Naslov
Antihyperglycemic 1-Sulfonyl-1a, 2, 6, 6a-tetrahydro-1H, 4H-[1, 3]-dioxepino[5, 6-b]azirines: Synthesis, X-ray Structure Analysis, Conformational Behavior, Quantitative Structure Property Relationships and Quantitative Structure Activity Relationships

Autori
Dumić, Miljenko ; Vinković, Mladen ; Filić, Darko ; Jamnicky, Blanka ; Eškinja, Mirela ; Kamenar, Boris

Izvornik
Journal of medicinal chemistry (0022-2623) 38 (1995), 16; 3034-3042

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Antihyperglycemic ; [1 ; 3]-dioxepino[5 ; 6-b]azirine ; N-sulfonyl-dioxepinoazirine ; X-ray structure analysis ; conformational behavior ; quantitative structure activity relationships

Sažetak
A series of 1-sulfonyl-1a, 2, 6, 6a-tetrahydro-1H, 4H-[1, 3]-dioxepino[5, 6-b]azirines, has been synthesized and evaluated for its effects on blood glucose-decreasing activity. These derivates were prepared from 4, 7-dihydro-1, 3-dioxepins via vic(acylamino)halogenodioxepanes and dioxepanoazirines. Quantitative structure-property relationship and quantitative structure-activity relationship models, based on X-ray and molecular mechanic analyses, to our knowledge the first in the fieldof antihyperglycemics, were developed. They allow the prediction of properties (RP-HPLC attention times) and activities (hypoglycemic ratio) by the Connollys molecular surface areas. The lead compound in these models, sulfonyldioxepinoazirine 4i, expressed superior antihypergglycemic activity in comparison to metformin in alloxanized mice, irrespective of rout of application. It sgnificantly reduced blood glucose levels in glucose-primed mice, but did not cause a dose dependent decrease of blood glucose level in healty (nondiabetic, control) animals.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA