5,6-Dichloro-1,3-dihydro-3-(4-chlorophenyl)-indole-2-one | 1118785-31-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 5,6-Dichloro-1,3-dihydro-3-(4-chlorophenyl)-indole-2-one
• 英文别名: 5,6-dichloro-1,3-dihydro-3-(4-chlorophenyl)indol-2-one；5,6-Dichloro-3-(4-chlorophenyl)-1,3-dihydroindol-2-one
• CAS: 1118785-31-1
• 化学式: C₁₄H₈Cl₃NO
• 分子量: 312.583
• InChiKey: WGURKWVPEGGKTB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  5,6-Dichloro-1,3-dihydro-3-(4-chlorophenyl)-indole-2-one 在 吡啶 、 lead(IV) tetraacetate 、 phenyltrimethylammonium tribromide 、 potassium carbonate 、 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 在 铁粉 、 溶剂黄146 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 5,6-Dichloro-1,3-dihydro-3-(4-chlorophenyl)-indole-2-one
  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

• 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。
• DÉRIVÉS DE L'IND0L-2-0NE DISUBSTITUES EN 3, LEUR PREPARATION ET LEUR APPLICATION EN THÉRAPEUTIQUE
  申请人：Sanofi-Aventis

  公开号：EP2188253A2

  公开（公告）日：2010-05-26
• Dérivés de l'indol-2-one disubstitués en 3, leur préparation et leur application en thérapeutique
  申请人：SANOFI

  公开号：EP2188253B1

  公开（公告）日：2012-03-07
• US8202871B2
  申请人：——

  公开号：US8202871B2

  公开（公告）日：2012-06-19
• [EN] INDOL-2-ONE DERIVATIVES DISUBSTITUTED IN THE 3-POSITION, PREPARATION THEREOF AND THERAPEUTIC USE THEREOF<br/>[FR] DÉRIVÉS DE L'IND0L-2-0NE DISUBSTITUES EN 3, LEUR PREPARATION ET LEUR APPLICATION EN THÉRAPEUTIQUE
  申请人：SANOFI AVENTIS

  公开号：WO2009056707A2

  公开（公告）日：2009-05-07

  La présente invention a pour objet des dérivés de Pindol-2-one disubstitués en 3, de formule générale (I) : dans laquelle, R1, R2, R3, R4, R5, Ar et n sont tels que définis dans la revendication 1, le procédé de préparation et l'application thérapeutique desdits composés.