Immunomodulating action and structure-activity relationships of substituted phenylamides of 5-amino-3-methylisoxazole-4-carboxylic acid

A series of 5-amino-3-methylisoxazole-4-carboxylic acid amides has been pre pared by condensation of 5-amino-3-methylisoxazole-4-carboxylic acid with e thyl chloroformate. The resulting mixed anhydride undergoes condensation wi th appropriate phenylamides to form the corresponding amides 6-16. The comp ounds obtained were evaluated for their immunological activities in culture s of human peripheral blood mononuclear cells (PMBC). We found that the act ivities of the compounds in the proliferation test and in :the lipopolysacc haride (LPS)-induced cytokine production in PBMC cultures were differential . The stimulatory or inhibitory effects depended strongly on the origin and location of substituents in the phenyl ring which is described in the disc ussion and was supported by QSAR studies.