An Imidazopiperidine Series of CCR5 Antagonists for the Treatment of HIV: The Discovery of N-{(1S)-1-(3-Fluorophenyl)-3-[(3-endo)-3-(5-isobutyryl-2-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]propyl}acetamide (PF-232798)

Autor:	Manos Perros, David C. Pryde, Rob Webster, Francesca Perruccio, Michelle Y. Platts, Rhys M. Jones, Deborah Rodrigues, David V. Batchelor, David Ellis, Donald Stuart Middleton, David R. Fenwick, Patrick Dorr, Stupple Paul Anthony, Mike Westby, Anthony Wood, Helen J. Mason, Nicholas Smith, Martin Corless, Sebastien Galan, Peter T. Stephenson
Rok vydání:	2010
Předmět:	biology Chemistry Stereochemistry Chemokine receptor CCR5 hERG Antagonist Stereoisomerism CCR5 receptor antagonist Pharmacology chemistry.chemical_compound Drug Discovery biology.protein Molecular Medicine Structure–activity relationship Acetamide Maraviroc
Zdroj:	Journal of Medicinal Chemistry. 54:67-77
ISSN:	1520-4804 0022-2623
Popis:	Preventing entry of HIV into human host cells has emerged as an attractive approach to controlling viral replication. Maraviroc 1 is an approved antagonist of the human CCR5 receptor which prevents the entry of HIV. Herein, we report the design and discovery of a series of imidazopiperidine CCR5 antagonists which retain the attractive antiviral profile and window over hERG activity of maraviroc 1, combined with improved absorption profiles in rat and dog. Furthermore, this series of compounds has been shown to retain activity against a laboratory generated maraviroc-resistant HIV-1 strain, which indicates an alternative resistance profile to that of maraviroc 1. Compound 41f (PF-232798) was selected as a clinical candidate from the imidazopiperidine series and is currently in phase II clinical trials.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::25d25891e80de63ffeeae1e4b692e76d https://doi.org/10.1021/jm100978n Zobrazit plný text záznamu