Title: Structure-Function Study of Quinazolinone-Based Vitronectin Receptor (αVβ3) Antagonists: Computer-Assisted Analysis of Ligand-Receptor Interactions
VOLUME: 1 ISSUE: 1
Author(s):Edward C. Lawson, William A. Kinney, Michael J. Costanzo, William J. Hoekstra, Jack A. Kauffman, Diane K. Luci, Rosemary Santulli, Brett A. Tounge, Stephen C. Yabut and Patricia Andrade-Gordon
Affiliation:Drug Discovery, Johnson&Johnson Pharmaceutical Research&Development, Spring House, Pennsylvania 19477-0776, USA.
Keywords:Quinazolinone, Vitronectin Receptor, Ligand-Receptor
Abstract: Modification of the pendant functionalities on a quinazolinone scaffold led to potent antagonist activity for integrin αVβ3 with selectivity over integrin αIIbβ3. Various guanidine mimetics, linkers, and arylsulfonamides were investigated to optimize the series. A molecular model was constructed based on a published X-ray structure and used to analyze ligand-receptor interactions. We identified key interactions for the quinazolinone and arylsulfonamide groups that may explain the changes in potency in the structure-function study.
