3-oxa-7-azabicyclo[3.3.1]nonan-9-ol

• 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: 3-oxa-7-azabicyclo[3.3.1]nonan-9-ol
• 英文别名: (1R,5S,9S)-3-oxa-7-azabicyclo[3.3.1]nonan-9-ol；(1R,5S)-3-oxa-7-azabicyclo[3.3.1]nonan-9-ol
• 化学式: C₇H₁₃NO₂
• 分子量: 143.186
• InChiKey: UGQYYCAVFWFHOP-MEKDEQNOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  41.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-oxa-7-azabicyclo[3.3.1]nonan-9-ol 在 盐酸 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 25.17h， 生成 1-methylcyclopropyl syn-9-[[6-[(2-chloro-4-cyanophenyl)amino]-5-fluoro-4-pyrimidinyl]oxy]-3-oxa-7-azabicyclo[3.3.1]nonane-7-carboxylate
  参考文献：
  名称：

  Discovery of MK-8282 as a Potent G-Protein-Coupled Receptor 119 Agonist for the Treatment of Type 2 Diabetes

  摘要：

  The ever-growing prevalence of type 2 diabetes in the world has necessitated an urgent need for multiple orally effective agents that can regulate glucose homeostasis with a concurrent reduction in body weight. G-Protein coupled receptor 119 (GPR119) is a GPCR target at which agonists have demonstrated glucose-dependent insulin secretion and shows beneficial effects on glycemic control. Herein, we describe our efforts leading to the identification of a potent, oral GPR-119 agonist, MK-8282, which shows improved glucose tolerance in multiple animal models and has excellent off-target profile. The key design elements in the compounds involved a combination of a fluoro-pyrimidine and a conformationally constrained bridged piperidine to impart good potency and efficacy.

  DOI：

  10.1021/acsmedchemlett.8b00073
• 作为产物：
  描述：

  N-Benzyl-3-oxa-7-azabicyclo<3.3.1>nonan-9anti-ol 在 氢气 作用下， 以 甲醇 为溶剂， 反应 24.0h， 生成 3-oxa-7-azabicyclo[3.3.1]nonan-9-ol
  参考文献：
  名称：

  Discovery of MK-8282 as a Potent G-Protein-Coupled Receptor 119 Agonist for the Treatment of Type 2 Diabetes

  摘要：

  The ever-growing prevalence of type 2 diabetes in the world has necessitated an urgent need for multiple orally effective agents that can regulate glucose homeostasis with a concurrent reduction in body weight. G-Protein coupled receptor 119 (GPR119) is a GPCR target at which agonists have demonstrated glucose-dependent insulin secretion and shows beneficial effects on glycemic control. Herein, we describe our efforts leading to the identification of a potent, oral GPR-119 agonist, MK-8282, which shows improved glucose tolerance in multiple animal models and has excellent off-target profile. The key design elements in the compounds involved a combination of a fluoro-pyrimidine and a conformationally constrained bridged piperidine to impart good potency and efficacy.

  DOI：

  10.1021/acsmedchemlett.8b00073

文献信息

• [EN] GPR 119 MODULATORS<br/>[FR] MODULATEURS DE GPR 119
  申请人：PFIZER

  公开号：WO2011036576A1

  公开（公告）日：2011-03-31

  Compounds of formula (I) that modulate the activity of the G-protein-coupled receptor GPR119 and their uses in the treatment of diseases linked to the modulation of the G-protein-coupled receptor GPR119 in animals are described herein.

  本文描述了式(I)的化合物，该化合物可以调节G蛋白偶联受体GPR119的活性，并用于治疗与动物中G蛋白偶联受体GPR119调节相关的疾病。
• [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 MK-8282 as a Potent G-Protein-Coupled Receptor 119 Agonist for the Treatment of Type 2 Diabetes
  作者：Santhosh F. Neelamkavil、Andrew W. Stamford、Timothy Kowalski、Dipshikha Biswas、Craig Boyle、Samuel Chackalamannil、Yan Xia、Charles Jayne、Bernard Neustadt、Jinsong Hao、Hong Liu、Xing Dai、Hana Baker、Brian Hawes、Kim O’Neill、Huadong Tang、William J. Greenlee

  DOI：10.1021/acsmedchemlett.8b00073

  日期：2018.5.10

  The ever-growing prevalence of type 2 diabetes in the world has necessitated an urgent need for multiple orally effective agents that can regulate glucose homeostasis with a concurrent reduction in body weight. G-Protein coupled receptor 119 (GPR119) is a GPCR target at which agonists have demonstrated glucose-dependent insulin secretion and shows beneficial effects on glycemic control. Herein, we describe our efforts leading to the identification of a potent, oral GPR-119 agonist, MK-8282, which shows improved glucose tolerance in multiple animal models and has excellent off-target profile. The key design elements in the compounds involved a combination of a fluoro-pyrimidine and a conformationally constrained bridged piperidine to impart good potency and efficacy.