(1H-INDOL-3-YL)PIPERIDIN-1-YL)ALKYL-5-(SUBSTITUTED PHENYL)-2,4-PENTADIENAMIDES AS ANTIALLERGIC AGENTS WITH ANTIHISTAMINIC AND ANTI SLOW-REACTING SUBSTANCE (SRS) ACTIVITIES

As an extension of our study aiming to discover a novel compound with dual activities against histamine and slow-reacting substance (SRS), w e synthesized two types of indolylpiperidine derivatives, 3 and 4-20. Testing for in vivo antianaphylactic activity and for in vitro anti-SR S activity revealed that ndol-3-yl)piperidin-1-yl)ethyl)-2,4-pentadien amide (11) exhibited potent dual activities with ED(50)=0.89 mg/kg and IC50=1.43 mu M, respectively. However, the plasma concentration of un changed 11 was very low when administered orally in guinea pigs. This result can be explained by fast formation of a glucuronic acid conjuga te.