Banavara L. Mylari

Design and synthesis of a novel family of triazine-based inhibitors of sorbitol dehydrogenase with oral activity: 1-{4-[3R,5S-dimethyl-4-(4-methyl-[1,3,5]triazin-2-yl)-piperazin-1-yl]-[1,3,5]triazin-2-yl}-(R) ethanol

Two new templates, (R) 2-hydroxyethyl-pyridine and (R) 2-hydroxyethyl-triazine, were used to design novel sorbitol dehydrogenase inhibitors (SDIs). The design concept included spawning of these templates to function as effective ligands to the catalytic zinc within the enzyme through incorporation of optimally substituted piperazino-triazine side chains so as to accommodate the active site in the enzyme for efficient binding. This strategy resulted in orally active SDIs, which penetrate key tissues, for example, sciatic nerve of chronically diabetic rats. The latter template led to the design of the title inhibitor, 33, which normalized the elevated sciatic nerve fructose by 96% at an oral dose of 10mg/kg.

2-Chloro-1,1,1-Triethoxyethane and its Use in a Versatile Synthesis of Substituted, 2-Chloromethyl Heterocycles Including Benzothiazole and Benzoxazole

Abstract An efficient procedure suitable for large scale preparation of 2-chloro-1,1,1-triethoxyethane and its use in a versatile synthesis of 2-chloromethyl derivatives of an assortment of heterocycles are described.