Non-peptide alpha(v)beta(3) antagonists. Part 4: potent and orally bioavailable chain-shortened RGD mimetics.
Potent non-peptidic alpha(v)beta(3) antagonists have been prepared where deletion of an amide bond from an earlier series of linear RGD-mimetics provides a novel series of chain-shortened alpha(v)beta(3) antagonists with significantly improved oral pharmacokinetics. These chain-shortened alpha(v)beta(3) antagonists represent structurally novel integrin inhibitors.
Coleman
Paul J
PJ
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. paul_coleman@merck.com
Askew
Ben C
BC
Hutchinson
John H
JH
Whitman
David B
DB
Perkins
James J
JJ
Hartman
George D
GD
Rodan
Gideon A
GA
Leu
Chih-Tai
CT
Prueksaritanont
Thomayant
T
Fernandez-Metzler
Carmen
C
Merkle
Kara M
KM
Lynch
Robert
R
Lynch
Joseph J
JJ
Rodan
Sevgi B
SB
Duggan
Mark E
ME
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D004285:Dogs; D006207:Half-Life; D020128:Inhibitory Concentration 50; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors*; D008657:Metabolic Clearance Rate; D018716:Molecular Mimicry; D009842:Oligopeptides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D039302:Integrin alphaVbeta3; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid