Improved glucose tolerance in rats treated with oxazolidinediones.
5-(2-Chloro-6-methoxyphenyl)oxazolidine-2,4-dione (49) is the most potent agent selected from a series of 5-substituted oxazolidinediones that were found to cause improvements in glucose tolerance in previously fasted rats and potentiation of insulin release in response to a glucose challenge. These compounds were unique in not producing hypoglycemia below the normal fasting glycemia levels. Substituent effects at positions 2-6 of the phenyl ring were investigated. Optimal positions for substitution were found to be the 2-, 5-, and 6-positions. Variations in the oxazolidinedione ring generally lead to loss of activity. The synthesis and structure-activity relationships of this series are detailed.
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Schnur
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Morville
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D008297:Male; D010080:Oxazoles / Q000494:pharmacology*; D051381:Rats; D013237:Stereoisomerism
D001786:Blood Glucose; D010080:Oxazoles