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2 results on '"heteroaryl carbamates"'

1. New heteroaryl carbamates: Synthesis and biological screening in vitro and in mammalian cells of wild-type and mutant HIV-protease inhibitors.

Author

Tramutola, Francesco, Armentano, Maria Francesca, Berti, Federico, Chiummiento, Lucia, Lupattelli, Paolo, D'Orsi, Rosarita, Miglionico, Rocchina, Milella, Luigi, Bisaccia, Faustino, and Funicello, Maria

Subjects
*CARBAMATES synthesis, *BIOSYNTHESIS, *HIV, *BENZYL group, *EPOXY compounds, *CELLS
Abstract

Graphical abstract Abstract New heteroaryl HIV-protease inhibitors bearing a carbamoyl spacer were synthesized in few steps and high yield, from commercially available homochiral epoxides. Different substitution patterns were introduced onto a given isopropanoyl-sulfonamide core that can have either H or benzyl group. The in vitro inhibition activity against recombinant protease showed a general beneficial effect of both carbamoyl moiety and the benzyl group, ranging the IC 50 values between 11 and 0.6 nM. In particular, benzofuryl and indolyl derivatives showed IC 50 values among the best for such structurally simple inhibitors. Docking analysis allowed to identify the favorable situation of such derivatives in terms of number of interactions in the active site, supporting the experimental results. The inhibition activity was also confirmed in HEK293 mammalian cells and was maintained against protease mutants. Furthermore, the metabolic stability was comparable with that of the commercially available inhibitors. [ABSTRACT FROM AUTHOR]

Published
2019
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2. New heteroaryl carbamates: Synthesis and biological screening in vitro and in mammalian cells of wild-type and mutant HIV-protease inhibitors

Author

Rocchina Miglionico, Paolo Lupattelli, Luigi Milella, Faustino Bisaccia, Maria Funicello, Federico Berti, Francesco Tramutola, Maria Francesca Armentano, Lucia Chiummiento, Rosarita D'Orsi, Tramutola, Francesco, Armentano, Maria Francesca, Berti, Federico, Chiummiento, Lucia, Lupattelli, Paolo, D'Orsi, Rosarita, Miglionico, Rocchina, Milella, Luigi, Bisaccia, Faustino, and Funicello, Maria

Subjects
synthesis, medicine.medical_treatment, Clinical Biochemistry, Mutant, Pharmaceutical Science, 01 natural sciences, Biochemistry, HIV-protease inhibitors, chemistry.chemical_compound, heteroaryl carbamate, drug-resistance, HIV Protease, biological screening, Catalytic Domain, Drug Discovery, medicine, HIV Protease Inhibitor, Humans, heteroaryl carbamates, synthesis, biological screening, Molecular Biology, HIV-protease inhibitor, modeling, Protease, Binding Sites, biology, 010405 organic chemistry, Chemistry, Organic Chemistry, Wild type, Active site, HIV Protease Inhibitors, In vitro, 0104 chemical sciences, Molecular Docking Simulation, 010404 medicinal & biomolecular chemistry, HEK293 Cells, Docking (molecular), Drug Resistance, Neoplasm, Mutation, biology.protein, Benzyl group, HIV-1, Molecular Medicine, Carbamates
Abstract

New heteroaryl HIV-protease inhibitors bearing a carbamoyl spacer were synthesized in few steps and high yield, from commercially available homochiral epoxides. Different substitution patterns were introduced onto a given isopropanoyl-sulfonamide core that can have either H or benzyl group. The in vitro inhibition activity against recombinant protease showed a general beneficial effect of both carbamoyl moiety and the benzyl group, ranging the IC50 values between 11 and 0.6 nM. In particular, benzofuryl and indolyl derivatives showed IC50 values among the best for such structurally simple inhibitors. Docking analysis allowed to identify the favorable situation of such derivatives in terms of number of interactions in the active site, supporting the experimental results. The inhibition activity was also confirmed in HEK293 mammalian cells and was maintained against protease mutants. Furthermore, the metabolic stability was comparable with that of the commercially available inhibitors.

Published
2019

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