Methods of using potassium channel inhibiting compounds

A pharmaceutical composition comprising a pharmacologically effective amount of at least one potassium Kv1.3 channel inhibitor wherein the one or more compounds optionally have one or more additional properties selected from the group consisting of:

• i. CB1 antagonist properties;
• ii. CB1 agonists properties;
• iii. CB2 agonists properties;
• and
• iv. potassium K(apt) channel opening properties.
• wherein the pharmaceutical composition is for treating, preventing or providing a medical condition selected from the group consisting of:
• obesity, diabetes mellitus, metabolic syndrome, syndrome X, insulinoma, familial hyperinsulemic hypoglycemia, male pattern baldness, detrusor hyperreactivity, asthma, insufficient glucose metabolism, insulin resistance, hyperglycaemea, glucose intolerance, neuroprotection, epilepsy, analgesia, cardioprotection, angina, cardioplegia, arrhythmia, coronary spasm, peripheral vascular disease, cerebral vasospasm, appetite regulation, neurodegeneration, pain, neuropathic pain, chronic pain and impotence.

A pharmaceutical composition prepared by a process comprising the steps of:

• a. selecting one or more potassium Kv1.3 channel inhibiting compounds wherein the one or more compounds optionally have one or more additional properties selected from the group consisting of:
• i. CB1 antagonist properties;
• ii. CB1 agonists properties;
• iii. CB2 agonists properties;
• and
• iv. potassium K(atp) channel opening properties.
• b. combining the one or more compounds with one or more pharmaceutically acceptable excipients to create a dosage form suitable for administration to a subject;
• wherein the pharmaceutical composition is used to treat, prevent or provide a medical condition in a subject, the medical condition is selected from the group consisting of:
• obesity, diabetes mellitus, metabolic syndrome, syndrome X, insulinoma, familial hyperinsulemic hypoglycemia, male pattern baldness, detrusor hyperreactivity, asthma, insufficient glucose metabolism, insulin resistance, hyperglycaemea, glucose intolerance, neuroprotection, epilepsy, analgesia, cardioprotection, angina, cardioplegia, arrhythmia, coronary spasm, peripheral vascular disease, cerebral vasospasm, appetite regulation, neurodegeneration, pain, neuropathic pain, chronic pain and impotence.

A method of inhibiting a potassium Kv1.3 channel in a subject comprising the step of administering one or more of the compounds selected from the group consisting of:

• a.)
• wherein:
• R and R1 are independently selected from the group consisting of:
• napthyl, phenyl, thienyl and pyridyl wherein phenyl, thienyl and pyridyl may be substituted with 1, 2 or 3 substitutents Y;
• R2 is selected from the group consisting of:
• hydrogen, hydroxy, C1-3-alkoxy, acetyloxy and propionyloxy;
• R3 is selected from the group consisting of:
• C1-8 branched or unbranched alkyl, C3-10 cycloalkyl, C3-8 alkenyl, C5-10 bicycloalkyl, C6-10 tricycloalkyl, C5-8 cycloalkenyl, NR10R11, naphtyl, benzyl, phenyl, thienyl and pyridyl wherein benzyl, phenyl, thienyl and pyridiyl may be substituted with 1, 2 or 3 substitutents Y;
• Aa is selected from the group consisting of:
• substitutents of formulae (i), (ii), (iii), (iv), (v) and (vi)
• Bb is selected elected from the group consisting of:
• sulfonyl and carbonyl;
• each Y is independently selected from the group consisting of:
• C1-3-alkyl, C1-3-alkoxy, hydroxy, halogen, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, nitro, amino, mono- or dialkyl (C1-2)-amino, mono- or dialkyl (C1-2)-amido, (C1-3)-alkyl sulfonyl, dimethylsulfamido, C1-3-alkoxycarbonyl, carboxyl, trifluoromethylsulfonyl, cyano, carbamoyl, sulfamoyl and acetyl;
• R4 is selected from the group consisting of:
• hydrogen, C1-8 branched or unbranched alkyl and C3-8 cycloalkyl;
• or R4 is selected from the group consisting of:
• acetamido, dimethylamino, 2,2,2-trifluoroethyl, phenyl and pyridyl with the proviso that R5 is hydrogen, wherein such C1-8 branched or unbranched alkyl and/or C3-8 cycloalkyl alkyl group may be substituted with a hydroxyl group;
