5-chloro-2-[4-((1R,2S)-2-{2-[4-(1H-1,2,3-triazol-1-yl)phenoxy]ethyl}cyclopropyl)piperidin-1-yl]pyrimidine | 1192063-14-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-chloro-2-[4-((1R,2S)-2-{2-[4-(1H-1,2,3-triazol-1-yl)phenoxy]ethyl}cyclopropyl)piperidin-1-yl]pyrimidine
• 英文别名: 2-(4-((1R,2S)-2-(2-(4-(1H-1,2,3-triazol-1-yl)phenoxy)ethyl)cyclopropyl)piperidin-1-yl)-5-chloropyrimidine；5-chloro-2-[4-[(1R,2S)-2-[2-[4-(triazol-1-yl)phenoxy]ethyl]cyclopropyl]piperidin-1-yl]pyrimidine
• CAS: 1192063-14-1
• 化学式: C₂₂H₂₅ClN₆O
• 分子量: 424.933
• InChiKey: XCMQGEUINVIVHT-DYESRHJHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  69
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  在 lead 、 偶氮二甲酸二叔丁酯 、 5% Pd-CaCO3 、 氢气 、 diethylzinc 、 palladium(II) hydroxide 、 sodium hydride 、 caesium carbonate 、 三苯基膦 、 三氟乙酸 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 喹啉 、 乙醇 、 二氯甲烷 、 乙酸乙酯 、 1,2-二氯乙烷 为溶剂， -18.0~20.0 ℃ 、344.75 kPa 条件下， 生成 5-chloro-2-[4-((1R,2S)-2-{2-[4-(1H-1,2,3-triazol-1-yl)phenoxy]ethyl}cyclopropyl)piperidin-1-yl]pyrimidine
  参考文献：
  名称：

  Design of potent and selective GPR119 agonists for type II diabetes

  摘要：

  Screening of the Merck sample collection identified compound 1 as a weakly potent GPR119 agonist (hEC(50) = 3600 nM). Dual termini optimization of 1 led to compound 36 having improved potency, selectivity, and formulation profile, however, modest physical properties (PP) hindered its utility. Design of a new core containing a cyclopropyl restriction yielded further PP improvements and when combined with the termini SAR optimizations yielded a potent and highly selective agonist suitable for further preclinical development (58). (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.086

文献信息

• SUBSTITUTED CYCLOPROPYL COMPOUNDS, COMPOSITIONS CONTAINING SUCH COMPOUNDS AND METHODS OF TREATMENT
  申请人：Wood Harold B

  公开号：US20110028501A1

  公开（公告）日：2011-02-03

  Substituted cyclopropyl compounds of formula (I) are disclosed as useful for treating or preventing type 2 diabetes and similar conditions. Pharmaceutically acceptable salts and solvates are included as well. The compounds are useful as agonists of the g-protein coupled receptor GPR-119.

  公开了化合物(I)的替代环丙基化合物，其可用于治疗或预防2型糖尿病和类似情况。还包括药学上可接受的盐和溶剂化物。该化合物可用作G蛋白偶联受体GPR-119的激动剂。
• US8343990B2
  申请人：——

  公开号：US8343990B2

  公开（公告）日：2013-01-01
• Design of potent and selective GPR119 agonists for type II diabetes
  作者：Jason W. Szewczyk、John Acton、Alan D. Adams、Gary Chicchi、Stanley Freeman、Andrew D. Howard、Yong Huang、Cai Li、Peter T. Meinke、Ralph Mosely、Elizabeth Murphy、Rachel Samuel、Conrad Santini、Meng Yang、Yong Zhang、Kake Zhao、Harold B. Wood

  DOI：10.1016/j.bmcl.2010.12.086

  日期：2011.5

  Screening of the Merck sample collection identified compound 1 as a weakly potent GPR119 agonist (hEC(50) = 3600 nM). Dual termini optimization of 1 led to compound 36 having improved potency, selectivity, and formulation profile, however, modest physical properties (PP) hindered its utility. Design of a new core containing a cyclopropyl restriction yielded further PP improvements and when combined with the termini SAR optimizations yielded a potent and highly selective agonist suitable for further preclinical development (58). (C) 2011 Elsevier Ltd. All rights reserved.