2,6,7,8 substituted purines as HDM2 inhibitors

A compound represented by Formula I:

• Wherein
• R1 is selected from the group consisting of C1-C6alkyl, —(CRa2)nCOOR11, —(CRa2)nNR5SO2R6, —(CRa2)nSO2NR5R6, —(CRa2)nC(O)NRcSO2N(Rc)2, —(CRa2)nC(O)R5, —(CRa2)nCONR5R6, —(CRa2)nCONR5SO2R6, —(CRa2)nCONR5OR6, —(CRa2)nOR5, —(CRa2)nS(O)Rc, —(CRa2)nS(O)2Rc, and nitrogen containing 5 or 6-membered heteroaryl, heterocyclic and heterocyclenyl ring, wherein the alkyl and 5 or 6-membered ring can be optionally substituted with ORc, SRc, NH2, nitro, CN, amide, COOR11, C1-C6alkyl, C1-C6haloalkyl, C1-C6haloalkyloxy, C1-C6hydroxyalkyl, C2-C6alkenyl, C1-C6alkyl-C(═O)O—, C1-C6alkyl-C(═O)—, C2-C6alkynyl, halo group, hydroxyalkoxy, —SO2NRcRc, —NRcSO2Rc, C1-C6alkylsulfonyl, C1-C6alkylamino or di(C1-C6)alkylamino;
• R2 is selected from the group consisting of aryl, heteroaryl, C3-C8cycloalkyl, —W—(CRaR9)tR7, and heterocyclic, wherein W is NRc or O, wherein the aryl, heteroaryl, cycloalkyl or heterocyclic is optionally substituted with R12 selected from the group consisting of halo, CN, haloC1-C6alkyl, C1-C6alkyl, —(CRa2)zOR8, —(CRa2)zNHR8, —(CRa2)zC(O)NRcRc, —(CRa2)zCOOR10, —(CRa2)zS(O)2Rc, —(CRa2)zaryl, —(CRa2)zheteroaryl, —(CRa2)zheterocyclic, —(CRa2)zC3-C8cycloalkyl, —(CRa2)zcyclenyl, and —(CRa2)zheterocyclenyl, wherein the alkyl, aryl, heteroaryl, heterocyclic, cycloalkyl, cyclenyl and heterocyclenyl of R12 can be optionally substituted with OH, NH2, nitro, CN, CON(Rc)2, —(CRa2)zCOOR10, C1-C6alkoxy, C1-C6alkyl, C1-C6haloalkyl, C1-C6haloalkyloxy, C1-C6hydroxyalkyl, C2-C6alkenyl, C1-C6alkyl-C(═O)O—, C1-C6alkyl-C(═O)—, C2-C6alkynyl, halo group, hydroxyalkoxy, —SO2NRcRc, —NRcSO2Rc, C1-C6alkylsulfonyl, C1-C6alkylamino or di(C1-C6)alkylamino;
• R3 is selected from the group consisting of —(CRa2)qNRcR8, —(CRa2)qOR8, —(CRa2)qSR8, —(CRa2)qC(O)R8, —(CRa2)qS(O)R8, —(CRa2)qS(O)2R8, —(CRa2)qCONRcR8, —(CRa2)qNRcC(O)R8, -T-C1-C6alkyl, C2-C6alkenyl, -T-aryl, -T-heteroaryl, -T-heterocyclic, -T-C3-C8cycloalkyl, -T-cyclenyl, and -T-heterocyclenyl,
• wherein the alkyl, alkenyl, aryl, heteroaryl, heterocyclic, cycloalkyl, cyclenyl and heterocyclenyl can be optionally substituted with halo, SRc, ORc, haloC1-C6alkyl, haloC1-C6alkoxy, —(CRa2)zCN, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, —(CRa2)zC(O)OR10, —(CRa2)zC(O)R8, —(CRa2)zOR8, —(CRa2)zNRcR8, —(CRa2)zS(O)2R8, —(CRa2)zC(O)NRcR8, —(CRa2)zaryl, —(CRa2)zheteroaryl, —(CRa2)z C3-C8cycloalkyl, —(CRa2)zheterocyclic,
