SUBSTITUTED PIPERIDINE COMPOUND AND USE THEREOF
Provided is a substituted piperidine compound having an orexin type 2 receptor agonist activity. A compound represented by the formula (I): wherein each symbol is as described in the DESCRIPTION, or a salt thereof has an orexin type 2 receptor agonist activity, and is useful as a prophylactic or therapeutic agent for narcolepsy.
21 . A compound represented by the formula:
wherein
R 1 is an acyl group, or a hydrogen atom;
R 2 is an optionally substituted 3- to 6-membered saturated cyclic group; and
R 3 is an optionally substituted C 1-6 alkyl group, a mono- or di-C 1-6 alkylamino group or a C 3-6 cycloalkyl group,
or a salt thereof.
22 . The compound according to claim 21 , wherein R 3 is an optionally substituted C 1-6 alkyl group or a mono- or di-C 1-6 alkylamino group, or a salt thereof.
23 . The compound according to claim 21 , which is represented by the formula:
wherein R 1 , R 2 and R 3 are as defined in claim 21 , or a salt thereof.
24 . The compound according to claim 21 , wherein R 1 is an acyl group, or a salt thereof.
25 . The compound according to claim 21 , wherein R 2 is a C 3-6 cycloalkyl group substituted by one optionally substituted phenyl group, or a salt thereof.
26 . The compound according to claim 21 , wherein R 3 is an optionally substituted C 1-6 alkyl group, or a salt thereof.
27 . The compound according to claim 21 , wherein R 1 is
(1) a hydrogen atom,
(2) an optionally substituted C 1-6 alkyl-carbonyl group,
(3) an optionally substituted C 3-10 cycloalkyl-carbonyl group,
(4) an optionally substituted C 1-6 alkoxy-carbonyl group,
(5) an optionally substituted C 3-10 cycloalkyloxy-carbonyl group,
(6) an optionally substituted C 6-14 aryl-carbonyl group,
(7) an optionally substituted C 6-14 aryloxy-carbonyl group,
(8) an optionally substituted 5- to 14-membered aromatic heterocyclylcarbonyl group,
(9) an optionally substituted 3- to 14-membered non-aromatic heterocyclylcarbonyl group,
(10) an optionally substituted mono- or di-C 1-6 alkyl-carbamoyl group,
(11) an optionally substituted mono- or di-C 3-10 cycloalkyl-carbamoyl group,
(12) an optionally substituted mono- or di-C 6-14 aryl-carbamoyl group,
(13) an optionally substituted C 1-6 alkylsulfonyl group,
(14) an optionally substituted C 3-10 cycloalkylsulfonyl group,
(15) an optionally substituted C 6-14 arylsulfonyl group,
(16) an optionally substituted heterocyclyl-sulfonyl group,
(17) an optionally substituted mono- or di-C 1-6 alkyl-sulfamoyl group or
(18) an optionally substituted C 1-6 alkyl-carbonyl-carbonyl group;
R 2 is a C 3-6 cycloalkyl group or a 3- to 6-membered saturated monocyclic non-aromatic heterocyclic group, each of which is optionally substituted by 1 to 3 substituents selected from
(1) deuterium,
(2) a halogen atom,
(3) a hydroxy group,
(4) an optionally substituted C 1-6 alkyl group,
(5) a C 3-10 cycloalkyl group,
(6) an optionally substituted C 1-6 alkoxy group,
(7) an optionally substituted C 6-14 aryl group,
(8) a C 6-14 aryloxy group,
(9) a tri-C 1-6 alkylsilyloxy group,
(10) an optionally substituted 5- to 14-membered aromatic heterocyclic group and
(11) an optionally substituted C 6-14 aryl-carbonyl group; and
R 3 is a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from a halogen atom and a C 6-14 aryl group, or a mono- or di-C 1-6 alkylamino group, or a salt thereof.
