Substituted pyrrolopyrimidines as HDM2 inhibitors

1. A compound represented by Formula I:

wherein

R 1 is selected from the group consisting of —(CR a 2 ) n COOR 11 , —(CR a 2 ) n SO 2 NR 5 R 6 , —(CR a 2 ) n C(O)NR c SO 2 N(R c ) 2 , —(CR a 2 ) n S(O)R c , —(CR a 2 ) n S(O) 2 R c and nitrogen containing 5-membered heterocyclic, heterocyclenyl or heteroaryl ring, wherein the 5-membered ring can be optionally substituted with OR c , SR c , NH 2 , nitro, CN, amide, COOR 11 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkyloxy, C 1 -C 6 hydroxyalkyl, C 2 -C 6 alkenyl, C 1 -C 6 alkyl-C(═O)O—, C 1 -C 6 alkyl-C(═O)—, C 2 -C 6 alkynyl, halo group, hydroxyalkoxy, —SO 2 NR c R c , —NR c SO 2 R c , C 1 -C 6 alkylsulfonyl, C 1 -C 6 alkylamino or di(C 1 -C 6 )alkylamino;

R 2 is selected from the group consisting of aryl, heteroaryl, —W—(CR a R 9 ) t R 7 , and heterocylic, wherein W is NR c or O, wherein the aryl, heteroaryl, or heterocylic is optionally substituted with R 12 selected from the group consisting of halo, CN, haloC 1 -C 6 alkyl, C 1 -C 6 alkyl, —(CR a 2 ) z OR a , —(CR a 2 ) z NR 8 , —(CR a 2 ) z C(O)NR c R c , —(CR a 2 ) z COOR 10 , —(CR a 2 ) z aryl, —(CR a 2 ) z heteroaryl, —(CR a 2 ) z heterocyclic, —(CR a 2 ) z C 3 -C 8 cycloalkyl, —(CR a 2 ) z cyclenyl, and —(CR a 2 ) z heterocyclenyl, wherein the alkyl, aryl, heteroaryl, heterocyclic, cycloalkyl, cyclenyl and heterocyclenyl of R 12 can be optionally substituted with OH, NH 2 , nitro, CN, CON(R c ) 2 , —(CR a 2 ) z COOR 10 , C 1 -C 6 alkoxy, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkyloxy, C 1 -C 6 hydroxyalkyl, C 2 -C 6 alkenyl, C 1 -C 6 alkyl-C(═O)O—, C 1 -C 6 alkyl-C(═O)—, C 2 -C 6 alkynyl, halo group, hydroxyalkoxy, —SO 2 NR c R c , —NR c SO 2 R c , C 1 -C 6 alkylsulfonyl, C 1 -C 6 alkylamino or di(C 1 -C 6 )alkylamino;

R 3 is selected from the group consisting of H, —(CR a 2 ) q NR c R 8 , —(CR a 2 ) q OR 8 , —(CR a 2 ) q SR 8 , —(CR a 2 ) q C(O)R 8 , —(CR a 2 ) q S(O)R 8 , —(CR a 2 ) q S(O) 2 R 8 , —(CR a 2 ) q CONR c R 8 , —(CR a 2 ) q NR c C(O)R 8 , -T-alkyl, C 2 -C 6 alkenyl, -T-aryl, -T-heteroaryl, -T-heterocyclic, -T-cycloalkyl, -T-cyclenyl, and -T-heterocyclenyl,

wherein the alkyl, alkenyl, aryl, heteroaryl, heterocyclic, cycloalkyl, cyclenyl and heterocyclenyl can be optionally substituted with halo, SH, OR c , haloC 1 -C 6 alkyl, haloC 1 -C 6 alkoxy, —(CR a 2 ) z CN, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, —(CR a 2 ) z C(O)OR 11 , —(CR a 2 ) z C(O)R 8 , —(CR a 2 ) z OR 8 , —(CR a 2 ) z NR c R 8 , —(CR a 2 ) z S(O) 2 R 8 , —(CR a 2 ) z C(O)NR c R 8 , —(CR a 2 ) z aryl, —(CR a 2 ) z heteroaryl, —(CR a 2 ) z C 3 -C 8 cycloalkyl, —(CR a 2 ) z heterocyclic, —(CR a 2 ) z heterocyclenyl, —(CR a 2 ) z cyclenyl, —(CR a 2 ) z SO 2 NR c R 8 , or —(CR a 2 ) z O(CR a 2 ) z Y(CR a 2 ) v U,

wherein alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heterocyclic, heterocyclenyl and cyclenyl can further be substituted with OH, SH, NH 2 , nitro, CN, CON(R c ) 2 , COOR 10 , C 1 -C 6 alkoxy, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkyloxy, C 1 -C 6 hydroxyalkyl, C 1 -C 6 alkyl-C(═O)O—, C 1 -C 6 alkyl-C(═O)—, C 2 -C 6 alkynyl, halo group, hydroxyalkoxy, —SO 2 NR c R c , —NR c SO 2 R c , C 1 -C 6 alkylsulfonyl, C 1 -C 6 alkylamino or di(C 1 -C 6 )alkylamino;

