Non-peptide alphavbeta3 antagonists. Part 6: design and synthesis of alphavbeta3 antagonists containing a pyridone or pyrazinone central scaffold

Michael J Breslin; Mark E Duggan; Wasyl Halczenko; Carmen Fernandez-Metzler; Cecilia A Hunt; Chih-Tai Leu; Kara M Merkle; Adel M Naylor-Olsen; Thomayant Prueksaritanont; Gary Stump; Audrey Wallace; Sevgi B Rodan; John H Hutchinson

doi:10.1016/s0960-894x(03)00254-3

Non-peptide alphavbeta3 antagonists. Part 6: design and synthesis of alphavbeta3 antagonists containing a pyridone or pyrazinone central scaffold

Bioorg Med Chem Lett. 2003 May 19;13(10):1809-12. doi: 10.1016/s0960-894x(03)00254-3.

Authors

Michael J Breslin¹, Mark E Duggan, Wasyl Halczenko, Carmen Fernandez-Metzler, Cecilia A Hunt, Chih-Tai Leu, Kara M Merkle, Adel M Naylor-Olsen, Thomayant Prueksaritanont, Gary Stump, Audrey Wallace, Sevgi B Rodan, John H Hutchinson

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 4, West Point, PA 19486, USA. john_hutchinson@merck.com

PMID: 12729670
DOI: 10.1016/s0960-894x(03)00254-3

Abstract

Two novel series of small-molecule RGD mimetics containing either a substituted pyridone or pyrazinone central constraint were prepared. Modification of the beta-alanine 3-substituent produced compounds that are potent and selective alpha(v)beta(3) antagonists and exhibit a range of physicochemical properties.

MeSH terms

Alanine / chemistry
Drug Design
Humans
Hydrophobic and Hydrophilic Interactions
Inhibitory Concentration 50
Integrin alphaVbeta3 / antagonists & inhibitors*
Molecular Mimicry
Oligopeptides
Protein Binding
Pyrazines / chemistry*
Pyrazines / pharmacokinetics
Pyridones / chemistry*
Pyridones / pharmacokinetics
Radioimmunoassay
Structure-Activity Relationship

Substances

Integrin alphaVbeta3
Oligopeptides
Pyrazines
Pyridones
arginyl-glycyl-aspartic acid
Alanine