Compounds that interact with kinases

Abstract

A method of inhibiting or effecting the activity of protein kinase activity which comprises contacting a protein kinase with a compound of formula (I) being a derivative of a furanose or pyranose form of a monosaccharide, or a pharmaceutically acceptable salt thereof.

1 - 66 . (canceled) 
     
     
         67 . A method of inhibiting or effecting protein kinase activity which comprises contacting a protein kinase with a compound of formula I being a derivative of a furanose or pyranose form of a monosaccharide, or a pharmaceutically acceptable salt thereof 
       
         
           
           
               
               
           
         
         Wherein; 
         n is 1 or 2, 
         X is selected from the group consisting of: OR1, an unsubstituted 5 or 6 membered heterocyclic moiety, a substituted 5 or 6 membered heterocyclic moiety, an unsubstituted 9 or 10 membered heterobicyclic moiety and a substituted 9 or 10 membered heterobicyclic moiety, 
         R1 is selected from the group consisting of: C1 to C7 alkyl, C1 to C7 alkenyl, C1 to C7 alkynyl, C1 to C7 heteroalkyl, C 6  to C 14  aryl, C 3  to C 14  heteroaryl, C 6  to C 14  arylalkyl and C 3  to C 14  heteroarylalkyl, 
         Y is selected from the group consisting of an unsubstituted 5 or 6 membered heterocyclic moiety; a substituted 5 or 6 membered heterocyclic moiety, an unsubstituted 9 or 10 membered heterobicyclic moiety and a substituted 9 or 10 membered heterobicyclic moiety; an amino acid, a dipeptide, and 
       
       
         
           
           
               
               
           
         
         R6 is selected from the group consisting of: H, C1 to C7 alkyl, C1 to C7 alkenyl, C1 to C7 alkynyl, C1 to C7 heteroalkyl, C6 to C14 aryl, C3 to C14 heteroaryl, C6 to C14 arylalkyl or C3 to C14 heteroarylalkyl, 
         with the proviso that R6, R7 and R8 are not all H, 
         R9 is selected from H, or —(CO)—R6, 
         R7, R8, R11, R12, R14, are independently selected from the group consisting of: H, C1 to C7 alkyl, C1 to C7 alkenyl, C1 to C7 alkynyl, C1 to C7 acyl, C1 to C7 heteroalkyl, C6 to C14 aryl, C6 to C14 arylacyl, C6 to C14 heteroaryl, C6 to C14 heteroarylacyl, C6 to C14 arylalkyl and C6 to C14 heteroarylalkyl, 
         R13 is selected from the group consisting of: unsubstituted phenyl unsubstituted benzyl, substituted phenyl, substituted benzyl, H, C1 to C7 alkyl, C1 to C7 alkenyl, C1 to C7 alkynyl, C1 to C7 acyl, C1 to C7 heteroalkyl, C6 to C14 aryl, C6 to C14 arylacyl, C6 to C14 heteroaryl, C6 to C14 heteroarylacyl, C6 to C14 arylalkyl or C6 to C14 heteroarylalkyl, —S—R6 and —O—R6, 
         R15 is absent or is at least one substituent on the aromatic ring which are independently selected from the group consisting of: OH, NO, NO 2 , NH 2 , N 3 , halogen, CF 3 , CHF 2 , CH 2 F, nitrile, alkoxy, aryloxy, amidine, guanidiniums, carboxylic acid, carboxylic acid ester, carboxylic acid amide, aryl, cycloalkyl, heteroalkyl, heteroaryl, aminoalkyl, aminodialkyl, aminotrialkyl, aminoacyl, carbonyl, substituted or unsubstituted imine, sulfate, sulfonamide, phosphate, phosphoramide, hydrazide, hydroxamate, hydroxamic acid, heteroaryloxy, alkyl, aminoaryl, aminoheteroaryl, thioalkyl, thioaryl and thioheteroaryl. 
       
     
     
         68 . The method of  claim 67 , wherein R1 is substituted, cyclic or acyclic, branched and/or linear. 
     
     
         69 . The method of  claim 67 , wherein R7 and R8 combine to form a cyclic structure. 
     
     
         70 . The method of  claim 67 , wherein R6 and one of R7 or R8 combine to form a cyclic structure. 
     
