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.
Research & Development Division, SmithKline Beecham Pharmaceuticals, Collegeville, PA 19426-0989, USA.
W H
WH
Miller
W E
WE
Bondinell
R D
RD
Cousins
K F
KF
Erhard
D R
DR
Jakas
R M
RM
Keenan
T W
TW
Ku
K A
KA
Newlander
S T
ST
Ross
R C
RC
Haltiwanger
J
J
Bradbeer
F H
FH
Drake
M
M
Gowen
S J
SJ
Hoffman
S M
SM
Hwang
I E
IE
James
M W
MW
Lark
B
B
Lechowska
D J
DJ
Rieman
G B
GB
Stroup
J A
JA
Vasko-Moser
D L
DL
Zembryki
L M
LM
Azzarano
P C
PC
Adams
W F
WF
Huffman
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