1H-Imidazo[4,5-c]pyridine-4-carbonitrile as cathepsin S inhibitors: Separation of desired cellular activity from undesired tissue accumulation through optimization of basic nitrogen pka

Autor:	John Bruin, William Hamilton, Emma Kinghorn, Kenneth S. Cameron, Paul Westwood, Jiaqiang Cai, Kathryn Everett, Clive Long, Maureen Dempster, Chris Claxton, Xavier Fradera, D. Jonathan Bennett, Robinson John E, Simone Belshaw, Philip Jones, Wullie Arbuckle, Mark Baugh, Iain Martin
Rok vydání:	2011
Předmět:	Cellular activity Nitrogen Pyridines Stereochemistry Organic Chemistry Clinical Biochemistry Pharmaceutical Science chemistry.chemical_element Cathepsins Biochemistry Rats Rats Sprague-Dawley Mice chemistry.chemical_compound chemistry In vivo Drug Discovery Pyridine Animals Molecular Medicine Protease Inhibitors Molecular Biology Cell based Cathepsin S
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 21:932-935
ISSN:	0960-894X
Popis:	Based on the theoretical understanding of the in vivo lysosomotropism, by adjusting the pka of basic nitrogen containing cathepsin S inhibitors, a set of compounds with pka 6–8 were identified to have excellent cell based Lip10 activity, yet avoiding undesired sequestration in spleen.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::476635684754e9aff8bc8031c6950b59 https://doi.org/10.1016/j.bmcl.2010.12.065 Zobrazit plný text záznamu Full Text from ScienceDirect