Benzimidazole quinolinones and uses thereof

Abstract

Methods of inhibiting various enzymes and treating various conditions are provided that include administering to a subject a compound of Structure I or IB, a pharmaceutically acceptable salt thereof, a tautomer thereof, or a pharmaceutically acceptable salt of the tautomer. Compounds having the Structure I and IB have the following structures and have the variables described herein. Such compounds may be used to prepare medicaments for use in inhibiting various enzymes and for use in treating conditions mediated by such enzymes.

1 . A method of inhibiting a serine/threonine kinase in a subject or treating a biological condition mediated by a serine/threonine kinase in a subject, comprising: administering to the subject a compound of Structure I, a tautomer of the compound, a pharmaceutically acceptable salt of the compound, a pharmaceutically acceptable salt of the tautomer, or mixtures thereof wherein Structure I has the following formula 
       
         
           
           
               
               
           
         
         wherein, 
         A, B, C, and D are independently selected from the group consisting carbon and nitrogen; 
         R 1  is selected from the group consisting of —H, —F, —Cl, —Br, —I, —CN, —NO 2 , substituted and unsubstituted alkyl groups having from 1 to 12 carbon atoms, substituted and unsubstituted alkenyl groups having from 1 to 12 carbon atoms, substituted and unsubstituted alkynyl groups having from 1 to 8 carbon atoms, substituted and unsubstituted heterocyclyl groups, substituted and unsubstituted heterocyclylalkyl groups, —SH, substituted and unsubstituted —S-alkyl groups, substituted and unsubstituted —S(═O) 2 —O-alkyl groups, substituted and unsubstituted —S(═O) 2 -alkyl groups, substituted and unsubstituted —S(═O)-alkyl groups, —S(═O)—NH 2 , substituted and unsubstituted —S(═O)—N(H)(alkyl) groups, substituted and unsubstituted —S(═O)—N(alkyl) 2  groups, —OH, substituted and unsubstituted alkoxy groups, substituted and unsubstituted aryloxy groups, substituted and unsubstituted arylalkoxy groups, substituted and unsubstituted heterocyclyloxy groups, substituted and unsubstituted heterocyclylalkoxy groups, —NH 2 , substituted and unsubstituted —N(H)(alkyl) groups, substituted and unsubstituted —N(alkyl) 2  groups, substituted and unsubstituted —N(H)(heterocyclyl) groups, substituted and unsubstituted —N(alkyl)(heterocyclyl) groups, substituted and unsubstituted —N(heterocyclyl) 2  groups, substituted and unsubstituted —N(H)(heterocyclylalkyl) groups, substituted and unsubstituted —N(alkyl)(heterocyclylalkyl) groups, substituted and unsubstituted —N(heterocyclylalkyl) 2  groups, substituted and unsubstituted —N(H)—C(═O)-alkyl groups, substituted and unsubstituted —N(H)—C(═O)-heterocyclyl groups, substituted and unsubstituted —N(H)—C(═O)-heterocyclylalkyl groups, substituted and unsubstituted —N(H)—S(═O)-alkyl groups, substituted and unsubstituted —C(═O)-alkyl groups, substituted and unsubstituted —C(═O)-heterocyclyl groups, substituted and unsubstituted —C(═O)-heterocyclylalkyl groups, —C(═O)—NH 2 , substituted and unsubstituted —C(═O)—N(H)(alkyl) groups, substituted and unsubstituted —C(═O)—N(alkyl) 2  groups, substituted and unsubstituted —C(═O)—N(H)(aralkyl) groups, substituted and unsubstituted —C(═O)—N(H)(heterocyclyl) groups, —C(═O)—N(H)(heterocyclylalkyl) groups, —CO 2 H, substituted and unsubstituted —C(═O)—O-alkyl groups, substituted and unsubstituted —C(═O)—O-heterocyclyl groups, and substituted and unsubstituted —C(═O)—O-heterocyclylalkyl groups; 
         R 2  and R 3  are independently selected from the group consisting of —H, —F, —Cl, —Br, —I, —CN, —NO 2 , substituted and unsubstituted alkyl groups having from 1 to 12 carbon atoms, substituted and unsubstituted alkenyl groups having from 1 to 12 carbon atoms, substituted and unsubstituted alkynyl groups having from 1 to 8 carbon atoms, substituted and unsubstituted aryl groups, substituted and unsubstituted aralkyl groups, substituted and unsubstituted heterocyclyl groups, substituted and unsubstituted heterocyclylalkyl groups, —SH, substituted and unsubstituted —S-alkyl groups, substituted and unsubstituted —S-aryl groups, substituted and unsubstituted —S-aralkyl groups, substituted and unsubstituted —S(═O) 2 —O-alkyl groups, substituted and unsubstituted —S(═O) 2 -alkyl groups, substituted and unsubstituted —S(═O) 2 -heterocyclyl groups, substituted and unsubstituted —S(═O)-alkyl groups, substituted and unsubstituted —S(═O)-heterocyclyl groups, —S(═O) 2 —NH 2 , substituted