Fluorinated dual antithrombotic compounds based on 1,4-benzoxazine scaffold

Miloš Ilić; Danijel Kikelj; Janez Ilaš

doi:10.1016/j.ejmech.2012.01.059

Fluorinated dual antithrombotic compounds based on 1,4-benzoxazine scaffold

Eur J Med Chem. 2012 Apr:50:255-63. doi: 10.1016/j.ejmech.2012.01.059. Epub 2012 Feb 8.

Authors

Miloš Ilić¹, Danijel Kikelj, Janez Ilaš

Affiliation

¹ University of Ljubljana, Faculty of Pharmacy, Aškerčeva cesta 7, SI-1000 Ljubljana, Slovenia.

PMID: 22365562
DOI: 10.1016/j.ejmech.2012.01.059

Abstract

Fluorinated 3,4-dihydro-2H-1,4-benzoxazine derivatives possessing both thrombin inhibitory and glycoprotein IIb/IIIa receptor antagonistic activities were prepared as potential dual antithrombotic compounds. Fluorine scan (3-fluorobenzyl, 4-fluorobenzyl, 3,4-difluorobenzyl and 3,5-difluorobenzyl substituted compounds) was performed in order to obtain 6-(carboxymethyl)(3,4-difluorobenzyl)amino compound (9i) as the most potent compound with balanced dual activity (K(i(Thr))=0.33±0.07μM, IC(50(GP IIb/IIIa))=1.1±0.6μM).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Benzoxazines / chemistry*
Halogenation
Hemostatics / antagonists & inhibitors*
Hemostatics / metabolism
Humans
Models, Molecular
Molecular Structure
Platelet Aggregation / drug effects*
Platelet Aggregation Inhibitors / chemistry*
Platelet Aggregation Inhibitors / pharmacology*
Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors*
Platelet Glycoprotein GPIIb-IIIa Complex / metabolism
Structure-Activity Relationship
Thrombin / antagonists & inhibitors*
Thrombin / metabolism

Substances

Benzoxazines
Hemostatics
Platelet Aggregation Inhibitors
Platelet Glycoprotein GPIIb-IIIa Complex
Thrombin