2(3H)-benzoxazolone and bioisosters as Privileged Scaffold in the design of pharmacological probes

The 2(3H)-benzoxazolone heterocycle and its bioisosteric Surrogates (such as 2(3H)-benzothiazolinone, beilzoxazinoile, etc.) have received considerable attention from the medicinal chemists owing to their capacity to mimic a phenol or a catechol moiety in a metabolically stable template. These heterocycles and pyrocatechol have indeed similar pKa's. electronic charge distribution, and chemical reactivity. Therapeutic applications of this template are very broad, and range from analgesic anti-inflammatory compounds (including PPAR-gamma antagonists) to antipsychotic and neuroprotective anticonvulsant compounds. High affinity ligands have been obtained also for dopaminergic (D2 and D4), serotoninergic (5-HT1A and 5-HT-2A), sigma-1 and sigma-2 receptors. Owing to the high number of positive hits encountered with this heterocycle and its congeners. 2(3H,)benzoxazolone template certainly deserves the title of privileged scaffold in medicinal chemistry.