     
         71 . The method of  claim 67 , wherein R11 and R12 combine to form a cyclic structure, 
     
     
         72 . The method of  claim 67 , wherein
 X is selected from: OR1,   
       
         
           
           
               
               
           
         
         R1 and R3 are independently selected from the group consisting of: C1 to C7 alkyl, C1 to C7 alkenyl, C1 to C7 alkynyl, C1 to C7 heteroalkyl, C6 to C14 aryl, C3 to C14 heteroaryl, C6 to C14 arylalkyl and C3 to C14 heteroarylalkyl, 
         R4 is selected from the group consisting of: H, C1 to C7 alkyl, C1 to C7 alkenyl, C1 to C7 alkynyl, C1 to C7 heteroalkyl, C6 to C14 aryl, C3 to C14 heteroaryl, C6 to C14 arylalkyl and C3 to C14 heteroarylalkyl, 
         R5 is selected from the group consisting of: H, C1 to C7 alkyl, C1 to C7 alkenyl, C1 to C7 alkynyl, C1 to C7 heteroalkyl, C6 to C14 aryl, C3 to C14 heteroaryl, C6 to C14 arylalkyl or C3 to C14 heteroarylalkyl, C1 to C7 acyl, C6 to C14 arylacyl, and C3 to C14 heteroarylacyl, 
         R2 is selected from the group consisting of: —(C═O)—R3, —(C═O)—OR4, and —(C═O)—NH—R4, 
         Y is selected from: 
       
       
         
           
           
               
               
           
         
       
     
     
         73 . The method of  claim 72 , wherein at least one of R1 to R5 is substituted, cyclic or acyclic, branched and/or linear. 
     
     
         74 . The method of  claim 72 , wherein R7 and R8 combine to form a cyclic structure. 
     
     
         75 . The method of  claim 72 , wherein R6 and one of R7 or R8 combine to form a cyclic structure. 
     
     
         76 . The method of  claim 72 , wherein R11 and R12 combine to form a cyclic structure. 
     
     
         77 . The method of  claim 67  wherein at least one of R1-R14 is substituted and these substituents and the substituents on the substituted 5 or 6 membered heterocyclic moiety and the substituted 9 or 10 membered heterobicyclic moiety are selected from the group consisting of: OH, NO, NO 2 , NH 2 , N 3 , halogen, CF 3 , CHF 2 , CH 2 F, nitrile, alkoxy, aryloxy, amidine, guanidiniums, carboxylic acid, carboxylic acid ester, carboxylic acid amide, aryl, cycloalkyl, heteroalkyl, heteroaryl, aminoalkyl, aminodialkyl, aminotrialkyl, aminoacyl, carbonyl, substituted or unsubstituted imine, sulfate, sulfonamide, phosphate, phosphoramide, hydrazide, hydroxamate, hydroxamic acid, heteroaryloxy, alkyl, aminoaryl, aminoheteroaryl, thioalkyl, thioaryl or thioheteroaryl, which may optionally be further substituted. 
     
     
         78 . The method of  claim 67  wherein the group X is 
       
         
           
           
               
               
           
         
       
     
     
         79 . The method of  claim 67 , wherein the group X is 
       
         
           
           
               
               
           
         
       
     
     
         80 . The method of  claim 67 , wherein X is —OR1 
     
     
         81 . The method of  claim 72  wherein the group Y is 
       
         
           
           
               
               
           
         
       
     
     
         82 . The method of  claim 72  wherein Y is 
       
         
           
           
               
               
           
         
       
     
     
         83 . The method of  claim 72 , wherein Y is 
       
         
           
           
               
               
           
         
       
     
     
         84 . The method of  claim 72 , wherein Y is 
       
         
           
           
               
               
           
         
       
     
     
         85 . The method of  claim 72 , wherein Y is 
       
         
           
           
               
               
           
         
       
     
     
         86 . The method of  claim 72 , wherein Y is 
       
         
           
           
               
               
           
         
       
     
     
         87 . The method of  claim 72 , wherein Y is 
       
         
           
           
               
               
           
         
       
     
     
         88 . The method of  claim 67  wherein the protein kinase is a serine or threonine kinase. 
     
     
         89 . The method of  claim 67  wherein the protein kinase is a tyrosine kinase. 
     
     
         90 . The method of  claim 67  wherein the protein kinase is selected from the group consisting of one or more of the isoforms of:
 A protein kinase C;   B Tie-2, also known as TEK, HPK-6, TIE-2, VMCM, VMCM1;   C c-Kit, also known as SCFR, CD117, PBT;   D VEGF-R2/KDR; also known as VEGFR2, VEGFR-2, VEGFR, Hs.KDR, Hs.12337, FLK1, FLK-1;   E EGF-R, also known as ERBB1, ERBB, EGFRvIII;   F Abl, also known as c-ab1, c-ABL, JTK7, p150, ABL1;   G MET, also known as HGFR, C-MET, RCCP2;   H CDK2, also known as p34CDK2, p33CDK2, p33CDK2;   I PDGF, also known as PDGFR1, PDGFR, PDGF-R-beta, JTK12, CD140B, PDGFRB;   J FGFR-1, also known as N-SAM, LOC51033, FLT2, FLJ14326, CEK, C-FGR, BFGFR, H5, H4, H3, H2, FLG; and   K P38 MAP Kinase, also known as p38alpha, p38ALPHA, SAPK2a, SAPK2A, PRKM15, PRKM14, Mxi2, MXI2, Exip, EXIP, CSPB1, CSBP2, CSBP1, p38, RK, P38, MAPK14.