2(3H)-Benzoxazolone and Bioisosters as “Privileged Scaffold” in the Design of Pharmacological Probes

Title: 2(3H)-Benzoxazolone and Bioisosters as “Privileged Scaffold” in the Design of Pharmacological Probes

Volume: 12 Issue: 7

Author(s): Jacques Poupaert, Pascal Carato and Evelina Colacino

Affiliation:

Keywords: bioisosterism, privileged scaffolds, 2(3h)-benzoxazolone, 2(3h)-benzothiazolinone, mixed affinity ligands

Abstract: The 2(3H)-benzoxazolone heterocycle and its bioisosteric surrogates (such as 2(3H)-benzothiazolinone, benzoxazinone, 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 pKas, 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.

Cite this article as:

Poupaert Jacques, Carato Pascal and Colacino Evelina, 2(3H)-Benzoxazolone and Bioisosters as “Privileged Scaffold” in the Design of Pharmacological Probes, Current Medicinal Chemistry 2005; 12 (7) . https://dx.doi.org/10.2174/0929867053507388