NOVEL ANTIALLERGIC AND ANTIINFLAMMATORY AGENTS - PART I - SYNTHESIS AND PHARMACOLOGY OF GLYCOLIC AMIDE DERIVATIVES

A series of mono-glycoloylamino derivatives was synthesized by treatme nt of the corresponding aromatic monoamine derivatives with glycoloyl chloride derivatives in pyridine or dichloromethane, in the presence o f a base such as triethylamine or pyridine. Hydrolysis of acetoxy comp ounds in aqueous ammonia and methanol solution produced hydroxy deriva tives with ease. These compounds were tested in the rat PCA (passive c utaneous anaphylaxis) assay by oral administration. Thiazole and thiad iazole derivatives showed moderate inhibition in this assay. In contra st, benzothiazole and benzonitrile derivatives exhibited marked inhibi tion. In particular, compound 5t also showed marked inhibition of eosi nophil adhesion to TNF (tumor necrosis factor) -alpha-treated HUVEC (h uman umbilical vein endothelial cells) in the range of 10(-8)-10(-5) M . (C) 1998 Elsevier Science Ltd. All rights reserved.