Piperidine compound and pharmaceutical composition thereof

A compound represented by the following formula, a salt thereof or a hydrate of them:

• wherein R1 is (1) a hydrogen atom, (2) a halogen atom, (3) a cyano group, (4) an optionally substituted C1-6 alkyl group, (5) an optionally substituted C2-6 alkenyl group, (6) an optionally substituted C2-6 alkynyl group, (7) an optionally substituted C3-8 cycloalkyl group, (8) an optionally substituted C3-8 cycloalkenyl group, (9) an optionally substituted C1-6 alkoxy group, (10) an optionally substituted C1-6 alkylthio group, (11) an optionally substituted C1-6 alkylsulfinyl group, (12) an optionally substituted C1-6 alylsulfonyl group, (13) an optionally substituted C6-14 aromatic hydrocarbon cyclic group or (14) an optionally substituted 5- to 14-membered aromatic heterocyclic group;
• R2 is (1) a hydrogen atom, (2) an optionally substituted C1-6 alkyl group, (3) an optionally substituted C2-6 alkenyl group, (4) an optionally substituted C2-6 alkynyl group, (5) an optionally substituted C3-8 cycloalkyl group, (6) an optionally substituted C3-8 cycloalkenyl group, (7) an optionally substituted amino group, (8) an optionally substituted C6-14 aromatic hydrocarbon cyclic group or (9) an optionally substituted 5- to 14-membered aromatic heterocyclic group;
• W is (1) a single bond, (2) an optionally substituted C1-6 alkylene group, (3) an optionally substituted C2-6 alkenylene group, (4) an optionally substituted C2-6 alkynylene group or (5) a group represented by the formula —U—V— (wherein U is (i) a single bond, (ii) an oxygen atom, (iii) a sulfur atom, (iv) a group represented by the formula —NH—, (v) an optionally substituted C1-6 alkylene group, (vi) an optionally substituted C2-6 alkenylene group or (vii) an optionally substituted C2-6 alkynylene group;
• V is (i) a single bond, (ii) an optionally substituted C1-6 alkylene group, (iii) an optionally substituted C2-6 alkenylene group, (iv) an optionally substituted C2-6 alkynylene group, (v) an oxygen atom, (vi) a sulfur atom, or (vii) a group represented by the formula —CO—, (viii) —SO— or (ix) —SO2—, provided that the case where U and V mean the same group in the above definition is excluded, and one of U and V is a single bond, an optionally substituted C1-6 alkylene group, an optionally substituted C2-6 alkenylene group or an optionally substituted C2-6 alkynylene group);
• Z is (1) an optionally substituted C6-14 aromatic hydrocarbon cyclic group, (2) an optionally substituted 5- to 14-membered aromatic heterocyclic group or (3) a group represented by the formula —N(R4)R5 (wherein R4 and R5 may be the same as or different from each other and each represents (i) a hydrogen atom, (ii) an optionally substituted C1-6 alkyl group, (iii) an optionally substituted C2-6 alkenyl group, (iv) an optionally substituted C2-6 alkynyl group, (v) an optionally substituted C3-8 cycloalkyl group, (vi) an optionally substituted C3-8 cycloalkenyl group, (vii) an optionally substituted C6-14 aromatic hydrocarbon cyclic group, (viii) an optionally substituted 5 to 14-membered aromatic heterocyclic group or (ix) a C1-6 aliphatic acyl group, or (x) R4 and R5 may be bound together to form a 3- to 8-membered nitrogen-containing cyclic group);
• and
• l represents an integer of 0 to 6.

A compound represented by the following formula, a salt thereof or a hydrate of them:

