Pyrazin-2(1H)-ones as a novel class of selective A3 adenosine receptor antagonists

Background: A(3)AR antagonists are promising drug candidates as neuroprotective agents as well as for the treatment of inflammation or glaucoma. The most widely known A(3)AR antagonists are derived from polyheteroaromatic scaffolds, which usually show poor pharmacokinetic properties. Accordingly, the identification of structurally simple A(3)AR antagonists by the exploration of novel diversity spaces is a challenging goal. Results: A convergent and efficient Ugi-based multicomponent approach enabled the discovery of pyrazin-2(1H)-ones as a novel class of A(3)AR antagonists. A combined experimental/computational strategy accelerated the establishment of the most salient features of the structure-activity and structure-selectivity relationships in this series. Conclusion: The optimization process provided pyrazin-2(1H)-ones with improved affinity and a plausible hypothesis regarding their binding modes was proposed.

Carbajales, Carlos (author)
Gonzalez-Gomez, Manuel (author)
Coelho, Alberto (author)
Caamano, Olga (author)
Gutierrez-de-Teran, HugoUppsala universitet,Beräknings- och systembiologi(Swepub:uu)hugut367 (author)
Sotelo, Eddy (author)
Uppsala universitetBeräknings- och systembiologi (creator_code:org_t)

In:Future Medicinal Chemistry: Future Science Ltd7:11, s. 1373-13801756-89191756-8927

By the author/editor: Azuaje, Jhonny; Carbajales, Carl ...; Gonzalez-Gomez, ...; Coelho, Alberto; Caamano, Olga; Gutierrez-de-Ter ...; show more...; Sotelo, Eddy; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Medical Biotechn ...; and Medical Biotechn ...

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