Isoindolin-1-on derivative, method for preparing same, and pharmaceutical composition comprising same as effective component for preventing or treating cancer

Patent metadata

Field	Value
Publication number	US-2021332029-A1
Application number	US-201917268869-A
Country	US
Kind code	A1
Filing date	Aug 12, 2019
Priority date	Aug 16, 2018
Publication date	Oct 28, 2021
Grant date	—

Abstract

The present invention relates to an isoindolin-1-on derivative, a method for preparing same, and a pharmaceutical composition comprising same as an effective component for preventing or treating tumors, wherein the isoindolin-1-on derivative exhibits a high inhibitory effect on EGFR mutations, and thus can be beneficially used for the treatment of EGFR-mutated tumors, and the isoindolin-1-on derivative exhibits a significant synergistic effect when co-administered, and thus can be beneficially used in concomitant therapy.

First claim

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

(In formula 1,
A 1 is CH or N;
A 2 is CH or N;
R 1 is hydrogen, C 3-10 cycloalkyl, C 6-10 aryl, 3-10 membered heterocycloalkyl containing one or more heteroatoms selected from the group consisting of N, O and S, or 5-10 membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, O and S, wherein the cycloalkyl and heterocycloalkyl may be unsaturated by including one double bond,
cycloalkyl, aryl, heterocycloalkyl and heteroaryl can be independently substituted with one or more substituents selected from the group consisting of —NR a R b ; straight or branched C 1-6 alkyl; acetyl; straight or branched C 1-6 alkylcarbonyl; straight or branched C 1-6 alkylaminocarbonyl; straight or branched C 1-6 alkylcarbonylamino; straight or branched C 1-6 alkylsulfonyl; saturated or unsaturated C 3-7 cycloalkyl including one double bond, which is nonsubstituted or substituted with one or more substituents selected from the group consisting of —NR c R d , acetyl, straight or branched C 1-6 alkyl, straight or branched C 1-6 alkylcarbonyl, straight or branched C 1-6 alkylaminocarbonyl, straight or branched C 1-6 alkylcarbonylamino straight or branched C 1-6 alkylsulfonyl, and 5 or 6 membered heterocycloalkyl nonsubstituted or substituted with one or more straight or branched C 1-4 alkyl containing one or more heteroatoms selected from the group consisting of N, O and S; saturated or unsaturated 3-7 membered heterocycloalkyl including one double bond and one or more heteroatoms selected from the group consisting of N, O and S, which is nonsubstituted or substituted with one or more substituents selected from the group consisting of —NR e R f , acetyl, straight or branched C 1-6 alkyl, straight or branched C 1-6 alkylcarbonyl, straight or branched C 1-6 alkylaminocarbonyl, straight or branched C 1-6 alkylcarbonylamino, straight or branched C 1-6 alkylsulfonyl, and 5 or 6 membered heterocycloalkyl nonsubstituted or substituted with one or more straight or branched C 1-4 alkyl containing one or more heteroatoms selected from the group consisting of N, O and S; and 5 or 6 membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, O and S, which is nonsubstituted or substituted with one or more substituents selected from the group consisting of —NR e R f , acetyl, straight or branched C 1-4 alkyl, straight or branched C 1-4 alkylcarbonyl, straight or branched C 1-4 alkylaminocarbonyl, straight or branched C 1-4 alkylcarbonylamino, straight or branched C 1-4 alkylsulfonyl, and 5 or 6 membered heterocycloalkyl nonsubstituted or substituted with one or more straight or branched C 1-4 alkyl containing one or more heteroatoms selected from the group consisting of N, O and S,
wherein R a , R b , R c , R d , R e and R f are independently hydrogen, straight or branched C 1-6 alkyl or straight or branched C 1-6 alkylsulfonyl;
R 2 , R 3 and R 4 are independently hydrogen, halogen or straight or branched C 1-6 alkyl, wherein the alkyl can be substituted with one or more halogens; and
R 5 and R 6 are independently hydrogen, halogen or straight or branched C 1-6 alkyl, wherein the alkyl can be substituted with one or more halogens).

