Solid-phase synthesis of naphthylamidines as factor VIIa/tissue factor inhibitors.
Reductive amination followed by acylation of polymer-linked formyl aryl amidines generate combinatorial libraries of aryl amidines 8-13. Potent small molecule naphthylamidine inhibitors 12 (Ki<100 nM) of FVIIa/TF have been discovered and their activity against other serine proteases in the coagulation cascade is reported.
Buckman
Brad O
BO
Berlex Biosciences, 2600 Hilltop Drive, Richmond, CA 94804, USA. brad_buckman@berlex.com
Chou
Yuo-Ling
YL
McCarrick
Meg
M
Liang
Amy
A
Lentz
Dao
D
Mohan
Raju
R
Morrissey
Michael M
MM
Shaw
Kenneth J
KJ
Trinh
Lan
L
Light
David R
DR
D000578:Amidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D015942:Factor VIIa / Q000037:antagonists & inhibitors*; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D008968:Molecular Conformation; D009284:Naphthols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013925:Thromboplastin / Q000037:antagonists & inhibitors*
D000578:Amidines; D009284:Naphthols; D013925:Thromboplastin; D015942:Factor VIIa