R 4 is selected from the group consisting of C 1 -C 6 alkyl, —(CR a 2 ) m aryl, —(CR a 2 ) m heteroaryl, —(CR a 2 ) m heterocyclic, —(CR a 2 ) m C 3 -C 8 cycloalkyl, —(CR a 2 ) m cyclenyl, and —(CR a 2 ) m heterocyclenyl, wherein the alkyl, aryl, heteroaryl, heterocyclic, cycloalkyl, cyclenyl, and heterocyclenyl can be optionally substituted with OH, SH, NH 2 , nitro, CN, CON(R c ) 2 , COOR 11 , C 1 -C 6 alkoxy, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, haloC 2 -C 6 alkenyl, C 2 -C 6 alkenyl, C 2 -C 6 alkenoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkyloxy, C 1 -C 6 hydroxyalkyl, C 1 -C 6 alkyl-C(═O)O—, C 1 -C 6 alkyl-C(═O)—, C 2 -C 6 alkynyl, halo group, hydroxyalkoxy, —SO 2 NR c R c , —NR c SO 2 R c , C 1 -C 6 alkylsulfonyl, C 1 -C 6 alkylamino or di(C 1 -C 6 )alkylamino;

R 5 is independently selected from the group consisting of H, C 1 -C 6 alkyl, —C 0 -C 6 alkyl-C 3 -C 8 cycloalkyl, —C 0 -C 6 alkyl-heteroaryl, —C 0 -C 6 alkyl-aryl, and —C 0 -C 6 alkylheterocyclic, wherein the alkyl, cycloalkyl, heteroaryl, aryl, and heterocyclic can be optionally substituted with C 2 -C 3 alkenyl, C 3 -C 6 cycloalkyl, C 1 -C 3 alkoxy, OH, halo, NH 2 , C 1 -C 3 alkylamino, C 1 -C 3 dialkylamino or COOR 11 ;

R 6 is independently selected from the group consisting of H, C 1 -C 6 alkyl, —C 0 -C 6 alkyl-C 3 -C 8 cycloalkyl, —C 0 -C 6 alkyl-heteroaryl, —C 0 -C 6 alkyl-aryl, and —C 0 -C 6 alkylheterocyclic, wherein the alkyl, cycloalkyl, heteroaryl, aryl, and heterocyclic can be optionally substituted with C 2 -C 3 alkenyl, C 3 -C 6 cycloalkyl, C 1 -C 3 alkoxy, OH, halo, NH 2 , C 1 -C 3 alkylamino, C 1 -C 3 dialkylamino or COOR 11 ;

R 7 is selected from the group consisting of C 1 -C 6 alkyl, C 2 -C 6 alkenyl, and C 3 -C 8 cycloalkyl, wherein the alkyl, alkenyl, or cycloalkyl can be optionally substituted with halo, nitro, CN, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkyloxy, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkyl, —C 0 -C 6 alkyl-C 3 -C 8 cycloalkyl, —C 0 -C 6 alkyl-heteroaryl, —C 0 -C 6 alkyl-aryl, —C 0 -C 6 alkylheterocyclic, —C 0 -C 6 alkylheterocyclenyl, —C 0 -C 6 alkylcyclenyl, —(CR a 2 ) z NR 5 , —(CR a 2 ) z NR 5 SO 2 R 6 , —(CR a 2 ) z SO 2 NR 5 R 6 , —(CR a 2 ) z C(O)R 5 , —(CR a 2 ) z C(O)OR 10 , —(CR a 2 ) z CONR 5 R 6 , —(CR a 2 ) z CONR 5 OR 6 , —(CR a 2 ) z NR 5 C(O)R 6 , —(CR a 2 ) z OR 5 , —(CR a 2 ) z S(O)R c , and —(CR a z ) z S(O) 2 R c ;

R 8 is independently selected from the group consisting of H, —(CR a 2 ) s -heteroaryl, —(CR a 2 ) s -aryl, —(CR a 2 ) s -heterocyclic, —(CR a 2 ) s -heterocyclenyl, —(CR a 2 ) s -cyclenyl, —(CR a 2 ) s cycloalkyl, and C 1 -C 6 alkyl, wherein the heteroaryl, aryl, heterocyclic, heterocyclenyl, cyclenyl, cycloalkyl, and alkyl can be optionally substituted with OH, NH 2 , nitro, CN, CON(R c ) 2 , COOR 11 , C 1 -C 6 alkoxy, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkyloxy, C 1 -C 6 hydroxyalkyl, C 1 -C 6 alkyl-C(═O)O—, C 1 -C 6 alkyl-C(═O)—, C 2 -C 6 alkynyl, halo group, hydroxyalkoxy, —SO 2 NR c R c , —NR c SO 2 R c , C 1 -C 6 alkylsulfonyl, C 1 -C 6 alkylamino or di(C 1 -C 6 )alkylamino;

