4-Hydroxy-6-methoxy-7-(3-piperidin-1-yl-propoxy)-quinoline-3-carbonitrile | 460088-39-5

• 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: 4-Hydroxy-6-methoxy-7-(3-piperidin-1-yl-propoxy)-quinoline-3-carbonitrile
• 英文别名: 6-methoxy-4-oxo-7-(3-piperidin-1-ylpropoxy)-1H-quinoline-3-carbonitrile
• CAS: 460088-39-5
• 化学式: C₁₉H₂₃N₃O₃
• 分子量: 341.41
• InChiKey: MOLWHQCTLSWLOH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  74.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-Hydroxy-6-methoxy-7-(3-piperidin-1-yl-propoxy)-quinoline-3-carbonitrile 在 氯化亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 4-[3-Cyano-6-methoxy-7-(3-piperidin-1-yl-propoxy)-quinolin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Identification of 4-piperazin-1-yl-quinazoline template based aryl and benzyl thioureas as potent, selective, and orally bioavailable inhibitors of platelet-derived growth factor (PDGF) receptor

  摘要：

  4-[4-(N-Substituted-thio-carbamoyl)-1-piperazinyl]-6-methoxy-7-alkoxyamino-quinazoline derivatives such as 14 (CT53986) have been identified to be potent and selective inhibitors of the phosphorylation of PDGFR. SAR-investigations are described in the arylamine segment, C-7 appendage, and the thiourea moiety. Bioisosteres of thiourea (cyanoguanidine), and of quinazoline (quinoline-3-carbonitrile) were synthesized and are compared for their in vitro inhibitory activity. PK profiles of the optimized compounds in rat, dog, and cynomolgus monkey are described. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.07.041
• 作为产物：
  描述：

  6-methoxy-7-(3-(piperidin-1-yl)propoxy)quinazolin-4-ol 在 正丁基锂 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-Hydroxy-6-methoxy-7-(3-piperidin-1-yl-propoxy)-quinoline-3-carbonitrile
  参考文献：
  名称：

  Identification of 4-piperazin-1-yl-quinazoline template based aryl and benzyl thioureas as potent, selective, and orally bioavailable inhibitors of platelet-derived growth factor (PDGF) receptor

  摘要：

  4-[4-(N-Substituted-thio-carbamoyl)-1-piperazinyl]-6-methoxy-7-alkoxyamino-quinazoline derivatives such as 14 (CT53986) have been identified to be potent and selective inhibitors of the phosphorylation of PDGFR. SAR-investigations are described in the arylamine segment, C-7 appendage, and the thiourea moiety. Bioisosteres of thiourea (cyanoguanidine), and of quinazoline (quinoline-3-carbonitrile) were synthesized and are compared for their in vitro inhibitory activity. PK profiles of the optimized compounds in rat, dog, and cynomolgus monkey are described. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.07.041

文献信息

• Nitrogen containing heterocyclic quinoline compounds
  申请人：——

  公开号：US20030004158A1

  公开（公告）日：2003-01-02

  The present invention relates to nitrogen-containing heterocyclic quinoline compounds and pharmaceutically acceptable salts thereof which have inhibitory activity on the phosphorylation of kinases, which inhibits the activity of such kinases. The invention is also related to a method of inhibiting kinases and treating disease states in a mammal by inhibiting the phosphorylation of kinases. More particularly, the present invention provides nitrogen-containing heterocyclic compounds and pharmaceutically acceptable salts thereof which inhibit phosphorylation of a PDGF receptor to hinder abnormal cell growth and cell wandering, and a method for preventing or treating cell-proliferative diseases such as arteriosclerosis, vascular reobstruction, cancer and glomerulosclerosis.

  本发明涉及含氮杂环喹啉化合物及其药学上可接受的盐，该化合物对激酶的磷酸化具有抑制活性，从而抑制这些激酶的活性。本发明还涉及通过抑制激酶的磷酸化来抑制激酶并治疗哺乳动物的疾病状态的方法。更具体地，本发明提供了含氮杂环化合物及其药学上可接受的盐，该化合物抑制PDGF受体的磷酸化，从而阻碍异常细胞生长和游走，并提供了一种预防或治疗细胞增殖性疾病，如动脉硬化、血管再狭窄、癌症和肾小球硬化的方法。
• (HOMO)PIPERAZINE SUBSTITUTED QUINOLINES FOR INHIBITING THE PHOSPHORYLATION OF KINASES
  申请人：Millennium Pharmaceuticals, Inc.

  公开号：EP1490362A2

  公开（公告）日：2004-12-29
• US6960580B2
  申请人：——

  公开号：US6960580B2

  公开（公告）日：2005-11-01
• [EN] NITROGEN CONTAINING HETEROCYCLIC QUINOLINE COMPOUNDS<br/>[FR] COMPOSES DE QUINOLINE HETEROCYCLIQUES CONTENANT DE L'AZOTE
  申请人：MILLENNIUM PHARMACEUTICALS

  公开号：WO2002072578A2

  公开（公告）日：2002-09-19

  The present invention relates to nitrogen-containing heterocyclic quinoline compounds and pharmaceutically acceptable salts thereof which have inhibitory activity on the phosphorylation of kinases, which inhibits the activity of such kinases. The invention is also related to a method of inhibiting kinases and treating disease states in a mammal by inhibiting the phosphorylation of kinases. More particularly, the present invention provides nitrogen-containing heterocyclic compounds and pharmaceutically acceptable salts thereof which inhibit phosphorylation of a PDGF receptor to hinder abnormal cell growth and cell wandering, and a method for preventing or treating cell-proliferative diseases such as arteriosclerosis, vascular reobstruction, cancer and glomerulosclerosis.
• Identification of 4-piperazin-1-yl-quinazoline template based aryl and benzyl thioureas as potent, selective, and orally bioavailable inhibitors of platelet-derived growth factor (PDGF) receptor
  作者：Julie A. Heath、Mukund M. Mehrotra、Shannon Chi、Jin-Chen Yu、Athiwat Hutchaleelaha、Stanley J. Hollenbach、Neill A. Giese、Robert M. Scarborough、Anjali Pandey

  DOI：10.1016/j.bmcl.2004.07.041

  日期：2004.10

  4-[4-(N-Substituted-thio-carbamoyl)-1-piperazinyl]-6-methoxy-7-alkoxyamino-quinazoline derivatives such as 14 (CT53986) have been identified to be potent and selective inhibitors of the phosphorylation of PDGFR. SAR-investigations are described in the arylamine segment, C-7 appendage, and the thiourea moiety. Bioisosteres of thiourea (cyanoguanidine), and of quinazoline (quinoline-3-carbonitrile) were synthesized and are compared for their in vitro inhibitory activity. PK profiles of the optimized compounds in rat, dog, and cynomolgus monkey are described. (C) 2004 Elsevier Ltd. All rights reserved.