4-amino-5,6-substituted thiopheno [2,3-d] pyrimidines, pharmaceutical compositions containing the same, and their use in the treatment or prevention of PDE7B-mediated diseases and conditions

A compound according to formula II:

• 145
• wherein
• R1 and R2 are independently selected from the group consisting of
• hydrogen,
• alkyl of 1-8 carbon atoms,
• alkenyl of 2-8 carbon atoms,
• alkynyl of 2-8 carbon atoms,
• cycloalkyl of 3-7 carbon atoms,
• heterocycloalkyl of 2-6 carbon atoms and 1-2 heteroatoms selected from NH, S and O,
• aryl of 6-12 carbon atoms, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O,
• heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, and
• R4—R5,
• or R1 and R2 combine to form, together with the nitrogen atom to which they are attached, a 5-7 membered saturated ring which may contain 1-2 additional heteroatoms selected from the group consisting of NH, NR1, S and O, or combine to form, together with the nitrogen atom to which they are attached, a 5-7 membered unsaturated ring which may contain 1-2 additional heteroatoms selected from the group consisting of N, S and O,
• wherein said saturated or unsaturated ring may be substituted with 1-2 substituents selected from the group consisting of OH, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 3-7 carbon atoms, heterocycloalkyl of 2-6 carbon atoms and 1-2 heteroatoms selected from NH, S and O, halogen, haloalkyl of 1-2 carbon atoms and a number of halogen atoms up to the perhalo level, alkoxy of 1-6 carbon atoms, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, and R9—R10;
• R3 is selected from the group consisting of:
• hydrogen,
• alkyl of 1-8 carbon atoms,
• alkenyl of 2-8 carbon atoms,
• alkynyl of 2-8 carbon atoms,
• cycloalkyl of 3-7 carbon atoms,
• heterocycloalkyl of 2-6 carbon atoms and 1-2 heteroatoms selected from NH, S and O,
• aryl of 6-12 carbon atoms, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O,
• heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, and
• R4—R5;
• R4 is selected from
• alkyl of 1-8 carbon atoms,
• alkenyl of 2-8 carbon atoms,
• alkynyl 2-8 carbon atoms,
• C(═O),
• S(═O)2, and
• C(═O)O—;
• R5 is selected from
• hydrogen,
• OH,
• alkyl of 1-8 carbon atoms,
• alkenyl 2-8 carbon atoms,
• alkynyl 2-8 carbon atoms,
• alkoxy of 1-8 carbon atoms,
• thioxy of 1-8 carbon atoms,
• aryl of 6-12 carbon atoms, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms and heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O,
• heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms and heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O,
• cycloalkyl of 3-7 carbon atoms,
• heterocycloalkyl of 2-6 carbon atoms and 1-2 heteroatoms selected from
• NH, S and O, and
• N—R6—R7,
• with the proviso that R5 is not OH, thioxy, alkoxy or N—R6—R7 when R4 is C(═O)O—, and with the further proviso that R5 is not alkyl when R4 is alkyl, alkenyl or alkynyl;
• R6 and R7 are independently selected from
• hydrogen,
• alkyl of 1-8 carbon atoms,
• alkenyl of 2-8 carbon atoms, and
• alkynyl of 2-8 carbon atoms,
• or R6 and R7 combine together with the nitrogen atom to which they are attached to form a 5-7 membered, unsaturated ring which may contain 1-2 additional heteroatoms selected from N, S and O or to form a 5-7 membered, saturated ring which may contain 1-2 additional heteroatoms selected from NH, NR11, S and O;
• R8 is selected from
• alkyl of 1-8 carbon atoms,
• alkenyl of 2-8 carbon atoms,
• alkynyl of 2-8 carbon atoms,
• R12—R13,
• cycloalkyl of 3-7 carbons atoms,
• heterocycloalkyl of 2-6 carbon atoms and 1-2 heteroatoms selected from NH, S and O,
• aryl of 6-12 carbon atoms, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O,
• heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O;
• R9 is selected from
• alkyl of 1-8 carbon atoms,
• alkenyl of 2-8 carbon atoms, and
