3-(2-(2-(isopropylamino)pyrimidin-5-yl)ethynyl)-4-methyl-N-(3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)benzamide | 1257628-81-1

• 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-(isopropylamino)pyrimidin-5-yl)ethynyl)-4-methyl-N-(3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)benzamide
• 英文别名: 4-methyl-N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[2-[2-(propan-2-ylamino)pyrimidin-5-yl]ethynyl]benzamide
• CAS: 1257628-81-1
• 化学式: C₂₈H₂₅F₃N₆O
• 分子量: 518.541
• InChiKey: FXYAYKHUOYATRN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  38
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 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-(isopropylamino)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
• [EN] HETEROCYCLIC ALKYNYL BENZENE COMPOUNDS AND MEDICAL COMPOSITIONS AND USES THEREOF<br/>[FR] COMPOSÉS BENZÈNE ALKYNYL HÉTÉROCYCLIQUES, COMPOSITIONS MÉDICALES ET LEURS UTILISATIONS
  申请人：GUANGZHOU INST OF BIOMEDICINE AND HEALTH

  公开号：WO2012000304A1

  公开（公告）日：2012-01-05

  Heterocyclic alkynyl benzene compounds of formula (I), pharmaceutically acceptable salts or stereomers thereof, as well as uses in preparing drugs for preventing or treating tumors. The compounds can overcome Gleevec induced drug resistance.
• Hybrid pyrimidine alkynyls inhibit the clinically resistance related Bcr-AblT315I mutant
  作者：Xiaoyun Lu、Zhang Zhang、Xiaomei Ren、Xiaofeng Pan、Deping Wang、Xiaoxi Zhuang、Jingfeng Luo、Rongmin Yu、Ke Ding

  DOI：10.1016/j.bmcl.2015.07.006

  日期：2015.9

  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.