HJMCe  >> Vol. 4 No. 4 (November 2016)

    Abemaciclib合成路线图解
    Graphical Synthetic Routes of Abemaciclib

  • 全文下载: PDF(407KB) HTML   XML   PP.38-41   DOI: 10.12677/HJMCe.2016.44005  
  • 下载量: 1,486  浏览量: 4,058   科研立项经费支持

作者:  

张 浩,张 剑:潍坊医学院药学院医用化学教研室,山东 潍坊;
陈奉泉:山东大学药学院药物化学教研室,山东 济南

关键词:
Abemaciclib合成CDK4/6Abemaciclib Synthesis CDK4/6

摘要:

Abemaciclib (Bemaciclib, LY-2835219)化学名称为N-[5-[(4-乙基-1-哌嗪)甲基]2-吡啶基]-5-氟-4-[4-氟-1-异丙基-2-甲基-1H-苯并咪唑-6-基]-2-嘧啶胺,是礼来公司研发的细胞周期蛋白依赖性激酶(cyclin-dependent kinase, CDK)4/6抑制剂。其单一用药对转移性乳腺癌有显著疗效,于2015年10月被美国FDA授予“突破性疗法”认证。本文综述了Abemaciclib及关键中间体的合成。

Abemaciclib (Bemaciclib, LY-2835219), whose chemical name is N-[5-[(4-ethyl-1-piperazinyl) methyl]-2-pyridinyl]-5-fluo-ro-4-[4-fluoro-2-methyl-1-(1-methylethyl)-1H-benzimidazol-6-yl]-2- pyrimidinamine, is a significant inhibitor of the cyclin-dependent kinase (CDK) 4/6 researched by Lilly, showing single-agent activity in metastatic breast cancer. Abemaciclib was granted “Breakthrough therapy designation” by the FDA in October 2015. In this paper, we summarized the synthesis of Abemaciclib and key intermediate.

文章引用:
张浩, 陈奉泉, 张剑. Abemaciclib合成路线图解[J]. 药物化学, 2016, 4(4): 38-41. http://dx.doi.org/10.12677/HJMCe.2016.44005

参考文献

[1] Patnaik, A., Rosen, L.S., Tolaney, S.M., et al. (2014) Abstract CT232: Clinical Activity of LY2835219, a Novel Cell Cycle Inhibitor Selective for CDK4 and CDK6, in Patients with Metastatic Breast Cancer. Cancer Research, 74, CT232-CT232. https://doi.org/10.1158/1538-7445.am2014-ct232
[2] DiGiulio, S. (2015) FDA’s Breakthrough Therapy Designation to Abemaciclib for Breast Cancer. Oncology Times, 2015.
[3] Sánchez-Martínez, C., Gelbert, L.M., Lallena, M.J., et al. (2015) Cyclin Dependent Kinase (CDK) Inhibitors as Anticancer Drugs. Bioorganic & Medicinal Chemistry Letters, 25, 3420-3435. https://doi.org/10.1016/j.bmcl.2015.05.100
[4] Finn, R.S., Aleshin, A. and Slamon, D.J. (2016) Targeting the Cyclin-Dependent Kinases (CDK) 4/6 in Estrogen Receptor-Positive Breast Cancers. Breast Cancer Research, 18, 17. https://doi.org/10.1186/s13058-015-0661-5
[5] Vidula, N. and Rugo, H.S. (2016) Cyclin-Dependent Kinase 4/6 Inhibitors for the Treatment of Breast Cancer: A Review of Preclinical and Clinical Data. Clinical Breast Cancer, 16, 8-17. https://doi.org/10.1016/j.clbc.2015.07.005
[6] Pascal, F., Diana, G.P. and Vito, G. (2009) Preparation of Quinoline and Quinoxaline Derivatives as Protein Tyrosine Kinase Inhibitors. WO Patent No. 2009141386A1.
[7] Andrew, C.D., Alfonso, D., Ana, D., et al. (2010) Protein Kinase Inhibitors. WO Patent No. 2010075074A1.
[8] Michale, C.E. (2015) Combination Therapy for Cancer. WO Patent No. 2015130540A1.
[9] Coates, D.A., Gelbert, L.M., Knobeloch, J.M., et al. (2010) Protein Kinase Inhibitors. US Patent No. 2010160340A1.
[10] 许学农. 玻玛西尼的制备方法[P]. 中国专利, 104529904A. 2015-04-22.
[11] Frederick, M.O. and Kjell, D.P. (2015) A Synthesis of Abemaciclib Utilizing a Leuckart-Wallach Reaction. Tetrahedron Letters, 56, 949-951. https://doi.org/10.1016/j.tetlet.2014.12.082