R 9 is independently selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 8 cycloalkyl, aryl, heteroaryl, and heterocyclic, wherein the alkyl, cycloalkyl, aryl, heteroaryl, and heterocyclic can be optionally substituted with —C 0 -C 6 alkylOR c , C 0 -C 6 alkylN(R c ) 2 , COOR 10 , nitro, CN, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkyloxy, C 1 -C 6 hydroxyalkyl, C 2 -C 6 alkenyl, C 1 -C 6 alkyl-C(═O)O—, C 1 -C 6 alkyl-C(═O)—, C 2 -C 6 alkynyl, halo group, hydroxyalkoxy, —SO 2 NR c R c , —NR c SO 2 R c , C 1 -C 6 alkylsulfonyl, heterocylic, or C(O)NHR c ;

R 10 is independently selected from the group consisting of C 1 -C 6 alkyl, —(CR c 2 ) z C 3 -C 8 cycloalkyl, —(CR c 2 ) z -heteroaryl, —(CR c 2 ) z -aryl, and —(CR c 2 ) z -heterocyclic, wherein the heteroaryl, aryl, heterocyclic, cycloalkyl and alkyl can be optionally substituted with C 1 -C 6 alkyl, OH, halo, or haloC 1 -C 6 alkyl;

R 11 is independently selected from the group consisting of H, C 1 -C 6 alkyl, —(CR c 2 ) z C 3 -C 8 cycloalkyl, —(CR c 2 ) z heteroaryl, —(CR c 2 ) z aryl, and —(CR c 2 ) z heterocyclic wherein the heteroaryl, aryl, heterocyclic, cycloalkyl and alkyl can be optionally substituted with C 1 -C 6 alkyl, OH, halo, or haloC 1 -C 6 alkyl;

R 17 is independently selected from the group consisting of H, halo, C 1 -C 6 alkyl, —(CR c 2 ) z C 3 -C 8 cycloalkyl, —(CR c 2 ) z heteroaryl, —(CR c 2 ) z aryl, and —(CR c 2 ) z heterocyclic wherein the heteroaryl, aryl, heterocyclic, cycloalkyl and alkyl can be optionally substituted with C 1 -C 6 alkyl, OH, halo, or haloC 1 -C 6 alkyl;

R a is independently H, OR c , NH 2 , halo, alkyl, or alkenyl, wherein alkyl or alkenyl is optionally substituted with OH, C 1 -C 4 alkoxy, NH 2 , halo, haloC 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, or C 2 -C 4 alkenyl;

R c is independently H or C 1 -C 3 alkyl optionally substituted with C 2 -C 3 alkenyl, C 3 -C 6 cycloalkyl, C 1 -C 3 alkoxy, OH, halo, NH 2 , C 1 -C 3 alkylamino, or C 1 -C 3 dialkylamino;

T is independently C 2 -C 3 alkenyl, —(CR a 2 ) q —, —C(═CH 2 )—, —(CR a 2 ) q —C(═CH 2 )—, —C(═CH 2 )—(CR a 2 ) q —, —C(═NH)—, —(CR a 2 ) q —C(═NH)—, or —C(═NH)—(CR a 2 ) q —;

Y is a bond, —C(O)NR c —, —NR c (O)—, or —NR c —;

U is H, COOR 11 , 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 stereoisomer thereof;

or a pharmaceutically acceptable salt thereof;

or a pharmaceutically acceptable salt of the stereoisomer thereof.

2. The compound of claim 1 , wherein

R 1 is selected from the group consisting of COOR 11 , —C(O)NR c SO 2 N(R c ) 2 , —S(O)R c , —S(O) 2 R c , and nitrogen containing 5-membered heterocyclenyl or heteroaryl ring, wherein the 5-membered ring can be optionally substituted with OR c , SR c , NH 2 , nitro, CN, amide, COOR 11 , C 1 -C 6 haloalkyl, C 1 -C 6 haloalkyloxy, C 1 -C 6 hydroxyalkyl, C 2 -C 6 alkenyl, C 1 -C 6 alkyl-C(═O)O—, C 1 -C 6 alkyl-C(═O)—, C 2 -C 6 alkynyl, halo group, hydroxyalkoxy, —SO 2 NR c R c , —NR c SO 2 R c , C 1 -C 6 alkylsulfonyl, C 1 -C 6 alkylamino or di(C 1 -C 6 )alkylamino;

R 2 is selected from the group consisting of aryl, heteroaryl, W—(CR a R 9 )R 7 , and heterocyclic, wherein W is NR c or O, wherein the aryl, heteroaryl, and heterocyclic is optionally substituted with R 12 selected from the group consisting of halo, CN, haloC 1 -C 6 alkyl, C 1 -C 6 alkyl, —(CR a 2 )OR a , and —(CR a 2 )C(O)NR c R c , wherein the alkyl of R 12 can be optionally substituted with OH, CN, halo, haloC 1 -C 6 alkyl, or CON(R c ) 2 ;

R 3 is selected from the group consisting of H, aryl, heteroaryl, and heterocyclic, wherein the aryl, heteroaryl, and heterocyclic can be optionally substituted with halo, SH, OR c , haloC 1 -C 6 alkyl, haloC 1 -C 6 alkoxy, —(CR a 2 ) z CN, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, —(CR a 2 ) z C(O)OR 11 , —(CR a 2 ) z C(O)R 8 , —(CR a 2 ) z OR 8 , —(CR a 2 ) z NR c R 8 , —(CR a 2 ) z S(O) 2 R 8 , —(CR a 2 ) z C(O)NR c R 8 , —(CR a 2 ) z aryl, —(CR a 2 ) z heteroaryl, —(CR a 2 ) z C 3 -C 8 cycloalkyl, —(CR a 2 ) z heterocyclic, —(CR a 2 ) z SO 2 NR c R 8 , or —(CR a 2 ) z O(CR a 2 ) z Y(CR a 2 ) v U;

wherein alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocyclic can further be substituted with OH, halo, or C 2 -C 6 alkenyl;

R 4 is selected from the group consisting of —(CR a 2 )aryl, —(CR a 2 )heteroaryl, —(CR a 2 )heterocyclic, —(CR a 2 )C 3 -C 8 cycloalkyl, —(CR a 2 )cyclenyl, and —(CR a 2 )heterocyclenyl, wherein the aryl, heteroaryl, heterocyclic, cycloalkyl, cyclenyl, and heterocyclenyl can be optionally substituted with OH, SH, NH 2 , nitro, CN, CON(R c ) 2 , COOR 11 , C 1 -C 6 alkoxy, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, haloC 2 -C 6 alkenyl, C 2 -C 6 alkenyl, C 2 -C 6 alkenoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkyloxy, C 1 -C 6 hydroxyalkyl, C 1 -C 6 alkyl-C(═O)O—, C 1 -C 6 alkyl-C(═O)—, C 2 -C 6 alkynyl, halo group, hydroxyalkoxy, —SO 2 NR c R c , —NR c SO 2 R c , C 1 -C 6 alkylsulfonyl, C 1 -C 6 alkylamino or di(C 1 -C 6 )alkylamino;

R 7 is C 3 -C 8 cycloalkyl optionally substituted with halo, nitro, CN, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkyloxy, C 1 -C 6 alkyl, or —(CR a 2 ) z OR 5 ;

R 8 is independently selected from the group consisting of —(CR a 2 )-heteroaryl, —(CR a 2 )-aryl, —(CR a 2 )-heterocyclic, —(CR a 2 )-heterocyclenyl, —(CR a 2 )cyclenyl, —(CR a 2 )cycloalkyl, and C 1 -C 6 alkyl, wherein the heteroaryl, aryl, heterocyclic, heterocyclenyl, cyclenyl, cycloalkyl, and alkyl can be optionally substituted with OH, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkyloxy, C 1 -C 6 hydroxyalkyl, or halo group;

R 9 is H, C 1 -C 3 haloalkyl, or C 3 -C 4 cycloalkyl, wherein the alkyl or cycloalkyl can be optionally substituted with OR c , N(R c ) 2 , heterocyclic, C(O)NHCH 2 CH 2 OH, C(O)NH 2 , or C(O)NHC 1 -C 3 alkyl;

R 11 is independently selected from the group consisting of H and C 1 -C 6 alkyl, wherein alkyl can be optionally substituted with OH or halo;

R 17 is independently selected from the group consisting of H, C 1 -C 3 alkyl, and aryl, wherein the aryl, and alkyl can be optionally substituted with C 1 -C 6 alkyl, OH, halo, or haloC 1 -C 6 alkyl;

R a is independently H, OR c , NH 2 , halo, alkyl, or alkenyl, wherein alkyl or alkenyl is optionally substituted with OH, C 1 -C 4 alkoxy, NH 2 , F, CF 3 , C 3 -C 6 cycloalkyl, or C 2 -C 4 alkenyl;

R c is independently H or C 1 -C 3 alkyl optionally substituted with C 2 -C 3 alkenyl, C 3 -C 6 cycloalkyl, C 1 -C 3 alkoxy, OH, halo, NH 2 , C 1 -C 3 alkylamino, or C 1 -C 3 dialkylamino;

Y is a bond, —C(O)NR c —, —NR c C(O)—, or —NR c —;

U is H, COOR 11 , OH, heteroaryl or heterocyclic;

v is independently 1 or 2; and

z is independently 0, 1 or 2.

