International Journal of Molecular Sciences (2017)
Update date:2022-08-02
Topics:
Lee, Soo Hyun
Lee, Wonhwa
Nguyen, ThiHa
Um, Il Soo
Bae, Jong-Sup
Ma, Eunsook
Thrombin (factor IIa) and factor Xa (FXa) are key enzymes at the junction of the intrinsic and extrinsic coagulation pathways and are the most attractive pharmacological targets for the development of novel anticoagulants. Twenty non-amidino N2-thiophencarbonyl- and N2-tosyl anthranilamides 1-20 and six amidino N2-thiophencarbonyl- and N2-tosylanthranilamides 21-26 were synthesized to evaluate their activated partial thromboplastin time (aPTT) and prothrombin time (PT) using human plasma at a concentration of 30 μg/mL in vitro. As a result, compounds 5, 9, and 21-23 were selected to study the further antithrombotic activity. The anticoagulant properties of 5, 9, and 21-23 significantly exhibited a concentration-dependent prolongation of in vitro PT and aPTT, in vivo bleeding time, and ex vivo clotting time. These compounds concentration-dependently inhibited the activities of thrombin and FXa and inhibited the generation of thrombin and FXa in human endothelial cells. In addition, data showed that 5, 9, and 21-23 significantly inhibited thrombin catalyzed fibrin polymerization and mouse platelet aggregation and inhibited platelet aggregation induced by U46619 in vitro and ex vivo. Among the derivatives evaluated, N-(30-amidinophenyl)-2-((thiophen-200-yl)carbonylamino)benzamide (21) was the most active compound.
View MoreContact:+86-511-88790000
Address:338 North Yushan Rd, Zhenjiang, Jiangsu 212016
SHAANXI FUJIE PHARMACEUTICAL CO.,LTD
website:http://www.fujiepharm.com
Contact:+86-29-63650906
Address:Yuanqu Yi Road, Qinghe Food Industrial Park, Sanyuan County, Shaanxi Province, China
Shanghai Massive Chemical Technology Co., Ltd.
website:http://www.massivechem.com/
Contact:+86 21 34943721
Address:Room 435, 4th floor, Building 9, No. 2568 Gudai Road,Minhang District, Shanghai,
ShiJiaZhuang Dowell Chemical Co.,Ltd.
website:http://www.dowechem.com
Contact:+86-13463963265
Address:Xiyangling village, high tech Zone, Shijiazhuang,Hebei, China
Tianjin SPHINX SCIENTIFIC LAB.
Contact:+86-022-66211289
Address:Tianda high-tech Park. No.80,the 4th Avenue
Doi:10.1055/s-1998-1954
(1998)Doi:10.1039/a806865h
(1998)Doi:10.1016/S0040-4039(01)02115-3
(2002)Doi:10.1002/(SICI)1521-3765(19990104)5:1<289::AID-CHEM289>3.0.CO;2-1
(1999)Doi:10.1016/j.bmcl.2012.07.081
(2012)Doi:10.1016/j.tet.2012.07.043
(2012)