Orally bioavailable nonpeptide vitronectin receptor antagonists with efficacy in an osteoporosis model.
A new series of potent nonpeptide vitronectin receptor antagonists, based on a novel carbocyclic Gly-Asp mimetic, has been discovered. A representative of this series, SB 265123 (4), has 100% oral bioavailability in rats, and is orally active in vivo in the ovariectomized rat model of osteoporosis.
Miller
W H
WH
Research & Development Division, SmithKline Beecham Pharmaceuticals, Collegeville, PA 19426-0989, USA.
Bondinell
W E
WE
Cousins
R D
RD
Erhard
K F
KF
Jakas
D R
DR
Keenan
R M
RM
Ku
T W
TW
Newlander
K A
KA
Ross
S T
ST
Haltiwanger
R C
RC
Bradbeer
J
J
Drake
F H
FH
Gowen
M
M
Hoffman
S J
SJ
Hwang
S M
SM
James
I E
IE
Lark
M W
MW
Lechowska
B
B
Rieman
D J
DJ
Stroup
G B
GB
Vasko-Moser
J A
JA
Zembryki
D L
DL
Azzarano
L M
LM
Adams
P C
PC
Huffman
W F
WF
D000085:Acetates / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000631:Aminopyridines / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D000818:Animals; D001570:Benzodiazepinones / Q000138:chemical synthesis / Q000493:pharmacokinetics; D001682:Biological Availability; D004195:Disease Models, Animal; D007700:Kinetics; D010024:Osteoporosis / Q000188:drug therapy*; D051381:Rats; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors*; D013997:Time Factors
D000085:Acetates; D000631:Aminopyridines; D001570:Benzodiazepinones; D019030:Receptors, Vitronectin; C121648:SB 223245; C121647:SB 265123