96865-93-9Relevant articles and documents
Functionalized Congeners of 1,3-Dialkylxanthines: Preparation of Analogues with High Affinity for Adenosine Receptors
Jacobson, Kenneth A.,Kirk, Kenneth L.,Padgett, William L.,Daly, John W.
, p. 1334 - 1340 (2007/10/02)
A series of functionalized congeners of 1,3-dialkylxanthines has been prepared as adenosine receptor antagonists.On the basis of high potency of 8-(p-hydroxyphenyl)-1,3-dialkylxanthines, the parent compounds were 8-phenyl> derivatives of theophylline and 1,3-dipropylxanthine.A series of analogues including esters of ethanol and N-hydroxysuccinimide, amides, a hydrazide, an acylurea, and anilides were prepared.The potency in blocking A1-adenosine receptors (inhibition of binding of N6-cyclohexyladenosine to brain membranes) and A2-adenosine receptors (inhibition of 2-chloroadenosine-elicited accumulations of cyclic AMP in brain slices) was markedly affected by structural changes distal to the primary pharmacophore (8-phenyl-1,3-dialkylxanthine).Potencies in the dipropyl series at the A1 receptor ranged from Ki values of 1.2 nM for a congener with a terminal amidoethyleneamine moiety to a Ki value of 58 nM for the parent carboxylic acid to a Ki of 96 nM for the bulky ureido congener.Certain congeners were up to 145-fold more active at A1 receptors than at A2 receptors.Various derivatives of the congeners should be useful as receptor probes and for radioidodination, avidin binding, and preparation of affinity columns.