• alkynyl of 2-8 carbon atoms;
• R10 is selected from
• OH,
• aryl of 6-12 carbon atoms, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, and
• heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O;
• R1 is benzyl which may be substituted with
• alkyl of 1-6 carbon atoms,
• alkenyl of 2-6 carbon atoms,
• alkynyl of 2-6 carbon atoms,
• halogen, and
• R14—R15;
• R12 is selected from
• alkyl of 1-8 carbon atoms,
• alkenyl of 2-8 carbon atoms, and
• alkynyl of 2-8 carbon atoms;
• R13 is selected from
• cycloalkyl of 3-7 carbon atoms,
• heterocycloalkyl of 2-6 carbon atoms and 1-2 heteroatoms selected from NH, S and O,
• aryl of 6-12 carbon atoms, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, and
• heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O;
• R14 is alkyl of 1-3 carbon atoms;
• R15 is cycloalkyl of 3-7 carbon atoms;
• with the proviso that when R3 is hydrogen,
• R1 and R2 are independently selected from the group consisting of
• hydrogen, with the further proviso that R1 and R2 are not both hydrogen,
• alkyl of 1-8 carbon atoms, with the further proviso that R1 and R are not both ethyl,
• alkenyl of 2-8 carbon atoms,
• alkynyl of 2-8 carbon atoms,
• heterocycloalkyl of 4-6 carbon atoms and 1-2 heteroatoms selected from NH, S
• and O, and
• bornyl,
• or R1 and R2 combine to form, together with the nitrogen atom to which they are attached,
• a 5-7 membered saturated ring which contains 1-2 sulfur atoms, or
• an 8-10 membered bicyclic saturated ring;
• and pharmaceutically acceptable salts thereof.

A compound according to formula III:

• 146
• wherein
• R1 and R2 are independently selected from the group consisting of
• hydrogen,
• alkyl of 1-8 carbon atoms,
• alkenyl of 2-8 carbon atoms,
• alkynyl of 2-8 carbon atoms,
• alkoxy of 1-8 carbon atoms,
• cycloalkyl of 3-7 carbon atoms,
• heterocycloalkyl of 2-6 carbon atoms and 1-2 heteroatoms selected from NH, S and O,
• aryl of 6-12 carbon atoms, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O,
• heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, and
• R4—R5,
• or R1 and R2 combine to form, together with the nitrogen atom to which they are attached, a 5-7 membered saturated ring which may contain 1-2 additional heteroatoms selected from the group consisting of NH, NR11, S and O, or combine to form, together with the nitrogen atom to which they are attached, a 5-7 membered unsaturated ring which may contain 1-2 additional heteroatoms selected from the group consisting of N, S and O,
• wherein said saturated or unsaturated ring may be substituted with 1-2 substituents selected from the group consisting of OH, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 3-7 carbon atoms, heterocycloalkyl of 2-6 carbon atoms and 1-2 heteroatoms selected from NH, S and O, halogen, haloalkyl of 1-2 carbon atoms and a number of halogen atoms up to the perhalo level, alkoxy of 1-6 carbon atoms, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, and R9—R10;
• R3 is selected from the group consisting of:
• hydrogen,
• alkyl of 1-8 carbon atoms,
• alkenyl of 2-8 carbon atoms,
• alkynyl of 2-8 carbon atoms,
• cycloalkyl of 3-7 carbon atoms,
• heterocycloalkyl of 2-6 carbon atoms and 1-2 heteroatoms selected from NH, S and O,
• aryl of 6-12 carbon atoms, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O,
• heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, and
• R4—R5,
• R4 is selected from
• alkyl of 1-8 carbon atoms,
• alkenyl of 2-8 carbon atoms,
• alkynyl of 2-8 carbon atoms,
• C(═O),
• S(═O)2, and
• C(═O)O—;
• R5 is selected from
• hydrogen,
• OH,
• alkyl of 1-8 carbon atoms,
• alkenyl 2-8 carbon atoms,
• alkynyl 2-8 carbon atoms,
• alkoxy of 1-8 carbon atoms,
• thioxy of 1-8 carbon atoms,
• aryl of 6-12 carbon atoms, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms and heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O,
• heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms and heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O,
• cycloalkyl of 3-7 carbon atoms,
• heterocycloalkyl of 2-6 carbon atoms and 1-2 heteroatoms selected from
• NH, S and O, and
• N—R6—R7,
• with the proviso that R5 is not OH, thioxy, alkoxy or N—R6—R7 when R4 is C(═O)O—, and with the further proviso that R5 is not alkyl when R4 is alkyl, alkenyl or alkynyl;
• R6 and R7 are independently selected from
• hydrogen,
• alkyl of 1-8 carbon atoms,
• alkenyl of 2-8 carbon atoms, and
• alkynyl of 2-8 carbon atoms,
• or R6 and R7 combine together with the nitrogen atom to which they are attached to form a 5-7 membered, unsaturated ring which may contain 1-2 additional heteroatoms selected from N, S and O or to form a 5-7 membered, saturated ring which may contain 1-2 additional heteroatoms selected from NH, NR11, S and O;
• R8 is selected from
• alkyl of 1-8 carbon atoms,
• alkenyl of 2-8 carbon atoms,
• alkynyl of 2-8 carbon atoms,
• R12—R13,
• cycloalkyl of 3-7 carbon atoms,
• heterocycloalkyl of 2-6 carbon atoms and 1-2 heteroatoms selected from NH, S and O,
• aryl of 6-12 carbon atoms, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O,
• heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O;
• R9 is selected from
• alkyl of 1-8 carbon atoms,
• alkenyl of 2-8 carbon atoms, and
• alkynyl of 2-8 carbon atoms;
• R10 is selected from
• OH,
• aryl of 6-12 carbon atoms, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, and
• heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O;
• R11 is benzyl which may be substituted with
• alkyl of 1-6 carbon atoms,
• alkenyl of 2-6 carbon atoms,
• alkynyl of 2-6 carbon atoms,
• halogen, and
• R14—R15;
• R12 is selected from
• alkyl of 1-8 carbon atoms,
• alkenyl of 2-8 carbon atoms, and
• alkynyl of 2-8 carbon atoms;
• R13 is selected from
• cycloalkyl of 3-7 carbon atoms,
• heterocycloalkyl of 2-6 carbon atoms and 1-2 heteroatoms selected from NH, S and O,
• aryl of 6-12 carbon atoms, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, and
• heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O;
• R14 is alkyl of 1-3 carbon atoms;
• R15 is cycloalkyl of 3-7 carbon atoms;
• with the proviso that when R3 is hydrogen,
• R1 and R2 are independently selected from the group consisting of
• hydrogen, with the further proviso that only one of R1 and R2 may be hydrogen,
• alkyl of 1-8 carbon atoms,
• alkenyl of 2-8 carbon atoms,
• alkynl of 2-8 carbon atoms,
• alkoxy of 1-8 carbon atoms,
• cycloalkyl of 3-7 carbon atoms,
• phenyl which may be substituted from one to five times with bromine, chlorine, CH3, or CF3, and
• R4—R5, with the further proviso that if R4 is methyl then R5 may not be a five membered ring that contains oxygen as one member of the ring and that if R4 is ethyl then R5 may not be substituted or unsubstituted phenyl, or
• R1 and R2 combine to form, together with the nitrogen atom to which they are attached, a 6-7 membered saturated ring which may contain 1-2 additional heteroatoms selected from the group consisting of NH, NR8, S, and O, or combine to form, together with the nitrogen atom to which they are attached, a 6-7 membered unsaturated ring which may contain 1-2 additional heteroatoms selected from the group consisting of N, S and O,
• wherein said saturated or unsaturated ring may be substituted with 1-2 substituents selected from the group consisting of OH, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 3-7 carbon atoms, heterocycloalkyl of 2-6 carbon atoms and 1-2 heteroatoms selected from NH, S and O, halogen, haloalkyl of 1-2 carbon atoms and a number of halogen atoms up to the perhalo level, alkoxy of 1-6 carbon atoms, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, and R9—R10;
• and pharmaceutically acceptable salts thereof.

