Nitrogen-containing condensed ring compounds having dopamine D3 antagonistic effect

Patent metadata

Field	Value
Publication number	US-11345716-B2
Application number	US-202017022558-A
Country	US
Kind code	B2
Filing date	Sep 16, 2020
Priority date	Jul 28, 2016
Publication date	May 31, 2022
Grant date	May 31, 2022

Abstract

Novel compounds having D3 receptor antagonistic activity are provided.
A compound represented by formula (I):

wherein

ring A is a heterocycle, X 1 is each independently CR 4a R 4b , X 2 is each independently CR 4c R 4d , Y 1 and Y 2 are each independently a carbon atom or a nitrogen atom,

L is —N(R 6 )—C(═O)— or the like, W is cyclyl or the like, R 2 and R 3 are each independently substituted or unsubstituted alkyl or the like, R 1a , R 1b , R 4a to R 4d , and R 6 are each independently hydrogen atoms or the like,

p is 1 or 2, q is an integer of 1 to 3, n is an integer of 1 to 4, s is an integer of 0 to 4, or a pharmaceutically acceptable salt thereof.

First claim

The invention claimed is:

1. A compound represented by Formula (I):

wherein

X 1 is each independently CR 4a R 4b ,
X 2 is each independently CR 4c R 4d ,
p is 2;
q is 2;
R 4a is each independently a hydrogen atom, halogen, hydroxy, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy;
R 4b is each independently a hydrogen atom, halogen, hydroxy, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy;
R 4a and R 4b attached to a same carbon atom may be taken together with the carbon atom to which they are attached to form a substituted or unsubstituted 3- to 5-membered non-aromatic carbocycle or a substituted or unsubstituted 3- to 5-membered non-aromatic heterocycle;
two R 4a s attached to adjacent carbon atoms may be taken together with the carbon atoms to which they are attached to form a substituted or unsubstituted 3- to 5-membered non-aromatic carbocycle or a substituted or unsubstituted 3- to 5-membered non-aromatic heterocycle;
R 4c is each independently a hydrogen atom, halogen, hydroxy, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy;
R 4d is each independently a hydrogen atom, halogen, hydroxy, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy;
R 4c and R 4d attached to a same carbon atom may be taken together with the carbon atom to which they are attached to form a substituted or unsubstituted 3- to 5-membered non-aromatic carbocycle or a substituted or unsubstituted 3- to 5-membered non-aromatic heterocycle;
two R 4c s attached to adjacent carbon atoms may be taken together with the carbon atoms to which they are attached to form a substituted or unsubstituted 3- to 5-membered non-aromatic carbocycle or a substituted or unsubstituted 3- to 5-membered non-aromatic heterocycle;
any one of R 4a s and any one of R 4c s may be taken together to form a substituted or unsubstituted (C1-C3) bridge, wherein one of carbon atoms constituting the (C1-C3) bridge may be replaced with an oxygen atom or a nitrogen atom;
R 1a is each independently a hydrogen atom, halogen, hydroxy, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy;
R 1b is each independently a hydrogen atom, halogen, hydroxy, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy;
n is an integer of 1 to 4;
—W— is a group represented by:

wherein
Ring B is a non-aromatic carbocycle, a non-aromatic heterocycle, an aromatic carbocycle, or an aromatic heterocycle;
R 5 is each independently halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkenylsulfanyl, substituted or unsubstituted alkynylsulfanyl, substituted or unsubstituted alkylamino, substituted or unsubstituted alkenylamino, substituted or unsubstituted alkynylamino, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkynylcarbonyl, substituted or unsubstituted alkyl sulfonyl, substituted or unsubstituted alkenyl sulfonyl, substituted or unsubstituted alkynylsulfonyl, substituted or unsubstituted alkylcarbonyloxy, substituted or unsubstituted alkenylcarbonyloxy, substituted or unsubstituted alkynylcarbonyloxy, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyloxycarbonyl, substituted or unsubstituted alkyl sulfonyloxy, substituted or unsubstituted alkenylsulfonyloxy, substituted or unsubstituted alkynylsulfonyloxy, substituted or unsubstituted alkyloxysulfonyl, substituted or unsubstituted alkenyloxysulfonyl, substituted or unsubstituted alkynyloxysulfonyl, substituted or unsubstituted alkylcarbamoyl, substituted or unsubstituted alkenylcarbamoyl, substituted or unsubstituted alkynylcarbamoyl, substituted or unsubstituted alkylsulfamoyl, substituted or unsubstituted alkenylsulfamoyl, substituted or unsubstituted alkynylsulfamoyl, substituted or unsubstituted alkylcarbonylamino, substituted or unsubstituted alkenylcarbonylamino, substituted or unsubstituted alkynylcarbonylamino, substituted or unsubstituted alkyl sulfonylamino, substituted or unsubstituted alkenylsulfonylamino, substituted or unsubstituted alkynylsulfonylamino, substituted or unsubstituted alkyloxycarbonylamino, substituted or unsubstituted alkenyloxycarbonylamino, or substituted or unsubstituted alkynyloxycarbonylamino;
two R 5 s attached to different ring-constituting atoms may be taken together to form a bond or a substituted or unsubstituted (C1-C3) bridge wherein one of carbon atoms constituting the (C1-C3) bridge may be replaced with an oxygen atom or a nitrogen atom; and
r is an integer of 0 to 4, or

—(CR 1c R 1d ) m —;
R 1c is each independently a hydrogen atom, halogen, hydroxy, substituted or unsubstituted alkyl (provided that the substituents are not aromatic heterocyclylcarbamoyloxy), or substituted or unsubstituted alkyloxy;
R 1d is each independently a hydrogen atom, halogen, hydroxy, substituted or unsubstituted alkyl (provided that the substituents are not aromatic heterocyclylcarbamoyloxy), or substituted or unsubstituted alkyloxy;
m is an integer of 1 to 3;
-L- is —N(R 6 )—C(═O)—, —C(═O)—N(R 6 )—, —N(R 6 )—SO 2 —, or —SO 2 —N(R 6 )—;
R 6 is a hydrogen atom, or substituted or unsubstituted alkyl;
R 2 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkylamino, substituted or unsubstituted alkenylamino, substituted or unsubstituted alkynylamino, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, substituted or unsubstituted non-aromatic heterocyclyl, substituted or unsubstituted aromatic carbocyclyloxy, substituted or unsubstituted non-aromatic carbocyclyloxy, substituted or unsubstituted aromatic heterocyclyloxy, substituted or unsubstituted non-aromatic heterocyclyloxy, substituted or unsubstituted aromatic carbocyclylamino, substituted or unsubstituted non-aromatic carbocyclylamino, substituted or unsubstituted aromatic heterocyclylamino, or substituted or unsubstituted non-aromatic heterocyclylamino;
R 3 is each independently halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkyl sulfanyl, substituted or unsubstituted alkenylsulfanyl, substituted or unsubstituted alkynylsulfanyl, substituted or unsubstituted alkylamino, substituted or unsubstituted alkenylamino, substituted or unsubstituted alkynylamino, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkynylcarbonyl, substituted or unsubstituted alkyl sulfonyl, su

Assignees

• Shionogi & Co

Inventors

• Tobinaga Hiroyuki
• Masuda Koji
• Kasuya Satoshi
• Inagaki Masanao
• Masuda Manami

Classifications

• A61P25/22

  Anxiolytics · CPC title

• A61P43/00

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

• A61K31/519

  ortho- or peri-condensed with heterocyclic rings · 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

• C07D471/04

  Ortho-condensed systems · CPC title