N4-(2'-methoxyphenyl)-N2-(4'-carboxyphenyl)pyrimidine-2,4-diamine hydrochloride | 1395885-38-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N4-(2'-methoxyphenyl)-N2-(4'-carboxyphenyl)pyrimidine-2,4-diamine hydrochloride
• 英文别名: 4-[[4-(2-Methoxyanilino)pyrimidin-2-yl]amino]benzoic acid;hydrochloride；4-[[4-(2-methoxyanilino)pyrimidin-2-yl]amino]benzoic acid;hydrochloride
• CAS: 1395885-38-7
• 化学式: C₁₈H₁₆N₄O₃*ClH
• 分子量: 372.811
• InChiKey: MIPUIHOSHUZRSM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.09
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  96.4
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  邻甲氧基苯胺 在 sodium carbonate 作用下， 以 乙醇 、 正丁醇 为溶剂， 反应 24.33h， 生成 N4-(2'-methoxyphenyl)-N2-(4'-carboxyphenyl)pyrimidine-2,4-diamine hydrochloride
  参考文献：
  名称：

  Development of o-Chlorophenyl Substituted Pyrimidines as Exceptionally Potent Aurora Kinase Inhibitors

  摘要：

  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.

  DOI：

  10.1021/jm300334d

文献信息

• [EN] AURORA KINASE INHIBITORS AND METHODS OF MAKING AND USING THEREOF<br/>[FR] INHIBITEURS DE KINASE AURORA ET PROCÉDÉS POUR LES FABRIQUER ET LES UTILISER
  申请人：H LEE MOFFITT CANCER CT AND RES INST

  公开号：WO2012135641A3

  公开（公告）日：2012-12-27
• 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.