3-(3-dimethylaminoprop-2-en-1-oyl)-2-methylimidazo[1,2-a]pyridine | 328062-28-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡啶类
• 英文名称: 3-(3-dimethylaminoprop-2-en-1-oyl)-2-methylimidazo[1,2-a]pyridine
• 英文别名: 3-(Dimethylamino)-1-(2-methylimidazo[1,2-a]pyridin-3-yl)-2-propen-1-one；3-(dimethylamino)-1-(2-methylimidazo[1,2-a]pyridin-3-yl)prop-2-en-1-one
• CAS: 328062-28-8
• 化学式: C₁₃H₁₅N₃O
• 分子量: 229.282
• InChiKey: XGBUIIXQUIOSSV-UHFFFAOYSA-N

物化性质

• 密度：
  1.11±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  37.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(3-dimethylaminoprop-2-en-1-oyl)-2-methylimidazo[1,2-a]pyridine 在 吡啶 、 一水合肼 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成 Imidazopyridine derivative, 3
  参考文献：
  名称：

  Synthesis and biological evaluation of imidazo[1,2-a]pyridine derivatives as novel PI3 kinase p110α inhibitors

  摘要：

  3-{1-[(4-Fluorophenyl)sulfonyl]-1H-pyrazol-3-yl}-2-methylimidazo[1,2-a]pyridine, 2a, was discovered in our chemical library as a novel p110 alpha inhibitor with an IC50 of 0.67 mu M, through screening in a scintillation proximity assay. Optimization of the substituents of 2a increased the p110 alpha inhibitory activity by more than 300-fold (2g: IC50 = 0.0018 mu M). Further structural modification of 2g afforded thiazole derivative 12, which has potent p110 alpha inhibitory activity (IC50 of 0.0028 mu M) and is highly selective for p110 alpha over other PI3K isoforms. Compound 12 also inhibited serum-induced cell proliferation of A375 and HeLa cells in vitro with IC50 values of 0.14 mu M and 0.21 mu M, respectively, and suppressed tumor growth by 37% in a mouse HeLa xenograft model when dosed intraperitoneally at 25 mg/kg. These results suggest that selective p110 alpha inhibitors may have potential as cancer therapeutic agents. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.09.047
• 作为产物：
  描述：

  2-氨基吡啶 以 乙二醇二甲醚 为溶剂， 生成 3-(3-dimethylaminoprop-2-en-1-oyl)-2-methylimidazo[1,2-a]pyridine
  参考文献：
  名称：

  抑制NF-κB诱导激酶（NIK）：发现，基于结构的设计，合成，结构与活性的关系以及共晶结构

  摘要：

  介绍了NIK抑制剂的发现，基于结构的设计，合成和优化。我们的工作始于HTS热门产品，咪唑并吡啶基嘧啶胺1。我们利用同源性建模和构象分析来优化吲哚骨架，从而导致发现新颖而有效的构象受限抑​​制剂，例如化合物25和28。化合物25和31与NIK激酶结构域共结晶以提供结构见解。

  DOI：

  10.1016/j.bmcl.2013.01.012

文献信息

• FUSED HETEROCYCLYC INHIBITOR COMPOUNDS
  申请人：Melvin, JR. Lawrence S.

  公开号：US20100029638A1

  公开（公告）日：2010-02-04

  The present invention provides a compound of general Formula (I) having histone deacetylase (HDAC) and/or Cyclin-dependent kinase (CDK) inhibitory activity, a pharmaceutical composition comprising the compound, and a method useful to treat diseases using the compound.

  本发明提供了一种具有组蛋白去乙酰化酶（HDAC）和/或 Cyclin 依赖性激酶（CDK）抑制活性的一般式（I）化合物，包括该化合物的药物组合物，以及使用该化合物治疗疾病的方法。
• Design, synthesis and bioevalution of novel benzamides derivatives as HDAC inhibitors
  作者：Yanyang Li、Yan Zhou、Pengyu Qian、Yongzhen Wang、Falong Jiang、Zhenglin Yao、Wenxiang Hu、Yanjin Zhao、Shuxin Li

  DOI：10.1016/j.bmcl.2012.10.114

  日期：2013.1

  A series of novel benzamides derivatives was designed and synthesized as HDAC inhibitors. Exploration of the structure–activity relationships resulted in compounds that are potent in vitro. In addition, the best compound 1a exhibited an acceptable pharmacokinetic profile with bioavailability in rat of 81% and could be considered as a candidate compound for further development.

