1-(2-chloroquinolin-6-yl)ethan-1-one | 1253972-47-2

• 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
• 英文名称: 1-(2-chloroquinolin-6-yl)ethan-1-one
• 英文别名: 1-(2-Chloroquinolin-6-yl)ethanone；1-(2-chloroquinolin-6-yl)ethanone
• CAS: 1253972-47-2
• 化学式: C₁₁H₈ClNO
• 分子量: 205.644
• InChiKey: ZPCMVVIPEADIAN-UHFFFAOYSA-N

物化性质

• 沸点：
  343.9±22.0 °C(Predicted)
• 密度：
  1.283±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  30
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(2-chloroquinolin-6-yl)ethan-1-one 在 1,1'-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex 、 盐酸羟胺 、 氨 、 氢气 、 potassium carbonate 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 、 水 为溶剂， 反应 11.0h， 生成 1-(2-(1-methyl-1H-pyrazol-4-yl)quinolin-6-yl)ethan-1-amine
  参考文献：
  名称：

  Identification of 3-substituted-6-(1-(1 H -[1,2,3]triazolo[4,5- b ]pyrazin-1-yl)ethyl)quinoline derivatives as highly potent and selective mesenchymal-epithelial transition factor (c-Met) inhibitors via metabolite profiling-based structural optimization

  摘要：

  c-Met/HGF signaling pathway plays an important role in cancer progression, and it was considered to be related to poor prognosis and drug resistance. Based on metabolite profiling of (S)-7-fluoro-6-(1-(6-(1methyl-1H-pyrazol-4-y1)-1H-imidazo[4,5-b]pyrazin-1-yl)ethypquinoline (1), a series of 2-substituted or 3-substituted-6-(1-(1H-[1,2,31triazolo[4,5-b]pyrazin-1-yl)ethyl)quinoline derivatives was rationally designed and evaluated. Most of the 3-substituted derivatives not only exhibited potent activities in both enzymatic and cellular assays, but also were stable in liver microsomes among different species (human, rat and monkey). SAR investigation revealed that introducing of N-methyl-IH-pyrazol-4-yl group at the 3-position of quinoline moiety is beneficial to improve the inhibitory potency, especially in the cellular assays. The influence of fluorine atom at 7-position or 5, 7-position of quinoline moiety and substituents at the 6-position of triazolo[4,5-b]pyrazine core on overall activity is not very significant. Racemate 14, an extremely potent and exquisitely selective c-Met inhibitor, demonstrated favorable pharmacokinetic properties in rats, no significant AO metabolism and effective tumor growth inhibition in c-Met over expressed NSCLC (H1993 cell line) and gastric cancer (SNU-5 cell line) xenograft models. Docking analysis indicated that besides the typical interactions of most selective c-Met inhibitors, the intramolecular halogen bond and additional hydrogen bond interactions with kinase are beneficial to the binding. These results may provide deep insight into potential structural modifications for developing potent c-Met inhibitors. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.03.085
• 作为产物：
  描述：

  1-(4-氨基-3-碘苯基)乙酮 在 盐酸 、 1,1'-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex 、 三乙胺 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 1-(2-chloroquinolin-6-yl)ethan-1-one
  参考文献：
  名称：

  Identification of 3-substituted-6-(1-(1 H -[1,2,3]triazolo[4,5- b ]pyrazin-1-yl)ethyl)quinoline derivatives as highly potent and selective mesenchymal-epithelial transition factor (c-Met) inhibitors via metabolite profiling-based structural optimization

  摘要：

  c-Met/HGF signaling pathway plays an important role in cancer progression, and it was considered to be related to poor prognosis and drug resistance. Based on metabolite profiling of (S)-7-fluoro-6-(1-(6-(1methyl-1H-pyrazol-4-y1)-1H-imidazo[4,5-b]pyrazin-1-yl)ethypquinoline (1), a series of 2-substituted or 3-substituted-6-(1-(1H-[1,2,31triazolo[4,5-b]pyrazin-1-yl)ethyl)quinoline derivatives was rationally designed and evaluated. Most of the 3-substituted derivatives not only exhibited potent activities in both enzymatic and cellular assays, but also were stable in liver microsomes among different species (human, rat and monkey). SAR investigation revealed that introducing of N-methyl-IH-pyrazol-4-yl group at the 3-position of quinoline moiety is beneficial to improve the inhibitory potency, especially in the cellular assays. The influence of fluorine atom at 7-position or 5, 7-position of quinoline moiety and substituents at the 6-position of triazolo[4,5-b]pyrazine core on overall activity is not very significant. Racemate 14, an extremely potent and exquisitely selective c-Met inhibitor, demonstrated favorable pharmacokinetic properties in rats, no significant AO metabolism and effective tumor growth inhibition in c-Met over expressed NSCLC (H1993 cell line) and gastric cancer (SNU-5 cell line) xenograft models. Docking analysis indicated that besides the typical interactions of most selective c-Met inhibitors, the intramolecular halogen bond and additional hydrogen bond interactions with kinase are beneficial to the binding. These results may provide deep insight into potential structural modifications for developing potent c-Met inhibitors. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.03.085

文献信息

• [EN] INHIBITORS OF ACETYL-COA CARBOXYLASE<br/>[FR] INHIBITEURS DE L'ACÉTYL-COA CARBOXYLASE
  申请人：FOREST LAB HOLDINGS LTD

  公开号：WO2010127208A1

  公开（公告）日：2010-11-04

  The present invention relates to compounds that act as acetyl-CoA carboxylase (ACC) inhibitors. The invention also relates to methods of preparing the compounds, compositions containing the compounds, and to methods of treatment using the compounds.

