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Discovery of ONO-8590580: A novel, potent and selective GABAA 5 negative allosteric modulator for the treatment of cognitive disorders

A. Lewis, A. Beresford,M. S. Chambers, G. Clark, D. C. Hartley, K. L. Hirst, M. Higashino, S. Kawahadara, M. Nakanishi,T. Saito, A. Imagawa, H. Habashita, S. Maidment,A. M. Macleod,A. P. Owens, A. Rae, C. Rouse, G. Wishart

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS（2020）

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Abstract
The identification and SAR development of a series of negative allosteric modulators of the GABAA alpha 5 receptor is described. This novel series of compounds was optimised to provide analogues with high GABAA alpha 5 binding affinity, high alpha 5 negative allosteric modulatory activity, good functional subtype selectivity and low microsomal turnover, culminating in identification of ONO-8590580.
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Key words
GABAA alpha 5,Negative allosteric modulator,Cognition enhancement,ONO-8590580
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