N⁴-(2-chlorophenyl)-N⁴-methyl-2-chloropyrimidine-4-amine | 1395887-00-9

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N⁴-(2-chlorophenyl)-N⁴-methyl-2-chloropyrimidine-4-amine
• 英文别名: 2-chloro-N-(2-chlorophenyl)-N-methylpyrimidin-4-amine
• CAS: 1395887-00-9
• 化学式: C₁₁H₉Cl₂N₃
• 分子量: 254.119
• InChiKey: PEPLGLUTHYIFKS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  29
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N⁴-(2-chlorophenyl)-N⁴-methyl-2-chloropyrimidine-4-amine 、 对氨基苯甲酸 以 乙醇 为溶剂， 反应 0.33h， 以80%的产率得到N4-(2'-chlorophenyl)-N2-(4'-carboxyphenyl)-N4-methylpyrimidine-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
• 作为产物：
  描述：

  邻氨基苯甲酸 在 盐酸 、 caesium carbonate 作用下， 以 水 、 乙腈 为溶剂， 反应 72.0h， 生成 N⁴-(2-chlorophenyl)-N⁴-methyl-2-chloropyrimidine-4-amine
  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

• AURORA KINASE INHIBITORS AND METHODS OF MAKING AND USING THEREOF
  申请人：Sebti Said M.

  公开号：US20140057913A1

  公开（公告）日：2014-02-27

  Described herein are inhibitors of Aurora kinase and their use in the treatment of cancer. Methods of screening for selective inhibitors of Aurora kinases are also disclosed.

  本文描述了Aurora激酶的抑制剂及其在癌症治疗中的应用。还公开了筛选选择性抑制Aurora激酶的方法。
• US9249124B2
  申请人：——

  公开号：US9249124B2

  公开（公告）日：2016-02-02
• US9597329B2
  申请人：——

  公开号：US9597329B2

  公开（公告）日：2017-03-21
• [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.