Reductions in log P Improved Protein Binding and Clearance Predictions Enabling the Prospective Design of Cannabinoid Receptor (CB1) Antagonists with Desired Pharmacokinetic Properties

Autor:	Kenneth E. Carlson, Olafur S. Gudmundsson, Bruce A. Ellsworth, Philip M. Sher, Susan Harvey, Eva Zuvich, Michael Thomas, William J. Keim, Gang Wu, Helen E. Godonis, Paul Stetsko, Brian J. Murphy, Richard B. Sulsky, Guixue Yu, William R. Ewing, Mary Jane Cullen, Mary Ann Pelleymounter, Doree F. Sitkoff, Susan Johnghar, Zhengxiang Gu, Ximao Wu, James Devenny, Rose Ann F Baska, Asoka Ranasinghe, Ning Lee, Kamelia Behnia, Anthony V. Azzara, Kenneth W. Rohrbach, Gerry Everlof, Liya Kang, Natesan Murugesan, Yeheng Zhu, Yifan Yang
Rok vydání:	2013
Předmět:	Cannabinoid receptor Drug discovery Chemistry medicine.medical_treatment Antagonist Triazoles Pharmacology Rats Pyridazines Structure-Activity Relationship Cytochrome P-450 Enzyme System Receptor Cannabinoid CB1 Pharmacokinetics In vivo Free fraction Drug Discovery medicine Animals Molecular Medicine Structure–activity relationship Cannabinoid Half-Life Protein Binding
Zdroj:	Journal of Medicinal Chemistry. 56:9586-9600
ISSN:	1520-4804 0022-2623
DOI:	10.1021/jm4010835
Popis:	Several strategies have been employed to reduce the long in vivo half-life of our lead CB1 antagonist, triazolopyridazinone 3, to differentiate the pharmacokinetic profile versus the lead clinical compounds. An in vitro and in vivo clearance data set revealed a lack of correlation; however, when compounds with
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::417c836ddf3010c89cd9792afb3349b0 https://doi.org/10.1021/jm4010835 Zobrazit plný text záznamu