Title:1, 2-Benzisoxazole: A Privileged Structure with a Potential for Polypharmacology
Volume: 22
Issue: 21
Author(s): Yoshikazu Uto
Affiliation:
Keywords:
1, 2-benzisoxazole, privileged structures, polypharmacology, antipsychotics, antiepileptics, Parkinson’s disease.
Abstract: Background: Privileged structures are potentially able to bind to a diverse range of biologically important
proteins with high affinities, thus benefiting the discovery of novel bioactive compounds. 1,2-Benxisoxazole
derivatives can be such important types of “privileged structures” possessing a rich diversity of biological properties
especially in the area of CNS disorders. Methods: This review seeks to explore the most significant examples
of 1,2-benzisoxazoles as privileged structures in terms of polypharmacology at the molecular level, specifically
focusing on four 1,2-benzisoxazoles (zonisamide, risperidone, paliperidone, and iloperidone) which have been in
clinical use and established as effective therapeutics. Furthermore, an updated and detailed account of the pharmacological
properties of 1,2-benzisoxazole derivatives as therapeutics for CNS disorders is described. And finally,
outlooks on current issues and future directions in this field are also provided. Results: 1,2-Benzisoxazole was successfully
employed in the discovery and development of zonisamide for the treatment of epilepsy and Parkinson’s disease. 1,2-
Benzisoxazole is also a significantly important structure for the development of atypical antipsychotics. Conclusion: It is very reasonable
to say that 1,2-benzisoxazole is a good example of a privileged structure because it forms the centerpiece of small molecule chemical entities
with a wide range of pharmacological properties, especially in the area of CNS disorders.
