2-chloro-4-(3-(3-methoxy-5-methylphenyl)-1H-pyrazol-4-yl)pyridine | 1192885-45-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-chloro-4-(3-(3-methoxy-5-methylphenyl)-1H-pyrazol-4-yl)pyridine
• 英文别名: 4-(2-chloropyridin-4-yl)-3-(3-methoxy-5-methylphenyl)-1H-pyrazol；2-chloro-4-[5-(3-methoxy-5-methylphenyl)-1H-pyrazol-4-yl]pyridine
• CAS: 1192885-45-2
• 化学式: C₁₆H₁₄ClN₃O
• 分子量: 299.76
• InChiKey: CXTZXYQUJOAFCV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  21
• 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：
  50.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-chloro-4-(3-(3-methoxy-5-methylphenyl)-1H-pyrazol-4-yl)pyridine 在 bis-triphenylphosphine-palladium(II) chloride 、 potassium carbonate 作用下， 以 四氢呋喃 、 水 、 丙酮 为溶剂， 反应 16.0h， 生成 2-(3-(3-methoxy-5-methylphenyl)-4-(2-(6-(methylthio)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 26.0h， 生成 2-chloro-4-(3-(3-methoxy-5-methylphenyl)-1H-pyrazol-4-yl)pyridine
  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

• Optimization of Bipyridinyl Pyrazole Scaffolds via Design, Synthesis and Screening of a New Series of ROS1 Kinase-modulating Compounds
  作者：Mohammad M. Al-Sanea、Byung Sun Park、Ahmed Z. Abdelazem、Khalid B. Selim、Kyung Ho Yoo、Taebo Sim、Jin Sung Tae、So Ha Lee

  DOI：10.1002/bkcs.10077

  日期：2015.1

  A series of rationally designed ROS1 tyrosine kinase inhibitors 6a–9b with bipyridinyl pyrazole scaffold was synthesized and screened. The scaffold itself has showed an exclusive selectivity profile over ROS1 closely related kinases, ALK and c‐Met. The aim of this study was to further explore the structure–activity relationships (SAR) of the bipyridinyl pyrazole core structure, and to improve its ROS1

  合成并筛选了一系列合理设计的带有联吡啶基吡唑支架的ROS1酪氨酸激酶抑制剂6a-9b。支架本身对ROS1密切相关的激酶ALK和c-Met表现出排他性选择性。这项研究的目的是进一步探索联吡啶基吡唑核心结构的结构-活性关系（SAR），并提高其ROS1抑制能力。这项研究的合理性是探究拟议的吡唑NH取代基结合位点的性质。考虑仔细选择吡唑NH取代基及其区域异构体。这些化合物显示出很高的效力，IC 50值为21–159 nM。最终确定了联吡啶基吡唑支架的详细SAR，并已通过分子对接对该类型的ROS1激酶抑制剂进行了虚拟筛选策略，并且对接的姿势以及活性数据与SAR规格一致。
• 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.
• US8273880B2
  申请人：——

  公开号：US8273880B2

  公开（公告）日：2012-09-25
• PYRAZOLE COMPOUNDS WITH INHIBITORY ACTIVITY AGAINST ROS KINASE
  申请人：LEE So Ha

  公开号：US20110015395A1

  公开（公告）日：2011-01-20

  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。