Inhibitor compounds of phosphodiesterase type 10A

A compound of formula (I)

• or a pharmaceutically acceptable salt thereof;
• where in form (I) the moiety of the formula Het1/2
• is selected from the following radicals Het1/2a to Het1/2q:
• where Rb is hydrogen or has one of the meanings given for R;
• Het2 is phenyl or a 5- or 6-membered monocyclic hetaryl, which has one heteroatom, selected from the group consisting of O, S and N as a ring member and optionally one or two further heteroatoms or heteroatom moieties independently selected from the group consisting of O, S, N and N—R1a as ring members, where phenyl and the 5- or 6 membered hetaryl are unsubstituted or carry, independently of each other, 1, 2 or 3, radicals R1;
• Cyc is selected from the group consisting of
• i. monocyclic 5-membered hetaryl having 1 or 2 nitrogen atoms and optionally a further heteroatom selected from the group consisting of O, S and N as ring members, which is unsubstituted or may carry 1, 2, 3 or 4 identical or different substituents R2, or
• monocyclic 6-membered hetaryl, which is selected from the group consisting of 2-pyrimidinyl, 4-pyrimidinyl, 2-pyrazinyl, and 3-pyridazinyl, where the monocyclic 6-membered hetaryl is unsubstituted or may carry 1, 2, 3 or 4 identical or different substituents R2,
• ii. fused 8-, 9- or 10-membered bicyclic hetaryl having one heteroatom selected from the group consisting of O, S and N and optionally 1, 2 or 3 nitrogen atoms as ring members, where the fused bicyclic hetaryl is selected from the group consisting of 3-isoquinolinyl, 2-quinoxalinyl, 1,5-naphthyridin-2-yl, 1,8-naphthyridin-2-yl, benzothiazol-1-yl, benzoxazol-1-yl, benzimidazol-2-yl, 1-methylbenzimidazol-2-yl, imidazo[1,2-a]pyridine-2-yl, pyrrolo[2,3-b]pyridine-6-yl, thieno[3,2-b]pyridine-5-yl, imidazo-[2,1-b]-thiazol-6-yl, and 1,2,4-triazolo[1,5-a]pyridine-2-yl, where the fused bicyclic hetaryl is unsubstituted or may carry 1, 2, 3 or 4 identical or different substituents R2,
• iii. phenyl, which carries a monocyclic hetaryl radical having 1 or 2 nitrogen atoms and optionally a further heteroatom selected from the group consisting of O, S and N as ring members, which in addition to monocyclic hetaryl, may carry 1, 2 or 3 identical or different substituents R2a, and
• iv. C5-C8-cycloalkyl or saturated or partially unsaturated, 5- to 10-membered heteromonocyclic or heterobicyclic radical, having 1, 2 or 3 heteroatoms or heteroatom moieties independently selected from the group consisting of O, S, S═O, S(═O)2, N and N—R1a as ring members, and which may carry 1, 2 or 3 identical or different substituents R2b;
• Ar is a radical of the following formula
• wherein
• X1 is N or C—Rx1;
• X2 is N or C—Rx2;
• X3 is N or C—Rx3;
• X4 is N or C—Rx4;
• provided that 0, 1 or 2 of X1, X2, X3 and X4 are N;
• and where Rx1, Rx2, Rx3, Rx4, independently of each other, are hydrogen or have one of the meanings given for R3;
• R is selected from the group consisting of halogen, CN, NR13R14, C(O)NR13R14, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, trimethylsilyl, C1-C6-alkylsulfanyl, C1-C6-alkylsulfonyl, fluorinated C1-C6-alkylsulfanyl, fluorinated C1-C6-alkylsulfonyl, C1-C4-alkyl-OR11, C1-C4-alkyl-SR12, C1-C4-alkyl-NR13R14, C1-C6-alkoxy, OC1-C4-alkyl-OR11, OC1-C4-alkyl-SR12, OC1-C4-alkyl-NR13R14, C2-C6-alkenyloxy, C1-C6-fluoroalkyl, C1-C6-fluoroalkoxy, C3-C6-cycloalkyl and C3-C6-cycloalkyl-C1-C4-alkyl, where the cycloalkyl moiety in the last two radicals is unsubstituted, partially or completely fluorinated, or substituted by 1, 2 or 3 methyl groups;
