34258-79-2

Upstream product

• 35511-15-0 methyl 2-methyl-4-hydroxy-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide 
• 62-53-3 aniline 
• 24683-26-9 ethyl 4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide 
• 24683-20-3 ethyl 2-(1,1-dioxido-3-oxobenzo[d]isothiazol-2(3H)-yl) acetate 
• 128-44-9 saccharin sodium salt 
• 24683-21-4 4-hydroxy-2H-1,2-benzothiazine-3-carboxylic acid ethyl ester 1,1-dioxide 
• 6639-62-9 methyl 3-oxo-2,3-dihydrobenzo[d][1,2]thiazol-2-acetate 1,1-dioxide 
• 35511-14-9 methyl 4-hydroxy-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide 
• 81-07-2 saccharin 

Downstream Products

• 40713-37-9 2-methyl-1,1-dioxo-4-propoxy-1,2-dihydro-1λ⁶-benzo[e][1,2]thiazine-3-carboxylic acid anilide 
• 36798-96-6 4-acetoxy-2-methyl-1,1-dioxo-1,2-dihydro-1λ⁶-benzo[e][1,2]thiazine-3-carboxylic acid anilide 
• 40713-44-8 5-methyl-6,6-dioxo-3-phenyl-5,6-dihydro-6λ⁶-benzo[5,6][1,2]thiazino[3,4-e][1,3]oxazine-2,4-dione 
• 40713-38-0 4-isopropoxy-2-methyl-1,1-dioxo-1,2-dihydro-1λ⁶-benzo[e][1,2]thiazine-3-carboxylic acid anilide 
• 40713-43-7 4-acetoxy-2-methyl-1,1-dioxo-1,2-dihydro-1λ⁶-benzo[e][1,2]thiazine-3-carboxylic acid N-acetyl-anilide 

Relevant academic research and scientific papers

Site-specific acid-base properties of tenoxicam

The Hammett approach, as a new deductive tool, was introduced to characterize the otherwise inaccessible minor protonation pathway of tenoxicam (1), the non-steroidal anti-inflammatory drug. A total of eight compounds, constituting a systematic series of side chain-substituted analogues of tenoxicam and piroxicam (2), were synthesized and studied in terms of acid-base properties and Hammett constants to identify the ideal replacement of the unprotonated pyridin-2-yl group, a key moiety in both molecules. Hammett constants of the phenyl substituents have been found to be in a linear correlation with the experimental log K values of the enolate sites, the basic moiety of the extended conjugated system in this family of piroxicam derivatives. Then, a similar correlation was observed for the analogous tenoxicam derivatives. After identifying the 2-aza Hammett constant of the pyridin-2-yl group and the corresponding log K value, the site-specific acid-base properties of tenoxicam could be quantitated. This novel method is assessed to be a fine-tuning tool to find the ideal substituent by using analogue-based deductive method to obtain site-specific constants of the minor protonation/deprotonation pathway in drugs and biomolecules. The tenoxicam microconstant values indicate that the enolate moiety is of extremely low basicity (reflected by the log kO = 3.70 and log kO N = 1.09 values), which can, however, be interpreted in terms of the peculiar ring system and the overwhelming electron-withdrawing effects of the adjacent heteroatoms. A diagram depicting the pH-dependent distribution of 1 microspecies is also presented.

Effect of structural modification of enol-carboxamide-type nonsteroidal antiinflammatory drugs on COX-2/COX-1 selectivity

Meloxicam (5), an NSAID in the enol-carboxamide class, was developed on the basis of its antiinflammatory activity and relative safety in animal models. In subsequent screening in microsomal assays using human COX-1 and COX-2, we discovered that it possessed a selectivity profile for COX-2 superior to piroxicam and other marketed NSAIDs. We therefore embarked on a study of enol-carboxamide type compounds to determine if COX-2 selectivity and potency could be dramatically improved by structural modification. 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 were all examined. In addition we explored several related systems including the isomeric 3-oxo-1,2-benzothiazine-4-carboxamides, thienothiazines, indolothiazines, benzothienothiazines, naphthothiazines, and 1,3- and 1,4- dioxoisoquinolines. While a few examples were found with greater potency in the COX-2 assay, no compound tested had a better COX-2/COX-1 selectivity profile than that of 5.