Indazolyl-oxo-isothiazole compounds

Patent metadata

Field	Value
Publication number	US-10201531-B2
Application number	US-201615751273-A
Country	US
Kind code	B2
Filing date	Aug 10, 2016
Priority date	Aug 12, 2015
Publication date	Feb 12, 2019
Grant date	Feb 12, 2019

Abstract

The present invention provides a compound represented by Formula (I) or a pharmaceutically acceptable salt thereof or a solvate of these. A compound having Nrf2 activation ability is provided by the present invention.

First claim

The invention claimed is:

1. A compound represented by Formula (I) below, or a pharmaceutically acceptable salt thereof or a solvate of these:

wherein the formula, R 1 represents a group arbitrarily selected from a hydrogen atom, a halogen atom, a C 1-6 alkyl group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, a halogenated C 1-6 alkyl group, a C 1-6 alkoxy group, a C 2-6 alkenyloxy group, a C 2-6 alkynyloxy group, a cyano group, a C 3-8 cycloalkyl group, a C 3-8 cycloalkenyl group, a C 6-14 aryl group, a non-aromatic heterocyclic group, a heteroaryl group and a C 6-14 arylcarbonyl group,
R 2 represents a group arbitrarily selected from a hydrogen atom, a halogen atom, a C 1-6 alkyl group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, a halogenated C 1-6 alkyl group, a C 1-6 alkoxy group, a C 2-6 alkenyloxy group, a C 2-6 alkynyloxy group, a cyano group, a C 3-8 cycloalkyl group, a C 3-8 cycloalkenyl group, a C 6-14 aryl group, a non-aromatic heterocyclic group, a heteroaryl group, a C 7-20 aralkyl group, a heteroaryl C 1-6 alkyl group, a C 6-14 aryloxy C 1-6 alkyl group and a heteroaryloxy C 1-6 alkyl group,
R 3 represents a group arbitrarily selected from a hydrogen atom, a halogen atom, a C 1-6 alkyl group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, a C 1-6 alkoxy group, a C 2-6 alkenyloxy group, a C 2-6 alkynyloxy group and a cyano group,
R 4 represents a group arbitrarily selected from a hydrogen atom, a halogen atom, a C 1-6 alkyl group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, a C 1-6 alkoxy group, a C 2-6 alkenyloxy group, a C 2-6 alkynyloxy group and a cyano group,
each of R 1 R 2 and R 3 is optionally substituted with 1 to 5 of R 5 ,
each R 5 independently represents a group arbitrarily selected from a halogen atom, a C 1-6 alkyl group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, a halogenated C 1-6 alkyl group, a C 1-6 alkoxy group, a C 2-6 alkenyloxy group, a C 2-6 alkynyloxy group, a cyano group, a C 1-6 alkoxycarbonyl group, a —NR b R c group (in which each of R b and R c independently represents a hydrogen atom, a C 1-6 alkyl group or a non-aromatic heterocyclic group), a mono/di-C 1-6 alkylamino C 1-6 alkyl group, a C 3-8 cycloalkyl group, a C 3-8 cycloalkenyl group, a C 6-14 aryl group, non-aromatic heterocyclic group, heteroaryl group, a C 3-8 cycloalkyl C 1-6 alkyl group, a C 7-20 aralkyl group, non-aromatic heterocyclic C 1-6 alkyl group, a heteroaryl C 1-6 alkyl group, a C 6-14 aryloxy group, heteroaryloxy group, a C 7-20 aralkyloxy group and a heteroaryl C 1-6 alkyloxy group,
each of the C 3-8 cycloalkyl group, C 3-8 cycloalkenyl group, C 6-14 aryl group, non-aromatic heterocyclic group, heteroaryl group, C 3-8 cycloalkyl C 1-6 alkyl group, C 7-20 aralkyl group, non-aromatic heterocyclic C 1-6 alkyl group, heteroaryl C 1-6 alkyl group,C 6-14 aryloxy group, heteroaryloxy group, C 7-20 aralkyloxy group or heteroaryl C 1-6 alkyloxy group in R 5 is optionally substituted with 1 to 5 of a group arbitrarily selected from a halogen atom, a C 1-6 alkyl group, a halogenated C 1-6 alkyl group, a C 1-6 alkoxy group, a cyano group, a C 1-6 alkoxycarbonyl group, a C 3-8 cycloalkyl group, a C 3-8 cycloalkenyl group, a C 6-14 aryl group (which is itself optionally substituted with 1 to 5 C 1-6 alkyl groups), a non-aromatic heterocyclic group and a heteroaryl group,
R 2 may bind with R 1 or R 3 to form a fused ring group together with part of a pyrazole ring, and this fused ring group is a 5- to 10-member heterocyclic group or C 6-10 aryl group optionally substituted with 1 to 5 of R 6 ,
each R 6 independently represents a group arbitrarily selected from a halogen atom, a C 1-6 alkyl group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, a halogenated C 1-6 alkyl group, a C 1-6 alkoxy group, a C 2-6 alkenyloxy group, a C 2-6 alkynyloxy group, a cyano group, a C 1-6 alkoxycarbonyl group, a C 3-8 cycloalkyl group, a C 3-8 cycloalkenyl group, a C 6-14 aryl group, a non-aromatic heterocyclic group, a heteroaryl group, a C 3-8 cycloalkyl C 1-6 alkyl group, a C 7-20 aralkyl group, a heteroaryl C 1-6 alkyl group, aC 6-14 aryloxy group, a heteroaryloxy group, a C 7-20 aralkyloxy group and a heteroaryl C 1-6 alkyloxy group,
each R 6 is optionally substituted with 1 to 5 of R 7 ,
each R 7 independently represents a group arbitrarily selected from a halogen atom, a C 1-6 alkyl group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, a halogenated C 1-6 alkyl group, a C 1-6 alkoxy group, a C 2-6 alkenyloxy group, a C 2-6 alkynyloxy group, a C 1-6 alkoxy C 1-6 alkyl group, a cyano group, a C 1-6 alkoxycarbonyl group, a —CONR d R e group (in which each of R d and R e independently represents a hydrogen atom, a C 1-6 alkyl group, a C 3-8 cycloalkyl group or a C 6-14 aryl group), a mono/di-C 2-7 alkanoylamino group, an amino group, a mono/di-C 1-6 alkylamino group, a mono/di-C 1-6 alkylamino C 1-6 alkyl group, a C 3-8 cycloalkyl group, a C 3-8 cycloalkenyl group, a C 6-14 aryl group, a non-aromatic heterocyclic group, a heteroaryl group, a C 3-8 cycloalkyl C 1-6 alkyl group, a C 7-20 aralkyl group, a non-aromatic heterocyclic C 1-6 alkyl group, a heteroaryl C 1-6 alkyl group, a C 6-14 aryloxy group, heteroaryloxy group, a C 3-8 cycloalkylcarbonyl group, a group, a C 6-14 arylcarbonyl group and a non-aromatic heterocyclic carbonyl group, and
each of the C 3-8 cycloalkyl group, C 3-8 cycloalkenyl group, C 6-14 aryl group, non-aromatic heterocyclic group, heteroaryl group, C 3-8 cycloalkyl C 1-6 alkyl group, C 7-20 aralkyl group, non-aromatic heterocyclic C 1-6 alkyl group, heteroaryl C 1-6 alkyl group, C 6-14 aryloxy group, heteroaryloxy group, C 3-8 cycloalkylcarbonyl group, C 6-14 arylcarbonyl group or non-aromatic heterocyclic carbonyl group of R 7 is optionally substituted with 1 to 5 of a halogen atom, a C 1-6 alkyl group, a halogenated C 1-6 alkyl group, a C 1-6 alkoxy group or a C 1-6 alkoxy C 1-6 alkyl group.

2. The compound represented by Formula (I)-1 below or a pharmaceutically acceptable salt thereof or a solvate of these according to claim 1 :

wherein the formula, R 1a a represents a group arbitrarily selected from a hydrogen atom, a halogen atom, a C 1-6 alkyl group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, a halogenated C 1-6 alkyl group, a C 1-6 alkoxy group, a C 2-6 alkenyloxy group, a C 2-6 alkynyloxy group, a cyano group, a C 3-8 cycloalkyl group and a C 6-14 arylcarbonyl group,
each R 1a is optionally substituted with 1 to 5 halogen atoms,
each R 6a independently represents a group arbitrarily selected from a halogen atom, a C 1-6 alkyl group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, a halogenated C 1-6 alkyl group, a C 1-6 alkoxy group, a C 2-6 alkenyloxy group, a C 2-6 alkynyloxy group, a cyano group, a C 3-8 cycloalkyl group, a C 3-8 cycloalkenyl group, a C 6-14 aryl group, a non-aromatic heterocyclic group, a heteroaryl group, a C 6-14 aryloxy group, a heteroaryloxy group, a C 7-20 aralkyloxy group and a heteroaryl C 1-6 alkyloxy group,
each R 6a is optionally substituted with 1 to 5 of R 7a ,
each R 7a independently represents a group arbitrarily selected from a halogen atom, a C 1-6 alkyl group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, a halogenated C 1-6 alkyl group, a C 1-6 alkoxy group, a C 2-6 alkenyloxy group, a C 2-6 alkynyloxy group, a C 1-6 alkoxy C 1-6 alkyl group, a cyano group, a C 1-6 alkoxycarbonyl group, a —CONR d R e group (in which each of R d and R e independently represents a hydrogen atom, a C 1-6 alkyl group, a

Assignees

• Mochida Pharm Co Ltd

Inventors

• Saitoh Fumihiko
• Kamino Tomoyuki
• Nakahara Motoi

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P43/00

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

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P9/12

  Antihypertensives · CPC title