28 . The compound according to claim 21 , wherein R 1 is
(1) a hydrogen atom,
(2) a C 1-6 alkyl-carbonyl group optionally substituted by 1 to 7 substituents selected from
(i) a halogen atom, (ii) a cyano group, (iii) a hydroxy group, (iv) a C 3-10 cycloalkyl group, (v) a C 1-6 alkoxy group, (vi) a C 6-14 aryl group, (vii) a C 6-14 aryloxy group, (viii) a pyrazolyl group, a thiazolyl group, a pyrimidinyl group or a pyridazinyl group, each of which is optionally substituted by an oxo group, (ix) a pyrazolyloxy group optionally substituted by 1 to 3 C 1-6 alkyl groups, (x) a C 1-6 alkyl-carbonyl group, (xi) a C 1-6 alkoxy-carbonyl group, (xii) a C 1-6 alkyl-carbonyloxy group, (xiii) a C 1-6 alkylsulfonyl group, (xiv) a mono- or di-C 1-6 alkylamino group, (xv) a C 1-6 alkyl-carbonylamino group and (xvi) a (C 1-6 alkyl) (C 1-6 alkyl-carbonyl)amino group,
(3) a C 3-10 cycloalkyl-carbonyl group optionally substituted by 1 to 3 substituents selected from a halogen atom, a cyano group, a hydroxy group, an oxo group and a C 1-6 alkyl group,
(4) a C 1-6 alkoxy-carbonyl group optionally substituted by 1 to 6 substituents selected from deuterium, a halogen atom and a C 6-14 aryl group,
(5) a C 3-10 cycloalkyloxy-carbonyl group optionally substituted by 1 to 3 substituents selected from a C 1-6 alkyl group,
(6) a C 6-14 aryl-carbonyl group optionally substituted by 1 to 3 substituents selected from a halogen atom and a C 6-14 aryl group,
(7) a C 6-14 aryloxy-carbonyl group,
(8) a furylcarbonyl group, a thienylcarbonyl group, a pyrazolylcarbonyl group, an isoxazolylcarbonyl group or a pyridylcarbonyl group, each of which is optionally substituted by 1 to 3 substituents selected from a C 1-6 alkyl group,
(9) an azetidinylcarbonyl group, an oxetanylcarbonyl group, a pyrrolidinylcarbonyl group, a tetrahydrofuranylcarbonyl group, a tetrahydropyranylcarbonyl group or a morpholinylcarbonyl group, each of which is optionally substituted by 1 to 3 substituents selected from an oxo group, a C 1-6 alkyl-carbonyl group, a C 1-6 alkoxy-carbonyl group and a C 1-6 alkylsulfonyl group,
(10) a mono- or di-C 16 alkyl-carbamoyl group optionally substituted by 1 to 3 substituents selected from a halogen atom, a cyano group, a hydroxy group and a C 1-6 alkoxy group,
(11) a mono- or di-C 3-10 cycloalkyl-carbamoyl group,
(12) a mono- or di-C 6-14 aryl-carbamoyl group,
(13) a C 1-6 alkylsulfonyl group,
(14) a C 3-10 cycloalkylsulfonyl group,
(15) a C 6-14 arylsulfonyl group optionally substituted by 1 to 3 halogen atoms,
(16) a thienylsulfonyl group, a pyrazolylsulfonyl group, an imidazolylsulfonyl group, a pyridylsulfonyl group or a dihydrochromenylsulfonyl group, each of which is optionally substituted by 1 to 3 substituents selected from a C 1-6 alkyl group,
(17) a mono- or di-C 1-6 alkyl-sulfamoyl group or
(18) a C 1-6 alkyl-carbonyl-carbonyl group;
R 2 is a C 3-6 cycloalkyl group, a pyrrolidinyl group, a piperidinyl group or a dioxanyl group, each of which is optionally substituted by 1 to 3 substituents selected from
(1) deuterium,
(2) a halogen atom,
(3) a hydroxy group,
(4) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from a halogen atom and a C 6-14 aryl group,
(5) a C 3-10 cycloalkyl group,
(6) a C 1-6 alkoxy group optionally substituted by a C 3-10 cycloalkyl group,
(7) a C 6-14 aryl group optionally substituted by 1 to 3 substituents selected from a halogen atom, a cyano group, a C 1-6 alkyl group optionally substituted by 1 to 3 halogen atoms, a C 1-6 alkoxy group optionally substituted by 1 to 3 halogen atoms and a hydroxy group,
(8) a C 6-14 aryloxy group,
(9) a tri-C 1-6 alkylsilyloxy group,
(10) a pyrazolyl group, a thiazolyl group, a pyridyl group, a pyrimidinyl group, a quinazolinyl group, a benzothiazolyl group or an isoquinolinyl group, each of which is optionally substituted by 1 to 3 substituents selected from a halogen atom, a C 1-6 alkyl group and a C 1-6 alkoxy group, and
(11) a C 6-14 aryl-carbonyl group; and
R 3 is a C 1-6 alkyl group, or a mono- or di-C 1-6 alkylamino group, or a salt thereof.
29 . The compound according to claim 21 , wherein R 1 is
(1) a hydrogen atom,
(2) a C 1-6 alkyl-carbonyl group optionally substituted by a hydroxy group,
(3) a cyclopropanecarbonyl group,
(4) a C 1-6 alkoxy-carbonyl group or
(5) a mono- or di-C 1-6 alkyl-carbamoyl group;
R 2 is
(A) a cyclohexyl group optionally substituted by 1 to 3 substituents selected from
(1) a C 1-6 alkyl group and
(2) a phenyl group optionally substituted by 1 to 3 substituents selected from a halogen atom, a C 1-6 alkyl group optionally substituted by 1 to 3 halogen atoms and a C 1-6 alkoxy group or
(B) a piperidinyl group optionally substituted by 1 to 3 pyrimidinyl groups; and
R 3 is a C 1-6 alkyl group or a di-C 1-6 alkylamino group, or a salt thereof.
30 . The compound according to claim 21 , wherein R 1 is
(1) a C 1-6 alkyl-carbonyl group optionally substituted by a hydroxy group,
(2) a C 1-6 alkoxy-carbonyl group or
(3) a mono- or di-C 1-6 alkyl-carbamoyl group;
R 2 is a cyclohexyl group optionally substituted by 1 to 3 substituents selected from
(1) a C 1-6 alkyl group and
(2) a phenyl group optionally substituted by 1 to 3 halogen atoms; and
R 3 is a C 1-6 alkyl group, or a salt thereof.
31 . A medicament comprising N-((2R,3S)-1-glycoloyl-2-(((cis-4-(2,3,6-trifluorophenyl)cyclohexyl)oxy)methyl)piperidin-3-yl)methanesulfonamide or a salt thereof.