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US 10,730,830 B2Granted
Tetrahydronaphthalene derivative
AssigneeOno Pharmaceutical Co., Ltd.
InventorsToshihide Watanabe, Kensuke Kusumi, Yuichi Inagaki
Life of this patent
Estimating the term…
Abstract
A compound of general formula (I-1): wherein the symbols are defined in the specification, has a selective S1P5 receptor binding activity and modulates the function of an S1P5 receptor, and can therefore be a therapeutic agent for a S1P5-mediated disease, for example, neurodegenerative diseases such as schizophrenia, Binswanger's disease and the like.
Claims17
A compound represented by general formula (I-1):
- wherein, X1 and X2 each represent independently a CH2 or an NH, provided that X1 and X2 are not represent NH at the same time,
- Y represents (1) —CH2—, (2) —NH—, (3) —S— or (4) —O—,
- WA represents (1) a C1-12 alkylene group, (2) a C2-12 alkenylene group, (3) a C2-12 alkynylene group, (4) —C1-12 alkylene-O—, (5) —C2-12 alkenylene-O—, (6) —C2-12 alkynylene-O—, (7) —C1-12 alkylene-ring2-, (8) —C2-12 alkenylene-ring2- or (9) —C2-12 alkynylene-ring2-, wherein, an alkylene group, an alkenylene group and an alkynylene group may be substituted with one to five halogen atoms,
- R1 represents (1) -L-, (2) -L-ring3- or (3) -L-NR13—,
- R2 represents (1) a halogen atom, (2) a C1-4 alkyl group, (3) a C1-4 haloalkyl group, or (4) a C1-4 haloalkoxy group,
- R3-1 represents (1) a halogen atom, (2) a C1-4 alkyl group, (3) a C1-4 haloalkyl group, (4) a C1-4 alkoxy group, (5) a C1-4 haloalkoxy group, (6) a nitrile group, (7) —S—C1-4 alkyl group, (8) —S—C1-4 haloalkyl group or (9) an oxo group, provided that the C1-4 alkyl group or the C1-4 haloalkyl group represented by R3-1 is branched chain, C1-2 alkyl groups branched from the same carbon atom may be taken together with a carbon atom to which they are bound, to form a C3-4 saturated carbocyclic ring,
- R13 represents (1) a hydrogen atom or (2) a C1-4 alkyl group,
- L represents a group represented by general formula
- wherein, R11 and R12 each represent independently a hydrogen atom or a C1-4 alkyl group, or R11 and R12 may be taken together with a carbon atom to which they are bound, to form a C3-7 carbocyclic ring, and t represents an integer of 1 to 6,
- Z represents (1) a carboxyl group which may be substituted with a C1-8 alkyl group, (2) a hydroxamic acid group which may be substituted with a C1-8 alkyl group, (3) a sulfonic acid group which may be substituted with a C1-8 alkyl group, (4) a boronic acid group which may be substituted with a C1-8 alkyl group, (5) a carbamoyl group which may be substituted with a C1-8 alkyl group, (6) a sulfamoyl group which may be substituted with a C1-8 alkyl group, (7) a sulfoximine group which may be substituted with a C1-8 alkyl group or (8) a tetrazolyl group,
- ring 1 represents a C3-10 carbocyclic ring,
- ring 2 represents (1) a C3-7 carbocyclic ring or (2) a 3- to 7-membered heterocyclic ring,
- ring 3 represents (1) a C3-7 carbocyclic ring which may be substituted with a C1-4 alkyl group or (2) a 3- to 7-membered heterocyclic ring which may be substituted with a C1-4 alkyl group,
- m represents an integer of 0 to 2,
- n represents an integer of 0 to 2,
- p represents an integer of 0 to 3,
- q represents an integer of 0 to 5,
- v represents an integer of 0 to 1,
- when p is 2 or more, a plurality of R2s may be the same or different,
- when q is 2 or more, a plurality of R3-1s may be the same or different,
- when t is 2 or more, a plurality of R11s may be the same or different, and
- when t is 2 or more, a plurality of R12s may be the same or different, or a pharmaceutically acceptable salt thereof.
