Novel Compounds Having Selective Inhibiting Effect at GSK3

Abstract

The present invention relates to new compounds, a process for their preparation and new intermediates used therein, pharmaceutical formulations containing said therapeutically active compounds and to the use of said active compounds in therapy, such as provide compounds having a selective inhibiting effect at GSK3.

1 - 26 . (canceled) 
   
   
       27 . A compound of the generic formula I: 
     
       
         
         
             
             
         
       
     
     wherein:
 Z is N; 
 Y is CONR 5 ; 
 X is N; 
 P is phenyl; 
 Q is a 6-membered heterocyclic ring having one nitrogen; 
 R is selected from C 0-6 alkyl(SO 2 )NR 1 R 2 , C 0-6 alkylCONR 1 R 2  or OC 1-6 alkylNR 1 R 2 ; 
 R 1  and R 2  are independently selected from hydrogen, C 1-6 alkyl, C 1-6 alkylNR 6 R 7 , C 1-6 alkylOR 6  or a 5- or 6-membered heterocyclic ring containing one or more heteroatoms independently selected from N, O, or S and wherein said C 1-6 alkyl or heterocyclic ring may be optionally substituted by A; 
 R 1  and R 2  may together form a substituted 5- or 6-membered heterocyclic ring containing one or more heteroatoms independently selected from N, O, or S and said heterocyclic ring may be optionally substituted by A; 
 R 3  and R 4  are at each occurrence independently selected from halo, nitro, trifluoromethyl, C 0-6 alkylCN, C 0-6 alkylOR 6 , C 0-6 alkylCONR 6 R 7 , C 0-6 alkylNR 6 (CO)R 7 , C 0-6 alkylCOR 6  or C 0-6 alkyl(SO 2 )NR 6 R 7 ; 
 m is 0 or 1; 
 n is 0 or 1; 
 R 5  is hydrogen; 
 R 6  and R 7  are independently selected from hydrogen or C 1-6 alkyl, or R 6  and R 7  together form a substituted 5- or 6-membered heterocyclic ring containing one or more heteroatoms independently selected from N, O, or S where said heterocyclic ring may be optionally substituted by A; 
 A is C 1-6 alkyl; 
 
     as a free base or a pharmaceutically acceptable salt, solvate or solvate of a salt thereof. 
   
   
       28 . A compound that is:
 3-amino-6-[4-({[(1R)-2-methoxy-1-methylethyl]amino}sulfonyl)phenyl]-N-pyridin-3-ylpyrazine-2-carboxamide hydrochloride;   3-amino-6-[4-({[(1S)-2-methoxy-1-methylethyl]amino}sulfonyl)phenyl]-N-pyridin-3-ylpyrazine-2-carboxamide hydrochloride;   3-amino-6-(4-{[(2-ethoxyethyl)amino]sulfonyl}phenyl)-N-pyridin-3-ylpyrazine-2-carboxamide hydrochloride;   3-amino-6-[3-fluoro-4-[2-(4-morpholinyl)ethoxy]phenyl]-N-3-pyridinyl-2-pyrazinecarboxamide hydrochloride;   3-amino-6-[4-[[bis(2-methoxyethyl)amino]sulfonyl]phenyl]-N-3-pyridinyl-2-pyrazinecarboxamide hydrochloride;   3-amino-6-[4-[[(3-methylbutyl)amino]sulfonyl]phenyl]-N-3-pyridinyl-2-pyrazinecarboxamide hydrochloride;   3-amino-6-[4-[[[(1S)-2-methoxy-1-methylethyl]amino]carbonyl]phenyl]-N-3-pyridinyl-2-pyrazinecarboxamide hydrochloride;   3-amino-N-3-pyridinyl-6-[4-[[[2-(1-pyrrolidinyl)ethyl]amino]carbonyl]phenyl]-2-pyrazinecarboxamide hydrochloride;   or a free base or an alternative pharmaceutically acceptable salt, solvate or solvate of a salt of any foregoing hydrochloride.   
   
   
       29 . A compound that is 3-amino-6-[4-[[(1-ethyl-3-piperidinyl)amino]sulfonyl]phenyl]-N-3-pyridinyl-2-pyrazinecarboxamide hydrochloride;
 or a free base or an alternative pharmaceutically acceptable salt, solvate or solvate of a salt of said hydrochloride.   
   
   
       30 . A pharmaceutical formulation comprising as active ingredient a therapeutically effective amount of the compound according to  claim 27  in association with a pharmaceutically acceptable carrier or diluent. 
   
   
       31 . A pharmaceutical formulation comprising as active ingredient a therapeutically effective amount of the compound according to  claim 28  in association with a pharmaceutically acceptable carrier or diluent. 
   
   
       32 . A pharmaceutical formulation comprising as active ingredient a therapeutically effective amount of the compound according to  claim 29  in association with a pharmaceutically acceptable carrier or diluent.