Azolopyridin-3-one derivatives as inhibitors of lipases and phospholipases

A compound of the formula I

• where:
• X is S Or SO2;
• R1 is (C5-C16)-alkyl,
• a radical of the formula Ia
• in which
• R5 is hydrogen, (C1-C3)-alkyl;
• R6, R7, R8, R9, R10
• are each independently hydrogen, F, Cl, Br, I, OH, CF3, NO2, CN, OCF3, OCHF2, O—(C1-C6)-alkyl, O—(C1-C4)-alkoxy-(C1-C4)-alkyl, S—(C1-C6)-alkyl, (C1-C6)-alkyl, (C2-C4)-haloalkyl, O—(C2-C4)-haloalkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, N(R11)(R12), SO2—CH3, SO2—N(R13)(R14), SF5, SCF3, COOH, COO—(C1-C6)-alkyl, CON(R15)(R16), N(R17)CO(R18), N(R19)SO2(R20), CO(R21), (CR22R23)x-O(R24), (CR22R23)x-CO—O(R24), O—(CR22R23)x-CO—O(R24), (CR22R23)x-N(R25)(R26), O—(CR22R23)x-N(R25)(R26), (CR22R23)x-CON(R25)(R26), O—(CR22R23)x-CON(R25)(R26), O—CO—N(R25)(R26), O—CO—(C1-C6)-alkylene-CO—O—(C1-C6)-alkyl, O—CO—(C1-C6)-alkylene-CO—OH, O—CO—(C1-C6)-alkylene-CO—N(R27)(R28);
• with the proviso that at least one R6, R7, R8, R9, R10 radical is not hydrogen;
• x is independently 0, 1, 2, 3, 4, 5, 6;
• or
• R7 or R8 is
• (O)y—(CH2—)y′—(O)y″—(CH2)y′″—R100;
• y, y″ are each independently 0,1;
• y′, y′″ are each independently 1, 2, 3, 4, 5, 6;
• R100 is a 4- to 10-membered mono- or bicyclic saturated, partly unsaturated or aromatic ring which may contain 1 to 4 heteroatoms selected from the group of oxygen, nitrogen and sulfur, where the ring system may optionally be mono- or polysubstituted by 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-C4)-haloalkyl, (C2-C6)-alkenyl, (C3-C8)-cycloalkyl, O—(C3-C8)-cycloalkyl, (C2-C6)-alkynyl, N(R29)(R30), SO2—CH3, SF5, COOH, COO—(C1-C6)-alkyl, CON(R31)(R32), N(R33)CO(R34), N(R35)SO2(R36), CO(R37), (CR38R39)x′-O(R40), (CR38R39)x′-CO—O(R40), O—(CR22R23)x′-CO—O(R40), (CR22R23)x′-N(R41)(R42), O—(CR38R39)x′-N(R41)(R42), (CR38R39)x′-CON(R41)(R42), O—(CR38R39)x′-CON(R41)(R42), O—CO—N(R41)(R42), O—CO—(C1-C6)-alkylene-CO—O—(C1-C6)-alkyl, O—CO—(C1-C6)-alkylene-CO—OH, O—CO—(C1-C6)-alkylene-CO—N(R43)(R44);
• x′ is 0, 1, 2, 3, 4, 5, 6;
• or
• R7 and R8 or R8 and R9 or R9 and R10
• together with the carbon atom which bears them form a monocyclic, 5- to 7-membered saturated, partly unsaturated or aromatic ring system whose individual members may be optionally substituted by —CHR45-, —CR46R47-, ═(C—R46)-, O, N or S;
• with the proviso that no two units from the group of —O—, N and —S— may be adjacent;
• R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, R21, R22, R23, R24, R25, R26, R27, R28, R29, R30, R31, R32, R33, R34, R35, R36, R37, R38, R39, R40, R41, R42, R43, R44
• are each independently hydrogen, (C1-C6)-alkyl;
• or
• R11 and R12, R13 and R14, R15 and R16, R25 and 26, R27 and R28, R29 and R30, R31 and R32, R41 and 42, R43 and 44
• each independently form, optionally together with the nitrogen atom to which they are bonded, a 5-6-membered ring which, apart from the nitrogen atom, may optionally include 0-1 further heteroatom from the group of NH, N—(C1-C6)-alkyl, oxygen and sulfur;
• R45, R46, R47 are the same or different and are each F, Cl, Br, I, OH, CF3, NO2, CN, OCHF2, OCF3, SF5, O—(C1-C6)-alkyl, O—(C1-C4)-alkoxy-(C1-C4)-alkyl, S—(C1-C6)-alkyl, (C1-C6)-alkyl, (C2-C4)-haloalkyl, O—(C2-C4)-haloalkyl, (C2-C6)-alkenyl, (C3-C8)-cycloalkyl, O—(C3-C8)-cycloalkyl, (C2-C6)-alkynyl, N(R134)(R135), SO2—CH3, COOH, COO—(C1-C6)-alkyl, CON(R136)(R137), N(R138)CO(R139), N(R140)SO2(R141), CO(R142), (CR143R144)x″-O(R145), (CR143R144)x″-CO—O(R145), O—(CR143R144)x″-CO—O(R145), (CR143R144)x″-N(R146)(R147), O—(CR143R144)x″-N(R146)(R147), (CR143R144)x″-CON(R146)(R147), O—(CR143R144)x″-CON(R146)(R147), O—CO—N(R146)(R147), O—CO—(C1-C6)-alkylene-CO—O—(C1-C6)-alkyl, O—CO—(C1-C6)-alkylene-CO—OH, O—CO—(C1-C6)-alkylene-CO—N(R148)(R149);
• x″ is independently 1, 2, 3, 4, 5, 6;
• R134, R135, R136, R137, R138, R139, R140, R141, R142, R143, R144, R145, R146, R147, R148, R149
• are the same or different and are each hydrogen, (C1-C6)-alkyl;
• a radical of the formula Ib
• in which
• R5 is hydrogen, (C1-C3)-alkyl;
• Het is a 4- to 10-membered mono- or bicyclic aromatic ring containing 1 to 4 heteroatoms selected from the group of oxygen, nitrogen and sulfur, where the ring system may optionally be mono- or polysubstituted independently by F, Cl, Br, I, OH, CF3, NO2, CN, OCF3, OCHF2, O—(C1-C6)-alkyl, O—(C1-C4)-alkoxy-(C1-C4)-alkyl, S—(C1-C6)-alkyl, (C1-C6)-alkyl, (C2-C4)-haloalkyl, O—(C2-C4)-haloalkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, N(R48)(R49), SO2—CH3, SO2—N(R50)(R51), SF5, SCF3, COOH, COO—(C1-C6)-alkyl, CON(R52)(R53), N(R54)CO(R55), N(R56)SO2(R57), CO(R58), (CR59R60)x′″-O(R61), (CR59R60)x′″-CO—O(R61), O—(CR59R60)x′″-CO—O(R61), (CR59R60)x′″-N(R62)(R63), O—(CR59R60)x′″-N(R62)(R63), (CR59R60)x′″-CON(R62)(R63), O—(CR59R60)x′″-CON(R62)(R63), O—CO—N(R62)(R63), O—CO—(C1-C6)-alkylene-CO—O—(C1-C6)-alkyl, O—CO—(C1-C6)-alkylene-CO—OH, O—CO—(C1-C6)-alkylene-CO—N(R64)(R65);
• or (O)y—(CH2—)y′—(O)y′″—(CH2)y′″—R101,
• x′″ is independently 1, 2, 3, 4, 5, 6;
• y, y″ are each independently 0,1;
• y′, y′″ are each independently 0, 1, 2, 3, 4, 5, 6;
• R101 is a 4- to 10-membered mono- or bicyclic saturated, partly unsaturated or aromatic ring which may contain 1 to 4 heteroatoms selected from the group of oxygen, nitrogen and sulfur, where the ring system may optionally be mono- or polysubstituted by F, Cl, Br, I, OH, CF3, NO2, CN, OCHF2, OCF3, O—(C1-C6)-alkyl, O—(C1-C4)-alkoxy-(C1-C4)-alkyl, S—(C1-C6)-alkyl, (C1-C6)-alkyl, (C2-C4)-haloalkyl, (C2-C6)-alkenyl, (C3-C8)-cycloalkyl, O—(C3-C8)-cycloalkyl, (C2-C6)-alkynyl, N(R66)(R67), SO2—CH3, SFS, COOH, COO—(C1-C6)-alkyl, CON(R68)(R69), (C), N(R70)CO(R71), N(R72)SO2(R73), CO(R74), (CR75R76)x″″-O(R77R75R76)x″″-CO—O(R77), O—(CR75R76)x″″-CO—O(R77), (CR75R76)x″″-N(R78)(R79), O—(CR75R76)x″″-N(R78)(R79), (CR75R76)x″″-CON(R78)(R79), O—(CR75R76)x″″-CON(R78)(R79), O—CO—N(R78)(R79), O—CO—(C1-C6)-alkylene-CO—O—(C1-C6)-alkyl, O—CO—(C1-C6)-alkylene-CO—OH, O—CO—(C1-C6)-alkylene-CO—N(R80)(R81);
• x″″ is independently 1, 2, 3, 4, 5, 6;
• R48, R49, R50, R51, R52, R53, R54, R55, R56, R57, R58, R59, R60, R61, R62, R63, R64, R65, R66, R67, R68, R69, R70, R71, R72, R73, R74, R75, R76, R77, R78, R79, R80, R81
• are each independently hydrogen, (C1-C6)-alkyl;
• or
• R48 and R49, R50 and R51, R52 and R53, R62 and R63, R64 and R65, R66 and R67, R68 and R69, R78 and R79, R80 and R81
• each independently form, optionally together with the nitrogen atom to which they are bonded, a 5-6-membered ring which, apart from the nitrogen atom, may optionally include 0-1 further heteroatom from the group of NH, N—(C1-C6)-alkyl, oxygen and sulfur;
• a radical of the formula Ic
• in which
• W is —C(R126)(R127)-, —C(R126)(R127)-C(R128)(R129)-, —C(R126)(R127)-O—;
• R120, R121, R122, R123, R124, R125, R126, R127, R128, R129
• are the same or different and are each hydrogen, F, Cl, Br, I, OH, CF3, NO2, CN, OCHF2, OCF3, SF5, O—(C1-C6)-alkyl, O—(C1-C4)-alkoxy-(C1-C4)-alkyl, S—(C1-C6)-alkyl, (C1-C6)-alkyl, (C2-C4)-haloalkyl, O—(C2-C4)-haloalkyl, (C2-C6)-alkenyl, (C3-C8)-cycloalkenyl, (C2-C6)-alkynyl, N(R90)(R91), SO2—CH3, COOH, COO—(C1-C6)-alkyl, CON(R92)(R93), N(R94)CO(R95), N(R96)SO2(R97), CO(R98), (CR99R102)z-O(R103), (CR99R76)z-CO—O(R103), O—(CR99R102)z-CO—O(R103), (CR99R102)z-N(R104)(R105), O—(CR99R102)z-N(R104)(R105), (CR99R102)z-CON(R104)(R105), O—(CR99R102)z-CON(R104)(R105), O—CO—N(R104)(R105), O—CO—(C1-C6)-alkylene-CO—O—(C1-C6)-alkyl, O—CO—(C1-C6)-alkylene-CO—OH, O—CO—(C1-C6)-alkylene-CO—N(R106)(R107);
• z is independently 1, 2, 3, 4, 5, 6;
• R90, R91, R92, R93, R94, R95, R96, R97, R98, R99, R102, R103, R104, R105, R106, R107
• are the same or different and are each hydrogen, (C1-C6)-alkyl;
• or
• R120 and R126 or R121 and R127 together with the carbon atom which bears them form a monocyclic, 5- or 6-membered saturated, partly unsaturated or aromatic ring system whose individual members may be optionally substituted by —CHR130-, —CR131R132-, ═(C—R133)-;
• or
• R122 and R124, or R123 and R125 together with the carbon atom which bears them form a monocyclic, 5- or 6-membered saturated, partly unsaturated or aromatic ring system whose individual members may be optionally substituted by —CHR130-, 13 CR131R132-, ═(C—R133)-;
