Non-peptide alpha(v)beta(3) antagonists. Part 5: identification of potent RGD mimetics incorporating 2-aryl beta-amino acids as aspartic acid replacements.
A series of novel, highly potent alpha(v)beta(3) receptor antagonists with favorable pharmacokinetic profiles has been identified. In this series of antagonists, 2-aryl beta-amino acids function as potent aspartic acid replacements.
Brashear
Karen M
KM
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. karen_brashear@merck.com
Hunt
Cecilia A
CA
Kucer
Brian T
BT
Duggan
Mark E
ME
Hartman
George D
GD
Rodan
Gideon A
GA
Rodan
Sevgi B
SB
Leu
Chi-Tai
CT
Prueksaritanont
Thomayant
T
Fernandez-Metzler
Carmen
C
Barrish
Andrea
A
Homnick
Carl F
CF
Hutchinson
John H
JH
Coleman
Paul J
PJ
D000596:Amino Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D001224:Aspartic Acid / Q000737:chemistry; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D020128:Inhibitory Concentration 50; D009842:Oligopeptides / Q000737:chemistry / Q000493:pharmacokinetics; D011485:Protein Binding; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
D000596:Amino Acids; D004952:Esters; D009842:Oligopeptides; D019030:Receptors, Vitronectin; D001224:Aspartic Acid; C047981:arginyl-glycyl-aspartic acid