(3R,3aS,4S,5R,6S,7aR)-4-[(E)-2-[5-(2,5-dichlorophenyl)pyridin-2-yl]ethenyl]-5-ethyl-3,6-dimethyl-3a,4,5,6,7,7a-hexahydro-3H-2-benzofuran-1-one | 380893-93-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: (3R,3aS,4S,5R,6S,7aR)-4-[(E)-2-[5-(2,5-dichlorophenyl)pyridin-2-yl]ethenyl]-5-ethyl-3,6-dimethyl-3a,4,5,6,7,7a-hexahydro-3H-2-benzofuran-1-one
• CAS: 380893-93-6
• 化学式: C₂₅H₂₇Cl₂NO₂
• 分子量: 444.401
• InChiKey: VSDFUEQXHLRUSH-BVLLJDPSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (3R,3aS,4S,5R,6S,7aR)-5-ethyl-4-(hydroxymethyl)-3,6-dimethyl-3a,4,5,6,7,7a-hexahydro-3H-2-benzofuran-1-one 在 titanium(IV) isopropylate 、 四丙基高钌酸铵 、 N-甲基吗啉氧化物 、 lithium hexamethyldisilazane 作用下， 生成 (3R,3aS,4S,5R,6S,7aR)-4-[(E)-2-[5-(2,5-dichlorophenyl)pyridin-2-yl]ethenyl]-5-ethyl-3,6-dimethyl-3a,4,5,6,7,7a-hexahydro-3H-2-benzofuran-1-one
  参考文献：
  名称：

  Discovery of nor-seco himbacine analogs as thrombin receptor antagonists

  摘要：

  Discovery of a novel nor-seco himbacine analog as potent thrombin receptor (PAR-1) antagonist is described. Despite low plasma level, these new analogs showed excellent ex vivo efficacy in the monkey platelet aggregation assay. A potent hydroxy metabolite generated in vivo was identified as the agent responsible for the ex vivo efficacy. Following this discovery, the metabolite series was optimized to obtain analogs that showed very good ex vivo efficacy along with excellent pharmacokinetic profile in c. monkey. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.138

文献信息

• Discovery of nor-seco himbacine analogs as thrombin receptor antagonists
  作者：Mariappan V. Chelliah、Samuel Chackalamannil、Yan Xia、Keith Eagen、William J. Greenlee、Ho-Sam Ahn、Jacqueline Agans-Fantuzzi、George Boykow、Yunsheng Hsieh、Matthew Bryant、Tze-Ming Chan、Madhu Chintala

  DOI：10.1016/j.bmcl.2012.01.138

  日期：2012.4

  Discovery of a novel nor-seco himbacine analog as potent thrombin receptor (PAR-1) antagonist is described. Despite low plasma level, these new analogs showed excellent ex vivo efficacy in the monkey platelet aggregation assay. A potent hydroxy metabolite generated in vivo was identified as the agent responsible for the ex vivo efficacy. Following this discovery, the metabolite series was optimized to obtain analogs that showed very good ex vivo efficacy along with excellent pharmacokinetic profile in c. monkey. (C) 2012 Elsevier Ltd. All rights reserved.