3. The compound of claim 1 , wherein

R 1 is selected from the group consisting of COOH and nitrogen containing 5-membered heteroaryl or heterocyclenyl ring, wherein the 5-membered ring can be optionally substituted with OR c , SR c , NH 2 , nitro, CN, amide, COOR 11 , C 1 -C 6 haloalkyl, C 1 -C 6 haloalkyloxy, C 1 -C 6 hydroxyalkyl, C 2 -C 6 alkenyl, C 1 -C 6 alkyl-C(═O)O—, C 1 -C 6 alkyl-C(═O)—, C 2 -C 6 alkynyl, halo group, hydroxyalkoxy, —SO 2 NR c R c , —NR c SO 2 R c , C 1 -C 6 alkylsulfonyl, C 1 -C 6 alkylamino or di(C 1 -C 6 )alkylamino.

4. The compound of claim 1 , wherein

R 2 is selected from the group consisting of aryl, heteroaryl, and —NR c —(CR a R 9 )R 7 , wherein the aryl, or heteroaryl is optionally substituted with R 12 selected from the group consisting of halo, CN, haloC 1 -C 6 alkyl, and C 1 -C 6 alkyl, —(CR a 2 )OR a , wherein the alkyl of R 12 can be optionally substituted with OH, CN, halo, haloC 1 -C 6 alkyl, or CON(R c ) 2 ;

R 4 is selected from the group consisting of —(CR a 2 )aryl, —(CR a 2 )C 3 -C 6 cycloalkyl, and —(CR a 2 )C 3 -C 6 cyclenyl, wherein the aryl, cycloalkyl, and cyclenyl can be optionally substituted with OH, SH, NH 2 , nitro, CN, CON(R c ) 2 , COOR 11 , C 1 -C 6 alkoxy, C 3 -C 6 cycloalkyl, haloC 2 -C 6 alkenyl, C 2 -C 6 alkenyl, C 2 -C 6 alkenoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkyloxy, C 1 -C 6 hydroxyalkyl, C 1 -C 6 alkyl-C(═O)O—, C 1 -C 6 alkyl-C(═O)—, C 2 -C 6 alkynyl, halo group, hydroxyalkoxy, —SO 2 NR c R c , —NR c SO 2 R c , C 1 -C 6 alkylsulfonyl, C 1 -C 6 alkylamino or di(C 1 -C 6 )alkylamino;

R 7 is C 3 -C 6 cycloalkyl optionally substituted with halo, nitro, CN, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkyloxy, C 1 -C 6 alkyl, or —(CR a 2 ) z OR 5 ;

R 9 is C 1 -C 3 alkyl;

R 17 is H;

and all other substituents are as defined in any one of claims 1 to 3 .

5. The compound of claim 1 , wherein R 1 is COOH and a nitrogen containing 5-membered heteroaryl, heterocyclyl or heterocyclenyl ring selected from the group consisting of tetrazolyl, oxadiazolyl, oxadiazolone, dihydro-oxadiazolyl, triazolyl, dihydro-triazolyl, dihydro-triazolone, pyrrolidinyl, and imidazolyl, wherein the nitrogen containing 5-membered ring can be optionally substituted with halo, C 1 -C 6 alkyl, haloC 1 -C 6 alkyl, NH 2 , OR c , SR c , COOH, or —NR c SO 2 R c .

6. The compound of claim 1 , wherein

R 1 is

wherein R d is CH 3 or H.

7. The compound of claim 1 , wherein

R 1 is

8. The compound of claim 1 , wherein R 2 is

R e is H, —(CR a 2 ) z C(O)OR 10 , halo, haloC 1 -C 3 alkyl or C 1 -C 3 alkyl;

K and L are independently CR 14 or N;

R 14 is independently H, halo, CN, haloC 1 -C 6 alkyl, C 1 -C 6 alkyl, —(CR a 2 ) z C(O)NR c R c , —(CR a 2 ) z OR a , —(CR a 2 ) z aryl, —(CR a 2 ) z heteroaryl, —(CR a 2 ) z heterocyclic, —(CR a 2 ) z C 3 -C 8 cycloalkyl, —(CR a 2 ) z cyclenyl, —(CR a 2 ) z heterocyclenyl, wherein the alkyl, aryl, heteroaryl, heterocyclic, cycloalkyl, cyclenyl or heterocyclenyl can be optionally substituted with OH, CN, halo, haloC 1 -C 3 alkyl, or CON(R c ) 2 ; and

h is 0 or 1.

