Novel compounds

Abstract

The invention provides new triazolo[4,5-d]pyrimidine compounds, their use as medicaments, compositions containing them and processes for their preparation.

1 - 18 . (canceled)  
     
     
         19 . A method of treatment of myocardial infarction, comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound of formula (I)  
       
         
           
           
               
               
           
         
         wherein:  
         R 1  is C 3-5  alkyl optionally substituted by one or more halogen atoms;  
         R 2  is a phenyl group, optionally substituted by one or more fluorine atoms;  
         R 3  and R 4  are both hydroxy;  
         R is XOH, where X is CH 2 , OCH 2 CH 2  or a bond;  
         or a pharmaceutically acceptable salt or solvate thereof, or a solvate of such a salt  
         provided that:  
         when X is CH 2  or a bond, R 1  is not propyl.  
         when X is CH 2  and R 1  is CH 2 CH 2 CF 3 , butyl or pentyl, the phenyl group at R 2  must be substituted by fluorine.  
         when X is OCH 2 CH 2  and R 1  is propyl, the phenyl group at R 2  must be substituted by fluorine.  
       
     
     
         20 . A method according to  claim 19  wherein R 1  is 3,3,3,-trifluoropropyl, butyl or propyl.  
     
     
         21 . A method according to  claim 19  wherein R 2  is phenyl or 4-fluorophenyl or 3,4-difluorophenyl.  
     
     
         22 . A method according to  claim 19  wherein R is CH 2 OH or OCH 2 CH 2 OH.  
     
     
         23 . A method according to  claim 19  wherein the compound is: 
 [1R-[1α,2α,3β(1R*,2S*),5β]]-3-[7-[[2-(4-Fluorophenyl)cyclopropyl]amino]-5-[(3,3,3-trifluoropropyl)thio]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(hydroxymethyl)-cyclopentane-1,2-diol;    [1R-[1α,2α,3β(1R*,2S*),5β]]-3-[7-[[2-(3,4-Difluorophenyl)cyclopropyl]amino]-5-[(3,3,3-trifluoropropyl)thio]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(hydroxymethyl)-cyclopentane-1,2-diol;    [1S-(1α,2α,3β(1 S*,2R*),5β]]-3-[7-[[2-(3,4-Difluorophenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethoxy)-cyclopentane-1,2-diol:    [1R-[1α,2α,3β(1R*,2S*),5β]]-3-[5-(Butylthio)-7-[[2-(3,4-difluorophenyl)cyclopropyl]amino]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(hydroxymethyl)-cyclopentane-1,2-diol;    [1S-[1α,2β,3β,4α(1S*,2R*)]]-4-[5-(Butylthio)-7-[[2-(4-fluorophenyl)cyclopropyl]amino]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2,3-triol;    [1S-(1α,2α,3β(1S*,2R*),5β)]-3-[7-[[2-(3,4-Difluorophenyl)cyclopropyl]amino]-5-[(3,3,3-trifluoropropyl)thio]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethoxy)-cyclopentane-1,2-diol;    [1S-[1α,2α,3β,5β(1S*,2R*)]]-3-(2-Hydroxyethoxy)-5-[7-(2-phenylcyclopropyl)amino]-5-[(3,3,3-trifluoropropyl)thio]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol[1S-[1α,2β,3β,4α(1S*,2R*]]-4-[5-(Butylthio)-7-[[2-(3,4-difluorophenyl)cyclopropyl]amino]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]cyclopentane-1,2,3-triol;    [1S-[1α,2α,3β(1S*,2R*),5β]]-3-[5-(Butylthio)-7-[(2-phenylcyclopropyl)amino]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxethoxy)-cyclopentane-1,2-diol;    or pharmaceutically acceptable salts or solvates thereof, or solvates of such salts.    
     
     
         24 . A method of treatment of transient ischemic attacks, comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound of formula (I)  
       
         
           
           
               
               
           
         
         wherein:  
         R 1  is C 3-5  alkyl optionally substituted by one or more halogen atoms;  
         R 2  is a phenyl group, optionally substituted by one or more fluorine atoms;  
         R 3  and R 4  are both hydroxy;  
         R is XOH, where X is CH 2 , OCH 2 CH 2  or a bond;  
         or a pharmaceutically acceptable salt or solvate thereof, or a solvate of such a salt  
         provided that:  
         when X is CH 2  or a bond, R 1  is not propyl,  
         when X is CH 2  and R 1  is CH 2 CH 2 CF 3 , butyl or pentyl, the phenyl group at R 2  must be substituted by fluorine,  
         when X is OCH 2 CH 2  and R 1  is propyl, the phenyl group at R 2  must be substituted by fluorine.  
       
     
     
         25 . A method according to  claim 24  wherein R 1  is 3,3,3,-trifluoropropyl, butyl or propyl.  
     
     
         26 . A method according to  claim 24  wherein R 2  is phenyl or 4-fluorophenyl or 3,4-difluorophenyl.  
     
     
         27 . A method according to  claim 24  wherein R is CH 2 OH or OCH 2 CH 2 OH.  
     