A compound according to the formula IV:

• 147
• wherein
• R1 and R2 are independently selected from the group consisting of
• hydrogen,
• alkyl of 1-8 carbon atoms,
• alkenyl of 2-8 carbon atoms,
• alkynyl of 2-8 carbon atoms,
• cycloalkyl of 3-7 carbon atoms,
• heterocycloalkyl of 2-6 carbon atoms and 1-2 heteroatoms selected from NH, S and O,
• aryl of 6-12 carbon atoms, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O,
• heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, and
• R4—R5,
• or R1 and R2 combine to form, together with the nitrogen atom to which they are attached, a 5-7 membered saturated ring which may contain 1-2 additional heteroatoms selected from the group consisting of NH, NR8, S and O, or combine to form, together with the nitrogen atom to which they are attached, a 5-7 membered unsaturated ring which may contain 1-2 additional heteroatoms selected from the group consisting of N, S and O,
• wherein said saturated or unsaturated ring may be substituted with 1-2 substituents selected from the group consisting of OH, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 3-7 carbon atoms, heterocycloalkyl of 2-6 carbon atoms and 1-2 heteroatoms selected from NH, S and O, halogen, haloalkyl of 1-2 carbon atoms and a number of halogen atoms up to the perhalo level, alkoxy of 1-6 carbon atoms, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, and R9—R10;
• R3 is selected from the group consisting of:
• hydrogen,
• alkyl of 1-8 carbon atoms,
• alkenyl of 2-8 carbon atoms,
• alkynyl of 2-8 carbon atoms,
• cycloalkyl of 3-7 carbon atoms,
• heterocycloalkyl of 2-6 carbon atoms and 1-2 heteroatoms selected from NH, S and O,
• aryl of 6-12 carbon atoms, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-1 1 carbon atoms and 1-2 heteroatoms selected from N, S and O,
• heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, and
• R4—R5,
• R4 is selected from
• alkyl of 1-8 carbon atoms,
• alkenyl of 2-8 carbon atoms,
• alkynyl 2-8 carbon atoms,
• C(═O),
• S(═O)2, and
• C(═O)O—;
• R5 is selected from
• hydrogen,
• OH,
• alkyl of 1-8 carbon atoms,
• alkenyl 2-8 carbon atoms,
• alkynyl 2-8 carbon atoms,
• alkoxy of 1-8 carbon atoms,
• thioxy of 1-8 carbon atoms,
• aryl of 6-12 carbon atoms, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms and heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O,
• heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms and heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O,
• cycloalkyl of 3-7 carbon atoms,
• heterocycloalkyl of 2-6 carbon atoms and 1-2 heteroatoms selected from
• NH, S and O, and
• N—R6—R7,
• with the proviso that R5 is not OH, thioxy, alkoxy or N—R6—R7 when R4 is C(═O)O—, that R5 is not alkyl when R4 is alkyl, alkenyl or alkynyl, and that R5 is not a 6-membered heterocycloalkyl having N and O as heteroatoms when R4 is CH2;
• R6 and R7 are independently selected from
• hydrogen,
• alkyl of 1-8 carbon atoms,
• alkenyl of 2-8 carbon atoms, and
• alkynyl of 2-8 carbon atoms,
• or R6 and R7 combine together with the nitrogen atom to which they are attached to form a 5-7 membered, unsaturated ring which may contain 1-2 additional heteroatoms selected from N, S and O or to form a 5-7 membered, saturated ring which may contain 1-2 additional heteroatoms selected from NH, NR1, S and O;
• R8 is selected from
• alkyl of 1-8 carbon atoms,
• alkenyl of 2-8 carbon atoms,
• alkynyl of 2-8 carbon atoms,
• R12—R13,
• cycloalkyl of 3-7 carbon atoms,
• heterocycloalkyl of 2-6 carbon atoms and 1-2 heteroatoms selected from NH, S and O,
• aryl of 6-12 carbon atoms, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O,
• heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O;
• R9 is selected from
