The Fate of the Saccharin Impurities Toluene-2-Sulphonamide and 2,3-Dihydrobenz( d]isothiazole 1,l-Dioxide in the Rat ANDREW G. R E W I C K * and LOUISE M. BALL? *Faculty of Medicine, University of Southampton, Southampton SO9 3 TU, U.K., and ?Pharmacology Branch, N.I.E.H.S., Research Triangle Park, NC 27709, U.S.A. The non-nutritive sweetener, saccharin (2,3-dihydro-3-oxobenz[d]isothiazole 1,l...

Sixteen new isothiazoloisoxazole 1,1-dioxides, one new isothiazolotriazole and one new isothiazolopyrazole have been synthesised by using 1,3-dipolar cycloadditions to isothiazole 1,1-dioxides. One sub-set of these isothiazoloisoxazoles showed low μM activity against a human breast carcinoma cell line, whilst a second sub-set plus the isothiazolotriazole demonstrated an interesting restricted r...

This follow-up paper completes the author's investigations to explore the in-solution structural preferences and relative free energies of all OH-substituted oxazole, thiazole, isoxazole, and isothiazole systems. The polarizable continuum dielectric solvent method calculations in the integral-equation formalism (IEF-PCM) were performed at the DFT/B97D/aug-cc-pv(q+(d))z level for the stable neut...

Regioselective palladium catalysed coupling reactions are achieved in good to high yields, starting from either 3,5-dichloro- or 3,5-dibromoisothiazole-4-carbonitriles 1 and 2, providing 3-halo-5-(hetero/aryl, alkenyl and alkynyl)isothiazoles 3, 4, 6-9 from Stille couplings, 3-halo-5-(hetero/arylethynyl)isothiazoles 14-19 from Sonogashira and 5,5'-bi(3-chloroisothiazole-4-carbonitrile) (13) fro...

1-N-Alkylated-6-sulfamoyl saccharin derivatives were prepared and assayed as carbonic anhydrase inhibitors (CAIs). During X-ray crystallographic experiments an unexpected hydrolysis of the isothiazole ring was evidenced which allowed us to prepare highly potent enzyme inhibitors with selectivity for some isoforms with medical applications.

A series of isothiazole dioxides was synthesized and evaluated as inhibitors of protein farnesyltransferase from the parasite that causes African sleeping sickness (Trypanosoma brucei). The most potent compound in the series inhibited the parasite enzyme with an IC(50) of 2 microM and blocked the growth of the bloodstream parasite in vitro with an ED(50) of 10 microM. The same compound inhibite...

3-Amino-l,2-benzisothiazole-1,1-dioxides (2b-n) have been prepared by heating saccharin (1) and the hydrochlorides of primary and secondary aliphatic amines with phosphorus pentoxide and N,N-dimethylcyclohexylamine at 240 °C. 3-Aminothieno[3,4-d]isothiazole-1,1-dioxides (6a-c) were similarly prepared from thieno[3,4-d]isothiazol3(2H)-one-1,1 -dioxide (5). 3 1 P NMR spectra were obtained of reac...

Several new compounds - 4 and 5-substituted derivatives of 3-methyl-4-isothiazolecarboxylic acid were synthesized. These compounds have aminoacylamino groups in position 5 of the isothiazole ring. In position 4, the carboxylic group was replaced by ethyl ester. The biological activites of the obtained compounds were analyzed in the humoral immune response and delayed type hypersensitivity react...