tert-butyl 4-[(1Z)-3-hydroxyprop-1-en-1-yl]piperidine-1-carboxylate

• 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-[(1Z)-3-hydroxyprop-1-en-1-yl]piperidine-1-carboxylate
• 英文别名: tert-butyl (Z)-4-(3-hydroxyprop-1-en-1-yl)piperidine-1-carboxylate；(Z)-1-Boc-4-(3-hydroxyprop-1-enyl)piperidine；tert-butyl 4-[(Z)-3-hydroxyprop-1-enyl]piperidine-1-carboxylate
• 化学式: C₁₃H₂₃NO₃
• 分子量: 241.331
• InChiKey: RSTQQYLKMXGLJQ-PLNGDYQASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-[(1Z)-3-hydroxyprop-1-en-1-yl]piperidine-1-carboxylate 在 copper(l) iodide 、 sodium azide 、 diethylzinc 、 sodium hydride 、 potassium carbonate 、 Ammonium hydroxide 作用下， 以 乙二醇二甲醚 、 二氯甲烷 、 溶剂黄146 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 54.75h， 生成 tert-butyl 4-((1R,2R)-2-((3-fluoro-4-(1H-tetrazol-1-yl)benzyloxy)methyl)cyclopropyl)piperidine-1-carboxylate
  参考文献：
  名称：

  [EN] SUBSTITUTED CYCLOPROPYL COMPOUNDS, COMPOSITIONS CONTAINING SUCH COMPOUNDS, AND METHODS OF TREATMENT
  [FR] COMPOSÉS CYCLOPROPYLÉS SUBSTITUÉS, COMPOSITIONS CONTENANT DE TELS COMPOSÉS ET PROCÉDÉS DE TRAITEMENT

  摘要：

  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。

  公开号：

  WO2012173917A1
• 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 、 氢气 作用下， 以 乙酸乙酯 为溶剂， 反应 1.0h， 以75%的产率得到tert-butyl 4-[(1Z)-3-hydroxyprop-1-en-1-yl]piperidine-1-carboxylate
  参考文献：
  名称：

  [EN] GPR119 AGONISTS
  [FR] AGONISTES DE GPR119

  摘要：

  本公开至少部分地涉及用于治疗涉及肠脑轴的疾病或疾病的GPR119激动剂。在某些实施例中，GPR119激动剂是肠道限制化合物。在某些实施例中，该疾病或疾病是代谢性疾病，例如糖尿病，肥胖症，非酒精性脂肪性肝炎（NASH）或营养失调，例如短肠综合症。

  公开号：

  WO2022216709A1

文献信息

• 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。
• Design of Potent and Orally Active GPR119 Agonists for the Treatment of Type II Diabetes
  作者：Ping Liu、Zhiyong Hu、Byron G. DuBois、Christopher R. Moyes、David N. Hunter、Cheng Zhu、Nam Fung Kar、Yuping Zhu、Joie Garfunkle、Ling Kang、Gary Chicchi、Anka Ehrhardt、Andrea Woods、Toru Seo、Morgan Woods、Margaret van Heek、Karen H. Dingley、Jianmei Pang、Gino M. Salituro、Joyce Powell、Jenna L. Terebetski、Viktor Hornak、Louis-Charles Campeau、Joe Lamberson、Fez Ujjainwalla、Michael Miller、Andrew Stamford、Harold B. Wood、Timothy Kowalski、Ravi P. Nargund、Scott D. Edmondson

  DOI：10.1021/acsmedchemlett.5b00207

  日期：2015.8.13

  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.
• 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.
• GPR119 AGONISTS
  申请人：Kallyope, Inc.

  公开号：US20220153719A1

  公开（公告）日：2022-05-19

  This disclosure is directed, at least in part, to GPR119 agonists useful for the treatment of conditions or disorders involving the gut-brain axis. In some embodiments, the GPR119 agonists are gut-restricted compounds. In some embodiments, the condition or disorder is a metabolic disorder, such as diabetes, obesity, nonalcoholic steatohepatitis (NASH), or a nutritional disorder such as short bowel syndrome.