N-substituted imide derivatives with serotonergic activity

A pharmaceutical composition comprising an effective amount of a compound of Formula (I)

• wherein:
• n is an integer of 0 to 5;
• X is a moiety
• Y is a moiety selected from the group consisting of:
• R1 is aryl of 6 to 12 carbon atoms optionally substituted with one or more substituents selected from alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms, hydroxy, alkoxy of 1 to 10 carbon atoms, perhaloalkyl of 1 to 10 carbon atoms, perhaloalkoxy of 1 to 10 carbon atoms, —CN, —NO2, and halogen;
• heteroaryl selected from 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl and 4-pyridyl;
• optionally substituted with 1 to 3 substituents which may be the same or different selected from alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —CN, —NO2, and halogen;
• bicyclic heteroaryl selected from indolyl, azaindolyl, benzimidazolyl, indazolyl, quinolinyl, isoquinolinyl, benzodioxanyl, benzopyranyl, benzofuranyl, dihydrobenzofuranyl, benzothiophenyl, benzothiazolyl, benzothiadiazolyl, benzooxazolyl and 2,3-dihydro-benzo[1,4]dioxinyl;
• optionally substituted with 1 to 3 substituents which may be the same or different, selected from alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —CN, —NO2, and halogen;
• R2 is independently H, alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms, alkoxy of 1 to 10 carbon atoms, hydroxy, —(CH2)z—O-alkyl of 1 to 6 carbon atoms, —(CH2)z—S-alkyl of 1 to 6 carbon atoms, —(CH2)zOH, perhaloalkyl of 1 to 10 carbon atoms, perhaloalkoxy of 1 to 10 carbon atoms, —CN, —NO2, and halogen;
• aryl of 6 to 12 carbon atoms optionally substituted with one or more substituents selected from alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms, hydroxy, alkoxy of 1 to 10 carbon atoms, perhaloalkyl of 1 to 10 carbon atoms, perhaloalkoxy of 1 to 10 carbon atoms, —CN, —NO2, and halogen;
• heteroaryl selected from 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl and 4-pyridyl;
• optionally substituted with 1 to 3 substituents which may be the same or different selected from alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —CN, —NO2, and halogen;
• bicyclic heteroaryl selected from indolyl, azaindolyl, benzimidazolyl, indazolyl, quinolinyl, isoquinolinyl, benzodioxanyl, benzopyranyl, benzofuranyl, dihydrobenzofuranyl, benzothiophenyl, benzothiazolyl, benzothiadiazolyl, benzooxazolyl and 2,3dihydro-benzo[1,4]-dioxinyl;
• optionally substituted with 1 to 3 substituents which may be the same or different, selected from alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —CN, —NO2, and halogen;
• z is an integer of 1 to 3;
• R3 is independently cycloalkyl or cycloalkenyl of 3 to 10 carbon atoms;
• R4 is aryl of 6 to 12 carbon atoms optionally substituted with one or more substituents selected from alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms, hydroxy, alkoxy of 1 to 10 carbon atoms, perhaloalkyl of 1 to 10 carbon atoms, perhaloalkoxy of 1 to 10 carbon atoms, —CN, —NO2, and halogen;
• heteroaryl selected from 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl and 4-pyridyl;
• optionally substituted with 1 to 3 substituents which may be the same or different selected from alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —CN, —NO2, and halogen;
• bicyclic heteroaryl selected from indolyl, azaindolyl, benzimidazolyl, indazolyl, quinolinyl, isoquinolinyl, benzodioxanyl, benzopyranyl, benzofuranyl, dihydrobenzofuranyl, benzothiophenyl, benzothiazolyl, benzothiadiazolyl, benzooxazolyl and 2,3-dihydro-benzo[1,4]-dioxinyl;
• optionally substituted with 1 to 3 substituents which may be the same or different, selected from alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —CN, —NO2, and halogen;
• with the proviso that X is not the radical
• when R5 is H, halogen, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms and hydroxyl;
• n is 0;
• R2 is H or alkyl of 1 to 6 carbon atoms;
• Y is the radical
• and R4 is phenyl unsubstituted or substituted with one to three substituents which are the same or different selected from halogen, alkyl of 1 to 6 carbon atoms and alkoxy of 1 to 6 carbon atoms;
• or a pharmaceutically acceptable salt thereof together with one or more pharmaceutically acceptable carriers.