9. The compound of claim 1 , wherein R 3 is H, -T-aryl or -T-heteroaryl, wherein the aryl or heteroaryl can be optionally substituted with halo, OR c , haloC 1 -C 6 alkyl, haloC 1 -C 6 alkoxy, —(CR a 2 ) z CN, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, wherein alkyl, alkenyl, or alkynyl can further be substituted with OH, NH 2 , nitro, CN, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkyloxy, C 1 -C 6 hydroxyalkyl, halo group, hydroxyalkoxy, C 1 -C 6 alkylsulfonyl, C 1 -C 6 alkylamino or di(C 1 -C 6 )alkylamino.

10. The compound of claim 1 , wherein R 3 is

X is NR 19 , CR 16 2 , S, or O;

R 15 is independently selected from the group consisting of phenyl, 5 or 6-membered heterocyclic or heteroaryl, haloC 1 -C 6 alkyl, halo, haloC 1 -C 6 alkoxy, C 1 -C 6 alkoxy, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 3 -C 6 cycloalkyl, CN, OH, and SH; two adjacent R 15 form a fused C 3 -C 7 cycloalkyl or heterocyclic ring; two non-adjacent R 15 form a C 1 -C 3 alkylene; or two R 15 attached to the same carbon form a C 3 -C 7 cycloalkyl or heterocyclic ring, wherein the phenyl, heteroaryl, cycloalkyl or hetrocyclic can be optionally substituted with R 13 selected from the group consisting of haloC 1 -C 6 alkyl, halo, haloC 1 -C 6 alkoxy, C 1 -C 6 alkoxy, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, amino, CN, OH, or SH;

R 16 is independently selected from the group consisting of H, haloC 1 -C 6 alkyl, halo, haloC 1 -C 6 alkoxy, C 1 -C 6 alkoxy, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, CN, OH, and SH;

R 19 is independently selected from the group consisting of H, haloC 1 -C 6 alkyl, C 1 -C 6 alkyl, and C 2 -C 6 alkenyl;

f is 0, 1 or 2;

g is 0, 1 or 2;

j is independently 0, 1, 2, 3, 4, 5, 6, 7, or 8.

11. The compound of claim 1 , wherein R 4 is —CH 2 —Y or —CH 2 (CH 3 )—Y, wherein Y is phenyl or cyclohexyl optionally substituted with haloC 1 -C 3 alkyl, haloC 2 -C 3 alkenyl, halo, C 3 -C 4 cycloalkyl, haloC 1 -C 3 alkoxy, C 1 -C 3 alkoxy, C 2 -C 3 alkenoxy, C 1 -C 3 alkyl, C 2 -C 3 alkenyl, amino, CN, OH, or SH.

12. The compound of claim 1 , wherein

R 4 is

R b and R s are independently H, halo, haloC 1 -C 3 alkyl or C 1 -C 3 alkyl;

R g is H, or methyl;

i and l are independently 0, 1, 2, 3, 4 or 5; and

e is 0 or 1.

13. The compound of claim 1 selected from the group consisting of:

(R)-4-((1-cyclobutylethyl) amino)-6-(2-fluoro-5-methylphenyl)-5-(4-(trifluoromethyl) benzyl)-5H-pyrrolo [3, 2-d] pyrimidine-2-carboxylic acid;

(R)-4-((1-cyclobutylethyl)amino)-7-(2-fluoro-5-methylphenyl)-5-(4-(trifluoromethyl)benzyl)-5H-pyrrolo[3,2-d]pyrimidine-2-carboxylic acid;

(R)-4-((1-cyclobutylethyl) amino)-6-(m-tolyl)-5-(4-(trifluoromethyl) benzyl)-5H-pyrrolo [3, 2-d] pyrimidine-2-carboxylic acid;

(R)-4-((1-cyclobutylethyl)amino)-7-methyl-6-(m-tolyl)-5-(4-(trifluoromethyl)benzyl)-5H-pyrrolo[3,2-d]pyrimidine-2-carboxylic acid;

4-{[(1R)-1-cyclobutylethyl]amino}-6-(2-methoxy-5-methylphenyl)-5-[4-(trifluoromethyl)benzyl]-5H-pyrrolo[3,2-d]pyrimidine-2-carboxylic acid;

6-(1-benzofuran-5-yl)-4-{[(1R)-1-cyclobutylethyl]amino}-5-[4-(trifluoromethyl)benzyl]-5H-pyrrolo[3,2-d]pyrimidine-2-carboxylic acid;

6-(2-chloro-5-methylphenyl)-4-{[(1R)-1-cyclobutylethyl]amino}-5-[4-(trifluoromethyl)benzyl]-5H-pyrrolo[3,2-d]pyrimidine-2-carboxylic acid;

7-(2-chloro-5-methylphenyl)-4-{[(1R)-1-cyclobutylethyl]amino}-5-[4-(trifluoromethyl)benzyl]-5H-pyrrolo[3,2-d]pyrimidine-2-carboxylic acid;

