tert-butyl 1'-(4-methylphenyl)-4,4'-bipiperidine-1-carboxylate | 1034822-42-8

• 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 1'-(4-methylphenyl)-4,4'-bipiperidine-1-carboxylate
• 英文别名: Tert-butyl 4-(1-p-tolylpiperidin-4-yl)piperidine-1-carboxylate；tert-butyl 4-[1-(4-methylphenyl)piperidin-4-yl]piperidine-1-carboxylate
• CAS: 1034822-42-8
• 化学式: C₂₂H₃₄N₂O₂
• 分子量: 358.524
• InChiKey: VJSRKELPFTVDAV-UHFFFAOYSA-N

物化性质

• 沸点：
  483.5±45.0 °C(Predicted)
• 密度：
  1.065±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  N-boc-4,4-联哌啶 、 alkaline earth salt of/the/ methylsulfuric acid 在 palladium diacetate 、 caesium carbonate 、 2-二苯基磷-2'-(N,N-二甲氨基)联苯 作用下， 以 甲苯 为溶剂， 生成 tert-butyl 1'-(4-methylphenyl)-4,4'-bipiperidine-1-carboxylate
  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

• ACYL BIPIPERIDINYL COMPOUNDS, COMPOSITIONS CONTAINING SUCH COMPOUNDS AND METHODS OF TREATMENT
  申请人：Wood Harold B.

  公开号：US20100075987A1

  公开（公告）日：2010-03-25

  Bipiperidyl compounds of the 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.

  公开了式子为(I)的双哌啶类化合物，用于治疗或预防2型糖尿病和类似疾病。同时包括药用可接受的盐和溶剂。这些化合物可作为G蛋白偶联受体GPR-119的激动剂。
• US8399485B2
  申请人：——

  公开号：US8399485B2

  公开（公告）日：2013-03-19
• [EN] ACYL BIPIPERIDINYL COMPOUNDS, COMPOSITIONS CONTAINING SUCH COMPOUNDS AND METHODS OF TREATMENT<br/>[FR] COMPOSÉS ACYL-BIPIPÉRIDINYLE, COMPOSITIONS CONTENANT DE TELS COMPOSÉS ET PROCÉDÉS DE TRAITEMENT
  申请人：MERCK & CO INC

  公开号：WO2008076243A2

  公开（公告）日：2008-06-26

  [EN] Bipiperidyl compounds of the 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.
  [FR] La présente invention concerne des composés bipipéridinyle de formule : (I) utiles dans le traitement ou la prévention du diabète de type 2 et d'affections similaires. Les sels et les solvates acceptables d'un point de vue pharmaceutique sont aussi bien compris. Les composés sont utiles en tant qu'agonistes du récepteur couplé à des protéines G, GPR-119.
• 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.