Aminobenzisoxazole compounds as agonists of α7 nicotinic acetylcholine receptors: a patent evaluation (WO 2017027600)

Abstract

ABSTRACTIntroduction: alpha 7 subtype nicotinic acetylcholine receptor (α7 nAChR) ligands, that is, ligands that interact with the orthosteric or allosteric binding sites of α7 nAChR, hold great potential for several therapeutic applications. Numerous compounds have been designed targeting α7 nAChR but most of them cannot be used therapeutically for various reasons.Areas covered: The patent application describes a series of germinal substituted aminobenzisoxazole compounds as α7 nAChR ligands. These compounds were claimed as potential therapeutics for treating and/or improving cognitive function. All of the (R)-stereoisomer presented high binding activities for α7 nAChR and several compounds displayed excellent selectivity over 5-HT3R.Expert opinion: The privileged structure-derived modification via bioisosterism and scaffold hopping is an important approach for seeking novel α7 nAChR ligands. The claimed germinal substituted aminobenzisoxazole derivatives with low tPSA values as well as low number of hydrogen bond donors and acceptors are supposed to have sufficient BBB penetration. Although there is a lack of essential biological data and the molecular mechanisms are not clear, these compounds stand for a new type of α7 nAChR ligands and deserve further studies.