tert-butyl (1R,3s,5S)-3-((6-chloro-5-methylpyrimidin-4-yl)oxy)-8-azabicyclo[3.2.1]octane-8-carboxylate | 1147557-54-7

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 英文名称: tert-butyl (1R,3s,5S)-3-((6-chloro-5-methylpyrimidin-4-yl)oxy)-8-azabicyclo[3.2.1]octane-8-carboxylate
• CAS: 1147557-54-7
• 化学式: C₁₇H₂₄ClN₃O₃
• 分子量: 353.849
• InChiKey: CZFBGRMMTIECTF-CLLJXQQHSA-N

物化性质

• 沸点：
  465.2±45.0 °C(Predicted)
• 密度：
  1.240±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.75
• 重原子数：
  24.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  64.55
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (1R,3s,5S)-3-((6-chloro-5-methylpyrimidin-4-yl)oxy)-8-azabicyclo[3.2.1]octane-8-carboxylate 在 三乙胺 、 三氟乙酸 作用下， 生成 (1R,3s,5S)-3-((6-chloro-5-methylpyrimidin-4-yl)oxy)-8-(cyclopropylsulfonyl)-8-azabicyclo[3.2.1]octane
  参考文献：
  名称：

  Discovery of a nortropanol derivative as a potent and orally active GPR119 agonist for type 2 diabetes

  摘要：

  The lead optimization studies of a series of GPR119 agonists incorporating a nortropanol scaffold are described. Extensive structure-activity relationship (SAR) studies of the lead compound 20f led to the identification of compound 36j as a potent, single digit nanomolar GPR119 agonist with high agonist activity. Compound 36j was orally active in lowering blood glucose levels in a mouse oral glucose tolerance test and increased plasma insulin levels in a rat hyperglycemic model. It showed good to excellent pharmacokinetic properties in rats and monkeys and no untoward activities in counter-screen assays. Compound 36j demonstrated an attractive in vitro and in vivo profile for further development. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.035
• 作为产物：
  描述：

  (1R,3S,5S)-tert-butyl 3-hydroxy-8-azabicyclo[3.2.1]octane-8-carboxylate 在 sodium hydride 、 三苯基膦 、 sodium hydroxide 、 偶氮二甲酸二乙酯 作用下， 以 水 为溶剂， 生成 tert-butyl (1R,3s,5S)-3-((6-chloro-5-methylpyrimidin-4-yl)oxy)-8-azabicyclo[3.2.1]octane-8-carboxylate
  参考文献：
  名称：

  Discovery of a nortropanol derivative as a potent and orally active GPR119 agonist for type 2 diabetes

  摘要：

  The lead optimization studies of a series of GPR119 agonists incorporating a nortropanol scaffold are described. Extensive structure-activity relationship (SAR) studies of the lead compound 20f led to the identification of compound 36j as a potent, single digit nanomolar GPR119 agonist with high agonist activity. Compound 36j was orally active in lowering blood glucose levels in a mouse oral glucose tolerance test and increased plasma insulin levels in a rat hyperglycemic model. It showed good to excellent pharmacokinetic properties in rats and monkeys and no untoward activities in counter-screen assays. Compound 36j demonstrated an attractive in vitro and in vivo profile for further development. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.035

文献信息

• [EN] BICYCLIC HETEROCYCLE DERIVATIVES AND THEIR USE AS MODULATORS OF THE ACTIVITY OF GPR119<br/>[FR] DÉRIVÉS HÉTÉROCYCLIQUES BICYCLIQUES ET LEURS PROCÉDÉS D'UTILISATION
  申请人：SCHERING CORP

  公开号：WO2009055331A3

  公开（公告）日：2009-07-30
• Discovery of a nortropanol derivative as a potent and orally active GPR119 agonist for type 2 diabetes
  作者：Yan Xia、Samuel Chackalamannil、William J. Greenlee、Charles Jayne、Bernard Neustadt、Andrew Stamford、Henry Vaccaro、Xiaoying (Lucy) Xu、Hana Baker、Kim O’Neill、Morgan Woods、Brian Hawes、Tim Kowalski

  DOI：10.1016/j.bmcl.2011.04.035

  日期：2011.6

  The lead optimization studies of a series of GPR119 agonists incorporating a nortropanol scaffold are described. Extensive structure-activity relationship (SAR) studies of the lead compound 20f led to the identification of compound 36j as a potent, single digit nanomolar GPR119 agonist with high agonist activity. Compound 36j was orally active in lowering blood glucose levels in a mouse oral glucose tolerance test and increased plasma insulin levels in a rat hyperglycemic model. It showed good to excellent pharmacokinetic properties in rats and monkeys and no untoward activities in counter-screen assays. Compound 36j demonstrated an attractive in vitro and in vivo profile for further development. (C) 2011 Elsevier Ltd. All rights reserved.