Inhibitors of GSK-3 and uses thereof

A method for enhancing glycogen synthesis or lowering blood levels of glucose in a patient in need thereof, comprising the step of administering to said patient:

• (a) a compound of formula I:
• 711
• or a pharmaceutically acceptable derivative or prodrug thereof, wherein:
• R1 is selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• heteroaryl;
• —CN;
• —C(O)R;
• —CO2R;
• or —CON(R)2;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, —NRS(O)2R, ═O, ═S, ═NN(R)2, ═N—OR, ═NN(R)COR, ═NNRCO2R, ═NNRSO2R, ═N—CN, or ═NR;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, or —NRS(O)2R;
• R2 is selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• or heteroaryl;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, —NRS(O)2R, ═O, ═S, ═NN(R)2, ═N—OR, ═NN(R)COR, ═NNRCO2R, ═NNRSO2R, ═N—CN, or ═NR;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, or —NRS(O)2R;
• X is O, S or —NH;
• Y is N or CH;
• each R is independently selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• heteroaryl;
• or any two R groups taken together form a carbocyclyl, heterocyclyl, aryl or heteroaryl group;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, —R′, —OR′, —SR′, —NO2, —CN, —N(R′)2, —NR′C(O)R′, —NR′C(O)N(R′)2, —N(R′)CO2R′, —CO2R′, —C(O)R′, —C(O)N(R′)2, —S(O)2R′, —S(O)2N(R′)2, —S(O)R′, —N(R′)S(O)2R′, ═O, ═S, ═NN(R′)2, ═N—OR′, ═NN(R′)COR′, ═NN(R′)CO2R′, ═NN(R′)SO2R′, ═N—CN, or ═NR′;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, —R′, —OR′, —SR′, —NO2, —CN, —N(R′)2, —NR′C(O)R′, —NR′C(O)N(R′)2, —N(R′)CO2R′, —CO2R′, —C(O)R′, —C(O)N(R′)2, —S(O)2R′, —S(O)2N(R′)2, —S(O)R′, or —N(R′)S(O)2R′;
• each R′ is independently selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• heteroaryl;
• or any two R′ groups taken together form a carbocyclyl, heterocyclyl, aryl or heteroaryl group;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, CF3, —R″, —OR″, —SR″, —NO2, —CN, —N(R″)2, —NR″C(O)R″, —NR″C(O)N(R″)2, —N(R″)CO2R″, —CO2R″, —C(O)R″, —C(O)N(R″)2, —S(O)2R″, —S(O)2N(R″)2, —S(O)R″, —N(R″)S(O)2R″, ═O, ═S, ═NN(R″)2, ═N—OR″, ═NN(R″)COR″, ═NN(R″)CO2R″, ═NN(R″)SO2R″, ═N—CN, or ═NR″;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, CF3, —R″, —OR″, —SR″, —NO2, —CN, —N(R″)2, —NR″C(O)R″, —NR″C(O)N(R″)2, —N(R″)CO2R″, —CO2R″, —C(O)R″, —C(O)N(R″)2, —S(O)2R″, —S(O)2N(R″)2, —S(O)R″, or —N(R″)S(O)2R″;
• and
• each R″ is independently selected from H or alkyl;
• or (b) a pharmaceutical composition comprising said compound and a pharmaceutically acceptable carrier, adjuvant, or vehicle;
• in an amount sufficient to enhance glycogen synthesis or lower blood glucose levels.

A method for inhibiting the production of hyperphosphorylated Tau protein in a patient in need thereof, comprising the step of administering to said patient:

