869358-02-1Relevant articles and documents
Quinolinonyl Non-Diketo Acid Derivatives as Inhibitors of HIV-1 Ribonuclease H and Polymerase Functions of Reverse Transcriptase
Messore, Antonella,Corona, Angela,Madia, Valentina Noemi,Saccoliti, Francesco,Tudino, Valeria,De Leo, Alessandro,Ialongo, Davide,Scipione, Luigi,De Vita, Daniela,Amendola, Giorgio,Novellino, Ettore,Cosconati, Sandro,Métifiot, Mathieu,Andreola, Marie-Line,Esposito, Francesca,Grandi, Nicole,Tramontano, Enzo,Costi, Roberta,Di Santo, Roberto
, p. 8579 - 8598 (2021/06/30)
Novel anti-HIV agents are still needed to overcome resistance issues, in particular inhibitors acting against novel viral targets. The ribonuclease H (RNase H) function of the reverse transcriptase (RT) represents a validated and promising target, and no inhibitor has reached the clinical pipeline yet. Here, we present rationally designed non-diketo acid selective RNase H inhibitors (RHIs) based on the quinolinone scaffold starting from former dual integrase (IN)/RNase H quinolinonyl diketo acids. Several derivatives were synthesized and tested against RNase H and viral replication and found active at micromolar concentrations. Docking studies within the RNase H catalytic site, coupled with site-directed mutagenesis, and Mg2+titration experiments demonstrated that our compounds coordinate the Mg2+cofactor and interact with amino acids of the RNase H domain that are highly conserved among na?ve and treatment-experienced patients. In general, the new inhibitors influenced also the polymerase activity of RT but were selective against RNase H vs the IN enzyme.
CARBAMATE LINKED MACROLIDES USEFUL FOR THE TREATMENT OF MICROBIAL INFECTIONS
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, (2010/02/14)
The present invention relates to 14- or 15-membered macrolides substituted at the 4" position of formula (I) and pharmaceutically acceptable derivatives thereof, to processes for their preparation and their use in therapy or prophylaxis of systemic or topical microbial infections in a human or animal body.
