IP Library › Granted Patent US 9,540,377

Granted Patent B2

US 9,540,377 · App. 14/762,827 · Granted Jan 10, 2017

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

Inventors: Carolyn Michele Cammarano (West Caldwell, NJ); Matthew P. Christopher (Brookline, MA); Christopher Dinsmore (Newton, MA); Ronald J. Doll (Convent Station, NJ); Francesc Xavier Fradera Llinas (Brookline, MA); Chaomin Li (Boston, MA); Michelle Machacek (Brookline, MA); Michelle Martinez (Watertown, MA); Latha G. Nair (Edison, NJ); Weidong Pan (Somerset, NJ); Michael Hale Reutershan (Brighton, MA); Manami Shizuka (Lexington, MA); Dietrich P. Steinhuebel (Boston, MA); Binyuan Sun (Boston, MA); Christopher Francis Thompson (Arlington, MA); B. Wesley Trotter (Medfield, MA); Yaolin Wang (Short Hills, NJ); Liping Yang (Arlington, MA); Stephane L. Bogen (Somerset, NJ); Matthew E. Voss (Ville De West, SG); Jagannath Panda (Singapore Science Park II, SG); Anthappan Tony Kurissery (Singapore Science Park II, SG)

Assignee: Merck Sharp & Dohme Corp.

C07D473/00 C07D473/16 C07D473/30 C07D473/34

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Quick Facts

Patent No.: US 9,540,377
App. No.: 14/762,827
Granted: Jan 10, 2017
Kind: B2

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Abstract

The present invention provides 2,6,7,8 Substituted Purines as described herein or a pharmaceutically acceptable salt thereof. The representative compounds are useful as inhibitors of the HDM2 protein. Also disclosed are pharmaceutical compositions comprising the above compounds and potential methods of treating cancer using the same.

Claims (1355)

1. A compound represented by Formula I:

Wherein

R 1 is selected from the group consisting of C 1 -C 6 alkyl, —(CR a 2 ) n COOR 11 , —(CR a 2 ) n NR 5 SO 2 R 6 , —(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 C(O)R 5 , —(CR a 2 ) n CONR 5 R 6 , —(CR a 2 ) n CONR 5 SO 2 R 6 , —(CR a 2 ) n CONR 5 OR 6 , —(CR a 2 ) n OR 5 , —(CR a 2 ) n S(O)R c , —(CR a 2 ) n S(O) 2 R c , 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 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, C 3 -C 8 cycloalkyl, —W—(CR a R 9 ) t R 7 , and heterocyclic, wherein W is NR c or O, wherein the aryl, heteroaryl, cycloalkyl or 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 ) z OR 8 , —(CR a 2 ) z NHR 8 , —(CR a 2 ) z C(O)NR c R c , —(CR a 2 ) z COOR 10 , —(CR a 2 ) z S(O) 2 R c , —(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 —(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-C 1 -C 6 alkyl, C 2 -C 6 alkenyl, -T-aryl, -T-heteroaryl, -T-heterocyclic, -T-C 3 -C 8 cycloalkyl, -T-cyclenyl, and -T-heterocyclenyl,

wherein the alkyl, alkenyl, aryl, heteroaryl, heterocyclic, cycloalkyl, cyclenyl and heterocyclenyl can be optionally substituted with halo, SR c , 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 10 , —(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 D(CR a 2 ) v Q, said alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heterocyclic, heterocyclenyl and cyclenyl can further be optionally substituted with SH, OH, NH 2 , nitro, CN, CON(R) 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 10 , 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 H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 3 -C 8 cycloalkyl, aryl, heteroaryl, and heterocyclic, wherein the alkyl, alkenyl, cycloalkyl, aryl, heteroaryl or heterocyclic 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 R 6 , —(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)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 2 ) 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 C 3 -C 8 cycloalkyl, and C 1 -C 6 alkyl, wherein the heteroaryl, aryl, heterocyclic, heterocyclenyl, cyclenyl, cycloalkyl, and alkyl can be optionally substituted with OH, —N(R c ) 2 , 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 3 -C 6 cycloalkyl, 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 1 -C 6 alkylsulfonyl, C 1 -C 6 alkylamino, di(C 1 -C 6 )alkylamino, heteroaryl, aryl, heterocyclic, heterocyclenyl, or cyclenyl;

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) 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 a is independently H, OR c , NH 2 , halo, C 1 -C 3 alkyl, or C 2 -C 4 alkenyl, said 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 —;

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

Q is H, COOR 10 , 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.

