Aminotriazine derivative and pharmaceutical composition comprising the same

Patent metadata

Field	Value
Publication number	US-2016115151-A1
Application number	US-201414897836-A
Country	US
Kind code	A1
Filing date	Jun 13, 2014
Priority date	Jun 14, 2013
Publication date	Apr 28, 2016
Grant date	—

Abstract

The present invention provides novel compounds having a P2X 3 and/or P2X 2/3 receptor antagonistic activity.
A compound of Formula (I):

wherein R a and R b , and R d and R e are taken together to form oxo or the like; R 4a and R 4b are hydrogen or the like; n is 1 or the like; R 2 is aryl or the like; s and s′ is 0 or the like; R 9 and R 9 ′ are halogen or the like; R 20a and R 20b are hydrogen, alkyl or the like; u is 1 to 4; R 13 is hydrogen or the like.

or its pharmaceutically acceptable salt.

First claim

1 . A compound of Formula (I):

wherein,
R a and R b are both hydrogen atoms, or R a and R b are taken together to form oxo, thioxo or ═N—R x ;
R d and R e are both hydrogen atoms, or R d and R e are taken together to form oxo, thioxo or ═N—R y ;
R x and R y are each independently a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, a substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;
R 4a is each independently a hydrogen atom or substituted or unsubstituted alkyl;
R 4b is each independently a hydrogen atom or substituted or unsubstituted alkyl; or R 4a and R 4b attached to the same carbon atom are taken together to form oxo or thioxo;
n is an integer of 1 to 4;
R 2 is substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, a substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 9 is each independently halogen, hydroxy, carboxy, cyano, nitro, 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 alkylthio, substituted or unsubstituted alkenylthio, substituted or unsubstituted alkynylthio, substituted or unsubstituted acyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyloxycarbonyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted amino, substituted or unsubstituted sulfamoyl, substituted sulfonyl, substituted sulfinyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, a substituted, or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyloxy, substituted or unsubstituted cycloalkenyloxy, substituted or unsubstituted non-aromatic heterocyclyloxy, substituted or unsubstituted aryloxy or substituted or unsubstituted heteroaryloxy;
R 9 ′ is each independently halogen, hydroxy, carboxy, cyano, nitro, 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 alkylthio, substituted or unsubstituted alkenylthio, substituted or unsubstituted alkynylthio, substituted or unsubstituted acyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyloxycarbonyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted amino, substituted or unsubstituted sulfamoyl, substituted sulfonyl, substituted sulfinyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, a substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyloxy, substituted or unsubstituted cycloalkenyloxy, substituted or unsubstituted non-aromatic heterocyclyloxy, substituted, or unsubstituted aryloxy or substituted or unsubstituted heteroaryloxy;
s and s′ are each independently an integer of 0 to 3;
R 20a is each independently a hydrogen atom, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, or substituted or unsubstituted alkyloxy;
R 20b is each independently a hydrogen atom, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, or substituted or unsubstituted alkyloxy; or R 20a and R 20b attached to the same carbon atom or the different carbon atoms are taken together to form substituted or unsubstituted cycloalkane, substituted or unsubstituted cycloalkene, or a substituted or unsubstituted non-aromatic heterocyclic ring; provided that all R 20a and R 20b are not hydrogen atoms at the same time;
u is an integer of 1 to 4; and
R 18 is a hydrogen atom or substituted or unsubstituted alkyl, provided that the following compounds:

are excluded,
or its pharmaceutically acceptable salt.

2 . The compound according to claim 1 , wherein the group represented by the formula:

is a group represented by the formula:

or its pharmaceutically acceptable salt.

3 . The compound according to claim 1 , wherein the group represented by the formula:

is a group represented by the formula:

or its pharmaceutically acceptable salt.

4 . The compound according to any one of claims 1 to 3 , wherein n is 1, R 4a and R 4b are both hydrogen atoms, and R 2 is substituted or unsubstituted phenyl or substituted or unsubstituted cycloalkyl, or its pharmaceutically acceptable salt.

5 . The compound according to any one of claims 1 to 4 , wherein n is 1, R 4a and R 4b are both hydrogen atoms, and R 2 is 4-methylphenyl, or its pharmaceutically acceptable salt.

6 . The compound according to any one of claims 1 to 4 , wherein n is 1, R 4a and R 4b are both hydrogen atoms, and R 2 is phenyl substituted with halogen, or its pharmaceutically acceptable salt.

7 . The compound according to claim 6 , wherein n is 1, R 4a and R 4b are both hydrogen atoms, and R 2 is 4-chlorophenyl, or its pharmaceutically acceptable salt.

8 . The compound according to any one of claims 1 to 7 , wherein R a and R b are taken together to form oxo, or its pharmaceutically acceptable salt.

9 . The compound according to any one of claims 1 to 8 , wherein R d and R e are taken together to form oxo, or its pharmaceutically acceptable salt.

10 . The compound according to any one of claims 1 to 9 , wherein s is 0, or its pharmaceutically acceptable salt.

11 . The compound according to any one of claims 1 to 9 , wherein s is 1 or 2, and R 9 is each independently halogen, unsubstituted alkyl, haloalkyl, unsubstituted alkenyl or unsubstituted alkynyl, or its pharmaceutically acceptable salt.

12 . The compound according to any one of claims 1 to 11 , wherein s′ is 0, or its pharmaceutically acceptable salt.

13 . The compound according to any one of claims 1 to 11 , wherein s′ is an integer of 1 to 3, or its pharmaceutically acceptable salt.

14 . The compound according to claim 13 , wherein s′ is 1 or 2, and R 9 ′ is each independently halogen, carboxy, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkyloxycarbonyl or substituted or unsubstituted aryl, or its pharmaceutically acceptable salt.

Assignees

• Shionogi & Co

Inventors

• Kai Hiroyuki

Classifications

• A61P43/00

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

• A61P25/04

  Centrally acting analgesics, e.g. opioids · CPC title

• A61P13/00

  Drugs for disorders of the urinary system · CPC title

• C07D405/14

  containing three or more hetero rings · CPC title

• A61P11/06

  Antiasthmatics · CPC title