Novel Chemical Transformations of Tenoxicam

Both N ‐ and O ‐substituted derivatives of the anti‐inflammatory drug tenoxicam (= 4‐hydroxy‐2‐methyl‐ N ‐(pyridin‐2‐yl)‐2 H ‐thieno[2,3 ‐e ] [1,2]thiazine‐3‐carboxamide 1,1‐dioxide; 1 ) were synthesized, and various chemical transformations were investigated. Both selective hydrolysis and reaction of 1′‐ N ‐methyltenoxicam ( 5 ) with a variety of N‐nucleophiles were performed ( Scheme 1 ). Also, five new 4‐ O ‐acyl derivatives 10 were prepared as potential prodrugs ( Scheme 2 ). The 4‐chloro derivatives of 1 and its analog 8 could be successfully transformed into the novel tetra‐ and tricyclic ring systems 12 and 13 , respectively, the latter being a conformationally restricted 1,5‐diaryl‐pyrazole designed as a potential COX‐2 inhibitor.