2-chloro-N-cyclopentyl-5-fluoropyrimidin-4-amine | 1338495-23-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-chloro-N-cyclopentyl-5-fluoropyrimidin-4-amine
• CAS: 1338495-23-0
• 化学式: C₉H₁₁ClFN₃
• mdl: MFCD20441389
• 分子量: 215.658
• InChiKey: HZWNTIIEAVMVKW-UHFFFAOYSA-N

物化性质

• 沸点：
  373.2±27.0 °C(Predicted)
• 密度：
  1.380±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  37.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-chloro-N-cyclopentyl-5-fluoropyrimidin-4-amine 在 盐酸 、 甲醇 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 sodium tetrahydroborate 、 potassium acetate 作用下， 以 1,4-二氧六环 、 乙醇 、 水 为溶剂， 反应 3.5h， 生成 5-((4-(cyclopentylamino)-5-fluoropyrimidin-2-yl)amino)benzo[c][1,2]oxaborol-1(3H)-ol
  参考文献：
  名称：

  [EN] CHEMICAL COMPOUNDS
  [FR] COMPOSÉS CHIMIQUES

  摘要：

  本公开描述了新颖的化合物，或其药用可接受的盐，含有它们的药物组合物，以及它们的医疗用途。本公开的化合物具有作为Janus激酶（JAK）的双重调节剂的作用，单独使用，或与一个或多个附加机制（包括酪氨酸激酶，如TrkA或Syk，以及PDE4）结合使用，并且在治疗或控制炎症、自身免疫疾病、癌症以及其他调节JAK会可取的失调和其他适应症中是有用的。此外，还描述了通过施用本处所述的化合物来治疗炎症、自身免疫疾病、癌症以及其他易受JAK和PDE4抑制的状况的方法。

  公开号：

  WO2021003501A1
• 作为产物：
  描述：

  2,4-二氯-5-氟嘧啶 、 环戊胺 以 四氢呋喃 为溶剂， 反应 3.0h， 以77%的产率得到2-chloro-N-cyclopentyl-5-fluoropyrimidin-4-amine
  参考文献：
  名称：

  Synthesis and biological evaluation of 2,4-diaminopyrimidines as selective Aurora A kinase inhibitors

  摘要：

  The Aurora kinases are a family of serine/threonine kinases that interact with components of the mitotic apparatus and serve as potential therapeutic targets in oncology. Here we synthesized 15 2,4diaminopyrimidines and evaluated their biological activities, including antiproliferation, inhibition against Aurora kinases and cell cycle effects. These compounds generally exhibited more potent cytotoxicity against tumor cell lines compared with the VX-680 control, especially compound 11c, which showed the highest cytotoxicities, with IC50 values of 0.5-4.0 mu M. Compound 11c had more than 35-fold more selectivity for Aurora A over Aurora B, and molecular docking analysis indicated that compound 11c form better interaction with Aurora A both from the perspective of structure and energy. Furthermore, compound 11c induced G2/M cell cycle arrest in HeLa cells. This series of compounds has the potential for further development as selective Aurora A inhibitors for anticancer activity. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.03.044

文献信息

• Discovery of a Novel, First-in-Class, Orally Bioavailable Azaindole Inhibitor (VX-787) of Influenza PB2
  作者：Michael P. Clark、Mark W. Ledeboer、Ioana Davies、Randal A. Byrn、Steven M. Jones、Emanuele Perola、Alice Tsai、Marc Jacobs、Kwame Nti-Addae、Upul K. Bandarage、Michael J. Boyd、Randy S. Bethiel、John J. Court、Hongbo Deng、John P. Duffy、Warren A. Dorsch、Luc J. Farmer、Huai Gao、Wenxin Gu、Katrina Jackson、Dylan H. Jacobs、Joseph M. Kennedy、Brian Ledford、Jianglin Liang、François Maltais、Mark Murcko、Tiansheng Wang、M. Woods Wannamaker、Hamilton B. Bennett、Joshua R. Leeman、Colleen McNeil、William P. Taylor、Christine Memmott、Min Jiang、Rene Rijnbrand、Christopher Bral、Ursula Germann、Azin Nezami、Yuegang Zhang、Francesco G. Salituro、Youssef L. Bennani、Paul S. Charifson

