Heterocyclic derivative having ampk-activating activity

Patent metadata

Field	Value
Publication number	US-2017333398-A1
Application number	US-201515522504-A
Country	US
Kind code	A1
Filing date	Oct 27, 2015
Priority date	Oct 28, 2014
Publication date	Nov 23, 2017
Grant date	—

Abstract

A compound represented by formula:

or its pharmaceutically acceptable salt,
wherein L is NR 2 R 3 , SR 7 , SO 2 R 8 , substituted or unsubstituted alkyl, or substituted or unsubstituted alkenyl; R 2 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, or the like; R 3 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, or the like; R 7 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, or the like; R 8 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, or the like, provided that R 8 is not unsubstituted methyl or trifluoromethyl; Y is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, or the like, provided that Y is not unsubstituted methyl or unsubstituted ethyl; Z is —CR 6 ═, or —N═; R 1 is hydrogen, or substituted or unsubstituted alkyl; R 4 , R 5 and R 6 are each independently hydrogen, halogen, hydroxy, cyano, nitro, carboxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, or the like.

First claim

1 . A compound of formula (I),

or a pharmaceutically acceptable salt thereof,
wherein
L is NR 2 R 3 , SR 7 , SO 2 R 8 , substituted or unsubstituted alkyl, or substituted or unsubstituted alkenyl;
R 2 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted acyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted alkyl sulfonyl, substituted or unsubstituted alkenylsulfonyl, substituted or unsubstituted alkynylsulfonyl , substituted or unsubstituted arylsulfonyl, substituted or unsubstituted heteroarylsulfonyl, substituted or unsubstituted cycloalkylsulfonyl, substituted or unsubstituted cycloalkenylsulfonyl, substituted or unsubstituted heterocyclylsulfonyl, or substituted or unsubstituted sulfamoyl;
R 3 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted acyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted alkyl sulfonyl, substituted or unsubstituted alkenylsulfonyl, substituted or unsubstituted alkynylsulfonyl, substituted or unsubstituted aryl sulfonyl, substituted or unsubstituted heteroarylsulfonyl, substituted or unsubstituted cycloalkylsulfonyl, substituted or unsubstituted cycloalkenylsulfonyl, substituted or unsubstituted heterocyclylsulfonyl, or substituted or unsubstituted sulfamoyl;
R 7 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted acyl, or substituted or unsubstituted carbamoyl;
R 8 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted acyl, substituted or unsubstituted carbamoyl, or substituted or unsubstituted amino, provided that R 8 is not unsubstituted methyl or unsubstituted ethyl;
Y is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, or substituted or unsubstituted heterocyclyl, provided that Y is not unsubstituted methyl or unsubstituted ethyl;
Z is —CR 6 ═, or —N═;
R 1 is hydrogen, or substituted or unsubstituted alkyl;
R 4 , R 5 and R 6 are each independently hydrogen, halogen, hydroxy, cyano, nitro, carboxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted cycloalkyloxy, substituted or unsubstituted cycloalkenyloxy, substituted or unsubstituted heterocyclyloxy, substituted or unsubstituted alkylthio, substituted or unsubstituted arylthio, substituted or unsubstituted heteroarylthio, substituted or unsubstituted cycloalkylthio, substituted or unsubstituted cycloalkenylthio, substituted or unsubstituted heterocyclylthio, substituted or unsubstituted alkyl sulfonyl, substituted or unsubstituted aryl sulfonyl, substituted or unsubstituted heteroarylsulfonyl, substituted or unsubstituted cycloalkylsulfonyl, substituted or unsubstituted cycloalkenylsulfonyl, substituted or unsubstituted heterocyclylsulfonyl, substituted or unsubstituted acyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted sulfamoyl, or substituted or unsubstituted amino;
R 1 is hydrogen when Z is —CR 6 ═ and L is SO 2 R 8 , and
with the proviso that excluded are compounds where Y is substituted or unsubstituted aryl, Z is —CR 6 ═, L is NR 2 R 3 and one of R 2 and R 3 is substituted or unsubstituted alkylsulfonyl, compounds where Z is —CR 6 ═ and L is substituted or unsubstituted alkyl, or substituted or unsubstituted alkenyl, and compounds,

2 . The compound according to claim 1 or pharmaceutically acceptable salt thereof, wherein Y is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, or substituted or unsubstituted heterocyclyl.

3 . The compound according to claim 1 or pharmaceutically acceptable salt thereof, wherein Y is substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, or substituted or unsubstituted heterocyclyl.

4 . The compound according to claim 1 or pharmaceutically acceptable salt thereof, wherein Y is substituted or unsubstituted heterocyclyl.

5 . The compound according to claim 4 or pharmaceutically acceptable salt thereof, wherein Y is substituted or unsubstituted heterocyclyl and the substituted or unsubstituted heterocyclyl is

where R 9 and R 10 are each independently hydrogen, halogen, hydroxy, cyano, nitro, carboxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylthio, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted acyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted sulfamoyl, or substituted or unsubstituted amino; R 11 is each independently halogen, hydroxy, cyano, nitro, carboxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylthio, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted acyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted sulfamoyl, or substituted or unsubstituted amino; and m is an integer from 0 to 6.

6 . The compound according to claim 1 or pharmaceutically acceptable salt thereof, wherein Z is 13 N═.

7 . The compound according to claim 1 or pharmaceutically acceptable salt thereof, wherein Z is —CR 6 ═.

8 . The compound according to claim 1 or pharmaceutically acceptable salt thereof, wherein L is NR 2 R 3 , SR 7 , or SO 2 R 8 .

9 . The compound according to claim 1 or pharmaceutically acceptable salt thereof, wherein L is NR 2 R 3 .

10 . The compound according to claim 9 or pharmaceutically acceptable salt thereof, wherein R 2 is hydrogen o

Assignees

• Shionogi & Co

Inventors

• Kojima Eiichi
• Hinata Yu
• Wada Toshihiro

Classifications

• C07D471/04 Primary

  Ortho-condensed systems · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61K31/4184

  condensed with carbocyclic rings, e.g. benzimidazoles · CPC title

• C07D401/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D235/26

  Oxygen atoms · CPC title