Development of a novel tricyclic class of potent and selective FIXa inhibitors

Autor:	Harold B. Wood, Kunal Desai, Daming Feng, Jamie McCabe-Dunn, Yi-Heng Chen, Edward C. Sherer, Jane Y. Wu, Marc Poirier, Hong Li, Dongfang Meng, Ting Zhang, Kenneth P. Ellsworth, Liangqin Guo, Teruyuki Nishimura, Jiayi Xu, Tomokazu Hirabayashi, Sunita V. Dewnani, Patrick Andre, Louis-Charles Campeau, Richard Tschirret-Guth, Isao Sakurada, Paul Reichert, Cameron J. Smith, Robert K. Orr, Lisa M. Sonatore, Wayne M. Geissler, Thomas Bateman, Kazuto Araki, Joe Metzger, Alan Hruza, Richard A. Berger, Dann L. Parker, Tianying Jian
Rok vydání:	2015
Předmět:	Drug media_common.quotation_subject Clinical Biochemistry High selectivity Administration Oral Pharmaceutical Science Crystallography X-Ray Biochemistry Thrombin generation Factor IXa Pharmacokinetics Drug Discovery Animals Humans Enzyme Inhibitors Molecular Biology media_common chemistry.chemical_classification Molecular Structure Chemistry Organic Chemistry Rats Enzyme Activation Human plasma Drug Design Pharmacodynamics Molecular Medicine Coagulation factor IXa Heterocyclic Compounds 3-Ring Tricyclic
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 25:5437-5443
ISSN:	0960-894X
Popis:	Using structure based drug design, a novel class of potent coagulation factor IXa (FIXa) inhibitors was designed and synthesized. High selectivity over FXa inhibition was achieved. Selected compounds were evaluated in rat IV/PO pharmacokinetic (PK) studies and demonstrated desirable oral PK profiles. Finally, the pharmacodynamics (PD) of this class of molecules were evaluated in thrombin generation assay (TGA) in Corn Trypsin Inhibitor (CTI) citrated human plasma and demonstrated characteristics of a FIXa inhibitor.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8ff96f55b80c75cf4042ca06570740e9 https://doi.org/10.1016/j.bmcl.2015.07.078 Zobrazit plný text záznamu Full Text from ScienceDirect