tert-butyl 4-{(1R,2R)-2-[({2-fluoro-4-[(2-hydroxyethyl)sulfonyl]benzyl} oxy)methyl]cyclopropyl}piperidine-1-carboxylate | 1416365-13-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: tert-butyl 4-{(1R,2R)-2-[({2-fluoro-4-[(2-hydroxyethyl)sulfonyl]benzyl} oxy)methyl]cyclopropyl}piperidine-1-carboxylate
• 英文别名: tert-butyl 4-[(1R,2R)-2-[[2-fluoro-4-(2-hydroxyethylsulfonyl)phenyl]methoxymethyl]cyclopropyl]piperidine-1-carboxylate
• CAS: 1416365-13-3
• 化学式: C₂₃H₃₄FNO₆S
• 分子量: 471.59
• InChiKey: JAGXLTKFSUJFKT-AZUAARDMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  32
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-{(1R,2R)-2-[({2-fluoro-4-[(2-hydroxyethyl)sulfonyl]benzyl} oxy)methyl]cyclopropyl}piperidine-1-carboxylate 在 caesium carbonate 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 21.75h， 生成 2-((4-((((1R,2R)-2-(1-(5-chloropyrimidin-2-yl)piperidin-4-yl)cyclopropyl)methoxy)methyl)-3-fluorophenyl)sulfonyl)ethanol
  参考文献：
  名称：

  Design of Potent and Orally Active GPR119 Agonists for the Treatment of Type II Diabetes

  摘要：

  We report herein the design and synthesis of a series of potent and selective GPR119 agonists. Our objective was to develop a GPR119 agonist with properties that were suitable for fixed-dose combination with a DPP4 inhibitor. Starting from a phenoxy analogue (1), medicinal chemistry efforts directed toward reducing half-life and increasing solubility led to the synthesis of a series of benzyloxy analogues. Compound 28 was chosen for further profiling because of its favorable physicochemical properties and excellent GPR119 potency across species. This compound exhibited a clean off-target profile in counterscreens and good in vivo efficacy in mouse oGTT.

  DOI：

  10.1021/acsmedchemlett.5b00207
• 作为产物：
  描述：

  4-(3-羟基丙-1-炔-1-基)哌啶-1-甲酸叔丁酯 在 喹啉 、 tris-(dibenzylideneacetone)dipalladium(0) 、 Oxone 、 水 、 氢气 、 diethylzinc 、 sodium hexamethyldisilazane 、 N,N-二异丙基乙胺 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙二醇二甲醚 、 二氯甲烷 、 乙酸乙酯 为溶剂， -20.0~20.0 ℃ 、101.33 kPa 条件下， 反应 4.5h， 生成 tert-butyl 4-{(1R,2R)-2-[({2-fluoro-4-[(2-hydroxyethyl)sulfonyl]benzyl} oxy)methyl]cyclopropyl}piperidine-1-carboxylate
  参考文献：
  名称：

  Design of Potent and Orally Active GPR119 Agonists for the Treatment of Type II Diabetes

  摘要：

  We report herein the design and synthesis of a series of potent and selective GPR119 agonists. Our objective was to develop a GPR119 agonist with properties that were suitable for fixed-dose combination with a DPP4 inhibitor. Starting from a phenoxy analogue (1), medicinal chemistry efforts directed toward reducing half-life and increasing solubility led to the synthesis of a series of benzyloxy analogues. Compound 28 was chosen for further profiling because of its favorable physicochemical properties and excellent GPR119 potency across species. This compound exhibited a clean off-target profile in counterscreens and good in vivo efficacy in mouse oGTT.

  DOI：

  10.1021/acsmedchemlett.5b00207

文献信息

• SUBSTITUTED CYCLOPROPYL COMPOUNDS, COMPOSITIONS CONTAINING SUCH COMPOUNDS, AND METHODS OF TREATMENT
  申请人：Miller Michael

  公开号：US20140128368A1

  公开（公告）日：2014-05-08

  Substituted cyclopropyl compounds of the formula I: and pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing type 2 diabetes and similar conditions. The compounds are useful as agonists of the G-protein coupled receptor GPR-119. Pharmaceutical compositions and methods of treatment are also included.

  公开了式I的替代环丙基化合物及其药学上可接受的盐，用于治疗或预防2型糖尿病和类似疾病。这些化合物可用作G蛋白偶联受体GPR-119的激动剂。还包括制药组合物和治疗方法。
• US9006228B2
  申请人：——

  公开号：US9006228B2

  公开（公告）日：2015-04-14