Quinazolinone and isoquinolinone derivative

Patent metadata

Field	Value
Publication number	US-10005739-B2
Application number	US-201415030804-A
Country	US
Kind code	B2
Filing date	Oct 23, 2014
Priority date	Oct 23, 2013
Publication date	Jun 26, 2018
Grant date	Jun 26, 2018

Abstract

The present invention relates to quinazolinone and isoquinolinone derivatives represented by formula (I) or pharmaceutically acceptable salts thereof.

First claim

The invention claimed is:

1. A compound represented by general formula (I) below or a pharmaceutically acceptable salt thereof:

wherein
A represents formula (1) or (2) below:

Q represents CH 2 or NH;
R 1 in formula (1) represents a C 1-6 alkyl group, C 1-6 alkoxy group, C 2-6 alkenyl group, C 2-6 alkynyl group, halogen atom, cyano group, nitro group or amino group, wherein the C 1-6 alkyl group, C 2-6 alkenyl group, C 2-6 alkynyl group, and C 1-6 alkoxy group may be substituted with 1 to 5 halogen atoms;
R 1 in formula (2) represents a hydrogen atom, C 1-6 alkyl group, C 1-6 alkoxy group, C 2-6 alkenyl group, C 2-6 alkynyl group, halogen atom, cyano group, nitro group or amino group, wherein the C 1-6 alkyl group, C 2-6 alkenyl group, C 2-6 alkynyl group, and C 1-6 alkoxy group may be substituted with 1 to 5 halogen atoms;
A 2 represents CR 2 or N;
R 2 represents a hydrogen atom, C 1-3 alkyl group, C 1-3 alkoxy group, or halogen atom;
A 3 represents CR 3 or N, wherein A 2 and A 3 are not both N;
R 3 represents a hydrogen atom, C 1-3 alkyl group, C 1-3 alkoxy group, or halogen atom;
R 4 represents a C 3-6 alkyl group, C 3-8 cycloalkyl group, (C 3-8 cycloalkyl)methyl group, C 1-6 alkylsulfonyl group, C 1-6 alkylsulfanyl group, C 1-6 alkylsulfinyl group, C 6-10 arylsulfonyl group, C 6-10 arylsulfanyl group, C 6-10 arylsulfinyl group, C 3-8 cycloalkylsulfonyl group, C 3-8 cycloalkylsulfanyl group or C 3-8 cycloalkylsulfinyl group, wherein the C 3-6 alkyl group, C 3-8 cycloalkyl group, (C 3-8 cycloalkyl)methyl group, C 1-6 alkylsulfonyl group, C 1-6 alkylsulfanyl group, C 1-6 alkylsulfinyl group, C 6-10 arylsulfonyl group, C 6-10 arylsulfanyl group, C 6-10 arylsulfinyl group, C 3-8 cycloalkylsulfonyl group, C 3-8 cycloalkylsulfanyl group, and C 3-8 cycloalkylsulfinyl group may be substituted with 1 to 5 halogen atoms;
R 5 represents a hydrogen atom, halogen atom, C 1-6 alkyl group, C 1-6 alkoxy group, C 2-6 alkenyl group, C 2-6 alkynyl group, nitro group, amino group, cyano group, C 1-6 alkylsulfonyl group, C 1-6 alkylsulfanyl group or C 1-6 alkylsulfinyl group, wherein the C 1-6 alkyl group, C 2-6 alkenyl group, C 2-6 alkynyl group, and C 1-6 alkoxy group may be substituted with 1 to 5 halogen atoms;
A 6 represents CR 6 ;
R 6 represents a hydrogen atom, C 1-6 alkyl group, C 1-6 alkoxy group, C 3-8 cycloalkyl group, C 2-6 alkenyl group, halogen atom, formyl group, [1,3]dioxolane, or a group represented by formula (i) below, wherein the C 1-6 alkyl group, C 1-6 alkoxy group, C 3-8 cycloalkyl group or C 2-6 alkenyl group may be substituted with 1 to 5 amino, hydroxyl, and/or OSO 2 CH 3 groups,
●-X—Y—Z  (i)

