35957-44-9Relevant academic research and scientific papers
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.
Structure-guided optimization of quinoline inhibitors of Plasmodium N-myristoyltransferase
Goncalves, Victor,Brannigan, James A.,Laporte, Alice,Bell, Andrew S.,Roberts, Shirley M.,Wilkinson, Anthony J.,Leatherbarrow, Robin J.,Tate, Edward W.
supporting information, p. 191 - 197 (2017/02/05)
The parasite Plasmodium vivax is the most widely distributed cause of recurring malaria. N-Myristoyltransferase (NMT), an enzyme that catalyses the covalent attachment of myristate to the N-terminal glycine of substrate proteins, has been described as a p
2,2-Bis(ethoxycarbonyl)vinyl (BECV) as a versatile amine protecting group for selective functional-group transformations
Ilangovan, Andivelu,Kumar, Rajendran Ganesh
supporting information; experimental part, p. 2938 - 2943 (2010/07/02)
A 2,2-Bis(ethoxycarbonyl) vinyl- (BECV) group was used for the selective protection of amines at room temperature in the presence of potentially interfering functional groups such as OH, SH, COOH as well as other NH 2 groups. Several functional group transformations such as esterification, O-alkylation, O-acylation, N-alkylation, N-acylation, S-alkylation can selectively be carried out in the presence of the BECV group. The selective deprotection of the BECV group was achieved in a short time using ethylenediamine at room temperature while several other functional groups such as benzoate, aliphatic esters, amides and ethers remain intact. The BECV group shows orthogonal stability against the common protecting groups such as Fmoc, Cbz and Boc.
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.
Computer-Aided Molecular Modeling, Synthesis, and Biological Evaluation of 8-(Benzyloxy)-2-phenylpyrazoloquinoline as a Novel Benzodiazepine Receptor Agonist Ligand
Wang, C.-G.,Langer, T.,Kamath, P. G.,Gu, Z.-Q.,Skolnick, P.,Fryer, R. Ian
, p. 950 - 957 (2007/10/02)
Using computer-aided conformational analysis, based on molecular dynamics simulation, cluster analysis, and Monte Carlo techniques, we have designed and synthesized compounds in which a benzyloxy substituent has been incorporated into a series of pyrazoloquinoline benzodiazepine receptor (BZR) ligands.Earlier studies had shown that the benzyloxy group could act as part of the agonist pharmacophoric determinant in the β-carboline ring system.Furthermore, the agonist β-carboline had been correlated with a binding site orientation and volume fit for an agonist 6-phenylimidazobenzodiazepine carboxylate.The present study was undertaken to determine whether the benzyloxy substituent could be used as an agonist pharmacophoric descriptor for the phenylpyrazoloquinolin-3-one BZR ligands.The results of a determination of GABA shift ratios for the synthetic ligands indicate that 8-(benzyloxy)-2-phenylpyrazoloquinolin-3-one can be predicted to be an agonist at the BZR.
