(R)-tert-butyl 3-((S)-4-amino-1-(6-chloro-3'-methylbiphenyl-2-yl)-1-hydroxybutyl)piperidine-1-carboxylate | 952593-28-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-tert-butyl 3-((S)-4-amino-1-(6-chloro-3'-methylbiphenyl-2-yl)-1-hydroxybutyl)piperidine-1-carboxylate
• 英文别名: tert-butyl (3R)-3-[(1S)-4-amino-1-[3-chloro-2-(3-methylphenyl)phenyl]-1-hydroxybutyl]piperidine-1-carboxylate
• CAS: 952593-28-1
• 化学式: C₂₇H₃₇ClN₂O₃
• 分子量: 473.055
• InChiKey: UEOZXKQINVSHGH-ZBLYBZFDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  75.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-tert-butyl 3-((S)-4-amino-1-(6-chloro-3'-methylbiphenyl-2-yl)-1-hydroxybutyl)piperidine-1-carboxylate 在 盐酸 、 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 16.0h， 生成 methyl N-[(4S)-4-[3-chloro-2-(3-methylphenyl)phenyl]-4-hydroxy-4-[(3R)-piperidin-3-yl]butyl]carbamate
  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
• 作为产物：
  描述：

  (3R)-3-[(甲氧基甲基氨基)羰基]-1-哌啶羧酸 1,1-二甲基乙酯 在 magnesium 作用下， 以 四氢呋喃 为溶剂， 反应 34.5h， 生成 (R)-tert-butyl 3-((S)-4-amino-1-(6-chloro-3'-methylbiphenyl-2-yl)-1-hydroxybutyl)piperidine-1-carboxylate
  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。
• Piperidine and Morpholine Renin Inhibitors
  申请人：Baldwin John J.

  公开号：US20090264432A1

  公开（公告）日：2009-10-22

  Described are compounds which are orally active and bind to renin to inhibit its activity. They are useful in the treatment or amelioration of diseases associated with renin activity. Also described are methods of use of these compounds for treating or ameliorating a renin mediated disorder in a subject.

  描述了一些口服的化合物，它们能够结合到肾素并抑制其活性。它们在治疗或改善与肾素活性相关的疾病方面是有用的。同时描述了使用这些化合物治疗或改善受肾素介导的疾病的方法。
• 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。
• Piperidine and morpholine renin inhibitors
  申请人：Vitae Pharmaceuticals, Inc.

  公开号：US07858624B2

  公开（公告）日：2010-12-28

  Described are compounds which are orally active and bind to renin to inhibit its activity. They are useful in the treatment or amelioration of diseases associated with renin activity. Also described are methods of use of these compounds for treating or ameliorating a renin mediated disorder in a subject.

  描述了一些口服活性化合物，它们能够结合到肾素上，从而抑制其活性。它们可用于治疗或缓解与肾素活性相关的疾病。同时，还描述了使用这些化合物治疗或缓解受体内肾素介导的疾病的方法。
• [EN] PIPERIDINE AND MORPHOLINE RENIN INHIBITORS<br/>[FR] PIPÉRIDINE ET MORPHOLINE INHIBITEURS DE LA RÉNINE
  申请人：VITAE PHARMACEUTICALS INC

  公开号：WO2007117560A3

  公开（公告）日：2007-12-06