[1,2,4]Triazolo[4,3-a]quinoxaline derivative, method for preparing same, and pharmaceutical composition for preventing or treating BET protein-related diseases, containing same as active ingredient

Patent metadata

Field	Value
Publication number	US-11028090-B2
Application number	US-201816480908-A
Country	US
Kind code	B2
Filing date	Jan 25, 2018
Priority date	Jan 26, 2017
Publication date	Jun 8, 2021
Grant date	Jun 8, 2021

Abstract

Provided are a novel [1,2,4]triazolo[4,3-a]quinoxaline derivative, a method for preparing the same, and a pharmaceutical composition for preventing or treating bromodomain extra-terminal (BET) protein-related diseases including cancer and autoimmune diseases, containing the same as an active ingredient.

First claim

What is claimed is:

1. A compound represented by formula 1, an optical isomer thereof or a pharmaceutically acceptable salt thereof:

wherein,
R 1 is C 1-20 straight or branched alkyl nonsubstituted or substituted with one or more halogens, or C 6-20 aryl;
R 2 is hydrogen, C 1-20 straight or branched alkyl, or C 1-20 straight or branched alkoxy;
R 3 is hydrogen, nitro, halogen, nonsubstituted or substituted C 1-20 straight or branched alkyl, nonsubstituted or substituted C 1-20 straight or branched alkoxy, 5-10 membered heteroaryl nonsubstituted or substituted with one or more methyl groups containing one or more heteroatoms selected from the group consisting of N, O and S,

which forms 6 membered cycloalkyl containing one or more heteroatoms selected from the group consisting of S and O along with R 4 ,
wherein, the substituted C 1-20 straight or branched alkyl and the substituted C 1-20 straight or branched alkoxy can be independently substituted with one or more substituents selected from the group consisting of halogen, C 1-3 straight or branched alkoxy, 5-10 membered heterocycloalkyl containing one or more heteroatoms selected from the group consisting of N, O and S, and C 6-10 aryl nonsubstituted or substituted with one or more nitro groups,
A 1 is hydrogen, or C 1-20 straight or branched alkyl,
B 1 and B 2 are independently hydrogen, C 1-20 straight or branched alkyl, diC 1-3 straight or branched alkylamino C 1-3 straight or branched alkyl, or C 6-10 aryl, and B 1 and B 2 are linked to each other to form 5-10 membered heterocycloalkyl nonsubstituted or substituted with one or more benzyl groups containing one or more heteroatoms selected from the group consisting of N, O and S,
C 1 is hydrogen, C 1-20 straight or branched alkyl, or C 1-20 straight or branched alkoxy,
D 1 and D 2 are independently hydrogen, hydroxy, C 1-20 straight or branched alkyl saturated or containing one or more carbon≡carbon unsaturated bonds, C 1-20 straight or branched alkyl nonsubstituted or substituted with one or more cyano groups, or C 1-20 straight or branched alkylsulfonyl,
E 1 is C 1-20 straight or branched alkyl, or C 6-10 aryl C 1-5 straight or branched alkyl,
F 1 is C 1-20 straight or branched alkyl, or C 6-10 aryl,
G 1 is C 1-20 straight or branched alkyl, or C 6-10 aryl;
R 4 is hydrogen, hydroxy, halogen, nitro, C 1-20 straight or branched alkyl nonsubstituted or substituted with one or more ═S groups, C 1-20 straight or branched alkylsulfanyl nonsubstituted or substituted with one or more oxo (═O) groups, C 1-20 straight or branched alkylsulfonyl, 5-10 membered heterocycloalkyloxy nonsubstituted or substituted with one or more C 1-5 straight or branched alkoxycarbonyl containing one or more heteroatoms selected from the group consisting of N, O and S, nonsubstituted or substituted 5-10 membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, O and S, nonsubstituted or substituted C 1-20 straight or branched alkoxy,

wherein, the substituted 5-10 membered heteroaryl can be substituted with one or more substituents selected from the group consisting of C 1-3 straight or branched alkyl, C 1-3 straight or branched alkoxy and C 1-3 straight or branched alkoxy C 1-3 straight or branched alkyl,
wherein, the substituted C 1-20 straight or branched alkoxy can be substituted with one or more substituents selected from the group consisting of halogen, cyano, C 1-3 straight or branched alkoxy, nonsubstituted or substituted 5-10 membered heterocycloalkyl containing one or more heteroatoms selected from the group consisting of N, O and S, and nonsubstituted or substituted C 6-10 aryl,
wherein, the substituted 5-10 membered heterocycloalkyl and the substituted C 6-10 aryl can be independently substituted with one or more substituents selected from the group consisting of cyano,

