Non-peptidic alpha(v)beta3 antagonists containing indol-1-yl propionic acids.
We describe the synthesis and structure/activity relationship of RGD mimetics that are potent inhibitors of the integrin alpha(v)beta3. Indol-1-yl propionic acids containing a variety of basic moieties at the 5-position, as well as substitutions alpha and beta to the carboxy terminus were synthesized and evaluated. Novel compounds with improved potency have been identified.
Leonard
Kristi
K
Johnson & Johnson, Pharmaceutical Research and Development, L.L.C., 665, Stockton Drive, Exton, PA 19341, USA.
Pan
Wenxi
W
Anaclerio
Beth
B
Gushue
Joan M
JM
Guo
Zihong
Z
DesJarlais
Renee L
RL
Chaikin
Marge A
MA
Lattanze
Jennifer
J
Crysler
Carl
C
Manthey
Carl L
CL
Tomczuk
Bruce E
BE
Marugan
Juan Jose
JJ
D007211:Indoles / Q000737:chemistry; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors*; D018716:Molecular Mimicry; D009842:Oligopeptides / Q000737:chemistry; D011422:Propionates / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D007211:Indoles; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D011422:Propionates; C047981:arginyl-glycyl-aspartic acid; C029658:propionic acid