((1S,3R,4S)-3-amino-4-hydroxycyclopentyl)((R)-3-((S)-1-(5-fluoro-3'-methylbiphenyl-2-yl)-1-hydroxy-5-methoxypentyl)piperidin-1-yl)methanone

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ((1S,3R,4S)-3-amino-4-hydroxycyclopentyl)((R)-3-((S)-1-(5-fluoro-3'-methylbiphenyl-2-yl)-1-hydroxy-5-methoxypentyl)piperidin-1-yl)methanone
• 英文别名: [(1S,3R,4S)-3-amino-4-hydroxycyclopentyl]-[(3R)-3-[(1S)-1-[4-fluoro-2-(3-methylphenyl)phenyl]-1-hydroxy-5-methoxypentyl]piperidin-1-yl]methanone
• 化学式: C₃₀H₄₁FN₂O₄
• 分子量: 512.665
• InChiKey: BOMSLDBQVVCUGK-SZTMJRGBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  96
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (1R,2S,4S)-N-BOC-1-氨基-2-羟基环戊烷-4-羧酸甲酯 在 盐酸 、 水 、 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 16.08h， 生成 ((1S,3R,4S)-3-amino-4-hydroxycyclopentyl)((R)-3-((S)-1-(5-fluoro-3'-methylbiphenyl-2-yl)-1-hydroxy-5-methoxypentyl)piperidin-1-yl)methanone
  参考文献：
  名称：

  Biphenyl/diphenyl ether renin inhibitors: Filling the S1 pocket of renin via the S3 pocket

  摘要：

  Structure-based design led to the discovery of a novel class of renin inhibitors in which an unprecedented phenyl ring filling the S1 site is attached to the phenyl ring filling the S3 pocket. Optimization for several parameters including potency in the presence of human plasma, selectivity against CYP3A4 inhibition and improved rat oral bioavailability led to the identification of 8d which demonstrated antihypertensive efficacy in a transgenic rat model of human hypertension. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.06.043

文献信息

• Renin Inhibitors
  申请人：Baldwin John J.

  公开号：US20090264428A1

  公开（公告）日：2009-10-22

  Described are compounds of the formula (I) which are orally active and bind to aspartic proteases to inhibit their activity. They are useful in the treatment or amelioration of diseases associated with aspartic protease activity. Also described are methods of use of the compounds described herein in ameliorating or treating aspartic protease related disorders in a subject in need thereof.

  本文描述了一种公式（I）的化合物，其具有口服活性并能结合天冬氨酸蛋白酶以抑制其活性。它们可用于治疗或改善与天冬氨酸蛋白酶活性相关的疾病。还描述了在需要改善或治疗天冬氨酸蛋白酶相关疾病的受试者中使用本文所述化合物的方法。
• RENIN INHIBITORS
  申请人：Baldwin John J.

  公开号：US20090275581A1

  公开（公告）日：2009-11-05

  Disclosed are compounds according to Formula I: wherein the variables are defined herein. Such compounds are can bind aspartic proteases to inhibit their activity. They are useful in the treatment or amelioration of diseases associated with aspartic protease activity. Also described herein are methods of antagonizing aspartic protease inhibitors in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound according to Formula I.

  本发明涉及公式I所示的化合物，其中变量在此定义。这些化合物能够结合天冬氨酸蛋白酶以抑制其活性。它们可用于治疗或改善与天冬氨酸蛋白酶活性相关的疾病。本发明还描述了拮抗需要受到天冬氨酸蛋白酶抑制剂的受试者的方法，包括向受试者施用公式I所示的化合物的治疗有效量。
• Biphenyl/diphenyl ether renin inhibitors: Filling the S1 pocket of renin via the S3 pocket
  作者：Jing Yuan、Robert D. Simpson、Wei Zhao、Colin M. Tice、Zhenrong Xu、Salvacion Cacatian、Lanqi Jia、Patrick T. Flaherty、Joan Guo、Alexey Ishchenko、Zhongren Wu、Brian M. McKeever、Boyd B. Scott、Yuri Bukhtiyarov、Jennifer Berbaum、Reshma Panemangalore、Ross Bentley、Christopher P. Doe、Richard K. Harrison、Gerard M. McGeehan、Suresh B. Singh、Lawrence W. Dillard、John J. Baldwin、David A. Claremon

  DOI：10.1016/j.bmcl.2011.06.043

  日期：2011.8

  Structure-based design led to the discovery of a novel class of renin inhibitors in which an unprecedented phenyl ring filling the S1 site is attached to the phenyl ring filling the S3 pocket. Optimization for several parameters including potency in the presence of human plasma, selectivity against CYP3A4 inhibition and improved rat oral bioavailability led to the identification of 8d which demonstrated antihypertensive efficacy in a transgenic rat model of human hypertension. (C) 2011 Elsevier Ltd. All rights reserved.