and unsubstituted —S(═O) 2 —N(H)(alkyl) groups, substituted and unsubstituted —S(═O) 2 —N(alkyl) 2  groups, substituted and unsubstituted —S(═O) 2 —N(H)(aryl) groups, substituted and unsubstituted —S(═O) 2 —N(alkyl)(aryl) groups, substituted and unsubstituted —S(═O) 2 —N(aryl) 2  groups, substituted and unsubstituted —S(═O) 2 —N(H)(aralkyl) groups, substituted and unsubstituted —S(═O) 2 —N(alkyl)(aralkyl) groups, substituted and unsubstituted —S(═O) 2 —N(aralkyl) 2  groups, —OH, substituted and unsubstituted alkoxy groups, substituted and unsubstituted aryloxy groups, substituted and unsubstituted arylalkoxy groups, substituted and unsubstituted heterocyclyloxy groups, substituted and unsubstituted heterocyclylalkoxy groups, —NH 2 , substituted and unsubstituted —N(H)(alkyl) groups, substituted and unsubstituted —N(alkyl) 2  groups, substituted and unsubstituted —N(H)(aryl) groups, substituted and unsubstituted —N(alkyl)(aryl) groups, substituted and unsubstituted —N(aryl) 2  groups, substituted and unsubstituted —N(H)(aralkyl) groups, substituted and unsubstituted —N(alkyl)(aralkyl) groups, substituted and unsubstituted —N(aralkyl) 2  groups, substituted and unsubstituted —N(H)(heterocyclyl) groups, substituted and unsubstituted —N(alkyl)(heterocyclyl) groups, substituted and unsubstituted —N(heterocyclyl) 2  groups, substituted and unsubstituted —N(H)(heterocyclylalkyl) groups, substituted and unsubstituted —N(alkyl)(heterocyclylalkyl) groups, substituted and unsubstituted —N(heterocyclylalkyl) 2  groups, substituted and unsubstituted —N(H)—S(═O) 2 -alkyl groups, substituted and unsubstituted —N(H)—S(═O) 2 -aryl groups, substituted and unsubstituted —N(H)—S(═O) 2 -aralkyl groups, substituted and unsubstituted —N(H)—S(═O) 2 -heterocyclyl groups, substituted and unsubstituted —N(H)—S(═O) 2 -heterocyclylalkyl groups, substituted and unsubstituted —N(H)—C(═O)-alkyl groups, substituted and unsubstituted —N(H)—C(═O)-aryl groups, substituted and unsubstituted —N(H)—C(═O)-aralkyl groups, substituted and unsubstituted —N(H)—C(═O)-heterocyclyl groups, substituted and unsubstituted —N(H)—C(═O)-heterocyclylalkyl groups, substituted and unsubstituted —N(alkyl)-C(═O)-alkyl groups, substituted and unsubstituted —N(alkyl)-C(═O)-aryl groups, substituted and unsubstituted —N(alkyl)-C(═O)-aralkyl groups, substituted and unsubstituted —N(alkyl)-C(═O)-heterocyclyl groups, substituted and unsubstituted —N(alkyl)-C(═O)-heterocyclylalkyl groups, substituted and unsubstituted —N(alkyl)-S(═O) 2 -alkyl groups, substituted and unsubstituted —N(alkyl)-S(═O) 2 -aryl groups, substituted and unsubstituted —N(alkyl)-S(═O) 2 -aralkyl groups, substituted and unsubstituted —N(alkyl)-S(═O) 2 -heterocyclyl groups, substituted and unsubstituted —N(alkyl)-S(═O) 2 -heterocyclylalkyl groups, —N(H)—C(═O)—NH 2 , substituted and unsubstituted —N(H)—C(═O)—N(H)(alkyl) groups, substituted and unsubstituted —N(H)—C(═O)—N(alkyl) 2  groups, substituted and unsubstituted —N(H)—C(═O)—N(H)(aryl) groups, substituted and unsubstituted —N(H)—C(═O)—N(alkyl)(aryl) groups, substituted and unsubstituted —N(H)—C(═O)—N(aryl) 2  groups, substituted and unsubstituted —N(H)—C(═O)—N(H)(aralkyl) groups, substituted and unsubstituted —N(H)—C(═O)—N(alkyl)(aralkyl) groups, substituted and unsubstituted —N(H)—C(═O)—N(aralkyl) 2  groups, substituted and unsubstituted —N(H)—C(═O)—N(H)(heterocyclyl) groups, substituted and unsubstituted —N(H)—C(═O)—N(alkyl)(heterocyclyl) groups, substituted and unsubstituted —N(H)—C(═O)—N(heterocyclyl) 2  groups, substituted and unsubstituted —N(H)—C(═O)—N(H)(heterocyclylalkyl) groups, substituted and unsubstituted —N(H)—C(═O)—N(alkyl)(heterocyclylalkyl) groups, substituted and unsubstituted —N(H)—C(═O)—N(heterocyclylalkyl) 2  groups, substituted and unsubstituted —N(alkyl)-C(═O)—NH 2  groups, substituted and unsubstituted —N(alkyl)-C(═O)—N(H)(alkyl) groups, substituted and unsubstituted —N(alkyl)-C(═O)—N(alkyl) 2  groups, substituted and unsubstituted —N(alkyl)-C(═O)—N(H)(aryl) groups, substituted and unsubstituted —N(alkyl)-C(═O)—N(alkyl)(aryl) groups, substituted and unsubstituted —N(alkyl)-C(═O)—N(aryl) 2  groups, substituted and unsubstituted —N(alkyl)-C(═O)—N(H)(aralkyl) groups, substituted and unsubstituted —N(alkyl)-C(═O)—N(alkyl)(aralkyl) groups, substituted and unsubstituted —N(alkyl)-C(═O)—N(aralkyl) 2  groups, substituted and unsubstituted —N(alkyl)-C(═O)—N(H)(heterocyclyl) groups, substituted and unsubstituted —N(alkyl)-C(═O)—N(alkyl)(heterocyclyl) groups, substituted and unsubstituted —N(alkyl)-C(═O)—N(heterocyclyl) 2  groups, substituted and unsubstituted —N(alkyl)-C(═O)—N(H)(heterocyclylalkyl) groups, substituted and unsubstituted —N(alkyl)-C(═O)—N(alkyl)(heterocyclylalkyl) groups, substituted and unsubstituted —N(alkyl)-C(═O)—N(heterocyclylalkyl) 2  groups, substituted and unsubstituted —C(═O)-alkyl groups, substituted and unsubstituted —C(═O)-aryl groups, substituted and unsubstituted —C(═O)-aralkyl groups, substituted and unsubstituted —C(═O)-heterocyclyl groups, substituted and unsubstituted —C(═O)-heterocyclylalkyl groups, —C(═O)—NH 2 , substituted and unsubstituted —C(═O)—N(H)(alkyl) groups, substituted and unsubstituted —C(═O)—N(alkyl) 2  groups, substituted and unsubstituted —C(═O)—N(H)(aryl) groups, substituted and unsubstituted —C(═O)—N(alkyl)(aryl) groups, substituted and unsubstituted —C(═O)—N(aryl) 2  groups, substituted and unsubstituted —C(═O)—N(H)(aralkyl) groups, substituted and unsubstituted —C(═O)—N(alkyl)(aralkyl) groups, substituted and unsubstituted —C(═O)—N(aralkyl) 2  groups, substituted and unsubstituted —C(═O)—N(H)(heterocyclyl) groups, substituted and unsubstituted —C(═O)—N(alkyl)(heterocyclyl) groups, substituted and unsubstituted —C(═O)—N(heterocyclyl) 2  groups, substituted and unsubstituted —C(═O)—N(H)(heterocyclylalkyl) groups, substituted and unsubstituted —C(═O)—N(alkyl)(heterocyclylalkyl) groups, substituted and unsubstituted —C(═O)—N(heterocyclylalkyl) 2  groups, —CO 2 H, substituted and unsubstituted —C(═O)—O-alkyl groups, substituted and unsubstituted —C(═O)—O-aryl groups, substituted and unsubstituted —C(═O)—O-heterocyclyl groups, and substituted and unsubstituted —C(═O)—O-heterocyclylalkyl groups; 
         R 4  is selected from the group consisting of —H, —F, —Cl, —Br, —I, —CN, —NO 2 , substituted and unsubstituted alkyl groups having from 1 to 12 carbon atoms, substituted and unsubstituted alkenyl groups having from 1 to 8 carbon atoms, substituted and unsubstituted alkynyl groups having from 1 to 8 carbon atoms, —SH, substituted and unsubstituted —S-alkyl groups, substituted and unsubstituted —S(═O) 2 —O-alkyl groups, substituted and unsubstituted —S(═O) 2 -alkyl groups, substituted and unsubstituted —S(═O)-alkyl groups, —S(═O) 2 —NH 2 , substituted and unsubstituted —S(═O) 2 —N(H)(alkyl) groups, substituted and unsubstituted —S(═O) 2 —N(alkyl) 2  groups, —OH, substituted and unsubstituted alkoxy groups, —NH 2 , substituted and unsubstituted —N(H)(alkyl) groups, substituted and unsubstituted —N(alkyl) 2  groups, substituted and unsubstituted —N(H)—C(═O)-alkyl groups, substituted and unsubstituted —N(H)—S(═O)-alkyl groups, —C(═O)—NH 2 , substituted and unsubstituted —C(═O)—N(H)(alkyl) groups, substituted and unsubstituted —C(═O)—N(alkyl) 2  groups, and substituted and unsubstituted —C(═O)—O-alkyl groups; 
         R 5  and R 8  are independently selected from the group consisting of —H, —F, —Cl, —Br, —I, —CN, —NO 2 , substituted and unsubstituted straight and branched chain alkyl groups having from 1 to 8 carbon atoms, substituted and unsubstituted alkenyl groups having from 1 to 8 carbon atoms, substituted and unsubstituted alkynyl groups having from 1 to 8 carbon atoms, substituted and unsubstituted heterocyclyl groups, —SH, substituted and unsubstituted —S-alkyl groups, substituted and unsubstituted —S(═O) 2 —O-alkyl groups, substituted and unsubstituted —S(═O) 2 -alkyl groups, substituted and unsubstituted —S(═O)-alkyl groups, —S(═O) 2 —NH 2 , substituted and unsubstituted —S(═O) 2 —N(H)(alkyl) groups, substituted and unsubstituted —S(═O) 2 —N(alkyl) 2  groups, —OH, substituted and unsubstituted alkoxy groups, —NH 2 , substituted and unsubstituted —N(H)(alkyl) groups, substituted and unsubstituted —N(alkyl) 2  groups, substituted and unsubstituted —N(H)—C(═O)-alkyl groups, substituted and unsubstituted —N(H)—S(═O)-alkyl groups, —C(═O)—NH 2 , substituted and unsubstituted —C(═O)—N(H)(alkyl) groups, substituted and unsubstituted —C(═O)—N(alkyl) 2  groups, and substituted and unsubstituted —C(═O)—O-alkyl groups; or R 5  may be absent if A is nitrogen; or R 8  may be absent if D is nitrogen; 
