Methyl 5-chloro-4-hy-droxy-2,2-dioxo-1-2λ,1-benzo-thia-zine-3-carboxyl-ate: structure and Hirshfeld surface analysis.

The title compound, CHClNOS, which has potential analgesic activity, crystallizes in space group 2/. The benzo-thia-zine ring system adopts an inter-mediate form between sofa and twist-boat conformations. The coplanarity of the ester substituent to the bicyclic fragment is stabilized by an O-H⋯O intra-molecular hydrogen bond.

Biological properties of two enantiomorphic forms of N-(2,6-dimethylphenyl)-4-hydroxy-2,2-dioxo-1H-2λ,1-benzothiazine-3-carboxamide, a structural analogue of piroxicam.

The title benzothiazine-3-carboxamide, CHNOS, crystallized in two enantiomorphic crystal forms with the space groups P3 and P3 despite the absence of a classic stereogenic atom. The molecular structures are mirror images of each other. Only one sulfonyl O atom takes part in intramolecular hydrogen bonding as a proton acceptor and this atom is different in the two enantiomorphic structures.

Synthesis, Structure, and Analgesic Properties of Halogen-Substituted 4-Hydroxy-2,2-dioxo-1H-2λ⁶,1-benzothiazine-3-carboxanilides.

As potential new analgesics, the corresponding 4-hydroxy-2,2-dioxo-1-2λ⁶,1-benzothiazine-3-carboxanilides have been obtained by amidation of ethyl 4-hydroxy-2,2-dioxo-1-2λ⁶,1-benzothiazine-3-carboxylate with aniline and its halogenated analogsin boiling dry xylene. The peculiarities of the mass and nuclear magnetic resonance (¹Н and С) spectra of the synthesized compounds are discussed. Using X-ray diffraction analysis, the ability of the compounds to form stable solvates with ,-dimethylformamide has been shown on the example of 4-bromo-substituted derivative.

The Study of Structure-Analgesic Activity Relationships in a Series of 4-Hydroxy-2,2-dioxo-1H-2λ⁶,1-benzothiazine-3-carboxylic Acid Toluidides and Xylidides.

In continuing the search for new analgesics among derivatives of 2,1-benzothiazines, a series of corresponding toluidides and xylidides of 4-hydroxy-2,2-dioxo-1-2λ⁶,1-benzothiazine-3-carboxylic acid has been synthesized by the reaction of ethyl 4-hydroxy-2,2-dioxo-1-2λ⁶,1-benzothiazine-3-carboxylate with equimolar amounts of mono- and dimethyl-substituted anilides in boiling dry xylene. Their structure has been confirmed by the data of elemental analysis, nuclear magnetic resonance (NMR) spectroscopy (¹Н and С), as well as mass spectrometry. All compounds obtained were subjected to pharmacological screening to identify their analgesic properties.

Synthesis, Spatial Structure and Analgesic Activity of Sodium 3-Benzylaminocarbonyl-1-methyl-2,2-dioxo-1H-2λ⁶,1-benzothiazin-4-olate Solvates.

In order to obtain and then test pharmocologically any possible conformers of the new feasible analgesic benzyl-4-hydroxy-1-methyl-2,2-dioxo-1-2λ⁶,1-benzothiazine-3-carboxamide, its 4--sodium salt was synthesized using two methods. X-ray diffraction study made possible to determine that, depending on the chosen synthesis conditions, the above-mentioned compound forms either monosolvate with methanol or monohydrate, where organic anion exists in the form of three different conformers. Pharmacological testing of the two known pseudo-enantiomeric forms of the original benzylamide and of the two solvates of its sodium salt was performed simultaneously under the same conditions and in equimolar doses.

Two pseudo-enantiomeric forms of N-benzyl-4-hydroxy-1-methyl-2,2-dioxo-1H-2λ(6),1-benzothiazine-3-carboxamide and their analgesic properties.

The fact that molecular crystals exist as different polymorphic modifications and the identification of as many polymorphs as possible are important considerations for the pharmaceutic industry. The molecule of N-benzyl-4-hydroxy-1-methyl-2,2-dioxo-1H-2λ(6),1-benzothiazine-3-carboxamide, C17H16N2O4S, does not contain a stereogenic atom, but intramolecular hydrogen-bonding interactions engender enantiomeric chiral conformations as a labile racemic mixture. The title compound crystallized in a solvent-dependent single chiral conformation within one of two conformationally polymorphic P212121 orthorhombic chiral crystals (denoted forms A and B).

The Effective Synthesis of N-(Arylalkyl)-1-R-4-hydroxy-2,2-dioxo- 1H-2λ(6),1-benzothiazine-3-carboxamides as Promising Analgesics of a New Chemical Class.

A new, effective preparative method has been proposed and the synthesis of a series of N-(arylalkyl)-1-R-4-hydroxy-2,2-dioxo-1H-2λ(6),1-benzothiazine-3-car-boxamides has been carried out. It has been shown that amidation of alkyl 1-R-4-hydroxy-2,2-dioxo-1H-2λ(6),1-benzothiazine-3-carboxylates with arylalkyl-amines in boiling xylene proceeds with good yield and purity to the corresponding N-(arylalkyl)-amides. However, the presence of water in the reaction mixture has been shown to cause the formation of specific impurities: N-(arylalkyl)-1-R-2,2-dioxo-1H-2λ(6),1-benzothiazin-4-amines.

(R,S)-2'-Amino-6'-methyl-2,5',5'-trioxo-6'H-spiro-[indoline-3,4'-pyrano[3,2-c][2,1]benzo-thia-zine]-3'-carbo-nitrile di-methyl-formamide monosolvate.

The title solvate, C20H14N4O4S·C3H7NO, comprises a stereogenic centre but the centrosymmetric space group causes the presence of the racemate in the crystal. The spiro-joined fragments are almost orthogonal, with a dihedral angle of 86.8 (2)° between the mean planes of the pyrane ring and the dihydroindolone ring system.

Methyl 1-allyl-4-hy-droxy-2,2-dioxo-1H-2λ(6),1-benzo-thia-zine-3-carboxyl-ate.

There are two independent mol-ecules in the asymmetric unit of the title compound, C13H13NO5S, in both of which the ester substituent is nearly coplanar [C-C-C-O torsion angles = 2.7 (7) and -0.8 (7)°] with the planar fragment of the bicycle due to the formation of a strong O-H⋯O intra-molecular hydrogen bond.