Em. Vanderwenden et al., 5'-SUBSTITUTED ADENOSINE-ANALOGS AS NEW HIGH-AFFINITY PARTIAL AGONISTS FOR THE ADENOSINE A(1) RECEPTOR, Journal of medicinal chemistry, 41(1), 1998, pp. 102-108
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.