Phenylbutyrates as potent, orally bioavailable vitronectin receptor (integrin alphavbeta3) antagonists.
In our continuing efforts to identify small molecule vitronectin receptor antagonists, we have discovered a series of phenylbutyrate derivatives, exemplified by 16, which have good potency and excellent oral bioavailability (approximately 100% in rats). This new series is derived conceptually from opening of the seven-membered ring of SB-265123.
Miller
William H
WH
GlaxoSmithKline Pharmaceuticals, 1250 S. Collegeville Rd., PO Box 5089, PA 19426, USA. william_h_miller@gsk.com
Manley
Peter J
PJ
Cousins
Russell D
RD
Erhard
Karl F
KF
Heerding
Dirk A
DA
Kwon
Chet
C
Ross
Stephen T
ST
Samanen
James M
JM
Takata
Dennis T
DT
Uzinskas
Irene N
IN
Yuan
Catherine C K
CC
Haltiwanger
R Curtis
RC
Gress
Catherine J
CJ
Lark
Michael W
MW
Hwang
Shing Mei
SM
James
Ian E
IE
Rieman
David J
DJ
Willette
Robert N
RN
Yue
Tian Li
TL
Azzarano
Leonard M
LM
Salyers
Kevin L
KL
Smith
Brian R
BR
Ward
Keith W
KW
Johanson
Kyung O
KO
Huffman
William F
WF
D000085:Acetates / Q000737:chemistry; D000284:Administration, Oral; D000631:Aminopyridines / Q000737:chemistry; D000818:Animals; D001682:Biological Availability; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D006207:Half-Life; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors*; D010654:Phenylbutyrates / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D051381:Rats
D000085:Acetates; D000631:Aminopyridines; D039302:Integrin alphaVbeta3; D010654:Phenylbutyrates; C121647:SB 265123