1.
Bioorg Med Chem Lett
; 27(11): 2622-2628, 2017 06 01.
Article
in English
| MEDLINE
| ID: mdl-28408226
ABSTRACT
Using structure based drug design, novel aminobenzisoxazoles as coagulation factor IXa inhibitors were designed and synthesized. Highly selective inhibition of FIXa over FXa was demonstrated. Anticoagulation profile of selected compounds was evaluated by aPTT and PT tests. In vitro ADMET and pharmacokinetic (PK) profiles were also evaluated.
Subject(s)
Factor IXa/antagonists & inhibitors , Isoxazoles/chemistry , Animals , Binding Sites , Blood Coagulation/drug effects , Crystallography, X-Ray , Dogs , Drug Design , Drug Evaluation, Preclinical , Factor IXa/metabolism , Half-Life , Humans , Inhibitory Concentration 50 , Isoxazoles/metabolism , Isoxazoles/pharmacology , Molecular Dynamics Simulation , Partial Thromboplastin Time , Protein Structure, Tertiary , Prothrombin Time , Rats , Structure-Activity Relationship
2.
Angew Chem Int Ed Engl
; 50(10): 2297-301, 2011 Mar 01.
Article
in English
| MEDLINE
| ID: mdl-21351340
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Biological Products/chemical synthesis , Heterocyclic Compounds, 4 or More Rings/chemical synthesis , Anti-Bacterial Agents/chemistry , Benzoin/chemistry , Biological Products/chemistry , Cyclization , Heterocyclic Compounds, 4 or More Rings/chemistry , Methane/analogs & derivatives , Methane/chemistry , Stereoisomerism
3.
Angew Chem Int Ed Engl
; 47(51): 9887-90, 2008.
Article
in English
| MEDLINE
| ID: mdl-19012304
4.
Angew Chem Int Ed Engl
; 47(39): 7446-9, 2008.
Article
in English
| MEDLINE
| ID: mdl-18712721