2-[1-[3-(4-fluorophenyl)prop-2-enoyl]piperidin-4-yl]-2-[[4-(1H-indol-3-yl)cyclohexyl]amino]acetamide | 1352428-56-8

• 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: 2-[1-[3-(4-fluorophenyl)prop-2-enoyl]piperidin-4-yl]-2-[[4-(1H-indol-3-yl)cyclohexyl]amino]acetamide
• CAS: 1352428-56-8
• 化学式: C₃₀H₃₅FN₄O₂
• 分子量: 502.632
• InChiKey: DGHYFBXFQMJKRH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  37
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  91.2
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氨基-2-(1-Boc-4-哌啶基)乙酸甲酯 在 盐酸 、 氨 、 三乙酰氧基硼氢化钠 、 三乙胺 、 bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 2-[1-[3-(4-fluorophenyl)prop-2-enoyl]piperidin-4-yl]-2-[[4-(1H-indol-3-yl)cyclohexyl]amino]acetamide
  参考文献：
  名称：

  The discovery of novel cyclohexylamide CCR2 antagonists

  摘要：

  As a result of further SAR studies on a piperidinyl piperidine scaffold, we report the discovery of compound 44, a potent, orally bioavailable CCR2 antagonist. While having some in vitro hERG activity, this molecule was clean in an in vivo model of QT prolongation. In addition, it showed excellent efficacy when dosed orally in a transgenic murine model of acute inflammation. (C) 2011 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2011.09.113

文献信息

• 4-SUBSTITUTED-CYCLOHEXYLAMINO-4-PIPERIDINYL-ACETAMIDE ANTAGONISTS OF CCR2
  申请人：Lanter James C.

  公开号：US20120142733A1

  公开（公告）日：2012-06-07

  The present invention comprises compounds of Formula (I). wherein: R 1 , R 2 , R 3 , R 4 , X, Y, and Z are as defined in the specification. The invention also comprises a method of preventing, treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is type II diabetes, obesity and asthma. The invention also comprises a method of inhibiting CCR2 activity in a mammal by administration of a therapeutically effective amount of at least one compound of Formula (I).

  本发明涉及式(I)的化合物。其中：R1、R2、R3、R4、X、Y和Z如规范中所定义。本发明还涉及一种预防、治疗或缓解综合症、疾病或疾病的方法，其中所述综合症、疾病或疾病为2型糖尿病、肥胖症和哮喘。本发明还涉及一种通过给哺乳动物以式(I)的至少一种化合物的治疗有效量来抑制CCR2活性的方法。
• US8921559B2
  申请人：——

  公开号：US8921559B2

  公开（公告）日：2014-12-30
• The discovery of novel cyclohexylamide CCR2 antagonists
  作者：James C. Lanter、Thomas P. Markotan、Xuqing Zhang、Nalin Subasinghe、Fu-An Kang、Cuifen Hou、Monica Singer、Evan Opas、Sandra McKenney、Carl Crysler、Dana Johnson、Christopher J. Molloy、Zhihua Sui

  DOI：10.1016/j.bmcl.2011.09.113

  日期：2011.12

  As a result of further SAR studies on a piperidinyl piperidine scaffold, we report the discovery of compound 44, a potent, orally bioavailable CCR2 antagonist. While having some in vitro hERG activity, this molecule was clean in an in vivo model of QT prolongation. In addition, it showed excellent efficacy when dosed orally in a transgenic murine model of acute inflammation. (C) 2011 Published by Elsevier Ltd.