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

Autor: Lewis A; Charles River Discovery Research Services, Chesterford Research Park, Little Chesterford, Essex CB10 1XL, United Kingdom., Beresford A; Charles River Discovery Research Services, Chesterford Research Park, Little Chesterford, Essex CB10 1XL, United Kingdom., Chambers MS; Charles River Discovery Research Services, Chesterford Research Park, Little Chesterford, Essex CB10 1XL, United Kingdom., Clark G; Charles River Discovery Research Services, Chesterford Research Park, Little Chesterford, Essex CB10 1XL, United Kingdom., Hartley DC; Charles River Discovery Research Services, Chesterford Research Park, Little Chesterford, Essex CB10 1XL, United Kingdom., Hirst KL; Charles River Discovery Research Services, Chesterford Research Park, Little Chesterford, Essex CB10 1XL, United Kingdom., Higashino M; Ono Pharmaceutical Co. Ltd., Minase Research Institute, Shimamoto-cho, Mishima-gun, Osaka 618-8585, Japan., Kawahadara S; Ono Pharmaceutical Co. Ltd., Minase Research Institute, Shimamoto-cho, Mishima-gun, Osaka 618-8585, Japan., Nakanishi M; Ono Pharmaceutical Co. Ltd., Minase Research Institute, Shimamoto-cho, Mishima-gun, Osaka 618-8585, Japan., Saito T; Ono Pharmaceutical Co. Ltd., Minase Research Institute, Shimamoto-cho, Mishima-gun, Osaka 618-8585, Japan., Imagawa A; Ono Pharmaceutical Co. Ltd., Minase Research Institute, Shimamoto-cho, Mishima-gun, Osaka 618-8585, Japan., Habashita H; Ono Pharmaceutical Co. Ltd., Minase Research Institute, Shimamoto-cho, Mishima-gun, Osaka 618-8585, Japan., Maidment S; Charles River Discovery Research Services, Chesterford Research Park, Little Chesterford, Essex CB10 1XL, United Kingdom., Macleod AM; Charles River Discovery Research Services, Chesterford Research Park, Little Chesterford, Essex CB10 1XL, United Kingdom., Owens AP; Charles River Discovery Research Services, Chesterford Research Park, Little Chesterford, Essex CB10 1XL, United Kingdom., Rae A; Charles River Discovery Research Services, Chesterford Research Park, Little Chesterford, Essex CB10 1XL, United Kingdom. Electronic address: alastair.rae@crl.com., Rouse C; Charles River Discovery Research Services, Chesterford Research Park, Little Chesterford, Essex CB10 1XL, United Kingdom., Wishart G; Charles River Discovery Research Services, Chesterford Research Park, Little Chesterford, Essex CB10 1XL, United Kingdom.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2020 Nov 15; Vol. 30 (22), pp. 127536. Date of Electronic Publication: 2020 Sep 06.
DOI: 10.1016/j.bmcl.2020.127536
Abstrakt: The identification and SAR development of a series of negative allosteric modulators of the GABA A α5 receptor is described. This novel series of compounds was optimised to provide analogues with high GABA A α5 binding affinity, high α5 negative allosteric modulatory activity, good functional subtype selectivity and low microsomal turnover, culminating in identification of ONO-8590580.
(Copyright © 2020 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: