Pyrazin-2(1H)-ones as a novel class of selective A3 adenosine receptor antagonists
2015 (English)In: Future Medicinal Chemistry, ISSN 1756-8919, E-ISSN 1756-8927, Vol. 7, no 11, 1373-1380 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2015. Vol. 7, no 11, 1373-1380 p.
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
IdentifiersURN: urn:nbn:se:uu:diva-261332DOI: 10.4155/fmc.15.69ISI: 000358928300003PubMedID: 26230877OAI: oai:DiVA.org:uu-261332DiVA: diva2:850470
FunderSwedish Research Council, 521-2014-2118eSSENCE - An eScience Collaboration