Indazole compound and pharmaceutical

Patent metadata

Field	Value
Publication number	US-2025059172-A1
Application number	US-202218723516-A
Country	US
Kind code	A1
Filing date	Dec 27, 2022
Priority date	Dec 28, 2021
Publication date	Feb 20, 2025
Grant date	—

Abstract

The present invention provides compounds indicated by general formula [1] and having mPGES-1 inhibitory activity, a pharmaceutically acceptable salt thereof, or a solvate thereof (in the formula, R1 and R2 each independently indicate hydrogen, halogen or substitutable alkyl, R3 indicates —SO2 R5 or —COR5, R4 indicates substitutable alkyl, cycloalkyl, aryl, heteroaryl, saturated heterocyclic group or arylalkyl, and R5 indicates a substitutable alkyl, cycloalkyl, aryl, heteroaryl, saturated heterocyclic group, alkynyl or arylalkyl).

First claim

1 : A compound represented by the Formula [1]:

wherein,
R 1 and R each independently represent hydrogen, halogen, or optionally substituted alkyl;
R 3 represents —SO 2 R 5 or —COR 5 ;
R 4 represents optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted saturated heterocyclic group, or optionally substituted arylalkyl; and
R 5 represents optionally substituted, alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted saturated heterocyclic group, optionally substituted alkynyl, or optionally substituted arylalkyl;
wherein said heteroaryl or saturated heterocyclic group is bound at a carbon atom on the ring,

or a pharmaceutically acceptable salt thereof, or a solvate thereof.

2 : The compound according to claim 1 , wherein
the alkyl in R 1 and R 2 is optionally substituted by 1 to 3 halogens: the heteroaryl in R 4 is optionally substituted by 1 to 3 groups independently selected from the group consisting of:
(1) alkoxy optionally substituted by 1 to 3 halogens,
(2) cyano,
(3) halogen,
(4) alkyl optionally substituted by (i) 1 to 3 halogens, (ii) hydroxy or (iii) alkoxy, and
(5) cycloalkyl;
the saturated heterocyclic group in R 4 is optionally substituted by 1 to 3 groups independently selected from the group consisting of alkyl, alkoxycarbonyl and alkylcarbonyl; the alkyl in R 4 is optionally substituted by a saturated heterocyclic group or cycloalkyl; the aryl in R 4 is optionally substituted by 1 to 3 groups independently selected from the group consisting of:
(1) alkoxy optionally substituted by 1 to 3 halogens,
(2) cyano,
(3) halogen,
(4) alkyl optionally substituted by (i) 1 to 3 halogens, (ii) hydroxy or (iii) alkoxy, and
(5) cycloalkyl;
the arylalkyl in R 4 is optionally substituted by alkyl or alkoxy optionally substituted by 1 to 3 halogens; the saturated heterocyclic group in R 5 is optionally substituted by 1 to 3 groups independently selected from the group consisting of alkyl and alkoxycarbonyl; the alkyl in R is optionally substituted by 1 to 3 groups independently selected from the group consisting of hydroxy, alkoxy, cycloalkyl, monoalkylamino, dialkylamino and halogen; and the cycloalkyl in R is optionally substituted by 1 to 3 groups independently selected from the group consisting of:
(1) hydroxy,
(2) cyano, and
(3) alkyl optionally substituted by 1 to 3 halogens,

or a pharmaceutically acceptable salt thereof, or a solvate thereof.

3 : The compound according to claim 1 , wherein
the aryl in R is phenyl optionally substituted by 1 to 3 groups independently selected from the group consisting of:
(1) alkoxy which is optionally substituted by 1 to 3 halogens,
(2) cyano,
(3) halogen,
(4) alkyl optionally substituted by (i) 1 to 3 halogens, (ii) hydroxy or (iii) alkoxy, and
(5) cycloalkyl,
the heteroaryl in R is imidazolyl, thiazolyl, pyridyl, pyridazinyl or pyrimidinyl, each of which is optionally substituted by 1 to 3 groups independently selected from the group consisting of:
(1) alkoxy which is optionally substituted by 1 to 3 halogens,
(2) cyano,
(3) halogen,
(4) alkyl optionally substituted by (i) 1 to 3 halogens, (ii) hydroxy, or (iii) alkoxy, and
(5) cycloalkyl; and
the saturated heterocyclic group in R 4 is piperidinyl or tetrahydropyranyl optionally substituted by alkyl, alkoxycarbonyl or alkylcarbonyl, or a pharmaceutically acceptable salt thereof, or a solvate thereof.

4 : The compound according to claim 1 , wherein
the aryl in R 5 is phenyl; the heteroaryl in R is furyl; and the saturated heterocyclic group in R 5 is piperidinyl, tetrahydrofuryl or tetrahydropyranyl, each of which is optionally substituted by 1 to 3 groups independently selected from the group consisting of alkyl and alkoxycarbonyl, or a pharmaceutically acceptable salt thereof, or a solvate thereof.

5 : The compound according to claim 1 , wherein R 4 is alkyl having 1 to 6 carbons optionally substituted by a saturated heterocyclic group or cycloalkyl, or a pharmaceutically acceptable salt thereof or a solvate thereof.

6 : The compound according to claim 1 , wherein R 4 is cycloalkyl having 3 to 10 carbons, or a pharmaceutically acceptable salt thereof, or a solvate thereof.

7 : The compound according to claim 1 , wherein
R 4 is phenyl optionally substituted by 1 to 3 groups independently selected from the group consisting of:
(1) alkoxy optionally substituted by 1 to 3 halogens,
(2) cyano,
(3) halogen,
(4) alkyl optionally substituted by (i) 1 to 3 halogens, (ii) hydroxy or (iii) alkoxy, and
(5) cycloalkyl,

or a pharmaceutically acceptable salt thereof, or a solvate thereof.

8 : The compound according to claim 1 , wherein
R 4 is imidazolyl, thiazolyl, pyridyl, pyridazinyl or pyrimidinyl, each of which is optionally substituted by 1 to 3 groups independently selected from the group consisting of:
(1) alkoxy optionally substituted by 1 to 3 halogens,
(2) cyano,
(3) halogen,
(4) alkyl optionally substituted by (i) 1 to 3 halogens, (ii) hydroxy or (iii) alkoxy, and
(5) cycloalkyl,

or a pharmaceutically acceptable salt thereof, or a solvate thereof.

9 : The compound according to claim 1 , wherein R 4 is piperidinyl or tetrahydropyranyl, each of which is optionally substituted by 1 to 3 groups independently selected from the group consisting of alkyl, alkoxycarbonyl and alkylcarbonyl, or a pharmaceutically acceptable salt thereof, or a solvate thereof.

10 : The compound of claim 1 , wherein R 4 is phenylalkyl, which is optionally substituted by alkyl or alkoxy of 1 to 6 carbons, each of which is optionally substituted by 1 to 3 halogens, or a pharmaceutically acceptable salt thereof, or a solvate thereof.

11 : The compound of claim 1 , wherein R 5 is alkyl having 1-6 carbons, which is optionally substituted by 1 to 3 groups independently selected from the group consisting of hydroxy, alkoxy, cycloalkyl, monoalkylamino, dialkylamino, and halogen, or a pharmaceutically acceptable salt thereof, or a solvate thereof.

12 : The compound according to claim 1 , wherein R 5 is cycloalkyl having 3 to 10 carbons optionally substituted by 1 to 3 groups independently selected from the group consisting of (1) hydroxy, (2) cyano and (3) alkyl optionally substituted by 1 to 3 halogens, or a pharmaceutically acceptable salt thereof, or a solvate thereof.

13 : The compound according to claim 1 , wherein R 5 is optionally substituted phenyl, or a pharmaceutically acceptable salt thereof, or a solvate thereof.

14 : The compound according to claim 1 , wherein R is optionally substituted furyl, or a pharmaceutically acceptable salt thereof, or a solvate thereof.

15 : The compound according to claim 1 , wherein R 5 is piperidinyl, tetrahydrofuryl or tetrahydropyranyl, each of which is optionally substituted by 1 to 3 groups independently selected from the group consisting of alkyl and alkoxycarbonyl, or a pharmaceutically acceptable salt thereof or a solvate thereof.

16 : The compound according to claim 1 , wherein R 5 is optionally substituted alkynyl having 2 to 6 carbons, or a pharmaceutically acceptable salt thereof, or a solvate thereof.

17 : The compound of claim 1 , wherein R 5 is optionally substituted phenylalkyl, or a pharmaceutically acceptable salt ther

Assignees

• Nippon Shinyaku Co Ltd

Inventors

• Hashimoto Kosuke
• Takita Hirofumi
• Kakutani Mai
• Yamaguchi Hiroshi
• Fukui Tomomi

Classifications

• C07D417/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D405/12

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

• C07D405/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• C07D405/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D403/04

  directly linked by a ring-member-to-ring-member bond · CPC title