380655-10-7Relevant academic research and scientific papers
Synthesis of dihydropyrimidine α,μ3-diketobutanoic acid derivatives targeting HIV integrase
Sari, Ozkan,Roy, Vincent,Métifiot, Mathieu,Marchand, Christophe,Pommier, Yves,Bourg, Stéphane,Bonnet, Pascal,Schinazi, Raymond F.,Agrofoglio, Luigi A.
, p. 127 - 138 (2015)
The synthesis and antiviral evaluation of a series of dihydropyrimidinone and thiopyrimidine derivatives bearing aryl α,γ-diketobutanoic acid moiety are described using the Biginelli multicomponent reaction as key step. The most active among 20 synthesized novel compounds were 4c, 4d and 5b, which possess nanomolar HIV-1 integrase (IN) stand transfer (ST) inhibition activities. In order to understand their mode of interactions within the IN active site, we docked all the compounds into the previously reported X-ray crystal structure of IN. We observed that compounds 4c, 4d and 5b occupied an area close to the two catalytic Mg2+ ions surrounded by their chelating triad (E221, D128 and D185), DC16, Y212 and the β-diketo acid moiety of 4c, 4d and 5b chelating Mg2+. As those compounds lack anti-HIV activities in cell, their prodrugs were synthetized. The prodrug 4c′ exhibited an anti-HIV activity of 0.19 μM in primary human lymphocytes with some cytotoxicity. All together, these results indicate that the new analogs potentially interact within the catalytic site with highly conserved residues important for IN catalytic activity.
Selective acylation of 5-nitro- and 5-ethoxycarbonyl-4,6-diaryl-3,4- dihydropyrimidin-2(1H)-ones
Sedova,Shkurko
experimental part, p. 1695 - 1701 (2011/03/18)
The acetylation and chloroacetylation of 5-nitro- and 5-ethoxycarbonyl- substituted 4,6-diaryl-3,4-dihydropyrimidin-2(1H)-ones proceeds regioselectively at the N3 atom of the heterocycle whereas the acetylation of the 5-aryloxy-substituted anal
A new approach to the synthesis of Biginelli compounds
Shutalev, Anatoly D.,Kurochkin, Nikolay N.
, p. 70 - 72 (2007/10/03)
A new synthesis of 4-aryl-2-oxo-l,2,3,4-tetrahydropyrimidine-5-carboxylic acid esters is based on the reactions of α-tosyl-substituted phenyl carbamates with the enolates of β-oxoesters followed by treatment with ammonia and dehydration of the resulting 4
