Discovery of selective urokinase plasminogen activator (uPA) inhibitors as a potential treatment for multiple sclerosis

Autor:	John Morser, Imadul Islam, Cornell Mallari, Elena Ho, Marc Adler, Kumar Emayan, Gary Phillips, Shendong Yuan, Marc Whitlow, Christopher W. West, David R. Light, Giovanna Gualtieri, Drew Sukovich, Ulrich Bothe, Zheng Chang, Kieu Chu, Judi Bryant, Deborah Chen, Caralee Schaefer, Brad O. Buckman
Rok vydání:	2018
Předmět:	Models Molecular 0301 basic medicine Benzylamines Multiple Sclerosis Serine Proteinase Inhibitors Clinical Biochemistry Pharmaceutical Science Biochemistry Mice Structure-Activity Relationship 03 medical and health sciences 0302 clinical medicine Drug Discovery medicine Animals Humans Molecular Biology Structural class Urokinase Serine protease Binding Sites Molecular Structure biology Chemistry Urokinase Plasminogen Activator Multiple sclerosis Organic Chemistry medicine.disease Urokinase-Type Plasminogen Activator Rats 030104 developmental biology Cancer research biology.protein Molecular Medicine Female 030217 neurology & neurosurgery medicine.drug
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 28:3372-3375
ISSN:	0960-894X
Popis:	We report here the design and synthesis of a novel series of benzylamines that are potent and selective inhibitors of uPA with promising oral availability in rat. Further evaluation of one representative (ZK824859) of the new structural class showed that this compound lowered clinical scores when dosed in either acute or chronic mouse EAE models, suggesting that uPA inhibitors of this type could be useful for the treatment of multiple sclerosis.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::09b761e7a2ae7d063c07c5d293801b02 https://doi.org/10.1016/j.bmcl.2018.09.001 Zobrazit plný text záznamu Full Text from ScienceDirect