4-N-(2-chlorophenyl)-5-fluoro-2-N-[4-(2H-tetrazol-5-yl)phenyl]pyrimidine-2,4-diamine;hydrochloride | 1395886-29-9

• 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-N-(2-chlorophenyl)-5-fluoro-2-N-[4-(2H-tetrazol-5-yl)phenyl]pyrimidine-2,4-diamine;hydrochloride
• CAS: 1395886-29-9
• 化学式: C₁₇H₁₂ClFN₈*ClH
• 分子量: 419.248
• InChiKey: NVULRZKLMNNTFR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.36
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  104
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  对硝基苯甲腈 在 palladium 10% on activated carbon sodium azide 、 氢气 、 三乙胺盐酸盐 作用下， 以 甲醇 、 乙醇 、 甲苯 为溶剂， 反应 0.67h， 生成 4-N-(2-chlorophenyl)-5-fluoro-2-N-[4-(2H-tetrazol-5-yl)phenyl]pyrimidine-2,4-diamine;hydrochloride
  参考文献：
  名称：

  [EN] AURORA KINASE INHIBITORS AND METHODS OF MAKING AND USING THEREOF
  [FR] INHIBITEURS DE KINASE AURORA ET PROCÉDÉS POUR LES FABRIQUER ET LES UTILISER

  摘要：

  公开号：

  WO2012135641A3

文献信息

• Development of <i>o</i>-Chlorophenyl Substituted Pyrimidines as Exceptionally Potent Aurora Kinase Inhibitors
  作者：Harshani R. Lawrence、Mathew P. Martin、Yunting Luo、Roberta Pireddu、Hua Yang、Harsukh Gevariya、Sevil Ozcan、Jin-Yi Zhu、Robert Kendig、Mercedes Rodriguez、Roy Elias、Jin Q. Cheng、Saïd M. Sebti、Ernst Schonbrunn、Nicholas J. Lawrence

  DOI：10.1021/jm300334d

  日期：2012.9.13

  The o-carboxylic acid substituted bisanilinopyrimidine 1 was identified as a potent hit (Aurora A IC50 = 6.1 +/- 1.0 nM) from in-house screening. Detailed structure-activity relationship (SAR) studies indicated that polar substituents at the para position of the B-ring are critical for potent activity. X-ray crystallography studies revealed that compound 1 is a type I inhibitor that binds the Aurora kinase active site in a DFG-in conformation. Structure-activity guided replacement of the A-ring carboxylic acid with halogens and incorporation of fluorine at the pyrimidine 5-position led to highly potent inhibitors of Aurora A that bind in a DFG-out conformation. B-Ring modifications were undertaken to improve the solubility and cell permeability. Compounds such as 9m with water-solubilizing moieties at the para position of the B-ring inhibited the autophosphorylation of Aurora A in MDA-MB-468 breast cancer cells.