Non-peptide alpha v beta 3 antagonists. Part 7: 3-Substituted tetrahydro-naphthyridine derivatives

Jiabing Wang; Michael J Breslin; Paul J Coleman; Mark E Duggan; Cecilia A Hunt; John H Hutchinson; Chih-Tai Leu; Sevgi B Rodan; Gideon A Rodan; Le T Duong; George D Hartman

doi:10.1016/j.bmcl.2003.11.036

Non-peptide alpha v beta 3 antagonists. Part 7: 3-Substituted tetrahydro-naphthyridine derivatives

Bioorg Med Chem Lett. 2004 Feb 23;14(4):1049-52. doi: 10.1016/j.bmcl.2003.11.036.

Authors

Jiabing Wang¹, Michael J Breslin, Paul J Coleman, Mark E Duggan, Cecilia A Hunt, John H Hutchinson, Chih-Tai Leu, Sevgi B Rodan, Gideon A Rodan, Le T Duong, George D Hartman

Affiliation

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

PMID: 15013021
DOI: 10.1016/j.bmcl.2003.11.036

Abstract

A series of 3-substituted tetrahydro-[1,8]naphthyridine containing alpha(v)beta(3) antagonists was prepared. A comparison of their in vitro IC(50) values to the electron properties of the 3-substituents revealed a good linear Hammett correlation (rho=-1.96, R(2)=0.959). Electron-withdrawing groups at the 3-position of the tetrahydro-[1,8]naphthyridine decreased potency while electron-donating groups enhanced potency.

MeSH terms

Adrenergic alpha-Antagonists / chemical synthesis
Adrenergic alpha-Antagonists / pharmacology*
Adrenergic beta-Antagonists / chemical synthesis
Adrenergic beta-Antagonists / pharmacology*
Humans
Integrin alphaVbeta3 / antagonists & inhibitors*
Molecular Structure
Naphthyridines / chemical synthesis
Naphthyridines / pharmacology*
Structure-Activity Relationship

Substances

Adrenergic alpha-Antagonists
Adrenergic beta-Antagonists
Integrin alphaVbeta3
Naphthyridines