N-[4,6-dichloro-3-(3,4-dichlorophenyl)-2-oxo-1H-indol-3-yl]-2-(1-ethylpiperidin-3-yl)acetamide | 1401324-43-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: N-[4,6-dichloro-3-(3,4-dichlorophenyl)-2-oxo-1H-indol-3-yl]-2-(1-ethylpiperidin-3-yl)acetamide
• CAS: 1401324-43-3
• 化学式: C₂₃H₂₃Cl₄N₃O₂
• 分子量: 515.267
• InChiKey: JAYGZFPMNNIDPY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  61.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1-乙基哌啶-3-酮 在 盐酸 、 五氯化磷 、 potassium carbonate 、 magnesium 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 45.92h， 生成 N-[4,6-dichloro-3-(3,4-dichlorophenyl)-2-oxo-1H-indol-3-yl]-2-(1-ethylpiperidin-3-yl)acetamide
  参考文献：
  名称：

  Synthesis and pharmacological evaluation of indolinone derivatives as novel ghrelin receptor antagonists

  摘要：

  The ghrelin receptor is a G-protein-coupled receptor (GPCR) widely expressed in the brain, stomach and the intestine. It was firstly identified during studies aimed to find synthetic modulators of growth hormone (GH) secretion. GHSR and its endogenous ligand ghrelin were found to be involved in hunger response. Through food intake regulation, they could affect body weight and adiposity. Thus GHSR antagonists rapidly became an attractive target to treat obesity and feeding disorders. In this study we describe the biological properties of new indolinone derivatives identified as a new, chiral class of ghrelin antagonists. Their synthesis as well as the structure-activity relationship will be discussed herein. The in vitro identified compound 14f was a potent GHSR1a antagonist (IC50 = 7 nM). When tested in vivo, on gastric emptying model, 14f showed an inhibitory intrinsic effect when given alone and it dose dependently inhibited ghrelin stimulation. Compound 14f also reduced food intake stimulated both by fasting condition (high level of endogenous ghrelin) and by icv ghrelin. Moreover this compound improved glucose tolerance in ipGTT test. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.07.018

文献信息

• Synthesis and pharmacological evaluation of indolinone derivatives as novel ghrelin receptor antagonists
  作者：Letizia Puleo、Pietro Marini、Roberta Avallone、Marco Zanchet、Silvio Bandiera、Marco Baroni、Tiziano Croci

  DOI：10.1016/j.bmc.2012.07.018

  日期：2012.9

  The ghrelin receptor is a G-protein-coupled receptor (GPCR) widely expressed in the brain, stomach and the intestine. It was firstly identified during studies aimed to find synthetic modulators of growth hormone (GH) secretion. GHSR and its endogenous ligand ghrelin were found to be involved in hunger response. Through food intake regulation, they could affect body weight and adiposity. Thus GHSR antagonists rapidly became an attractive target to treat obesity and feeding disorders. In this study we describe the biological properties of new indolinone derivatives identified as a new, chiral class of ghrelin antagonists. Their synthesis as well as the structure-activity relationship will be discussed herein. The in vitro identified compound 14f was a potent GHSR1a antagonist (IC50 = 7 nM). When tested in vivo, on gastric emptying model, 14f showed an inhibitory intrinsic effect when given alone and it dose dependently inhibited ghrelin stimulation. Compound 14f also reduced food intake stimulated both by fasting condition (high level of endogenous ghrelin) and by icv ghrelin. Moreover this compound improved glucose tolerance in ipGTT test. (C) 2012 Elsevier Ltd. All rights reserved.