1,2-disubstituted cyclohexane derived tripeptide aldehydes as novel selective thrombin inhibitors.
A series of tripeptide arginine aldehydes was synthesized by replacement of proline with 1,2-disubstituted cyclohexane derivatives in the sequence of D-MePhe-Pro-Arg-H. Based on molecular modeling, further modification of the D-MePhe residue resulted in a potent and selective thrombin inhibitor.
Harmat
N J
NJ
Menarini Ricerche S.p.A. Laboratori di Firenze, Italy.
Di Bugno
C
C
Criscuoli
M
M
Giorgi
R
R
Lippi
A
A
Martinelli
A
A
Monti
S
S
Subissi
A
A
D000447:Aldehydes; D000595:Amino Acid Sequence; D000991:Antithrombins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001120:Arginine; D001665:Binding Sites; D003510:Cyclohexanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007202:Indicators and Reagents; D007700:Kinetics; D008958:Models, Molecular; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011487:Protein Conformation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000378:metabolism
D000447:Aldehydes; D000991:Antithrombins; D003510:Cyclohexanes; D007202:Indicators and Reagents; D009842:Oligopeptides; D001120:Arginine; D013917:Thrombin; C064289:efegatran