A method of treating anxiety in a warm-blooded animal in need thereof, which comprises administering to said warm-blooded animal an effective amount of a compound of Formula (I)

• wherein:
• n is an integer of 0 to 5;
• X is a moiety
• Y is a moiety selected from the group consisting of:
• R1 is aryl of 6 to 12 carbon atoms optionally substituted with one or more substituents selected from alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms, hydroxy, alkoxy of 1 to 10 carbon atoms, perhaloalkyl of 1 to 10 carbon atoms, perhaloalkoxy of 1 to 10 carbon atoms, —CN, —NO2, and halogen;
• heteroaryl selected from 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyrddyl, 3pyridyl and 4-pyridyl;
• optionally substituted with 1 to 3 substituents which may be the same or different selected from alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —CN, —NO2, and halogen;
• bicyclic heteroaryl selected from indolyl, azaindolyl, benzimidazolyl, indazolyl, qutinolinyl, isoqulnolinyl, benzodioxanyl, benzopyranyl, benzofuranyl, dihydrobenzoturanyl, benzothlophenyl, benzothiazolyl, benzothiadiazolyl, benzooxazolyl and 2,3-dihydro-benzo[1,4]dioxinyl;
• optionally substituted with 1 to 3 substituents which may be the same or different, selected from alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —CN, —N2, and halogen;
• R2 is independently H, alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms, alkoxy of 1 to 10 carbon atoms, hydroxy, —(CH2)z—O-alkyl of 1 to 6 carbon atoms, —(CH2)z—S-alkyl of 1 to 6 carbon atoms, —(CH2)zOH, perhaloalkyl of 1 to 10 carbon atoms, perhaloalkoxy of 1 to 10 carbon atoms, —CN, —NO2, and halogen;
• aryl of 6 to 12 carbon atoms optionally substituted with one or more substituents selected from alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms, hydroxy, alkoxy of 1 to 10 carbon atoms, perhaloalkyl of 1 to 10 carbon atoms, perhaloalkoxy of 1 to 10 carbon atoms, —CN, —NO2, and halogen;
• heteroaryl selected from 2-furyl, 3furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl and 4-pyridyl;
• optionally substituted with 1 to 3 substituents which may be the same or different selected from alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —CN, —NO2, and halogen;
• bicyclic heteroaryl selected from indolyl, azaindolyl, benzimidazolyl, indazolyl, quinolinyl, isoquinolinyl, benzodioxanyl, benzopyranyl, benzofuranyl, dihydrobenzofuranyl, benzothiophenyl, benzothiazolyl, benzothiadiazolyl, benzooxazolyl and 2,3-dihydro-benzo[1,4]-dioxinyl;
• optionally substituted with 1 to 3 substituents which may be the same or different, selected from alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —CN, —NO2 and halogen;
• z is an integer of 1 to 3;
• R3 independently cycloalkyl or cycloalkenyl of 3 to 10 carbon atoms;
• R4 is aryl of 6 to 12 carbon atoms optionally substituted with one or more substituents selected from alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms, hydroxy, alkoxy of 1 to 10 carbon atoms, perhaloalkyl of 1 to 10 carbon atoms, perhaloalkoxy of 1 to 10 carbon atoms, —CN, —NO2, and halogen, heteroaryl selected from 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl and 4-pyridyl;
• optionally substituted with 1 to 3 substituents which may be the same or different selected from alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —CN, —NO2, and halogen;
• bicyclic heteroaryl selected from indolyl, azaindolyl, benzimidazolyl, indazolyl, quinolinyl, isoquinolinyl, benzodioxanyl, benzopyranyl, benzofuranyl, dihydrobenzofuranyl, benzothiophenyl, benzothiazolyl, benzothiadiazolyl, benzooxazolyl and 2,3-dihydro-benzo[1,4]-dioxinyl;
• optionally substituted with 1 to 3 substituents which may be the same or different. selected from alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —CN, —NO2, and halogen;
• with the proviso that X is not the radical
• when R5 is H, halogen, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms and hydroxyl;
• n is 0;
• R2 is H or alkyl of 1 to 6 carbon atoms;
• Y is the radical
• and R4 is phenyl unsubstituted or substituted with one to three substituents which are the same or different selected from halogen, alkyl of 1 to 6 carbon atoms and alkoxy of 1 to 6 carbon atoms;
• or a pharmaceutically acceptable salt thereof.

