Benzimidazole cannabinoid agonists bearing a substituted heterocyclic group

Compound of formula (I)

• the pharmaceutically acceptable acid addition salts and the stereochemically isomeric forms thereof, wherein
• n is an integer 1 or 2;
• R1is C2-6alkyl;
• C1-6akyl substituted with 1, 2 or 3 substituents each independently selected from halo, hydroxy, C1-4akyl, C1-4alkyloxy, cyano, nitro, amino, and mono- or di(C1-4 alkyl)amino;
• C1-6alkyl substituted with a cyclic group selected from C3-8cycloalkyl, oxoC3-8cycloalkyl, C5-8cycloalkenyl, bicycle[2.2.1]hept-2-enyl, bicyclo[2.2.1]octanyl and bicycle[3.1.1]heptanyl, wherein said cyclic group is optionally substituted with one or more substituents each independently selected from halo, hydroxy, C1-4alkyl, C1-4alkyloxy, cyano, nitro, NR5R6 or CONR5R6 wherein R5 and R6 are independently selected from hydrogen or C1-4alkyl;
• or
• C1-6alkyl substituted with a heterocycle selected from pyrrolidinyl, piperidinyl, homopiperidinyl, piperazinyl, morpholinyl, tetrahydrofuranyl, tetrahydropyranyl, 1,1-dioxo-tetrahydro-thiopyranyl, [1,3]dioxolanyl, [1,4]dioxolanyl, [1,3]dioxanyl, 5-oxo-pyrrolidin-2-yl, or 2-oxo-oxepanyl;
• wherein said heterocycle is optionally substituted with one or two substituents each independently selected from C1-4alkyl, polyhaloC1-4alkyl, halo, hydroxy, C1-4alkyloxy, cyano, trifluoromethyl, COR5, COOR5, CONR5R6, SO2R5 wherein R5 and R6 are independently selected from hydrogen or C1-4alkyl or polyhaloC1-4alkyl;
• R2 is C2-6alkyl;
• C1-6alkyl substituted with 1, 2 or 3 substituents each independently selected from halo, hydroxy, C1-4alkyl, C3-6cycloalkyl, C1-4alkyloxy, polyhaloC1-4alkyloxy, trifluoromethyl, cyano, nitro, NR7R8, CONR7R8, or NHCOR7 wherein R7 and R8 are independently selected from hydrogen, C1-4alkyl or polyhaloC1-4alkyl;
• C3-6alkenyl;
• C3-6alkynyl;
• C3-6cycloalkyl;
• or
• cyclic group selected from pyrrolidininyl, piperidinyl, piperazinyl, morpholinyl, tetrahydrofuranyl, tetrahydropyranyl, [1,3]dioxolanyl, [1,3]dioxanyl, [1,4]dioxanyl, 5-oxo-pyrrolidin-2-yl, bicycle[2.2.1]hept-2-enyl, and bicycle[3.1.1]heptanyl;
• wherein said cyclic group is optionally substituted with one or two substituents each independently selected from C1-4alkyl, halo, hydroxy, C1-4alkyloxy, or trifluoromethyl;
• R3 is hydrogen, halo, C1-4alkyl, C1-4alkyloxy, trifluoromethyl or cyano;
• R4 is heteroaryl;
• heteroaryl is selected from N-oxy-pyridinyl, N-oxy-pyridazinyl, N-oxy-pyrimidinyl or N-oxy-pyrazinyl;
• or
• selected from furanyl, thiophenyl, pyrrolyl, pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, triazolyl, tetrazolyl, isothiazolyl, thiadiazolyl, oxadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, N-oxy-pyridinyl, N-oxy-pyridazinyl, N-oxy-pyrimidinyl, N-oxy-pyrazinyl or 2-oxo-1,2-dihydro-pyridinyl, each substituted with 1, 2 or 3 substituents each independently selected from halo;
• hydroxy;
• C1-4alkyl;
• C3-6cycloalkyl;
• C2-6alkenyl;
• C2-6alkenyl substituted with 1 or 2 substituents selected from halo;
• C2-6alkynyl;
• C2-6alkynyl substituted with C1-4alkyloxy;
• C1-4alkyloxy;
• C1-4alkyloxyC1-4alkyl;
• polyhaloC1-4alkyl;
• polyhaloC1-4alkyloxy;
• cyano;
• nitro;
• NR9R10;
• R11-carbonyl;
• R11—SO2—;
• C1-4alkyl substituted with hydroxy, NR9R10, R11-carbonyl or R11—SO2—;
• oxadiazolyl optionally substituted with C1-4alkyl, polyhaloC1-4alkyl or C3-6cycloalkyl;
• or dioxolanyl optionally substituted with 1 or 2 C1-4alkyl;
• C1-4alkyloxy substituted with hydroxy, C1-4alkyloxy, C1-4alkylcarbonylamino, C1-4alkyloxycarbonylamino, amino, di(C1-4akyl)amino or morpholinyl;
• C1-4alkylcarbonylaminoC1-4alkylamino;
• C1-4alkyloxyC1-4alkylamino;
• wherein R9 and R10are independently from another selected from hydrogen, C1-4alkyl, polyhaloC1-4alkyl, aminosulfonyl, or C1-8alkylsulfonyl;
• or R11-carbonyl;
• wherein R9 and R10are taken together with the nitrogen atom bearing R9 and R10 may form a pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl ring;
• and
• wherein R11 is C1-4alkyl, C1-4alkyloxy, hydroxy, amino, mono- or di-(C1-4alkyl)amino, (hydroxyC1-4alkyl)amino, (C1-4alkyloxyC1-4alkyl)amino, di(C1-4alkyl)aminoC1-4alkyl, pyrrolidinyl, piperidinyl, morpholinyl, N-methyl-piperazinyl, or C1-4alkyl substituted with hydroxy, C1-4alkyloxy, trifluoromethyl, C1-4alkyloxyC1-4alkyl, pyrrolidinyl, piperidinyl, morpholinyl, N-methyl-piperazinyl, or 2-oxo-imidazolidin-1-yl.