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Novel Chemical Transformations of Tenoxicam
Author(s) -
Kóczián Kristóf,
Kökösi József,
Mazák Károly,
Noszál Béla
Publication year - 2005
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.200590171
Subject(s) - chemistry , tenoxicam , prodrug , ring (chemistry) , carboxamide , tricyclic , stereochemistry , thiazine , hydrolysis , nucleophile , medicinal chemistry , combinatorial chemistry , organic chemistry , piroxicam , medicine , biochemistry , alternative medicine , pathology , catalysis
Abstract 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.