2-(4-fluorophenyl)-3-(2-(methylthio)pyrimidin-4-yl)imidazo[1,2-a]pyrimidin-7-amine | 340042-06-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(4-fluorophenyl)-3-(2-(methylthio)pyrimidin-4-yl)imidazo[1,2-a]pyrimidin-7-amine
• 英文别名: 2-(4-fluorophenyl)-3-[2-(methylthio)-4-pyrimidinyl]imidazo[1,2-a]pyrimidin-7-amine；2-(4-Fluorophenyl)-3-(2-methylsulfanylpyrimidin-4-yl)imidazo[1,2-a]pyrimidin-7-amine
• CAS: 340042-06-0
• 化学式: C₁₇H₁₃FN₆S
• 分子量: 352.395
• InChiKey: BVOXXCFSYHFTLW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  107
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-(4-fluorophenyl)-3-(2-(methylthio)pyrimidin-4-yl)imidazo[1,2-a]pyrimidin-7-amine 在 Oxone 作用下， 以 甲醇 、 水 为溶剂， 生成 2-(4-fluorophenyl)-3-(2-(methylsulfonyl)pyrimidin-4-yl)imidazo[1,2-a]pyrimidin-7-amine
  参考文献：
  名称：

  Synthesis and structure–activity relationships of 4-fluorophenyl-imidazole p38α MAPK, CK1δ and JAK2 kinase inhibitors

  摘要：

  The synthesis and structure-activity relationships of novel 4-(4 '-fluorophenyl)imidazoles as selective p38 alpha MAPK, CK1 delta and JAK2 inhibitors with improved water solubility are described. Microwave-assisted multicomponent reactions afforded 4-fluorophenyl-2,5-disubstituted imidazoles. Carboxylate and phosphonate groups were introduced via 'click' reactions. The kinase selectivity was influenced by the heteroaryl group at imidazole C-5 and the position of a carboxylic acid or tetrazole at imidazole C-2. For example, pyrimidines 15 and 34 inhibited p38 alpha MAPK with IC50 = 250 nM and 96 nM, respectively. Pyridine 3 gave CK1 delta inhibition with IC50 = 89 nM and pyridin-2-one 31 gave JAK2 inhibition with IC50 = 62 nM. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.05.080
• 作为产物：
  描述：

  2,4-二氨基嘧啶 、 2-bromo-1-(4-fluorophenyl)-2-(2-methylsulfanylpyrimidin-4-yl)ethanone 以 乙醇 为溶剂， 反应 12.67h， 以42%的产率得到2-(4-fluorophenyl)-3-(2-(methylthio)pyrimidin-4-yl)imidazo[1,2-a]pyrimidin-7-amine
  参考文献：
  名称：

  Synthesis and structure–activity relationships of 4-fluorophenyl-imidazole p38α MAPK, CK1δ and JAK2 kinase inhibitors

  摘要：

  The synthesis and structure-activity relationships of novel 4-(4 '-fluorophenyl)imidazoles as selective p38 alpha MAPK, CK1 delta and JAK2 inhibitors with improved water solubility are described. Microwave-assisted multicomponent reactions afforded 4-fluorophenyl-2,5-disubstituted imidazoles. Carboxylate and phosphonate groups were introduced via 'click' reactions. The kinase selectivity was influenced by the heteroaryl group at imidazole C-5 and the position of a carboxylic acid or tetrazole at imidazole C-2. For example, pyrimidines 15 and 34 inhibited p38 alpha MAPK with IC50 = 250 nM and 96 nM, respectively. Pyridine 3 gave CK1 delta inhibition with IC50 = 89 nM and pyridin-2-one 31 gave JAK2 inhibition with IC50 = 62 nM. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.05.080

文献信息

• SUBSTITUTED 2-ARYL-3-(HETEROARYL)-IMIDAZO[1,2-ALPHA]PYRIMIDINES, AND RELATED PHARMACEUTICAL COMPOSITIONS AND METHODS
  申请人：Ortho-McNeil Pharmaceutical, Inc.

  公开号：EP1140939A1

  公开（公告）日：2001-10-10
• US6610697B1
  申请人：——

  公开号：US6610697B1

  公开（公告）日：2003-08-26
• [EN] SUBSTITUTED 2-ARYL-3-(HETEROARYL)-IMIDAZO[1,2-a]PYRIMIDINES, AND RELATED PHARMACEUTICAL COMPOSITIONS AND METHODS<br/>[FR] 2-ARYL-3-(HETEROARYL)-IMIDAZO[1,2-a]PYRIMIDINES SUBSTITUEES, ET COMPOSITIONS PHARMACEUTIQUES ET PROCEDES ASSOCIES
  申请人：ORTHO MCNEIL PHARM INC

  公开号：WO2001034605A1

  公开（公告）日：2001-05-17

  This invention relates to a series of imidazopyrimidines of Formula (I), and pharmaceutical compositions containing them. The compounds of the invention inhibit the production of a number of inflammatory cytokines and are useful in the treatment and prevention of diseases associated with the overproduction thereof.
• Synthesis and structure–activity relationships of 4-fluorophenyl-imidazole p38α MAPK, CK1δ and JAK2 kinase inhibitors
  作者：Jean-Paul G. Seerden、Gabriela Leusink-Ionescu、Titia Woudenberg-Vrenken、Bas Dros、Grietje Molema、Jan A.A.M. Kamps、Richard M. Kellogg

  DOI：10.1016/j.bmcl.2014.05.080

  日期：2014.8

  The synthesis and structure-activity relationships of novel 4-(4 '-fluorophenyl)imidazoles as selective p38 alpha MAPK, CK1 delta and JAK2 inhibitors with improved water solubility are described. Microwave-assisted multicomponent reactions afforded 4-fluorophenyl-2,5-disubstituted imidazoles. Carboxylate and phosphonate groups were introduced via 'click' reactions. The kinase selectivity was influenced by the heteroaryl group at imidazole C-5 and the position of a carboxylic acid or tetrazole at imidazole C-2. For example, pyrimidines 15 and 34 inhibited p38 alpha MAPK with IC50 = 250 nM and 96 nM, respectively. Pyridine 3 gave CK1 delta inhibition with IC50 = 89 nM and pyridin-2-one 31 gave JAK2 inhibition with IC50 = 62 nM. (C) 2014 Elsevier Ltd. All rights reserved.