Development of active center-directed inhibitors against plasmin.
Active center-directed inhibitors of plasmin were designed based on the structure of specific substrates of plasmin and then synthesized. Their effects on plasmin were examined and the structure-inhibitory activity relationship was studied. N alpha-trans-4-Aminomethylcyclohexanecarbonyllysine 4-benzoylanilide (Tra-Lys-BZA) inhibited plasmin activities toward S-2251 and fibrin with IC50 values of 15 and 6.1 microM, respectively and N alpha-trans-4-aminomethylcyclohexane-carbonyllysine 4-benzylpiperidine amide (Tra-Lys-BPP) did not show any detectable inhibitory activity. Moreover, it was revealed that Tra-Lys-4-methoxycarbonylanilide inhibited plasma kallikrein more potently than plasmin.
Teno
N
N
Faculty of Pharmaceutical Sciences, Kobe-Gakuin University, Japan.
Wanaka
K
K
Okada
Y
Y
Tsuda
Y
Y
Okamoto
U
U
Hijikata-Okunomiya
A
A
Naito
T
T
Okamoto
S
S
D001665:Binding Sites; D005341:Fibrinolysin / Q000037:antagonists & inhibitors*
D005341:Fibrinolysin