Tetrahydroquinazoline N-oxide derivatives inhibit reproduction of tick-borne and mosquito-borne flaviviruses.

Tick-borne encephalitis virus (TBEV), yellow fever virus (YFV), and West Nile virus (WNV) are flaviviruses causing emerging arthropod-borne infections of a great public health concern. Clinically approved drugs are not available to complement or replace the existing vaccines, which do not provide sufficient coverage. Thus, the discovery and characterization of new antiflaviviral chemotypes would advance studies in this field.

An improved synthesis of some 5-substituted indolizines using regiospecific lithiation.

Various 2-substituted indolizines can be directly and selectively lithiated in the 5 position and subsequent reactions with different electrophiles lead to some novel classes of indolizines. In particular, previously unknown 5-formyl- and 5-iodoindolizine have been prepared by this way and the molecular structure of 5-formyl-2- phenylindolizine was confirmed by X-Ray analysis. The reactivity of the 5-CHO- and 5- COPh groups toward some nucleophiles has been examined, and some additional classes of derivatives (oximes and alcohols) have been obtained.