Azabenzimidazole derivatives

摘要

The present invention relates to compounds of general formula I,;
wherein the group R1, R2, X and Y are defined as in claim 1, which have valuable pharmacological properties, in particular bind to the AMP-activated protein kinase (AMPK) and modulate its activity. The compounds are suitable for treatment and prevention of diseases which can be influenced by this receptor, such as metabolic diseases, in particular diabetes type 2.

主权项

1. A compound of formula I, wherein R1 is selected from the group consisting of R2 is selected from the group consisting of F, Cl, Br, C1-4-alkyl, and C1-4-alkyl-O—, wherein any alkyl group and subgroup is optionally substituted with 1 or more F atoms; X is selected from the group consisting of a bond, a divalent piperidinyl, a divalent piperazinyl, a phenylene, pyridinylene, pyrimidinylene, and pyridazinylene group,
wherein said divalent piperidinyl and piperazinyl group is optionally substituted with F, H3C—, or H3C—O—, andwherein said phenylene, pyridinylene, pyrimidinylene, and pyridazinylene group are optionally substituted with F, Cl, Br, NC—, HO2C—, H3C—, H3C—O—, F3C—, or F3CO—; and Y is selected from the group consisting of cyclohexyl, cyclohexenyl, piperidinyl, phenyl, pyridinyl, pyridazinyl, pyrazinyl, isoindolinyl, azaisoindolinyl, and pyrimidinyl, which are mandatorily substituted with a group selected from RSRS′(O═)S═N—, RSRS′(O═)S═N—C1-3-alkyl-, RSRS′(O═)S═N—C(═O)—, (RN)N═S(═O)(RS)—, (RN)N═S(═O)(RS)—C1-3-alkyl-, and RSRS′(RN′—N═)S═N—,
andwherein said cyclohexyl, cyclohexenyl and piperidinyl groups are optionally substituted with F, H3C—, and H3C—O—, andwherein said phenyl, pyridinyl, pyridazinyl, pyrazinyl, isoindolinyl, azaisoindolinyl and pyrimidinyl groups are optionally substituted with F, Cl, Br, NC—, HO2C—, H3C—, H3C—O—, F3C—, or F3CO—; a saturated or partly unsaturated heterocyclyl group selected from cyclohexyl, cyclohexenyl, piperidinyl and aza- bicyclooctyl each containing a —S(═O)(═N—RN)—group, optionally substituted with 1 to 3 groups independently selected from F, HO—, NC—, C1-4-alkyl- and C1-4-alkyl-O—,
wherein RN is selected from H, NC—, C1-4-alkyl, C1-4-alkyl-C(═O)—, C1-4-alkyl-O—C(═O)—, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-3-alkyl-, C3-7-cycloalkyl-C(═O)—, heterocyclyl, heterocyclyl-CH2—, heterocyclyl-C(═O)—, aryl, aryl-C1-3-alkyl-, aryl -C(═O)—, heteroaryl, heteroaryl-C1-3-alkyl-, and heteroaryl-C(═O)—, and RN′ is selected from H, NC—, C1-4-alkyl-, aryl, aryl-C1-3-alkyl-, heteroaryl, heteroaryl-C1-3-alkyl-,
wherein any alkyl, cycloalkyl and heterocyclyl group is optionally substituted with 1 to 3 groups independently selected from F, C1-3-alkyl-O—, (C1-3-alkyl)2-N—, HO2C—, C1-3-alkyl-C(═O)—, and C1-3-alkyl-S(═O)2—, andwherein any aryl and heteroaryl group is optionally substituted with 1 to 3 groups independently selected from F, Cl, Br, I, HO—, NC—, HO2C—, C1-3-alkyl, C1-3-alkyl-O—, H2N—, C1-3-alkyl-NH—, (C1-3-alkyl)2-N—, and C1-3-alkyl -S(═O)2—, andwherein RN′ is selected from H, NC—, C1-4-alkyl, C3-7-cycloalkyl, aryl-C1-3-alkyl-, heteroaryl, heteroaryl-C1-3-alkyl-,
wherein any alkyl and cycloalkyl optionally substituted with 1 to 3 groups independently selected from F, C1-3-alkyl-O—, (C1-3-alkyl)2-N—, HO2C—, C1-3-alkyl-C(═O)—, and C1-3-alkyl-S(═O)2—,and wherein any aryl and heteroaryl group is optionally substituted with 1 to 3 groups independently selected from F, Cl, Br, I, HO—, NC—, HO2C—, C1-3-alkyl, C1-3-alkyl-O—, H2N—, C1-3-alkyl-NH—, (C1-3-alkyl)2-N—, and C1-3-alkyl -S(═O)2—, andwherein RS and RS′ are independently selected from C1-4-alkyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-3-alkyl-, heterocyclyl, heterocyclyl-C1-3-alkyl-, aryl, aryl-CH2—, heteroaryl, and heteroaryl-C1-3-alkyl-,
wherein any alkyl, cycloalkyl and heterocyclyl group is optionally substituted with 1 to 3 groups independently selected from C1-3-alkyl-O—, (C1-3-alkyl)2-N—, HO2C—, C1-3-alkyl-C(═O)—, and C1-3-alkyl-S(═O)2—, andwherein any aryl and heteroaryl group is optionally substituted with 1 to 3 groups independently selected from F, Cl, Br, I, HO—, NC—, C1-3-alkyl, C1-3-alkyl-O—, H2N—, C1-3-alkyl-NH—, (C1-3-alkyl)2-N—, and C1-3-alkyl-S(═O)2,or RS and RS′ together with the S-atom these groups are attached to form a 5-7 membered saturated monocyclic ring system containing 0 to 1 heteroatoms selected from —NRN″— and O, optionally substituted with 1 to 3 groups independently selected from F, HO—, C1-3-alkyl, C1-3-alkyl-O—, H2N—, C1-3-alkyl-NH—, (C1-3-alkyl)2-N—, and C1-3-alkyl-S(═O)2—, and
wherein RN″ is selected from H, H3C—, H5C2—, and cyclopropyl; or a salt thereof.