wherein in formula (i),
X represents —(CH 2 ) n —, —(CH 2 ) n NH(CH 2 ) l —, or —(CH 2 ) n O(CH 2 ) l —;
Y represents a C 3-8 cycloalkyl group, 4- to 10-membered aromatic ring, 3- to 12-membered heterocycle, or 4- to 10-membered aromatic heterocycle, wherein the C 3-8 cycloalkyl group, 4- to 10-membered aromatic ring, 3- to 12-membered heterocycle, and 4- to 10-membered aromatic heterocycle may be substituted with 1 to 5 halogen atoms, oxo groups and/or C 1-3 alkyl groups;
Z represents a hydrogen atom, a C 1-6 alkyl group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, a C 3-8 cycloalkyl group, —(CH 2 ) m NRaRb, —NHCO(CH 2 ) m Rc, —(CH 2 ) m NHCORc, —NH(CH 2 ) m CORc, —(CH 2 ) m N(CH 3 )CORc, —(CH 2 ) m ORd, —(CH 2 ) m CORe, —(CH 2 ) m COORe, —(CH 2 ) m NHSO 2 Rf, —(CH 2 ) m SO 2 Rf, —(CH 2 ) m CONRgRh, a 4- to 10-membered aromatic ring, 4- to 10-membered aromatic heterocycle, or a 3- to 12-membered heterocycle, wherein the C 1-6 alkyl group may be substituted with 1 to 5 halogen atoms, hydroxyl groups, C 3-8 cycloalkyl groups, 4- to 10-membered aromatic rings, 4- to 10-membered aromatic heterocycles, 3- to 12-membered heterocycles, and/or cyano groups; and the 3- to 12-membered heterocycle and 4- to 10-membered aromatic heterocycle may be substituted with 1 to 5 halogen atoms, C 1-3 alkyl groups and/or oxo groups;
n represents 0, 1, 2, or 3;
1 represents 0, 1, 2, or 3;
m represents 0, 1, 2, or 3;
Ra and Rb are identical or different, each representing a hydrogen atom, C 1-6 alkyl group, C 2-6 alkenyl group, C 2-6 alkynyl group, 3- to 12-membered heterocycle, 4- to 10-membered aromatic heterocycle, or —SO 2 CH 3 , wherein the C 1-6 alkyl group may be substituted with 1 to 5 halogen atoms, amino groups, mono-C 1-6 alkylamino groups, di-C 1-6 alkylamino groups, hydroxyl groups, and/or cyano groups;
Rc represents a C 1-6 alkyl group, C 2-6 alkenyl group, C 2-6 alkynyl group, C 1-6 alkoxy group, C 3-8 cycloalkyl group, amino group, mono-C 1-6 alkylamino group, di-C 1-6 alkylamino group or 3- to 12-membered heterocycle, wherein the C 1-6 alkyl group may be substituted with 1 to 3 amino groups, mono-C 1-6 alkylamino groups, di-C 1-6 alkylamino groups, and/or 3- to 12-membered heterocycles;
Rd represents a hydrogen atom, C 1-6 alkyl group, C 2-6 alkenyl group or C 2-6 alkynyl group, wherein the C 1-6 alkyl group, C 2-6 alkenyl group, and C 2-6 alkynyl group may be substituted with 1 to 5 C 1-6 alkoxy groups and/or amino groups;
Re represents a hydrogen atom or C 1-6 alkyl group, wherein the C 1-6 alkyl group may be substituted with an amino group;
Rf represents a C 1-6 alkyl group, an amino group, a mono-C 1-6 alkylamino group, or a di-C 1-6 alkylamino group, wherein the C 1-6 alkyl group, mono-C 1-6 alkylamino group, and di-C 1-6 alkylamino group may be substituted with 1 to 5 halogen atoms;
Rg and Rh are identical or different, each representing a hydrogen atom, C 1-6 alkyl group, or 3- to 12-membered heterocycle, wherein the C 1-6 alkyl group may be substituted with 1 to 3 amino groups, mono-C 1-6 alkylamino groups, and/or di-C 1-6 alkylamino groups;
A 7 represents CR 7 ; and
R 7 represents a hydrogen atom, halogen atom, C 1-6 alkyl group, C 2-6 alkenyl group, C 1-6 alkoxy group, or a cyano group;
A 8 represents N; and
R 9 represents a hydrogen atom or amino group.

2. The compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein A is formula (3) below:

3. The compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein R 4 is a C 1-6 alkylsulfonyl group or C 1-6 alkylsulfanyl group.

4. The compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein R 5 represents a halogen atom, C 1-3 alkyl group, or C 1-3 alkoxy group, wherein the C 1-3 alkyl group or C 1-3 alkoxy group may be substituted with 1 to 5 halogen atoms.

5. The compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein
R 6 represents a hydrogen atom or a group represented by formula (i) below:
●-X—Y—Z  (i)

wherein X represents CH 2 or (CH 2 ) 2 NH(CH 2 ) 2 ;
Y represents piperazine, pyrrolidine, piperidine, morpholine, homomorpholine, 3,3-dimethylpiperazine, (R) or (S)-hexahydro-pyrrolo[1,2-a]pyrazine, 3-oxopiperazine, azetidine or 2-oxo-imidazolidine;
Z represents a hydrogen atom, a C 1-3 alkyl group, a C 4-6 cycloalkyl group, —(CH 2 ) m NRaRb, —NHCO(CH 2 ) m Rc, —(CH 2 ) m NHCORc, —NH(CH 2 ) m CORc, —(CH 2 ) m N(CH 3 )CORc, ORd, —CORe, —COORe,

Assignees

• Chugai Pharmaceutical Co Ltd

Inventors

• Murata Takeshi
• Hara Sousuke
• Niizuma Satoshi
• Hada Kihito
• Kawada Hatsuo
• Sakaitani Masahiro
• Shimada Hideaki
• Nakanishi Yoshito

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P35/04

  specific for metastasis · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• C07D239/94

  Nitrogen atoms · CPC title

• C07D401/06

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