Syntheses of [14C]-labeled 2-(3-chlorophenyloxy)-3-[3-(3-hydroxy) pyridin-4-yl propoxy]pyridine, a phosphodiesterase 4 inhibitor and its metabolites.

We describe here the synthesis of [(14)C]-2-(3-chlorophenyloxy)-3-[3-(3-hydroxy)pyridin-4-yl propoxy]pyridine (1), a phosphodiesterase 4 inhibitor. [(14)C]-Labeled 1 was prepared in three steps from [(14)C]-2-bromopyridin-3-ol in an overall yield of 32%. Preparation of [(14)C]-labeled 2 and 3, two metabolites of 1, is also described.

Syntheses and properties of the major hydroxy metabolites in humans of blonanserin AD-5423, a novel antipsychotic agent.

Two major metabolites in humans of blonanserin, 2-(4-ethyl-1-piperazinyl)-4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta-[b]pyridine (code name AD-5423), were synthesized. The first, 7-hydroxylated AD-5423, was synthesized through a four-step process starting from 4-fluorobenzoylacetonitrile (1), and the second, 8-hydroxylated AD-5423, a nine-step process also from 1. The optical resolution, structures, and receptor binding properties of the metabolites were documented.