19 more elements
A method for treating a S1P5-mediated disease, comprising administering to a mammal in need thereof an effective amount of a compound represented by general formula (I-1), or a pharmaceutically acceptable salt thereof:
- wherein, X1 and X2 each represent independently a CH2 or an NH, provided that X1 and X2 are not represent NH at the same time,
- Y represents (1) —CH2— (2) —NH—, (3) —S— or (4) —O—,
- WA represents (1) a C1-12 alkylene group, (2) a C2-12 alkenylene group, (3) a C2-12 alkynylene group, (4) —C1-12 alkylene-O—, (5) —C2-12 alkenylene-O—, (6) —C2-12 alkynylene-O—, (7) —C1-12 alkylene-ring2-, (8) —C2-12 alkenylene-ring2-, or (9) —C2-12 alkynylene-ring2-, wherein, an alkylene group, an alkenylene group and an alkynylene group may be substituted with one to five halogen atoms,
- R1 represents (1) -L-, (2) -L-ring3- or (3) -L-NR13-,
- R2 represents (1) a halogen atom, (2) a C1-4 alkyl group, (3) a C1-4 haloalkyl group, or (4) a C1-4 haloalkoxy group,
- R3-1 represents (1) a halogen atom, (2) a C1-4 alkyl group, (3) a C1-4 haloalkyl group, (4) a C1-4 alkoxy group, (5) a C1-4 haloalkoxy group, (6) a nitrile group, (7) —S—C1-4 alkyl group, (8) —S—C1-4 haloalkyl group or (9) an oxo group, provided that the C1-4 alkyl group or the C1-4 haloalkyl group represented by R3-1 is branched chain, C1-2 alkyl groups branched from the same carbon atom may be taken together with a carbon atom to which they are bound, to form a C3-4 saturated carbocyclic ring,
- R13 represents (1) a hydrogen atom or (2) a C1-4 alkyl group,
- L represents (1) a bond or (2) a group represented by general formula
- wherein, R11 and R12 each represent independently a hydrogen atom or a C1-4 alkyl group, or R11 and R12 may be taken together with a carbon atom to which they are bound, to form a C3-7 carbocyclic ring, and t represents an integer of 1 to 6,
- Z represents (1) a carboxyl group which may be substituted with a C1-8 alkyl group, (2) a hydroxy group which may be substituted with a C1-8 alkyl group, (3) a hydroxamic acid group which may be substituted with a C1-8 alkyl group, (4) a sulfonic acid group which may be substituted with a C1-8 alkyl group, (5) a boronic acid group which may be substituted with a C1-8 alkyl group, (6) a carbamoyl group which may be substituted with a C1-8 alkyl group, (7) a sulfamoyl group which may be substituted with a C1-8 alkyl group, (8) a sulfoximine group which may be substituted with a C1-8 alkyl group or (9) a tetrazolyl group,
- ring 1 represents (1) a C3-10 carbocyclic ring,
- ring 2 represents (1) a C3-7 carbocyclic ring or (2) a 3- to 7-membered heterocyclic ring,
- ring 3 represents (1) a C3-7 carbocyclic ring which may be substituted with a C1-4 alkyl group or (2) a 3- to 7-membered heterocyclic ring which may be substituted with a C1-4 alkyl group,
- m represents an integer of 0 to 2,
- n represents an integer of 0 to 2,
- p represents an integer of 0 to 3,
- q represents an integer of 0 to 5,
- v represents an integer of 0 to 1,
- when p is 2 or more, a plurality of R2s may be the same or different,
- when q is 2 or more, a plurality of R3-1s may be the same or different,
- when t is 2 or more, a plurality of R11s may be the same or different, and
- when t is 2 or more, a plurality of R12s may be the same or different, or a pharmaceutically acceptable salt thereof.