         R 6  and R 7  are independently selected from the group consisting of —H, —F, —Cl, —Br, —I, —NO 2 , —CN, substituted and unsubstituted alkyl groups having from 1 to 12 carbon atoms, substituted and unsubstituted alkenyl groups having from 1 to 12 carbon atoms, substituted and unsubstituted alkynyl groups having from 1 to 8 carbon atoms, substituted and unsubstituted heterocyclyl groups, substituted and unsubstituted heterocyclylalkyl groups, —SH, substituted and unsubstituted —S-alkyl groups, substituted and unsubstituted —S(═O) 2 —O-alkyl groups, substituted and unsubstituted —S(═O) 2 -alkyl groups, substituted and unsubstituted —S(═O) 2 -heterocyclyl groups, substituted and unsubstituted —S(═O)-alkyl groups, substituted and unsubstituted —S(═O)-heterocyclyl groups, —S(═O) 2 —NH 2 , substituted and unsubstituted —S(═O) 2 —N(H)(alkyl) groups, substituted and unsubstituted —S(═O) 2 —N(alkyl) 2  groups, substituted and unsubstituted —S(═O) 2 —N(H)(heterocyclyl) groups, substituted and unsubstituted —S(═O) 2 —N(alkyl)(heterocyclyl) groups, substituted and unsubstituted —S(═O) 2 —N(heterocyclyl) 2  groups, substituted and unsubstituted —S(═O) 2 —N(H)(heterocyclylalkyl) groups, substituted and unsubstituted —S(═O) 2 —N(alkyl)(heterocyclylalkyl) groups, substituted and unsubstituted —S(═O) 2 —N(heterocyclylalkyl) 2  groups, —OH, substituted and unsubstituted alkoxy groups, substituted and unsubstituted aryloxy groups, substituted and unsubstituted arylalkoxy groups, substituted and unsubstituted heterocyclyloxy groups, substituted and unsubstituted heterocyclylalkoxy groups, —NH 2 , substituted and unsubstituted —N(H)(alkyl) groups, substituted and unsubstituted —N(alkyl) 2  groups, substituted and unsubstituted —N(H)(aryl) groups, substituted and unsubstituted —N(alkyl)(aryl) groups, substituted and unsubstituted —N(aryl) 2  groups, substituted and unsubstituted —N(H)(aralkyl) groups, substituted and unsubstituted —N(alkyl)(aralkyl) groups, substituted and unsubstituted —N(aralkyl) 2  groups, substituted and unsubstituted —N(H)(heterocyclyl) groups, substituted and unsubstituted —N(alkyl)(heterocyclyl) groups, substituted and unsubstituted —N(heterocyclyl) 2  groups, substituted and unsubstituted —N(H)(heterocyclylalkyl) groups, substituted and unsubstituted —N(alkyl)(heterocyclylalkyl) groups, substituted and unsubstituted —N(heterocyclylalkyl) 2  groups, substituted and unsubstituted —N(H)—S(═O) 2 -alkyl groups, substituted and unsubstituted —N(H)—S(═O) 2 -heterocyclyl groups, substituted and unsubstituted —N(H)—S(═O) 2 -heterocyclylalkyl groups, substituted and unsubstituted —N(H)—C(═O)-alkyl groups, substituted and unsubstituted —N(H)—C(═O)-heterocyclyl groups, substituted and unsubstituted —N(H)—C(═O)-heterocyclylalkyl groups, substituted and unsubstituted —N(alkyl)-C(═O)-alkyl groups, substituted and unsubstituted —N(alkyl)-C(═O)-heterocyclyl groups, substituted and unsubstituted —N(alkyl)-C(═O)-heterocyclylalkyl groups, substituted and unsubstituted —N(alkyl)-S(═O) 2 -alkyl groups, substituted and unsubstituted —N(alkyl)-S(═O) 2 -heterocyclyl groups, substituted and unsubstituted —N(alkyl)-S(═O) 2 -heterocyclylalkyl groups, substituted and unsubstituted —C(═O)-alkyl groups, substituted and unsubstituted —C(═O)-heterocyclyl groups, substituted and unsubstituted —C(═O)-heterocyclylalkyl groups, —C(═O)—NH 2 , substituted and unsubstituted —C(═O)—N(H)(alkyl) groups, substituted and unsubstituted —C(═O)—N(alkyl) 2  groups, substituted and unsubstituted —C(═O)—N(H)(aryl) groups, substituted and unsubstituted —C(═O)—N(alkyl)(aryl) groups, substituted and unsubstituted —C(═O)—N(aryl) 2  groups, substituted and unsubstituted —C(═O)—N(H)(aralkyl) groups, substituted and unsubstituted —C(═O)—N(alkyl)(aralkyl) groups, substituted and unsubstituted —C(═O)—N(aralkyl) 2  groups, substituted and unsubstituted —C(═O)—N(H)(heterocyclyl) groups, substituted and unsubstituted —C(═O)—N(alkyl)(heterocyclyl) groups, substituted and unsubstituted —C(═O)—N(heterocyclyl) 2  groups, substituted and unsubstituted —C(═O)—N(H)(heterocyclylalkyl) groups, substituted and unsubstituted —C(═O)—N(alkyl)(heterocyclylalkyl) groups, substituted and unsubstituted —C(═O)—N(heterocyclylalkyl) 2  groups, —CO 2 H, substituted and unsubstituted —C(═O)—O-alkyl groups, substituted and unsubstituted —C(═O)—O-heterocyclyl groups, and substituted and unsubstituted —C(═O)—O-heterocyclylalkyl groups; or R 6  may be absent if B is nitrogen; or R 7  may be absent if C is nitrogen; 
         R 9  is selected from the group consisting of —H, substituted and unsubstituted alkyl groups having from 1 to 12 carbon atoms, substituted and unsubstituted aryl groups, substituted and unsubstituted aralkyl groups, substituted and unsubstituted heterocyclyl groups, substituted and unsubstituted heterocyclylalkyl groups, substituted and unsubstituted heterocyclylaminoalkyl groups, substituted and unsubstituted alkoxy groups, and —NH 2 , or R 9  and R 1  join together to form one or more rings, each having 5, 6, or 7 ring members; and 
         R 10  is —H, or R 9  and R 10  join together to form one or more rings, each having 5, 6, or 7 ring members. 
       
