Azaspiro derivatives

A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula I

• wherein
• U—V is —CH═CH—, or
• U—V is —CH2—CH2—,
• one of the variables W, X, Y and Z are nitrogen, the remaining variables being CR8;
• R1 is H,
• C1-12-alkyl, optionally substituted with CN or OH,
• C1-6-haloalkyl,
• C2-12-alkenyl,
• —(CRiRii)m—Ra,
• wherein Ri and Rii are independently from each other H, methyl, or ethyl;
• wherein m is from 0 to 4;
• wherein Ra is
• phenyl, 5- to 6-membered heteroaryl, 3- to 7-membered heterocycloalkyl or 3 to 7-membered cyloalkyl, which are optionally substituted with one or more A, or
• —NRbRc, wherein Rb and Rc are each independently
• hydrogen,
• hydroxy,
• C1-6-alkyl,
• —S(O)2—C1-6-alkyl, or
• —C(O)—C1-6-alkyl,
• —(CRiiiRiv)n—C(O)Rd,
• wherein Riii and Riv are independently from each other H, methyl, or ethyl;
• wherein n is from 0 to 4;
• wherein Rd is
• C1-6-alkoxy,
• —NReRf, wherein Re and Rf are each independently
• hydrogen,
• C1-6-alkyl, or
• —(C2-6-alkylene)-NRgRh;
• wherein Rg and Rh are each independently hydrogen, C1-6-alkyl, or —C(O)O—C1-6-alkyl, or
• phenyl, 5- to 6-membered heteroaryl, 3- to 7-membered heterocycloalkyl or 3 to 7-membered cyloalkyl, which are optionally substituted with one or more A, —S(O)2-phenyl, wherein phenyl is optionally substituted with one or more halo,
• C1-6-haloalkyl, C1-6-alkoxy, C1-6-haloalkoxy, nitro, hydroxy or cyano;
• —S(O)2—C1-6-alkyl,
• —S(O)2N(C1-6-alkyl)2, or
• —S(O)2NH(C1-6-alkyl);
• A is halo, C1-6-alkyl, C1-6-haloalkyl, C1-6-hydroxyalkyl, C1-6-cyanoalkyl, C1-6-alkoxy, C1-6-haloalkoxy, —S(O)0-2C1-6-alkyl, nitro, hydroxy, cyano, —(C1-6-alkylene)-O—C1-6-alkyl, —(C1-6-alkylene)-O—C1-6-haloalkyl, —(C1-6-alkylene)-OR″′, —C(O)OC1-6-alkyl, —C(O)OR″′, —C(O)R″′, —C(O)NR′R″, —S(O)2NR′R″, —(CH2)x—NR′R″, —(CH2)x—NR′C(O)—C1-6-alkyl, —(CH2)x—NR′S(O)2—C1-6-alkyl, —(CH2)x—C3-6-cycloalkyl, or —(CH2)x—R′″,
• wherein x is from 0 to 4,
• R′ and R″ are each independently H or C1-6-alkyl, or
• R′ and R″ together with the nitrogen to which they are bound form a 5 or 6-membered heterocycle comprising one or two heteroatoms selected from N, O and S, and
• R″′ is phenyl or 5- to 6-membered heteroaryl, optionally substituted with one, two, or three halo, C1-6-haloalkyl, C1-6-alkyl, or C1-6-alkoxy,
• R2 is hydrogen, C1-6-alkyl, or —C(O)Rn, wherein Rn is C1-6-alkyl, 3 to 7-membered heterocycloalkyl, optionally substituted with one, two or three C1-6-alkyl, —C(O)O—C1-6-alkyl, or —S(O)2—C1-6-alkyl, or
• NRjRk, wherein Rj and Rk are each independently
• hydrogen,
• C1-6-alkyl, or
• —(C2-6-alkylene)-NRlRm;
• wherein Rl and Rm are each independently hydrogen, C1-6-alkyl, or —C(O)O—C1-6-alkyl;
• R3, R4, R5, R6 are each independently hydrogen, halo, C1-6-alkyl, halo-C1-6-alkyl, C1-6-alkoxy or halo-C1-6-alkoxy;
• or R1 and R6 together with the indole ring to which they are attached form a 6 membered heterocycle which is optionally substituted with residues selected from ═O, C(O)O—C1-6-alkyl and C1-6-alkyl;
• R7 is hydrogen or C1-6-alkyl;
• R8 is hydrogen, halo, methyl, methoxy, CF3, or OCF3;
• wherein 5- to 6-membered heteroaryl is selected from the group consisting of pyrrolyl, pyrazolyl, imidazolyl, furanyl, thiophenyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, and pyridazinyl;
• and
• 3- to 7-membered heterocycloalkyl is selected from the group consisting of oxiranyl, thiiranyl, aziridinyl, oxetanyl, azetidinyl, tetrahydro-furanyl, tetrahydro-thiophenyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, oxazidinyl, isoxazidinyl, thiazolidinyl, isothiazolidinyl, piperidinyl, piperazidinyl, morpholinyl, and tetrahydropyranyl;
• or a pharmaceutically acceptable salt thereof.