• —(CRa2)zheterocyclenyl, —(CRa2)zcyclenyl, —(CRa2)zSO2NRcR8, or —(CRa2)zO(CRa2)zD(CRa2)vQ, said alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heterocyclic, heterocyclenyl and cyclenyl can further be optionally substituted with SH, OH, NH2, nitro, CN, CON(R)2, COOR10C1-C6alkoxy, C1-C6alkyl, C2-C6alkenyl, C1-C6haloalkyl, C1-C6haloalkyloxy, C1-C6hydroxyalkyl, C1-C6alkyl-C(═O)O—, C1-C6alkyl-C(═O)—, C2-C6alkynyl, halo group, hydroxyalkoxy, —SO2NRcRc, —NRcSO2Rc, C1-C6alkylsulfonyl, C1-C6alkylamino or di(C1-C6)alkylamino;
• R4 is selected from the group consisting of C1-C6alkyl, —(CRa2)maryl, —(CRa2)mheteroaryl, —(CRa2)mheterocyclic, —(CRa2)mC3-C8cycloalkyl, —(CRa2)mcyclenyl, and —(CRa2)mheterocyclenyl, wherein the alkyl, aryl, heteroaryl, heterocyclic, cycloalkyl, cyclenyl, and heterocyclenyl can be optionally substituted with OH, SH, NH2, nitro, CN, CON(Rc)2, COOR10, C1-C6alkoxy, C1-C6alkyl, C3-C6cycloalkyl, haloC2-C6alkenyl, C2-C6alkenyl, C2-C6alkenoxy, C1-C6haloalkyl, C1-C6haloalkyloxy, C1-C6hydroxyalkyl, C1-C6alkyl-C(═O)O—, C1-C6alkyl-C(═O)—, C2-C6alkynyl, halo group, hydroxyalkoxy, —SO2NRcRc, —NRcSO2Rc, C1-C6alkylsulfonyl, C1-C6alkylamino or di(C1-C6)alkylamino;
• R5 is independently selected from the group consisting of H, C1-C6alkyl, —C0-C6alkyl-C3-C8cycloalkyl, —C0-C6alkyl-heteroaryl, —C0-C6alkyl-aryl, and —C0-C6alkylheterocyclic, wherein the alkyl, cycloalkyl, heteroaryl, aryl, and heterocyclic can be optionally substituted with C2-C3alkenyl, C3-C6cycloalkyl, C1-C3alkoxy, OH, halo, NH2, C1-C3alkylamino, C1-C3dialkylamino or COOR11;
• R6 is independently selected from the group consisting of H, C1-C6alkyl, —C0-C6alkyl-C3-C8cycloalkyl, —C0-C6alkyl-heteroaryl, —C0-C6alkyl-aryl, and —C0-C6alkylheterocyclic, wherein the alkyl, cycloalkyl, heteroaryl, aryl, and heterocyclic can be optionally substituted with C2-C3alkenyl, C3-C6cycloalkyl, C1-C3alkoxy, OH, halo, NH2, C1-C3alkylamino, C1-C3dialkylamino or COOR11;
• R7 is selected from the group consisting of H, C1-C6alkyl, C2-C6alkenyl, C3-C8cycloalkyl, aryl, heteroaryl, and heterocyclic, wherein the alkyl, alkenyl, cycloalkyl, aryl, heteroaryl or heterocyclic can be optionally substituted with halo, nitro, CN, C1-C6haloalkyl, C1-C6haloalkyloxy, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkyl, —C0-C6alkyl-C3-C8cycloalkyl, —C0-C6alkyl-heteroaryl, —C0-C6alkyl-aryl, —C0-C6alkylheterocyclic, —C0-C6alkylheterocyclenyl, —C0-C6alkylcyclenyl, —(CRa2)zNR5R6, —(CRa2)zNR5 SO2R6, —(CRa2)zSO2NR5R6, —(CRa2)zC(O)R5, —(CRa2)zC(O)OR10, —(CRa2)zCONR5R6, —(CRa2)zCONR5OR6, —(CRa2)zNR5C(O)OR6, —(CRa2)zNR5C(O)R6, —(CRa2)zOR5, —(CRa2)zS(O)Rc, and —(CRa2)zS(O)2Rc;
