130569-96-9Relevant articles and documents
6-(1-benzyl-1 h -pyrrol-2-yl)-2,4-dioxo-5-hexenoic acids as dual inhibitors of recombinant HIV-1 integrase and ribonuclease H, synthesized by a parallel synthesis approach
Costi, Roberta,Métifiot, Mathieu,Esposito, Francesca,Cuzzucoli Crucitti, Giuliana,Pescatori, Luca,Messore, Antonella,Scipione, Luigi,Tortorella, Silvano,Zinzula, Luca,Novellino, Ettore,Pommier, Yves,Tramontano, Enzo,Marchand, Christophe,Di Santo, Roberto
, p. 8588 - 8598 (2013/12/04)
The increasing efficiency of HAART has helped to transform HIV/AIDS into a chronic disease. Still, resistance and drug-drug interactions warrant the development of new anti-HIV agents. We previously discovered hit 6, active against HIV-1 replication and targeting RNase H in vitro. Because of its diketo-acid moiety, we speculated that this chemotype could serve to develop dual inhibitors of both RNase H and integrase. Here, we describe a new series of 1-benzyl-pyrrolyl diketohexenoic derivatives, 7a-y and 8a-y, synthesized following a parallel solution-phase approach. Those 50 analogues have been tested on recombinant enzymes (RNase H and integrase) and in cell-based assays. Approximately half (22) exibited inhibition of HIV replication. Compounds 7b, 7u, and 8g were the most active against the RNase H activity of reverse-transcriptase, with IC50 values of 3, 3, and 2.5 μM, respectively. Compound 8g was also the most potent integrase inhibitor with an IC50 value of 26 nM.
Non-steroidal antiinflammatory agents. VI. Synthesis of 10-oxo-5H-pyrrolo[1,2-b]isoquinoline-3-acetic acid, a conformationally restricted analogue of tolmetin
Coreli,Garofalo,Massa,Silvestri,Prosini,Artico
, p. 1489 - 1493 (2007/10/02)
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