Pyrazolo-quinazoline derivatives, process for their preparation and their use as kinase inhibitors

Patent metadata

Field	Value
Publication number	US-10280176-B2
Application number	US-201715467323-A
Country	US
Kind code	B2
Filing date	Mar 23, 2017
Priority date	May 22, 2003
Publication date	May 7, 2019
Grant date	May 7, 2019

Abstract

Pyrazolo-quinazoline derivatives of formula (Ia) or (Ib) as defined in the specification, and pharmaceutically acceptable salts thereof, process for their preparation and pharmaceutical compositions comprising them are disclosed; the compounds of the invention may be useful, in therapy, in the treatment of diseases associated with a disregulated protein kinase activity, like cancer.

First claim

The invention claimed is:

1. A pyrazolo-quinazoline derivative of formula (Ia):

or a pharmaceutically acceptable salt thereof, wherein
R is substituted or unsubstituted phenyl;
X is —NH—;
R 1 is an optionally substituted straight or branched C 1 -C 6 alkyl;
R 2 is —NR″R″, wherein
R″ is hydrogen or an optionally substituted straight or branched C 1 -C 6 alkyl;
R′″ is hydrogen or an optionally substituted group selected from phenyl and straight or branched C 1 -C 6 alkyl; and

A is —(CH 2 ) 2 —, —CH 2 —C(CH 3 ) 2 —, or —C(CH 3 ) 2 —CH 2 —.

2. The compound of claim 1 , wherein R is phenyl substituted with heterocyclyl or heterocyclylalkyl.

3. The compound of claim 2 , wherein the heterocyclyl is selected from piperazinyl, morpholinyl, and imidazolyl.

4. The compound of claim 1 , wherein R is phenyl substituted with one or more groups independently selected from halogen, hydroxy, polyfluorinated alkyl, and aminocarbonyl.

5. The compound of claim 1 , wherein R 1 is straight or branched C 1 -C 6 alkyl substituted with one or more groups independently selected from halogen and hydroxy.

6. The compound of claim 1 , wherein R 1 is unsubstituted straight or branched C 1 -C 6 alkyl.

7. The compound of claim 1 , wherein R 1 is methyl.

8. The compound of claim 1 , wherein R′″ is unsubstituted straight or branched C 1 -C 6 alkyl or straight or branched C 1 -C 6 alkyl substituted with one or more groups independently selected from halogen, hydroxy, aryl, heterocyclyl, and di-(C 1 -C 6 alkyl)amino.

9. The compound of claim 8 , wherein the aryl is phenyl.

10. The compound of claim 8 , wherein the heterocyclyl is pyridyl.

11. The compound of claim 1 , wherein A is —CH 2 —C(CH 3 ) 2 —.

Assignees

• Nerviano Medical Sciences Srl

Inventors

• Traquandi Gabriella
• Brasca Maria Gabriella
• D'Alessio Roberto
• Polucci Paolo
• Roletto Fulvia
• Vulpetti Anna
• Pevarello Paolo
• Panzeri Achille
• Quartieri Francesca
• Ferguson Ron
• Vianello Paola
• Fancelli Daniele

Classifications

• A61P43/00

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

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P35/04

  specific for metastasis · CPC title