SYNTHESES AND ANTIINFLAMMATORY ACTIVITIES OF O-ACYLOXIMES .2.

Novel O-acyloximes having an acetyl group or N-protected amino acid as an O-acyl group were synthesized by reaction with acetyl chloride or by a mixed anhydride method, 4'-Morpholinoacetophenone oxime (oxime-2) was determined to be the (E) isomer by X-ray crystal structure analys is, The anti-inflammatory activities of the test compounds were assess ed in terms of the inhibitory effect on increased vascular permeabilit y induced by histamine, and several compounds were assessed together b y means of the carrageenan-induced paw edema assay, In general, acetyl oximes and tert-butyloxycarbonylphenylalanyl oximes showed inhibitory action on increased vascular permeability, Particularly important for the appearance of anti-inflammatory activity was direct attachment of the acetyl group to the oxime. Of the two isoforms of cyclooxygenase (COX-1 and COX-2), COX-1 activity was inhibited by oxime-2 and 4'-pipe ridinoacetophenone oxime (oxime-3) with IC50 values of 50 and 130 mu M , respectively, while COX-2 activity was not inhibited. The in vitro i nhibitory effect of oxime-2 and oxime-3 on COX-1 activity decreased wi th O-acylation of the oximes.