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Projeto de investigação
COMPUTATIONAL MODELING OF PHOSPHODIESTERASE 3 INHIBITORS
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Publicações
Study on the cyclization of 6-arylethynylpyrimidine-5-carbaldehydes with tert-butylamine: microwave versus thermal preparation of pyrido[4,3-d]pyrimidines
Publication . Cikotiene, Inga; Kairys, Visvaldas; Buksnaitiene, Rita; Morkunas, Marius; Rudys, Simonas; Brukstus, Algirdas; Fernandes, Miguel X.
Thermal and microwave initiated cyclization of 2,4-disubstituted 6-arylethynylpyrimidine-5-carbalde hydes with tert-butylamine has been studied. A novel high-yielding preparation of 2,4-disubstituted 7-
arylpyrido[4,3-d]pyrimidines has been developed. The intermediate compounds were isolated and
possible mechanism of the reactions is discussed.
Toward the design of mutation‐resistant enzyme inhibitors: further evaluation of the substrate envelope hypothesis
Publication . Kairys, Visvaldas; Gilson, Michael K.; Lather, Viney; Schiffer, Celia A.; Fernandes, Miguel X.
Previous studies have shown the usefulness of
the substrate envelope concept in the analysis and
prediction of drug resistance profiles for human
immunodeficiency virus protease mutants. This
study tests its applicability to several other thera peutic targets: Abl kinase, chitinase, thymidylate
synthase, dihydrofolate reductase, and neuramini dase. For the targets where many (‡6) mutation data
are available to compute the average mutation sen sitivity of inhibitors, the total volume of an inhibitor
molecule that projects outside the substrate enve lope Vout, is found to correlate with average muta tion sensitivity. Analysis of a locally computed
volume suggests that the same correlation would
hold for the other targets, if more extensive muta tion data sets were available. It is concluded that
the substrate envelope concept offers a promising
and easily implemented computational tool for
the design of drugs that will tend to resist muta tions. Software implementing these calculations is
provided with the ’Supporting Information’.
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Entidade financiadora
Fundação para a Ciência e a Tecnologia
Programa de financiamento
PIDDAC
Número da atribuição
SFRH/BPD/41787/2007