     
         28 . A method according to  claim 24  wherein the compound is: 
 [1R-[1α,2α,3β(1R*,2S*),5β]]-3-[7-[[2-(4-Fluorophenyl)cyclopropyl]amino]-5-[(3,3,3-trifluoropropyl)thio]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(hydroxymethyl)-cyclopentane-1,2-diol;    [1R-[1α,2α,3β(1R*,2S*),5β]]-3-[7-[[2-(3,4-Difluorophenyl)cyclopropyl]amino]-5-[(3,3,3-trifluoropropyl)thio]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(hydroxymethyl)-cyclopentane-1,2-diol;    [1S-(1α,2α,3β(1S*,2R*),5β]]-3-[7-[[2-(3,4-Difluorophenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethoxy)-cyclopentane-1,2diol:    [1R-[1α,2α,3β(1R*,2S*),5β]]-3-[5-(Butylthio)-7-[[2-(3,4-difluorophenyl)cyclopropyl]amino]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(hydroxymethyl)-cyclopentane-1,2-diol;    [1S-[1α,2β,3β,4α(1S*,2R*)]]-4-[5-(Butylthio)-7-[[2-(4-fluorophenyl)cyclopropyl]amino]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2,3-triol;    [1S-(1α,2α,3β(1S*,2R*) ,5β)]-3-[7-[[2-(3,4-Difluorophenyl)cyclopropyl]amino]-5-[(3,3,3-trifluoropropyl)thio]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethoxy)-cyclopentane-1,2-diol;    [1S-[1α,2α,3β,5β(1S*,2R*)]]-3-(2-Hydroxyethoxy)-5-[7-(2-phenylcyclopropyl)amino]-5-[(3,3,3-trifluoropropyl)thiol-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol[1S-[1α,2β,3β,4α(1S*,2R*]]-4-[5-(Butylthio)-7-[[2-(3,4-difluorophenyl)cyclopropyl]amino]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]cyclopentane-1,2,3-triol;    [1S-[1α,2α,3β(1S*,2R*),5β]]-3-[5-(Butylthio)-7-[(2-phenylcyclopropyl)amino]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxethoxy)-cyclopentane-1,2-diol;    or pharmaceutically acceptable salts or solvates thereof, or solvates of such salts.    
     
     
         29 . A method of treatment of angina, comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound of formula (I)  
       
         
           
           
               
               
           
         
         wherein:  
         R 1  is C 3-5  alkyl optionally substituted by one or more halogen atoms;  
         R 2  is a phenyl group, optionally substituted by one or more fluorine atoms;  
         R 3  and R 4  are both hydroxy;  
         R is XOH, where X is CH 2 , OCH 2 CH 2  or a bond;  
         or a pharmaceutically acceptable salt or solvate thereof, or a solvate of such a salt  
         provided that:  
         when X is CH 2  or a bond, R 1  is not propyl,  
         when X is CH 2  and R 1  is CH 2 CH 2 CF 3 , butyl or pentyl, the phenyl group at R 2  must be substituted by fluorine.  
         when X is OCH 2 CH 2  and R 1  is propyl, the phenyl group at R 2  must be substituted by fluorine.  
       
     
     
         30 . A method according to  claim 29  wherein R 1  is 3,3,3,-trifluoropropyl, butyl or propyl.  
     
     
         31 . A method according to  claim 29  wherein R 2  is phenyl or 4-fluorophenyl or 3,4-difluorophenyl.  
     
     
         32 . A method according to  claim 29  wherein R is CH 2 OH or OCH 2 CH 2 OH.  
     
     
         33 . A method according to  claim 29  wherein the compound is: 
 [1R-[1α,2α,3β(1R*,2S*),5β]]-3-[7-[[2-(4-Fluorophenyl)cyclopropyl]amino]-5-[(3,3,3-trifluoropropyl)thio]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(hydroxymethyl)-cyclopentane-1,2-diol;    [1R-[1α,2α,3β(1R*,2S*),5β]]-3-[7-[[2-(3,4-Difluorophenyl)cyclopropyl]amino]-5-[(3,3,3-trifluoropropyl)thio]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl-5-(hydroxymethyl)-cyclopentane-1,2-diol;    [1S-(1α,2α,3β(1S*,2R*),5β]]-3-[7-[[2-(3,4-Difluorophenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethoxy)-cyclopentane-1,2-diol:    [1R-[1α,2α,3β(1R*,2S*),5β]]-3-[5-(Butylthio)-7-[[2-(3,4-difluorophenyl)cyclopropyl]amino]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5(hydroxymethyl)-cyclopentane-1,2diol;    [1S-[1α,2β,3β,4α(1S*,2R*)]]-4-[5-(Butylthio)-7-[[2-(4-fluorophenyl)cyclopropyl]amino]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2,3-triol;    [1S-(1α,2α,3β(1S*,2R*),5β)]-3-[7-[[2-(3,4-Difluorophenyl)cyclopropyl]amino]-5-[(3,3,3-trifluoropropyl)thio]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethoxy)-cyclopentane-1,2-diol;    [1S-[1α,2α,3β,5β(1S*,2R*)]]-3-(2-Hydroxyethoxy)-5-[7-(2-phenylcyclopropyl)amino]-5-[(3,3,3-trifluoropropyl)thio]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-cyclopentane-1,2-diol[1S-[1α,2β,3β,4α(1S*,2R*]]-4-[5-(Butylthio)-7-[[2-(3,4-difluorophenyl)cyclopropyl]amino]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]cyclopentane-1,2,3-trio;    [1S-[1α,2α,3β(1S*,2R*),5β]]-3-[5-(Butylthio)-7-[(2-phenylcyclopropyl)amino]-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxethoxy)-cyclopentane-1,2-diol;    or pharmaceutically acceptable salts or solvates thereof, or solvates of such salts.