     
     
         2 . The method of  claim 1 , wherein the serine/threonine kinase is glycogen synthase kinase 3, cyclin dependent kinase 2, cyclin dependent kinase 4, checkpoint kinase 1, NEK-2, CHK2, MEK1, CK1ε, Raf, ribosomal S6 kinase 2, or PAR-1. 
     
     
         3 . A method of inhibiting a serine/threonine kinase in a subject or treating a biological condition mediated by a serine/threonine kinase in a subject, comprising: administering to the subject a compound of Structure I, a tautomer of the compound, a pharmaceutically acceptable salt of the compound, a pharmaceutically acceptable salt of the tautomer, or mixtures thereof wherein Structure I has the following formula and the serine/threonine kinase is cyclin dependent kinase 2 
       
         
           
           
               
               
           
         
         wherein, 
         A, B, C, and D are independently selected from the group consisting of carbon and nitrogen; 
         R 1 , R 4 , R 5 , and R 8  are independently selected from the group consisting of —H and substituted and unsubstituted straight and branched chain alkyl groups having from 1 to 8 carbon atoms; or R 5  may be absent if A is nitrogen; or R 8  may be absent if D is nitrogen; 
         R 2  and R 3  are independently selected from the group consisting of —H, —F, —Cl, —Br, —I, —CN, —NO 2 , substituted and unsubstituted alkyl groups having from 1 to 12 carbon atoms, substituted and unsubstituted alkenyl groups having from 1 to 12 carbon atoms, substituted and unsubstituted aryl groups, substituted and unsubstituted aralkyl groups, substituted and unsubstituted heterocyclyl groups, substituted and unsubstituted heterocyclylalkyl groups, —NH 2 , substituted and unsubstituted —N(H)(alkyl) groups, substituted and unsubstituted —N(alkyl) 2  groups, substituted and unsubstituted —N(H)(aryl) groups, substituted and unsubstituted —N(alkyl)(aryl) groups, substituted and unsubstituted —N(aryl) 2  groups, substituted and unsubstituted —N(H)(heterocyclyl) groups, substituted and unsubstituted —N(alkyl)(heterocyclyl) groups, substituted and unsubstituted —N(heterocyclyl) 2  groups; 
         R 6  and R 7  are independently selected from the group consisting of —H, —F, —Cl, —Br, —I, —CN, —NO 2 , substituted and unsubstituted alkyl groups having from 1 to 12 carbon atoms, substituted and unsubstituted alkenyl groups having from 1 to 12 carbon atoms, substituted and unsubstituted heterocyclyl groups, substituted and unsubstituted heterocyclylalkyl groups, —OH, substituted and unsubstituted alkoxy groups, substituted and unsubstituted heterocyclyloxy groups, substituted and unsubstituted heterocyclylalkoxy groups, —NH 2 , substituted and unsubstituted —N(H)(alkyl) groups, substituted and unsubstituted —N(alkyl) 2  groups, substituted and unsubstituted —N(H)(heterocyclyl) groups, substituted and unsubstituted —N(alkyl)(heterocyclyl) groups, substituted and unsubstituted —N(heterocyclyl) 2  groups, substituted and unsubstituted —N(H)(heterocyclylalkyl) groups, substituted and unsubstituted —N(alkyl)(heterocyclylalkyl) groups, substituted and unsubstituted —N(heterocyclylalkyl) 2  groups, substituted and unsubstituted —N(H)—C(═O)-alkyl groups, substituted and unsubstituted —N(H)—C(═O)-heterocyclyl groups, and substituted and unsubstituted —N(H)—C(═O)-heterocyclylalkyl groups; or R 6  may be absent if B is nitrogen; or R 7  may be absent if C is nitrogen; 
         R 9  is selected from the group consisting of —H, substituted and unsubstituted alkyl groups having from 1 to 12 carbon atoms, substituted and unsubstituted alkenyl groups having from 1 to 12 carbon atoms, substituted and unsubstituted heterocyclyl groups, substituted and unsubstituted heterocyclylalkyl groups, —OH, substituted and unsubstituted alkoxy groups, substituted and unsubstituted heterocyclyloxy groups, substituted and unsubstituted heterocyclylalkoxy groups, substituted and unsubstituted —C(═O)-alkyl groups, substituted and unsubstituted —C(═O)-heterocyclyl groups, and substituted and unsubstituted —C(═O)-heterocyclylalkyl groups; 
         R 10  is —H. 
       
     
     
         4 . The method of  claim 3 , wherein R 9  is selected from the group consisting of —H, substituted and unsubstituted straight or branched chain alkyl groups having from 1-8 carbon atoms, substituted and unsubstituted saturated heterocyclyl groups, substituted and unsubstituted heterocyclylalkyl groups wherein the heterocyclyl moiety is saturated, substituted and unsubstituted alkoxy groups, and substituted and unsubstituted heterocyclylalkoxy groups wherein the heterocyclyl moiety is saturated. 
     
     
         5 . The method of  claim 3 , wherein R 2  is selected from the group consisting of —H, —F, —Cl, —Br, —I, —NO 2 , —CN, —NH 2 , substituted and unsubstituted straight or branched chain alkyl groups having from 1 to 8 carbons, substituted and unsubstituted aryl groups, and substituted and unsubstituted pyridinyl groups. 
     
     
         6 . The method of  claim 3 , wherein R 3  is selected from the group consisting of —H, —F, —Cl, —Br, —I, substituted and unsubstituted straight or branched chain alkyl groups having from 1 to 8 carbon atoms, substituted and unsubstituted aryl groups, substituted and unsubstituted aralkyl groups. 
     
