Synthesis and biological evaluation of novel tricyclic oxazine and oxazepine fused quinazolines. Part 1: Erlotinib analogs |
| |
| Institution: | 1. Peoples'' Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya Street, Moscow 117198, Russian Federation;2. Institute of Macromolecular Compounds of the Russian Academy of Sciences, Bolshoi pr. VO 31, St. Petersburg 199004, Russian Federation;3. Saint-Petersburg National Research University of Information Technologies, Mechanics, and Optics, Kronverkskii pr. 49, 197101 St. Petersburg, Russian Federation;4. Vitebsk State Medical University, Frunze av. 27, Vitebsk 210009, Belarus |
| |
| Abstract: | Two series of novel tricyclic oxazine and oxazepine fused quinazolines have been designed and synthesized. The in vitro antitumor effect of the title compounds was screened on N87, A431, H1975, BT474 and Calu-3 cell lines. Compared to erlotinib and gefitinib, compounds 1a–1h were found to demonstrate more potent antitumor activities. Several derivatives could counteract EGF-induced phosphorylation of EGFR in cells, and their potency was comparable to the reference compounds. Compounds 1a–1h were chosen for further evaluation of EGFR and HER2 in vitro kinase inhibitory activity. Compounds 1b–1f, 1h effectively inhibited the in vitro kinase activity of EGFR and HER2 with similar efficacy as erlotinib and gefitinib. |
| |
| Keywords: | Tricyclic fused quinazolines Antitumor activity EGFR HER2 |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
