1-(6-甲基吡啶)-2-喹啉-4-乙酮 | 476472-02-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: 1-(6-甲基吡啶)-2-喹啉-4-乙酮
• 英文名称: 1-(6-methylpyridin-2-yl)-2-(quinolin-4-yl)ethan-1-one
• 英文别名: 1-(6-Methylpyridyl)-2-quinolin-4-yl ethanone；1-(6-methylpyridin-2-yl)-2-quinolin-4-ylethanone
• CAS: 476472-02-3
• 化学式: C₁₇H₁₄N₂O
• 分子量: 262.311
• InChiKey: RYBJNXHNLNYRDT-UHFFFAOYSA-N

物化性质

• 沸点：
  449.9±35.0 °C(Predicted)
• 密度：
  1.200±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  42.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(6-甲基吡啶)-2-喹啉-4-乙酮 在 吡啶 、 sodium hydride 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-quinoline
  参考文献：
  名称：

  Synthesis and activity of new aryl- and heteroaryl-substituted 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole inhibitors of the transforming growth factor-β type I receptor kinase domain

  摘要：

  We have expanded our previously reported series of pyrazole-based inhibitors of the TGF-beta type I receptor kinase domain (TbetaR-I) to now include new 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole analogues. Limited examination of the SAR of this new series in both enzyme and cell based in vitro assays has revealed selectivity differences with respect to p38 MAP kinase (p38 MAPK) depending on the nature of the 'warhead' group on the dihydropyrrolopyrazole ring. As with our original pyrazole series, phenyl substituents tended to show greater selectivity against p38 MAPK than those comprised of the quinoline-4-yl moiety. We have also achieved co-crystallization and X-ray analysis of compounds 3 and 15, two potent examples of this new series, with the TbetaR-I receptor kinase domain.

  DOI：

  10.1016/j.bmcl.2004.04.007
• 作为产物：
  描述：

  6-甲基-2-吡啶甲酸 在 硫酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 22.5h， 生成 1-(6-甲基吡啶)-2-喹啉-4-乙酮
  参考文献：
  名称：

  [EN] BENZYLAMIDE DERIVATIVES AS INHIBITORS OF TRANSFORMING GROWTH FACTOR-BETA RECEPTOR I/ALK5
  [FR] DÉRIVÉS DE BENZYLAMIDE UTILISÉS EN TANT QU'INHIBITEURS DU RÉCEPTEUR I/ALK5 DU FACTEUR DE CROISSANCE TRANSFORMANT BÊTA

  摘要：

  本发明涉及式(I)的新型苄酰胺衍生物，以及制备该化合物的方法；包括该化合物的药物组合物，以及用于治疗可以通过抑制转化生长因子-β受体I（TGFβRI）/ALK5改善的病理状况或疾病，例如与胃肠道、皮肤和眼睛纤维化病症相关的疾病和紊乱；用于治疗和/或预防上述疾病或病理状况的方法，以及包括该化合物的组合物，进一步包括对治疗上述疾病或病理状况有用的其他治疗剂的治疗有效量。

  公开号：

  WO2021105317A1

文献信息

• Synthesis and evaluation of the HIF-1α inhibitory activity of 3(5)-substituted-4-(quinolin-4-yl)- and 4-(2-phenylpyridin-4-yl)pyrazoles as inhibitors of ALK5
  作者：Yan-Wei Li、Xiang-Yu Li、Shanji Li、Li-Min Zhao、Juan Ma、Hu-Ri Piao、Zhe Jiang、Cheng Hua Jin、Xuejun Jin

  DOI：10.1016/j.bmcl.2019.126822

  日期：2020.1

  recognized as an important potential therapeutic target for cancer. Six series of 3(5)-(6-methylpyridin-2-yl)-4-(quinolin-4-yl)pyrazoles (11a-d, 12a-d, and 18a-d) and 3(5)-(6-methylpyridin-2-yl)-4-(2-phenyl-pyridin-4-yl)pyrazoles (19a-d, 20a-d, and 21a-d) were synthesized and evaluated for activin receptor-like kinase 5 (ALK5) and HIF-1α inhibitory activity at the enzyme and cell levels. The effect of

  转录因子缺氧诱导因子-1α（HIF-1α）在细胞凋亡，转移和增殖中起着重要作用，并且被认为是重要的潜在癌症治疗靶标。六个系列的3（5）-（6-甲基吡啶-2-基）-4-（喹啉-4-基）吡唑（11a-d，12a-d和18a-d）和3（5）-（6合成了-甲基吡啶-2-基）-4-（2-苯基吡啶-4-基）吡唑（19a-d，20a-d和21a-d）并评估了激活素受体样激酶5（ALK5）和HIF-1α在酶和细胞水平的抑制活性。研究了铅化合物20d（J-1012）对HCT116细胞中HIF-1α活化的影响。J-1012剂量依赖性地显着降低了缺氧诱导或TNF诱导的HIF-1α蛋白积累。分析表明，J-1012抑制了HIF-1α蛋白质的合成，而没有影响HIF-1α蛋白质的降解。此外，通过抑制HIF-1α的活化，J-1012抑制了HCT116细胞的转移和增殖，并促进了HCT116细胞的凋亡。这些结果表明，J-1012可能是抗人类结肠癌的潜在治疗剂。
• 2-(3-PYRIDIN-2-YL-4-QUINOLIN-4-YL-PYRAZOL-1-YL)-ACETAMIDE DERIVATIVES AS INHIBITORS OF TRANSFORMING GROWTH FACTOR-BETA RECEPTOR I/ALK5
  申请人：Origo Biopharma, S.L.