• R5 is selected from the group consisting of:
• hydrogen, C1-8 branched or unbranched alkyl, C3-8 cycloalkyl, C2-10 branched or unbranched heteroalkyl, C3-8 non-aromatic heterocycloalkyl, C4-10 non-aromatic heterocycloalkyl-alkyl, amino, hydroxy, phenoxy, benzyloxy, C1-8 alkoxy, C3-8 alkenyl, C5-8 cycloalkenyl, C6-9 cycloalkenylalkyl, imidazolylalkyl, phenyl, benzyl, pyridyl, thienyl, pyridylmethyl and phenethyl;
• or R5 is NR8R9 with the proviso that R4 is H or methyl;
• or R4 and R5 together with the nitrogen atom to which they are bonded form a saturated or unsaturated, monocyclic or bicyclic heterocyclic moiety having 4 to 10 ring atoms,
• wherein such C1-8 branched or unbranched alkyl and/or C3-8 cycloalkyl group may be substituted with hydroxyl and/or fluoro,
• wherein such C2-10 branched or unbranched heteroalkyl, C3-8 non-aromatic heterocycloalkyl and/or C4-10 non-aromatic heterocycloalkyl-alkyl groups may contain one or more heteroatoms selected from the group consisting of:
• O, N and S,
• wherein such C2-10 branched or unbranched heteroalkyl, C3-8 non-aromatic heterocycloalkyl and/or C4-10 non-aromatic heterocycloalkyl-alkyl groups may contain a SO2— group,
• wherein such C2-10 branched or unbranched heteroalkyl group, C3-8 non-aromatic heterocycloalkyl group and/or C4-10 non-aromatic heterocycloalkylalkyl group may be substituted with keto, trifluoromethyl, C1-3 alkyl, hydroxy, amino, monoalkylamino, dialkylamino or fluoro,
• wherein such amino, hydroxy, phenoxy, benzyloxy, C1-8 alkoxy, C3-8 alkenyl, C5-8 cycloalkenyl, C6-9 cycloalkenylalkyl may contain one or more heteroatoms selected from the group consisting of:
• O, N and S,
• wherein such amino, hydroxy, phenoxy, benzyloxy, C1-8 alkoxy, C3-8 alkenyl, C5-8 cycloalkenyl, C6-9 cycloalkenylalkyl may contain a keto or —SO2— group,
• wherein such C1-8 alkoxy, C3-8 alkenyl and C5-8 cycloalkenyl groups may be substituted with a hydroxy group, a trifluoromethyl group, an amino group, a monoalkylamino group or dialkylamino group or a fluoro atom,
• wherein such phenyl, benzyl, pyridyl, thienyl, pyridylmethyl or phenethyl group may be substituted with 1, 2 or 3 of the substitutents Y,
• wherein such monocyclic or bicyclic heterocyclic moiety having 4 to 10 ring atoms may contain one or more heteroatoms selected from the group consisting of:
• O, N and S,
• wherein such monocyclic or bicyclic heterocyclic moiety having 4 to 10 ring atoms may contain a keto or —SO2— group,
• wherein such monocyclic or bicyclic heterocyclic moiety having 4 to 10 ring atoms may be substituted with a C1-4 alkyl, hydroxyalkyl, phenyl, thienyl, pyridyl, amino, monoalkylaminoalkyl, dialkylaminoalkyl, monoalkylamino, dialkylamino, aminoalkyl, azetidinyl, pyrrolidinyl, piperidinyl or hexahydro-1H-azepinyl group;
• R6 is selected from the group consisting of:
• hydrogen and C1-3 unbranched alkyl;
• R7 is C1-3 unbranched alkyl;
• R8 and R9 are the same or different and are selected elected from the group consisting of:
• C2-4 alkyl and C2-4 trifluoroalkyl;
• or R8 is methyl with the proviso that R9 is C2-4 alkyl;
• or R8 and R9—together with the nitrogen atom to which they are bonded—form a saturated or unsaturated heterocyclic moiety having 4 to 8 ring atoms,
• wherein such saturated or unsaturated heterocyclic moiety having 4 to 8 ring atoms may contain an additional heteroatom selected from the group consisting of:
• N, O and S or may contain a group selected from the group consisting of:
• a keto or —SO2— group,
• wherein such saturated or unsaturated heterocyclic moiety having 4 to 8 ring atoms may be substituted with C1-4 alkyl;
• R10 and R11 are independently selected from the group consisting of:
• hydrogen, branched or unbranched C1-8 alkyl, branched or unbranched C1-8 alkenyl, C3-8 cycloalkyl, C3-8 cycloalkenyl, naphtyl and phenyl;
• or R10 and R11-together with the nitrogen atom to which they are bonded—form a monocyclic, bicyclic or tricyclic alkyl or alkenyl group,
