Non-peptide alpha(v)beta(3) antagonists. Part 4: potent and orally bioavailable chain-shortened RGD mimetics

Paul J Coleman; Ben C Askew; John H Hutchinson; David B Whitman; James J Perkins; George D Hartman; Gideon A Rodan; Chih-Tai Leu; Thomayant Prueksaritanont; Carmen Fernandez-Metzler; Kara M Merkle; Robert Lynch; Joseph J Lynch; Sevgi B Rodan; Mark E Duggan

doi:10.1016/s0960-894x(02)00396-7

Non-peptide alpha(v)beta(3) antagonists. Part 4: potent and orally bioavailable chain-shortened RGD mimetics

Bioorg Med Chem Lett. 2002 Sep 2;12(17):2463-5. doi: 10.1016/s0960-894x(02)00396-7.

Authors

Paul J Coleman¹, Ben C Askew, John H Hutchinson, David B Whitman, James J Perkins, George D Hartman, Gideon A Rodan, Chih-Tai Leu, Thomayant Prueksaritanont, Carmen Fernandez-Metzler, Kara M Merkle, Robert Lynch, Joseph J Lynch, Sevgi B Rodan, Mark E Duggan

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. paul_coleman@merck.com

PMID: 12161158
DOI: 10.1016/s0960-894x(02)00396-7

Abstract

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.

MeSH terms

Administration, Oral
Animals
Biological Availability
Dogs
Half-Life
Inhibitory Concentration 50
Integrin alphaVbeta3 / antagonists & inhibitors*
Metabolic Clearance Rate
Molecular Mimicry
Oligopeptides / administration & dosage
Oligopeptides / pharmacokinetics*
Oligopeptides / pharmacology
Structure-Activity Relationship

Substances

Integrin alphaVbeta3
Oligopeptides
arginyl-glycyl-aspartic acid