(3R,3aS,4S,5R,6S,7aR)-4-[(E)-2-(5-bromopyridin-2-yl)ethenyl]-5-ethyl-3,6-dimethyl-3a,4,5,6,7,7a-hexahydro-3H-2-benzofuran-1-one | 380893-62-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异苯并呋喃
• 英文名称: (3R,3aS,4S,5R,6S,7aR)-4-[(E)-2-(5-bromopyridin-2-yl)ethenyl]-5-ethyl-3,6-dimethyl-3a,4,5,6,7,7a-hexahydro-3H-2-benzofuran-1-one
• CAS: 380893-62-9
• 化学式: C₁₉H₂₄BrNO₂
• 分子量: 378.309
• InChiKey: VDZRNQUTMHMFHE-ILTPWHBPSA-N

物化性质

• 沸点：
  486.4±45.0 °C(predicted)
• 密度：
  1.289±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3R,3aS,4S,5R,6S,7aR)-4-[(E)-2-(5-bromopyridin-2-yl)ethenyl]-5-ethyl-3,6-dimethyl-3a,4,5,6,7,7a-hexahydro-3H-2-benzofuran-1-one 在 四(三苯基膦)钯 、 (2R,8aS)-(+)-(camphorylsulfonyl)oxaziridine 、 lithium hexamethyldisilazane 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 生成 (3R,3aR,4S,5R,6S,7aS)-5-ethyl-7a-hydroxy-3,6-dimethyl-4-[(E)-2-[5-(2-methylphenyl)pyridin-2-yl]ethenyl]-3,3a,4,5,6,7-hexahydro-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
• 作为产物：
  描述：

  (1R,3aR,4aS,8aS,9S,9aS)-decahydro-1-methyl-3-oxo-3H-thiopyrano[3,4-f]isobenzofuran-9-carboxaldehyde 在 titanium(IV) isopropylate 、 sodium tetrahydroborate 、 四丙基高钌酸铵 、 N-甲基吗啉氧化物 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 (3R,3aS,4S,5R,6S,7aR)-4-[(E)-2-(5-bromopyridin-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

• Thrombin receptor antagonists
  申请人：——

  公开号：US20040152736A1

  公开（公告）日：2004-08-05

  A series of compounds represented by the structural formulas 1 2 and pharmaceutically acceptable isomers, salts, solvates and polymorphs thereof are disclosed. Also disclosed are pharmaceutical compositions containing said compounds and their use as thrombin receptor antagonists and binders to cannabinoid receptors.

  本文披露了一系列化合物，其结构式表示为12，并且包括其药学上可接受的异构体、盐、溶剂合物和多晶形式。还披露了含有这些化合物的制药组合物，并将其用作凝血酶受体拮抗剂和大麻素受体结合剂。
• Derivatives of hexahydrobenzofuranone useful for the treatment of (inter alia) auto-immune or inflammatory disorders
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP2301930B1

  公开（公告）日：2016-01-06
• Thrombin Receptor Antagonists
  申请人：Chackalamannil Samuel

  公开号：US20090069383A1

  公开（公告）日：2009-03-12

  A series of compounds represented by the structural formulas and pharmaceutically acceptable isomers, salts, solvates and polymorphs thereof are disclosed. Also disclosed are pharmaceutical compositions containing said compounds and their use as thrombin receptor antagonists and binders to cannabinoid receptors.
• US7488742B2
  申请人：——

  公开号：US7488742B2

  公开（公告）日：2009-02-10
• 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.