     
         7 . The method of  claim 3 , wherein R 6  and R 7  are independently selected from the group consisting of —H, —F, —Cl, —Br, —I, —OH, substituted and unsubstituted —N(alkyl)(piperidinyl), substituted and unsubstituted piperidinyl groups, substituted and unsubstituted morpholinyl groups, substituted and unsubstituted piperazinyl groups; or R 6  may be absent if B is nitrogen; or R 7  may be absent if C is nitrogen. 
     
     
         8 . A method of inhibiting a serine/threonine kinase in a subject or treating a biological condition mediated by a serine/threonine kinase in a subject, comprising: administering to the subject a compound of Structure I, a tautomer of the compound, a pharmaceutically acceptable salt of the compound, a pharmaceutically acceptable salt of the tautomer, or mixtures thereof wherein Structure I has the following formula and the serine/threonine kinase is PAR-1 
       
         
           
           
               
               
           
         
         wherein, 
         A, B, C, and D are independently selected from the group consisting of carbon and nitrogen; 
         R 1  is selected from the group consisting of —H, —F, —Cl, —Br, —I, —CN, —NO 2 , substituted and unsubstituted alkyl groups having from 1 to 12 carbon atoms, substituted and unsubstituted alkenyl groups having from 1 to 12 carbon atoms, substituted and unsubstituted heterocyclyl groups, and substituted and unsubstituted heterocyclylalkyl groups; 
         R 2  is selected from the group consisting of —H, —F, —Cl, —Br, —I, —NO 2 , —CN, substituted and unsubstituted alkyl groups having from 1 to 12 carbon atoms, substituted and unsubstituted alkenyl groups having from 1 to 12 carbon atoms, substituted and unsubstituted aryl groups, substituted and unsubstituted aralkyl groups, —OH, substituted and unsubstituted alkoxy, substituted and unsubstituted heterocyclyloxy, substituted and unsubstituted heterocyclylalkoxy, substituted and unsubstituted —C(═O)-alkyl groups, substituted and unsubstituted —C(═O)-aryl, substituted and unsubstituted —C(═O)-aralkyl, —CO 2 H, substituted and unsubstituted —C(═O)—O-alkyl groups, substituted and unsubstituted —C(═O)—O-aryl groups, and substituted and unsubstituted —C(═O)—O-aralkyl groups; 
         R 3  is selected from the group consisting of —H, —F, —Cl, —Br, —I, —NO 2 , —CN, substituted and unsubstituted alkyl groups having from 1 to 12 carbon atoms, substituted and unsubstituted alkenyl groups having from 1 to 12 carbon atoms, substituted and unsubstituted aryl groups, substituted and unsubstituted aralkyl groups, substituted and unsubstituted heterocyclyl groups, substituted and unsubstituted heterocyclylalkyl groups, —SH, substituted and unsubstituted —S-alkyl groups, substituted and unsubstituted —S(═O) 2 —O-alkyl groups, substituted and unsubstituted —S(═O) 2 -alkyl groups, substituted and unsubstituted —S(═O) 2 -heterocyclyl groups, —S(═O) 2 —NH 2 , substituted and unsubstituted —S(═O) 2 —N(H)(alkyl) groups, substituted and unsubstituted —S(═O) 2 —N(alkyl) 2  groups, substituted and unsubstituted —S(═O)-alkyl groups, substituted and unsubstituted —S(═O)-aryl groups, substituted and unsubstituted —S(═O)-heterocyclyl groups, —OH, substituted and unsubstituted alkoxy groups, substituted and unsubstituted aryloxy groups, substituted and unsubstituted heterocyclyloxy groups, substituted and unsubstituted heterocyclylalkoxy groups, —NH 2 , substituted and unsubstituted —N(H)(alkyl) groups, substituted and unsubstituted —N(alkyl) 2  groups, substituted and unsubstituted —N(H)(aryl) groups, substituted and unsubstituted —N(alkyl)(aryl) groups, substituted and unsubstituted —N(aryl) 2  groups, substituted and unsubstituted —N(H)(aralkyl) groups, substituted and unsubstituted —N(alkyl)(aralkyl) groups, substituted and unsubstituted —N(aralkyl) 2  groups, substituted and unsubstituted —N(H)(heterocyclyl) groups, substituted and unsubstituted —N(alkyl)(heterocyclyl) groups, substituted and unsubstituted —N(heterocyclyl) 2  groups, substituted and unsubstituted —N(H)(heterocyclylalkyl) groups, substituted and unsubstituted —N(alkyl)(heterocyclylalkyl) groups, substituted and unsubstituted —N(heterocyclylalkyl) 2  