Orally bioavailable nonpeptide vitronectin receptor antagonists containing 2-aminopyridine arginine mimetics.
A peptide RGD analog containing a novel 2-aminopyridine arginine mimetic was discovered to have good affinity and selectivity for the vitronectin receptor. Incorporation of the 2-aminopyridine arginine mimetic into the 3-oxo-1,4-benzodiazepine-2-acetic acid integrin antagonist series led to novel and potent nonpeptide vitronectin receptor antagonists with promising levels of oral bioavailability.
Keenan
R M
RM
Research & Development Division, SmithKline Beecham Pharmaceuticals, Collegeville, PA 19426-0989, USA.
Miller
W H
WH
Barton
L S
LS
Bondinell
W E
WE
Cousins
R D
RD
Eppley
D F
DF
Hwang
S M
SM
Kwon
C
C
Lago
M A
MA
Nguyen
T T
TT
Smith
B R
BR
Uzinskas
I N
IN
Yuan
C C
CC
D000284:Administration, Oral; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001682:Biological Availability; D004285:Dogs; D007700:Kinetics; D051381:Rats; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors*
D000631:Aminopyridines; D019030:Receptors, Vitronectin; D001120:Arginine