(1'R,3'aR,4'aR,8'aR,9'S,9'aS)-9'-[(E)-2-(5-hydroxypyridin-2-yl)ethenyl]-1'-methylspiro[1,3-dioxolane-2,6'-1,3a,4,4a,5,7,8,8a,9,9a-decahydrobenzo[f][2]benzofuran]-3'-one | 618386-08-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 萘并呋喃类
• 英文名称: (1'R,3'aR,4'aR,8'aR,9'S,9'aS)-9'-[(E)-2-(5-hydroxypyridin-2-yl)ethenyl]-1'-methylspiro[1,3-dioxolane-2,6'-1,3a,4,4a,5,7,8,8a,9,9a-decahydrobenzo[f][2]benzofuran]-3'-one
• CAS: 618386-08-6
• 化学式: C₂₂H₂₇NO₅
• 分子量: 385.46
• InChiKey: YOHAHBFWDCDPQE-KWNMAUFOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  28
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  77.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (1'R,3'aR,4'aR,8'aR,9'S,9'aS)-9'-[(E)-2-(5-hydroxypyridin-2-yl)ethenyl]-1'-methylspiro[1,3-dioxolane-2,6'-1,3a,4,4a,5,7,8,8a,9,9a-decahydrobenzo[f][2]benzofuran]-3'-one 在 三氟甲磺酸酐 作用下， 以 吡啶 为溶剂， 以80%的产率得到[6-[(E)-2-[(1'R,3'aR,4'aR,8'aR,9'S,9'aS)-1'-methyl-3'-oxospiro[1,3-dioxolane-2,6'-1,3a,4,4a,5,7,8,8a,9,9a-decahydrobenzo[f][2]benzofuran]-9'-yl]ethenyl]pyridin-3-yl] trifluoromethanesulfonate
  参考文献：
  名称：

  Discovery of a Novel, Orally Active Himbacine-Based Thrombin Receptor Antagonist (SCH 530348) with Potent Antiplatelet Activity

  摘要：

  The discovery of an exceptionally potent series of thrombin receptor (PAR-1) antagonists based on the natural product himbacine is described. Optimization of this series has led to the discovery of 4 (SCH 530348), a potent, oral antiplatelet agent that is currently undergoing Phase-III clinical trials for acute coronary syndrome (unstable angina/non-ST segment elevation myocardial infarction) and secondary prevention of cardiovascular events in high-risk patients.

  DOI：

  10.1021/jm800180e
• 作为产物：
  描述：

  (1'R,3'aR,4'aR,8'aR,9'S,9'aS)-1'-methyl-9'-[(E)-2-[5-tri(propan-2-yl)silyloxypyridin-2-yl]ethenyl]spiro[1,3-dioxolane-2,6'-1,3a,4,4a,5,7,8,8a,9,9a-decahydrobenzo[f][2]benzofuran]-3'-one 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 0.08h， 以100%的产率得到(1'R,3'aR,4'aR,8'aR,9'S,9'aS)-9'-[(E)-2-(5-hydroxypyridin-2-yl)ethenyl]-1'-methylspiro[1,3-dioxolane-2,6'-1,3a,4,4a,5,7,8,8a,9,9a-decahydrobenzo[f][2]benzofuran]-3'-one
  参考文献：
  名称：

  Discovery of a Novel, Orally Active Himbacine-Based Thrombin Receptor Antagonist (SCH 530348) with Potent Antiplatelet Activity

  摘要：

  The discovery of an exceptionally potent series of thrombin receptor (PAR-1) antagonists based on the natural product himbacine is described. Optimization of this series has led to the discovery of 4 (SCH 530348), a potent, oral antiplatelet agent that is currently undergoing Phase-III clinical trials for acute coronary syndrome (unstable angina/non-ST segment elevation myocardial infarction) and secondary prevention of cardiovascular events in high-risk patients.

  DOI：

  10.1021/jm800180e

文献信息

• THROMBIN RECEPTOR ANTAGONISTS
  申请人：Chackalamannil Samuel

  公开号：US20070179187A1

  公开（公告）日：2007-08-02

  Heterocyclic-substituted tricyclics of the formula or a pharmaceutically acceptable salt thereof, wherein: the dotted line represents an optional single bond; represents an optional double bond, n is 0-2; Q is cycloalkyl, optionally substituted by R 13 and R 14 ; R 13 and R 14 are independently selected from (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, —OH, (C 1 -C 6 )alkoxy, R 27 -aryl(C 1 -C 6 )alkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halogen and haloalkyl; or R 13 and R 14 together form a spirocyclic or a heterospirocyclic ring of 3-6 atoms, Het is a mono- or bi-cyclic optionally substituted heteroaryl group; and B is a bond, alkylene, or optionally substituted alkenylene or alkynylene, wherein the remaining substituents are as defined in the specification, are disclosed, as well as pharmaceutical compositions containing them and a method of treating diseases associated with thrombosis, atherosclerosis, restenosis, hypertension, angina pectoris, arrhythmia, heart failure, and cancer by administering said compounds. Combination therapy with other cardiovascular agents is also claimed.

  公式为Heterocyclic-substituted tricyclics或其药学上可接受的盐，其中：虚线代表可选的单键；代表可选的双键，n为0-2；Q为环烷基，可选地由R13和R14取代；R13和R14独立地选择自（C1-C6）烷基，（C3-C8）环烷基，—OH，（C1-C6）烷氧基，R27-芳基（C1-C6）烷基，杂芳基，杂芳基烷基，杂环基，杂环基烷基，卤素和卤基；或R13和R14一起形成3-6个原子的螺环或杂螺环；Het是一个单环或双环的可选取代杂芳基基团；B为键，烷基，或可选取代的烯烃基或炔基，其中其余取代基如规范中所定义。还公开了含有这些化合物的制药组合物以及通过给予这些化合物治疗与血栓形成、动脉粥样硬化、再狭窄、高血压、心绞痛、心律失常、心力衰竭和癌症相关的疾病的方法。还声称与其他心血管药物的联合治疗。
• US7304078B2
  申请人：——

  公开号：US7304078B2

  公开（公告）日：2007-12-04
• US7713999B2
  申请人：——

  公开号：US7713999B2

  公开（公告）日：2010-05-11
• Discovery of a Novel, Orally Active Himbacine-Based Thrombin Receptor Antagonist (SCH 530348) with Potent Antiplatelet Activity
  作者：Samuel Chackalamannil、Yuguang Wang、William J. Greenlee、Zhiyong Hu、Yan Xia、Ho-Sam Ahn、George Boykow、Yunsheng Hsieh、Jairam Palamanda、Jacqueline Agans-Fantuzzi、Stan Kurowski、Michael Graziano、Madhu Chintala

  DOI：10.1021/jm800180e

  日期：2008.6.1

  The discovery of an exceptionally potent series of thrombin receptor (PAR-1) antagonists based on the natural product himbacine is described. Optimization of this series has led to the discovery of 4 (SCH 530348), a potent, oral antiplatelet agent that is currently undergoing Phase-III clinical trials for acute coronary syndrome (unstable angina/non-ST segment elevation myocardial infarction) and secondary prevention of cardiovascular events in high-risk patients.