2 . The compound, the isomer thereof, the solvate thereof, the hydrate thereof or the pharmaceutically acceptable salt thereof according to claim 1 , wherein:
R 1 is hydrogen, C 3-7 cycloalkyl, phenyl, 3-7 membered heterocycloalkyl containing one or more heteroatoms selected from the group consisting of N, O and S, or 5-8 membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, O and S, wherein the cycloalkyl and heterocycloalkyl may be unsaturated by including one double bond, cycloalkyl, phenyl, heterocycloalkyl and heteroaryl can be independently substituted with one or more substituents selected from the group consisting of —NR a R b ; straight or branched C 1-4 alkyl; acetyl; straight or branched C 1-4 alkylcarbonyl; straight or branched C 1-4 alkylaminocarbonyl; straight or branched C 1-4 alkylcarbonylamino; straight or branched C 1-4 alkylsulfonyl; saturated or unsaturated C 3-6 cycloalkyl including one double bond, which is nonsubstituted or substituted with one or more substituents selected from the group consisting of —NR c R d , acetyl, straight or branched C 1-4 alkyl, straight or branched C 1-4 alkylcarbonyl, straight or branched C 1-4 alkylaminocarbonyl, straight or branched C 1-4 alkylcarbonylamino, straight or branched C 1-4 alkylsulfonyl, and 5 or 6 membered heterocycloalkyl nonsubstituted or substituted with one or more straight or branched C 1-4 alkyl containing one or more heteroatoms selected from the group consisting of N, O and S; saturated or unsaturated 5 or 6 membered heterocycloalkyl including one double bond and one or more heteroatoms selected from the group consisting of N, O and S, which is nonsubstituted or substituted with one or more substituents selected from the group consisting of —NR e R f , acetyl, straight or branched C 1-4 alkyl, straight or branched C 1-4 alkylcarbonyl, straight or branched C 1-4 alkylaminocarbonyl, straight or branched C 1-4 alkylcarbonylamino, straight or branched C 1-4 alkylsulfonyl, and 5 or 6 membered heterocycloalkyl nonsubstituted or substituted with one or more straight or branched C 1-4 alkyl containing one or more heteroatoms selected from the group consisting of N, O and S; and 5 or 6 membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, O and S, which is nonsubstituted or substituted with one or more substituents selected from the group consisting of —NR e R f , acetyl, straight or branched C 1-4 alkyl, straight or branched C 1-4 alkylcarbonyl, straight or branched C 1-4 alkylaminocarbonyl, straight or branched C 1-4 alkylcarbonylamino, straight or branched C 1-4 alkylsulfonyl, and 5 or 6 membered heterocycloalkyl nonsubstituted or substituted with one or more straight or branched C 1-4 alkyl containing one or more heteroatoms selected from the group consisting of N, O and S, wherein R a , R b , R c , R d , R e and R f are independently hydrogen, straight or branched C 1-4 alkyl or straight or branched C 1-4 alkylsulfonyl.

3 . The compound, the isomer thereof, the solvate thereof, the hydrate thereof or the pharmaceutically acceptable salt thereof according to claim 1 , wherein:
R 1 is hydrogen, C 5-6 cycloalkyl, phenyl, 5 or 6 membered heterocycloalkyl containing one or more heteroatoms selected from the group consisting of N, O and S, or 5 or 6 membered heteroaryl containing one or more heteroatoms selected from the group consisting of N, O and S, wherein the cycloalkyl and heterocycloalkyl may be unsaturated by including one double bond, cycloalkyl, phenyl, heterocycloalkyl and heteroaryl can be independently substituted with one or more substituents selected from the group consisting of —NR a R b ; straight or branched C 1-4 alkyl; acetyl; straight or branched C 1-4 alkylcarbonyl; straight or branched C 1-4 alkylaminocarbonyl; straight or branched C 1-4 alkylcarbonylamino; straight or branched C 1-4 alkylsulfonyl; saturated or unsaturated C 5-6 cycloalkyl nonsubstituted or substituted with one or more substituents selected from the group consisting of —NR c R d , acetyl, straight or branched C 1-4 alkyl, straight or branched C 1-4 alkylcarbonyl, straight or branched C 1-4 alkylaminocarbonyl, straight or branched C 1-4 alkylcarbonylamino straight or branched C 1-4 alkylsulfony

Assignees

• Korea Res Inst Chemical Tech
• Korea Res Inst Chemical Tech

Inventors

• Lee Kwangho
• Choi Gildon
• Lee Seoyoung
• Kim Jiwon
• Cho Byoung Chul
• Park Chae Won
• Yun Jiyeon

Classifications

• C07D471/04

  Ortho-condensed systems · CPC title

• C07D403/14 Primary

  containing three or more hetero rings · CPC title

• A61K31/5377

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title

• C07D401/14

  containing three or more hetero rings · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title