19 more elements
A method for modulating a S1P5 receptor, comprising contacting the S1P5 receptor with the compound represented by general formula (I-1), or a pharmaceutically acceptable salt thereof:
- wherein, X1 and X2 each represent independently a CH2 or an NH, provided that X1 and X2 are not represent NH at the same time,
- Y represents (1) —CH2—, (2) —NH—, (3) —S— or (4) —O—,
- WA represents (1) a C1-12 alkylene group, (2) a C2-12 alkenylene group, (3) a C2-12 alkynylene group, (4) —C1-12 alkylene-O—, (5) —C2-12 alkenylene-O—, (6) —C2-12 alkynylene-O—, (7) —C1-12 alkylene-ring2-, (8) —C2-12 alkenylene-ring2- or (9) —C2-12 alkynylene-ring2-, wherein, an alkylene group, an alkenylene group and an alkynylene group may be substituted with one to five halogen atoms,
- R1 represents (1) -L-, (2) -L-ring3- or (3) -L-NR13,
- R2 represents (1) a halogen atom, (2) a C1-4 alkyl group, (3) a C1-4 haloalkyl group, or (4) a C1-4 alkoxy group,
- R3-1 represents (1) a halogen atom, (2) a C1-4 alkyl group, (3) a C1-4 haloalkyl group, (4) a C1-4 alkoxy group, (5) a C1-4 haloalkoxy group, (6) a nitrile group, (7) —S—C1-4 alkyl group, (8) —S—C1-4 haloalkyl group or (9) an oxo group, provided that the C1-4 alkyl group or the C1-4 haloalkyl group represented by R3-1 is branched chain, C1-2 alkyl groups branched from the same carbon atom may be taken together with a carbon atom to which they are bound, to form a C3-4 saturated carbocyclic ring,
- R13 represents (1) a hydrogen atom or (2) a C1-4 alkyl group,
- L represents (1) a bond or (2) a group represented by general formula
- wherein, R11 and R12 each represent independently a hydrogen atom or a C1-4 alkyl group, or R11 and R12 may be taken together with a carbon atom to which they are bound, to form a C3-7 carbocyclic ring, and t represents an integer of 1 to 6,
- Z represents (1) a carboxyl group which may be substituted with a C1-8 alkyl group, (2) a hydroxy group which may be substituted with a C1-8 alkyl group, (3) a hydroxamic acid group which may be substituted with a C1-8 alkyl group, (4) a sulfonic acid group which may be substituted with a C1-8 alkyl group, (5) a boronic acid group which may be substituted with a C1-8 alkyl group, (6) a carbamoyl group which may be substituted with a C1-8 alkyl group, (7) a sulfamoyl group which may be substituted with a C1-8 alkyl group, (8) a sulfoximine group which may be substituted with a C1-8 alkyl group or (9) a tetrazolyl group,
- ring 1 represents (1) a C3-10 carbocyclic ring,
- ring 2 represents (1) a C3-7 carbocyclic ring or (2) a 3- to 7-membered heterocyclic ring,
- ring 3 represents (1) a C3-7 carbocyclic ring which may be substituted with a C1-4 alkyl group or (2) a 3- to 7-membered heterocyclic ring which may be substituted with a C1-4 alkyl group,
- m represents an integer of 0 to 2,
- n represents an integer of 0 to 2,
- p represents an integer of 0 to 3,
- q represents an integer of 0 to 5,
- v represents an integer of 0 to 1,
- when p is 2 or more, a plurality of R2s may be the same or different,
- when q is 2 or more, a plurality of R3-1s may be the same or different,
- when t is 2 or more, a plurality of R11s may be the same or different, and
- when t is 2 or more, a plurality of R12s may be the same or different, or a pharmaceutically acceptable salt thereof.
19 more elements
Dependencies are inferred from the claim text.