• R130, R131, R132, R133 are the same or different and are each F, Cl, Br, I, OH, CF3, NO2, CN, OCHF2, OCF3, SF5, O—(C1-C6)-alkyl, O—(C1-C4)-alkoxy-(C1-C4)-alkyl, S—(C1-C6)-alkyl, (C1-C6)-alkyl, (C2-C4)-haloalkyl, O—(C2-C4)-haloalkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, N(R160)(R161), SO2—CH3, COOH, COO—(C1-C6)-alkyl, CON(R162)(R163), N(R164)CO(R165), N(R166)SO2(R167), CO(R168), (CR169R170)z′-O(R171), (CR169R170)z′-CO—O(R77), O—(CR169R170)z′-CO—O(R171), (CR169R170)z′-N(R172)(R173), O—(CR169R170)z′-N(R172)(R173), (CR169R170)z′-CON(R172)(R173), O—(CR169R170)z′-CON(R172)(R173), O—CO—N(R172)(R173), O—CO—(C1-C6)-alkylene-CO—O—(C1-C6)-alkyl, O—CO—(C1-C6)-alkylene-CO—OH, O—CO—(C1-C6)-alkylene-CO—N(R172)(R173);
• z′ is independently 1, 2, 3, 4, 5, 6;
• R160, R161, R162, R163, R164, R165, R166, R167, R168, R169, R170, R171, R172, R173 are the same or different and are each hydrogen, (C1-C6)-alkyl;
• or
• R160 and R161, R162 and R163, R172 and R173 each independently form, optionally together with the nitrogen atom to which they are bonded, a 5-6-membered ring which, apart from the nitrogen atom, may also optionally include 0-1 further heteroatom from the group of NH, N—(C1-C6)-alkyl, oxygen and sulfur;
• R2, R3, R4 are the same or different and are each hydrogen, F, Cl, Br, I, OH, CF3, NO2, CN, OCHF2, OCF3, SF5, O—(C1-C6)-alkyl, O—(C1-C4)-alkoxy-(C1-C4)-alkyl, S—(C1-C6)-alkyl, (C1-C6)-alkyl, (C2-C4)-haloalkyl, O—(C2-C4)-haloalkyl, (C2-C6)-alkenyl, (C3-C8)-cycloalkyl, O—(C3-C8)-cycloalkyl, (C3-C8)-cycloalkenyl, aryl, (C2-C6)-alkynyl, N(R200)(R201), SO2—CH3, COOH, COO—(C1-C6)-alkyl, CON(R202)(R203), N(R204)CO(R205), N(R206)SO2(R207), CO(R208), (CR209R210)z″-O(R211), (CR209R210)z″-CO—O(R211), O—(CR209R210)z″-CO—O(R211), (CR209R210)z″-N(R212)(R213), O—(CR209R210)z″-N(R212)(R213), (CR209R210)z″-CON(R212)(R213), O—(CR209R210)z″-CON(R212)(R213), O—CO—N(R212)(R213), O—CO—(C1-C6)-alkylene-CO—O—(C1-C6)-alkyl, O—CO—(C1-C6)-alkylene-CO—OH, O—CO—(C1-C6)-alkylene-CO—N(R212)(R213);
• z″ is independently 1, 2, 3, 4, 5, 6;
• R200, R201, R202, R203, R204R205, R206, R207, R208, R209, R210, R211, R212, R213 are the same or different and are each hydrogen, (C1-C6)-alkyl;
• or
• R200 and R201, R202 and R203, R212 and R213
• each independently form, optionally together with the nitrogen atom to which they are bonded, a 5-6-membered ring which, apart from the nitrogen atom, may optionally include 0-1 further heteroatom from the group of NH, N—(C1-C6)-alkyl, oxygen and sulfur;
• the tautomeric forms of the compound and the physiologically compatible salts and N-oxides thereof;
• with the proviso that the compounds where R2, R3, R4=hydrogen, X═S and R1=heptyl, nonyl or cyclohexyl are excluded.