  设计并合成了一系列新颖的苯甲酰胺衍生物作为HDAC抑制剂。对结构-活性关系的探索导致了在体外有效的化合物。此外，最佳化合物1a在大鼠体内的生物利用度为81％，表现出可接受的药代动力学特征，可以被视为进一步开发的候选化合物。
• Discovery and SAR Studies of Potent Modulators of BMI‐1 Expression
  作者：Ramil Y. Baiazitov、Nadiya Sydorenko、Wu Du、Hongyu Ren、Liang Cao、Thomas Davis、Katherine Cintron‐Lue、Min‐Jung Kim、Jin Zhuo、Shreshtha Mody、Marla Weetall、Josephine Sheedy、Nicole Risher、Neil Almstead、Young‐Choon Moon

  DOI：10.1002/hlca.202300076

  日期：2023.9

  first-in-class series of small molecules that modulate the expression of BMI1 protein in cancer cells. Structure–activity and structure–property relationships associated with this series were investigated through medicinal chemistry efforts. These studies revealed important structural features required for achieving anti-tumor activity and acceptable pharmacokinetic properties within this series. The 4-CF3−Ph

  在我们努力识别选择性降低干细胞基因 BMI1 表达的分子的过程中，我们发现并鉴定了一系列首创的小分子，这些小分子可调节癌细胞中 BMI1 蛋白的表达。通过药物化学工作研究了与该系列相关的结构-活性和结构-性质关系。这些研究揭示了该系列中实现抗肿瘤活性和可接受的药代动力学特性所需的重要结构特征。4-CF 3-Ph位于分子的左侧，N原子正确放置在中间的六元杂环上，并与右侧的适当取代的C(2)-甲基苯并咪唑相结合，以实现口服给药后达到效力、微粒体稳定性和暴露。鉴定出一种化合物 (PTC-02) 具有可接受的药理学特性，并且在多种肿瘤动物模型中体内有效。
• IMIDAZO[1,2-A]PYRIDINE AND PYRAZOLO[2,3-A]PYRIDINE DERIVATIVES
  申请人：AstraZeneca AB

  公开号：EP1214318B1

  公开（公告）日：2003-10-08
• Synthesis and biological evaluation of imidazo[1,2-a]pyridine derivatives as novel PI3 kinase p110α inhibitors
  作者：Masahiko Hayakawa、Hiroyuki Kaizawa、Ken-ichi Kawaguchi、Noriko Ishikawa、Tomonobu Koizumi、Takahide Ohishi、Mayumi Yamano、Minoru Okada、Mitsuaki Ohta、Shin-ichi Tsukamoto

  DOI：10.1016/j.bmc.2006.09.047

  日期：2007.1.1

  3-1-[(4-Fluorophenyl)sulfonyl]-1H-pyrazol-3-yl}-2-methylimidazo[1,2-a]pyridine, 2a, was discovered in our chemical library as a novel p110 alpha inhibitor with an IC50 of 0.67 mu M, through screening in a scintillation proximity assay. Optimization of the substituents of 2a increased the p110 alpha inhibitory activity by more than 300-fold (2g: IC50 = 0.0018 mu M). Further structural modification of 2g afforded thiazole derivative 12, which has potent p110 alpha inhibitory activity (IC50 of 0.0028 mu M) and is highly selective for p110 alpha over other PI3K isoforms. Compound 12 also inhibited serum-induced cell proliferation of A375 and HeLa cells in vitro with IC50 values of 0.14 mu M and 0.21 mu M, respectively, and suppressed tumor growth by 37% in a mouse HeLa xenograft model when dosed intraperitoneally at 25 mg/kg. These results suggest that selective p110 alpha inhibitors may have potential as cancer therapeutic agents. (c) 2006 Elsevier Ltd. All rights reserved.