Heterocyclic compound and pharmaceutical composition comprising same

Abstract

A novel heterocyclic compound inhibiting a cyclin-dependent kinase (CDK) and a pharmaceutical composition containing the compound as an effective ingredient are disclosed. The heterocyclic compound according to the present invention or pharmaceutically acceptable salt thereof can be effectively used in treating or preventing cancers, degenerative brain diseases, etc.

1 . A method for treating a cancer in a subject in need thereof, comprising administering a composition comprising a compound of the following formula (I) or pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein, 
         X is nitrogen, Y and Z are carbon; 
         R 1  is phenyl, pyridine, or pyrimidine substituted or unsubstituted with one or more substituents selected from the group consisting of hydroxy, amino, and halogen; 
         R 2  is hydrogen; and 
         R 3  is pyrimidine substituted or unsubstituted with one or more substituents selected from the group consisting of C 1 C 6  alkyl, tetrahydropyranyl, piperidinyl substituted or unsubstituted with C 1 -C 6  alkyl, morpholino, piperazinyl substituted or unsubstituted with C 1 -C 6  alkyl, amino, C 1 -C 6  alkylamino, and halogen, 
         to the subject. 
       
     
     
         2 . The method according to  claim 1 , wherein the compound of formula (I) or a pharmaceutically acceptable salt thereof is selected from the group consisting of the following compounds:
 2,6-bis(2-aminopyrimidin-4-yl)pyridin-3-ol;   2′-amino-6-(2-aminopyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2-(2-aminopyrimidin-4-yl)-6-(4-hydroxyphenyl)pyridin-3-ol;   2′-amino-6-(2-aminopyrimidin-4-yl)-[2,4′-bipyridin]-5-ol;   6-(2-aminopyrimidin-4-yl)-[2,3′-bipyridin]-5-ol;   6-(2-aminopyrimidin-4-yl)-[2,4′-bipyridin]-5-ol;   2-(2-aminopyrimidin-4-yl)-6-(3-hydroxyphenyl)pyridin-3-ol;   6-(2-aminopyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   6-(4-amino-2-fluorophenyl)-2-(2-aminopyrimidin-4-yl)pyridin-3-ol;   6-(3-aminophenyl)-2-(2-aminopyrimidin-4-yl)pyridin-3-ol;   2-(2-aminopyrimidin-4-yl)-6-(2-fluoro-4-hydroxyphenyl)pyridin-3-ol;   6-(3-amino-2-fluorophenyl)-2-(2-aminopyrimidin-4-yl)pyridin-3-ol;   2-(2-aminopyrimidin-4-yl)-6-(3-fluoro-4-hydroxyphenyl)pyridin-3-ol;   2-(2-aminopyrimidin-4-yl)-6-(2,3-difluoro-4-hydroxyphenyl)pyridin-3-ol;   2′-amino-6-(2-aminopyrimidin-4-yl)-[2,4′-bipyridin]-3′,5-diol;   2′-amino-6-(2-amino-6-methylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   6-(2-amino-6-methylpyrimidin-4-yl)-[2,4′-bipyridin]-5-ol;   6-(2-amino-6-methylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2-(2-amino-6-methylpyrimidin-4-yl)-6-(4-hydroxyphenyl)pyridin-3-ol;   2-(2-amino-6-methylpyrimidin-4-yl)-6-(2,3-difluoro-4-hydroxyphenyl)pyridin-3-ol;   2-(2-amino-6-methylpyrimidin-4-yl)-6-(2-fluoro-4-hydroxyphenyl)pyridin-3-ol;   2-(2-amino-6-methylpyrimidin-4-yl)-6-(3-aminophenyl)pyridin-3-ol;   2′-amino-6-(2-amino-6-isopropylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-6-(tetrahydro-2H-pyran-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-6-(piperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-6-(1-methylpiperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-6-(1-ethylpiperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-6-(1-propylpiperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-6-(1-isopropylpiperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-6-(1-methylpiperidin-3-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-6-(1-ethylpiperidin-3-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-6-(1-propylpiperidin-3-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-6-(1-isopropylpiperidin-3-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-5-methyl-6-(1-methylpiperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-6-(1-ethylpiperidin-4-yl)-5-methylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-5-methyl-6-(1-propylpiperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-6-(1-isopropylpiperidin-4-yl)-5-methylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-5-methyl-6-(1-methylpiperidin-3-yl)pyrimidin-3-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-5-methyl-6-(1-propylpiperidin-3-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-6-(1-isopropylpiperidin-3-yl)-5-methylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-5-ethyl-6-(1-isopropylpiperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-6-(1-isopropylpiperidin-4-yl)-5-propylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-6-morpholinopyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-6-(dimethylamino)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   