4-{[(1R)-1-cyclobutylethyl]amino}-6-(4-methylpyridin-2-yl)-5-[4-(trifluoromethyl)benzyl]-5H-pyrrolo[3,2-d]pyrimidine-2-carboxylic acid;

4-{[(1R)-1-cyclobutylethyl]amino}-6-[4-(1-methylethyl)pyridin-2-yl]-5-[4-(trifluoromethyl)benzyl]-5H-pyrrolo[3,2-d]pyrimidine-2-carboxylic acid;

4-{[(1R)-1-cyclobutylethyl]amino}-7-methyl-6-[4-(1-methylethyl)pyridin-2-yl]-5-[4-(trifluoromethyl)benzyl]-5H-pyrrolo[3,2-d]pyrimidine-2-carboxylic acid;

5-[2-amino-4-(trifluoromethyl)benzyl]-4-{[(1R)-1-cyclobutylethyl]amino}-6-(3-methylphenyl)-5H-pyrrolo[3,2-d]pyrimidine-2-carboxylic acid;

4-{[(1R)-1-cyclobutylethyl]amino}-6-(3-methylphenyl)-5-{[5-(trifluoromethyl)pyridin-2-yl]methyl}-5H-pyrrolo[3,2-d]pyrimidine-2-carboxylic acid;

4-{[(1R)-1-cyclobutylethyl]amino}-6-(3-methylphenyl)-5-[4-(trifluoromethoxy)benzyl]-5H-pyrrolo[3,2-d]pyrimidine-2-carboxylic acid;

4-{[(1R)-1-cyclobutylethyl]amino}-5-[3-fluoro-4-(trifluoromethoxy)benzyl]-6-(3-methylphenyl)-5H-pyrrolo[3,2-d]pyrimidine-2-carboxylic acid;

4-{[(1R)-1-cyclobutylethyl]amino}-5-[2-methoxy-4-(trifluoromethoxy)benzyl]-6-(3-methylphenyl)-5H-pyrrolo[3,2-d]pyrimidine-2-carboxylic acid;

4-{[(1R)-1-cyclobutylethyl]amino}-5-[4-(difluoromethoxy)benzyl]-6-(3-methylphenyl)-5H-pyrrolo[3,2-d]pyrimidine-2-carboxylic acid;

4-{[(1R)-1-cyclobutylethyl]amino}-5-[3-fluoro-4-(trifluoromethyl)benzyl]-6-(3-methylphenyl)-5H-pyrrolo[3,2-d]pyrimidine-2-carboxylic acid;

4-{[(1R)-1-cyclobutylethyl]amino}-5-(4-methoxybenzyl)-6-(3-methylphenyl)-5H-pyrrolo[3,2-d]pyrimidine-2-carboxylic acid;

5-(4-chloro-3-fluorobenzyl)-4-{[(1R)-1-cyclobutylethyl]amino}-6-(3-methylphenyl)-5H-pyrrolo[3,2-d]pyrimidine-2-carboxylic acid;

4-{[(1R)-1-cyclobutylethyl]amino}-5-[4-(difluoromethyl)benzyl]-6-(3-methylphenyl)-5H-pyrrolo[3,2-d]pyrimidine-2-carboxylic acid;

4-{[(1R)-1-cyclobutylethyl]amino}-6-(3-methylphenyl)-5-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5H-pyrrolo[3,2-d]pyrimidine-2-carboxylic acid;

5-(4-bromo-3-fluorobenzyl)-4-{[(1R)-1-cyclobutylethyl]amino}-6-(3-methylphenyl)-5H-pyrrolo[3,2-d]pyrimidine-2-carboxylic acid;

4-{[(1R)-1-cyclobutylethyl]amino}-5-(3,4-difluorobenzyl)-6-(3-methylphenyl)-5H-pyrrolo[3,2-d]pyrimidine-2-carboxylic acid; and

4-{[(1R)-1-cyclobutylethyl]amino}-5-(3-fluoro-4-methylbenzyl)-6-(3-methylphenyl)-5H-pyrrolo[3,2-d]pyrimidine-2-carboxylic acid;

or a stereoisomer thereof;

or a pharmaceutically acceptable salt thereof;

or a pharmaceutically acceptable salt of the stereoisomer thereof.

