methyl 2-[(3-{[4-(phenylsulfonyl)piperazin-1-yl]methyl}-2-phenylquinolin-4-yl)carbonyl]-1-phenylhydrazinecarboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: methyl 2-[(3-{[4-(phenylsulfonyl)piperazin-1-yl]methyl}-2-phenylquinolin-4-yl)carbonyl]-1-phenylhydrazinecarboxylate
• 英文别名: N''-[3-(4-benzenesulfonyl-piperazin-1-ylmethyl)-2-phenyl-quinoline-4-carbonyl]-N-phenyl-hydrazinecarboxylic acid methyl ester；methyl N-[[3-[[4-(benzenesulfonyl)piperazin-1-yl]methyl]-2-phenylquinoline-4-carbonyl]amino]-N-phenylcarbamate
• 化学式: C₃₅H₃₃N₅O₅S
• 分子量: 635.744
• InChiKey: CIOJAMZWKYLIDE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  46
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  121
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3-methyl-2-phenyl-4-quinolinecarboxylic acid, 2-(methoxycarbonyl)-2-phenylhydrazide 在 N-溴代丁二酰亚胺(NBS) 、 sodium hydride 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 四氯化碳 、 二氯甲烷 为溶剂， 生成 methyl 2-[(3-{[4-(phenylsulfonyl)piperazin-1-yl]methyl}-2-phenylquinolin-4-yl)carbonyl]-1-phenylhydrazinecarboxylate
  参考文献：
  名称：

  N′,2-Diphenylquinoline-4-carbohydrazide based NK3 receptor antagonists II

  摘要：

  Introduction of selected amine containing side chains into the 3-position of N',2-diphenylquinoline-4-carbohydrazide based NK3 antagonists abolishes unwanted hPXR activation. Introduction of a fluorine at the 8-position is necessary to minimize unwanted hIK(r) affinity and a piperazine N-tert-butyl group is necessary for metabolic stability. The lead compound (8m) occupies receptors within the CNS following oral dosing (Occ(90) 7 mg/kg po; plasma Occgo 0.4 mu M) and has good selectivity and excellent PK properties. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.08.085

文献信息

• Quinoline derivatives as neurokinin receptor antagonists
  申请人：Carling William Robert

  公开号：US20090054440A1

  公开（公告）日：2009-02-26

  The present invention relates to substituted quinoline hydrazides of Formula (I): wherein R 1 , R 2 , R 3 , R 4 , R 5 , X, Y and Z are defined herein, pharmaceutical compositions comprising them and their use in treating diseases mediated by neurokinin-2 and/or neurokinin-3 (NK-3) receptors. These compounds can thus be used in methods of treatment to suppress and treat such disorders.

  本发明涉及式(I)所示的取代喹啉酰肼：其中R1、R2、R3、R4、R5、X、Y和Z在此定义，包含它们的药物组合物及其在治疗由神经激肽-2和/或神经激肽-3 (NK-3)受体介导的疾病中的用途。因此，这些化合物可用于治疗方法，以抑制和治疗这些疾病。
• N′,2-Diphenylquinoline-4-carbohydrazide based NK3 receptor antagonists II
  作者：Jason M. Elliott、Robert W. Carling、Gary G. Chicchi、James Crawforth、Peter H. Hutson、A. Brian Jones、Sarah Kelly、Rose Marwood、Georgina Meneses-Lorente、Elena Mezzogori、Fraser Murray、Michael Rigby、Inmaculada Royo、Michael G.N. Russell、Duncan Shaw、Bindi Sohal、Kwei Lan Tsao、Brian Williams

  DOI：10.1016/j.bmcl.2006.08.085

  日期：2006.11

  Introduction of selected amine containing side chains into the 3-position of N',2-diphenylquinoline-4-carbohydrazide based NK3 antagonists abolishes unwanted hPXR activation. Introduction of a fluorine at the 8-position is necessary to minimize unwanted hIK(r) affinity and a piperazine N-tert-butyl group is necessary for metabolic stability. The lead compound (8m) occupies receptors within the CNS following oral dosing (Occ(90) 7 mg/kg po; plasma Occgo 0.4 mu M) and has good selectivity and excellent PK properties. (c) 2006 Elsevier Ltd. All rights reserved.