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

概要

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A series of 2-[4-(thiazol-2-yl)phenyl]propionic acids substituted at various positions were propared by the reaction of diethyl 2-methyl-2-(4-thiocarbamoylphenyl)malonates with α-bromoaldehyde diethyl acetals or α-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 subsititution pattern with halogens at position 3 (R_1) of the benzene ring and a methyl group in position 4 (R_2) and/or 5 (R_3) of the thiazole ring were favorable for inhibitory activity. The compounds bearing bulky alkyl or polar functional groups at the R_2 position were weak inhibitors. The potent inhibitors of cyclooxygenase were tested for their ability to reduce carrageenin-induced inflammation of rat paws. These derivatives had strong anti-inflammatory activity based on their strong inhibition of cyclooxygenase, with some exceptions, including those with a thiomethyl group at R_1.
公益社団法人日本薬学会の論文
1991-09-25