• (a) a compound of formula I:
• 712
• or a pharmaceutically acceptable derivative or prodrug thereof, wherein:
• R1 is selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• heteroaryl;
• —CN;
• —C(O)R;
• —CO2R;
• or —CON(R)2;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, —NRS(O)2R, ═O, ═S, ═NN(R)2, ═N—OR, ═NN(R)COR, ═NNRCO2R, ═NNRSO2R, ═N—CN, or ═NR;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, or —NRS(O)2R;
• R2 is selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• or heteroaryl;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, —NRS(O)2R, ═O, ═S, ═NN(R)2, ═N—OR, ═NN(R)COR, ═NNRCO2R, ═NNRSO2R, ═N—CN, or ═NR;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, or —NRS(O)2R;
• X is O, S or —NH;
• Y is N or CH;
• each R is independently selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• heteroaryl;
• or any two R groups taken together form a carbocyclyl, heterocyclyl, aryl or heteroaryl group;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, —R′, —OR′, —SR′, —NO2, —CN, —N(R′)2, —NR′C(O)R′, —NR′C(O)N(R′)2, —N(R′)CO2R′, —CO2R′, —C(O)R′, —C(O)N(R′)2, —S(O)2R′, —S(O)2N(R′)2, —S(O)R′, —N(R′)S(O)2R′, ═O, ═S, ═NN(R′)2, ═N—OR′, ═NN(R′)COR′, ═NN(R′)CO2R′, ═NN(R′)SO2R′, ═N—CN, or ═NR′;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, —R′, —OR′, —SR′, —NO2, —CN, —N(R′)2, —NR′C(O)R′, —NR′C(O)N(R′)2, —N(R′)CO2R′, —CO2R′, —C(O)R′, —C(O)N(R′)2, —S(O)2R′, —S(O)2N(R′)2, —S(O)R′, or —N(R′)S(O)2R′;
• each R′ is independently selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• heteroaryl;
• or any two R′ groups taken together form a carbocyclyl, heterocyclyl, aryl or heteroaryl group;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, CF3, —R″, —OR″, —SR″, —NO2, —CN, —N(R″)2, —NR″C(O)R″, —NR″C(O)N(R″)2, —N(R″)CO2R″, —CO2R″, —C(O)R″, —C(O)N(R″)2, —S(O)2R″, —S(O)2N(R″)2, —S(O)R″, —N(R″)S(O)2R″, ═O, ═S, ═NN(R″)2, ═N—OR″, ═NN(R″)COR″, ═NN(R″)CO2R″, ═NN(R″)SO2R″, ═N—CN, or ═NR″;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, CF3, —R″, —OR″, —SR″, —NO2, —CN, —N(R″)2, —NR″C(O)R″, —NR″C(O)N(R″)2, —N(R″)CO2R″, —CO2R″, —C(O)R″, —C(O)N(R″)2, —S(O)2R″, —S(O)2N(R″)2, —S(O)R″, or —N(R″)S(O)2R″;
• and
• each R″ is independently selected from H or alkyl;
• or (b) a pharmaceutical composition comprising said compound and a pharmaceutically acceptable carrier, adjuvant, or vehicle;
• in an amount sufficient to inhibit hyperphosphorylation of Tau protein.

A method for inhibiting the phosphorylation of β-catenin in a patient in need thereof, comprising the step of administering to said patient:

• (a) a compound of formula I:
• 713
• or a pharmaceutically acceptable derivative or prodrug thereof, wherein:
• R1 is selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• heteroaryl;
• —CN;
• —C(O)R;
• —CO2R;
• or —CON(R)2;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, —NRS(O)2R, ═O, ═S, ═NN(R)2, ═N—OR, ═NN(R)COR, ═NNRCO2R, ═NNRSO2R, ═N—CN, or ═NR;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, or —NRS(O)2R;
• R2 is selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• or heteroaryl;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, —R. —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, —NRS(O)2R, ═O, ═S, ═NN(R)2, ═N—OR, ═NN(R)COR, ═NNRCO2R, ═NNRSO2R, ═N—CN, or ═NR;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, or —NRS(O)2R;
• X is O, S or —NH;
• Y is N or CH;
• each R is independently selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• heteroaryl;
• or any two R groups taken together form a carbocyclyl, heterocyclyl, aryl or heteroaryl group;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, —R′, —OR′, —SR′, —NO2, —CN, —N(R′)2, —NR′C(O)R′, —NR′C(O)N(R′)2, —N(R′)CO2R′, —CO2R′, —C(O)R′, —C(O)N(R′)2, —S(O)2R′, —S(O)2N(R′)2, —S(O)R′, —N(R′)S(O)2R′, ═O, ═S, ═NN(R′)2, ═N—OR′, ═NN(R′)COR′, ═NN(R′)CO2R′, ═NN(R′)SO2R′, ═N—CN, or ═NR′;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, —R′, —OR′, —SR′, —NO2, —CN, —N(R′)2, —NR′C(O)R′, —NR′C(O)N(R′)2, —N(R′)CO2R′, —CO2R′, —C(O)R′, —C(O)N(R′)2, —S(O)2R′, —S(O)2N(R′)2, —S(O)R′, or —N(R′)S(O)2R′;
• each R′ is independently selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• heteroaryl;
• or any two R′ groups taken together form a carbocyclyl, heterocyclyl, aryl or heteroaryl group;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, CF3, —R″, —OR″, —SR″, —NO2, —CN, —N(R″)2, —NR″C(O)R″, —NR″C(O)N(R″)2, —N(R″)CO2R″, —CO2R″, —C(O)R″, —C(O)N(R″)2, —S(O)2R″, —S(O)2N(R″)2, —S(O)R″, —N(R″)S(O)2R″, ═O, ═S, ═NN(R″)2, ═N—OR″, ═NN(R″)COR″, ═NN(R″)CO2R″, ═NN(R″)SO2R″, ═N—CN, or ═NR″;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, CF3, —R″, —OR″, —SR″, —NO2, —CN, —N(R″)2, —NR″C(O)R″, —NR″C(O)N(R″)2, —N(R″)CO2R″, —CO2R″, —C(O)R″, —C(O)N(R″)2, —S(O)2R″, —S(O)2N(R″)2, —S(O)R″, or —N(R″)S(O)2R″;
• and
• each R″ is independently selected from H or alkyl;
• or (b) a pharmaceutical composition comprising said compound and a pharmaceutically acceptable carrier, adjuvant, or vehicle;
• in an amount sufficient to inhibit phosphorylation of β-catenin.

A method for inhibiting GSK-3 activity in a biological sample, comprising the step of contacting the biological sample with:

• (a) a compound of formula I:
• 714
• or a pharmaceutically acceptable derivative or prodrug thereof, wherein:
• R1 is selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• heteroaryl;
• —CN;
• —C(O)R;
• —CO2R;
• or —CON(R)2;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, —NRS(O)2R, ═O, ═S, ═NN(R)2, ═N—OR, ═NN(R)COR, ═NNRCO2R, ═NNRSO2R, ═N—CN, or ═NR;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R) 2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, or —NRS(O)2R;
• R2 is selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• or heteroaryl;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, —NRS(O)2R, ═O, ═S, ═NN(R)2, ═N—OR, ═NN(R)COR, ═NNRCO2R, ═NNRSO2R, ═N—CN, or ═NR;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, or —NRS(O)2R;
• X is O, S or —NH;
• Y is N or CH;
• each R is independently selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• heteroaryl;
• or any two R groups taken together form a carbocyclyl, heterocyclyl, aryl or heteroaryl group;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, —R′, —OR′, —SR′, —NO2, —CN, —N(R′)2, —NR′C(O)R′, —NR′C(O)N(R′)2, —N(R′)CO2R′, —CO2R′, —C(O)R′, —C(O)N(R′)2, —S(O)2R′, —S(O)2N(R′)2, —S(O)R′, —N(R′)S(O)2R′, ═O, ═S, ═NN(R′)2, ═N—OR′, ═NN(R′)COR′, ═NN(R′)CO2R′, ═NN(R′)SO2R′, ═N—CN, or ═NR′;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, —R′, —OR′, —SR′, —NO2, —CN, —N(R′)2, —NR′C(O)R′, —NR′C(O)N(R′)2, —N(R′)CO2R′, —CO2R′, —C(O)R′, —C(O)N(R′)2, —S(O)2R′, —S(O)2N(R′)2, —S(O)R′, or —N(R′)S(O)2R′;
• each R′ is independently selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• heteroaryl;
• or any two R′ groups taken together form a carbocyclyl, heterocyclyl, aryl or heteroaryl group;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, CF3, —R″, —OR″, —SR″, —NO2, —CN, —N(R″)2, —NR″C(O)R″, —NR″C(O)N(R″)2, —N(R″)CO2R″, —CO2R″, —C(O)R″, —C(O)N(R″)2, —S(O)2R″, —S(O)2N(R″)2, —S(O)R″, —N(R″)S(O)2R″, ═O, ═S, ═NN(R″)2, ═N—OR″, ═NN(R″)COR″, —NN(R″)CO2R″, ═NN(R″)SO2R″, ═N—CN, or ═NR″;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, CF3, —R″, —OR″, —SR″, —NO2, —CN, —N(R″)2, —NR″C(O)R″, —NR″C(O)N(R″)2, —N(R″)CO2R″, —CO2R″, —C(O)R″, —C(O)N(R″)2, —S(O)2R″, —S(O)2N(R″)2, —S(O)R″, or —N(R″)S(O)2R″;
• and
• each R″ is independently selected from H or alkyl;
• or (b) a composition comprising said compound and a carrier, adjuvant, or vehicle;
• in an amount effective to inhibit GSK-3 activity.

A method for inhibiting Aurora-2 activity in a patient comprising the step of administering to said patient:

• (a) a compound of formula I:
• 715
• or a pharmaceutically acceptable derivative or prodrug thereof, wherein:
• R1 is selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• heteroaryl;
• —CN;
• —C(O)R;
• —CO2R;
• or —CON(R)2;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R) 2, —S(O)2R, —S(O)2N(R)2, —S(O)R, —NRS(O)2R, ═O, ═S, ═NN(R)2, ═N—OR, ═NN(R)COR, ═NNRCO2R, ═NNRSO2R, ═N—CN, or ═NR;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, or —NRS(O)2R;
• R2 is selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• or heteroaryl;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, —NRS(O)2R, ═O, ═S, ═NN(R)2, ═N—OR, ═NN(R)COR, ═NNRCO2R, ═NNRSO2R, ═N—CN, or ═NR;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N (R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, or —NRS(O)2R;
• X is O, S or —NH;
• Y is N or CH;
• each R is independently selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• heteroaryl;
• or any two R groups taken together form a carbocyclyl, heterocyclyl, aryl or heteroaryl group;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, —R′, —OR′, —SR′, —NO2, —CN, —N(R′)2, —NR′C(O)R′, —NR′C(O)N(R′)2, —N(R′)CO2R′, —CO2R′, —C(O)R′, —C(O)N(R′)2, —S(O)2R′, —S(O)2N(R′)2, —S(O)R′, —N(R′)S(O)2R′, ═O, ═S, ═NN(R′)2, ═N—OR′, ═NN(R′)COR′, ═NN(R′)CO2R′, ═NN(R′)SO2R′, ═N—CN, or ═NR′;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, —R′, —OR′, —SR′, —NO2, —CN, —N(R′)2, —NR′C(O)R′, —NR′C(O)N(R′)2, —N(R′)CO2R′, —CO2R′, —C(O)R′, —C(O)N(R′)2, —S(O)2R′, —S(O)2N(R′)2, —S(O)R′, or —N(R′)S(O)2R′;
• each R′ is independently selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• heteroaryl;
• or any two R′ groups taken together form a carbocyclyl, heterocyclyl, aryl or heteroaryl group;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, CF3, —R″, —OR″, —SR″, —NO2, —CN, —N(R″)2, —NR″C(O)R″, —NR″C(O)N(R″)2, —N(R″)CO2R″, —CO2R″, —C(O)R″, —C(O)N(R″)2, —S(O)2R″, —S(O)2N(R″)2, —S(O)R″, —N(R″)S(O)2R″, ═O, ═S, ═NN(R″)2, ═N—OR″, ═NN(R″)COR″, ═NN(R″)CO2R″, ═NN(R″)SO2R″, ═N—CN, or ═NR″;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, CF3, —R″, —OR″, —SR″, —NO2, —CN, —N(R″)2, —NR″C(O)R″, —NR″C(O)N(R″)2, —N(R″)CO2R″, —CO2R″, —C(O)R″, —C(O)N(R″)2, —S(O)2R″, —S(O)2N (R″)2, —S(O)R″, or —N(R″)S(O)2R″;
• and
• each R″ is independently selected from H or alkyl;
• or (b) a pharmaceutical composition comprising said compound and a pharmaceutically acceptable carrier, adjuvant, or vehicle;
• in an amount effective to inhibit Aurora-2 activity.

A method for inhibiting Aurora-2 activity in a biological sample, comprising the step of contacting the biological sample with:

• (a) a compound of formula I:
• 716
• or a pharmaceutically acceptable derivative or prodrug thereof, wherein:
• R1 is selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• heteroaryl;
• —CN;
• —C(O)R;
• —CO2R;
• or —CON(R)2;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, —NRS(O)2R, ═O, ═S, ═NN(R)2, ═N—OR, ═NN(R)COR, ═NNRCO2R, ═NNRSO2R, ═N—CN, or ═NR;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, or —NRS(O)2R;
• R2 is selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• or heteroaryl;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, —NRS(O)2R, ═O, ═S, ═NN(R)2, ═N—OR, ═NN(R)COR, ═NNRCO2R, ═NNRSO2R, ═N—CN, or ═NR;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, or —NRS(O)2R;
• X is O, S or —NH;
• Y is N or CH;
• each R is independently selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• heteroaryl;
• or any two R groups taken together form a carbocyclyl, heterocyclyl, aryl or heteroaryl group;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, —R′, —OR′, —SR′, —NO2, —CN, —N(R′)2, —NR′C(O)R′, —NR′C(O)N(R′)2, —N(R′)CO2R′, —CO2R′, —C(O)R′, —C(O)N(R′)2, —S(O)2R′, —S(O)2N(R′)2, —S(O)R′, —N(R′)S(O)2R′, ═O, ═S, ═NN(R′)2, ═N—OR′, ═NN(R′)COR′, ═NN(R′)CO2R′, ═NN(R′)SO2R′, ═N—CN, or ═NR′;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, —R′, —OR′, —SR′, —NO2, —CN, —N(R′)2, —NR′C(O)R′, —NR′C(O)N(R′)2, —N(R′)CO2R′, —CO2R′, —C(O)R′, —C(O)N(R′)2, —S(O)2R′, —S(O)2N(R′)2, —S(O)R′, or —N(R′)S(O)2R′;
• each R′ is independently selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• heteroaryl;
• or any two R′ groups taken together form a carbocyclyl, heterocyclyl, aryl or heteroaryl group;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, CF3, —R″, —OR″, —SR″, —NO2, —CN, —N (R″)2, —NR″C(O)R″, —NR″C(O)N(R′)2, —N(R″)CO2R″, —CO2R′, —C(O)R″, —C(O)N(R″)2, —S(O)2R″, —S(O)2N(R″)2, —S(O)R″, —N(R″)S(O)2R″, ═O, ═S, ═NN(R″)2, ═N—OR″, ═NN(R″)COR″, ═NN(R″)CO2R″, ═NN(R″)SO2R″, ═N—CN, or ═NR″;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, CF3, —R″, —OR″, —SR″, —NO2, —CN, —N(R″)2, —NR″C(O)R″, —NR″C(O)N(R″)2, —N(R″)CO2R″, —CO2R″, —C(O)R″, —C(O)N(R″)2, —S(O)2R″, —S(O)2N (R″)2, —S(O)R″, or —N(R″)S(O)2R″;
• and
• each R″ is independently selected from H or alkyl;
• or (b) a composition comprising said compound and a carrier, adjuvant, or vehicle;
• in an amount effective to inhibit Aurora-2 activity.

A method for inhibiting CDK—2 activity in a patient comprising the step of administering to said patient:

• (a) a compound of formula I:
• 717
• or a pharmaceutically acceptable derivative or prodrug thereof, wherein:
• R1 is selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• heteroaryl;
• —CN;
• —C(O)R;
• —CO2R;
• or —CON(R)2;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, —NRS(O)2R, ═O, ═S, ═NN(R)2, ═N—OR, ═NN(R)COR, ═NNRCO2R, ═NNRSO2R, ═N—CN, or ═NR;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, or —NRS(O)2R;
• R2 is selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• or heteroaryl;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, —NRS(O)2R, ═O, ═S, ═NN(R)2, ═N—OR, ═NN(R)COR, ═NNRCO2R, ═NNRSO2R, ═N—CN, or ═NR;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, or —NRS(O)2R;
• x is O, S or —NH;
• Y is N or CH;
• each R is independently selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• heteroaryl;
• or any two R groups taken together form a carbocyclyl, heterocyclyl, aryl or heteroaryl group;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, —R′, —OR′, —SR′, —NO2, —CN, —N(R′)2, —NR′C(O)R′, —NR′C(O)N(R′)2, —N(R′)CO2R′, —CO2R′, —C(O)R′, —C(O)N(R′)2, —S(O)2R′, —S(O)2N(R′)2, —S(O)R′, —N(R′)S(O)2R′, ═O, ═S, ═NN(R′)2, ═N—OR′, ═NN(R′)COR′, ═NN(R′)CO2R′, ═NN(R′)SO2R′, ═N—CN, or ═NR′;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, —R′, —OR′, —SR′, —NO2, —CN, —N(R′)2, —NR′C(O)R′, —NR′C(O)N(R′)2, —N(R′)CO2R′, —CO2R′, —C(O)R′, —C(O)N(R′)2, —S(O)2R′, —S(O)2N (R′)2, —S(O)R′, or —N(R′)S(O)2R′;
• each R′ is independently selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• heteroaryl;
• or any two R′ groups taken together form a carbocyclyl, heterocyclyl, aryl or heteroaryl group;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, CF3, —R″, —OR″, —SR″, —NO2, —CN, —N (R″)2, —NR″C(O)R″, —NR″C(O)N(R″)2, —N(R″)CO2R″, —CO2R″, —C(O)R″, —C(O)N(R″)2, —S(O)2R″, —S (O)2N (R″)2, —S(O)R″, —N (R″)S(O)2R″, ═O, ═S, ═NN(R″)2, ═N—OR″, ═NN(R″)COR″, ═NN(R″)CO2R″, ═NN(R″)SO2R″, ═N—CN, or ═NR″;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, CF3, —R″, —OR″, —SR″, —NO2, —CN, —N(R″)2, —NR″C(O)R″, —NR″C(O)N(R″)2, —N(R″)CO2R″, —CO2R″, —C(O)R″, —C(O)N(R″)2, —S(O)2R″, —S(O)2N(R″)2, —S(O)R″, or —N (R″)S(O)2R″;
• and
• each R″ is independently selected from H or alkyl;
• or (b) a pharmaceutical composition comprising said compound and a pharmaceutically acceptable carrier, adjuvant, or vehicle;
• in an amount effective to inhibit CDK-2 activity.

A method for inhibiting CDK-2 activity in a biological sample, comprising the step of contacting the biological sample with:

• (a) a compound of formula I:
• 718
• or a pharmaceutically acceptable derivative or prodrug thereof, wherein:
• R1 is selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• heteroaryl;
• —CN;
• —C(O)R;
• —CO2R;
• or —CON(R)2;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, —NRS(O)2R, ═O, ═S, ═NN(R)2, ═N—OR, ═NN(R)COR, ═NNRCO2R, ═NNRSO2R, ═N—CN, or ═NR;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, or —NRS(O)2R;
• R2 is selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• or heteroaryl;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, —NRS(O)2R, ═O, ═S, ═NN(R)2, ═N—OR, ═NN(R)COR, ═NNRCO2R, ═NNRSO2R, ═N—CN, or ═NR;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, or —NRS(O)2R;
• X is 0, S or —NH;
• Y is N or CH;
• each R is independently selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• heteroaryl;
• or any two R groups taken together form a carbocyclyl, heterocyclyl, aryl or heteroaryl group;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, —R′, —OR′, —SR′, —NO2, —CN, —N(R′)2, —NR′C(O)R′, —NR′C(O)N(R′)2, —N(R′)CO2R′, —CO2R′, —C(O)R′, —C(O)N(R′)2, —S(O)2R′, —S(O)2N(R′)2, —S(O)R′, —N(R′)S(O)2R′, ═O, ═S, ═NN(R′)2, ═N—OR′, ═NN(R′)COR′, ═NN(R′)CO2R′, ═NN(R′)SO2R′, ═N—CN, or ═NR′;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, —R′, —OR′, —SR′, —NO2, —CN, —N(R′)2, —NR′C(O)R′, —NR′C(O)N(R′)2, —N(R′)CO2R′, —CO2R′, —C(O)R′, —C(O)N(R′)2, —S(O)2R′, —S(O)2N(R′)2, —S(O)R′, or —N(R′)S(O)2R′;
• each R′ is independently selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• heteroaryl;
• or any two R′ groups taken together form a carbocyclyl, heterocyclyl, aryl or heteroaryl group;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, CF3, —R″, —OR″, —SR″, —NO2, —CN, —N(R″)2, —NR″C(O)R″, —NR″C(O)N(R″)2, —N(R″)CO2R″, —CO2R″, —C(O)R″, —C(O)N(R″)2, —S(O)2R″, —S(O)2N(R″)2, —S(O)R″, —N(R″)S(O)2R″, ═O, ═S, ═NN(R″)2, ═N—OR″, ═NN(R″)COR″, ═NN(R″)CO2R″, ═NN(R″)SO2R″, ═N—CN, or ═NR″;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, CF3, —R″, —OR″, —SR″, —NO2, —CN, —N(R″)2, —NR″C(O)R″, —NR″C(O)N(R″)2, —N(R″)CO2R″, —CO2R″, —C(O)R″, —C(O)N(R″)2, —S(O)2R″, —S(O)2N(R″)2, —S(O)R″, or —N(R″)S(O)2R″;
• and
• each R″ is independently selected from H or alkyl;
• or (b) a composition comprising said compound and a carrier, adjuvant, or vehicle;
• in an amount effective to inhibit CDK-2 activity.