  本发明涉及作为乙酰辅酶A羧化酶（ACC）抑制剂的化合物。该发明还涉及制备这些化合物的方法、含有这些化合物的组合物，以及使用这些化合物进行治疗的方法。
• Design, synthesis and biological evaluation of novel benzoxaborole derivatives as potent PDE4 inhibitors for topical treatment of atopic dermatitis
  作者：Zhaoxing Chu、Qinlong Xu、Qihua Zhu、Xiaodong Ma、Jiajia Mo、Gaofeng Lin、Yan Zhao、Yuanfeng Gu、Lincui Bian、Li Shao、Jing Guo、Wenfeng Ye、Jiaming Li、Guangwei He、Yungen Xu

  DOI：10.1016/j.ejmech.2021.113171

  日期：2021.3

  series of structurally novel benzoxaborole derivatives were designed, synthesized and biologically evaluated as PDE4 inhibitors for battling atopic dermatitis (AD). Among them, the majority exhibited superior PDE4B inhibitory activities to that of the lead compound Crisaborole, an approved PDE4 inhibitor. In particular, 72, the most potent PDE4B inhibitor throughout this series, displayed 136-fold

  在这项工作中，设计，合成和生物学评估了一系列结构新颖的苯并x硼烷衍生物作为抗特应性皮炎（AD）的PDE4抑制剂。在它们之中，大多数表现出比已批准的PDE4抑制剂先导化合物Crisaborole更好的PDE4B抑制活性。特别是，在整个系列中最有效的PDE4B抑制剂72 与Crisaborole（IC 50  = 57.20 nM）相比，显示出136倍的酶活性（IC 50 = 0.42 nM）改善的同工型特异性。在佛波酯（PMA）诱导的小鼠耳部水肿模型中，在相同剂量下72的功效显着大于Crisaborole（P <0.05）。而且， 在卡泊三醇诱导的小鼠AD模型中，软膏72的药效比Crisaborole的软膏显着增强（P <0.05）。除有效的体外和体内活性外，72在重复的口服剂量毒性研究中显示出良好的安全性，并且未显示出光毒性。凭借上述引人入胜的生物学性能，作为一种新型的抗AD治疗剂，值得进一步研究72。
• TRPM8 ANTAGONISTS AND THEIR USE IN TREATMENTS
  申请人：Biswas Kaustav

  公开号：US20130157996A1

  公开（公告）日：2013-06-20

  Compounds of Formula I are useful as antagonists of TRPM8. Such compounds are useful in treating a number of TRPM8 mediated disorders and conditions and may be used to prepare medicaments and pharmaceutical compositions useful for treating such disorders and conditions. Examples of such disorders include, but are not limited to, migraines and neuropathic pain. Compounds of Formula I have the following structure: where the definitions of the variables are provided herein.

  公式I的化合物可用作TRPM8的拮抗剂。这些化合物在治疗许多TRPM8介导的疾病和病症方面非常有用，并可用于制备用于治疗此类疾病和病症的药物和制剂。此类疾病的示例包括但不限于偏头痛和神经病性疼痛。公式I的化合物具有以下结构：其中变量的定义在此提供。
• COMPOUND CAPABLE OF INHIBITING PHOSPHODIESTERASE 4, PREPARATION METHOD, AND MEDICAL USE THEREOF
  申请人：Hefei Industrial Pharmaceutical Institute Co., Ltd

  公开号：EP3708568A1

  公开（公告）日：2020-09-16

  The disclosure relates to the field of medicinal chemistry, in particular, to a class of small molecule compounds for inhibiting phosphodiesterase 4 (I), a preparation method thereof and a pharmaceutical composition comprising the compound. The pharmacodynamic test proves that the compound of the disclosure has the inhibitory activity of PDE-4 enzyme and the efficacy of inflammation treatment.

  本公开涉及药物化学领域，尤其涉及一类抑制磷酸二酯酶4(I)的小分子化合物、其制备方法以及包含该化合物的药物组合物。药效学试验证明，本公开的化合物具有抑制 PDE-4 酶的活性和治疗炎症的疗效。
• Compound having effects of inhibiting phosphodiesterase 4, preparation method thereof and pharmaceutical use thereof
  申请人：Hefei Industrial Pharmaceutical Institute Co., Ltd.

  公开号：US11161860B2

  公开（公告）日：2021-11-02

  The disclosure relates to the field of medicinal chemistry, in particular, to a class of small molecule compounds for inhibiting phosphodiesterase 4 (I), a preparation method thereof and a pharmaceutical composition comprising the compound. The pharmacodynamic test proves that the compound of the disclosure has the inhibitory activity of PDE-4 enzyme and the efficacy of inflammation treatment.

  本公开涉及药物化学领域，尤其涉及一类抑制磷酸二酯酶4(I)的小分子化合物、其制备方法以及包含该化合物的药物组合物。药效学试验证明，本公开的化合物具有抑制 PDE-4 酶的活性和治疗炎症的疗效。