Synthesis and biological evaluation of 4-phenylquinazoline-2-carboxamides designed as a novel class of potent ligands of the translocator protein.

doi:10.1021/jm201703k

Paper

DOI: 10.1021/jm201703k

Synthesis and biological evaluation of 4-phenylquinazoline-2-carboxamides designed as a novel class of potent ligands of the translocator protein.

Published Apr 25, 2012 · S. Castellano, S. Taliani, Ciro Milite

Journal of medicinal chemistry

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Abstract

A series of novel 4-phenylquinazoline-2-carboxamides (1-58) were designed as aza-isosters of PK11195, the well-known 18 kDa translocator protein (TSPO) reference ligand, and synthesized by means of a very simple and efficient procedure. A number of these derivatives bind to the TSPO with K(i) values in the nanomolar/subnanomolar range, show selectivity toward the central benzodiazepine receptor (BzR) and exhibit structure-affinity relationships consistent with a previously published pharmacophore/topological model of ligand-TSPO interaction.

Study Snapshot

These novel 4-phenylquinazoline-2-carboxamides show potential as potent ligands of the translocator protein, with selectivity for the central benzodiazepine receptor and consistent structure-affinity relationships.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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