2-(2-chloropyridin-4-yl)-1-(3-methoxy-5-methylphenyl)ethanone | 1217181-38-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-(2-chloropyridin-4-yl)-1-(3-methoxy-5-methylphenyl)ethanone
• CAS: 1217181-38-8
• 化学式: C₁₅H₁₄ClNO₂
• 分子量: 275.735
• InChiKey: USZJSTUYWGNJGW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(2-chloropyridin-4-yl)-1-(3-methoxy-5-methylphenyl)ethanone 在 bis-triphenylphosphine-palladium(II) chloride 、 potassium carbonate 作用下， 以 四氢呋喃 、 水 、 丙酮 为溶剂， 反应 30.0h， 生成 2-(3-(3-methoxy-5-methylphenyl)-4-(2-(6-(1-pyrrolidinyl)pyridin-3-yl)pyridin-4-yl)-1H-pyrazole-1-yl)acetonitrile
  参考文献：
  名称：

  Synthesis and in Vitro Screening of Phenylbipyridinylpyrazole Derivatives as Potential Antiproliferative Agents

  摘要：

  一系列苯基双吡啶基吡唑化合物通过2-(4-(2-氯吡啶-4-基)-3-(3-甲氧基-5-甲基苯基)-1H-吡唑-1-基)乙腈（4）与不同的6-取代吡啶-3-基硼酸的反应合成。最终化合物5a–j在美国国家癌症研究所（NCI）以10 µM的浓度筛选了超过60种肿瘤细胞系。根据NCI的结果，化合物5c和5h对NCI细胞系展现出广泛的活性，平均抑制率分别为53%和58%。化合物5e的表现有所不同，其在10 µM浓度下对白血病SR细胞系的生长抑制率达到96%，表现出高度选择性和效能。标准COMPARE分析在GI50水平上进行，结果显示当前三种化合物与三种已知抗癌药物之间的成对相关系数(PCC)高于0.6。化合物5e与美巴龙（NSC S336628）表现出较高的相关性，PCC值为0.631。化合物5h与二氯烯丙基溶碱素的PCC值为0.626，而化合物5i与二氯烯丙基溶碱素和N,N-二苄基道努霉素（NSC S268242）的PCC值分别为0.601和0.604。这三种标准药物通过两种主要机制发挥抗癌活性，即抑制拓扑异构酶 II 和抑制嘧啶核苷酸的生物合成，因此，化合物5a–j是针对不同人类恶性肿瘤的有希望的治疗剂。此外，还考虑了这些新合成衍生物的药物相似性和毒性预测。

  DOI：

  10.3390/molecules20011031
• 作为产物：
  描述：

  3-羟基-5-甲基苯甲酸 在 4-二甲氨基吡啶 potassium carbonate 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 反应 12.0h， 生成 2-(2-chloropyridin-4-yl)-1-(3-methoxy-5-methylphenyl)ethanone
  参考文献：
  名称：

  PYRAZOLE COMPOUNDS WITH INHIBITORY ACTIVITY AGAINST ROS KINASE

  摘要：

  本文披露了新型吡唑化合物，其药用盐，其制备方法，以及作为抗癌剂的用途。

  公开号：

  US20110015395A1

文献信息

• Design, Synthesis and in-vitro Screening of New 1H-Pyrazole and 1,2-Isoxazole Derivatives as Potential Inhibitors for ROS and MAPK14 Kinases
  作者：Mohammad M. Al-Sanea、Ibrahim M. El-Deeb、So Ha Lee

  DOI：10.5012/bkcs.2013.34.2.437

  日期：2013.2.20

  A new series of 4-(2-(substituted)pyridin-4-yl)-3-(3-methoxy-5-methylphenyl)-1H-pyrazoles (4a-f) and their 1,2-isoxazole analogues (5a-f) has been rationally designed, synthesized and screened against both ROS and MAPK14 kinases. Compounds 4b, 4c and 4e showed moderate inhibitions against both ROS and MAPK14 kinases. Compound 4e has showed the strongest inhibitions with IC50 values of 1.25 $\mu}M$ and 3.00 $\mu}M$ against ROS and MAPK14 kinases, respectively. A brief structure-activity relationship study and a molecular modeling study were made revealing a group of essential structural features for good kinase inhibitory activity within this new class of kinase inhibitors.