• wherein such branched or unbranched C1-8 alkyl and/or branched or unbranched C1-8 alkenyl groups may contain one or more heteroatoms selected from the group consisting of:
• O, N, and S,
• wherein such branched or unbranched C1-8 alkyl and/or branched or unbranched C1-8 alkenyl groups may contain a group selected from the group consisting of:
• keto and —SO2-group and wherein such keto and —SO2-group may be substituted with a hydroxy or amino group,
• wherein such C3-8cycloalkyl and/or C3-8cycloalkenyl group may contain one or more ring heteroatoms selected from the group consisting of:
• O, N and S,
• wherein such C3-8 cycloalkyl and/or C3-8 cycloalkenyl group may be substituted with hydroxy, C1-3 alkyl, —SO2—, keto, amino, C1-3 monoalkylamino and/or C1-3 dialkylamino,
• wherein such phenyl group may be substituted with 1, 2 or 3 substitutents Y with the proviso that R11 is selected from the group consisting of:
• hydrogen, branched or unbranched C1-5 alkyl group wherein such branched or unbranched C1-5 alkyl group may contain one or more heteroatoms selected from the group consisting of:
• O, N and S or wherein such branched or unbranched C1-5 alkyl group may contain SO2— and wherein such branched or unbranched C1-5 alkyl group may be substituted with a hydroxy, keto or amino group,
• wherein such monocyclic, bicyclic or tricyclic alkyl or alkenyl group may contain ring heteroatoms selected from the group consisting of:
• O, N and S,
• wherein such monocyclic, bicyclic or tricyclic alkyl or alkenyl group may contain a group selected from the group consisting of:
• keto and SO2,
• wherein such monocyclic, bicyclic or tricyclic alkyl or alkenyl group may be substituted with hydroxy, C1-3 alkyl, SO2—, keto, amino, C1-3 monoalkylamino, C1-3 dialkylamino, pyrrolidinyl, or piperidinyl,
• wherein such monocyclic, bicyclic or tricyclic alkyl or alkenyl group may contain an annelated phenyl group which annelated phenyl group may be substituted with 1 or 2 substitutents Y;
• and
• a prodrug thereof, a tautomer thereof or a pharmaceutically acceptable salt thereof;
• b.)
• wherein
• R12 and R13 are independently selected from the group consisting of:
• hydrogen, C1-3 alkyl and C3-6 cycloalkyl which may contain from 1 to 3 heteroatoms selected from the group consisting of:
• N, O and S;
• R14 is phenyl which may be substituted with 1, 2 or 3 substitutents Z which can be the same or different and wherein Z is selected from the group consisting of:
• C1-3-alkyl, C1-3-alkoxy, hydroxy, halogen, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, nitro, amino, mono- or dialkyl (C1-2)-amino, mono- or dialkyl (C1-2)-amido, (C1-3)-alkyl sulfonyl, dimethylsulfamido, C1-3-alkoxycarbonyl, carboxyl, trifluoromethylsulfonyl, cyano, carbamoyl, sulfamoyl and acetyl;
• and
• a prodrug thereof, a tautomer thereof or a pharmaceutically acceptable salt thereof;
• c.)
• wherein
• Q is phenyl which may be substituted with 1, 2 or 3 substitutents Z which can be the same or different and wherein Z is selected from the group consisting of:
• C1-3-alkyl, C1-3-alkoxy, hydroxy, halogen, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, nitro, amino, mono- or dialkyl (C1-2)-amino, mono- or dialkyl (C1-2)-amido, (C1-3)-alkyl sulfonyl, dimethylsulfamido, C1-3-alkoxycarbonyl, carboxyl, trifluoromethylsulfonyl, cyano, carbamoyl, sulfamoyl and acetyl;
• T is selected from the group consisting of:
• hydrogen, C1-3 alkyl and C3-6 cycloalkyl which may contain from 1 to 3 heteroatoms selected from the group consisting of:
• N, O and S;
• R15 is selected from the group consisting of:
• C1-3 alkyl and C3-6 cycloalkyl which may contain from 1 to 3 heteroatoms selected from the group consisting of:
• N, O and S;
• and
• a prodrug thereof, a tautomer thereof or a pharmaceutically acceptable salt thereof;
• d.) Diazoxide, NN414, R(+)-WIN55212-2, HU-308, Rimonabant, SR-147778;
• and a prodrug thereof, a tautomer thereof or a pharmaceutically acceptable salt thereof;
• and
• e.) mixtures of any of the foregoing.

