Novel 2-Chloro-8-arylthiomethyldipyridodiazepinone Derivatives with Activity against HIV-1 Reverse Transcriptase

Abstract

Based on the molecular modeling analysis against Y181C HIV-1 RT, dipyridodiazepinone derivatives containing an unsubstituted lactam nitrogen and 2-chloro-8-arylthiomethyl were synthesized via an efficient route. Some of them were evaluated for their antiviral activity against HIV-1 RT subtype E and were found to exhibit virustatic activity comparable to some clinically used therapeutic agents.

Dipyridodiazepinone derivatives; synthesis and anti HIV-1 activity

“…Compounds 2 – 9 were synthesized via efficient routes as shown in Scheme 1 and Scheme 2 . The aminopyridinecarboxamide 15a (R = H) was prepared from 2-(ethylamino)-3-pyridinecarboxylic acid ( 13 ) and 3-amino-2,6-dichloropyridine ( 14 ) ( Scheme 1 ) [ 9 ]. However, by using the same procedure to prepare aminopyridinecarboxamide 15b (R = CH 3 ), only poor yields of 15b were obtained.…”

“…The 8-amino derivative of nevirapine and its hydrochloride salt also provided interesting potency. The first two compounds, 2 and 3 , were synthesized and their virustatic and virucidal activities against HIV-1 subtype E were reported previously [ 9 ]. As part of our continuing efforts directed towards the development of potential HIV-1 RT inhibitors, we have extended the synthesis of dipyridodiazepinone derivatives ( Fig.…”