Non-peptide alpha(v)beta(3) antagonists. Part 3: identification of potent RGD mimetics incorporating novel beta-amino acids as aspartic acid replacements.
Potent non-peptidic alpha(v)beta(3) antagonists have been prepared incorporating various beta-amino acids as aspartic acid mimetics. Modification of the beta-alanine 3-substituents alters the potency and physicochemical properties of these receptor antagonists and in some cases provides orally bioavailable alpha(v)beta(3) inhibitors.
Coleman
Paul J
PJ
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. paul_coleman@merck.com
Brashear
Karen M
KM
Hunt
Cecilia A
CA
Hoffman
William F
WF
Hutchinson
John H
JH
Breslin
Michael J
MJ
McVean
Carol A
CA
Askew
Ben C
BC
Hartman
George D
GD
Rodan
Sevgi B
SB
Rodan
Gideon A
GA
Leu
Chih Tai
CT
Prueksaritanont
Thomayant
T
Fernandez-Metzler
Carmen
C
Ma
Bennett
B
Libby
Laura A
LA
Merkle
Kara M
KM
Stump
Gary L
GL
Wallace
Audrey A
AA
Lynch
Joseph J
JJ
Lynch
Robert
R
Duggan
Mark E
ME
D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D001224:Aspartic Acid; D001667:Binding, Competitive; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D006801:Humans; D020128:Inhibitory Concentration 50; D018716:Molecular Mimicry; D009842:Oligopeptides / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D010024:Osteoporosis / Q000517:prevention & control; D011485:Protein Binding; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
D000596:Amino Acids; D009842:Oligopeptides; D019030:Receptors, Vitronectin; D001224:Aspartic Acid; C047981:arginyl-glycyl-aspartic acid