Both N- and O-substituted derivatives of the anti-inflammatory drug tenoxicam (= 4-hydroxy-2-methyl-N-(pyridin-2-yl)-2H-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-nucIeophiles 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.
ASJC Scopus subject areas
- Drug Discovery
- Physical and Theoretical Chemistry
- Organic Chemistry
- Inorganic Chemistry