Amino alcohol-substituted arylthienopyrimidinones, process for their preparation and their use as medicaments

摘要

The invention relates to amino alcohol-substituted arylthienopyrimidinones having a formula I;
and their derivatives, and their physiologically tolerated salts and physiologically functional derivatives, their preparation, medicaments comprising at least one amino alcohol-substituted arylthienopyrimidinone of the invention or its derivative, and the use of the amino alcohol-substituted arylthienopyrimidinones of the invention and their derivatives as MCH antagonists.

主权项

1. A compound of formula Iwherein:D is N, or C(R1″);R1, R1′, R1′″ are independently of one another H, F, Cl, Br, I, OH, CF3, NO2, CN, OCF3, O—(C1-C6)-alkyl, (C1-C4)-alkoxy-(C1-C4)-alkyl, S—(C1-C6)-alkyl, (C1-C6)-alkyl, (C2-C6)-alkenyl, (C3-C8)-cycloalkyl, O—(C3-C8)-cycloalkyl, (C3-C8)-cycloalkenyl, (C2-C6)-alkynyl, (C1-C8)-alkylene-(C3-C8)-cycloalkyl, S-aryl, N(R3)(R4), SO2—CH3, COOH, COO—(C1-C6)-alkyl, CON(R5)(R6), N(R7)CO(R8), N(R9)SO2(R10), CO(R11), (C(R12)(R13))x-O(R14), or (C2-C6)-alkynyl-O(R14′);R3, R4, R5, R6, R7, and R9 areindependently of one another H, or (C1-C8)-alkyl,orR3 and R4, or R5 and R6independently of one another taken together with the nitrogen atom to which they are bonded form a 5-6 membered ring which optionally comprises one additional heteroatom selected from the group consisting of NH, N—(C1-C6)-alkyl, oxygen and sulfur;R8, R10, and R11 areindependently of one another H, or (C1-C8)-alkyl;R12 and R13 are independently of one another H, or (C1-C8)-alkyl;R14, and R14′ areindependently of one another H, or (C1-C6)-alkyl;x is 0, 1, 2, 3, 4, 5, or 6;R2 is H, F, Cl, Br, I, OH, CF3, NO2, CN, OCF3, O—(C1-C6)-alkyl, O—(C1-C4)-alkoxy-(C1-C4)-alkyl, S—(C1-C6)-alkyl, (C1-C6)-alkyl, (C2-C6)-alkenyl, (C3-C8)-cycloalkyl, O—(C3-C8)-cycloalkyl, (C2-C6)-alkynyl, aryl which is optionally substituted with F, Cl, Br, O—(C1-C6)-alkyl, (C1-C6)-alkyl, CO(C1-C6)-alkyl;R27 is H, or (C1-C6)-alkyl;X is S or O;A is a bond or a linker having 1 to 8 members, where the members are selected from the group consisting of O, S, SO2, N(R31), CO, C(R32)(R33), C(R34)=C(R34′), cyclopropylene, andC≡C;R31, R34, and R34′ areindependently of one another H, or (C1-C8)-alkyl;R32 and R33 areindependently of one another H, (C1-C6)-alkyl, OH, or O—(C1-C6)-alkyl;B is H, N(R35)(R36), hydroxy-(C1-C4)-alkyl, (C1-C8)-alkyl, (C1-C4)-alkoxy-(C1-C4)-alkyl, (C2-C8)-alkenyl, (C2-C8)-alkynyl, or a 3 to 10-membered mono-, bi-, tri- or spirocyclic nonaromatic ring which optionally comprises 0 to 4 heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur, wherein the ring system is optionally substituted one or more times by F, Cl, Br, CF3, NO2, CN, (C1-C6)-alkyl, O—(C1-C8)-alkyl, (C1-C4)-alkoxy-(C1-C4)-alkyl, hydroxy-(C1-C4)-alkyl, oxo, CO(R37), CON(R38)(R39), hydroxy, COO(R40), N(R41)CO(C1-C6)-alkyl, N(R42)(R43), SO2CH3, SCF3 or S—(C1-C6)-alkyl, and the ring system may be linked to A by ═C(R43′);R35, R36, R37, R38, R39, R40, R41, R42, R43, and R43′ are independently of one another H, or (C1-C8)-alkyl,orR38 and R39, or R42 and R43independently of one another taken together with the nitrogen atom to which they are bonded form a 5-6 membered ring which optionally comprises one additional heteroatom selected from the group consisting of NH, N—(C1-C6)-alkyl, oxygen and sulfur;L is a bond, or (C1-C3)-alkylene;Q is a group selected fromis independently of one another H, (C(C1-C4)-alkoxy-(C1-C4)-alkyl, (C3-C8)-alkenyl, (C3-C8)-alkynyl, CO—(C1-C6)-alkyl, CO(R57), (C(R58)(R59))q-R60, CO(C(R61)(R62)), R63, CO(C(R61)(R62))rN(R76)(R77), or CO—(CH2)o′—O—(C1-C6)-alkyl,o′ is 0, 1, 2, 3, 4, 5 or 6;R58 and R59 areindependently of one another H, (C1-C6)-alkyl, or OH;R57, R61, R62, R64, R65, R66, R67, R68, R69, R70, and R71 are independently of one another H, or (C1-C6)-alkyl,orR69 and R70taken together with the nitrogen atom to which they are bonded form a 5-6 membered ring which optionally comprises one additional heteroatom selected from the group consisting of NH, N—(C1-C6)-alkyl, oxygen and sulfur;q and r are independently of one another 0, 1, 2, 3, 4, 5 or 6;R60 and R63 areindependently of one another OH, F, O—(C1-C6)-alkyl, CN, COO(R78), N(R74)CO(C1-C6)-alkyl, N(R76)(R77), CON(R72)(R73), SO2(C1-C6)-alkyl, or a 3-12 membered mono-, bi- or spirocyclic ring which optionally comprises one or more heteroatoms from the group consisting of N, O and S, and the 3-12 membered ring is optionally substituted by F, Cl, Br, OH, CF3, NO2, CN, OCF3, oxo, O—(C1-C6)-alkyl, (C1-C4)-alkoxy-(C1-C4)-alkyl, S—(C1-C6)-alkyl, (C1-C6)-alkyl, (C2-C6)-alkenyl, (C3-C8)-cycloalkyl, O—(C3-C8)-cycloalkyl, (C3-C8)-cycloalkenyl, O—(C3-C8)-cycloalkenyl, (C2-C6)-alkynyl, N(R76)(R77), COO(R78), SO2(C1-C6)-alkyl or COOH; andR72, R73, R74, R76, R77, and R78 areindependently of one another H, or (C1-C8)-alkyl,orR72 and R73, or R76 and R77independently of one another taken together with the nitrogen atom to which they are bonded form a 5-6 membered ring which optionally comprises one additional heteroatom selected from the group of NH, N—(C1-C6)-alkyl, oxygen and sulfur;provided that when L is (C1-C3)-alkylene, then B is not, a cycloalkyl radical, an alk-2-en-1-yl radical or a cycloalk-2-en-1-yl radical, and A does not contain the moiety C(R34)=C(R34′);or a pharmaceutically acceptable salt thereof.