Synthesis and Binding Affinity of 2-Phenylimidazo[1,2-a]pyridine Derivatives for Both Central and Peripheral Benzodiazepine Receptors. A New Series of High-Affinity and Selective Ligands for the Peripheral Type.

A number of 6-substituted or 6,8-disubstituted alkyl 2-phenylimidazo[1,2-a]pyridine-3-carboxylates 5a−h, -acetates 5i−s, 6a−g, and -propionates 5t, 6h and of N,N-dialkyl-2-phenylimidazo[1,2-a]pyridine-3-carboxamides 7a−d, -acetamides 7e−t or -propionamide 7u were prepared following new synthetic methods, and their affinities for both the central (CBR) and the peripheral (PBR) benzodiazepine receptors evaluated. The compounds of the ester series displayed low affinity for both receptor types. Conversely, most of N,N-dialkyl(2-phenylimidazo[1,2-a]pyridin-3-yl)acetamides 7e−t proved to possess high affinity and selectivity for CBR or PBR depending on the nature of substituents at C(6)- and/or C(8) on the heterocyclic ring system. In particular, the 6-substituted compounds 7f−n displayed ratios of IC50 values (IC50(CBR)/IC50(PBR)) ranging from 0.32 (7m) to 232 (7k), while the 6,8-disubstituted compounds 7o−t were more than 1000-fold more selective for PBR versus CBR. Compounds 7f,m were examined in several di...