Bitopic fluorescent antagonists of the A_2A adenosine receptor based on pyrazolo[4,3-<i>e</i>][1,2,4]triazolo[1,5-<i>c</i>]pyrimidin-5-amine functionalized congeners.

ABSTRACT: A pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine antagonist of the A_2A adenosine receptor (AR) was functionalized as amine congeners, fluorescent conjugates and a sulfonate, and the A_2AAR binding modes were predicted computationally. The optimal n-butyl spacer was incorporated into the following A_2AAR-selective (K_i, nM) conjugates: BODIPY630/650 derivative 11 (MRS7396, 24.6) and AlexaFluor488 derivative 12 (MRS7416, 30.3). Flow cytometry of 12 in hA_2AAR-expressing HEK-293 cells displayed saturable binding (low nonspecific) and inhibition by known A_2AAR antagonists. Water-soluble sulfonate 13 was a highly potent (K_i = 6.2 nM) and selective A

SUBMITTER: Duroux R 

PROVIDER: S-EPMC5729930 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature