Aromatic heterocyclylamine derivative having trpv4-inhibiting activity

Patent metadata

Field	Value
Publication number	US-2016200721-A1
Application number	US-201615076728-A
Country	US
Kind code	A1
Filing date	Mar 22, 2016
Priority date	Sep 25, 2013
Publication date	Jul 14, 2016
Grant date	—

Abstract

The present invention is related to a compound represented by formula (I)

wherein —X— is —NH— or —S—; —Z— is —O— or —S—; R 3 , R 5 and R 6 are each independently a hydrogen atom, substituted or unsubstituted alkyl, or the like; R 7 is a cyano, substituted or unsubstituted amino, or the like; R 7 ′ is each independently a halogen; b is 0 or 1; or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising thereof.

First claim

1 . A compound of formula (I):

wherein:
—X— is —NH— or —S—;
—Z— is —O— or —S—;
R 3 , R 5 and R 6 are each independently a hydrogen atom, 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 amino, substituted or unsubstituted carbamoyl, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, or substituted or unsubstituted non-aromatic heterocyclyl;
R 7 is a cyano, substituted or unsubstituted amino, 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 alkylcarbonyl, substituted or unsubstituted alkyl sulfonyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted sulfamoyl, substituted or unsubstituted aromatic carbocyclylcarbonyl, substituted or unsubstituted non-aromatic carbocyclylcarbonyl, substituted or unsubstituted aromatic heterocyclylcarbonyl, or substituted or unsubstituted non-aromatic heterocyclylcarbonyl;
R 7 ′ is each independently a halogen;
b is 0 or 1;

or a pharmaceutically acceptable salt thereof.

2 . The compound according to claim 1 ,
wherein —X— is —S—; —Z— is —S—,
or a pharmaceutically acceptable salt thereof.

3 . The compound according to claim 2 ,
wherein R 7 is a group represented by the following formula:

wherein ring B is non-bridged non-aromatic heterocyclyl, or bridged non-aromatic heterocyclyl;
R 8 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclyl, or substituted or unsubstituted aromatic heterocyclyl;
R 8a is each independently halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;
c is 0, 1, or 2;

or a pharmaceutically acceptable salt thereof.

4 . The compound according to claim 3 ,
wherein R 7 is a group represented by the following formula:

wherein m is 2;
two R 9 groups may be taken together to form (C2-C4) bridge;
the carbon atoms that consist of the bridge are each independently substituted with the substituent selected from R a ;
R a is a hydrogen atom, halogen, hydroxy, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;
R 8 is the same as above;

or a pharmaceutically acceptable salt thereof.

5 . A compound of formula (III):

wherein R 7 is substituted or unsubstituted non-aromatic heterocyclylcarbonyl;
D is a group represented by the following formula:

wherein R 4 ′ is a hydrogen atom, or substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;
R 5 ′ is a hydrogen atom, or substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;
—Z— is —O— or —S—;
R 3 is each independently a hydrogen atom, 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 amino, substituted or unsubstituted carbamoyl, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, or substituted or unsubstituted non-aromatic heterocyclyl;
R 7 ′ is each independently a halogen;
b is 0 or 1;

or a pharmaceutically acceptable salt thereof.

6 . A pharmaceutical composition containing the compound according to claim 1 , or a pharmaceutically acceptable salt thereof.

7 . A pharmaceutical composition containing the compound according to claim 2 , or a pharmaceutically acceptable salt thereof.

8 . A pharmaceutical composition containing the compound according to claim 3 , or a pharmaceutically acceptable salt thereof.

9 . A pharmaceutical composition containing the compound according to claim 4 , or a pharmaceutically acceptable salt thereof.

10 . A pharmaceutical composition containing the compound according to claim 5 , or a pharmaceutically acceptable salt thereof.

Assignees

• Shionogi & Co

Inventors

• Yukimasa Akira
• Tsuno Naoki
• Fujiu Motohiro
• Yamaguchi Hiroki
• Kudo Hiromi
• Ueno Tatsuhiko
• Ichihashi Yusuke
• Inoue Takatsugu
• Suzuki Shinji

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P35/04

  specific for metastasis · CPC title

• A61P43/00

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

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title