  一系列4-(2-(取代)吡啶-4-基)-3-(3-美克氧-5-甲基苯基)-1H-哌唑（4a-f）及其1,2-异噁唑类似物（5a-f）经过合理设计、合成，并对ROS和MAPK14激酶进行了筛选。化合物4b、4c和4e对ROS和MAPK14激酶表现出中等抑制活性。化合物4e在对ROS和MAPK14激酶的抑制中表现出最强的活性，其IC50值分别为1.25 $\mu}M$和3.00 $\mu}M$。进行了一项简要的结构-活性关系研究和分子建模研究，揭示了一组在这一新类激酶抑制剂中具有良好激酶抑制活性的关键结构特征。
• Design and synthesis of novel phenylaminopyrimidines with antiproliferative activity against colorectal cancer
  作者：Hanan A. Henidi、Ahmed M. Al-Abd、Fahad A. Al-Abbasi、Hawazen A. BinMahfouz、Ibrahim M. El-Deeb

  DOI：10.1039/c9ra03359a

  日期：——

  synthesised as potential tyrosine kinase inhibitors for the treatment of cancer. The synthesized compounds share a general structure and vary in the substitution pattern at position-2 of the pyridine ring. Several derivatives have demonstrated potent anticancer activities against HCT-116, HT-29 and LS-174T colorectal cancer cells. Furthermore, a number of hits showed good selectivity to Src-kinase. The

  新的苯氨基嘧啶（PAP）衍生物已被设计和合成为潜在的酪氨酸激酶抑制剂，用于治疗癌症。合成的化合物具有通用结构，但吡啶环 2 位的取代模式有所不同。几种衍生物已证明对 HCT-116、HT-29 和 LS-174T 结直肠癌细胞具有有效的抗癌活性。此外，许多命中结果显示出对 Src 激酶的良好选择性。还通过研究这些化合物对细胞周期分布的影响来研究它们的细胞毒性机制。在所有检查的化合物中，化合物8b（在吡啶环上带有末端吡啶-3-基部分）对结直肠癌中的 src 激酶表现出最高的抑制选择性，同时伴有细胞周期停滞、细胞凋亡和自噬干扰细胞。该报告介绍了一类新型 PAP 衍生物，具有对结肠癌具有良好的激酶抑制和抗癌作用。
• Pyrazole compounds with inhibitory activity against ROS kinase
  申请人：Korea Institute of Science and Technology

  公开号：US08273880B2

  公开（公告）日：2012-09-25

  Disclosed herein are novel pyrazole compounds, pharmaceutically acceptable salts thereof, a method for preparing the same, and uses thereof as anticancer agents.

  本文披露了一种新型吡唑化合物、其药学上可接受的盐的制备方法，以及其作为抗癌剂的用途。
• Design, synthesis, screening, and molecular modeling study of a new series of ROS1 receptor tyrosine kinase inhibitors
  作者：Ibrahim M. El-Deeb、Byung Sun Park、Su Jin Jung、Kyung Ho Yoo、Chang-Hyun Oh、Seung Joo Cho、Dong Keun Han、Jae Yeol Lee、So Ha Lee

  DOI：10.1016/j.bmcl.2009.08.029

  日期：2009.10

  A series of rationally designed ROS1 tyrosine kinase inhibitors was synthesized and screened. Compound 12b has showed good potency with IC50 value of 209 nM, which is comparable with that of the reference lead compound 1. Molecular modeling studies have been performed, that is, a homology model for ROS1 was built, and the screened inhibitors were docked into its major identified binding site. The docked poses along with the activity data have revealed a group of the essential features for activity. Overall, simplification of the lead compound 1 into compound 12b has maintained the activity, while facilitated the synthetic advantages. A molecular interaction model for ROS1 kinase and inhibitors has been proposed. (C) 2009 Elsevier Ltd. All rights reserved.
• Design and synthesis of new potent anticancer pyrazoles with high FLT3 kinase inhibitory selectivity
  作者：Ibrahim Mustafa El-Deeb、So Ha Lee

  DOI：10.1016/j.bmc.2010.04.029

  日期：2010.6.1

  A new series of 1H- and 2H-pyrazole derivatives (35 final compounds) has been designed and synthesized in this study. A selected group (13 compounds) was then tested over a panel of 60 cancer cell lines at a single dose concentration of 10 mu M. At this concentration, six compounds have showed moderate to strong mean inhibitions, and were further tested at five-dose testing mode to determine their IC(50) over the 60 cell lines. The IC(50) values of the tested compounds indicated high potency (as for compound 10f) as well as high efficacy (as for compound 11e). Accordingly, compound 10f was then tested at a single dose concentration of 10 mu M over a panel of 54 kinases to determine its kinase inhibitory pro. le. The compound has showed good selectivity towards FLT3 kinase, associated with a moderate potency, with an IC(50) value of 1.74 mu M. (C) 2010 Elsevier Ltd. All rights reserved.