Discovery of ONO-8590580: a novel, potent and selective GABAA α5 negative allosteric modulator for the treatment of cognitive disorders.

Discovery of ONO-8590580: a novel, potent and selective GABAA α5 negative allosteric modulator for the treatment of cognitive disorders.
Bioorg Med Chem Lett. 2020 Sep 05;:127536
Authors: Lewis A, Beresford A, Chambers MS, Clark G, Hartley DC, Hirst KL, Higashino M, Kawahadara S, Nakanishi M, Saito T, Imagawa A, Habashita H, Maidment S, Macleod AM, Owens AP, Rae A, Rouse C, Wishart G
Abstract
The identification and SAR development of a series of negative allosteric modulators of the GABAA α5 receptor is described. This novel series of compounds was optimised to provide analogues with high GABAA α5 binding affinity, high α5 negative allosteric modulatory activity, good functional subtype selectivity and low microsomal turnover, culminating in identification of ONO-8590580.
PMID: 32898695 [PubMed - as supplied by publisher]

Source: Bioorganic and Medicinal Chemistry Letters - September 4, 2020 Category: Chemistry Authors: Lewis A, Beresford A, Chambers MS, Clark G, Hartley DC, Hirst KL, Higashino M, Kawahadara S, Nakanishi M, Saito T, Imagawa A, Habashita H, Maidment S, Macleod AM, Owens AP, Rae A, Rouse C, Wishart G Tags: Bioorg Med Chem Lett Source Type: research