Add time:08/11/2019         Source:sciencedirect.com

Aldose reductase (EC 1.1.1.21) is believed to be involved in the pathogenesis of diabetic complications. Inhibitors of this enzyme could be useful for the treatment of diabetic cataracts and neuropathies. A series of spiro[chroman-4,5′-thiazolidine]-2′,4′-diones, substituted at the aromatic ring, has been synthesized as potential inhibitors of this enzyme. Their activity was determined with in vitro and in vivo tests. The compounds are very potent inhibitors of aldose reductase. Activity in galactosemic rats was found, especially for derivatives bearing alkyl-carbamate substituents. Drug levels in plasma, lens and nerve were determined with radioactively labelled compounds and by high performance liquid chromatography. The latter method was also used to determine in vivo degradation of the carbamates.

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