Heterocyclic boronic acid compounds

C - Chemistry – Metallurgy – 07 – F

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C07F 5/02 (2006.01) C07D 403/12 (2006.01)

Patent

CA 2545311

Dipeptidyl peptidase IV (DPP-IV)-inhibiting compounds are provided that have formula I: wherein n is 1 to 3; X is CH2; S; O; CF2 or C (CH3)2; Z is H; halogen; hydroxyl; (C1-6)alkoxy; (C1-12)alkyl; (C3-12)cycloalkyl; phenyl; or heteroaryl; where the phenyl and heteroaryl groups are optionally mono- or independently plurisubstituted with R7; optionally, X together with an adjacent ring carbon and Z form a fused cyclopropyl; and optionally, one of the bonds in the ring containing X is a double bond; and CriRii, R1, R1, R3, R4 and R5 are as described herein. Methods for preparing these compounds, and methods for treating diabetes, especially Type II diabetes, and other related diseases are described using the compounds of formula I in pharmaceutical compositions which contain these compounds. Pharmaceutical compositions which contain combinations of these compounds with other antidiabetic agents are also described herein.

La présente invention a trait à des composés d'inhibition de la dipeptidyle peptidase IV de formule (I), dans laquelle : n est 1 à 3 ; X est CH¿2?, S, O, CF¿2? ou C(CH¿3?)¿2 ?; Z est H, halogène, hydroxyle, alcoxy en C¿1?-C¿6?, alkyle en C¿1?-C¿12?, cycloalkyle en C¿3?-C¿12?, phényle, ou hétéroaryle, où les groupes phényle et hétéroaryle sont éventuellement mono- ou polysubstitués indépendamment avec R?7 ¿; éventuellement, X ensemble avec un carbone cyclique adjacent et Z forment un cyclopropyle accolé ; et CR?i¿, R?ii¿,, R?1¿, R?2¿, R?3¿, R?4¿ et R?5¿ sont tels que définis dans la description. L'invention a également trait à des procédés pour la préparation desdits composés, et à des procédés pour le traitement du diabète, notamment du diabète de type II, et d'autres maladies associées mettant en oeuvre les composés de formule I dans des compositions pharmaceutiques qui contiennent ces composés et à des compositions pharmaceutiques contenant des combinaisons de ces compositions avec d'autres agents anti-diabétiques.

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