  DOI：10.1021/jm5007275

  日期：2014.8.14

  In our effort to develop agents for the treatment of influenza, a phenotypic screening approach utilizing a cell protection assay identified a series of azaindole based inhibitors of the cap-snatching function of the PB2 subunit of the influenza A viral polymerase complex. Using a bDNA viral replication assay (Wagaman, P. C.; Leong, M. A.; Simmen, K. A. Development of a novel influenza A antiviral assay. J. Virol. Methods 2002, 105, 105-114) in cells as a direct measure of antiviral activity, we discovered a set of cyclohexyl carboxylic acid analogues, highlighted by VX-787 (2). Compound 2 shows strong potency versus multiple influenza A strains, including pandemic 2009 H1N1 and avian H5N1 flu strains, and shows an efficacy profile in a mouse influenza model even when treatment was administered 48 h after infection. Compound 2 represents a first-in-class, orally bioavailable, novel compound that offers potential for the treatment of both pandemic and seasonal influenza and has a distinct advantage over the current standard of care treatments including potency, efficacy, and extended treatment window.
• CHEMICAL COMPOUNDS
  申请人：Borah, Inc.

  公开号：EP3994142A1

  公开（公告）日：2022-05-11
• Synthesis and biological evaluation of 2,4-diaminopyrimidines as selective Aurora A kinase inhibitors
  作者：Wen-Wen Qin、Chun-Yan Sang、Lin-Lin Zhang、Wei Wei、Heng-Zhi Tian、Huan-Xiang Liu、Shi-Wu Chen、Ling Hui

  DOI：10.1016/j.ejmech.2015.03.044

  日期：2015.5

  The Aurora kinases are a family of serine/threonine kinases that interact with components of the mitotic apparatus and serve as potential therapeutic targets in oncology. Here we synthesized 15 2,4diaminopyrimidines and evaluated their biological activities, including antiproliferation, inhibition against Aurora kinases and cell cycle effects. These compounds generally exhibited more potent cytotoxicity against tumor cell lines compared with the VX-680 control, especially compound 11c, which showed the highest cytotoxicities, with IC50 values of 0.5-4.0 mu M. Compound 11c had more than 35-fold more selectivity for Aurora A over Aurora B, and molecular docking analysis indicated that compound 11c form better interaction with Aurora A both from the perspective of structure and energy. Furthermore, compound 11c induced G2/M cell cycle arrest in HeLa cells. This series of compounds has the potential for further development as selective Aurora A inhibitors for anticancer activity. (C) 2015 Elsevier Masson SAS. All rights reserved.
• [EN] CHEMICAL COMPOUNDS<br/>[FR] COMPOSÉS CHIMIQUES
  申请人：BORAGEN INC

  公开号：WO2021003501A1

  公开（公告）日：2021-01-07

  The present disclosure describes novel compounds, or their pharmaceutically acceptable salts, pharmaceutical compositions containing them, and their medical uses. Compounds of the disclosure have activity as dual modulators of Janus kinase (JAK), alone, or in combination with one or more of an additional mechanism, including a tyrosine kinase, such as TrkA or Syk, and PDE4, and are useful in the in the treatment or control of inflammation, auto-immune diseases, cancer, and other disorders and indications where modulation of JAK would be desirable. Also described herein are methods of treating inflammation, auto-immune diseases, cancer, and other conditions susceptible to inhibition of JAK and PDE4 by administering a compound herein described.

  本公开描述了新颖的化合物，或其药用可接受的盐，含有它们的药物组合物，以及它们的医疗用途。本公开的化合物具有作为Janus激酶（JAK）的双重调节剂的作用，单独使用，或与一个或多个附加机制（包括酪氨酸激酶，如TrkA或Syk，以及PDE4）结合使用，并且在治疗或控制炎症、自身免疫疾病、癌症以及其他调节JAK会可取的失调和其他适应症中是有用的。此外，还描述了通过施用本处所述的化合物来治疗炎症、自身免疫疾病、癌症以及其他易受JAK和PDE4抑制的状况的方法。