3-Amino-6-methyl-4-(methylthio)thieno[2,3-b]pyridine-2-carboxamide | 635732-14-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并吡啶类
• 英文名称: 3-Amino-6-methyl-4-(methylthio)thieno[2,3-b]pyridine-2-carboxamide
• 英文别名: 3-amino-6-methyl-4-methylsulfanylthieno[2,3-b]pyridine-2-carboxamide
• CAS: 635732-14-8
• 化学式: C₁₀H₁₁N₃OS₂
• 分子量: 253.349
• InChiKey: RURKZBBDSJAHAZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  136
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-Amino-6-methyl-4-(methylthio)thieno[2,3-b]pyridine-2-carboxamide 、 2-吡啶硼酸 在 tris-(dibenzylideneacetone)dipalladium(0) 、 噻吩-2-甲酸亚铜(I) 、 三(2-呋喃基)膦 作用下， 以 四氢呋喃 为溶剂， 生成 3-Amino-6-methyl-4-(pyridin-2-yl)thieno[2,3-b]pyridine-2-carboxamide
  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
• 作为产物：
  描述：

  4,4-bis(methylthio)but-3-en-2-one 在 sodium methylate 、 sodium 作用下， 以 甲醇 、 异丙醇 为溶剂， 反应 32.0h， 生成 3-Amino-6-methyl-4-(methylthio)thieno[2,3-b]pyridine-2-carboxamide
  参考文献：
  名称：

  [EN] SUBSTITUTED 3-AMINO-THIENO[2,3-b]PYRIDINE-2-CARBOXYLIC ACID AMIDE COMPOUNDS AND PROCESSES FOR PREPARING AND THEIR USES
  [FR] COMPOSES AMIDE D'ACIDE 3-AMINO-THIENO[2,3-b]PYRIDINE-2-CARBOXYLIQUE SUBSTITUES ET PROCESSUS DE PREPARATION ET D'UTILISATION DE CES COMPOSES

  摘要：

  公开的是式(I)的化合物，其中R1和R2如本文所定义，这些化合物可用作IκB激酶（IKK）复合物激酶活性的抑制剂。因此，这些化合物在治疗IKK介导的疾病，包括自身免疫疾病、炎症性疾病和癌症方面是有用的。还公开了包含这些化合物的药物组合物以及制备这些化合物的方法。

  公开号：

  WO2003103661A1

文献信息

• US7405225B2
  申请人：——

  公开号：US7405225B2

  公开（公告）日：2008-07-29
• [EN] SUBSTITUTED 3-AMINO-THIENO[2,3-b]PYRIDINE-2-CARBOXYLIC ACID AMIDE COMPOUNDS AND PROCESSES FOR PREPARING AND THEIR USES<br/>[FR] COMPOSES AMIDE D'ACIDE 3-AMINO-THIENO[2,3-b]PYRIDINE-2-CARBOXYLIQUE SUBSTITUES ET PROCESSUS DE PREPARATION ET D'UTILISATION DE CES COMPOSES
  申请人：BOEHRINGER INGELHEIM PHARMA

  公开号：WO2003103661A1

  公开（公告）日：2003-12-18

  Disclosed are compounds of formula (I), wherein R1 and R2 are defined herein, which are useful as inhibitors of the kinase activity of the IκB kinase (IKK) complex. The compounds are therefore useful in the treatment of IKK mediated diseases including autoimmune diseases inflammatory diseases and cancer. Also disclosed are pharmaceutical compositions comprising these compounds and processes for preparing these compounds.

  公开的是式(I)的化合物，其中R1和R2如本文所定义，这些化合物可用作IκB激酶（IKK）复合物激酶活性的抑制剂。因此，这些化合物在治疗IKK介导的疾病，包括自身免疫疾病、炎症性疾病和癌症方面是有用的。还公开了包含这些化合物的药物组合物以及制备这些化合物的方法。
• 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.