14. The compound of claim 1 selected from the group consisting of:

4-(3-chlorophenyl)-5-[(trans-4-methylcyclohexyl)methyl]-5H-pyrrolo[3,2-d]pyrimidine-2-carboxylic acid;

3-{4-(3-chlorophenyl)-5-[(trans-4-methylcyclohexyl)methyl]-5H-pyrrolo[3,2-d]pyrimidin-2-yl}-1,2,4-oxadiazol-5(4H)-one;

4-(5-chloropyridin-3-yl)-5-[(trans-4-methylcyclohexyl)methyl]-5H-pyrrolo[3,2-d]pyrimidine-2-carboxylic acid;

3-{4-(5-chloropyridin-3-yl)-5-[(trans-4-methylcyclohexyl)methyl]-5H-pyrrolo[3,2-d]pyrimidin-2-yl}-1,2,4-oxadiazol-5(4H)-one;

5-{4-(5-chloropyridin-3-yl)-5-[(trans-4-methylcyclohexyl)methyl]-5H-pyrrolo[3,2-d]pyrimidin-2-yl}-1,3,4-oxadiazol-2(3H)-one;

4-(3-chlorophenyl)-7-methyl-5-[(trans-4-methylcyclohexyl)methyl]-5H-pyrrolo[3,2-d]pyrimidine-2-carboxylic acid;

3-{4-(3-chlorophenyl)-7-methyl-5-[(trans-4-methylcyclohexyl)methyl]-5H-pyrrolo[3,2-d]pyrimidin-2-yl}-1,2,4-oxadiazol-5(4H)-one;

4-(5-chloropyridin-3-yl)-7-methyl-5-[(trans-4-methylcyclohexyl)methyl]-5H-pyrrolo[3,2-d]pyrimidine-2-carboxylic acid;

3-{4-(5-chloropyridin-3-yl)-7-methyl-5-[(trans-4-methylcyclohexyl)methyl]-5H-pyrrolo[3,2-d]pyrimidin-2-yl}-1,2,4-oxadiazol-5(4H)-one;

4-(5-chloropyridin-3-yl)-5-[(trans-4-methylcyclohexyl)methyl]-7-phenyl-5H-pyrrolo[3,2-d]pyrimidine-2-carboxylic acid;

5-{7-benzyl-4-(5-chloropyridin-3-yl)-5-[(trans-4-methylcyclohexyl)methyl]-5H-pyrrolo[3,2-d]pyrimidin-2-yl}-1,3,4-oxadiazol-2(3H)-one;

4-(5-chloropyridin-3-yl)-5-[(trans-4-methylcyclohexyl)methyl]-7-(2-methylpropyl)-5H-pyrrolo[3,2-d]pyrimidine-2-carboxylic acid;

3-[4-(5-chloropyridin-3-yl)-5-[(trans-4-methylcyclohexyl)methyl]-7-(2-methylpropyl)-5H-pyrrolo[3,2-d]pyrimidin-2-yl]-1,2,4-oxadiazol-5(4H)-one;

4-(5-chloropyridin-3-yl)-5-[(trans-4-methylcyclohexyl)methyl]-7-(2-pyridin-3-ylethyl)-5H-pyrrolo[3,2-d]pyrimidine-2-carboxylic acid;

3-[4-(5-chloropyridin-3-yl)-5-[(trans-4-methylcyclohexyl)methyl]-7-(2-pyridin-3-ylethyl)-5H-pyrrolo[3,2-d]pyrimidin-2-yl]-1,2,4-oxadiazol-5(4H)-one;

3-[4-(5-chloropyridin-3-yl)-5-[(trans-4-methylcyclohexyl)methyl]-7-(pyridin-3-ylmethyl)-5H-pyrrolo[3,2-d]pyrimidin-2-yl]-1,2,4-oxadiazol-5(4H)-one;

4-(5-chloropyridin-3-yl)-6-[fluoro(2-fluorophenyl)methyl]-5-[(trans-4-methylcyclohexyl)methyl]-5H-pyrrolo[3,2-d]pyrimidine-2-carboxylic acid;

3-{4-(5-chloropyridin-3-yl)-6-[fluoro(2-fluorophenyl)methyl]-5-[(trans-4-methylcyclohexyl)methyl]-5H-pyrrolo[3,2-d]pyrimidin-2-yl}-1,2,4-oxadiazol-5 (4H)-one;

4-(5-chloropyridin-3-yl)-6-[(1R or S)-1-fluoro-1-(3-fluoropyridin-2-yl)ethyl]-5-[(trans-4-methylcyclohexyl)methyl]-5H-pyrrolo[3,2-d]pyrimidine-2-carboxylic acid; and

3-{4-(5-chloropyridin-3-yl)-6-[(1R or S)-1-fluoro-1-(3-fluoropyridin-2-yl)ethyl]-5-[(trans-4-methylcyclohexyl)methyl]-5H-pyrrolo[3,2-d]pyrimidin-2-yl}-1,2,4-oxadiazol-5(4H)-one;

or a stereoisomer thereof;

or a pharmaceutically acceptable salt thereof;

or a pharmaceutically acceptable salt of the stereoisomer thereof.

15. A pharmaceutical composition comprising a therapeutically effective amount of at least one compound of claim 1 or a pharmaceutically acceptable salt thereof, in combination with at least one pharmaceutically acceptable carrier.