo-4-((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-5a,5b,8,8,11a-pentamethyl-1-(1-methylethyl)-2-oxo-3a-{oxo[(2-thienylmethyl)amino]acetyl}-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)oxylbutanoic acid；2,2-dimethyl-4-oxo-4-({(3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-5a,5b,8,8,11a-pentamethyl-1-(1-methylethyl)-2-oxo-3a-{oxo[(2-thienylmethyl)amino]acetyl}-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}oxy)butanoic acid；4-[[(3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-5a,5b,8,8,11a-pentamethyl-2-oxo-3a-[2-oxo-2-(thiophen-2-ylmethylamino)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: 1326312-43-9
• 化学式: C₄₂H₅₉NO₇S
• 分子量: 721.999
• InChiKey: BYJMJSVHCWTLHJ-TWMJUEBWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8
• 重原子数：
  51
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  155
• 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)-5a,5b,8,8,11a-pentamethyl-3a-(2-nitroacetyl)-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3H-cyclopenta[a]chrysen-9-yl] acetate 在 吡啶 、 4-二甲氨基吡啶 、 草酰氯 、 溶剂黄146 、 sodium nitrite 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 2.0h， 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[(thiophen-2-ylmethyl)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

文献信息

• [EN] DERIVATIVES OF BETULIN<br/>[FR] DÉRIVÉS DE BÉTULINE
  申请人：GLAXOSMITHKLINE LLC

  公开号：WO2011100308A1

  公开（公告）日：2011-08-18

  The present invention relates to a compound characterized by Formula I or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, X, and Y are as described herein. Compounds of the present invention are useful for the treatment of HIV-1.

  本发明涉及一种由化学式I或其药用可接受盐所表征的化合物，其中R1、R2、R3、X和Y如本文所述。本发明的化合物对HIV-1的治疗具有用途。
• DERIVATIVES OF BETULIN
  申请人：Gao Daxin

  公开号：US20120302534A1

  公开（公告）日：2012-11-29

  The present invention relates to a compound characterized by the following Formula I: or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 , X, and Y are as described herein. Compounds of the present invention are useful for the treatment of HIV-1.