3-iodo-4-methyl-N-[4-(piperazin-1-ylmethyl)-3-(trifluoromethyl)phenyl]benzamide | 1232836-37-1

• 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-iodo-4-methyl-N-[4-(piperazin-1-ylmethyl)-3-(trifluoromethyl)phenyl]benzamide
• CAS: 1232836-37-1
• 化学式: C₂₀H₂₁F₃IN₃O
• 分子量: 503.306
• InChiKey: RCJUIOJNPMMLHK-UHFFFAOYSA-N

物化性质

• 沸点：
  467.5±45.0 °C(Predicted)
• 密度：
  1.560±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  44.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-iodo-4-methyl-N-[4-(piperazin-1-ylmethyl)-3-(trifluoromethyl)phenyl]benzamide 在 聚合甲醛 、 硼氘化钠 、 溶剂黄146 作用下， 以 甲醇 、 水 为溶剂， 以300 mg的产率得到N-[4-(4-deuteromethylpiperazin-1-ylmethyl)-3-trifluoromethylphenyl]-3-iodo-4-methylbenzamide
  参考文献：
  名称：

  氘代乙炔衍生物、其药物组合物及应用

  摘要：

  本发明公开了一类氘代乙炔衍生物、其药物组合物及应用。该药物组合物，包含治疗有效量的氘代乙炔衍生物（I）、其药学上可接受的盐、立体异构体、溶剂化物、多晶型物、互变异构体、代谢产物和其药物前体中的一种或多种，及至少一种药学上可接受的辅料。本发明还提供了该氘代乙炔衍生物（I）、其药学上可接受的盐、立体异构体、溶剂化物、多晶型物、互变异构体、代谢产物或其药物前体，或该药物组合物制备一种或多种蛋白激酶抑制剂的应用，以及在制备治疗和/或预防肿瘤药物中的应用。本发明的氘代乙炔衍生物（I）可有效抑制一种以上的蛋白激酶活性和肿瘤细胞的生长，并表现出优异的药代动力学性质以及体内外药效。（I）。

  公开号：

  CN104341425B
• 作为产物：
  描述：

  3-碘-4-甲基苯甲酰氯 在 盐酸 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 3-iodo-4-methyl-N-[4-(piperazin-1-ylmethyl)-3-(trifluoromethyl)phenyl]benzamide
  参考文献：
  名称：

  BCR-ABL DIPLOID INHIBITOR, PREPARATION METHOD THEREFOR, AND USES THEREOF

  摘要：

  公开号：

  EP3133069B1

文献信息

• Discovery of 3-[2-(Imidazo[1,2-<i>b</i>]pyridazin-3-yl)ethynyl]-4-methyl-<i>N</i>-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide (AP24534), a Potent, Orally Active Pan-Inhibitor of Breakpoint Cluster Region-Abelson (BCR-ABL) Kinase Including the T315I Gatekeeper Mutant
  作者：Wei-Sheng Huang、Chester A. Metcalf、Raji Sundaramoorthi、Yihan Wang、Dong Zou、R. Mathew Thomas、Xiaotian Zhu、Lisi Cai、David Wen、Shuangying Liu、Jan Romero、Jiwei Qi、Ingrid Chen、Geetha Banda、Scott P. Lentini、Sasmita Das、Qihong Xu、Jeff Keats、Frank Wang、Scott Wardwell、Yaoyu Ning、Joseph T. Snodgrass、Marc I. Broudy、Karin Russian、Tianjun Zhou、Lois Commodore、Narayana I. Narasimhan、Qurish K. Mohemmad、John Iuliucci、Victor M. Rivera、David C. Dalgarno、Tomi K. Sawyer、Tim Clackson、William C. Shakespeare

  DOI：10.1021/jm100395q

  日期：2010.6.24

  In the treatment of chronic myeloid leukemia (CML) with BCR-ABL kinase inhibitors, the T315I gatekeeper mutant has emerged as resistant to all currently approved agents. This report describes the structure-guided design of a novel series of potent pan-inhibitors of BCR-ABL, including the T315I mutation. A key structural feature is the carbon-carbon triple bond linker which skirts the increased bulk of I1e315 side chain. Extensive SAR studies led to the discovery of development candidate 20g (AP24534), which inhibited the kinase activity of both native BCR-ABL and the T315I mutant with low nM IC(50)s, and potently inhibited proliferation of corresponding Ba/F3-derived cell lines. Daily oral administration of 20g significantly prolonged survival of mice injected intravenously with BCR-ABL(T315I) expressing Ba/F3 cells. These data, coupled with a favorable ADME profile, support the potential of 20g to be an effective treatment for CM L, including patients refractory to all currently approved therapies.
• BCR-ABL Diploid Inhibitor, Synthesizing Method Therefor, and Uses Thereof
  申请人：CHENGDU UNIVERSITY

  公开号：US20170037061A1

  公开（公告）日：2017-02-09

  Disclosed are compounds or pharmaceutically acceptable salts thereof having the following general formula: R-Linker-R. The compounds or pharmaceutically acceptable salts thereof provided by the present invention are used as Bcr-Abl diploid inhibitors, which can effectively inhibit the activity of tyrosine kinase, are applicable in treating diseases concerning abnormal activation of such kinases, and have good effects in treating malignant tumors. The method for preparing such inhibitors is simple and convenient, has low cost, and has good application prospects.
• US9969753B2
  申请人：——

  公开号：US9969753B2

  公开（公告）日：2018-05-15