1-(6-bromo-2-methylimidazo[1,2-a]pyridin-3-yl)ethanone | 154877-65-3

• 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: 1-(6-bromo-2-methylimidazo[1,2-a]pyridin-3-yl)ethanone
• CAS: 154877-65-3
• 化学式: C₁₀H₉BrN₂O
• 分子量: 253.098
• InChiKey: PPFSZNZUCAFALT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  34.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(6-bromo-2-methylimidazo[1,2-a]pyridin-3-yl)ethanone 在 potassium carbonate 作用下， 以 正丁醇 为溶剂， 生成
  参考文献：
  名称：

  新型苯甲酰胺衍生物作为HDAC抑制剂的设计，合成和生物评价

  摘要：

  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。

  DOI：

  10.1016/j.bmcl.2012.10.114
• 作为产物：
  描述：

  2-氨基-5-溴吡啶 、 3-氯乙酰丙酮 在 氮气 、 silica gel 、 乙酸乙酯 作用下， 以 丙醇 为溶剂， 反应 0.5h， 以to give 620 mg (21%) of 1-(6-bromo-2-methylimidazo[1,2-a]pyridin-3-yl)ethanone as a tan solid的产率得到1-(6-bromo-2-methylimidazo[1,2-a]pyridin-3-yl)ethanone
  参考文献：
  名称：

  THIOZOLIDINEDIONE DERIVATIVES AS PI3 KINASE INHIBITORS

  摘要：

  发明了一种使用噻唑烷二酮衍生物抑制PI3激酶活性/功能的方法。同时，还发明了一种使用噻唑烷二酮衍生物治疗以下一种或多种疾病状态的方法：自身免疫疾病、炎症性疾病、心血管疾病、神经退行性疾病、过敏、哮喘、胰腺炎、多器官衰竭、肾脏疾病、血小板聚集、癌症、精子运动能力、移植排斥、移植物排斥和肺损伤。

  公开号：

  US20090215818A1

文献信息

• [EN] THIOZOLIDINEDIONE DERIVATIVES AS P13 KINASE INHIBITORS<br/>[FR] DÉRIVÉS DE THIOZOLIDINEDIONE UTILISÉS EN TANT QU'INHIBITEURS DE LA P13-KINASE
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2008014219A8

  公开（公告）日：2009-03-12
• 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.
• Synthesis and biological evaluation of sulfonylhydrazone-substituted imidazo[1,2-a]pyridines as novel PI3 kinase p110α inhibitors
  作者：Masahiko Hayakawa、Ken-ichi Kawaguchi、Hiroyuki Kaizawa、Tomonobu Koizumi、Takahide Ohishi、Mayumi Yamano、Minoru Okada、Mitsuaki Ohta、Shin-ichi Tsukamoto、Florence I. Raynaud

  DOI：10.1016/j.bmc.2007.05.070

  日期：2007.9.1

  We have previously reported the imidazo[1,2-a]pyridine derivative 4 as a novel p110 alpha inhibitor; however, although 4 is a potent inhibitor of p110 alpha enzymatic activity and tumor cell proliferation in vitro, it is unstable in solution and ineffective in vivo. To increase stability the pyrazole of 4 was replaced with a hydrazone and a moderately potent p110 alpha inhibitor 7a was obtained. Subsequent optimization of 7a afforded exceptionally potent p110 alpha inhibitors, including 8c and 8h, with IC(50) values of 0.30 nM and 0.26 nM, respectively; to the best of our knowledge, these compounds are the most potent PI3K p110 alpha inhibitors reported to date. Compound 8c was also stable in solution and exhibited significant anti-tumor effectiveness in vivo. (c) 2007 Elsevier Ltd. All rights reserved.
• 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。
• THIOZOLIDINEDIONE DERIVATIVES AS PI3 KINASE INHIBITORS
  申请人：Adams Nicholas D.

  公开号：US20090215818A1

  公开（公告）日：2009-08-27

  Invented is a method of inhibiting the activity/function of PI3 kinases using thiozolidinedione derivatives. Also invented is a method of treating one or more disease states selected from: autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, allergy, asthma, pancreatitis, multiorgan failure, kidney diseases, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection and lung injuries by the administration of thiozolidinedione derivatives.

  发明了一种使用噻唑烷二酮衍生物抑制PI3激酶活性/功能的方法。同时，还发明了一种使用噻唑烷二酮衍生物治疗以下一种或多种疾病状态的方法：自身免疫疾病、炎症性疾病、心血管疾病、神经退行性疾病、过敏、哮喘、胰腺炎、多器官衰竭、肾脏疾病、血小板聚集、癌症、精子运动能力、移植排斥、移植物排斥和肺损伤。