New azolidinediones as antihyperglycemic agents

C - Chemistry – Metallurgy – 07 – D

Patent

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C07D 413/12 (2006.01) A61K 31/41 (2006.01) A61K 31/44 (2006.01) A61K 31/695 (2006.01) C07D 263/44 (2006.01) C07D 413/14 (2006.01) C07D 417/12 (2006.01) C07D 417/14 (2006.01) C07F 7/10 (2006.01)

Patent

CA 2190015

This invention relates to novel compounds which have demonstrated oral antihyperglycemic activity in diabetic ob/ob and db/db mice, animal models on non-insulin dependent diabetes mellitus (NIDDM or Type II diabetes). These compounds have formula (I), wherein: R1 is C1-C6 alkyl, C3-C8 cycloalkyl, thienyl, furyl, pyridyl, (a) or (b), where R10 is hydrogen, C1-C6 alkyl, fluorine, chlorine, bromine, iodine, C1-C6 alkyoxy, trifluoroalkyl or trifluoroalkoxy; R2 is hydrogen or C1-C6 alkyl; X is O or S; n is 0, 1, or 2; A is (c) or (d); where R3 is hydrogen, C1-C6 alkyl, halogen, C1-C6 alkoxy, trifluoroalkyl or trifluoroalkoxy; B is (e), (f) or (g), where R4 is hydrogen, C1-C6 alkyl, allyl, C6-C10 aryl, C6-C10 aryl-(CH2)1-6-, fluorine, chlorine, bromine, iodine, trimethylsilyl or C3-C8 cycloalkyl; R5 is hydrogen, C1-C6 alkyl, C6-C10 aryl, or C6-C10 aryl-(CH2)1-6-; m is 0, 1, or 2; R6 is hydrogen or C1-C6 alkyl; R7 is hydrogen or C1-C6 alkyl; R8 and R9 are selected independently from hydrogen, C1-C6 alkyl, fluorine, chlorine, bromine, or iodine; Y is O or S; Z is N or CH when Y is O and Z is CH when Y is S; or a pharmaceutically acceptable salt thereof.

Cette invention concerne de nouveaux composés ou un sel pharmaceutiquement acceptable de ces derniers qui ont fait preuve d'une activité antihyperglycémique orale chez des souris diabétiques ob/ob et db/db, des modèles d'animaux souffrant de diabète sucré non insulino-dépendant (DSNID ou de diabète du type II). Ces composés répondent à la formule I, dans laquelle R?1¿ représente alkyle C¿1?-C¿6?, cycloalkyle C¿3?-C¿8?, thiényle, furyle, pyridyle, (a) or (b) dans laquelle R?10¿ représente hydrogène, alkyle C¿1?-C¿6?, fluor, chlore, brome, iode, alkyoxy C¿1?-C¿6?, trifluoroalkyle ou trifluoroalcoxy; R?2¿ représente hydrogène ou alkyle C¿1?-C¿6?; X représente O ou S; n représente 0, 1 ou 2; A représente (c) ou (d), dans laquelle R?3¿ représente hydrogène, alkyle C¿1?-C¿6?, halogène, alcoxy C¿1?-C¿6?, trifluoroalkyle ou trifluoroalcoxy; B représente (e), (f), (g) dans laquelle R?4¿ représente hydrogène, alkyle C¿1?-C¿6?, allyle, aryle C¿6?-C¿10?, aryle C¿6?-C¿10?-(CH¿2?)¿1-6?-, fluor, chlore, brome, iode, triméthylsilyle ou cycloalkyle C¿3?-C¿8?; R?5¿ représentant hydrogène, alkyle C¿1?-C¿6?, aryle C¿6?-C¿10?, ou aryle C¿6?-C¿10?-(CH¿2?)¿1-6?; m représente 0, 1 ou 2; R?6¿ représente hydrogène ou alkyle C¿1?-C¿6?; R?7¿ représente hydrogène ou alkyle C¿1?-C¿6?; R?8¿ et R?9¿ étant sélectionnés indépendamment parmi hydrogène, alkyle C¿1?-C¿6?, fluor, chlore, brome et iode; Y représente O ou S; Z représente N ou CH quand Y représente O et Z représente CH quand Y représente S.

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