SUBSTITUTED INDANONE COMPOUNDS AS GPR119 MODULATORS FOR THE TREATMENT OF DIABETES, OBESITY, DYSLIPIDEMIA AND RELATED DISORDERS

摘要

The present invention relates to indanone compounds. The indanone compounds are GPR119 modulators and useful for the prevention and/or treatment of diabetes, obesity, dyslipidemia and related disorders. The invention furthermore relates to the use of indanone compounds as active ingredients in pharmaceuticals, and pharmaceutical compositions comprising them.

主权项

1: A compound of the formula I in which R30 is (CR11′R12′)-R32, NR17R18 or OR17; R31 is H or (CR11′R12′)-R32; n is 0, 1 or 2; m is 0, 1, 2 or 3; R11, R12 are independently of each other H or (C1-C6)-alkyl;
or R11 and R12 form together the group ═O; R11′, R12′ are independently of each other H or (C1-C6)-alkyl; R32 is (C1-C6)-alkyl, COOR13, CONR14R15, SO2R16 or OH; R13 is H or (C1-C6)-alkyl; R14, R15 are independently of each other H, (C1-C6)-alkyl, (C1-C6)-alkyl substituted with OR17, or (C3-C6)-cycloalkyl;
or R14 and R15 form together with the N-atom on which they are attached, a 4-, 5- or 6-membered heterocycle, optionally containing an additional heteroatom selected from the list O, S and NR18;
wherein the 4-, 5- or 6-membered heterocycle may be optionally substituted with 1 to 3 groups selected from the list (C1-C4)-alkyl and OR19; R16 is (C1-C6)-alkyl; R17 is H or (C1-C6)-alkyl; R18 is H or (C1-C6)-alkyl; R19 is H or (C1-C6)-alkyl; R1a, R1b, R1c are independently of each other H, F, Cl, Br, (C1-C6)-alkyl or CN; R2a, R2b, R2c are independently of each other H, F, Cl, Br, (C1-C6)-alkyl or CN; Y is N or CH; Z is a bond, O, CR5R5′, NR6, C═O, S, SO or SO2; R5, R5′, R6 are independently of each other H or (C1-C4)-alkyl; R3 is a bond or (CR7R7′)p; p is 0, 1, 2, 3 or 4; R7, R7′ are independently of each other H or (C1-C6)-alkyl; R4 is (C1-C6)-alkyl, OR8, (C3-C8)-cycloalkyl, (C5-C8)-bicycloalkyl, 4-, 5- or 6-membered heterocycle, phenyl or 5- or 6-membered heteroaryl ring;
wherein the groups (C3-C8)-cycloalkyl, (C5-C8)-bicycloalkyl, 4-, 5- or 6-membered heterocycle, phenyl, 5- or 6-membered heteroaryl ring may be optionally substituted with 1 to 3 groups selected from (C1-C4)-alkyl, (C1-C4)-alkanoyl, hydroxy, hydroxy-(C1-C4)-alkyl, (C1-C3)-alkyloxy-(C1-C4)-alkyl, oxo, F or Cl; R8 is H, (C1-C6)-alkyl, hydroxy-(C1-C4)-alkyl or (C1-C3)-alkyloxy-(C1-C4)-alkyl; wherein at each occurrence the hydrogen atoms of alkyl groups may be partially or fully replaced by fluorine atoms; in any of its stereoisomeric forms, or a mixture of stereoisomeric forms in any ratio, or a physiologically acceptable salt thereof.