Discovery of LB30057, a benzamidrazone-based selective oral thrombin inhibitor.
Systematic variation of the so-called P-pocket moiety of benzamidrazone-based selective thrombin inhibitors led to the discovery of LB30057. It is potent (Ki = 0.38 nM for human thrombin), selective (Ki = 3290 nM for bovine trypsin), and orally bioavailable (58% oral bioavailability in dogs). LB30057 was efficacious in thrombosis animal models.
Oh
Y S
YS
Biotech Research Institute, LG Chemical LTD, Taejon, Korea.
Yun
M
M
Hwang
S Y
SY
Hong
S
S
Shin
Y
Y
Lee
K
K
Yoon
K H
KH
Yoo
Y J
YJ
Kim
D S
DS
Lee
S H
SH
Lee
Y H
YH
Park
H D
HD
Lee
C H
CH
Lee
S K
SK
Kim
S
S
D000818:Animals; D001549:Benzamides / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001682:Biological Availability; D002417:Cattle; D004195:Disease Models, Animal; D004285:Dogs; D006207:Half-Life; D006801:Humans; D008958:Models, Molecular; D051381:Rats; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors*; D013927:Thrombosis / Q000188:drug therapy
D001549:Benzamides; C116605:LB 30057; D013917:Thrombin