3-Amino-4-sulfonylpyridinone acetamide and related pyridothiadiazine thrombin inhibitors

Autor:	Dennis L. Bohn, Sanderson Philip E, Bobby J. Lucas, Adel M. Naylor-Olsen, Julie A. Krueger, Elizabeth A. Lyle, Franklin C. Clayton, Youwei Yan, S. Dale Lewis, Denise J. Bickel, Denice C. Welsh, Kellie J. Cutrona, Audrey A. Wallace, Kelly L. Savage
Rok vydání:	2003
Předmět:	Models Molecular Pyridones medicine.drug_class Stereochemistry Clinical Biochemistry Administration Oral Pharmaceutical Science Carboxamide Ferric Compounds Biochemistry Structure-Activity Relationship chemistry.chemical_compound Dogs Thrombin Acetamides Drug Discovery medicine Animals Humans Sulfones Molecular Biology chemistry.chemical_classification Sulfonyl Thiadiazines Bicyclic molecule Chemistry Organic Chemistry Thrombosis Rats Sulfonamide Disease Models Animal Lactam Molecular Medicine Trypsin Inhibitors Acetamide medicine.drug Discovery and development of direct thrombin inhibitors
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 13:1441-1444
ISSN:	0960-894X
Popis:	We describe a series of highly potent and efficacious thrombin inhibitors based on a 3-amino-4-sulfonylpyridinone acetamide template. The functionally dense sulfonyl group stabilizes the aminopyridinone, conformationally constrains the 4-substituent, and forms a hydrogen bond to the insertion loop tyrosine OH. We also describe a related series of fused bicyclic dihydrothiadiazinedioxide derivatives, of which one had improved pharmacokinetics in dogs after oral dosing.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::30a3f85d29d442aecdb880527dce76d0 https://doi.org/10.1016/s0960-894x(03)00154-9 Zobrazit plný text záznamu Full Text from ScienceDirect