1-(2-Naphthyl)-1 H -pyrazole-5-carboxylamides as potent factor Xa inhibitors. Part 3: Design, synthesis and SAR of orally bioavailable benzamidine-P4 inhibitors

Autor:	Athiwat Hutchaleelaha, Robert M. Scarborough, Penglie Zhang, Susan Edwards, Yanhong Wu, Uma Sinha, Zhaozhong J. Jia, John Woolfrey, Wenrong Huang, Stanley J. Hollennbach, Joseph L. Lambing, Ann E. Arfsten, Yonghong Song, Bing-Yan Zhu
Rok vydání:	2004
Předmět:	medicine.drug_mechanism_of_action Stereochemistry Antithrombin III Clinical Biochemistry Factor Xa Inhibitor Administration Oral Biological Availability Pharmaceutical Science Pyrazole Biochemistry Chemical synthesis Benzamidine Rats Sprague-Dawley Amidine Structure-Activity Relationship chemistry.chemical_compound Drug Discovery medicine Animals Humans Structure–activity relationship Molecular Biology biology Organic Chemistry Amides Benzamidines Rats chemistry Enzyme inhibitor Drug Design biology.protein Pyrazoles Molecular Medicine
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 14:1229-1234
ISSN:	0960-894X
DOI:	10.1016/j.bmcl.2003.12.054
Popis:	Using N,N-dialkylated benzamidines as the novel P4 motifs, we have designed and synthesized a class of 1-(2-naphthyl)-1H-pyrazole-5-carboxylamides as highly potent and selective fXa inhibitors with significantly improved hydrophilicity and in vitro anticoagulant activity. These benzamidine-P4 fXa inhibitors have displayed excellent oral bioavailability and long half-life.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2cf6e59bdd393461f089032d7d0bc858 https://doi.org/10.1016/j.bmcl.2003.12.054 Zobrazit plný text záznamu Full Text from ScienceDirect