4-[6-(cyclopropylmethyl-amino)-imidazo[1,2-b]pyridazin-3-yl]-benzoic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-[6-(cyclopropylmethyl-amino)-imidazo[1,2-b]pyridazin-3-yl]-benzoic acid
• 英文别名: 4-[6-(Cyclopropylmethylamino)imidazo[1,2-b]pyridazin-3-yl]benzoic acid
• 化学式: C₁₇H₁₆N₄O₂
• 分子量: 308.34
• InChiKey: BVUMSYXOGPTUHI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  79.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-[6-(cyclopropylmethyl-amino)-imidazo[1,2-b]pyridazin-3-yl]-benzoic acid 、 1,2-丙二胺 在 4-(4,6-二甲氧基三嗪-2-基)-4-甲基吗啉盐酸盐 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-(2-aminopropyl)-4-(6-(cyclopropylmethylamino)imidazo[1,2-b]pyridazin-3-yl)benzamide
  参考文献：
  名称：

  Discovery of imidazo[1,2-b]pyridazine derivatives as IKKβ inhibitors. Part 1: Hit-to-lead study and structure–activity relationship

  摘要：

  Imidazo[1,2-b] pyridazine derivatives from high-throughput screening were developed as IKK beta inhibitors. By the optimization of the 3- and 6-position of imidazo[1,2-b] pyridazine scaffold, cell-free IKK beta inhibitory activity and TNF alpha inhibitory activity in THP-1 cell increased. Also, these compounds showed high kinase selectivity. The structure-activity relationship was revealed and the interaction model of imidazo[ 1,2-b] pyridazine compounds with IKKb was constructed. (C) 2010 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2010.07.026
• 作为产物：
  描述：

  4-(6-chloroimidazo[1,2-b]pyridazin-3-yl)benzoic acid 、 环丙基甲胺 生成 4-[6-(cyclopropylmethyl-amino)-imidazo[1,2-b]pyridazin-3-yl]-benzoic acid
  参考文献：
  名称：

  Discovery of imidazo[1,2-b]pyridazine derivatives as IKKβ inhibitors. Part 1: Hit-to-lead study and structure–activity relationship

  摘要：

  Imidazo[1,2-b] pyridazine derivatives from high-throughput screening were developed as IKK beta inhibitors. By the optimization of the 3- and 6-position of imidazo[1,2-b] pyridazine scaffold, cell-free IKK beta inhibitory activity and TNF alpha inhibitory activity in THP-1 cell increased. Also, these compounds showed high kinase selectivity. The structure-activity relationship was revealed and the interaction model of imidazo[ 1,2-b] pyridazine compounds with IKKb was constructed. (C) 2010 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2010.07.026

文献信息

• Substituted imidazo[1,2b]pyridazines as kinase inhibitors, their preparation and use as medicaments
  申请人：Prien Olaf

  公开号：US20070093490A1

  公开（公告）日：2007-04-26

  The invention relates to novel inhibitors of kinases, methods for preparing such inhibitors, intermediates for the preparation of such inhibitors and uses of such inhibitors.

  这项发明涉及新型激酶抑制剂，制备这种抑制剂的方法，制备这种抑制剂的中间体以及这种抑制剂的用途。
• Discovery of imidazo[1,2-b]pyridazines as IKKβ inhibitors. Part 2: Improvement of potency in vitro and in vivo
  作者：Hiroki Shimizu、Isao Yasumatsu、Tomoaki Hamada、Yoshiyuki Yoneda、Tomonori Yamasaki、Shinji Tanaka、Tadashi Toki、Mika Yokoyama、Kaoru Morishita、Shin Iimura

  DOI：10.1016/j.bmcl.2010.12.078

  日期：2011.2

  We have increased the potency of imidazo[1,2-b]pyridazine derivatives as IKK beta inhibitors with two strategies. One is to enhance the activity in cell-based assay by adjusting the polarity of molecules to improve permeability. Another is to increase the affinity for IKK beta by the introduction of additional substituents based on the hypothesis derived from an interaction model study. These improved compounds showed inhibitory activity of TNF alpha production in mice. (C) 2010 Elsevier Ltd. All rights reserved.
• US7750000B2
  申请人：——

  公开号：US7750000B2

  公开（公告）日：2010-07-06
• Discovery of imidazo[1,2-b]pyridazine derivatives as IKKβ inhibitors. Part 1: Hit-to-lead study and structure–activity relationship
  作者：Hiroki Shimizu、Shinji Tanaka、Tadashi Toki、Isao Yasumatsu、Toshihiko Akimoto、Kaoru Morishita、Tomonori Yamasaki、Takanori Yasukochi、Shin Iimura

  DOI：10.1016/j.bmcl.2010.07.026

  日期：2010.9

  Imidazo[1,2-b] pyridazine derivatives from high-throughput screening were developed as IKK beta inhibitors. By the optimization of the 3- and 6-position of imidazo[1,2-b] pyridazine scaffold, cell-free IKK beta inhibitory activity and TNF alpha inhibitory activity in THP-1 cell increased. Also, these compounds showed high kinase selectivity. The structure-activity relationship was revealed and the interaction model of imidazo[ 1,2-b] pyridazine compounds with IKKb was constructed. (C) 2010 Published by Elsevier Ltd.