A compound of formula I:

• 720
• or a pharmaceutically acceptable derivative or prodrug thereof, wherein:
• R1 is selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• heteroaryl;
• —CN;
• —C(O)R;
• —CO2R;
• or —CON(R)2;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, —NRS(O)2R, ═O, ═S, ═NN(R)2, ═N—OR, ═NN(R)COR, ═NNRCO2R, ═NNRSO2R, ═N—CN, or ═NR;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, or —NRS(O)2R;
• R2 is selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• or heteroaryl;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, —NRS(O)2R, ═O, ═S, ═NN(R)2, ═N—OR, ═NN(R)COR, ═NNRCO2R, ═NNRSO2R, ═N—CN, or ═NR;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, or —NRS(O)2R;
• X is O, S or —NH;
• Y is CH;
• each R is independently selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• heteroaryl;
• or any two R groups taken together form a carbocyclyl, heterocyclyl, aryl or heteroaryl group;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, —R′, —OR′, —SR′, —NO2, —CN, —N(R′)2, —NR′C(O)R′, —NR′C(O)N(R′)2, —N(R′)CO2R′, —CO2R′, —C(O)R′, —C(O)N(R′)2, —S(O)2R′, —S(O)2N(R′)2, —S(O)R′, —N(R′)S(O)2R′, ═O, ═S, ═NN(R′)2, ═N—OR′, ═NN(R′)COR′, ═NN(R′)CO2R′, ═NN(R′)SO2R′, ═N—CN, or ═NR′;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, —R′, —OR′, —SR′, —NO2, —CN, —N(R′)2, —NR′C(O)R′, —NR′C(O)N(R′)2, —N(R′)CO2R′, —CO2R′, —C(O)R′, —C(O)N(R′)2, —S(O)2R′, —S(O)2N(R′)2, —S(O)R′, or —N(R′)S(O)2R′;
• each R′ is independently selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• heteroaryl;
• or any two R′ groups taken together form a carbocyclyl, heterocyclyl, aryl or heteroaryl group;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, CF3, —R″, —OR″, —SR″, —NO2, —CN, —N (R″)2, —NR″C(O)R″, —NR″C(O)N(R″)2, —N(R″)CO2R″, —CO2R″, —C(O)R″, —C(O)N(R″)2, —S(O)2R″, —S(O)2N(R″)2, —S(O)R″, —N(R″)S(O)2R″, ═O, ═S, ═NN(R″)2, ═N—OR″, ═NN(R″)COR″, ═NN(R″)CO2R″, ═NN(R″)SO2R″, ═N—CN, or ═NR″;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, CF3, —R″, —OR″, —SR″, —NO2, —CN, —N(R″)2, —NR″C(O)R″, —NR″C(O)N(R″)2, —N(R″)CO2R″, —CO2R″, —C(O)R″, —C(O)N(R″)2, —S(O)2R″, —S(O)2N(R″)2, —S(O)R″, or —N(R″)S(O)2R″;
• and
• each R″ is independently selected from H or alkyl;
• with the proviso that when X is NH and R1 is an unsubstituted phenyl, then R2 is not
• 721