A method of treating depression in a warm-blooded animal in need thereof, which comprises administering to said warm-blooded animal an effective amount of a compound of Formula (I)

• wherein:
• n is an integer of 0 to 5;
• X is a moiety
• Y is a moiety selected from the group consisting of:
• R1 is aryl of 6 to 12 carbon atoms optionally substituted with one or more substituents selected from alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms, hydroxy, alkoxy of 1 to 10 carbon atoms, perhaloalkyl of 1 to 10 carbon atoms, perhaloalkoxy of 1 to 10 carbon atoms, —CN, —NO2, and halogen;
• heteroaryl selected from 2-furyl, 3-furyl, 2-thienyl, 3thienyl, 2-pyridyl, 3-pyridyl and 4-pyridyl;
• optionally substituted with 1 to 3 substituents which may be the same or different selected from alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —CN, —NO2, and halogen;
• bicyclic heteroaryl selected from indolyl, azaindolyl, benzimidazolyl, indazolyl, quinolinyl, isoquinolinyl, benzodioxanyl, benzopyranyl, benzofuranyl, dihydrobenzofuranyl, benzothiophenyl, benzothiazolyl, benzothiadiazolyl, benzooxazolyl and 2,3-dihydro-benzo[1,4]dioxinyl;
• optionally substituted with 1 to 3 substituents which may be the same or different selected from alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —CN, —NO2, and halogen;
• R2 is independently H, alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms, alkoxy of 1 to 10 carbon atoms, hydroxy, —(CH2)z—O-alkyl of 1 to 6 carbon atoms, —(CH2)z—S-alkyl of 1 to 6 carbon atoms, —(CH2)zOH, perhaloalkyl of 1 to 10 carbon atoms, perhaloalkoxy of 1 to 10 carbon atoms, —CN, —NO2, and halogen;
• aryl of 6 to 12 carbon atoms optionally substituted with one or more substituents selected from alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms, hydroxy, alkoxy of 1 to 10 carbon atoms, perhaloalkyl of 1 to 10 carbon atoms, perhaloalkoxy of 1 to 10 carbon atoms, —CN, —NO2, and halogen;
• teteroaryl selected from 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl and 4-pyridyl;
• optionally substituted with 1 to 3 substituents which may be the same or different selected from alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —CN, —NO2, and halogen;
• bicyclic heteroaryl selected from indolyl, azaindolyl, benzimidazolyl, indazolyl, quinolinyl, isoquinolinyl, benzodioxanyl, benzopyranyl, benzofuranyl, dihydrobenzofuranyl, benzothiophenyl, benzothiazolyl, benzothiadiazolyl, benzooxazolyl and 2,3-dihydrobenzo[1,4]-dioxinyl;
• optionally substituted with 1 to 3 substituents which may be the same or different, selected from alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —CN, —NO2, and halogen;
• z is an integer of 1 to 3,
• R3 is independently cycloalkyl or cycloalkenyl of 3 to 10 carbon atoms;
• R4 is aryl of 6 to 12 carbon atoms optionally substituted with one or more substituents selected from alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms, hydroxy, alkoxy of 1 to 10 carbon atoms, perhaloalkyl of 1 to 10 carbon atoms, perhaloalkoxy of 1 to 10 carbon atoms, —CN, —NO2, and halogen;
• heteroaryl selected from 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl and 4-pyridyl;
• optionally substituted with 1 to 3 substituents which may be the same or different selected from alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —CN, —NO2, and halogen;
• bicyclic heteroaryl selected from indolyl, azaindolyl, benzimidazolyl, indazolyl, quinolinyl, isoqulnolinyl, benzodioxanyl, benzopyranyl, benzofuranyl, dihydrobenzofuranyl, benzothiophenyl, benzothiazolyl, benzothiadiazolyl, benzooxazolyl and 2,3-dihydro-benzo[1,4]-dioxinyl;
• optionally substituted with 1 to 3 substituents which may be the same or different, selected from alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —CN, —NO2, and halogen;
• with the proviso that X is not the radical
• when R5 is H, halogen, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms and hydroxyl;
• n is 0;
• R2 is H or alkyl of 1 to 6 carbon atoms;
• Y is the radical
• and R4 is phenyl unsubstituted or substituted with one to three substituents which are the same or different selected from halogen, alkyl of 1 to 6 carbon atoms and alkoxy of 1 to 6 carbon atoms;
• or a pharmaceutically acceptable salt thereof.