标题：Privileged Scaffolds or Promiscuous Binders: A Glance of Pyrrolo[2,1-f][1,2,4]triazines and Related Bridgehead Nitrogen Heterocycles in Medicinal Chemistry
作者：Song, Yu'ning; Zhan, Peng; Zhang, Qingzhu; Liu, Xinyong
作者机构：[Zhan, Peng; Liu, Xinyong] Shandong Univ, Sch Pharmaceut Sci, Minist Educ, Key Lab Chem Biol,Dept Med Chem, Jinan 250012, Shandong, Peoples R China.; 更多
通讯作者地址：[Zhan, P]Shandong Univ, Sch Pharmaceut Sci, Minist Educ, Key Lab Chem Biol,Dept Med Chem, 44 West Culture Rd, Jinan 250012, Shandong, Peoples R China.
来源：CURRENT PHARMACEUTICAL DESIGN
关键词：Heterocycle; Bridgehead nitrogen heterocycle; Privileged scaffold;; Bioisosters; Pyrrolo[2,1-f][1,2,4]triazine; Biological activities; Drug; design
摘要：Pyrrolo[2,1-f][1,2,4]triazine template, a unique bridgehead nitrogen heterocycle, certainly deserves the title of "privileged scaffold" in the drug discovery field because of the versatility and potential to yield derivatives with a wide range of biological activities, such as anti-anaplastic lymphoma kinase (ALK), Janus kinase 2 (JAK2), VEGFR-2, EGFR and/or HER2, Met kinase, p38 mitogen-activated protein (MAP) kinase and insulin-like growth factor receptor (IGF-1R) kinase activities, etc. These different biological properties of pyrrolo[2,1-f][1,2,4]triazine derivatives have motivated new studies in searching for novel derivatives with improved activity and also other applications in pharmaceutical field. However, no systematic review is available in the literature on the pyrrolo[2,1-f][1,2,4]triazine derivatives concerning the design of potent drug-like compounds. Owing to the importance of this heterocyclic system, the present paper is an attempt to the pharmacological activities, structural modifications and the structure-activity relationship (SAR) reported for bridgehead nitrogen heterocycles in the current literature, making an effort to highlight the importance and therapeutic potentials of the pyrrolo[2,1-f][1,2,4]triazine scaffold and its bridgehead nitrogen bioisosters as heterocyclic privileged medicinal scaffolds.