Synthesis and anti-inflammatory study of novel fluoro-benzothiazole derivatives

N-{6-fluoro-7-[(substituted)-amino] 1, 3-benzothiazole-2-yl}-2-nitrobenzamides; N-{6-fluoro-7-[(substituted)-amino] 1, 3-benzothiazole-2-yl}-3-nitrobenzamides and N-{6-fluoro-7-[(substituted)-amino] 1, 3-benzothiazole-2-yl}-4-nitrobenzamides derivatives were synthesized. Sythesised compounds were tested for anti-inflammatory activity bycarrageenin induced rat hind paw edema method compared to standard Diclofenac.Cyclisation Mechanismof BenzothiazoleSince, in 3-chloro -4fluoro aniline, the 2nd and 6th position is the most positive center but 2nd position behave as a more electrophilic centre. As the attack however was on the 2nd position, which is the electrophilic center and it is probable that bromine being as pseudohalogen, behaves as an electrophile by attacking this electrophilic center followed by replacement of hydrogen of 2nd position as one hydrogen bromide while one bromine atom remain attached. Replacement of bromine takes place by attack of thiocyanogen,behaves as a pseudo halogen (electrophile) followed by elimination of potassium bromide. Finally ring closure occur when pH adjusted at pH6 with ammonia and further rearrangement produce 2-amino-6-fluoro-7-chloro-(1, 3)-benzothiazole. Thus the reaction sequence can be as follows.RESULTS AND DISCUSSIONIn the present work, fluorochloroaniline was treated with KSCN in presence of bromine in glacial acetic acid and ammonia to get 2-amino-6-fluro-7-chloro (1, 3)-benzothiazolewith yield around 51%, which was condensed with 2 (3 or 4)- nitrobenzoyl chloride in presence of dry pyridine and acetone to get N-(7-chloro-6-fluoro-1, 3-benzothiazole-2-yl)-2 (3 or 4)-nitrobenzamides with yield around 45-55% . To the above product 2-chloroaniline, 3-chloroaniline, 4-chloroaniline, o-toludine, m-toludine, p-toludine, 2-nitroaniline, 3-nitroaniline, 4-nitroaniline, 2-aminophenol, 3-aminophenol, 4-aminophenol, 2-anisidine, 3-anisidine and 4-anisidine in presence of DMF were treated toget newly synthesized N-{6-fluoro-7-[(substituted)-amino] 1, 3-benzothiazole-2-yl}-4-nitrobenzamides derivatives through replacing at 7th position chlorine with yield around58-78%. Reaction progress was monitored by thin layer chromatography. All the synthesized compounds of were characterized by melting point, solubility, TLC, IR,1HNMR spectra studies.All the newly synthesized compounds were evaluated for anti-inflammatory activity. Anti-inflammatory activity of synthesized compounds were perform by carrageenininduced rat hind paw edema method on healthy wistar albino rats of either sex weighing between 100-200gm using dose 20 mg/kg body weight (b.w.) for all the synthesizedcompounds as well as for diclofenac as standard.The response to injected carrageenin provides a convenient experimental model of inflammation which has been widely used for evaluating anti-inflammatory drugs.However, from the obtained results by anti-inflammatory activity it found that compound S-7, S-8, S-9, S-202, S-21, S-22 and S-35 exhibited excellent percentage of inhibition as compared to diclofenac.<br>