A method of treating a medical condition comprising the step of inhibiting a potassium Kv1.3 channel by administering one or more compounds having a potassium Kv1.3 channel inhibition of greater than about 40% and selected from the group consisting of:

• a.)
• wherein:
• R and R1 are independently selected from the group consisting of:
• napthyl, phenyl, thienyl and pyridyl wherein phenyl, thienyl and pyridyl may be substituted with 1, 2 or 3 substitutents Y;
• R2 is selected from the group consisting of:
• hydrogen, hydroxy, C1-3-alkoxy, acetyloxy and propionyloxy;
• R3 is selected from the group consisting of:
• C1-8 branched or unbranched alkyl, C3-10 cycloalkyl, C3-8 alkenyl, C5-10 bicycloalkyl, C6-10 tricycloalkyl, C5-8 cycloalkenyl, NR10R11, naphtyl, benzyl, phenyl, thienyl and pyridyl wherein benzyl, phenyl, thienyl and pyridiyl may be substituted with 1, 2 or 3 substitutents Y;
• Aa is selected from the group consisting of:
• substitutents of formulae (i), (ii), (iii), (iv), (v) and (vi)
• Bb is selected elected from the group consisting of:
• sulfonyl and carbonyl;
• each Y is independently selected from the group consisting of:
• C1-3-alkyl, C1-3-alkoxy, hydroxy, halogen, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, nitro, amino, mono- or dialkyl (C1-2)-amino, mono- or dialkyl (C1-2)-amido, (C1-3)-alkyl sulfonyl, dimethylsulfamido, C1-3-alkoxycarbonyl, carboxyl, trifluoromethylsulfonyl, cyano, carbamoyl, sulfamoyl and acetyl;
• R4 is selected from the group consisting of:
• hydrogen, C1-8 branched or unbranched alkyl and C3-8 cycloalkyl;
• or R4 is selected from the group consisting of:
• acetamido, dimethylamino, 2,2,2-trifluoroethyl, phenyl and pyridyl with the proviso that R5 is hydrogen,
• wherein such C1-8 branched or unbranched alkyl and/or C3-8 cycloalkyl alkyl group may be substituted with a hydroxyl group;
• R5 is selected from the group consisting of:
• hydrogen, C1-8 branched or unbranched alkyl, C3-8 cycloalkyl, C2-10 branched or unbranched heteroalkyl, C3-8 non-aromatic heterocycloalkyl, C4-10 non-aromatic heterocycloalkyl-alkyl, amino, hydroxy, phenoxy, benzyloxy, C1-8 alkoxy, C3-8 alkenyl, C5-8 cycloalkenyl, C6-9 cycloalkenylalkyl, imidazolylalkyl, phenyl, benzyl, pyridyl, thienyl, pyridylmethyl and phenethyl;
• or R5 is NR8R9 with the proviso that R4 is H or methyl;
• or R4 and R5 together with the nitrogen atom to which they are bonded form a saturated or unsaturated, monocyclic or bicyclic heterocyclic moiety having 4 to 10 ring atoms,
• wherein such C1-8 branched or unbranched alkyl and/or C3-8 cycloalkyl group may be substituted with hydroxyl and/or fluoro,
• wherein such C2-10 branched or unbranched heteroalkyl, C3-8 non-aromatic heterocycloalkyl and/or C4-10 non-aromatic heterocycloalkyl-alkyl groups may contain one or more heteroatoms selected from the group consisting of:
• O, N and S,
• wherein such C2-10 branched or unbranched heteroalkyl, C3-8 non-aromatic heterocycloalkyl and/or C4-10 non-aromatic heterocycloalkyl-alkyl groups may contain a SO2— group,
• wherein such C2-10 branched or unbranched heteroalkyl group, C3-8 non-aromatic heterocycloalkyl group and/or C4-10 non-aromatic heterocycloalkylalkyl group may be substituted with keto, trifluoromethyl, C1-3 alkyl, hydroxy, amino, monoalkylamino, dialkylamino or fluoro,
• wherein such amino, hydroxy, phenoxy, benzyloxy, C1-8 alkoxy, C3-8 alkenyl, C5-8 cycloalkenyl, C6-9 cycloalkenylalkyl may contain one or more heteroatoms selected from the group consisting of:
• O, N and S,
• wherein such amino, hydroxy, phenoxy, benzyloxy, C1-8 alkoxy, C3-8 alkenyl, C5-8 cycloalkenyl, C6-9 cycloalkenylalkyl may contain a keto or —SO2— group,
• wherein such C1-8 alkoxy, C3-8 alkenyl and C5-8 cycloalkenyl groups may be substituted with a hydroxy group, a trifluoromethyl group, an amino group, a monoalkylamino group or dialkylamino group or a fluoro atom,