6-(2-amino-6-chloropyrimidin-4-yl)-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-5-methylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-5-ethylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-5-propylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-5-isopropylpyrimidin-5-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-3′-fluoro-6-(2-(methylamino)-6-(1-methylpiperidin-4-yl)pyrimidin-4-yl)-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-5,6-dimethylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2,6-bis(2-aminopyrimidin-4-yl)pyridin-3-ol 3hydrochloride;   2,6-bis(2-aminopyrimidin-4-yl)pyridin-3-ol oxalate;   2,6-bis(2-aminopyrimidin-4-yl)pyridin-3-ol malonate;   2,6-bis(2-aminopyrimidin-4-yl)pyridin-3-ol sulfate;   2′-amino-4-(2-aminopyrimidin-4-yl)-[2,4′-bipyridin]-5-ol oxalate;   2′-amino-6-(2-aminopyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 3hydrochloride;   2′-amino-6-(2-aminopyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol acetate;   2′-amino-6-(2-aminopyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol oxalate;   2′-amino-6-(2-aminopyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 2malonate;   2-(2-aminopyrimidin-4-yl)-6-(2-fluoro-4-hydroxyphenyl)pyridin-3-ol 2hydrochloride;   2′-amino-6-(2-amino-6-methylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 3hydrochloride;   2′-amino-6-(2-amino-6-morpholinopyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride;   2′-amino-6-(2-amino-6-morpholinopyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol acetate;   2′-amino-6-(2-amino-6-(dimethylamino)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride;   2′-amino-6-(2-amino-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 5hydrochloride;   2′-amino-6-(2-amino-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol acetate;   2′-amino-6-(2-amino-(6-(1-methylpiperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride;   2′-amino-6-(2-amino-6-(1-methylpiperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 2acetate;   2′-amino-6-(2-amino-6-(1-methylpiperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol oxalate;   2′-amino-6-(2-amino-6-(1-methylpiperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol malonate;   2′-amino-6-(2-amino-6-isopropylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 3hydrochloride;   2′-amino-6-(2-amino-6-isopropylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 2acetate;   2′-amino-6-(2-amino-6-(piperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride;   2′-amino-6-(2-amino-6-(piperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol acetate;   2′-amino-6-(2-amino-6-(tetrahydro-2H-pyran-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 3hydrochloride;   2′-amino-6-(2-amino-6-(1-ethylpiperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride;   2′-amino-6-(2-amino-6-(1-propylpiperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride;   2′-amino-6-(2-amino-6-(1-isopropylpiperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride;   2′-amino-6-(2-amino-6-(1-methylpiperidin-3-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride;   2′-amino-6-(2-amino-6-(1-ethylpiperidin-3-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride;   2′-amino-6-(2-amino-6-(1-propylpiperidin-3-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride;   2′-amino-6-(2-amino-6-(1-isopropylpiperidin-3-yl)pyrimidin-4-yl)-3′-fluoro[2,4′-bipyridin]-5-ol 4hydrochloride;   2′-amino-6-(2-amino-5-methyl-6-(1-methylpiperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride;   2′-amino-6-(2-amino-6-(1-ethylpiperidin-4-yl)-5-methylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride;   2′-amino-6-(2-amino-5-methyl-6-(1-propylpiperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride;   2′-amino-6-(2-amino-6-(1-isopropylpiperidin-4-yl)-5-methylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride;   2′-amino-6-(2-amino-5-methyl-6-(1-methylpiperidin-3-yl)pyrimidin-3-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride;   2′-amino-6-(2-amino-5-methyl-6-(1-propylpiperidin-3-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride;   2′-amino-6-(2-amino-6-(1-isopropylpiperidin-3-yl)-5-methylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride;   2′-amino-6-(2-amino-5-methylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 3hydrochloride;   2′-amino-6-(2-amino-5,6-dimethylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 3hydrochloride;   2′-amino-6-(2-amino-5-ethylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 3hydrochloride;   2′-amino-6-(2-amino-5-propylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 3hydrochloride;   2′-amino-6-(2-amino-5-isopropylpyrimidin-5-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 3hydrochloride;   2′-amino-6-(2-amino-5-ethyl-6-(1-isopropylpiperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride; and   2′-amino-6-(2-amino-6-(1-isopropylpiperidin-4-yl)-5-propylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride.   
     
