Substituted thieno [2,3-c] pyrazoles and their use as medicinal products

• US 20050026984A1
• Filed: 07/28/2004
• Published: 02/03/2005
• Est. Priority Date: 07/29/2003
• Status: Abandoned Application

• Current Assignee: Aventis Pharma SA (Sanofi )
• Original Assignee: Aventis Pharma SA (Sanofi )
• Inventors: Bigot, Antony, Doerflinger, Gilles, Mignani, Serge, Minoux, Herve, Clerc, Francois
• Application Number:
  US10/900,549
• Publication Number:
  US 20050026984A1
• Time in Patent Office: Days
• US Class Current: 514/406
• CPC Class Codes: C07D 495/04 Ortho-condensed systems

Abstract

The present invention relates in particular to novel chemical compounds, particularly novel substituted thieno[2,3-c]pyrazoles, to the compositions containing them and to their use as medicinal products for treating cancers and also neurodegenerative diseases.

Claims

1. A compound of formula (I):

2. The compound according to claim 1, wherein Y is a monocyclic or polycyclic heteroaryl group.

3. The compound according to claim 2, wherein Y is a polycyclic heteroaryl group.

4. The compound according to claim 1, wherein X is alkylene, alkenylene, alkynylene, —

NR—

CO—

, —

SO₂NR—

, —

NRSO₂—

, alkyleneoxy, oxyalkylene, ureido, —

NR—

O—

, —

O—

NR—

, —

O—

NR—

CO—

, —

S—

, —

SO₂—

, —

SO—

, —

O—

, —

OSO₂—

, —

NRCOO—

, —

NRCSNR—

, alkylenethio, alkylenesulphone, alkylene sulphoxide, thialkylene, sulphonealkylene or —

SO-alkylene.

5. The compound according to claim 1, wherein R2 is hydroxamate.

6. The compound according to claim 1, wherein R2 is —

CO—

NH—

C(CH₃)₂—

R1, wherein R1 is chosen from aryl, substituted aryl, heteroaryl and substituted heteroaryl.

7. The compound according to claim 1 wherein

R1 is —

X—

Y

wherein Y is aryl, heteroaryl, alkyl or cycloalkyl,

X is alkylene, alkenylene, alkynylene, NR—

CO, SO₂NR, NRSO₂, alkyleneoxy, oxyalkylene or ureido, R2 is same as R1 or halogen, (C₁-C₃)alkyl, (C₂-C₃)alkylene, (C₂-C₃)alkynyl, cycloalkyl or heterocycloalkyl group, or perhaloalkyl, perhaloalkoxy, perhaloalkylthio, hydroxycarbonyl, alkoxycarbonyl, Ar(CH₂)n(SO₂)NH, Ar(CH₂)n(SO₂)O, Ar(CH₂)n(S)NH, Ar(CH₂)n(S)O, Ar(CH₂)nC(O)O, Ar(CH₂)nC(O)NH, Ar(CH₂)nZC(O), heterocycloalkyl, Alk(CH₂)nZC(O)(CH₂)a, Ar(CH₂)nZC(O)(CH₂)a, Alk(CH₂)a, Ar(CH₂)a, AlkZ(CH₂)a, ArZ(CH₂)a, Alk(CH₂)Z, or Ar(CH₂)Z group, wherein Z represents O or NR, Alk is alkyl and Ar is aryl;

wherein R is hydrogen or alkyl, n is 0, 1 or 2 and a is 1 or 2;

wherein all above groups are optionally substituted with alkyl, aryl, amino and/or alkoxy groups

with the proviso that when R2 is R1, then X is not —

NH—

CO—

or —

NH—

SO₂ or ureido.

8. The compound according to claim 1 , wherein aryl and heteroaryl are selected from the group consisting of phenyl, pyridyl, pyrimidine, triazine, pyrrolyl, imidazolyl, thiazolyl, furyl, thienyl, indolyl, azaindazolyl, isobenzofuranyl, isobenzothienyl, benzoxazolyl, benzothiazolyl, arylvinylene, arylamido, arylcarboxamide, aralkylamine, quinoleyl, isoquinoleyl, cinnolyl, quinazolyl and naphthyridyl.

9. The compound according to claim 8, wherein aryl and heteroaryl are selected from the group consisting of phenyl, pyrrolyl, imidazolyl, thienyl and indolyl.

10. The compound according to claim 9 wherein said heteroaryl is indolyl.

11. The compound according to claim, 1 wherein, X is NR—

CO.

12. The compound according to claim 1, wherein R2 is

halogen,

—

X—

Y wherein X is —

CONR—

or NR—

CO;

Ar(CH₂)n(SO₂)NH,

Ar(CH₂)n(SO₂)O,

Ar(CH₂)nC(O)NH,

or Ar(CH₂)nZC(O) wherein Z represents O or NR, and R3 is hydrogen.

13. A pharmaceutical composition comprising a compound of claim 1 and one or more physiologically acceptable excipients.

14. A method of treating a disease in a patient amenable to modulation of protein kinases selected from the group consisting of KDR, Aurora-2 and GSK-30β

, comprising administering to said patient a therapeutically effective amount of a compound according to claim 1.

15. The method according to claim 14 wherein said protein kinase is GSK-3β

.

16. The method according to claim 14 wherein said protein kinase is KDR.

17. The method according to claim 14 wherein said protein kinase is Aurora-2.

18. The method according to claim 14 wherein said patient is suffering from cancer caused by the effects of said kinase.

19. The method according to claim 14 wherein said patient is suffering from a neurodegenerative disease.

20. The method according to claim 19 wherein said neurodegenerative disease is caused by the effects of said kinase.