Convergent, parallel synthesis of a series of beta-substituted 1,2,4-oxadiazole butanoic acids as potent and selective alpha(v)beta3 receptor antagonists.
We describe a series of 1,2,4-oxadiazoles, which are potent antagonists of the integrin alpha(v)beta3 and, in addition, show selectivity relative to the other beta3 integrin alpha(IIb)beta3. In whole cells, the majority of these analogs also demonstrated modest selectivity against other alpha(v) integrins such as alpha(v)beta1 and alpha(v)beta6.
Boys
Mark L
ML
Department of Chemistry, PfizerGlobal Research and Development, 2800 Plymouth Rd., Ann Arbor, MI 48105, USA. mark.l.boys@pfizer.com
Schretzman
Lori A
LA
Chandrakumar
Nizal S
NS
Tollefson
Michael B
MB
Mohler
Scott B
SB
Downs
Victoria L
VL
Penning
Thomas D
TD
Russell
Mark A
MA
Wendt
John A
JA
Chen
Barbara B
BB
Stenmark
Heather G
HG
Wu
Hongwei
H
Spangler
Dale P
DP
Clare
Michael
M
Desai
Bipin N
BN
Khanna
Ish K
IK
Nguyen
Maria N
MN
Duffin
Tiffany
T
Engleman
V Wayne
VW
Finn
Mary Beth
MB
Freeman
Sandra K
SK
Hanneke
Melanie L
ML
Keene
Jeffery L
JL
Klover
Jon A
JA
Nickols
G Allen
GA
Nickols
Maureen A
MA
Steininger
Christina N
CN
Westlin
Marisa
M
Westlin
William
W
Yu
Yi X
YX
Wang
Yaping
Y
Dalton
Christopher R
CR
Norring
Sarah A
SA
D000951:Antigens, Neoplasm; D002087:Butyrates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors*; D016023:Integrins / Q000037:antagonists & inhibitors; D015394:Molecular Structure; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
D000951:Antigens, Neoplasm; D002087:Butyrates; D039302:Integrin alphaVbeta3; D016023:Integrins; D010069:Oxadiazoles; D019030:Receptors, Vitronectin; C094340:integrin alphavbeta1; C073878:integrin alphavbeta6