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dc.contributor.author | Val García, Cristina |
dc.contributor.author | Rodríguez García, Carlos |
dc.contributor.author | Prieto Díaz, Rubén |
dc.contributor.author | Crespo Gavilán, Abel |
dc.contributor.author | Azuaje Guerrero, Jhonny Alberto |
dc.contributor.author | Carbajales Pérez, Carlos |
dc.contributor.author | Majellaro, María |
dc.contributor.author | Díaz Holguín, Alejandro |
dc.contributor.author | Brea Floriani, José Manuel |
dc.contributor.author | Loza García, María Isabel |
dc.contributor.author | Gioé Gallo, Claudia |
dc.contributor.author | Contino, Marialessandra |
dc.contributor.author | Stefanachi, Angela |
dc.contributor.author | García Mera, Xerardo Xusto |
dc.contributor.author | Estévez Cabanas, Juan Carlos |
dc.contributor.author | Gutiérrez de Terán, Hugo |
dc.contributor.author | Sotelo, Eddy |
dc.date.accessioned | 2022-09-16T10:54:03Z |
dc.date.available | 2022-09-16T10:54:03Z |
dc.date.issued | 2022 |
dc.identifier.citation | J. Med. Chem. 2022, 65, 3, 2091–2106 |
dc.identifier.issn | 0022-2623 |
dc.identifier.uri | http://hdl.handle.net/10347/29223 |
dc.description.abstract | We herein document a large collection of 108 2-amino-4,6-disubstituted-pyrimidine derivatives as potent, structurally simple, and highly selective A1AR ligands. The most attractive ligands were confirmed as antagonists of the canonical cyclic adenosine monophosphate pathway, and some pharmacokinetic parameters were preliminarilly evaluated. The library, built through a reliable and efficient three-component reaction, comprehensively explored the chemical space allowing the identification of the most prominent features of the structure–activity and structure–selectivity relationships around this scaffold. These included the influence on the selectivity profile of the aromatic residues at positions R4 and R6 of the pyrimidine core but most importantly the prominent role to the unprecedented A1AR selectivity profile exerted by the methyl group introduced at the exocyclic amino group. The structure–activity relationship trends on both A1 and A2AARs were conveniently interpreted with rigorous free energy perturbation simulations, which started from the receptor-driven docking model that guided the design of these series |
dc.language.iso | eng |
dc.publisher | ACS Publications |
dc.rights | © 2022 The Authors. Published by American Chemical Society. This work is under a CC Attribution 4.0 International (CC BY 4.0) |
dc.rights | Atribución 4.0 Internacional |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ |
dc.title | Optimization of 2-Amino-4,6-diarylpyrimidine-5-carbonitriles as Potent and Selective A1 Antagonists |
dc.type | journal article |
dc.identifier.doi | 10.1021/acs.jmedchem.1c01636 |
dc.relation.publisherversion | https://doi.org/10.1021/acs.jmedchem.1c01636 |
dc.type.hasVersion | VoR |
dc.identifier.essn | 1520-4804 |
dc.rights.accessRights | open access |
dc.contributor.affiliation | Universidade de Santiago de Compostela. Centro de Investigación en Medicina Molecular e Enfermidades Crónicas |
dc.contributor.affiliation | Universidade de Santiago de Compostela. Centro de Investigación en Química Biolóxica e Materiais Moleculares |
dc.contributor.affiliation | Universidade de Santiago de Compostela. Departamento de Química Orgánica |
dc.description.peerreviewed | SI |
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