The title compounds were easily synthesized by reacting the 4-aminopyrazole hydrochloride 2 and the substituted 2-nitrobenzoyl chlorides 3a-d. The obtained 2-nitrobenzamides 4a-d were methylated and then reduced to give the corresponding amines 6a-d. These were hydrolyzed then directly converted into 4,10-dihydro-1H-pyrazolo[3,4-c][1,5]benzodiazocine-5,11-diones 1a-d by the action of SOCl 2 in benzene. These were tested for their COX inhibitory activity, showing an inhibitory profile against

more »

... h COX-1 and COX-2, being slightly more selective against COX-2 with a percentage of inhibition, at the concentration of 10 µM, in the range 42.0 -55.0. General Procedures. All melting points were taken on a Büchi-Tottoli capillary apparatus and are uncorrected. IR spectra were recorded on a Perkin-Elmer Infracord 137 spectrophotometer as Nujol mulls; 1 H-and 13 C-NMR spectra were obtained in DMSO-d 6 at 300.13 and 75.47 MHz respectively, using a Bruker AC series 300 MHz spectrometer (TMS as internal reference). Mass spectra were recorded on a JEOL jms-0I-SG-2 spectrometer at 75 eV (100µA). General procedure for methyl 1-ethyl-3-methyl-4-(2-nitrobenzamido)-1H-pyrazole-5carboxylates (4a-d) A solution of 4-aminopyrazole hydrochloride 2 (2 mmol), the appropriate 2-nitrobenzoyl chloride derivative 3a-d (2 mmol), and triethylamine (6 mmol) in toluene (100 mL) was heated under reflux for 8 h. The solvent was then evaporated under reduced pressure and the residue was taken up with water, filtered, and recrystallized from ethanol. 4a: yield 65%; mp 160-161°C