Heterocyclic compounds and their use as glycogen synthase kinase-3 inhibitors

A method for treating Alzheimer's disease, behavioural and psychiatric symptoms of dementia, Parkinson's disease, tauopathies, vascular dementia, acute stroke, peripheral neuropathies, bipolar disorders, retinopathies, glaucoma, pain, rheumatoid arthritis or osteoarthritis, the method comprising administering an effective amount of at least one heterocyclic compound of formula (I)

• or a stereoisomer, N-oxide, tautomer and/or physiologically tolerated acid addition salt thereof, or a compound of formula I, wherein at least one of the atoms has been replaced by its stable, non-radioactive isotope, wherein
• A is NRB, where RB is hydrogen;
• X1 and X2 are CR2;
• X3 is selected from the group consisting of CR3, CR4, and N;
• X4, X5, and X6 are independently of each other selected from the group consisting of CR3 and CR4;
• with the proviso that no more than two of X3, X4, X5, and X6 are CR4;
• Y1, Y2, Y3, and Y4 are independently of each other selected from the group consisting of CR4, CR5, and N;
• with the proviso that at most one of Y1, Y2, Y3, and Y4 is N and with the proviso that at most one of Y1, Y2, Y3, and Y4 is CR4;
• and
• with the proviso that one of Y1, Y2, Y3, and Y4 is CR4 or C—CF3 if none of X3, X4, X5, and X6 is CR4;
• R1 is hydrogen;
• each R2 is independently selected from the group consisting of hydrogen, OH, halogen, CN, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, and NRaRb;
• or two radicals R2 bonded at the carbon atoms of groups X1 and X2, together with the carbon atoms to which they are bonded, form a 5- or 6-membered saturated or unsaturated ring which may contain 1 or 2 heteroatoms as ring members selected from the group consisting of N, O, and S and which optionally carries 1, 2, or 3 substituents R6;
• each R3 is independently selected from the group consisting of hydrogen, CN, NRaRb, OH, halogen, C1-C6-alkyl, C1-C6-haloalkyl, C3-C7-cycloalkyl, C3-C7-halocycloalkyl, C2-C4-alkenyl, C2-C4-haloalkenyl, C1-C6-alkoxy, C1-C6-haloalkoxy, formyl, C1-C6-alkylcarbonyl, C1-C6-haloalkylcarbonyl, C1-C6-alkoxycarbonyl, C1-C6-haloalkoxycarbonyl, C1-C6-alkyl-NRaRb, and an aromatic radical Ar, which is selected from the group consisting of phenyl and a 5- or 6-membered N- or C-bound heteroaromatic radical comprising one nitrogen atom and optionally 1, 2, or 3 further heteroatoms independently selected from the group consisting of O, S, and N as ring members, wherein Ar is unsubstituted or carries one or two radicals R7 and wherein Ar may also be bonded via a CH2 group;
• R4 is a C-bound saturated or partially unsaturated monocyclic 3-, 4-, 5-, 6-, or 7-membered heterocyclic ring containing 1, 2, or 3 heteroatoms or heteroatom-containing groups selected from the group consisting of O, N, S, NO, SO, and SO2 as ring members, where the heterocyclic ring optionally carries 1, 2, or 3 C- or N-bound substituents R8;
• R5 is selected from the group consisting of hydrogen, CN, NRaRb, OH, halogen, C1-C6-alkyl, C1-C6-haloalkyl, C3-C7-cycloalkyl, C3-C7-halocycloalkyl, C2-C4-alkenyl, C2-C4-haloalkenyl, C1-C6-alkoxy, C1-C6-haloalkoxy, formyl, C1-C6-alkylcarbonyl, C1-C6-haloalkylcarbonyl, C1-C6-alkoxycarbonyl, C1-C6-haloalkoxycarbonyl, C1-C6-alkyl-NRaRb, and an aromatic radical Ar, which is selected from the group consisting of phenyl and a 5- or 6-membered N- or C-bound heteroaromatic radical comprising one nitrogen atom and optionally 1, 2, or 3 further heteroatoms independently selected from the group consisting of O, S, and N as ring members, wherein Ar is unsubstituted or carries one or two radicals R7 and wherein Ar may also be bonded via a CH2 group;
• R6 and R8, independently of each other and independently of each occurrence, are selected from the group consisting of CN, NRaRb, OH, halogen, C1-C6-alkyl, C1-C6-haloalkyl, C3-C7-cycloalkyl, C3-C7-halocycloalkyl, C2-C4-alkenyl, C2-C4-haloalkenyl, C1-C6-alkoxy, C1-C6-haloalkoxy, formyl, C1-C6-alkylcarbonyl, C1-C6-haloalkylcarbonyl, C1-C6-alkoxycarbonyl, C1-C6-haloalkoxycarbonyl, C1-C6-alkyl-NRaRb, and an aromatic radical Ar, which is selected from the group consisting of phenyl and a 5- or 6-membered N- or C-bound heteroaromatic radical comprising one nitrogen atom and optionally 1, 2, or 3 further heteroatoms independently selected from the group consisting of O, S, and N as ring members, wherein Ar is unsubstituted or carries one or two radicals R7 and wherein Ar may also be bonded via a CH2 group;
• each R7 is independently selected from the group consisting of halogen, CN, C1-C6-alkyl, C1-C6-haloalkyl, C3-C6-cycloalkyl, C3-C6-halocycloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, NRaRb, a phenyl group, and a 5- or 6-membered heteroaromatic radical comprising one nitrogen atom and optionally 1, 2, or 3 further heteroatoms independently selected from the group consisting of O, S, and N as ring members, wherein phenyl and the heteroaromatic radical are, independently of each other, unsubstituted or substituted by 1, 2, 3, or 4 radicals selected from the group consisting of halogen, cyano, C1-C4-alkyl C1-C4-haloalkyl, C1-C4-alkoxy, and C1-C4-haloalkoxy;
• and
• Raand Rb are independently of each other selected from the group consisting of hydrogen, C1-C6-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C4-alkylcarbonyl, and C1-C4-haloalkylcarbonyl;
• or Ra and Rb form, together with the nitrogen atom to which they are bonded, a 3-, 4-, 5-, 6-, or 7-membered saturated or unsaturated aromatic or non-aromatic N-heterocyclic ring, which may contain 1 further heteroatom or heteroatom containing group selected from the group consisting of O, S, SO, SO2, and N as a ring member.