     
         3 . The method of  claim 1 , which further comprises administering one or more anticancer agents selected from the group consisting of capecitabine, 5-fluorouracil, thioguanine, chlorambucil, oxaliplatin, cisplatin, carboplatin, paclitaxel, docetaxel, irinotecan, doxorubicin, vinorelbin, gemcitabine, pemetrexed, etoposide, vincristine, citarabine, cyclophosphamide, iphosphamide, tamoxifen, anastrozole, retrozole, exemestane, fulvestrant, temozolomide, camustine, lomustine, epirubicine, eribulin, toremifene, goserelin, megestrol, vinblastine, bendamustine, thiotepa, bleomycin, topotecan, leucovorin, trifluridine, tipiracil, mitomycin C, aldesleukin, temsirolimus, everolimus, mitoxantrone, mecloretamine, methotrexate, trastuzumab, bevacizumab, cetuximab, aflibercept, pertuzumab, ramucirumab, panitumumab, nivolumab, necitumumab, pembrolizumab, obinutuzumab, ofatumumab, erlotinib, gefitinib, sorafenib, lapatinib, palbociclib, regorafenib, imatinib, sunitinib, axitinib, pazopanib, apatinib, ceritinib, crizotinib, osimertinib, bosutinib, dasatinib, nilotinib, ponatinib, hydroxyurea, and procarbazine. 
     
     
         4 . A method for treating a degenerative brain disease in a subject in need thereof, comprising administering a composition comprising a compound of the following formula (I) or pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein, 
         X is nitrogen, Y and Z are carbon; 
         R 1  is phenyl, pyridine, or pyrimidine substituted or unsubstituted with one or more substituents selected from the group consisting of hydroxy, amino, and halogen; 
         R 2  is hydrogen; and 
         R 3  is pyrimidine substituted or unsubstituted with one or more substituents selected from the group consisting of C 1 -C 6  alkyl, tetrahydropyranyl, piperidinyl substituted or unsubstituted with C 1 -C 6  alkyl, morpholino, piperazinyl substituted or unsubstituted with C 1 -C 6  alkyl, amino, C 1 -C 6  alkylamino, and halogen, 
         to the subject. 
       