• wherein such phenyl, benzyl, pyridyl, thienyl, pyridylmethyl or phenethyl group may be substituted with 1, 2 or 3 of the substitutents Y,
• wherein such monocyclic or bicyclic heterocyclic moiety having 4 to 10 ring atoms may contain one or more heteroatoms selected from the group consisting of:
• O, N and S,
• wherein such monocyclic or bicyclic heterocyclic moiety having 4 to 10 ring atoms may contain a keto or —SO2— group,
• wherein such monocyclic or bicyclic heterocyclic moiety having 4 to 10 ring atoms may be substituted with a C1-4 alkyl, hydroxyalkyl, phenyl, thienyl, pyridyl, amino, monoalkylaminoalkyl, dialkylaminoalkyl, monoalkylamino, dialkylamino, aminoalkyl, azetidinyl, pyrrolidinyl, piperidinyl or hexahydro-1H-azepinyl group;
• R6 is selected from the group consisting of:
• hydrogen and C1-3 unbranched alkyl;
• R7 is C1-3 unbranched alkyl;
• R8 and R9 are the same or different and are selected elected from the group consisting of:
• C2-4 alkyl and C2-4 trifluoroalkyl;
• or R8 is methyl with the proviso that R9 is C2-4 alkyl;
• or R8 and R9—together with the nitrogen atom to which they are bonded—form a saturated or unsaturated heterocyclic moiety having 4 to 8 ring atoms,
• wherein such saturated or unsaturated heterocyclic moiety having 4 to 8 ring atoms may contain an additional heteroatom selected from the group consisting of:
• N, O and S or may contain a group selected from the group consisting of:
• a keto or —SO2— group,
• wherein such saturated or unsaturated heterocyclic moiety having 4 to 8 ring atoms may be substituted with C1-4 alkyl;
• R10 and R11 are independently selected from the group consisting of:
• hydrogen, branched or unbranched C1-8 alkyl, branched or unbranched C1-8 alkenyl, C3-8 cycloalkyl, C3-8 cycloalkenyl, naphtyl and phenyl;
• or R10 and R11-together with the nitrogen atom to which they are bonded—form a monocyclic, bicyclic or tricyclic alkyl or alkenyl group,
• wherein such branched or unbranched C1-8 alkyl and/or branched or unbranched C1-8 alkenyl groups may contain one or more heteroatoms selected from the group consisting of:
• O, N, and S,
• wherein such branched or unbranched C1-8 alkyl and/or branched or unbranched C1-8 alkenyl groups may contain a group selected from the group consisting of:
• keto and —SO2-group and wherein such keto and —SO2-group may be substituted with a hydroxy or amino group,
• wherein such C3-8 cycloalkyl and/or C3-8 cycloalkenyl group may contain one or more ring heteroatoms selected from the group consisting of:
• O, N and S,
• wherein such C3-8 cycloalkyl and/or C3-8 cycloalkenyl group may be substituted with hydroxy, C1-3 alkyl, —SO2—, keto, amino, C1-3 monoalkylamino and/or C1-3 dialkylamino,
• wherein such phenyl group may be substituted with 1, 2 or 3 substitutents Y with the proviso that R11 is selected from the group consisting of:
• hydrogen, branched or unbranched C1-5 alkyl group wherein such branched or unbranched C1-5 alkyl group may contain one or more heteroatoms selected from the group consisting of:
• O, N and S or wherein such branched or unbranched C1-5 alkyl group may contain SO2— and wherein such branched or unbranched C1-5 alkyl group may be substituted with a hydroxy, keto or amino group,
• wherein such monocyclic, bicyclic or tricyclic alkyl or alkenyl group may contain ring heteroatoms selected from the group consisting of:
• O, N and S,
• wherein such monocyclic, bicyclic or tricyclic alkyl or alkenyl group may contain a group selected from the group consisting of:
• keto and SO2,
• wherein such monocyclic, bicyclic or tricyclic alkyl or alkenyl group may be substituted with hydroxy, C1-3 alkyl, SO2—, keto, amino, C1-3 monoalkylamino, C1-3 dialkylamino, pyrrolidinyl, or piperidinyl,
• wherein such monocyclic, bicyclic or tricyclic alkyl or alkenyl group may contain an annelated phenyl group which annelated phenyl group may be substituted with 1 or 2 substitutents Y;
• and
• a prodrug thereof, a tautomer thereof or a pharmaceutically acceptable salt thereof;
• b.)