groups, substituted and unsubstituted —N(H)—C(═O)-alkyl groups, substituted and unsubstituted —N(alkyl)-C(═O)-alkyl groups, substituted and unsubstituted —N(H)—C(═O)-aryl groups, substituted and unsubstituted —N(alkyl)-C(═O)-aryl groups, substituted and unsubstituted —N(H)—C(═O)-aralkyl groups, substituted and unsubstituted —N(alkyl)-C(═O)-aralkyl groups, substituted and unsubstituted —N(H)—C(═O)-heterocyclyl groups, substituted and unsubstituted —N(alkyl)-C(═O)-heterocyclyl groups, substituted and unsubstituted —N(H)—C(═O)-heterocyclylalkyl groups, substituted and unsubstituted —N(alkyl)-C(═O)-heterocyclylalkyl groups, substituted and unsubstituted —N(H)—S(═O) 2 -alkyl groups, substituted and unsubstituted —N(H)—S(═O) 2 -aryl, substituted and unsubstituted —N(H)—S(═O) 2 -heterocyclyl groups, substituted and unsubstituted —C(═O)-alkyl groups, substituted and unsubstituted —C(═O)-aryl, substituted and unsubstituted —C(═O)-aralkyl, substituted and unsubstituted —C(═O)-heterocyclyl groups, substituted and unsubstituted —C(═O)-heterocyclylalkyl groups, —C(═O)—NH 2 , substituted and unsubstituted —C(═O)—N(H)(alkyl) groups, substituted and unsubstituted —C(═O)—N(alkyl) 2  groups, substituted and unsubstituted —C(═O)—N(H)(aryl) groups, substituted and unsubstituted —C(═O)—N(alkyl)(aryl) groups, substituted and unsubstituted —C(═O)—N(aryl) 2  groups, substituted and unsubstituted —C(═O)—N(H)(aralkyl) groups, substituted and unsubstituted —C(═O)—N(alkyl)(aralkyl) groups, substituted and unsubstituted —C(═O)—N(aralkyl) 2  groups, substituted and unsubstituted —C(═O)—N(H)(heterocyclyl) groups, substituted and unsubstituted —C(═O)—N(alkyl)(heterocyclyl) groups, substituted and unsubstituted —C(═O)—N(heterocyclyl) 2  groups, substituted and unsubstituted —C(═O)—N(H)(heterocyclylalkyl) groups, substituted and unsubstituted —C(═O)—N(alkyl)(heterocyclylalkyl) groups, substituted and unsubstituted —C(═O)—N(heterocyclylalkyl) 2  groups, —CO 2 H, substituted and unsubstituted —C(═O)—O-alkyl groups, substituted and unsubstituted —C(═O)—O-aryl groups, substituted and unsubstituted —C(═O)—O-aralkyl groups, substituted and unsubstituted —C(═O)—O-heterocyclyl groups, and substituted and unsubstituted —C(═O)—O-heterocyclylalkyl groups; 
         R 4 , R 5  and R 8  are independently selected from the group consisting of —H and substituted and unsubstituted alkyl groups having from 1 to 12 carbon atoms; or R 5  may be absent if A is nitrogen; or R 8  may be absent if D is nitrogen; 
         R 6  and R 7  are independently selected from the group consisting of —H, —F, —Cl, —Br, —I, —CN, —NO 2 , substituted and unsubstituted alkyl groups having from 1 to 12 carbon atoms, substituted and unsubstituted alkenyl groups having from 1 to 12 carbon atoms, substituted and unsubstituted heterocyclyl groups, substituted and unsubstituted heterocyclylalkyl groups, —SH, substituted and unsubstituted —S-alkyl groups, substituted and unsubstituted —S-heterocyclyl groups, —OH, substituted and unsubstituted alkoxy groups, substituted and unsubstituted heterocyclyloxy groups, substituted and unsubstituted heterocyclylalkoxy groups, —NH 2 , substituted and unsubstituted —N(H)(alkyl) groups, substituted and unsubstituted —N(alkyl) 2  groups, substituted and unsubstituted —N(H)(heterocyclyl) groups, substituted and unsubstituted —N(alkyl)(heterocyclyl) groups, substituted and unsubstituted —N(heterocyclyl) 2  groups, substituted and unsubstituted —N(H)(heterocyclylalkyl) groups, substituted and unsubstituted —N(alkyl)(heterocyclylalkyl) groups, and substituted and unsubstituted —N(heterocyclylalkyl) 2  groups; or R 6  is absent if B is nitrogen; or R 7  is absent if C is nitrogen; 
         R 9  is selected from the group consisting of —H, substituted and unsubstituted alkyl groups having from 1 to 12 carbon atoms, substituted and unsubstituted alkenyl groups having from 1 to 12 carbons, substituted and unsubstituted aryl groups, substituted and unsubstituted aralkyl groups, substituted and unsubstituted heterocyclyl groups, substituted and unsubstituted heterocyclylalkyl groups, —OH, substituted and unsubstituted alkoxy groups, and substituted and unsubstituted heterocyclylalkoxy groups; and 
         R 10  is —H. 
       
