tert-butyl (3R)-3-([6-(4-fluorophenyl)-2-isopropyl-4-oxoquinazolin-3(4H)-yl]methyl)piperidine-1-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: tert-butyl (3R)-3-([6-(4-fluorophenyl)-2-isopropyl-4-oxoquinazolin-3(4H)-yl]methyl)piperidine-1-carboxylate
• 英文别名: tert-butyl (3R)-3-[[6-(4-fluorophenyl)-4-oxo-2-propan-2-ylquinazolin-3-yl]methyl]piperidine-1-carboxylate
• 化学式: C₂₈H₃₄FN₃O₃
• 分子量: 479.595
• InChiKey: PPVNAHBFUGAZPS-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  62.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (3R)-3-([6-(4-fluorophenyl)-2-isopropyl-4-oxoquinazolin-3(4H)-yl]methyl)piperidine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 6-(4-fluorophenyl)-2-isopropyl-3-[(3S)-piperidin-3-ylmethyl]-quinazolin-4(3H)-one
  参考文献：
  名称：

  Quinazolinone Derivatives as Orally Available Ghrelin Receptor Antagonists for the Treatment of Diabetes and Obesity

  摘要：

  The peptide hormone ghrelin is the endogenous ligand for the type l a growth hormone secretagogue receptor (GHS-R1a) and the only currently known circulating appetite stimulant. GHS-R1a antagonism has therefore been proposed as a potential approach for obesity treatment. More recently, ghrelin has been recognized to also play a role in controlling glucose-induced insulin secretion, which suggests another possible benefit for a GHS-R1a antagonist, namely, the role as an insulin secretagogue with potential value for diabetes treatment. In our laboratories, piperidine- substituted quinazolinone derivatives were identified as a new class of small-molecule GHS-R1a antagonists. Starting from an agonist with poor oral bioavailability, optimization led to potent, selective, and orally bioavailable antagonists. In vivo efficacy evaluation of selected compounds revealed suppression of food intake and body weight reduction as well as glucose-lowering effects mediated by glucose-dependent insulin secretion.

  DOI：

  10.1021/jm070071+
• 作为产物：
  描述：

  tert-butyl (3R)-3-[(6-bromo-2-isopropyl-4-oxoquinazolin-3(4H)-yl)methyl]piperidine-1-carboxylate 、 4-氟苯硼酸 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride potassium carbonate 作用下， 以 1,4-二氧六环 、 水 、 甲苯 为溶剂， 以94%的产率得到tert-butyl (3R)-3-([6-(4-fluorophenyl)-2-isopropyl-4-oxoquinazolin-3(4H)-yl]methyl)piperidine-1-carboxylate
  参考文献：
  名称：

  [EN] QUINAZOLINONE DERIVATIVES USEFUL FOR THE REGULATION OF GLUCOSE HOMEOSTASIS AND FOOD INTAKE
  [FR] DERIVES DE LA QUINAZOLINONE UTILES POUR LA REGULATION DE L'HOMEOSTASIE DU GLUCOSE ET DE PRISE D'ALIMENTS

  摘要：

  公开号：

  WO2006012577A3

文献信息

• Quinazolinone Derivatives as Orally Available Ghrelin Receptor Antagonists for the Treatment of Diabetes and Obesity
  作者：Joachim Rudolph、William P. Esler、Stephen O'Connor、Philip D. G. Coish、Philip L. Wickens、Michael Brands、Donald E. Bierer、Brian T. Bloomquist、Georgiy Bondar、Libing Chen、Chih-Yuan Chuang、Thomas H. Claus、Zahra Fathi、Wenlang Fu、Uday R. Khire、James A. Kristie、Xiao-Gao Liu、Derek B. Lowe、Andrea C. McClure、Martin Michels、Astrid A. Ortiz、Philip D. Ramsden、Robert W. Schoenleber、Tatiana E. Shelekhin、Alexandros Vakalopoulos、Weifeng Tang、Lei Wang、Lin Yi、Stephen J. Gardell、James N. Livingston、Laurel J. Sweet、William H. Bullock

  DOI：10.1021/jm070071+

  日期：2007.10.1

  The peptide hormone ghrelin is the endogenous ligand for the type l a growth hormone secretagogue receptor (GHS-R1a) and the only currently known circulating appetite stimulant. GHS-R1a antagonism has therefore been proposed as a potential approach for obesity treatment. More recently, ghrelin has been recognized to also play a role in controlling glucose-induced insulin secretion, which suggests another possible benefit for a GHS-R1a antagonist, namely, the role as an insulin secretagogue with potential value for diabetes treatment. In our laboratories, piperidine- substituted quinazolinone derivatives were identified as a new class of small-molecule GHS-R1a antagonists. Starting from an agonist with poor oral bioavailability, optimization led to potent, selective, and orally bioavailable antagonists. In vivo efficacy evaluation of selected compounds revealed suppression of food intake and body weight reduction as well as glucose-lowering effects mediated by glucose-dependent insulin secretion.
• [EN] QUINAZOLINONE DERIVATIVES USEFUL FOR THE REGULATION OF GLUCOSE HOMEOSTASIS AND FOOD INTAKE<br/>[FR] DERIVES DE LA QUINAZOLINONE UTILES POUR LA REGULATION DE L'HOMEOSTASIE DU GLUCOSE ET DE PRISE D'ALIMENTS
  申请人：BAYER PHARMACEUTICALS CORP

  公开号：WO2006012577A3

  公开（公告）日：2006-09-28