• wherein
• R12 and R13 are independently selected from the group consisting of:
• hydrogen, C1-3 alkyl and C3-6 cycloalkyl which may contain from 1 to 3 heteroatoms selected from the group consisting of:
• N, O and S;
• R14 is phenyl which may be substituted with 1, 2 or 3 substitutents Z which can be the same or different and wherein Z is selected from the group consisting of:
• C1-3-alkyl, C1-3-alkoxy, hydroxy, halogen, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, nitro, amino, mono- or dialkyl (C1-2)-amino, mono- or dialkyl (C1-2)-amido, (C1-3)-alkyl sulfonyl, dimethylsulfamido, C1-3-alkoxycarbonyl, carboxyl, trifluoromethylsulfonyl, cyano, carbamoyl, sulfamoyl and acetyl;
• and
• a prodrug thereof, a tautomer thereof or a pharmaceutically acceptable salt thereof;
• c.)
• wherein
• Q is phenyl which may be substituted with 1, 2 or 3 substitutents Z which can be the same or different and wherein Z is selected from the group consisting of:
• C1-3-alkyl, C1-3-alkoxy, hydroxy, halogen, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, nitro, amino, mono- or dialkyl (C1-2)-amino, mono- or dialkyl (C1-2)-amido, (C1-3)-alkyl sulfonyl, dimethylsulfamido, C1-3-alkoxycarbonyl, carboxyl, trifluoromethylsulfonyl, cyano, carbamoyl, sulfamoyl and acetyl;
• T is selected from the group consisting of:
• hydrogen, C1-3 alkyl and C3-6 cycloalkyl which may contain from 1 to 3 heteroatoms selected from the group consisting of:
• N, O and S;
• R15 is selected from the group consisting of:
• C1-3 alkyl and C3-6 cycloalkyl which may contain from 1 to 3 heteroatoms selected from the group consisting of:
• N, O and S;
• and
• a prodrug thereof, a tautomer thereof or a pharmaceutically acceptable salt thereof;
• d.) Diazoxide, NN414, R(+)-WIN55212-2, HU-308, Rimonabant, SR-147778;
• and a prodrug thereof, a tautomer thereof or a pharmaceutically acceptable salt thereof;
• and
• e.) mixtures of any of the foregoing.

A pharmaceutical composition comprising a pharmacologically effective amount of one or more potassium Kv1.3 channel inhibitor selected from the group consisting of:

• a.)
• wherein:
• R and R1 are independently selected from the group consisting of:
• napthyl, phenyl, thienyl and pyridyl wherein phenyl, thienyl and pyridyl may be substituted with 1, 2 or 3 substitutents Y;
• R2 is selected from the group consisting of:
• hydrogen, hydroxy, C1-3-alkoxy, acetyloxy and propionyloxy;
• R3 is selected from the group consisting of:
• C1-8 branched or unbranched alkyl, C3-10 cycloalkyl, C3-8 alkenyl, C5-10 bicycloalkyl, C6-10 tricycloalkyl, C5-8 cycloalkenyl, NR10R11, naphtyl, benzyl, phenyl, thienyl and pyridyl wherein benzyl, phenyl, thienyl and pyridiyl may be substituted with 1, 2 or 3 substitutents Y;
• Aa is selected from the group consisting of:
• substitutents of formulae (i), (ii), (iii), (iv), (v) and (vi)
• Bb is selected elected from the group consisting of:
• sulfonyl and carbonyl;
• each Y is independently selected from the group consisting of:
• C1-3-alkyl, C1-3-alkoxy, hydroxy, halogen, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, nitro, amino, mono- or dialkyl (C1-2)-amino, mono- or dialkyl (C1-2)-amido, (C1-3)-alkyl sulfonyl, dimethylsulfamido, C1-3-alkoxycarbonyl, carboxyl, trifluoromethylsulfonyl, cyano, carbamoyl, sulfamoyl and acetyl;
• R4 is selected from the group consisting of:
• hydrogen, C1-8 branched or unbranched alkyl and C3-8 cycloalkyl;
• or R4 is selected from the group consisting of:
• acetamido, dimethylamino, 2,2,2-trifluoroethyl, phenyl and pyridyl with the proviso that R5 is hydrogen,
• wherein such C1-8 branched or unbranched alkyl and/or C3-8 cycloalkyl alkyl group may be substituted with a hydroxyl group;
• R5 is selected from the group consisting of:
• hydrogen, C1-8 branched or unbranched alkyl, C3-8 cycloalkyl, C2-10 branched or unbranched heteroalkyl, C3-8 non-aromatic heterocycloalkyl, C4-10 non-aromatic heterocycloalkyl-alkyl, amino, hydroxy, phenoxy, benzyloxy, C1-8 alkoxy, C3-8 alkenyl, C5-8 cycloalkenyl, C6-9 cycloalkenylalkyl, imidazolylalkyl, phenyl, benzyl, pyridyl, thienyl, pyridylmethyl and phenethyl;
• or R5 is NR8R9 with the proviso that R4 is H or methyl;
• or R4 and R5 together with the nitrogen atom to which they are bonded form a saturated or unsaturated, monocyclic or bicyclic heterocyclic moiety having 4 to 10 ring atoms,
• wherein such C1-8 branched or unbranched alkyl and/or C3-8 cycloalkyl group may be substituted with hydroxyl and/or fluoro,
• wherein such C2-10 branched or unbranched heteroalkyl, C3-8 non-aromatic heterocycloalkyl and/or C4-10 non-aromatic heterocycloalkyl-alkyl groups may contain one or more heteroatoms selected from the group consisting of:
• O, N and S,
• wherein such C2-10 branched or unbranched heteroalkyl, C3-8 non-aromatic heterocycloalkyl and/or C4-10 non-aromatic heterocycloalkyl-alkyl groups may contain a SO2— group,
• wherein such C2-10 branched or unbranched heteroalkyl group, C3-8 non-aromatic heterocycloalkyl group and/or C4-10 non-aromatic heterocycloalkylalkyl group may be substituted with keto, trifluoromethyl, C1-3 alkyl, hydroxy, amino, monoalkylamino, dialkylamino or fluoro,
• wherein such amino, hydroxy, phenoxy, benzyloxy, C1-8 alkoxy, C3-8 alkenyl, C5-8 cycloalkenyl, C6-9 cycloalkenylalkyl may contain one or more heteroatoms selected from the group consisting of:
• O, N and S,
• wherein such amino, hydroxy, phenoxy, benzyloxy, C1-8 alkoxy, C3-8 alkenyl, C5-8 cycloalkenyl, C6-9 cycloalkenylalkyl may contain a keto or —SO2— group,
• wherein such C1-8 alkoxy, C3-8 alkenyl and C5-8 cycloalkenyl groups may be substituted with a hydroxy group, a trifluoromethyl group, an amino group, a monoalkylamino group or dialkylamino group or a fluoro atom,
• wherein such phenyl, benzyl, pyridyl, thienyl, pyridylmethyl or phenethyl group may be substituted with 1, 2 or 3 of the substitutents Y,
• wherein such monocyclic or bicyclic heterocyclic moiety having 4 to 10 ring atoms may contain one or more heteroatoms selected from the group consisting of:
• O, N and S,
• wherein such monocyclic or bicyclic heterocyclic moiety having 4 to 10 ring atoms may contain a keto or —SO2— group,
• wherein such monocyclic or bicyclic heterocyclic moiety having 4 to 10 ring atoms may be substituted with a C1-4 alkyl, hydroxyalkyl, phenyl, thienyl, pyridyl, amino, monoalkylaminoalkyl, dialkylaminoalkyl, monoalkylamino, dialkylamino, aminoalkyl, azetidinyl, pyrrolidinyl, piperidinyl or hexahydro-1H-azepinyl group;
• R6 is selected from the group consisting of:
• hydrogen and C1-3 unbranched alkyl;
• R7 is C1-3 unbranched alkyl;
• R8 and R9 are the same or different and are selected elected from the group consisting of:
• C2-4 alkyl and C2-4 trifluoroalkyl;
• or R8 is methyl with the proviso that R9 is C2-4 alkyl;
• or R8 and R9—together with the nitrogen atom to which they are bonded—form a saturated or unsaturated heterocyclic moiety having 4 to 8 ring atoms,
• wherein such saturated or unsaturated heterocyclic moiety having 4 to 8 ring atoms may contain an additional heteroatom selected from the group consisting of:
• N, O and S or may contain a group selected from the group consisting of:
• a keto or —SO2— group,
• wherein such saturated or unsaturated heterocyclic moiety having 4 to 8 ring atoms may be substituted with C1-4 alkyl;
• R10 and R11 are independently selected from the group consisting of:
• hydrogen, branched or unbranched C1-8 alkyl, branched or unbranched C1-8 alkenyl, C3-8 cycloalkyl, C3-8 cycloalkenyl, naphtyl and phenyl;
• or R10 and R11—together with the nitrogen atom to which they are bonded—form a monocyclic, bicyclic or tricyclic alkyl or alkenyl group,
• wherein such branched or unbranched C1-8 alkyl and/or branched or unbranched C1-8 alkenyl groups may contain one or more heteroatoms selected from the group consisting of:
• O, N, and S,
• wherein such branched or unbranched C1-8 alkyl and/or branched or unbranched C1-8 alkenyl groups may contain a group selected from the group consisting of:
• keto and —SO2-group and wherein such keto and —SO2-group may be substituted with a hydroxy or amino group,
• wherein such C3-8 cycloalkyl and/or C3-8 cycloalkenyl group may contain one or more ring heteroatoms selected from the group consisting of:
• O, N and S,
• wherein such C3-8 cycloalkyl and/or C3-8 cycloalkenyl group may be substituted with hydroxy, C1-3 alkyl, —SO2—, keto, amino, C1-3 monoalkylamino and/or C1-3 dialkylamino,
• wherein such phenyl group may be substituted with 1, 2 or 3 substitutents Y with the proviso that R11 is selected from the group consisting of:
• hydrogen, branched or unbranched C1-5 alkyl group wherein such branched or unbranched C1-5 alkyl group may contain one or more heteroatoms selected from the group consisting of:
• O, N and S or wherein such branched or unbranched C1-5 alkyl group may contain SO2— and wherein such branched or unbranched C1-5 alkyl group may be substituted with a hydroxy, keto or amino group,
• wherein such monocyclic, bicyclic or tricyclic alkyl or alkenyl group may contain ring heteroatoms selected from the group consisting of:
• O, N and S,
• wherein such monocyclic, bicyclic or tricyclic alkyl or alkenyl group may contain a group selected from the group consisting of:
• keto and SO2,
• wherein such monocyclic, bicyclic or tricyclic alkyl or alkenyl group may be substituted with hydroxy, C1-3 alkyl, SO2—, keto, amino, C1-3 monoalkylamino, C1-3 dialkylamino, pyrrolidinyl, or piperidinyl,
• wherein such monocyclic, bicyclic or tricyclic alkyl or alkenyl group may contain an annelated phenyl group which annelated phenyl group may be substituted with 1 or 2 substitutents Y;
• and
• a prodrug thereof, a tautomer thereof or a pharmaceutically acceptable salt thereof;
• b.)
• wherein
• R12 and R13 are independently selected from the group consisting of:
• hydrogen, C1-3 alkyl and C3-6 cycloalkyl which may contain from 1 to 3 heteroatoms selected from the group consisting of:
• N, O and S;
• R14 is phenyl which may be substituted with 1, 2 or 3 substitutents Z which can be the same or different and wherein Z is selected from the group consisting of:
• C1-3-alkyl, C1-3-alkoxy, hydroxy, halogen, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, nitro, amino, mono- or dialkyl (C1-2)-amino, mono- or dialkyl (C1-2)-amido, (C1-3)-alkyl sulfonyl, dimethylsulfamido, C1-3-alkoxycarbonyl, carboxyl, trifluoromethylsulfonyl, cyano, carbamoyl, sulfamoyl and acetyl;
• and
• a prodrug thereof, a tautomer thereof or a pharmaceutically acceptable salt thereof;
• c.)
• wherein
• Q is phenyl which may be substituted with 1, 2 or 3 substitutents Z which can be the same or different and wherein Z is selected from the group consisting of:
• C1-3-alkyl, C1-3-alkoxy, hydroxy, halogen, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, nitro, amino, mono- or dialkyl (C1-2)-amino, mono- or dialkyl (C1-2)-amido, (C1-3)-alkyl sulfonyl, dimethylsulfamido, C1-3-alkoxycarbonyl, carboxyl, trifluoromethylsulfonyl, cyano, carbamoyl, sulfamoyl and acetyl;
• T is selected from the group consisting of:
• hydrogen, C1-3 alkyl and C3-6 cycloalkyl which may contain from 1 to 3 heteroatoms selected from the group consisting of:
• N, O and S;
• R15 is selected from the group consisting of:
• C1-3 alkyl and C3-6 cycloalkyl which may contain from 1 to 3 heteroatoms selected from the group consisting of:
• N, O and S;
• and
• a prodrug thereof, a tautomer thereof or a pharmaceutically acceptable salt thereof;
• d.) Diazoxide, NN414, R(+)-WIN55212-2, HU-308, Rimonabant, SR-147778;
• and
• a prodrug thereof, a tautomer thereof or a pharmaceutically acceptable salt thereof;
• and
• e.) mixtures of any of the foregoing.