Improved glucose tolerance in rats treated with oxazolidinediones

Abstract

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.

Adamantane derivatives: a new class of insulin secretagogues

“…During the last few years, several compounds unrelated to sulphonylureas have been found to stimulate insulin release in vivo and in vitro (Kameda et al, 1981;Iwai et al, 1983;Hanson et al, 1985;Schnur & Morville, 1986), but their mode of action was only partially or not at all elucidated. It has also been shown recently that benzoic acid derivatives corre-'Author for correspondence at University of Louvain, Brussels.…”

Synthesis and Inverse Electron Demand Diels−Alder Reactions of 3,6-Bis(3,4-dimethoxybenzoyl)-1,2,4,5-tetrazine

“…The preparation commenced with the formation of TMS-protected 3,4-dimethoxybenzaldehyde cyanohydrin 4 (TMSCN, ZnI 2 ) in quantitative yield . Treatment of 4 with saturated ethanolic HCl promoted ethanol addition to the nitrile and deprotection of the benzylic alcohol to provide 5 . , Imidate 5 was most conveniently purified by repeated washings with Et 2 O or EtOAc, and the off-white solid was then added in portions to neat hydrazine hydrate 7,14-16 at 0 °C to afford the 1,4-dihydrotetrazine 6 . Like 5 , the dihydrotetrazine 6 could be conveniently purified by repeated washings with EtOAc 14 to afford 6 as a white solid, although air oxidation to the more soluble tetrazine during this purification may result in a loss of material in the EtOAc trituration.…”

Organocatalytic Enantioselective and Diastereodivergent Mannich Reactions of 5‐Substituted Oxazolidin‐2,4‐Diones

“…Moreover, they are useful synthetic precursors owing to the ability to being readily transformed into many important molecular architectures, such as α‐tertiary alcohol‐based carboxylates and the derivatives [7–9] . Accordingly, development of synthetic methods to access these valuable entities has long been pursued by chemists [1–14] . Nevertheless, the catalytic asymmetric formation of optically pure variants still remains underdeveloped.…”

“…[7][8][9] Accordingly, development of synthetic methods to access these valuable entities has long been pursued by chemists. [1][2][3][4][5][6][7][8][9][10][11][12][13][14] Nevertheless, the catalytic asymmetric formation of optically pure variants still remains underdeveloped.…”