Discovery of diphenylmethanepropionic and dihydrostilbeneacetic acids as antagonists of the integrin alphavbeta3.
A peptidomimetic inhibitor of the integrin alpha(v)beta(3) has been substantially modified to produce several new nonpeptidic antagonists. These inhibitors are simpler to synthesize and belong to new classes of scaffolds. Some of the compounds served as the initial lead for further optimization, which led to the discovery of potent and selective inhibitors of the integrin alpha(v)beta(3).
Nagarajan
Srinivasan R
SR
Pfizer Global Research and Development, St Louis Laboratories, Pfizer, Inc., Chesterfield, MO 63017, USA. srinivasan.nagarajan@pfizer.com
Meyer
Jane M
JM
Miyashiro
Julie M
JM
Engleman
V Wayne
VW
Freeman
Sandra K
SK
Griggs
David W
DW
Klover
Jon A
JA
Nickols
G Alan
GA
D000085:Acetates / Q000138:chemical synthesis* / Q000737:chemistry; D000818:Animals; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011422:Propionates / Q000138:chemical synthesis* / Q000737:chemistry; D013267:Stilbenes / Q000138:chemical synthesis* / Q000737:chemistry
D000085:Acetates; D039302:Integrin alphaVbeta3; D011422:Propionates; D013267:Stilbenes