Substituted N-(3,5-Dichlorobenzenesulfonyl)-l-prolyl-phenylalanine analogues as potent VLA-4 antagonists

Autor:	Plato A. Magriotis, John A. Schmidt, Stella H. Vincent, Junying Wang, Linus S. Lin, Dorothy Levorse, Sharon Tong, Zhen Wang, Linda E Egger, Ihor E. Kopka, Richard A. Mumford, Sander G. Mills, William K. Hagmann, Ralph A. Stearns, David N. Young, Malcolm MacCoss, Usha Kidambi, Ermengilda McCauley, Kathryn A. Lyons, Karen Owens, Gail Van Riper, Song Zheng, Adria Colletti
Rok vydání:	2002
Předmět:	Metabolic Clearance Rate Stereochemistry Phenylalanine Clinical Biochemistry Biological Availability Vascular Cell Adhesion Molecule-1 Pharmaceutical Science Peptide Integrin alpha4beta1 Ring (chemistry) Biochemistry Chemical synthesis Rats Sprague-Dawley Inhibitory Concentration 50 Structure-Activity Relationship chemistry.chemical_compound Dogs Drug Discovery Animals Structure–activity relationship Sulfones Molecular Biology IC50 chemistry.chemical_classification Sheep Dipeptide Organic Chemistry Dipeptides Haplorhini Rats chemistry Polar effect Molecular Medicine
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 12:637-640
ISSN:	0960-894X
DOI:	10.1016/s0960-894x(01)00821-6
Popis:	A series of substituted N-(3,5-dichlorobenzenesulfonyl)-L-prolyl- and alpha-methyl-L-prolyl-phenylalanine derivatives was prepared as VLA-4/VCAM antagonists. The compounds showed excellent potency with a wide variety of neutral, polar, electron withdrawing or donating groups on the phenylalanine ring (IC50 approximately 1 nM). Heteroaryl ring substitution for phenylalanine was also well tolerated. Pharmacokinetic studies in rat were performed on a representative set of compounds in both series.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::63055d86099dad6304a5f734a44d503d https://doi.org/10.1016/s0960-894x(01)00821-6 Zobrazit plný text záznamu Full Text from ScienceDirect