• Ra is selected from the group consisting of hydrogen, C(O)NR13R14, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, trimethylsilyl, C1-C4-alkyl-OR11, C1-C4-alkyl-SR12, C1-C4-alkyl-NR13R14, C1-C6-fluoroalkyl, C1-C6-fluoroalkoxy, C3-C6-cycloalkyl and C3-C6-cycloalkyl-C1-C4-alkyl, where the cycloalkyl moiety in the last two radicals is unsubstituted, partially or completely fluorinated, or substituted by 1, 2 or 3 methyl groups;
• two radicals R or the radical R together with the radical Ra, if attached to adjacent ring atoms, may also form a linear C3-C5-alkanediyl, wherein 1 or 2 CH2 moieties can be replaced by C═O, O, S, S(═O), S(═O)2 or NR′, and where alkanediyl is unsubstituted or may carry 1 or 2 radicals independently selected from the group consisting of halogen, C1-C4-alkyl, C1-C4-fluoroalkyl, C1-C4-alkoxy and C1-C4-fluoroalkoxy;
• R1 is attached to a carbon atom of Het2 and selected from the group consisting of halogen, CN, NR13R14, C(O)NR13R14, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, trimethylsilyl, C1-C6-alkylsulfanyl, C1-C6-alkylsulfonyl, fluorinated C1-C6-alkylsulfanyl, fluorinated C1-C6-alkylsulfonyl, C1-C4-alkyl-OR11, C1-C4-alkyl-SR12, C1-C4-alkyl-NR13R14, C1-C6-alkoxy, OC1-C4-alkyl-OR11, OC1-C4-alkyl-SR12, OC1-C4-alkyl-NR13R14, C2-C6-alkenyloxy, C1-C6-fluoroalkyl, C1-C6-fluoroalkoxy, C3-C6-cycloalkyl and C3-C6-cycloalkyl-C1-C4-alkyl, where the cycloalkyl moiety in the last two radicals is unsubstituted, partially or completely fluorinated, or substituted by 1, 2 or 3 methyl groups;
• R1a is selected from the group consisting of hydrogen, C(O)NR13R14, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, trimethylsilyl, C1-C4-alkyl-OR11, C1-C4-alkyl-SR12, C1-C4-alkyl-NR13R14, C1-C6-fluoroalkyl, C1-C6-fluoroalkoxy, C3-C6-cycloalkyl and C3-C6-cycloalkyl-C1-C4-alkyl, where the cycloalkyl moiety in the last two radicals is unsubstituted, partially or completely fluorinated, or substituted by 1, 2 or 3 methyl groups;
• R2 is selected from the group consisting of halogen, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-fluoroalkyl, C1-C4-fluoroalkoxy, C1-C4-alkoxy-C1-C4-alkoxy, C1-C4-alkoxy-C1-C4-alkyl, OH, hydroxy-C1-C4-alkyl, O—C3-C6-cycloalkyl, benzyloxy, C(O)O—(C1-C4-alkyl), O—(C1-C4-alkyl)-CO2H, NR23R24, C(O)NR23R24, C1-C4-alkyl-NR23R24, —NR25—C(O)—NR23R24, NR25—C(O)O—(C1-C4-alkyl), —NR25—SO2—R22, phenyl, CN, —SF5, —OSF5, —SO2R22, —SR22, trimethylsilyl and C3-C6-cycloalkyl, where the cycloalkyl moiety in the last radical is unsubstituted, partially or completely fluorinated, or substituted by 1, 2 or 3 methyl groups, or two radicals R2, which are bound to adjacent ring atoms may also form a linear C3-C5-alkanediyl, wherein 1 or 2 CH2 moieties can be replaced by C═O, O, S, S(═O), S(═O)2 or NR′, and where alkanediyl is unsubstituted or may carry 1 or 2 radicals independently selected from the group consisting of halogen, C1-C4-alkyl, C1-C4-fluoroalkyl, C1-C4-alkoxy and C1-C4-fluoroalkoxy;
