Investigation of the S3 site of thrombin: design, synthesis and biological activity of 4-substituted 3-amino-2-pyridones incorporating P1-argininals.
A novel scaffold for P4-P2 dipeptide mimics containing a rigid pyridone spacer was designed based on a virtual library strategy. Several selected nonpeptidic 4-aralkyl or 4-alkylpyridones incorporating a P1-argininal sequence were prepared. The modeling studies, synthesis and biological activities of these unique pyridone derivatives are reported herein.
Reiner
J E
JE
Corvas International, Inc., Department of Medicinal Chemistry, San Diego, California 92121, USA.
Lim-Wilby
M S
MS
Brunck
T K
TK
Ha-Uong
T
T
Goldman
E A
EA
Abelman
M A
MA
Nutt
R F
RF
Semple
J E
JE
Tamura
S Y
SY
D001120:Arginine / Q000737:chemistry*; D015951:Factor Xa / Q000494:pharmacology; D005341:Fibrinolysin / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008956:Models, Chemical; D011728:Pyridones / Q000138:chemical synthesis*; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D014357:Trypsin / Q000494:pharmacology
D011728:Pyridones; D001120:Arginine; D014357:Trypsin; D013917:Thrombin; D015951:Factor Xa; D005341:Fibrinolysin