3-(2-(2-(cyclohexylamino)pyrimidin-5-yl)ethynyl)-4-methyl-N-(3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)benzamide | 1257628-65-1

• 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: 3-(2-(2-(cyclohexylamino)pyrimidin-5-yl)ethynyl)-4-methyl-N-(3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)benzamide
• 英文别名: 3-[2-[2-(cyclohexylamino)pyrimidin-5-yl]ethynyl]-4-methyl-N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]benzamide
• CAS: 1257628-65-1
• 化学式: C₃₁H₂₉F₃N₆O
• 分子量: 558.606
• InChiKey: JMMFXXPAQAEXJE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  41
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  84.7
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  N-(3-(三氟甲基)-5-(4-甲基-1H-咪唑-1-基)苯基)-3-碘-4-甲基苯甲酰胺 在 copper(l) iodide 、 palladium bis[bis(diphenylphosphino)ferrocene] dichloride 、 palladium diacetate 、 三乙胺 、 N,N-二异丙基乙胺 、 三环己基膦 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 5.0h， 生成 3-(2-(2-(cyclohexylamino)pyrimidin-5-yl)ethynyl)-4-methyl-N-(3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)benzamide
  参考文献：
  名称：

  Hybrid pyrimidine alkynyls inhibit the clinically resistance related Bcr-AblT315I mutant

  摘要：

  A series of pyrimidine alkynyl derivatives were designed and synthesized as new Bcr-Abl inhibitors by hybriding the structural moieties from GNF-7, ponatinib and nilotinib. One of the most potent compounds 4e strongly suppresses Bcr-Abl(WT) and Bcr-Abl(T315I) kinase with IC50 values of 5.0 and 9.0 nM, and inhibits the proliferation of K562 and murine Ba/F3 cells ectopically expressing Bcr-Abl(T315I) cells with IC50 values of 2 and 50 nM, respectively. It also displays good pharmacokinetics properties with an oral bioavailability of 35.3% and T-1/2 value of 48.7 h, and demonstrates significantly suppression on tumor growth in xenografted mice of K562 and Ba/F3 cells expressing Bcr-Abl(T315I). These inhibitors may serve as lead compounds for further developing new anticancer drugs overcoming the clinically acquired resistance against current Bcr-Abl inhibitors. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.07.006

文献信息

• HETEROCYCLIC ALKYNYL BENZENE COMPOUNDS AND MEDICAL COMPOSITIONS AND USES THEREOF
  申请人：Guangzhou Healthquest Pharma Co., Ltd.

  公开号：EP2594567B1

  公开（公告）日：2020-07-29
• Pharmaceutical Combination and Use Thereof
  申请人：ASCENTAGE PHARMA (SUZHOU) CO., LTD.

  公开号：US20220142975A1

  公开（公告）日：2022-05-12

  The invention discloses a novel pharmaceutical combination and a use thereof. The pharmaceutical combination comprises a compound of formula (I), a pharmaceutically acceptable salt thereof or a solvate thereof; and a compound of formula (II), a pharmaceutically acceptable salt thereof or a solvate thereof. The pharmaceutical combination can be used to treat cancer.
• US8846671B2
  申请人：——

  公开号：US8846671B2

  公开（公告）日：2014-09-30