3-ethynyl-4-methyl-N-(3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)benzamide | 1257628-83-3

• 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-ethynyl-4-methyl-N-(3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)benzamide
• 英文别名: 3‐ethynyl‐4‐methyl‐N‐(3‐(4‐methyl‐1H‐imidazol‐1‐yl)‐5‐(trifluoromethyl)phenyl)benzamide；3-ethynyl-4-methyl-N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]benzamide
• CAS: 1257628-83-3
• 化学式: C₂₁H₁₆F₃N₃O
• 分子量: 383.373
• InChiKey: BNRGCYLFZDIUNR-UHFFFAOYSA-N

物化性质

• 沸点：
  468.9±45.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  46.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-ethynyl-4-methyl-N-(3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)benzamide 、 5-溴-2-甲基氨基嘧啶 在 copper(l) iodide 、 palladium diacetate 、 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 为溶剂， 生成 4-methyl-N-(3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-(2-(2-(methylamino)pyrimidin-5-yl)ethynyl)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
• 作为产物：
  描述：

  3-(4-甲基-1H-咪唑-1-基)-5-(三氟甲基)苯胺 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙腈 为溶剂， 反应 6.0h， 生成 3-ethynyl-4-methyl-N-(3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)benzamide
  参考文献：
  名称：

  HETEROCYCLIC ALKYNYL BENZENE COMPOUNDS AND MEDICAL COMPOSITIONS AND USES THEREOF

  摘要：

  式（I）的杂环炔基苯化合物，其药用盐及其立体异构体，以及在制备用于预防或治疗肿瘤的药物中的应用。这些化合物可以克服临床诱导的对格列卫（Gleevec）的耐药性。

  公开号：

  US20130196985A1

文献信息

• 3-ACETYLENYL-PYRAZOLE-PYRIMIDINE DERIVATIVE, AND PREPARATION METHOD THEREFOR AND USES THEREOF
  申请人：Si Chuan University

  公开号：US20170305920A1

  公开（公告）日：2017-10-26

  The present invention relates to the field of chemical and medicine, more particularly, 3-ethynylpyrazolopyrimidine derivatives and their preparation methods and uses. The invention provides a 3-ethynylpyrazolopyrimidine derivative, and the structure is shown in formula I. The present invention also provides preparation methods and use of 3-ethynylpyrazolopyrimidine derivatives, comprising the compounds and derivatives, and their pharmaceutical compositions for the use of the treatment and prevention of tumors.

  本发明涉及化学和药物领域，更具体地涉及3-乙炔吡唑吡嘧啶衍生物及其制备方法和用途。该发明提供了一种3-乙炔吡唑吡嘧啶衍生物，其结构如公式I所示。本发明还提供了3-乙炔吡唑吡嘧啶衍生物的制备方法和用途，包括该化合物和衍生物，以及它们的药物组合物，用于治疗和预防肿瘤。
• ALKYNYL HETEROAROMATIC COMPOUND AND USE THEREOF
  申请人：Nanjing Sanhome Pharmaceutical Co., Ltd.

  公开号：US20150152088A1

  公开（公告）日：2015-06-04

  The present invention belongs to the field of pharmaceutical chemistry, and specifically relates to compounds having an alkynyl heteroaromatic ring structure and pharmaceutically acceptable salts, stereoisomers, N-oxides, solvates, or prodrugs thereof, and pharmaceutical compositions comprising these compounds, as well as uses of these compounds and compositions in the manufacture of a medicament. The compounds of the present invention and the pharmaceutically acceptable salts, stereoisomers, N-oxides, solvates or prodrugs thereof and the pharmaceutical compositions comprising the compounds have better anti-tumor activity.

