SYNTHESIS, CHARACTERIZATION AND ANTI-INFLAMMATORY EVALUATION OF SOME NEW 2-(3-FLUOROBIPHENYL-4-YL) PROPANOIC ACID DERIVATIVES

Different new compounds derived from 2-(3-flourobiphenyl-4-yl) propanohydrazide [2] as starting material were synthesized. Reaction [2] with maleic anhydride, succinic anhydride and phthalic anhydride gave the corresponding cyclicimides [3a-c]. The hydrazone derivatives [4a-d] were obtained by condensation of compound [2] with 2,4-dimethoxybenzaldehyde, 4-(N,N-dimethylamino)benzaldehyde, 3-hydroxybenzaldehyde and 2-hydroxybenzaldehyde. The cyclization of [2] with CS₂ in presence potassium hydroxide and hydrazine hydrate gave 1,2,4-triazole compound [5], that condensation either with 2,4-dimethoxybenzaldehyde, 4-(N,N-dimethyl amino) benzaldehyde, 3-hydroxybenzaldehyde and 2-hydroxybenzaldehyde to give the corresponding Schiff-bases [6a-d]. The cyclization of hydrazone derivatives [4a-d] with phenyl isocyanate, maleic anhydride, succinic anhydride and phthalic anhydride gave the corresponding aza-β-lactams [7a-d], oxazepine [8,9,10 a-d]. The structures of new compounds are supported by FT-IR, ¹H-NMR and ¹³C-NMR. Compounds [3c], [4c], [8d], [7d] and [4b] were evaluated in vivo for their anti-inflammatory activity comparable to the standard drug flurbiprofen. Compound 2-(2-hydroxyphenyl)-3-[2-(3-fluorobiphenyl-4-yl)] propan- amido-2,3-dihydro-1,3-oxazepine-4,7-dione [8d]  showed anti-inflammatory activity more than the standard drug flurbiprofen, in the egg-albumin induced paw edema in rats.