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.
Research & Development Division, SmithKline Beecham Pharmaceuticals, Collegeville, PA 19426-0989, USA.
R M
RM
Keenan
W H
WH
Miller
L S
LS
Barton
W E
WE
Bondinell
R D
RD
Cousins
D F
DF
Eppley
S M
SM
Hwang
C
C
Kwon
M A
MA
Lago
T T
TT
Nguyen
B R
BR
Smith
I N
IN
Uzinskas
C C
CC
Yuan
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