US 2017/0290795 A1 · URAT1 INHIBITOR

Abstract

Provided are a compound represented by the following Formula (III), a tautomer or stereoisomer of the compound, or a pharmaceutically acceptable salt or solvate thereof used as a therapeutic agent for gout or hyperuricemia. (In the Formula (III), R1a, R2a, R6a, and R7a represent a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, or a cyano group, R3a and R8a form a benzene ring or a 5-membered heteroaryl ring containing 1 to 3 heteroatoms, as a ring constituent element, selected from nitrogen atoms, oxygen atoms, and sulfur atoms together with two carbon atoms to which R3a and R8a are bonded, R4a and R5a form a benzene ring together with two carbon atoms to which R4a and R5a are bonded or represent any of the groups represented by R1a described above, Wa represents CR10a or N, and where, R10a represents any of the groups represented by R1a, Xa represents an oxygen atom or a sulfur atom, Ya represents an alkylene chain having 1 to 8 carbon atoms, and where, the alkylene chain may be substituted with an alkyl group having 1 to 8 carbon atoms and the alkylene chain may be a linear or branched alkylene chain, the branched alkylene chain may have a 3- to 7-membered ring formed by side chains bonded to carbon atoms which are the same as or different from each other, together with the carbon atoms to which the side chains are bonded and may have a double bond in the middle thereof, and Za represents CO2H.)

A compound represented by the following Formula (I), a tautomer or stereoisomer of the compound, or a pharmaceutically acceptable salt or solvate thereof:

(in the formula, a dotted line represents a single bond or a double bond,
Q represents CR8, NR9, or N,
in a case where Q represents CR8, R3 and R8 are bonded to each other to form a naphthalene ring or a quinoline ring together with a ring formed of dotted lines, or a combination of R1 and R2, R2 and R8, or R3 and R8 are bonded to each other to form a 5-membered heteroaryl ring containing 1 to 3 heteroatoms, as a ring constituent element, selected from a nitrogen atom, an oxygen atom, and a sulfur atom together with two carbon atoms to which the combination is bonded, and the heteroaryl ring forms a fused ring together with the ring formed of dotted lines,
where, the ring formed of dotted lines is a ring in which the number of double bonds in the ring is the maximum,
in a case where Q represents N, R1 and R2 are bonded to each other to form a quinoline ring together with the ring formed of dotted lines,
in a case where Q represents NR9, R3 and R9 or R2 and R9 are bonded to each other to form an imidazo[1,2-a]pyridine ring together with the ring formed of dotted lines,
in a case where R1, R2, R3, and R8 do not constitute a ring, R1, R2, R3, and R8 may be the same as or different from each other and represent a hydrogen atom, a halogen atom, an alkyl group having 1 to 8 carbon atoms, a 3- to 7-membered ring cycloalkyl group, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkenyl group having 2 to 8 carbon atoms, an alkynyl group having 2 to 8 carbon atoms, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 12 carbon atoms, an alkyloxycarbonyl group in which the number of carbon atoms of the alkyl group is in a range of 1 to 8, a hydroxy group, an amino group, a carboxyl group, a nitro group, a cyano group, CONR′R″, SR′, or SO2NR′R″,
where, R′ and R″ may be the same as or different from each other and represent a hydrogen atom or an alkyl group having 1 to 8 carbon atoms,
in a case where R1, R2, R3, and R8 constitute a ring, the ring may have 1 to 4 substituents which are the same as the substituent for R1 in the case where R1, R2, R3, and R8 do not constitute a ring, the substituents being the same or different from each other,
A represents a phenyl group, a naphthyl group, a pyridyl group, a pyrimidyl group, a pyrazyl group, a pyridazyl group, a quinolyl group, or an isoquinolyl group which may have 1 to 5 substituents same as that of R1 in the case where R1 does not form a ring, the substituents may be the same as or different from each other,
where, A is bonded to the ring formed of dotted lines through a carbon atom constituting the ring of the A group,
X represents NR11, an oxygen atom, or a sulfur atom,
where, R11 represents a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, or an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms,
Y represents an alkylene chain having 1 to 8 carbon atoms,
where, the alkylene chain may be substituted with 1 to 4 same or different groups selected from an alkyl group having 1 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a 3- to 7-membered cycloalkyl group, or a 4- to 7-membered saturated hetero ring having one or two heteroatoms, as a ring constituent element, selected from an oxygen atom, a sulfur atom, and a nitrogen atom, the alkylene chain may be a linear or branched alkylene chain, the branched alkylene chain may have a 3- to 7-membered ring formed by side chains bonded to same carbon atom or different carbon atoms, together with the or each carbon atom to which the side chains are bonded, and the alkylene chain may have a double bond in the chain thereof in a case where the alkylene chain is an alkylene chain having 2 to 8 carbon atoms,
Z represents CO2H, CON(R12)(R13), CO2(R14), SO2N(R15)(R16), or a tetrazolyl group,
where, R12, R14, and R15 represent a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms,
R13 and R16 represent a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a phenyl group which may have a substituent, a pyridyl group which may have a substituent, a pyridazyl group, a pyrimidyl group, or a pyrazyl group, or a 5-membered heteroaryl ring and contains 1 to 3 heteroatoms, as a ring constituent element, selected from a nitrogen atom which may have a substituent, an oxygen atom, and a sulfur atom, and
in a case where R3 and R8 are bonded to each other to form a naphthalene ring together with the ring formed of dotted lines, X represents an oxygen atom, A represents naphthalene, and the 1-position of A is bonded to the ring formed of dotted lines, the 2-position of A does not represent any of an alkoxy group having 1 to 8 carbon atoms, a hydroxy group, and ethyl 3-[[1-(2-fluorophenyl)naphthalen-2-yl]thio]propanoate.)

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Urat1 inhibitor

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Urat1 inhibitor

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Abstract

Claims61