Tocco, Graziella; Esposito, Francesca; Caboni, Pierluigi; Laus, Antonio; Beutler, John A.; Wilson, Jennifer A.; Corona, Angela; Le Grice, Stuart F. J.; Tramontano, Enzo published the artcile< Scaffold hopping and optimisation of 3′,4′-dihydroxyphenyl- containing thienopyrimidinones: synthesis of quinazolinone derivatives as novel allosteric inhibitors of HIV-1 reverse transcriptase-associated ribonuclease H>, SDS of cas: 5004-88-6, the main research area is HIV1 virus allosteric inhibitors reverse transcriptase RNase H; Bioisosters; HIV-1 virus; RNase H; RNase H allosteric inhibitors; integrase.
Bioisosteric replacement and scaffold hopping are powerful strategies in drug design useful for rationally modifying a hit compound towards novel lead therapeutic agents. Recently, we reported a series of thienopyrimidinones that compromise dynamics at the p66/p51 HIV-1 reverse transcriptase (RT)-associated RNase H (RNase H) dimer interface, thereby allosterically interrupting catalysis by altering the active site geometry. Although they exhibited good submicromolar activity, the isosteric replacement of the thiophene ring, a potential toxicophore, is warranted. Thus, in this article, the most active 2-(3,4-dihydroxyphenyl)-5,6-dimethylthieno[2,3-d]pyrimidin-4(3H)-one was selected as the hit scaffold and several isosteric substitutions of the thiophene ring were performed. A novel series of highly active RNase H allosteric quinazolinone inhibitors was thus obtained. To determine their target selectivity, they were tested against RT-associated RNA-dependent DNA polymerase (RDDP) and integrase (IN). Interestingly, none of the compounds were particularly active on (RDDP) but many displayed micromolar to submicromolar activity against IN.
Journal of Enzyme Inhibition and Medicinal Chemistry published new progress about Antiviral agents. 5004-88-6 belongs to class amides-buliding-blocks, and the molecular formula is C9H12N2O3, SDS of cas: 5004-88-6.
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