Tetrahydro-quinazolinone derivatives as TANK and PARP inhibitors

Patent metadata

Field	Value
Publication number	US-9339503-B2
Application number	US-201314378009-A
Country	US
Kind code	B2
Filing date	Jan 14, 2013
Priority date	Feb 9, 2012
Publication date	May 17, 2016
Grant date	May 17, 2016

Abstract

Compounds of the formula I

in which U, V and W 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 selected from the following compounds:

No.
Name and/or structure

“A5”
2-[4-(3-fluorophenyl)piperazin-1-yl]-5,6,7,8-tetrahydro-3H-

quinazolin-4-one

“A6”
2-[4-(4-fluorophenyl)piperazin-1-yl]-5,6,7,8-tetrahydro-3H-

quinazolin-4-one

“A8”
2-[4-(4-chlorophenyl)piperazin-1-yl]-5,6,7,8-tetrahydro-3H-

quinazolin-4-one

“A9”
2-[4-(2-chlorophenyl)piperazin-1-yl]-5,6,7,8-tetrahydro-3H-

quinazolin-4-one

“A10”
2-(4-trifluoromethylpiperidin-1-yl)-5,6,7,8-tetrahydro-3H-

quinazolin-4-one

“A11”
2-[4-(3-chlorophenyl)piperazin-1-yl]-5,6,7,8-tetrahydro-3H-

quinazolin-4-one

“A13”
2-(4-tert-butylpiperazin-1-yl)-5,6,7,8-tetrahydro-3H-quinazolin-

4-one

“A14”
2-[4-(4-methoxyphenyl)-3-oxopiperazin-1-yl]-5,6,7,8-tetrahydro-

3H-quinazolin-4-one

“A15”
2-[4-(piperidine-1-carbonyl)piperazin-1-yl]-5,6,7,8-tetrahydro-

3H-quinazolin-4-one

“A16”
2-[4-(6-hydroxypyridin-2-yl)piperazin-1-yl]-5,6,7,8-tetrahydro-

3H-quinazolin-4-one

“A18”
N-pyridin-2-yl-2-[4-(4-oxo-3,4,5,6,7,8-hexahydroquinazolin-2-

yl)piperazin-1-yl]acetamide

“A19”
2-(4-acetylpiperazin-1-yl)-5,6,7,8-tetrahydro-3H-quinazolin-4-

one

“A20”
2-[4-(morpholine-4-carbonyl)piperazin-1-yl]-5,6,7,8-tetrahydro-

3H-quinazolin-4-one

“A21”
2-[4-(3-aminopropanoyl)piperazin-1-yl]-5,6,7,8-tetrahydro-3H-

quinazolin-4-one

“A22”
2-[4-(4-oxo-5,6,7,8-tetrahydro-3H-quinazolin-2-yl)piperazin-1-

yl]pyridine-3-carboxamide

“A23”
2-[4-(4-oxo-3,4,5,6,7,8-hexahydroquinazolin-2-yl)piperazin-1-

yl]-N-pyridin-3-ylacetamide

“A24”
2-[4-(2,2-dimethylpropanoyl)piperazin-1-yl]-5,6,7,8-tetrahydro-

3H-quinazolin-4-one

“A25”
2-[4-(2-hydroxyethyl)piperazin-1-yl]-5,6,7,8-tetrahydro-3H-

quinazolin-4-one

“A26”
2-[4-[2-(2-pyridyl)ethyl]piperazin-1-yl]-5,6,7,8-tetrahydro-

3H-quinazolin-4-one

“A27”
2-[4-(piperidine-2-carbonyl)piperazin-1-yl]-5,6,7,8-tetrahydro-

3H-quinazolin-4-one

“A28”
4-(4-oxo-5,6,7,8-tetrahydro-3H-quinazolin-2-yl)piperazine-2-

carboxamide

“A29”
2-[3-(hydroxymethyl)piperazin-1-yl]-5,6,7,8-tetrahydro-3H-

quinazolin-4-one

“A30”
(2R)-1-(4-oxo-5,6,7,8-tetrahydro-3H-quinazolin-2-yl)piperazine-

2-carboxamide

“A31”
2-[(2R)-2-(hydroxymethyl)piperazin-1-yl]-5,6,7,8-tetrahydro-

3H-quinazolin-4-one

“A32”
2-[4-(3-pyridyl)piperazin-1-yl]-5,6,7,8-tetrahydro-3H-

quinazolin-4-one

“A33”
2-[4-(4-oxo-5,6,7,8-tetrahydro-3H-quinazolin-2-yl)piperazin-1-

yl]benzonitrile

“A34”
2-[4-(4-oxo-5,6,7,8-tetrahydro-3H-quinazolin-2-yl)piperazin-1-

yl]benzamide

“A35”
2-(4-hydroxy-4-phenyl-1-piperidyl)-5,6,7,8-tetrahydro-3H-

quinazolin-4-one

“A36”
2-[4-(4-fluoro-2-methoxy-phenyl)piperazin-1-yl]-5,6,7,8-

tetrahydro-3H-quinazolin-4-one

“A37”
2-[4-(2,4-dimethoxyphenyl)piperazin-1-yl]-5,6,7,8-tetrahydro-

3H-quinazolin-4-one

“A38”
2-[4-(2-chloro-4-methoxy-phenyl)piperazin-1-yl]-5,6,7,8-

tetrahydro-3H-quinazolin-4-one

“A39”
2-[4-(2-chloro-4-fluoro-phenyl)piperazin-1-yl]-5,6,7,8-tetra-

hydro-3H-quinazolin-4-one

“A40”
2-[4-(4-oxo-5,6,7,8-tetrahydro-3H-quinazolin-2-yl)piperazin-1-

yl]acetamide

“A41”
2-(3-phenylpiperazin-1-yl)-5,6,7,8-tetrahydro-3H-quinazolin-4-

one

“A42”
2-[4-(2-isopropoxyphenyl)piperazin-1-yl]-5,6,7,8-tetrahydro-3H-

quinazolin-4-one

“A43”
2-[4-[2-(trifluoromethoxy)phenyl]piperazin-1-yl]-5,6,7,8-

tetrahydro-3H-quinazolin-4-one

“A44”
2-[4-(6-methoxypyridazin-3-yl)piperazin-1-yl]-5,6,7,8-tetra-

hydro-3H-quinazolin-4-one

“A45”
4-[4-(4-oxo-5,6,7,8-tetrahydro-3H-quinazolin-2-yl)piperazin-1-

Assignees

• Merck Patent Gmbh

Inventors

• Buchstaller Hans-Peter
• Esdar Christina
• Leuthner Birgitta

Classifications

• A61P35/02

  specific for leukemia · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

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

• A61P29/00

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