C 1-5 straight or branched alkoxycarbonyl, and 5-8 membered heteroaryl nonsubstituted or substituted with one or more N groups,
A 3 is hydrogen, or C 1-20 straight or branched alkyl,
B 3 and B 4 are independently hydrogen, C 1-20 straight or branched alkyl, diC 1-3 straight or branched alkylamino C 1-3 straight or branched alkyl, nonsubstituted or substituted C 6-10 aryl, nonsubstituted or substituted C 6-10 aryl C 1-3 straight or branched alkyl, and B 3 and B 4 are linked to each other to form 5-10 membered heterocycloalkyl nonsubstituted or substituted with one or more benzyl groups containing one or more heteroatoms selected from the group consisting of N, O and S,
wherein, the substituted C 6-10 aryl can be substituted with one or more substituents selected from the group consisting of amine, halogen, C 1-5 straight or branched alkyl and C 1-5 straight or branched alkoxy,
C 3 , C 4 and C 5 are independently hydrogen, amine, halogen, C 1-20 straight or branched alkyl, or C 1-20 straight or branched alkoxy,
D 3 and D 4 are independently hydrogen, hydroxy, C 1-20 straight or branched alkyl saturated or containing one or more carbon≡carbon unsaturated bonds, C 1-20 straight or branched alkyl nonsubstituted or substituted with one or more cyano groups, or C 1-20 straight or branched alkylsulfonyl nonsubstituted or substituted with one or more halogens, and D 3 and D 4 are linked to each other to form 5-10 membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, O and S, or 5-10 membered heterocycloalkyl fused with 5 membered heteroaryl nonsubstituted or substituted with one or more methyl groups or containing one S group and one or more heteroatoms selected from the group consisting of N, O and S,
E 3 is C 1-20 straight or branched alkyl, or C 6-10 aryl C 1-5 straight or branched alkyl,
F 3 is C 1-20 straight or branched alkyl, or C 6-10 aryl,
G 3 is C 1-20 straight or branched alkyl, or C 6-10 aryl,
H 3 is C 6-10 aryl, 5-10 membered heterocycloalkyl containing one or more heteroatoms selected from the group consisting of N, O and S, or 5-10 membered heteroaryl nonsubstituted or substituted with one or more methyl groups containing one or more heteroatoms selected from the group consisting of N, O and S,
I 3 is diC 1-3 straight or branched alkylamino;
R 5 is hydrogen, halogen, C 1-20 straight or branched alkyl nonsubstituted or substituted with one or more halogens, or C 1-20 straight or branched alkoxy;
R 6 is

B 5 and B 6 are independently hydrogen, C 1-20 straight or branched alkyl, C 6-10 aryl C 1-3 straight or branched alkyl, or 5-10 membered heteroaryl C 1-3 straight or branched alkyl containing one or more heteroatoms selected from the group consisting of N, O and S,
D 5 and D 6 are independently hydrogen, hydroxy, C 1-20 straight or branched alkyl saturated or containing one or more carbon≡carbon unsaturated bonds, C 1-20 straight or branched alkyl nonsubstituted or substituted with one or more cyano groups, or C 1-20 straight or branched alkylsulfonyl nonsubstituted or substituted with one or more halogens,
E 5 is C 1-20 straight or branched alkyl saturated or containing one or more carbon≡carbon unsaturated bonds, C 1-20 straight or branched alkoxy saturated or containing one or more carbon═carbon unsaturated bonds, C 3-10 cyclo

Assignees

• Dong Wha Pharm Co Ltd
• Korea Res Inst Chemical Tech

Inventors

• Lee Kwangho
• Choi Gildon
• Ali Imran
• Lee Joo Yun
• Lee Jin Soo
• Park Whui Jung
• Kim Yong Tae
• Kim Seung Hwan
• Kim Jung Hwan
• Lim Jae-Kyung

Classifications

• A61P35/00 Primary

  Antineoplastic agents · CPC title

• A61K31/4196

  1,2,4-Triazoles · CPC title

• C07D487/04 Primary

  Ortho-condensed systems · CPC title

• C07D519/00

  Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00 · CPC title

• A61K31/4985

  Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems · CPC title