A compound of formula I:

• 722
• or a pharmaceutically acceptable derivative or prodrug thereof, wherein:
• R1 is selected from carbocyclyl;
• heterocyclyl;
• aryl;
• heteroaryl;
• or —CN;
• wherein said carbocyclyl or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, —NRS(O)2R, ═O, ═S, ═NN(R)2, ═N—OR, ═NN(R)COR, ═NNRCO2R, ═NNRSO2R, ═N—CN, or ═NR;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, or —NRS(O)2R;
• R2 is selected from aryl;
• heteroaryl;
• carbocyclyl;
• or heterocyclyl;
• wherein said carbocyclyl or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N (R)2, —NRC (O)R, —NRC (O)N (R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, —NRS(O)2R, ═O, ═S, ═NN(R)2, ═N—OR, ═NN(R)COR, ═NNRCO2R, ═NNRSO2R, ═N—CN, or ═NR;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, —R, —OR, —SR, —NO2, —CN, —N(R)2, —NRC(O)R, —NRC(O)N(R)2, —NRCO2R, —CO2R, —C(O)R, —C(O)N(R)2, —S(O)2R, —S(O)2N(R)2, —S(O)R, or —NRS(O)2R;
• X is O, S or —NH;
• Y is N;
• each R is independently selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• heteroaryl;
• or any two R groups taken together form a carbocyclyl, heterocyclyl, aryl or heteroaryl group;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, —R′, —OR′, —SR′, —NO2, —CN, —N(R′)2, —NR′C(O)R′, —NR′C(O)N(R′)2, —N(R′)CO2R′, —CO2R′, —C(O)R′, —C(O)N(R′)2, —S(O)2R′, —S(O)2N(R′)2, —S(O)R′, —N(R′)S(O)2R′, ═O, ═S, ═NN(R′)2, ═N—OR′, ═NN(R′)COR′, ═NN(R′)CO2R′, ═NN(R′)SO2R′, ═N—CN, or ═NR′;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, —R′, —OR′, —SR′, —NO2, —CN, —N(R′)2, —NR′C(O)R′, —NR′C(O)N(R′)2, —N(R′)CO2R′, —CO2R′, —C(O)R′, —C(O)N(R′)2, —S(O)2R′, —S(O)2N(R′)2, —S(O)R′, or —N(R′)S(O)2R′;
• each R′ is independently selected from H;
• alkyl;
• carbocyclyl;
• heterocyclyl;
• aryl;
• heteroaryl;
• or any two R′ groups taken together form a carbocyclyl, heterocyclyl, aryl or heteroaryl group;
• wherein said alkyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four substituents independently selected from halo, CF3, —R″, —OR″, —SR″, —NO2, —CN, —N(R″)2, —NR″C(O)R″, —NR″C(O)N(R″)2, —N(R″)CO2R″, —CO2R″, —C(O)R″, —C(O)N(R″)2, —S(O)2R″, —S(O)2N(R″)2, —S(O)R″, —N(R″)S(O)2R″, ═O, ═S, ═NN(R″)2, ═N—OR″, ═NN(R″)COR″, ═NN(R″)CO2R″, ═NN(R″)SO2R″, ═N—CN, or ═NR″;
• and wherein said aryl or heteroaryl is optionally substituted with one to four substituents independently selected from halo, CF3, —R″, —OR″, —SR″, —NO2, —CN, —N(R″)2, —NR″C(O)R″, —NR″C(O)N(R″)2, —N(R″)CO2R″, —CO2R″, —C(O)R″, —C(O)N(R″)2, —S(O)2R″, —S(O)2N(R″)2, —S(O)R″, or —N(R″)S(O)2R″;
• and
• each R″ is independently selected from H or alkyl;
• with the proviso that:
• i)when X is —NH and R2 is an unsubstituted phenyl, then R1 is not an unsubstituted phenyl;
• ii) when X is O and R1 is heterocyclyl, aryl or heteroaryl, then R2 is not heteroaryl or heterocyclyl;
• and
• iii) R1 excludes the following groups:
• unsubstituted 3-pyridyl, unsubstituted naphthyl,
• 723