     
     
         5 . The method according to  claim 4 , wherein the compound of formula (I) or a pharmaceutically acceptable salt thereof is selected from the group consisting of the following compounds:
 2,6-bis(2-aminopyrimidin-4-yl)pyridin-3-ol;   2′-amino-6-(2-aminopyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2-(2-aminopyrimidin-4-yl)-6-(4-hydroxyphenyl)pyridin-3-ol;   2′-amino-6-(2-aminopyrimidin-4-yl)-[2,4′-bipyridin]-5-ol;   6-(2-aminopyrimidin-4-yl)-[2,3′-bipyridin]-5-ol;   6-(2-aminopyrimidin-4-yl)-[2,4′-bipyridin]-5-ol;   2-(2-aminopyrimidin-4-yl)-6-(3-hydroxyphenyl)pyridin-3-ol;   6-(2-aminopyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   6-(4-amino-2-fluorophenyl)-2-(2-aminopyrimidin-4-yl)pyridin-3-ol;   6-(3-aminophenyl)-2-(2-aminopyrimidin-4-yl)pyridin-3-ol;   2-(2-aminopyrimidin-4-yl)-6-(2-fluoro-4-hydroxyphenyl)pyridin-3-ol;   6-(3-amino-2-fluorophenyl)-2-(2-aminopyrimidin-4-yl)pyridin-3-ol;   2-(2-aminopyrimidin-4-yl)-6-(3-fluoro-4-hydroxyphenyl)pyridin-3-ol;   2-(2-aminopyrimidin-4-yl)-6-(2,3-difluoro-4-hydroxyphenyl)pyridin-3-ol;   2′-amino-6-(2-aminopyrimidin-4-yl)-[2,4′-bipyridin]-3′,5-diol;   2′-amino-6-(2-amino-6-methylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   6-(2-amino-6-methylpyrimidin-4-yl)-[2,4′-bipyridin]-5-ol;   6-(2-amino-6-methylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2-(2-amino-6-methylpyrimidin-4-yl)-6-(4-hydroxyphenyl)pyridin-3-ol;   2-(2-amino-6-methylpyrimidin-4-yl)-6-(2,3-difluoro-4-hydroxyphenyl)pyridin-3-ol;   2-(2-amino-6-methylpyrimidin-4-yl)-6-(2-fluoro-4-hydroxyphenyl)pyridin-3-ol;   2-(2-amino-6-methylpyrimidin-4-yl)-6-(3-aminophenyl)pyridin-3-ol;   2′-amino-6-(2-amino-6-isopropylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-6-(tetrahydro-2H-pyran-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-6-(piperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-6-(1-methylpiperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-6-(1-ethylpiperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-6-(1-propylpiperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-6-(1-isopropylpiperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-6-(1-methylpiperidin-3-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-6-(1-ethylpiperidin-3-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-6-(1-propylpiperidin-3-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-6-(1-isopropylpiperidin-3-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-5-methyl-6-(1-methylpiperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-6-(1-ethylpiperidin-4-yl)-5-methylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-5-methyl-6-(1-propylpiperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-6-(1-isopropylpiperidin-4-yl)-5-methylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-5-methyl-6-(1-methylpiperidin-3-yl)pyrimidin-3-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-5-methyl-6-(1-propylpiperidin-3-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-6-(1-isopropylpiperidin-3-yl)-5-methylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-5-ethyl-6-(1-isopropylpiperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-6-(1-isopropylpiperidin-4-yl)-5-propylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-6-morpholinopyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-6-(dimethylamino)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   6-(2-amino-6-chloropyrimidin-4-yl)-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-5-methylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-5-ethylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-5-propylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-5-isopropylpyrimidin-5-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2′-amino-3′-fluoro-6-(2-(methylamino)-6-(1-methylpiperidin-4-yl)pyrimidin-4-yl)-[2,4′-bipyridin]-5-ol;   2′-amino-6-(2-amino-5,6-dimethylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol;   2,6-bis(2-aminopyrimidin-4-yl)pyridin-3-ol 3hydrochloride;   2,6-bis(2-aminopyrimidin-4-yl)pyridin-3-ol oxalate;   2,6-bis(2-aminopyrimidin-4-yl)pyridin-3-ol malonate;   2,6-bis(2-aminopyrimidin-4-yl)pyridin-3-ol sulfate;   2′-amino-4-(2-aminopyrimidin-4-yl)-[2,4′-bipyridin]-5-ol oxalate;   2′-amino-6-(2-aminopyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 3hydrochloride;   2′-amino-6-(2-aminopyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol acetate;   2′-amino-6-(2-aminopyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol oxalate;   2′-amino-6-(2-aminopyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 2malonate;   2-(2-aminopyrimidin-4-yl)-6-(2-fluoro-4-hydroxyphenyl)pyridin-3-ol 2hydrochloride;   2′-amino-6-(2-amino-6-methylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 3hydrochloride;   2′-amino-6-(2-amino-6-morpholinopyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride;   2′-amino-6-(2-amino-6-morpholinopyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol acetate;   2′-amino-6-(2-amino-6-(dimethylamino)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride;   2′-amino-6-(2-amino-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 5hydrochloride;   2′-amino-6-(2-amino-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol acetate;   2′-amino-6-(2-amino-(6-(1-methylpiperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride;   2′-amino-6-(2-amino-6-(1-methylpiperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 2acetate;   2′-amino-6-(2-amino-6-(1-methylpiperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol oxalate;   2′-amino-6-(2-amino-6-(1-methylpiperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol malonate;   2′-amino-6-(2-amino-6-isopropylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 3hydrochloride;   2′-amino-6-(2-amino-6-isopropylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 2acetate;   2′-amino-6-(2-amino-6-(piperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride;   2′-amino-6-(2-amino-6-(piperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol acetate;   2′-amino-6-(2-amino-6-(tetrahydro-2H-pyran-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 3hydrochloride;   2′-amino-6-(2-amino-6-(1-ethylpiperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride;   2′-amino-6-(2-amino-6-(1-propylpiperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride;   2′-amino-6-(2-amino-6-(1-isopropylpiperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride;   2′-amino-6-(2-amino-6-(1-methylpiperidin-3-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride;   2′-amino-6-(2-amino-6-(1-ethylpiperidin-3-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride;   2′-amino-6-(2-amino-6-(1-propylpiperidin-3-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride;   2′-amino-6-(2-amino-6-(1-isopropylpiperidin-3-yl)pyrimidin-4-yl)-3′-fluoro[2,4′-bipyridin]-5-ol 4hydrochloride;   2′-amino-6-(2-amino-5-methyl-6-(1-methylpiperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride;   2′-amino-6-(2-amino-6-(1-ethylpiperidin-4-yl)-5-methylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride;   2′-amino-6-(2-amino-5-methyl-6-(1-propylpiperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride;   2′-amino-6-(2-amino-6-(1-isopropylpiperidin-4-yl)-5-methylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride;   2′-amino-6-(2-amino-5-methyl-6-(1-methylpiperidin-3-yl)pyrimidin-3-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride;   2′-amino-6-(2-amino-5-methyl-6-(1-propylpiperidin-3-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride;   2′-amino-6-(2-amino-6-(1-isopropylpiperidin-3-yl)-5-methylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride;   2′-amino-6-(2-amino-5-methylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 3hydrochloride;   2′-amino-6-(2-amino-5,6-dimethylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 3hydrochloride;   2′-amino-6-(2-amino-5-ethylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 3hydrochloride;   2′-amino-6-(2-amino-5-propylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 3hydrochloride;   2′-amino-6-(2-amino-5-isopropylpyrimidin-5-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 3hydrochloride;   2′-amino-6-(2-amino-5-ethyl-6-(1-isopropylpiperidin-4-yl)pyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride; and   2′-amino-6-(2-amino-6-(1-isopropylpiperidin-4-yl)-5-propylpyrimidin-4-yl)-3′-fluoro-[2,4′-bipyridin]-5-ol 4hydrochloride.   
     
     
         6 . The method of  claim 5 , which further comprises administering one or more drugs selected from the group consisting of levodopa, bromocriptine, ropinirole, pramipexole, rotigotine, trihexyphenidyl, benztropine, procyclidine, entacapone, selegiline, rasagiline, amantadine, tetrabenazine, donepezil, rivastigmine, galantamine and memantine