5'-SUBSTITUTED ADENOSINE-ANALOGS AS NEW HIGH-AFFINITY PARTIAL AGONISTS FOR THE ADENOSINE A(1) RECEPTOR

5'-(Alkylthio)-, 5'-(methylseleno)-, and 5'-(alkylamino)-substituted a nalogues of N-6-cyclopentyladenosine (CPA) were synthesized in 30-50% overall yields. The affinities of these compounds for the adenosine A( 1) and A(2A) receptors were determined in rat brain membranes. The 5'- substituted CPA analogues proved selective for the adenosine A(1) rece ptors, displaying affinities in the nanomolar range. The compounds wer e also evaluated for their ability to stimulate [S-35]GTP gamma S bind ing, also in rat brain membranes. The K-i values in receptor binding s tudies corresponded well to the EC50 values thus obtained. Intrinsic a ctivities of the compounds were tested in vitro by determining the GTP shift in receptor binding studies as well as the maximal binding of [ S-35]GTP gamma S. It appeared that the 5'-thio and 5'-seleno derivativ es in particular behaved as partial agonists.