• alkyl of 1-8 carbon atoms,
• alkenyl of 2-8 carbon atoms, and
• alkynyl of 2-8 carbon atoms;
• R10 is selected from
• OH,
• aryl of 6-12 carbon atoms, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, and
• heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O;
• R11 is selected from benzyl which may be substituted with
• alkyl of 1-6 carbon atoms,
• alkenyl of 2-6 carbon atoms,
• alkynyl of 2-6 carbon atoms,
• halogen, and
• R14—R15;
• R12 is selected from
• alkyl of 1-8 carbon atoms,
• alkenyl of 2-8 carbon atoms, and
• alkynyl of 2-8 carbon atoms;
• R13 is selected from
• cycloalkyl of 3-7 carbon atoms,
• heterocycloalkyl of 2-6 carbon atoms and 1-2 heteroatoms selected from NH, S and O,
• aryl of 6-12 carbon atoms, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, and
• heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O;
• R14 is alkyl of 1-3 carbon atoms;
• R15 is cycloalkyl of 3-7 carbon atoms;
• with the proviso that when R3 is hydrogen,
• R1 and R2 are independently selected from
• hydrogen, with the further proviso that only one of R1 and R2 may be hydrogen,
• CH2—CH2—N(CH2CH3)2,
• CH2—CH2—SCH3,
• bornyl, and
• 148
• or R1 and R2 combine to form, together with the nitrogen atom to which they are attached, a six membered saturated ring which may contain 1-2 sulfur atoms,
• wherein said ring may be substituted with 1-2 substituents selected from the group consisting of alkyl of 2-8 carbon atoms, OH, CH2OH,
• or R1 and R2 combine to form, together with the nitrogen atom to which they are attached, a five membered saturated ring which also contains 1-2 sulfur atoms, or R1 and R2 combine to form, together with the nitrogen atom to which they are attached, an 8-10 membered bicyclic saturated ring;
• with the further proviso that when R3 is methyl,
• R1 and R2 are independently selected from the group consisting of
• hydrogen,
• alkyl of 1-8 carbon atoms,
• alkenyl of 2-8 carbon atoms,
• alkynyl of 2-8 carbon atoms,
• cycloalkyl of 3-7 carbon atoms,
• bornyl;
• and pharmaceutically acceptable salts thereof.

A method of treating or preventing a PDE7B-mediated disease or condition comprising administering to a mammal an effective amount of a compound of formula V:

• 149
• wherein
• R1 and R2 are independently selected from the group consisting of
• hydrogen,
• alkyl of 1-8 carbon atoms,
• alkenyl of 2-8 carbon atoms,
• alkynyl of 2-8 carbon atoms,
• cycloalkyl of 3-7 carbon atoms,
• heterocycloalkyl of 2-6 carbon atoms and 1-2 heteroatoms selected from NH, S and O,
• aryl of 6-12 carbon atoms, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O,
• heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, and
• R5—R6,
• or R1 and R2 combine to form, together with the nitrogen atom to which they are attached, a 5-7 membered saturated ring which may contain 1-2 additional heteroatoms selected from the group consisting of NH, NR9, S and O, or combine to form, together with the nitrogen atom to which they are attached, a 5-7 membered unsaturated ring which may contain 1-2 additional heteroatoms selected from the group consisting of N, S and O,
• wherein said saturated or unsaturated ring may be substituted with 1-2 substituents selected from the group consisting of OH, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 3-7 carbon atoms, heterocycloalkyl of 2-6 carbon atoms and 1-2 heteroatoms selected from NH, S and O, halogen, haloalkyl of 1-2 carbon atoms and a number of halogen atoms up to the perhalo level, alkoxy of 1-6 carbon atoms, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, and R10—R11;
• R3 and R4 combine to form, together with the carbon atoms to which they are attached, a 5-7 membered ring containing 2-5 (—CH2—) groups, 0-1