• R8 is independently selected from the group consisting of H, —(CRa2)s-heteroaryl, —(CRa2)s-aryl, —(CRa2)s-heterocyclic, —(CRa2)s-heterocyclenyl, —(CRa2)s-cyclenyl, —(CRa2)sC3-C8cycloalkyl, and C1-C6alkyl, wherein the heteroaryl, aryl, heterocyclic, heterocyclenyl, cyclenyl, cycloalkyl, and alkyl can be optionally substituted with OH, —N(Rc)2, NH2, nitro, CN, CON(Rc)2, COOR10, C1-C6alkoxy, C1-C6alkyl, C2-C6alkenyl, C3-C6cycloalkyl, C1-C6haloalkyl, C1-C6haloalkyloxy, C1-C6hydroxyalkyl, C1-C6alkyl-C(═O)O—, C1-C6alkyl-C(═O)—, C2-C6alkynyl, halo group, hydroxyalkoxy, —SO2NRcRc, —NRcSO2R, C1-C6alkylsulfonyl, C1-C6alkylamino, di(C1-C6)alkylamino, heteroaryl, aryl, heterocyclic, heterocyclenyl, or cyclenyl;
• R9 is independently selected from the group consisting of H, C1-C6alkyl, C1-C6haloalkyl, C3-C8cycloalkyl, aryl, heteroaryl, and heterocyclic, wherein the alkyl, cycloalkyl, aryl, heteroaryl, and heterocyclic can be optionally substituted with —C0-C6alkylORc, C0-C6alkylN(R)2, COOR10, nitro, CN, C1-C6alkyl, C1-C6haloalkyl, C1-C6haloalkyloxy, C1-C6hydroxyalkyl, C2-C6alkenyl, C1-C6alkyl-C(═O)O—, C1-C6alkyl-C(═O)—, C2-C6alkynyl, halo group, hydroxyalkoxy, —SO2NRcRc, —NRcSO2Rc, C1-C6alkylsulfonyl, heterocylic, or C(O)NHRc;
• R10 is independently selected from the group consisting of C1-C6alkyl, —(CRc2)zC3-C8cycloalkyl, —(CRc2)z-heteroaryl, —(CRc2)z-aryl, and —(CRc2)z-heterocyclic, wherein the heteroaryl, aryl, heterocyclic, cycloalkyl and alkyl can be optionally substituted with C1-C6alkyl, OH, halo, or haloC1-C6alkyl;
• R11 is independently selected from the group consisting of H, C1-C6alkyl, —(CRc2)zC3-C8cycloalkyl, —(CRc2)zheteroaryl, —(CRc2)zaryl, and —(CRc2)zheterocyclic wherein the heteroaryl, aryl, heterocyclic, cycloalkyl and alkyl can be optionally substituted with C1-C6alkyl, OH, halo, or haloC1-C6alkyl;
• Ra is independently H, ORc, NH2, halo, C1-C3alkyl, or C2-C4alkenyl, said alkyl or alkenyl is optionally substituted with OH, C1-C4alkoxy, NH2, halo, haloC1-C4alkyl, C3-C6cycloalkyl, or C2-C4alkenyl;
• Rc is independently H or C1-C3alkyl optionally substituted with C2-C3alkenyl, C3-C6cycloalkyl, C1-C3alkoxy, OH, halo, NH2, C1-C3alkylamino, or C1-C3dialkylamino;
• T is independently C2-C3alkenyl, —(CRa2)q—, —C(═CH2)—, —(CRa2)q—C(═CH2)—, —C(═CH2)—(CRa2)q—, —C(═NH)—, —(CRa2)q—C(═NH)—, or —C(═NH)—(CRa2)q—;
• D is a bond, —C(O)NRc—, —NRcC(O)—, or —NRc—;
• Q is H, COOR10, OH, heteroaryl or heterocyclic;
• n is independently 0, 1, 2 or 3;
• m is independently 0, 1 or 2;
• q is independently 0, 1, 2, or 3;
• s is independently 0, 1 or 2;
• t is independently 0, 1, or 2;
• v is independently 1, 2, 3 or 4;
• z is independently 0, 1, 2 or 3;
• or a pharmaceutically acceptable salt thereof.