Mtp inhibiting aryl piperydines or piperazines substituted with 5-membered heterocycles

A compound of formula (I)

• the N-oxides, the pharmaceutically acceptable acid addition salts and the stereochemically isomeric forms thereof, wherein
• the dotted line is an optional bond and is absent when X2 represents nitrogen;
• the radical —Y1—Y2— is a radical of formula
• —N═CH— (a-1),
• —CH═N— (a-2),
• —CH2—CH2— (a-3),
• —CH═CH— (a-4),
• wherein in the bivalent radicals of formula (a-1) or (a-2) the hydrogen atom may optionally be replaced by C1-6alkyl or phenyl;
• or in the bivalent radicals of formula (a-3) or (a-4) one or two hydrogen atoms may optionally be replaced by C1-6alkyl or phenyl;
• X1 is carbon or nitrogen;
• at least one of X2 or X3 represents nitrogen and the other X2 or X3 represents CH or carbon when the dotted line represents a bond, or both X2 and X3 represent nitrogen;
• R1 is C1-6alkyl;
• aryl1;
• C1-6alkyl substituted with hydroxy, C3-6cycloalkyl, aryl1 or naphthalenyl;
• C3-6cycloalkyl;
• C3-6cycloalkenyl;
• C3-6alkenyl;
• C3-6alkenyl substituted with aryl1;
• C3-6alkynyl;
• C3-6alkynyl substituted with aryl1;
• C1-4alkyloxyC1-4alkanediyl optionally substituted with aryl1;
• or when —Y1—Y2— is a radical of formula (a-1) than R1 may be taken together with Y2 to form a radical of formula —CH═CH—CH═CH— wherein each hydrogen may optionally be replaced by a substituent independently selected from C1-4alkyl, C1-4alkyloxy, polyhaloC1-4alkyl, halo, cyano, trifluoromethyl or aryl1;
• wherein aryl1 is phenyl;
• or phenyl substituted with from one or five substituents each independently selected from C1-4alkyl, C1-4alkyloxy, polyhaloC1-4alkyl, halo, cyano, or trifluoromethyl;
• R2 is hydrogen, C1-4alkyl, or halo;
• A is C1-6alkanediyl;
• C1-6alkanediyl substituted with one or two groups selected from aryl2, heteroaryl1 and C3-8cycloalkyl;
• or provided X3 represents CH said radical A may also represent NH optionally substituted with aryl2, heteroaryl1 or C3-8cycloalkyl;
• wherein aryl2 is phenyl;
• or phenyl substituted with from one to five substituents each independently selected from C1-4alkyl, C1-4alkyloxy, halo, cyano or trifluoromethyl;
• heteroaryl1 is furanyl, thienyl, pyridinyl, pyrazinyl, pyrimidinyl, or pyridazinyl;
• and said heteroaryl1 is optionally substituted with one or two substituents each independently selected from C1-4alkyl, C1-4alkyloxy, halo, cyano or trifluoromethyl;
• B is N3R4, or
• OR9;
• wherein each R3 and R4 are independently selected from hydrogen,
• C1-8alkyl,
• C1-8alkyl substituted with one, two or three substituents each independently from one another selected from hydroxy, halo, cyano, C1-4alkyloxy, C1-4alkyloxycarbonyl, C3-8cycloalkyl,
• polyhaloC1-4alkyl, NR5R6, CONR7R8, aryl3, polycyclic aryl, or heteroaryl2;
• C3-8cycloalkyl;
• C3-8cycloalkenyl;
• C3-8alkenyl;
• C3-8alkynyl;
• aryl3;
• polycyclic aryl;
• heteroaryl2;
• or
• R3 and R4 combined with the nitrogen atom bearing R3 and R4 may form an azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, azepanyl, or azocanyl ring wherein each of these rings may optionally be substituted by C1-4alkyloxycarbonyl, C1-4alkyloxycarbonylC1-4alkyl, carbonylamino, C1-4alkylcarbonylamino, CONR7R8 or C1-4alkylCONR7R8;
• wherein
• R5 is hydrogen, C1-4alkyl, aryl3, polycyclic aryl, or heteroaryl2;
• R6 is hydrogen or C1-4alkyl;
• R7 is hydrogen, C1-4alkyl or phenyl;
• R8 is hydrogen, C1-4alkyl or phenyl;
• or
• R9 is C1-6alkyl, or C1-6alkyl substituted with one, two or three substituents each independently from one another selected from hydroxy, halo, cyano, C1-4alkyloxy, C1-4alkyloxycarbonyl, C3-8cycloalkyl, C3-8cycloalkenyl, trifluoromethyl, NR5R6, CONR7R8, aryl3, polycyclic aryl, or heteroaryl2;
• wherein
• aryl3 is phenyl;
• phenyl substituted with one to five substituents each independently selected from C1-4alkyl, C1-4alkyloxy, halo, hydroxy, trifluoromethyl, cyano, C1-4alkyloxycarbonyl, C1-4alkyloxycarbonylC1-4alkyl, methylsulfonylamino, methylsulfonyl, NR5R6, C1-4alkylNR5R6, CONR7R8 or C1-4alkylCONR7R8;
• polycyclic aryl is naphthalenyl, indanyl, fluorenyl, or 1,2,3,4-tetrahydronaphtalenyl, and said polycyclic aryl is optionally substituted with one or two substituents each independently selected from C1-6alkyl, C1-6alkyloxy, phenyl, halo, cyano, C1-4alkylcarbonyl, C1-4alkyloxycarbonyl, C1-4alkyloxycarbonylC1-4alkyl, NR5R6, C1-4alkylNR5R6, CONR7R8, C1-4alkylCONR7R8 or C1-4alkyloxycarbonylamino and
• heteroaryl2 is pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, triazolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, pyrrolyl, furanyl, thienyl;
• quinolinyl;
• isoquinolinyl;
• 1,2,3,4-tetrahydro-isoquinolinyl;
• benzothiazolyl;
• benzo[1,3]dioxolyl;
• 2,3-dihydro-benzo[1,4]dioxinyl;
• indolyl;
• 2,3-dihydro-1H-indolyl;
• 1H-benzoimidazolyl;
• and said heteroaryl2 is optionally substituted with one or two substituents each independently selected from C1-6alkyl, C1-6alkyloxy, phenyl, halo, cyano, C1-4alkylcarbonyl, C1-4alkyloxycarbonyl, C1-4alkyloxycarbonylC1-4alkyl, NR5R6, C1-4alkylNR5R5, CONR7R8 or C1-4alkylCONR7R8.