     
     
         9 . The method of  claim 8 , wherein
 R 3  is selected from the group consisting of —H, —F, —Cl, —Br, —I, —NO 2 , —CN, substituted and unsubstituted alkyl groups having from 1 to 12 carbon atoms, substituted and unsubstituted alkenyl groups having from 1 to 12 carbon atoms, substituted and unsubstituted aryl groups, substituted and unsubstituted aralkyl groups, substituted and unsubstituted heterocyclyl groups, substituted and unsubstituted heterocyclylalkyl groups, —OH, substituted and unsubstituted alkoxy groups, substituted and unsubstituted aryloxy groups, substituted and unsubstituted heterocyclyloxy groups, substituted and unsubstituted heterocyclylalkoxy groups, —NH 2 , substituted and unsubstituted —N(H)(alkyl) groups, substituted and unsubstituted —N(alkyl) 2  groups, substituted and unsubstituted —N(H)(aryl) groups, substituted and unsubstituted —N(alkyl)(aryl) groups, substituted and unsubstituted —N(aryl) 2  groups, substituted and unsubstituted —N(H)(aralkyl) groups, substituted and unsubstituted —N(alkyl)(aralkyl) groups, substituted and unsubstituted —N(aralkyl) 2  groups, substituted and unsubstituted —N(H)(heterocyclyl) groups, substituted and unsubstituted —N(alkyl)(heterocyclyl) groups, substituted and unsubstituted —N(heterocyclyl) 2  groups, substituted and unsubstituted —N(H)(heterocyclylalkyl) groups, substituted and unsubstituted —N(alkyl)(heterocyclylalkyl) groups, substituted and unsubstituted —N(heterocyclylalkyl) 2  groups, substituted and unsubstituted —C(═O)-alkyl groups, substituted and unsubstituted —C(═O)-heterocyclyl groups, substituted and unsubstituted —C(═O)-heterocyclylalkyl groups, —C(═O)—NH 2 , substituted and unsubstituted —C(═O)—N(H)(alkyl) groups, substituted and unsubstituted —C(═O)—N(alkyl) 2  groups, substituted and unsubstituted —C(═O)—N(H)(aryl) groups, substituted and unsubstituted —C(═O)—N(alkyl)(aryl) groups, substituted and unsubstituted —C(═O)—N(aryl) 2  groups, substituted and unsubstituted —C(═O)—N(H)(aralkyl) groups, substituted and unsubstituted —C(═O)—N(alkyl)(aralkyl) groups, substituted and unsubstituted —C(═O)—N(aralkyl) 2  groups, substituted and unsubstituted —C(═O)—N(H)(heterocyclyl) groups, substituted and unsubstituted —C(═O)—N(alkyl)(heterocyclyl) groups, substituted and unsubstituted —C(═O)—N(heterocyclyl) 2  groups, substituted and unsubstituted —C(═O)—N(H)(heterocyclylalkyl) groups, substituted and unsubstituted —C(═O)—N(alkyl)(heterocyclylalkyl) groups, substituted and unsubstituted —C(═O)—N(heterocyclylalkyl) 2  groups, —CO 2 H, substituted and unsubstituted —C(═O)—O-alkyl groups, substituted and unsubstituted —C(═O)—O-heterocyclyl groups, and substituted and unsubstituted —C(═O)—O-heterocyclylalkyl groups;   R 6  and R 7  are independently selected from the group consisting of —H, —F, —Cl, —Br, —I, —CN, —NO 2 , substituted and unsubstituted alkyl groups having from 1 to 12 carbon atoms, substituted and unsubstituted alkenyl groups having from 1 to 12 carbon atoms, substituted and unsubstituted heterocyclyl groups, substituted and unsubstituted heterocyclylalkyl groups, —OH, substituted and unsubstituted alkoxy groups, substituted and unsubstituted heterocyclyloxy groups, and substituted and unsubstituted heterocyclylalkoxy groups; or R 6  is absent if B is nitrogen; or R 7  is absent if C is nitrogen.   
     
     
         10 . The method of  claim 8 , wherein R 9  is selected from the group consisting of —H, substituted and unsubstituted straight and branched chain alkyl groups having from 1 to 8 carbon atoms, substituted and unsubstituted cycloalkyl groups, substituted and unsubstituted heterocyclyl groups, and substituted and unsubstituted heterocyclylalkyl groups. 
     
     
         11 . The method of  claim 8 , wherein R 1  is selected from the group consisting of —H, —F, —Cl, —Br, —I, substituted and unsubstituted straight and branched chain alkyl groups having from 1 to 8 carbon atoms, substituted and unsubstituted cycloalkyl groups, and substituted and unsubstituted heterocyclyl groups. 
     
     
         12 . The method of  claim 8 , wherein R 2  is selected from the group consisting of —H, —F, —Cl, —Br, —I, —NO 2 , —CN, substituted and unsubstituted straight and branched chain alkyl groups having from 1 to 12 carbon atoms, substituted and unsubstituted cycloalkyl groups, substituted and unsubstituted aryl groups, and substituted and unsubstituted aralkyl groups. 
     
     
         13 . The method of  claim 8 , wherein R 3  is selected from the group consisting of —H, —F, —Cl, —Br, —I, —CN, substituted and unsubstituted straight or branched chain alkyl groups having from 1 to 8 carbon atoms, substituted and unsubstituted cycloalkyl groups, substituted and unsubstituted aryl groups, substituted and unsubstituted aralkyl groups, substituted and unsubstituted heterocyclyl groups, substituted and unsubstituted heterocyclylalkyl groups, —OH, substituted and unsubstituted alkoxy groups, substituted and unsubstituted heterocyclyloxy groups, substituted and unsubstituted heterocyclylalkoxy groups, substituted and unsubstituted —N(H)(alkyl) groups, substituted and unsubstituted —N(alkyl) 2  groups, and substituted and unsubstituted —N(H)(heterocyclylalkyl) groups. 
     
     
         14 . The method of  claim 8 , R 6  and R 7  are independently selected from the group consisting of —H, —F, —Cl, —Br, —I, —CN, —NO 2 , substituted and unsubstituted straight or branched chain alkyl groups having from 1 to 8 carbon atoms, substituted and unsubstituted cycloalkyl groups, substituted and unsubstituted heterocyclyl groups, substituted and unsubstituted heterocyclylalkyl groups, —OH, substituted and unsubstituted alkoxy groups, substituted and unsubstituted heterocyclyloxy groups, and substituted and unsubstituted heterocyclylalkoxy groups; or R 6  is absent if B is nitrogen; or R 7  is absent if C is nitrogen. 
     
     
         15 . The method of  claim 3 , wherein R 9  is selected from the group consisting of quinuclidinyl groups, piperidinyl groups, piperidinylalkyl groups, pyrrolidinyl groups, and aminocyclohexyl groups. 
     
     
         16 . The method of  claim 8 , wherein R 9  is selected from the group consisting of quinuclidinyl groups, piperidinyl groups, piperidinylalkyl groups, pyrrolidinyl groups, and aminocyclohexyl groups. 
     
     
         17 . The method of  claim 3  wherein the biological condition is diabetes. 
     
     
         18 . The method of  claim 3 , wherein the biological condition is Alzheimer's disease. 
     
     
         19 . The method of  claim 8  wherein the biological condition is diabetes. 
     
     
         20 . The method of  claim 8 , wherein the biological condition is Alzheimer's disease.