tert-butyl 4-((1R,2R)-2-(((3,5-difluoro-4-(methylsulfonyl)benzyl)oxy)methyl)cyclopropyl)piperidine-1-carboxylate | 1416364-78-7

• 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-(((3,5-difluoro-4-(methylsulfonyl)benzyl)oxy)methyl)cyclopropyl)piperidine-1-carboxylate
• 英文别名: tert-butyl 4-[(1R,2R)-2-[(3,5-difluoro-4-methylsulfonylphenyl)methoxymethyl]cyclopropyl]piperidine-1-carboxylate
• CAS: 1416364-78-7
• 化学式: C₂₂H₃₁F₂NO₅S
• 分子量: 459.555
• InChiKey: UNHBVHHKTJWQEJ-DLBZAZTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  81.3
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-((1R,2R)-2-(((3,5-difluoro-4-(methylsulfonyl)benzyl)oxy)methyl)cyclopropyl)piperidine-1-carboxylate 在 盐酸 、 caesium carbonate 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 1.08h， 生成 2-(4-((1R,2R)-2-(((3,5-difluoro-4-(methylsulfonyl)benzyl)oxy)methyl)cyclopropyl)piperidin-1-yl)-5-(methoxymethyl)pyrimidine
  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：

  [3,5-difluoro-4-(methylthio)phenyl]methanol 在 四溴化碳 、 sodium hydride 、 间氯过氧苯甲酸 、 三苯基膦 作用下， 以 二氯甲烷 、 mineral oil 为溶剂， 反应 48.08h， 生成 tert-butyl 4-((1R,2R)-2-(((3,5-difluoro-4-(methylsulfonyl)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

• [EN] SUBSTITUTED CYCLOPROPYL COMPOUNDS, COMPOSITIONS CONTAINING SUCH COMPOUNDS, AND METHODS OF TREATMENT<br/>[FR] COMPOSÉS CYCLOPROPYLÉS SUBSTITUÉS, COMPOSITIONS CONTENANT DE TELS COMPOSÉS ET PROCÉDÉS DE TRAITEMENT
  申请人：MERCK SHARP & DOHME

  公开号：WO2012173917A1

  公开（公告）日：2012-12-20

  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.

  公开了具有以下化学式I的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。还包括药物组合物和治疗方法。
• Substituted cyclopropyl compounds, compositions containing such compounds, and methods of treatment
  申请人：Miller Michael

  公开号：US09006228B2

  公开（公告）日：2015-04-14

  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.

  本发明公开了式I的取代环丙基化合物及其药学上可接受的盐，其可用于治疗或预防2型糖尿病和类似疾病。该化合物可用作G蛋白偶联受体GPR-119的激动剂。本发明还包括药物组合物和治疗方法。
• 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