methyl 2-({3-[(piperidin-4-yl)methyl]-2-phenylquinolin-4-yl}carbonyl)-1-phenylhydrazinecarboxylate | 914654-70-9

• 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-[(piperidin-4-yl)methyl]-2-phenylquinolin-4-yl}carbonyl)-1-phenylhydrazinecarboxylate
• 英文别名: N-phenyl-N''-(2-phenyl-3-piperidin-4-ylmethyl-quinoline-4-carbonyl)-hydrazinecarboxylic acid methyl ester；methyl N-phenyl-N-[[2-phenyl-3-(piperidin-4-ylmethyl)quinoline-4-carbonyl]amino]carbamate
• CAS: 914654-70-9
• 化学式: C₃₀H₃₀N₄O₃
• 分子量: 494.593
• InChiKey: PBTLGBUWEUHXKQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  37
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  83.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 2-({3-[(piperidin-4-yl)methyl]-2-phenylquinolin-4-yl}carbonyl)-1-phenylhydrazinecarboxylate 、 四氢吡喃酮 在 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 生成 methyl 1-phenyl-2-(2-phenyl-3-((1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)methyl)quinoline-4-carbonyl)hydrazinecarboxylate
  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
• 作为产物：
  描述：

  Methyl 2-{[3-({1-[(1,1-Dimethylethoxy)carbonyl]piperidin-4-yl}methyl)-2-phenylquinolin-4-yl]carbonyl}-1-phenylhydrazinecarboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 methyl 2-({3-[(piperidin-4-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。
• QUINOLINE DERIVATIVES AS NEUROKININ RECEPTOR ANTAGONISTS
  申请人：MERCK SHARP & DOHME LTD.

  公开号：EP1888530A2

  公开（公告）日：2008-02-20
• [EN] QUINOLINE DERIVATIVES AS NEUROKININ RECEPTOR ANTAGONISTS<br/>[FR] DERIVES DE QUINOLINE UTILISES COMME ANTAGONISTES DU RECEPTEUR DE LA NEUROKININE
  申请人：MERCK SHARP & DOHME

  公开号：WO2006120478A2

  公开（公告）日：2006-11-16

  [EN] The present invention relates to substituted quinoline hydrazides of Formula (I): (CH2) 0-6 -Z- (CHR5V- R2 (I) wherein R1, R2, R3, R4, R5, 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.
  [FR] La présente invention concerne des hydrazides de quinoline substitués de formule (I) (CH2) 0-6 -Z- (CHR5V- R2), dans laquelle R1, R2, R3, R4, R5, X, Y et Z sont tels que définis dans le mémorandum descriptif. Elle concerne également des compositions pharmaceutiques comprenant ces composés et leur utilisation dans le traitement de maladies induites par les récepteurs de la neurokinine 2 et/ou de la neurokinine 3 (NK3). Ces composés peuvent donc être utilisés dans des méthodes de traitement pour traiter et vaincre ces troubles.
• 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.