• R2a has one of the meanings given for R2 or one radical R2a may also be a 5- or 6-membered hetaryl having 1 or 2 nitrogen atoms and optionally a further heteroatom selected from the group consisting of O, S and N as ring members, where hetaryl is unsubstituted or may carry 1, 2 or 3 radicals independently selected from the group consisting of halogen, OH, C1-C4-haloalkyl, C1-C4-alkoxy and C1-C4-haloalkoxy;
• R2b is selected from the group consisting of halogen, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-fluoroalkyl, C1-C4-fluoroalkoxy, C3-C6-cycloalkyl, C1-C4-alkoxy-C1-C4-alkoxy, C1-C4-alkoxy-C1-C4-alkyl, OH, hydroxy-C1-C4-alkyl, O—C3-C6-cycloalkyl, benzyloxy, C(O)O—(C1-C4-alkyl), O—(C1-C4-alkyl)-CO2H, NR23R24, C(O)NR23R24, C1-C4-alkyl-NR23R24, —NR25—C(O)—NR23R24, NR25—C(O)O—(C1-C4-alkyl), —NR25—SO2—R22, phenyl, CN, —SF5, —OSF5, —SO2R22, —SR22 and trimethylsilyl, or
• two radicals R2a, which are bound to adjacent ring atoms may also form a fused benzene ring or a fused 5- or 6-membered heteroaromatic ring, having 1 ring member selected from the group consisting of O, S, N or NR′ and optionally 1 or 2 further N-atoms as ring members, where the fused benzene or heteroaromatic ring is unsubstituted or may carry 1, 2, 3 or 4 radicals independently selected from the group consisting of halogen, OH, C1-C4-alkyl, C1-C4-fluoroalkyl, C1-C4-alkoxy and C1-C4-fluoroalkoxy;
• R3 independently of each other, are selected from the group consisting of halogen, CN, NR33R34, C(O)NR33R34, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, trimethylsilyl, C1-C6-alkylsulfanyl, C1-C6-alkylsulfonyl, fluorinated C1-C6-alkylsulfanyl, fluorinated C1-C6-alkylsulfonyl, C1-C4-alkyl-OR31, C1-C4-alkyl-SR32, C1-C4-alkyl-NR33R34, C1-C6-alkoxy, OC1-C4-alkyl-OR31, OC1-C4-alkyl-SR32, OC1-C4-alkyl-NR33R34, C2-C6-alkenyloxy, C1-C6-fluoroalkyl, C1-C6-fluoroalkoxy, C3-C6-cycloalkyl and C3-C6-cycloalkyl-C1-C4-alkyl, where the cycloalkyl moiety in the last two radicals is unsubstituted, partially or completely fluorinated, or substituted by 1, 2 or 3 methyl groups;
• R11, and R12 independently of each other are selected from the group consisting of hydrogen, C1-C4-alkyl, C1-C4-fluoroalkyl, C3-C6-cycloalkyl and C3-C6-cycloalkyl-C1-C4-alkyl, where R11 may also be C1-C4-alkylsulfonyl or C1-C4-fluoroalkylsulfonyl;
• R13, and R14 independently of each other are selected from the group consisting of hydrogen, C1-C4-alkyl, C1-C4-fluoroalkyl C3-C6-cycloalkyl and C3-C6-cycloalkyl-C1-C4-alkyl, or
• R13 and R14 together with the N atom to which they are attached form a 3- to 7-membered, nitrogen heterocycle which may have 1, 2 or 3 further different or identical heteroatoms or heteroatom containing groups selected from the group consisting of O, N, S, SO and SO2 as ring members and which may carry 1, 2, 3, 4, 5 or 6 substituents independently selected from the group consisting of C1-C4-alkyl and fluorine;
• R22, R31 and R32 have one of the meanings given for R11, or R12;
• R23, R24, R33 and R34 have one of the meanings given for R13, or R14;
• R25 is selected from the group consisting of hydrogen, C1-C4-alkyl, C1-C4-fluoroalkyl, C3-C6-cycloalkyl and C3-C6-cycloalkyl-C1-C4-alkyl;
• and
• R′ is selected from the group consisting of hydrogen, C1-C4-alkyl, C1-C4-fluoroalkyl, C3-C6-cycloalkyl and C3-C6-cycloalkyl-C1-C4-alkyl.