Novel 3,3a,4,5,6,7-hexahydroindazole and arylthiazolyipyrazoline derivatives as anti-inflammatory agents

A novel series of 7-benzylidene-3,3a,4,5,6,7-hexahydro-3-phenyl-2H-indazole substituted at the 2-position were synthesized. The reaction of 2,6-bis-benzylidenecyclohexanone (1) with thiosemicarbazide in the presence of NaOH afforded a mixture of the 3-H, 3a-H trans 2 and cis 2a diastereoisomers which have been separated by fractional recrystallization. Interaction of the first intermediate 2 with substituted phenacyl bromides, aromatic aldehydes and chloroacetic acid in presence of a mixture of acetic acid and acetic anhydride, and 2,3-dichloroquinoxaline yielded the corresponding 7-benzylidene-3,3a,4,5,6,7-hexahydro-3-phenyl-2H-indazole derivatives substituted at the 2-position with 4-aryl-2-thiazolyl 3 a, b, 5-arylidene-4,5dihydro-4-oxo-2-thiazolyl 4a, b and thiazolo[4,5-b]quinoxalin-2-yl 5, respectively. Moreover, the other intermediates 3,5-diaryl-1-thiocarbamoyl-2-pyrazolines 7 a-d were reacted with the p reviously- mentioned reagents and gave the corresponding 3,5-diaryl-1-(4-aryl-2-thiazolyl)-2-pyrazolines 8a-h, 3,5-diaryl-1-(5-arylidene-4,5dihydro-4-oxo-2-thiazolyl)-2-pyrazolines 9 a-d and 3,5-diaryl-1-(thiazolo[4,5-b]quinoxalin-2-yl)-2-pyrazoline derivatives 10 a, b, respectively. Some of the newly prepared compounds were subjected to evaluation for their anti-inflammatory activity The structures of the new compounds were confirmed by elemental analyses as well as H-1-NMR, IR, and MS data.