(S)-1-((2-chloro-6-(3-(3-methoxy-5-methylphenyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)propan-2-ol | 1188271-31-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (S)-1-((2-chloro-6-(3-(3-methoxy-5-methylphenyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)propan-2-ol
• 英文别名: (S)-1-(2-chloro-6-(3-(3-methoxy-5-methylphenyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)propan-2-ol；4-[2-chloro-6-(2(S)-hydroxypropylamino)-pyrimidin-4-yl]-3-(3-methoxy-5-methylphenyl)-1H-pyrazol；(2S)-1-[[2-chloro-6-[5-(3-methoxy-5-methylphenyl)-1H-pyrazol-4-yl]pyrimidin-4-yl]amino]propan-2-ol
• CAS: 1188271-31-9
• 化学式: C₁₈H₂₀ClN₅O₂
• 分子量: 373.842
• InChiKey: FKYZSHFWMXKWIJ-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  96
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-1-((2-chloro-6-(3-(3-methoxy-5-methylphenyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)propan-2-ol 在 bis-triphenylphosphine-palladium(II) chloride 、 potassium carbonate 作用下， 以 水 、 丙酮 、 乙腈 为溶剂， 反应 5.0h， 生成 (S)-2-(4-(6-((2-hydroxypropyl)amino)-2-(4-phenoxyphenyl)pyrimidin-4-yl)-3-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl)acetonitrile
  参考文献：
  名称：

  ＲＯＳ 카이네이즈 저해활성을 갖는 2,4,6-삼치환된 피리미딘 화합물

  摘要：

  This is the Chinese translation of the text you provided: 该发明涉及新型2,4,6-三取代嘧啶化合物及其药学上可接受的盐，该化合物的制备方法，以及将该化合物用作抗癌药物的药用用途。根据本发明，这些新型化合物对ROS激酶酶表现出非常优异的活性，因此对治疗和预防脑癌、与中枢神经系统相关的癌症、脑膜瘤（meningiomas）和星形胶质细胞瘤（astrocytomas）、多形性胶质母细胞瘤（glioblastoma multiforme）、非小细胞肺癌（NSCLC）等疾病具有用处。

  公开号：

  KR101556317B1
• 作为产物：
  描述：

  2,4-二氯-6-甲基嘧啶 在 N,N-二甲基甲酰胺二甲基缩醛 、 N,N-二异丙基乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 38.0h， 生成 (S)-1-((2-chloro-6-(3-(3-methoxy-5-methylphenyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)propan-2-ol
  参考文献：
  名称：

  ＲＯＳ 카이네이즈 저해활성을 갖는 2,4,6-삼치환된 피리미딘 화합물

  摘要：

  This is the Chinese translation of the text you provided: 该发明涉及新型2,4,6-三取代嘧啶化合物及其药学上可接受的盐，该化合物的制备方法，以及将该化合物用作抗癌药物的药用用途。根据本发明，这些新型化合物对ROS激酶酶表现出非常优异的活性，因此对治疗和预防脑癌、与中枢神经系统相关的癌症、脑膜瘤（meningiomas）和星形胶质细胞瘤（astrocytomas）、多形性胶质母细胞瘤（glioblastoma multiforme）、非小细胞肺癌（NSCLC）等疾病具有用处。

  公开号：

  KR101556317B1

文献信息

• 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。
• 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 and biological evaluation of new potent and highly selective ROS1-tyrosine kinase inhibitor
  作者：Byung Sun Park、Ibrahim M. El-Deeb、Kyung Ho Yoo、Chang-Hyun Oh、Seung Joo Cho、Dong Keun Han、Hye-Seung Lee、Jae Yeol Lee、So Ha Lee

  DOI：10.1016/j.bmcl.2009.06.066

  日期：2009.8

  ROS1 protein is a receptor tyrosine kinase that has been reported mainly in meningiomas and astrocytomas, and until now, there is no selective inhibitor for this kinase. In this study, we illustrate for the synthesis of a highly potent and selective inhibitor for ROS1 kinase. The synthesized compound 1 was tested initially at a single dose concentration of 10 mu M over 45 different kinases. At this concentration, a 94% inhibition of the enzymatic activity of ROS1 kinase was observed, while the inhibition in activity was below 30% in all of the other kinases. The pyrazole compound 1 was further tested in a 10-dose IC50 mode and showed an IC50 value of 199 nM for ROS1 kinase. The compound 1 can be used as a promising lead for the development of new selective inhibitors for ROS1 kinase, and it may open the way for new selective therapeutics for astrocytomas. (C) 2009 Elsevier Ltd. All rights reserved.
• Structure-based optimization and biological evaluation of trisubstituted pyrazole as a core structure of potent ROS1 kinase inhibitors
  作者：Byung Sun Park、Mohammad M. Al-Sanea、Ahmed Z. Abdelazem、Hye Mi Park、Eun Joo Roh、Hyun-Mee Park、Kyung Ho Yoo、Taebo Sim、Jin Sung Tae、So Ha Lee

  DOI：10.1016/j.bmc.2014.06.020

  日期：2014.8

  Recently inhibition of ROS1 kinase has proven to be a promising strategy for several indications such as glioblastoma, non-small cell lung cancer (NSCLC), and cholangiocarcinoma. Our team reported trisubstituted pyrazole-based ROS1 inhibitors by which two inhibitors showed good IC₅₀ values in enzyme-based screening. To develop more advanced ROS1 inhibitors through SAR this trisubstituted pyrazole-based scaffold has been built. Consequently, 16 compounds have been designed, synthesized and shown potent IC₅₀ values in the enzymatic assay, which are from 13.6 to 283 nM. Molecular modeling studies explain how these ROS1 kinase inhibitors revealed effectively the key interactions with ROS1 ATP binding site. Among these compounds, compound 9a (IC₅₀=13.6 nM) has exerted 5 fold potency than crizotinib and exhibited high degree of selectivity (selectivity score value=0.028) representing the number of non-mutant kinases with biological activity over 90% at 10 μM.
• US8273880B2
  申请人：——

  公开号：US8273880B2

  公开（公告）日：2012-09-25