In search for new chemical entities as adenosine receptor ligands: development of agents based on benzo-γ-pyrone skeleton.
A selected series of chromone carboxamides synthesized in our laboratory were evaluated by radioligand binding studies towards adenosine receptors. All the chromone-3-carboxamides (compounds 8-12) exhibit A(2B) receptor displacement percentage superior to 50%. The best results were obtained with phenolic substituents (compounds 9 and 12) in the position 3 of pyrone ring with a K(i) value of 2890 and 1350 nM. In addition, the predicted ADME properties for the chromone carboxamides under study are in accordance with the general requirements for the drug discovery and development process and in turn they have potential to emerge as a drug candidate. In summary, N-phenylchromone-3-carboxamide may be proposed as a promising scaffold that can undergo optimization as a selective A(2B)AR antagonist given its lower affinity for A(1)AR and A(2A)AR. Accordingly, one can propose this new chromone class as a promising scaffold for tackling adenosine receptors, namely of A(2B) subtype.
CIQUP/Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Porto, Portugal.
Alexandra
A
Gaspar
Joana
J
Reis
Maria João
MJ
Matos
Eugenio
E
Uriarte
Fernanda
F
Borges
D000042:Absorption; D000818:Animals; D002460:Cell Line; D002867:Chromones / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D006224:Cricetinae; D055808:Drug Discovery; D006801:Humans; D008024:Ligands; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D013329:Structure-Activity Relationship
D002867:Chromones; D008024:Ligands; D018047:Receptors, Purinergic P1