ChemInform Abstract: Novel Azo Derivatives as Prodrugs of 5-Aminosalicylic Acid and Amino Derivatives with Potent Platelet Activating Factor Antagonist Activity

This paper describes the synthesis of a series of azo compounds able to deliver 5-aminosalicylic acid (5-ASA) and a potent platelet activating factor (PAF) antagonist in a colon-specific manner for the purpose of treating ulcerative colitis. We found it possible to add an amino group on the aromatic moiety of our reported 1-[(1-acyl-4-piperidyl)methyl]-1H-2-methylimidazo[4,5-c]pyridine derivatives or on British Biotech compounds BB-882 and BB-823 maintaining a high level of activity as PAF antagonist. A selected compound UR-12715 (49c) showed an IC50 of 8 nM in the in vitro PAF-induced aggregation assay, and an ID50 of 29 μg/kg in the in vivo PAF-induced hypotension test in normotensive rats. Through attachment of 49c to the 5-ASA via azo functionality we obtained UR-12746 (70). Pharmacokinetics experiments with [14C]-70 allow us to reach the following conclusions, critical in the design of these new prodrugs of 5-ASA. Neither the whole molecule 70 nor the carrier 49c were absorbed after oral administrati...