Document Report Card

ID: ALA1134511

Journal: J Med Chem

Title: Development of potent non-carbohydrate imidazole-based small molecule selectin inhibitors with antiinflammatory activity.

Authors: Slee DH, Romano SJ, Yu J, Nguyen TN, John JK, Raheja NK, Axe FU, Jones TK, Ripka WC.

Abstract: A novel series of non-carbohydrate imidazole-based selectin inhibitors has been discovered via high-throughput screening using a P-selectin ELISA-based assay system. The initial lead 1 had an IC(50) of 17 microM in the P-selectin ELISA; this potency was significantly improved via an extensive SAR exploration. One of the current lead compounds (29) has an IC(50) of 300 nM in a P-selectin ELISA; it also has good activity in P- and E-selectin cell adhesion assays and shows efficacy in vivo. These compounds represent a novel series of sLe(X) mimetics with antiinflammatory activity. Their unique profile supports our interest in their further evaluation as drug candidates for the treatment of inflammation. Herein we describe the syntheses, optimization, and SAR of this series of novel potent selectin antagonists.

CiteXplore: 11405647

DOI: 10.1021/jm000508c