1,2-dichloro-4-[2-(methyl 4-chlorophenylacetate)]-5-nitrobenzene | 1118785-34-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1,2-dichloro-4-[2-(methyl 4-chlorophenylacetate)]-5-nitrobenzene
• 英文别名: Methyl (4-chlorophenyl)(4,5-dichloro-2-nitrophenyl)acetate；methyl 2-(4-chlorophenyl)-2-(4,5-dichloro-2-nitrophenyl)acetate
• CAS: 1118785-34-4
• 化学式: C₁₅H₁₀Cl₃NO₄
• 分子量: 374.608
• InChiKey: USEDOKMMQWLASL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  72.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,2-dichloro-4-[2-(methyl 4-chlorophenylacetate)]-5-nitrobenzene 在 吡啶 、 lead(IV) tetraacetate 、 phenyltrimethylammonium tribromide 、 铁粉 、 potassium carbonate 、 溶剂黄146 、 sodium iodide 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 8.0h， 生成 (+)-N-[5,6-dichloro-3-(4-chlorophenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-2-(4-methyl-piperazin-1-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
• 作为产物：
  描述：

  对氯苯乙酸甲酯 、 1,2-二氯-4-氟-5-硝基苯 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 1,2-dichloro-4-[2-(methyl 4-chlorophenylacetate)]-5-nitrobenzene
  参考文献：
  名称：

  INDOL-2-ONE DERIVATIVES DISUBSTITUTED IN THE 3-POSITION, PREPARATION THEREOF AND THERAPEUTIC USE THEREOF

  摘要：

  本发明涉及3-二取代吲哚-2-酮衍生物，它们的制备方法以及它们的药用应用。

  公开号：

  US20100210662A1

文献信息

• INDOL-2-ONE DERIVATIVES DISUBSTITUTED IN THE 3-POSITION, PREPARATION THEREOF AND THERAPEUTIC USE THEREOF
  申请人：BARONI Marco

  公开号：US20100210662A1

  公开（公告）日：2010-08-19

  The present invention relates to 3-disubstituted indol-2-one derivatives, to their preparation and to their therapeutic application.

  本发明涉及3-二取代吲哚-2-酮衍生物，它们的制备方法以及它们的药用应用。
• Indol-2-one derivatives disubstituted in the 3-position, preparation thereof and therapeutic use thereof
  申请人：Sanofi-Aventis

  公开号：US08202871B2

  公开（公告）日：2012-06-19

  The present application discloses compounds of the formula: and pharmaceutical compositions containing same and their use for treating and preventing various pathologies, including obesity, appetite disorders, excess weight and diabetes.

  本申请公开了以下式子的化合物： 并且包含这些化合物的药物组合物，以及它们用于治疗和预防各种病理情况，包括肥胖症、食欲紊乱、超重和糖尿病。
• 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.