Vários ésteres e sulfonatos derivados da piroxicam foram preparados por acilação e sulfonação da hidroxila fenólica da piroxicam. Todos os compostos foram avaliados quanto à estabilidade química e às propriedades de inibição da ciclooxigenase. Os dados sugeriram que os ésteres poderiam ser o ponto de partida para o desenvolvimento de fármacos em potencial. Os sulfonatos derivados, preparados pela primeira vez, apresentaram estabilidade. Entre eles, um demonstrou uma moderada seletividade de inibição da COX-2 sobre a COX-1 e teria menor efeito colateral para o sistema gastrintestinal que a piroxicam devido ao grupo OH enólico mascarado. Um mecanismo plausível para o processo de acilação e sulfonação foi proposto, envolvendo a participação da porção da piridina presente na piroxicam. A estrutura molecular de um dos ésteres foi estabelecida, pela primeira vez, por meio de análise cristalográfica dos dados de raio-X de difração de pó.A number of ester and sulfonate derivatives of piroxicam were prepared via acylation/ sulfonation of the enolic OH of piroxicam. All the compounds were evaluated for their chemical stability and cyclooxygenase inhibiting properties. Data suggested that esters could be useful for the development of potential prodrugs. The sulfonate derivatives prepared for the first time were found to be stable. One of them showed a moderately selective COX-2 inhibition over COX-1 and would have lower gastrointestinal side effects than piroxicam due to the masked enolic OH group. A plausible mechanism for the acylation/sulfonation process has been proposed that involves participation of the pyridine moiety of piroxicam. Molecular structure of one of the ester was established for the first time by the crystal structure analysis from X-ray powder data. Keywords: piroxicam, esters, sulfonates, cyclooxygenase IntroductionPiroxicam (1, 1,2-benzothiazine-3-carboxamide-4-hydroxy-2-methyl-N-(2-pyridyl)-1,1-dioxide, Figure 1), 1 a nonsteroidal anti-inflammatory drug (NSAID) that belongs to the enol-carboxamide class, was developed prior to the discovery of cyclooxygenase-2 (COX-2, the second and inducible isoform of cyclooxygenase responsible for inflammation) on the basis of its anti-inflammatory activity and relative safety in animal models. In subsequent studies it was discovered that it possessed moderate COX-2 selectivity in compared to other COX-2 inhibitors. Several attempts were made to improve its pharmacological profile in addition to gastrointestinal side effects. For example, extensive SAR studies have been carried out in order to improve its COX-2/COX-1 selectivity profile which includes substitution at the 6-and 7-positions of the 4-oxo-1,2-benzothiazine-3-carboxamide, alteration of the N-methyl substituent, and amide modification.1 In another approach, the enolic OH group thought to be responsible for its COX-2 selectivity has been exploited as a "handle" for the preparation of various piroxicam derivatives. [2][3][4][5] These derivatives are inactive against cyclooxygenase but converted to piroxic...

4-o-(4-methoxybenzoyl)-2-methyl-N-(2-pyridal)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide, C23H19N3O6S (I), a piroxicam derivative has been synthesized and characterized by X-ray powder structure analysis. The molecules of (I) are linked through pairs of intermolecular N–H···O and C–H···O hydrogen bonds forming centrosymmetric dimeric R 2 2(14)(M) and R 2 2(22)(N) rings which combine to form infinite one-dimensional MNMN… chain along the [2¯11] direction. The C–H···π (arene) hydrogen bonds interlink the parallel chains into two-dimensional sheets lying in the (102) plane. These sheets are further connected through intermolecular C–H···O and C–H···N bonds, so generating a three-dimensional framework structure in (I).