  本发明属于药物化学领域，具体涉及具有炔基杂芳环结构和药学上可接受的盐、立体异构体、N-氧化物、溶剂合物或前药的化合物，以及包含这些化合物的药物组合物，以及这些化合物和组合物在制备药物中的用途。本发明的化合物和药学上可接受的盐、立体异构体、N-氧化物、溶剂合物或前药以及包含这些化合物的药物组合物具有更好的抗肿瘤活性。
• Heterocyclic alkynyl benzene compounds and medical compositions and uses thereof
  申请人：Ding Ke

  公开号：US08846671B2

  公开（公告）日：2014-09-30

  The heterocyclic alkynyl benzene compounds of formula (I), their pharmaceutically acceptable salts and stereoisomers thereof, as well as application in preparing drugs for preventing or treating tumors. The compounds can overcome the clinically induced resistance against Gleevec.

  化合物公式为(I)的杂环炔基苯化合物及其药学上可接受的盐和立体异构体，以及其在制备预防或治疗肿瘤药物方面的应用。这些化合物可以克服对格列卫（Gleevec）的临床诱导耐药性。
• Designing Novel BCR-ABL Inhibitors for Chronic Myeloid Leukemia with Improved Cardiac Safety
  作者：Mallesh Pandrala、Arne Antoon N. Bruyneel、Anna P. Hnatiuk、Mark Mercola、Sanjay V. Malhotra

  DOI：10.1021/acs.jmedchem.1c01853

  日期：2022.8.25

  tyrosine kinase inhibitors (TKIs) targeting the BCR-ABL oncogene constitutes an effective approach for the treatment of chronic myeloid leukemia (CML) and/or acute lymphoblastic leukemia. However, currently available inhibitors are limited by drug resistance and toxicity. Ponatinib, a third-generation inhibitor, has demonstrated excellent efficacy against both wild type and mutant BCR-ABL kinase, including

  开发靶向 BCR-ABL 致癌基因的酪氨酸激酶抑制剂 (TKI) 构成了治疗慢性粒细胞白血病 (CML) 和/或急性淋巴细胞白血病的有效方法。然而，目前可用的抑制剂受到耐药性和毒性的限制。Ponatinib 是第三代抑制剂，已证明对野生型和突变型 BCR-ABL 激酶具有出色的疗效，包括对所有其他目前可用的 TKI 具有耐药性的“看门人”T315I 突变。然而，它是 FDA 批准的 TKI 中心脏毒性最强的一种。在此，我们报告了一系列新型有效 BCR-ABL 抑制剂的结构导向设计，特别是针对 T315I 突变。我们的药物设计范例与 iPSC-心肌细胞模型相结合。系统构效关系研究确定了两种化合物，如图 33a和36a 所示，它显着抑制了天然 BCR-ABL 和 T315I 突变体的激酶活性。我们已经确定了迄今为止报道的对心脏最安全的 TKI，它们可用于有效治疗具有 T315I 突变的 CML
• ALKYNYL HETEROAROMATIC RING COMPOUND AND APPLICATION THEREOF
  申请人：Nanjing Sanhome Pharmaceutical Co., Ltd.

  公开号：EP2896620A1

  公开（公告）日：2015-07-22

  The present invention belongs to the field of pharmaceutical chemistry, and specifically relates to compounds having an alkynyl heteroaromatic ring structure and pharmaceutically acceptable salts, stereoisomers, N-oxides, solvates, or prodrugs thereof, and pharmaceutical compositions comprising these compounds, as well as uses of these compounds and compositions in the manufacture of a medicament. The compounds of the present invention and the pharmaceutically acceptable salts, stereoisomers, N-oxides, solvates or prodrugs thereof and the pharmaceutical compositions comprising the compounds have better anti-tumor activity.

  本发明属于药物化学领域，具体涉及具有炔杂芳环结构的化合物及其药学上可接受的盐、立体异构体、N-氧化物、溶解物或原药，以及包含这些化合物的药物组合物，以及这些化合物和组合物在制造药物中的用途。本发明的化合物及其药学上可接受的盐、立体异构体、N-氧化物、溶解物或原药以及包含这些化合物的药物组合物具有更好的抗肿瘤活性。