Structure-based design of novel groups for use in the P1 position of thrombin inhibitor scaffolds. Part 2: N-acetamidoimidazoles

Autor:	S. D. Lewis, Youwei Yan, Richard C.A. Isaacs, M. G. Solinsky, Lawrence Kuo, Julie A. Krueger, Bobby J. Lucas, Kellie J. Cutrona, Elizabeth A. Lyle, Adel M. Naylor-Olsen, Christina L. Newton, Daniel R. McMasters, J.J. Lynch
Rok vydání:	2008
Předmět:	Models Molecular Molecular model Stereochemistry Clinical Biochemistry Administration Oral Biological Availability Pharmaceutical Science Crystallography X-Ray Ferric Compounds Biochemistry Antithrombins Structure-Activity Relationship chemistry.chemical_compound Dogs Thrombin Chlorides Drug Discovery medicine Animals Structure–activity relationship Potency Trypsin Molecular Biology Molecular Structure biology Chemistry Organic Chemistry Imidazoles Anticoagulants Ligand (biochemistry) Macaca mulatta Rats Enzyme inhibitor Drug Design biology.protein Molecular Medicine Partial Thromboplastin Time Acetamide medicine.drug
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 18:2062-2066
ISSN:	0960-894X
Popis:	Guided by X-ray crystallography of thrombin-inhibitor complexes and molecular modeling, alkylation of the N1 nitrogen of the imidazole P1 ligand of the pyridinoneacetamide thrombin inhibitor 1 with various acetamide moieties furnished inhibitors with significantly improved thrombin potency, trypsin selectivity, functional in vitro anticoagulant potency and in vivo antithrombotic efficacy. In the pyrazinoneacetamide series, oral bioavailability was also improved.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::da1f51337db1ab8622bb97fcfc58a61e https://doi.org/10.1016/j.bmcl.2008.01.098 Zobrazit plný text záznamu Full Text from ScienceDirect