Preparation and Biological Activity of 2-(4-(Thiazol-2-yl)phenyl)propionic Acid Derivatives Inhibiting Cyclooxygenase

A series of 2-(4-(thiazol-2-yl)phenyl)propionic acids substituted at various positions were prepared by the reaction of diethyl 2-methyl-2-(4-thiocarbamoylphenyl)-malonates with alpha -bromoaldehyde diethyl acetals or alpha -haloketones followed by hydrolysis of esters. The inhibition of prostaglandin H synthetase (cyclooxygenase) was assayed by use of an enzyme preparation from guinea pig polymorphonuclear leukocytes. Examination of the structure-activity relationship of these compounds indicated that the substitution pattern with halogens at position 3 (R sub(1)) of the benzene ring and a methyl group in position 4 (R sub(2)) and/or 5 (R sub(3)) of the thiazole ring were favorable for inhibitory activity. The compounds bearing bulky alkyl or polar functional groups at the R sub(2) position were weak inhibitors.