  公开号：EP3978487A1

  公开（公告）日：2022-04-06

  The present invention relates to novel 2-(3-pyridin-2-yl-4-quinolin-4-yl-pyrazol-1-yl)-acetamide derivatives as potent inhibitors of transforming growth factor-β receptor I, (also named activin receptor-like kinase 5) (TGFβRI)/ALK5. Other objectives of the present invention are to provide a procedure for preparing these compounds; pharmaceutical compositions comprising an effective amount of these compounds; the use of the compounds for manufacturing a medicament for the treatment of pathological conditions or diseases that can improve by inhibition of transforming growth factor-β receptor I (TGFβRI)/ALK5, such as respiratory diseases including idiopathic pulmonary fibrosis, asthma, COPD and lung cancer, and dermal and ocular fibrotic conditions.

  本发明涉及新型2-(3-吡啶-2-基-4-喹啉-4-基-吡唑-1-基)-乙酰胺衍生物，作为转化生长因子-β受体I（也称为活化素样激酶5）（TGFβRI）/ALK5的有效抑制剂。本发明的其他目标是提供制备这些化合物的方法；包含这些化合物的有效量的制药组合物；使用这些化合物制造治疗可以通过抑制转化生长因子-β受体I（TGFβRI）/ALK5改善的病理状况或疾病的药物，如呼吸道疾病，包括特发性肺纤维化、哮喘、COPD和肺癌，以及皮肤和眼部纤维化病症。
• [EN] NOVEL ISOTHIAZOLE AND ISOXAZOLE COMPOUNDS AS TRANSFORMING GROWTH FACTOR (TGF) INHIBITORS<br/>[FR] NOUVEAUX COMPOSES D'ISOTHIAZOLE ET D'ISOXAZOLE UTILISES COMME INHIBITEURS DU FACTEUR DE CROISSANCE TRANSFORMANT (TGF)
  申请人：PFIZER PROD INC

  公开号：WO2004026865A1

  公开（公告）日：2004-04-01

  Novel isothiazole and isoxazole compounds, including derivatives thereof, to intermediates for their preparation, to pharmaceutical compositions containing them and to their medicinal use are described. The compounds of the present invention are potent inhibitors of transforming growth factor ('TGF')-P signaling pathway. They are useful in the treatment of various TGF-related disease states including, for example, cancer, and fibrotic diseases.

  本发明涉及新型的异噻唑和异噁唑化合物及其衍生物，以及其制备中间体、含有它们的制药组合物和它们的药用。本发明的化合物是转化生长因子（“TGF”）-P信号通路的有效抑制剂。它们在治疗各种TGF相关疾病状态中具有用途，包括癌症和纤维性疾病等。
• Synthesis and Activity of New Aryl- and Heteroaryl-Substituted Pyrazole Inhibitors of the Transforming Growth Factor-β Type I Receptor Kinase Domain
  作者：J. Scott Sawyer、Bryan D. Anderson、Douglas W. Beight、Robert M. Campbell、Michael L. Jones、David K. Herron、John W. Lampe、Jefferson R. McCowan、William T. McMillen、Nicholas Mort、Stephen Parsons、Edward C. R. Smith、Michal Vieth、Leonard C. Weir、Lei Yan、Faming Zhang、Jonathan M. Yingling

  DOI：10.1021/jm0205705

  日期：2003.9.1

  Pyrazole-based inhibitors of the transforming growth factor-beta type I receptor kinase domain (TbetaR-I) are described. Examination of the SAP, in both enzyme- and cell-based in vitro assays resulted in the emergence of two subseries featuring differing selectivity versus p38 MAP kinase. A common binding mode at the active site has been established by successful cocrystallization and X-ray analysis of potent inhibitors with the TbetaR-I receptor kinase domain.
• Synthesis and biological evaluation of 2-pyridyl-substituted pyrazoles and imidazoles as transforming growth factor-β type 1 receptor kinase inhibitors
  作者：Purushottam M. Dewang、Dae-Kee Kim

  DOI：10.1016/j.bmcl.2010.05.032

  日期：2010.7

  A series of 2-pyridyl-substituted pyrazoles (16a-d, 17, 18, and 28a-e) and imidazoles (22 and 23) has been synthesized and evaluated for their ALK5 inhibitory activity in cell-based luciferase reporter assays. Among them, 3-(3-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-pyrazole-1-carbothioamido)benzamide (28c) showed 96% and 93% inhibition at 0.1 mu M in luciferase reporter assays using HaCaT cells transiently transfected with p3TP-luc reporter construct and ARE-luc reporter construct, respectively. (C) 2010 Elsevier Ltd. All rights reserved.