Oxoquinazolinyl-butanamide derivatives

Patent metadata

Field	Value
Publication number	US-9901577-B2
Application number	US-201414909365-A
Country	US
Kind code	B2
Filing date	Jul 10, 2014
Priority date	Jul 31, 2013
Publication date	Feb 27, 2018
Grant date	Feb 27, 2018

Abstract

Compounds of the formula I

in which R 1 -R 3 and Z have the meanings indicated in Claim 1 , are inhibitors of Tankyrase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation.

First claim

The invention claimed is:

1. A compound of formula I

in which
Z denotes

X denotes CH or N,
R 1 , R 2 each, independently of one another, denote H, F or Cl,
R 3 denotes H, F, Cl, CH 3 or OCH 3 ,
R 4 denotes H, F, A, CN, OA or Y,
R 5 denotes H, F, A or OA,
R 6 denotes CN or 2-pyrimidinyl,
R 7 denotes Het 2 ,
A denotes unbranched or branched alkyl with 1-8 C-Atoms, wherein one or two non-adjacent CH- and/or CH 2 -groups may be replaced by N- or O-atoms and wherein 1-7 H-atoms may be replaced by F, Cl and/or OH,
Y denotes pyrazolyl, which may be substituted by A or (CH 2 ) n Het 1 ,
Het 1 denotes pyrrolidinyl, piperidinyl, morpholinyl or piperazinyl, each of which may be substituted by A,
Het 2 denotes pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, pyrrolyl, thiazolyl, furanyl or thienyl, each of which may be substituted by A,
n 0, 1, 2, 3 or 4,

or a pharmaceutically acceptable salt, tautomer, stereoisomer or mixture thereof in all ratios.

2. The compound according to claim 1 in which
A denotes unbranched or branched alkyl with 1-6 C-Atoms, wherein one or two non-adjacent CH 2 -groups may be replaced by 0-atoms and wherein 1-7 H-atoms may be replaced by F and/or OH,

or a pharmaceutically acceptable salt, tautomer, stereoisomer or mixture thereof in all ratios.

3. The compound according to claim 1 , in which
R 1 , R 2 each, independently of one another, denote H, F or Cl,
R 3 denotes H, F, Cl, CH 3 or OCH 3 ,
R 4 denotes H, F, A, CN, OA or Y,
R 5 denotes H, F, A or OA,
A denotes unbranched or branched alkyl with 1-6 C-Atoms, wherein 1-3 H-atoms may be replaced by F and/or OH,
Y denotes pyrazolyl, which may be substituted by A, methoxyethyl, or (CH 2 ) n Het 1 ,
Het 1 denotes pyrrolidinyl, piperidinyl, morpholinyl or piperazinyl, each of which may br substituted by A,
Het 2 denotes pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, pyrrolyl, thiazolyl, furanyl or thienyl, each of which may be substituted by A,
A denotes unbranched or branched alkyl with 1-6 C-Atoms, wherein 1-3 H-atoms may be replaced by F and/or OH,
n 0, 1, 2, 3 or 4,

or a pharmaceutically acceptable salt, tautomer, stereoisomer or mixture thereof in all ratios.

4. The compound according to claim 1 , in which
R 1 denotes H,
R 2 denotes H or F,
R 3 denotes H, CH 3 or F,
R 4 denotes H, CN, OCH 3 , 1-ethyl-1H-pyrazol-4-yl, 1-(2-methoxy-ethyl)-1H-pyrazol-4-yl or 1-(2-pyrrolidin-1-yl-ethyl)-1H-pyrazol-4-yl,
R 5 denotes H, CH 3 , F or OCH 3 ,
Het 2 denotes pyrazolyl or imidazolyl, each of which may be substituted by A,
A denotes unbranched or branched alkyl with 1-6 C-Atoms, wherein 1-3 H-atoms may be replaced by F and/or OH,

or a pharmaceutically acceptable salt, tautomer, stereoisomer or mixture thereof in all ratios.

5. The compound according to claim 1 , of the formula

No.
Name

“A1”
2-{4-[4-(4-methoxy-benzoyl)-piperidin-1-yl]-4-oxo-butyl}-3H-

quinazolin-4-one

“A2”
2-[4-(4-benzoyl-piperidin-1-yl)-4-oxo-butyl]-3H-quinazolin-4-one

“A3”
2-[4-(4-benzoyl-piperidin-1-yl)-4-oxo-butyl]-6-fluoro-8-methyl-

3H-quinazolin-4-one

“A4”
6-fluoro-2-{4-[4-(4-methoxy-benzoyl)-piperidin-1-yl]-4-oxo-

butyl}-8-methyl-3H-quinazolin-4-one

“A5”
6,8-difluoro-2-{4-[4-(4-methoxy-benzoyl)-piperidin-1-yl]-4-oxo-

butyl}-3H-quinazolin-4-one

“A6”
2-[4-(4-benzoyl-piperidin-1-yl)-4-oxo-butyl]-6,8-difluoro-3H-

quinazolin-4-one

“A7”
2-{4-[4-(3-methyl-benzoyl)-piperidin-1-yl]-4-oxo-butyl}-3H-

quinazolin-4-one

“A8”
2-{4-[4-(3-fluoro-4-methoxy-benzoyl)-piperidin-1-yl]-4-oxo-

butyl}-3H-quinazolin-4-one

“A9”
2-{4-[4-(3-methoxy-benzoyl)-piperidin-1-yl]-4-oxo-butyl}-3H-

quinazolin-4-one

“A10”
2-(4-{4-[4-(1-ethyl-1H-pyrazol-4-yl)-benzoyl]-piperidin-1-yl}-4-

oxo-butyl)-3H-quinazolin-4-one

“A11”
2-[4-(4-{4-[1-(2-methoxy-ethyl)-1H-pyrazol-4-yl]-benzoyl}-

piperidin-1-yl)-4-oxo-butyl]-3H-quinazolin-4-one

“A12”
2-[4-oxo-4-(4-{4-[1-(2-pyrrolidin-1-yl-ethyl)-1H-pyrazol-4-yl]-

benzoyl}-piperidin-1-yl)-butyl]-3H-quinazolin-4-one

“A13”
2-[4-[4-(4-methoxy-3-methyl-benzoyl)-1-piperidyl]-4-oxo-butyl]-

3H-quinazolin-4-one

“A14”
6,8-difluoro-2-[4-[4-(4-methoxy-3-methyl-benzoyl)-1-piperidyl]-

4-oxo-butyl]-3H-quinazolin-4-one

“A15”
6-fluoro-2-[4-[4-(4-methoxy-3-methyl-benzoyl)-1-piperidyl]-4-

oxo-butyl]-8-methyl-3H-quinazolin-4-one

“A16”
2-{4-[4-(6-Methoxy-pyridine-3-carbonyl)-piperidin-1-yl]-4-oxo-

butyl}-3H-quinazolin-4-one

“A17”
4-{1-[4-(4-Oxo-3,4-dihydro-quinazolin-2-yl)-butyryl]-piperidin-4-

yloxy}-benzonitrile

“A18”
2-{4-[4-(4-Fluoro-benzoyl)-p

Assignees

• Merck Patent Gmbh

Inventors

• Dorsch Dieter
• Buchstaller Hans Peter

Classifications

• A61P43/00

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

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title