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

Patent metadata

Field	Value
Publication number	US-2017190714-A1
Application number	US-201715467323-A
Country	US
Kind code	A1
Filing date	Mar 23, 2017
Priority date	May 22, 2003
Publication date	Jul 6, 2017
Grant date	—

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

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 —.

12 . A method for treating a disease selected from the group consisting of ovarian cancer, acute myeloid leukemia, prostate cancer, breast cancer, liver cancer, melanoma, colon cancer, non-small lung cancer, pancreatic cancer, and pancreatic adenocarcinoma, comprising administering to a mammal in need thereof an effective amount of a compound of claim 1 .

13 . The method of claim 12 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

14 . A method for inhibiting Aurora 2 activity, comprising administering to a mammal in need thereof an effective amount of a compound of claim 1 .

15 . The method of claim 14 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

16 . A method for inhibiting cell cycle dependent kinase activity, comprising administering to a mammal in need thereof an effective amount of a compound of claim 1 .

17 . The method of claim 16 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

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

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P37/06

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

• A61P43/00

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