Studies on the derivatives of thiazole acetic acid. II. Syntheses and pharmacological analysis of 2-N-aralkylidene and 2-N-aralkyl derivatives of 2-amino-4-p-chlorophenylthiazole-5-acetic acid.

A number of 2-N-aralkylidene, 2-N-aralkyl and 2-N-aralkyl-alpha-sulphoderivatives of 2-amino-4-p-chlorophenylthiazole-5-acetic acid (I, R = H) and its methyl ester (I, R = CH3) were synthesized. As a result of condensation of methyl ester I with various aromatic aldehydes in boiling benzene solution, the Schiff-bases (anils) II--VIII were obtained. After reduction with NaBH4 compounds II--VIII were transformed into adequate amino esters IX--XV. Esters IX--XV heated with diluted aqueous solution of sodium hydroxide underwent selective hydrolysis giving the respective amino acids XVI--XXII. Some of Schiff bases (II, III, V, VII, VIII) reacted with aqueous alcoholic solution of sodium bisulphite after its several (XXIII--XXVII). alpha-sulphoderivatives had been obtained. Several tests were performed in order to detect the anti-inflammatory and immunosuppressive activity of the compounds. The pharmacological analysis allowed us to draw conclusions concerning the relationship between chemical structure and biological activity in this group of compounds. The most efficacious immunosuppressive and anti-inflammatory activity exhibited 2-aralkyl-alpha-sulphoderivatives.