Hydroxycarbonylphenyl substituted 4-(aminomethyl)-piperidine benzamides as 5ht4 antagonists

A compound of formula (I)

• a stereochemically isomeric form thereof, an N-oxide form thereof, or a pharmaceutically acceptable acid or base addition salt thereof, wherein
• —R1—R2— is a bivalent radical of formula
• —O—CH2—O— (a-1),
• —O—CH2—CH2— (a-2),
• —O—CH2—CH2—O— (a-3),
• —O—CH2—CH2—CH2— (a-4),
• —O—CH2—CH2—CH2—O— (a-5),
• —O—CH2—CH2—CH2—CH2— (a-6),
• —O—CH2—CH2—CH2—CH2—O— (a-7),
• —O—CH2—CH2—CH2—CH2—CH2— (a-8),
• wherein in said bivalent radicals optionally one or two hydrogen atoms on the same or a different carbon atom may be replaced by C1-16alkyl or hydroxy,
• R3 is hydrogen, halo, C1-14alkyl;
• R4 is C1-6alkyl;
• C1-6alkyl substituted with cyano, or C1-6alkyloxy;
• C1-6alkyloxy;
• cyano;
• amino or mono or di(C1-6alkyl)amino;
• R5 is hydrogen or C1-6alkyl, and the —OR5 radical is situated at the 3- or 4-position of the piperidine moiety;
• L is hydrogen, or L is a radical of formula
• -Alk-R6 (b-1),
• -Alk-X—R7 (b-2),
• -Alk-Y—C(═O)—R9 (b-3), or
• -Alk-Z-C(═O)—NR11R12 (b-4),
• wherein each Alk is C1-12alkanediyl;
• and
• R6 is hydrogen;
• hydroxy;
• cyano;
• C3-6cycloalkyl;
• C1-16alkylsulfonylamino;
• aryl or Het;
• R7 is C1-16alkyl;
• C1-16alkyl substituted with hydroxy;
• C3-6cycloalkyl;
• aryl or Het;
• X is O, S, SO2 or NR8;
• said R8 being hydrogen or C1-6alkyl;
• R9 is hydrogen, C1-6alkyl, C3-6cycloalkyl, hydroxy or aryl;
• Y is a direct bond, or NR10 wherein R10 is hydrogen or C1-6alkyl;
• Z is a direct bond, O, S, or NR10 wherein R10 is hydrogen or C1-6alkyl;
• R11 and R12 each independently are hydrogen, C1-6alkyl, C3-6cycloalkyl, or R11 and R12 combined with the nitrogen atom bearing R11 and R12 may form a pyrrolidinyl, piperidinyl, piperazinyl or 4-morpholinyl ring both being optionally substituted with C1-6alkyl;
• aryl represents unsubstituted phenyl or phenyl substituted with 1, 2 or 3 substituents each independently selected from halo, hydroxy, C1-6alkyl, C1-6alkyloxy, C1-6alkylcarbonyl, nitro, trifluoromethyl, amino, aminocarbonyl, and aminosulfonyl;
• and
• Het is furanyl;
• furanyl substituted with C1-6alkyl or halo;
• tetrahydrofuranyl;
• tetrahydrofuranyl substituted with C1-16alkyl;
• dioxolanyl;
• dioxolanyl substituted with C1-16alkyl;
• dioxanyl;
• dioxanyl substituted with C1-6alkyl;
• tetrahydropyranyl;
• tetrahydropyranyl substituted with C1-6alkyl;
• 2,3-dihydro-2-oxo-1H-imidazolyl;
• 2,3-dihydro-2-oxo-1H-imidazolyl substituted with one or two substituents each independently selected from halo, or C1-16alkyl;
• pyrrolidinyl;
• pyrrolidinyl substituted with one or two substituents each independently selected from halo, hydroxy, or C1-6alkyl;
• pyridinyl;
• pyridinyl substituted with one or two substituents each independently selected from halo, hydroxy, C1-6alkyl;
• pyrimidinyl;
• pyrimidinyl substituted with one or two substituents each independently selected from halo, hydroxy, or C1-6alkyl;
• pyridazinyl;
• pyridazinyl substituted with one or two substituents each independently selected from hydroxy, C1-6alkyloxy, C1-6alkyl or halo;
• pyrazinyl;
• pyrazinyl substituted with one ore two substituents each independently selected from hydroxy, C1-6alkyloxy, C1-6alkyl or halo.