URAT1 inhibitor

Patent metadata

Field	Value
Publication number	US-10173990-B2
Application number	US-201515507888-A
Country	US
Kind code	B2
Filing date	Dec 28, 2015
Priority date	Dec 29, 2014
Publication date	Jan 8, 2019
Grant date	Jan 8, 2019

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), R 1a , R 2a , R 6a , and R 7a 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, R 3a and R 8a 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 R 3a and R 8a are bonded, R 4a and R 5a form a benzene ring together with two carbon atoms to which R 4a and R 5a are bonded or represent any of the groups represented by R 1a described above, W a represents CR 10a or N, and where, R 10a represents any of the groups represented by R 1a , X a represents an oxygen atom or a sulfur atom, Y a 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 Z a represents CO 2 H).

First claim

The invention claimed is:

1. 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 CR 8 , NR 9 , or N,
if Q represents CR 8 , then R 3 and R 8 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 R 1 and R 2 , R 2 and R 8 , or R 3 and R 8 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,
if Q represents N, then R 1 and R 2 are bonded to each other to form a quinoline ring together with the ring formed of dotted lines,
if Q represents NR 9 , then R 3 and R 9 or R 2 and R 9 are bonded to each other to form an imidazo[1,2-a]pyridine ring together with the ring formed of dotted lines,
any of R 1 , R 2 , R 3 , and R 8 that do not bond to constitute a ring 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 SO 2 NR′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,
when one or more of R 1 , R 2 , R 3 , and R 8 bond to constitute a ring, the ring may have 1 to 4 substituents which are the same as the substituent for R 1 in the case where R 1 , R 2 , R 3 , and R 8 do not bond to 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 R 1 in the case where R 1 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 a sulfur atom,
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 CO 2 H, CON(R 12 )(R 13 ), CO 2 (R 14 ), SO 2 N(R 15 )(R 16 ), or a tetrazolyl group,
where, R 12 , R 14 , and R 15 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, and
R 13 and R 16 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
wherein ethyl 3-[[1-(2-fluorophenylnaphthalen-2-yl]thio]propanoate is excluded.

2. The compound, a tautomer or stereoisomer of the compound, or a pharmaceutically acceptable salt or solvate thereof according to claim 1 ,
wherein A represents a phenyl group, a naphthyl group, or a pyridyl group which may have a substituent selected from 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, a hydroxy group, an amino group, a carboxyl group, a nitro group, and a cyano group.

3. The compound, a tautomer or stereoisomer of the compound, or a pharmaceutically acceptable salt or solvate thereof according to claim 1 ,
wherein A is represented by the following Formula (II),

where,
R 4 and R 5 may form a benzene ring together with two carbon atoms to which R 4 and R 5 are bonded, or 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, a hydroxy group, an amino group, a carboxyl group, a mercapto group, an alkylsulfanyl group having 1 to 8 carbon atoms, a nitro group, or a cyano group,
where, the benzene ring may have 1 to 4 same or different substituents selected from 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, a hydroxy group, an amino group, a carboxyl group, a mercapto group, an alkylsulfanyl group having 1 to 8 carbon atoms, a nitro group, and a cyano group,
R 6 and R 7 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, a hydroxy group, an amino group, a carboxyl group, a mercapto group, an alkylsulfanyl group having

Assignees

• Nippon Chemiphar Co
• J Pharma Co Ltd
• Dethree Res Lab Inc

Inventors

• Endo Tsuyoshi
• Kobayashi Kunio
• Tanaka Hiroto
• Saito Daisuke
• Hirano Masuharu
• Endou Hitoshi
• Anzai Naohiko

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P19/06

  Antigout agents, e.g. antihyperuricemic or uricosuric agents · CPC title

• C07D213/30

  Oxygen atoms · CPC title

• A61K31/404

  Indoles, e.g. pindolol · CPC title

• A61K31/437

  the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline · CPC title