• 150
• groups, and 0-2 heteroatoms selected from NH, NR11, S and O;
• R5 is selected from
• alkyl of 1-8 carbon atoms,
• alkenyl of 2-8 carbon atoms,
• alkynyl of 2-8 carbon atoms,
• C(═O),
• S(═O)2, and
• C(═O)O—;
• R6 is selected from
• hydrogen,
• OH,
• alkyl of 1-8 carbon atoms,
• alkenyl of 2-8 carbon atoms,
• alkynyl of 2-8 carbon atoms,
• alkoxy of 1-8 carbon atoms, thioxy of 0.1-8 carbon atoms,
• aryl of 6-12 carbon atoms, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms and heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O,
• heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms and heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O,
• cycloalkyl of 3-7 carbon atoms,
• heterocycloalkyl of 2-6 carbon atoms and 1-2 heteroatoms selected from
• NH, S and O, and
• N—R7—R8,
• with the proviso that R6 is not OH, thioxy, alkoxy or N—R7—R8 when R5 is C(═O)O—, and with the further proviso that R6 is not alkyl when R5 is alkyl, alkenyl or alkynyl;
• R7 and R8 are independently selected from
• hydrogen,
• alkyl of 1-8 carbon atoms,
• alkenyl of 2-8 carbon atoms, and
• alkynyl of 2-8 carbon atoms,
• or R7 and R8 combine to form, together with the nitrogen atom to which they are attached, a 5-7 membered, unsaturated ring which may contain 1-2 additional heteroatoms selected from N, S and O, or combine to form, together with the nitrogen atom to which they are attached, a 5-7 membered, saturated ring which may contain 1-2 additional heteroatoms selected from NH, NR12, S and O;
• R9 is selected from
• alkyl of 1-8 carbon atoms,
• alkenyl of 2-8 carbon atoms,
• alkynyl of 2-8 carbon atoms,
• R3—R14
• cycloalkyl of 3-7 carbon atoms,
• heterocycloalkyl of 2-6 carbon atoms and 1-2 heteroatoms selected from NH, S and O,
• aryl of 6-12 carbon atoms, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O,
• heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O;
• R10 is selected from
• alkyl of 1-8 carbon atoms,
• alkenyl of 2-8 carbon atoms, and
• alkynyl of 2-8 carbon atoms;
• R11 is selected from
• OH,
• aryl of 6-12 carbon atoms, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, and
• heteroaryl of 4-1 1 carbon atoms and 1-2 heteroatoms selected from N, S and O, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O;
• R12 is benzyl which may be substituted with
• alkyl of 1-6 carbon atoms,
• alkenyl of 2-6 carbon atoms,
• alkynyl of 2-6 carbon atoms,
• halogen, and
• R15—R16;
• R13 is selected from
• alkyl of 1-8 carbon atoms,
• alkenyl of 2-8 carbon atoms, and
• alkynyl of 2-8 carbon atoms;
• R14 is selected from
• cycloalkyl of 3-7 carbon atoms,
• heterocycloalkyl of 2-6 carbon atoms and 1-2 heteroatoms selected from NH, S and O,
• aryl of 6-12 carbon atoms, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, and
• heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O;
• R15 is alkyl of 1-3 carbon atoms;
• R16 is cycloalkyl of 3-7 carbon atoms;
• R17 is selected from the group consisting of
• hydrogen,
• alkyl of 1-8 carbon atoms,
• alkenyl of 2-8 carbon atoms,
• alkynyl of 2-8 carbon atoms,
• cycloalkyl of 3-7 carbon atoms,
• heterocycloalkyl of 2-6 carbon atoms and 1-2 heteroatoms selected from NH, S and O,
• aryl of 6-12 carbon atoms, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O,
• heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, which may be substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, haloalkyl of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, haloalkoxy of 1-6 carbon atoms and a number of halogen atoms up to the perhalo level, aryl of 6-12 carbon atoms or heteroaryl of 4-11 carbon atoms and 1-2 heteroatoms selected from N, S and O, and
• and pharmaceutically acceptable salts thereof.