Development of plasmin-selective inhibitors and studies of their structure-activity relationship.
Various compounds were synthesized by combining three components at positions P1, P1' and P2'. Of these, N-(trans-4-aminomethylcyclohexanecarbonyl)-Tyr(O-2-bromobenzylo xycarbonyl)- octylamide inhibited plasmin selectively with IC50 values of 0.80 and 0.23 microM towards S-2251 and fibrin, respectively. This compound also inhibited plasma kallikrein, urokinase, thrombin and trypsin with IC50 values of 10, > 50, > 50 and 1.6 microM, respectively.
Okada
Y
Y
Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Japan.
Matsumoto
Y
Y
Tsuda
Y
Y
Tada
M
M
Wanaka
K
K
Hijikata-Okunomiya
A
A
Okamoto
S
S
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002855:Chromatography, Thin Layer; D005341:Fibrinolysin / Q000037:antagonists & inhibitors*; D006801:Humans; D009904:Optical Rotation; D047428:Protein Kinase Inhibitors; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
C406461:N-(4-aminomethylcyclohexanecarbonyl)tyrosine(O-2-bromobenzyloxycarbonyl)octylamide; D047428:Protein Kinase Inhibitors; D015842:Serine Proteinase Inhibitors; D014443:Tyrosine; D005341:Fibrinolysin