2-Chloro-4-propoxypyridine-3-carbonitrile | 1196835-34-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-Chloro-4-propoxypyridine-3-carbonitrile
• 英文别名: 2-chloro-4-propoxypyridine-3-carbonitrile
• CAS: 1196835-34-3
• 化学式: C₉H₉ClN₂O
• 分子量: 196.636
• InChiKey: DWDZOMIUIBUOSH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  45.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-chloro-3-cyano-4-hydroxypyridine 、 溴丙烷 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 2-bromo-4-propoxynicotinonitrile 、 2-Chloro-4-propoxypyridine-3-carbonitrile
  参考文献：
  名称：

  The discovery of thienopyridine analogues as potent IκB kinase β inhibitors. Part II

  摘要：

  An SAR study that identified a series of thienopyridine-based potent I kappa B Kinase beta (IKK beta) inhibitors is described. With focuses on the structural optimization at C(4) and C(6) of structure 1 (Fig. 1), the study reveals that small alkyl and certain aromatic groups are preferred at C(4), whereas polar groups with proper orientation at C(6) efficiently enhance compound potency. The most potent analogues inhibit IKKb with IC(50)s as low as 40 nM, suppress LPS-induced TNF-alpha production in vitro and in vivo, display good kinase selectivity profiles, and are active in a HeLa cell NF-kappa B reporter gene assay, demonstrating that they directly interfere with the NF-kappa B signaling pathway. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.08.054

文献信息

• BORON-CONTAINING SMALL MOLECULES AS ANTI-INFLAMMATORY AGENTS
  申请人：Anacor Pharmaceuticals, Inc.

  公开号：EP2187893A2

  公开（公告）日：2010-05-26
• [EN] BORON-CONTAINING SMALL MOLECULES AS ANTI-INFLAMMATORY AGENTS<br/>[FR] PETITES MOLÉCULES CONTENANT DU BORE UTILISÉES EN TANT QU'AGENTS ANTI-INFLAMMATOIRES
  申请人：ANACOR PHARMACEUTICALS INC

  公开号：WO2009111676A2

  公开（公告）日：2009-09-11

  Compounds and methods of treating anti-inflammatory conditions are disclosed.
• The discovery of thienopyridine analogues as potent IκB kinase β inhibitors. Part II
  作者：Jiang-Ping Wu、Roman Fleck、Janice Brickwood、Alison Capolino、Katrina Catron、Zhidong Chen、Charles Cywin、Jonathan Emeigh、Melissa Foerst、John Ginn、Matt Hrapchak、Eugene Hickey、Ming-Hong Hao、Mohammed Kashem、Jun Li、Weimin Liu、Tina Morwick、Richard Nelson、Daniel Marshall、Leslie Martin、Peter Nemoto、Ian Potocki、Michel Liuzzi、Gregory W. Peet、Erika Scouten、David Stefany、Michael Turner、Steve Weldon、Clare Zimmitti、Denise Spero、Terence A. Kelly

  DOI：10.1016/j.bmcl.2009.08.054

  日期：2009.10

  An SAR study that identified a series of thienopyridine-based potent I kappa B Kinase beta (IKK beta) inhibitors is described. With focuses on the structural optimization at C(4) and C(6) of structure 1 (Fig. 1), the study reveals that small alkyl and certain aromatic groups are preferred at C(4), whereas polar groups with proper orientation at C(6) efficiently enhance compound potency. The most potent analogues inhibit IKKb with IC(50)s as low as 40 nM, suppress LPS-induced TNF-alpha production in vitro and in vivo, display good kinase selectivity profiles, and are active in a HeLa cell NF-kappa B reporter gene assay, demonstrating that they directly interfere with the NF-kappa B signaling pathway. (C) 2009 Elsevier Ltd. All rights reserved.