• wherein R1 is (1) a hydrogen atom, (2) a halogen atom, (3) a cyano group, (4) an optionally substituted C1-6 alkyl group, (5) an optionally substituted C1-6 alkenyl group, (6) an optionally substituted C2-6 alkynyl group, (7) an optionally substituted C3-8 cycloalkyl group, (8) an optionally substituted C3-8 cycloalkenyl group, (9) an optionally substituted C1-6 alkoxy group, (10) an optionally substituted C1-6 alkylthio group, (11) an optionally substituted C1-6 alkylsulfinyl group, (12) an optionally substituted C1-6 aralkylsulfonyl group, (13) an optionally substituted C6-14 aromatic hydrocarbon cyclic group or (14) an optionally substituted 5- to 14-membered aromatic heterocyclic group;
• W is (1) a single bond, (2) an optionally substituted C1-6 alkylene group, (3) an optionally substituted C2-6 alkenylene group, (4) an optionally substituted C2-6 alkynylene group or (5) a group represented by the formula —U—V— (wherein U is (i) a single bond, (ii) an oxygen atom, (iii) a sulfur atom, (iv) a group represented by the formula —NH—, (v) an optionally substituted C1-6 alkylene group, (vi) an optionally substituted C2-6 alkenylene group or (vii) an optionally substituted C2-6 alkynylene group;
• V is (i) a single bond, (ii) an optionally substituted C1-6 alkylene group, (iii) an optionally substituted C2-6 alkenylene group, (iv) an optionally substituted C2-6 alkynylene group, (v) an oxygen atom, (vi) a sulfur atom, or (vii) a group represented by the formula —CO—, (viii) —SO— or (ix) —SO2—, provided that the case where U and V mean the same group in the above definition is excluded, and one of U and V is a single bond, an optionally substituted C1-6 alkylene group, an optionally substituted C2-6 alkenylene group or an optionally substituted C2-6 alkynylene group);
• Z is (1) an optionally substituted C6-14 aromatic hydrocarbon cyclic group, (2) an optionally substituted 5- to 14-membered aromatic heterocyclic group or (3) a group represented by the formula —N(R4)R5 (wherein R4 and R5 may be the same as or different from each other and each represents (i) a hydrogen atom, (ii) an optionally substituted C1-6 alkyl group, (iii) an optionally substituted C2-6 alkenyl group, (iv) an optionally substituted C2-6 alkynyl group, (v) an optionally substituted C3-8 cycloalkyl group, (vi) an optionally substituted C3-8 cycloalkenyl group, (vii) an optionally substituted C6-14 aromatic hydrocarbon cyclic group, (viii) an optionally substituted 5- to 14-membered aromatic heterocyclic group or (ix) a C1-6 aliphatic acyl group, or (x) R4 and R5 may be bound together to form a 3- to 8-membered nitrogen-containing cyclic group);
• and
• la represents an integer of 1 or 2.

A compound, a salt thereof or a hydrate of them, selected from the group consisting of 1-[(2-Oxo-1,2-dihydro-3-pyridinyl)methyl]-4-[2-[2-(cyclohexylmethyloxy)phenyl]ethyl]piperidine,

• 1-[(5-chloro-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-4-[2-[2,3-(methylenedioxy)phenyl]ethyl]piperidine,
• 1-[(5-chloro-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-4-[2-(2-(fluorophenyl)ethyl]piperidine,
• 1-[(5-chloro-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-4-[2-[2-(isobutyloxy)phenyl]ethyl]piperidine,
• 1-[(5-chloro-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-4-[(E)-2-(2-fluorophenyl)-1-ethenyl]piperidine,
• 1-[(5-fluoro-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-4-[(E)-2-(2-fluorophenyl)-1-ethenyl]piperidine,
• 1-[(2-oxo-1,2-dihydro-3-pyridinyl)methyl]-4-[(E)-2-[2-(benzyloxy)phenyl]-1-ethenyl]piperidine,
• 1-[(2-oxo-1,2-dihydro-3-pyridinyl)methyl]-4-[(E)-2-[(2-cyclohexylmethyloxy)phenyl]-1-ethenyl]piperidine,
• 1-[(2-oxo-1,2-dihydro-3-pyridinyl)methyl]-4-[(Z)-2-[(2-cyclohexylmethyloxy)phenyl]-1-ethenyl]piperidine,
• 1-[(5-fluoro-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-4-[(E)-2-[(2-cyclohexylmethyloxy)phenyl]-1-ethenyl]piperidine,
• 1-[(2-oxo-1,2-dihydro-3-pyridinyl)methyl]-4-[2-(2-cyclohexylmethyloxy)phenyl]-1-ethynyl]piperidine,
• 1-[(5-chloro-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-4-[2,4-(difluorophenoxy)methyl]piperidine;
• and
• 1-[(5-chloro-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-4-[2,5-(difluorophenoxy)methyl]piperidine.