Synthesis and biological evaluation of a new series of 1,2,4-triazolo[1,5-a]-1,3,5-triazines as human A(2A) adenosine receptor antagonists with improved water solubility.

ABSTRACT: The structure-activity relationship (SAR) of 1,2,4-triazolo[1,5-a]-1,3,5-triazine derivatives related to ZM241385 as antagonists of the A(2A) adenosine receptor (AR) was explored through the synthesis of analogues substituted at the 5 position. The A(2A) AR X-ray structure was used to propose a structural basis for the activity and selectivity of the analogues and to direct the synthetic design strategy to provide access to solvent-exposed regions. Thus, we have identified a point of substitution for the attachment of solubilizing groups to enhance both aqueous solubility and physicochemical properties, maintaining potent interactions with the A(2A) AR and, in some cases, receptor subtype selectivity. Among the most potent and selective novel compounds were a long-chain ether-containing am

SUBMITTER: Federico S 

PROVIDER: S-EPMC3578427 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature