4-methyl-3-((1-methyl-1H-imidazol-5-yl)ethynyl)-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)benzamide | 1056942-46-1

• 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: 4-methyl-3-((1-methyl-1H-imidazol-5-yl)ethynyl)-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)benzamide
• 英文别名: 4-methyl-3-[2-(3-methylimidazol-4-yl)ethynyl]-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]benzamide
• CAS: 1056942-46-1
• 化学式: C₂₇H₂₈F₃N₅O
• 分子量: 495.547
• InChiKey: CNDIRRPUJPHPNW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  53.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  5-[(三甲基硅烷)乙炔基])-1-甲基咪唑 在 甲醇 、 copper(l) iodide 、 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-methyl-3-((1-methyl-1H-imidazol-5-yl)ethynyl)-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)benzamide
  参考文献：
  名称：

  Discovery of 5-(arenethynyl) hetero-monocyclic derivatives as potent inhibitors of BCR–ABL including the T315I gatekeeper mutant

  摘要：

  Ponatinib (AP24534) was previously identified as a pan-BCR-ABL inhibitor that potently inhibits the T315I gatekeeper mutant, and has advanced into clinical development for the treatment of refractory or resistant CML. In this study, we explored a novel series of five and six membered monocycles as alternate hinge-binding templates to replace the 6,5-fused imidazopyridazine core of ponatinib. Like ponatinib, these monocycles are tethered to pendant toluanilides via an ethynyl linker. Several compounds in this series displayed excellent in vitro potency against both native BCR-ABL and the T315I mutant. Notably, a subset of inhibitors exhibited desirable PK and were orally active in a mouse model of T315I-driven CML. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.060

文献信息

• Monocyclic Heterocyclic Compounds
  申请人：Shakespeare William C.

  公开号：US20090149471A1

  公开（公告）日：2009-06-11

  This invention relates to compounds of the general formula: in which the variable groups are as defined herein, and to their preparation and use.

  本发明涉及具有以下一般式的化合物：其中变量基团的定义如本文所述，以及它们的制备和使用。
• COMPOSITIONS AND METHODS FOR MODULATING T CELL EXHAUSTION
  申请人：The Board of Trustees of the Leland Stanford Junior University

  公开号：US20210393628A1

  公开（公告）日：2021-12-23

  This invention is in the field of medicinal chemistry. In particular, provided herein are compositions and methods for preventing or reversing T cell exhaustion. In certain embodiments, the present invention relates to methods of preventing or reversing T cell exhaustion by exposing T cells experiencing T cell exhaustion to a new class of small-molecules having a thiazole, imidazolepyridiazine or piperazinyl-methyl-aniline structure, or by expanding genetically engineered T cells in the presence of such small molecules.
• US8278307B2
  申请人：——

  公开号：US8278307B2

  公开（公告）日：2012-10-02