Abstract

A FACILE SYNTHESIS OF TRIAZOLOQUINAZOLINONE DERIVATIVES AS POTENTIAL Α-GLUCOSIDASE INHIBITORS

Suresh Poudapally, Venkateshwarlu Gurram, Chiranjeevi Thulluri, Pavan Kumar Machiraju, Anji Karun Mutha, Subhabrata Sen* and Vidya Katangoor*

Abstract

In continuation of our efforts to develop a lead antidiabetic compound, a series of eighteen novel triazoloquinazolinone derivatives have been synthesized and screened against α-glucosidase. The binding mode of the compounds at the active site of α-glucosidase was explored using Glide docking method. 6-Bromo-2,3-disubstituted quinazoline-4(3H)- one analogues are readily converted to the amino derivatives via Buchwald amination that upon diazotization with t-BuONO and TMSN3 yield the stable C-6 azido derivatives. Screening of conditions for the ligation of the azido quinazolinones with alkynes showed that CuSO4 in t-BuOH/H2O is optimal, yielding C-6 modified 1,2,3- triazolyl quinazolinones in 70−82% yields (eighteen compounds). Based on the interaction profile and docking score, all these compounds were selected for in vitro enzymatic screening. Eight of these eighteen compounds showed

Keywords: Triazoloquinazolinones, Amination, Azide formation, Click chemistry, Docking studies, ?-Glucosidase inhibitors.