Sulfathiazole, structure

The structure of sulfonamides is shown for representative purposes. Among the several thousand compounds in existence, about 25-30 have found widespread use. Sulfanilamide itself is, by present-day standards, very inactive. It was the development of heterocyclic derivatives that produced the highly potent sulfathiazole (9.90). When a succinyl or phthalyl group is attached to the aniline nitrogen, the inactive acylanilide derivatives will not be absorbed from the intestinal tract. Slow deacylation by intestinal... 

The structural formulas of several cyclic compounds containing both nitrogen and sulfur are shown in Figure 17.4. Basic to the structures of these compounds is the simple ring structure of thiazole. It is a colorless liquid (bp, 117°C). One of its major uses has been for the manufacture of sulfathiazole, one of the oldest of the sulfonamide class of antibacterial drugs. The use of sulfathiazole is now confined to the practice of veterinary medicine because of its serious side effects. 

Coccidiostatic, 152 Coding structures. 139 Color-coupling agents, 159 Colorimetry, in sulfathiazole determination. 116... 

Figure 6.6 Structure of sulfathiazole and part of its predicted activity spectrum. Activities contained in the SAR Base of PASS version 2007 are marked in bold.

Antipin, M. Y, Timofeeva, T. V., Clark, R. D., Nesterov, V. N., Dolgushin, F. M., Wu, J. and Leyderman, A. (2001). Crystal structures and molecular mechanics calculation of nonlinear optical compounds 2-cyclooctylamino-5-nitropyridine (COANP) and 2-adamantylamino-5-nitropyridine (AANP). New Polymorphic modifcation of AANP and electrooptic effects. /. Mater. Chem., 11, 351-8. [213] Apperley, D. C., Fletton, R. A., Harris, R. K., Lancaster, R. W., Tavener, S. and Threlfall, T. L. (1999). Sulfathiazole polymorphism studied by magic-angle spinning NMR. / Pharm. ScL, 88, 1275-80. [135,139f]... 

Chamot, E. M. and Mason, C. W. (1973). Handbook of chemical microscopy. Vol. 1, 3rd edn. Principles and Use of Microscopes and Accessories. Physical Methods for the Study of Chemical Problems, Wiley-Interscience, New York. [22,46,48, 95] Chan, F. C., Anwar, J., Cernik, R., Barnes, R. and Wilson, R. M. (1999). Ab initio structure determination of sulfathiazole polymorph V from synchroton x-ray powder diffraction data. J. Appl Crystallogr, 32,436 1. [111]... 

The supramolecular assembly process can be controlled so that the precursor nuclei in solution adopt a structure that resembles the structure of the desired crystalline modification. " This concept has been used in the design of nucleation inhibitors to prevent growth of the stable polymorph and enhance the growth of the metastable polymorph. Davey and coworkers have explained the solvent dependent polymorph appearance of sulfathiazole by analyzing the intermolecular interactions in the various polymorphic structures, and comparing them with the supramolecular assemblies that could exist in the different solvents. In this case, however, the solvent dependent selective crystallization of a polymorph was not correlated with solubility. 

Most of the sulfa drugs possess the general structure (17), and many of the most useful compounds contain a heterocyclic nucleus. Important examples include sulfapyridine (18), sulfadiazine (19), sulfathiazole (20) and sulfamethoxazole (21) (Figure 3). Sulfapyridine... 

The antibacterial sulfathiazole presents five polymorphic structures. The modification of the operating conditions in a DG antisolvent process allowed control over product composition so that it was possible to produce three of the polymorphic forms separately. 

The same lead structure, sulfisoxazole (11), was also identified by Bristol Meyers Squibb, via the screening hit sulfathiazole (14). In this instance modification of the aniline led, via a naphthalene ring, to the substituted biphenyl 15 " however, preclinical PK studies indicated that the attached isobutyl group was subject to extensive hydroxy-lation. Replacement of this group with an isoxazole ring imparted metabolic stability, and expansion of the SAR at the tolerant 2 -position provided the clinical candidate edo-nentan (16). ... 

Not all polymorphism originates from conformational requirements, and many polymorphic situations exist because of different modes of molecular packing in the solid-state structures. For example, the two polymorphs of enalapril maleate exhibit very similar molecular conformations (as evidenced by the similarity in spectral characteristics), and the observed differences in crystal structure, therefore, are attributed to different modes of crystal packing. Sufficient differences in the solid-state C-NMR spectra of the four polymorphs of sulfathiazole were observed to enable the use of this technique as an analytical tool, but these differences could not be ascribed to differences in molecular conformations among the polymorphs. ... 

Chan FC, Anwar J, Cernik R, Barnes P, Wilson RM. Ab initio structure determination of sulfathiazole pol5miorph V from synchrotron X-ray powder diffraction data. J Appl Crystallogs 1999 32 436 41. 

The snlfonamides are structurally related to p-aminoben-zoic acid. The presence of a free p-amino gronp is essential for the antibacterial action. Succinylsulfathiazole (sulfasuxi-dine) and phthalysnlfathiazole (sulfathalidine) are agents with a snbstitnted p-amino group. These intestinal antiseptics are slowly hydrolyzed in the intestine, releasing sulfathiazole, which exerts antiseptic effects against the coliform and clostridial organisms. 

The layer-type structure is observed in jS-CyD complexes with triethylenediamine [128] 18 and sulfathiazole [129] 19. The jS-CyD ring is arranged in a molecular layer stacked along the crystallographic two-fold axis. A part of the guest molecule... 

Fig. 7.17. Ciystal structure of the f-CyD complex with sulfathiazole, showing layer-type packing.

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