Patent Evaluation Pulmonary-Allergy, Dermatological, Gastrointestinal & Arthritis: New heterocyclic compounds with cell adhesion inhibitory activity

Abstract

This patent discloses compounds shown to be effective in blocking both the adhesion of leukocytes to the vascular endothelium and the activation of human immunodeficiency virus (HIV). The methods used to establish activity in the aforementioned biological processes include assays of intercellular adhesion molecule-1 (ICAM-1) and E-selectin human umbilical vein endothelial cell (HUVEC) expression and, neutrophil adhesion to tumour necrosis factor α (TNF-α) stimulated HUVEC cells. Additionally, an in vivo assay of neutrophil influx was used. The compounds disclosed in this invention are tricyclic compounds containing at least two fused heterocycles and are capable of modulating bioprocesses involved in the progression of inflammatory disorders and AIDS.