Abstract
A series of spiro hydantoins derived from 8-azachromanones (2,3-dihydro-4H-pyrano[2,3-b]pyridin-4-ones) has been prepared and tested for aldose reductase inhibitory activity. The standard Bucherer-Bergs conditions had to be drastically modified to increase yields from less than 1% to an acceptable 50% range. One of the most potent compounds was cis-6'-chloro-2',3'-dihydro-2'-methylspiro[imidazolidine-4,4'-4'H- pyrano[2,3-b]pyridine]-2,5-dione; resolution of this compound showed that the 2'R,4'S enantiomer 16 was the most active spiro hydantoin in this series with an IC50 of 7.5 x 10(-9) against human placenta aldose reductase.
MeSH terms
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Aldehyde Reductase / antagonists & inhibitors*
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Aldehyde Reductase / isolation & purification
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Animals
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Aza Compounds
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Benzopyrans*
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Chromans*
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Diabetes Mellitus, Experimental / enzymology
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Diabetes Mellitus, Experimental / metabolism
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Female
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Humans
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Hydantoins / chemical synthesis*
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Hydantoins / pharmacology
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Indicators and Reagents
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Lens, Crystalline / drug effects
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Lens, Crystalline / metabolism
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Magnetic Resonance Spectroscopy
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Mass Spectrometry
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Molecular Structure
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Placenta / enzymology
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Pregnancy
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Rats
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Sciatic Nerve / drug effects
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Sciatic Nerve / metabolism
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Sorbitol / metabolism
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Spiro Compounds / chemical synthesis*
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Spiro Compounds / pharmacology
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Stereoisomerism
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Structure-Activity Relationship
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Sugar Alcohol Dehydrogenases / antagonists & inhibitors*
Substances
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Aza Compounds
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Benzopyrans
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Chromans
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Hydantoins
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Indicators and Reagents
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Spiro Compounds
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Sorbitol
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Sugar Alcohol Dehydrogenases
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Aldehyde Reductase