2. The compound of claim 1 , wherein

R 2 is selected from the group consisting of aryl, heteroaryl, —W—(CR a R 9 ) t R 7 , and heterocyclic, wherein W is NR c or O, wherein the aryl, heteroaryl, or 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 ) z OR c , —(CR a 2 ) z NHR 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 —(CR a 2 ) q NR c R 8 , —(CR a 2 ) q OR, —(CR a 2 ) q SR 8 , —(CR a 2 ) q C(O)R 8 , —(CR a 2 ) q S(O)R, —(CR a 2 ) q S(O) 2 R, —(CR a 2 ) q CONR c R 8 , —(CR a 2 ) q NR c C(O)R 8 , -T-C 1 -C 6 alkyl, C 2 -C 6 alkenyl, -T-aryl, -T-heteroaryl, -T-heterocyclic, -T-C 3 -C 8 cycloalkyl, -T-cyclenyl, and -T-heterocyclenyl,

wherein the alkyl, alkenyl, aryl, heteroaryl, heterocyclic, cycloalkyl, cyclenyl and heterocyclenyl can be optionally substituted with halo, OR c , SH, 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 10 , —(CR a 2 ) z C(O)R, —(CR a 2 ) z OR, —(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 D(CR a 2 ) v Q, said alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heterocyclic, heterocyclenyl and cyclenyl can further be optionally 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 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 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;

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

Q is H, COOR 10 , 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.

3. The compound of claim 2 , wherein

R 1 is selected from the group consisting of C 1 -C 6 alkyl, COOR 11 , —NR c SO 2 R c , —SO 2 NR c R c , —C(O)NR c SO 2 N(R c ) 2 , —C(O)R c , —CONR c R c , —CONR c OR c , —CONR c SO 2 R c , —OR, —S(O)R c , —S(O) 2 R c , and nitrogen containing 5-membered heteroaryl, heterocyclic and heterocyclenyl ring, wherein the alkyl and 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 )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 c , 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 —NR c R 8 , —OR 8 , —SR 8 , —C(O)R 8 , —S(O)R 8 , —S(O) 2 R 8 , —CONR c R 8 , —NR c C(O)R 8 , -T-C 1 -C 6 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, OR c , SH, 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 10 , —(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 D(CR a 2 ) v Q,

said alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocyclic can further be optionally substituted with OH, SH, 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 10 , 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 selected from the group consisting of C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, heteroaryl, aryl, and heterocyclic, wherein the alkyl, cycloalkyl, heteroaryl, aryl or heterocyclic can be 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 c ;

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, N(R c ) 2 , C 1 -C 6 alkoxy, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, 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 alkyl, C 1 -C 3 haloalkyl, 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 10 is independently C 1 -C 6 alkyl optionally substituted with OH, halo, or haloC 1 -C 6 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 a is independently H, OR c , NH 2 , halo, C 1 -C 3 alkyl, or C 2 -C 4 alkenyl, said 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;

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

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

Q is H, COOR 10 , OH, heteroaryl or heterocyclic;

q is independently 0 or 1;

v is independently 1 or 2; and

z is independently 0, 1 or 2.

4. The compound of claim 2 , wherein

R 1 is selected from the group consisting of COOR 11 , —NR c SO 2 R c , —SO 2 NR c R c , —C(O)NR c SO 2 N(R c ) 2 , C(O)NR c SO 2 R c , —C(O)R c , —CONR c R c , —CONR c OR c , —OR c , —S(O)R c , —S(O) 2 R c , and nitrogen containing 5-membered heterocyclic, heteroaryl and heterocyclenyl ring, wherein the 5-membered ring can be optionally substituted with OR c , SR c , NH 2 , nitro, CN, amide, COOR 1 1, 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, 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, C 1 -C 6 alkyl, —(CR a 2 )OR 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 —NR c R 8 , -T-heteroaryl, and -T-heterocyclic, wherein the heteroaryl, and heterocyclic can be optionally substituted with halo, OR c , SH, 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 10 , —(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 D(CR a 2 ) v Q;

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

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 10 , 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 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 c ;

R 9 is C 1 -C 3 alkyl;

and all other substituents are as defined in claim 2 .

5. The compound of claim 2 , wherein R 1 is COOH or a nitrogen containing 5-membered heteroaryl, heterocyclic 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 2 , wherein

R 1 is COOH,

wherein R d is CH 3 or H.

7. The compound of claim 2 , 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 c , —(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) 2 ; and

h is 0 or 1.

8. The compound of claim 2 , wherein R 3 is -T-heterocyclic or -T-heteroaryl, wherein the heterocyclic or heteroaryl can be optionally substituted with halo, OR c , SH, haloC 1 -C 6 alkyl, haloC 1 -C 6 alkoxy, CN, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, —(CR a 2 ) z C(O)OR 10 , —(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 D(CR a 2 ) v Q;

said alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocyclic can further be optionally substituted with OH, SH, halo, or C 2 -C 6 alkenyl.

9. The compound of claim 2 , wherein R 3 is

X is NR 19 , CR 16 2 , S, S(O) 2 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, haloC 2 -C 6 alkenyl, halo, C(O)R c , S(O) 2 R c , haloC 1 -C 6 alkoxy, C 1 -C 6 alkoxy, C 1 -C 6 alkoxyC 1 -C 6 alkyl, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 3 -C 6 cycloalkyl, amino, 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 heterocyclic can be optionally substituted with R 13 selected from the group consisting of haloC 1 -C 6 alkyl, haloC 2 -C 6 alkenyl, halo, haloC 1 -C 6 alkoxy, C 1 -C 6 alkoxy, C 1 -C 6 alkoxyC 1 -C 6 alkyl, 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, haloC 2 -C 6 alkenyl, halo, haloC 1 -C 6 alkoxy, C 1 -C 6 alkoxy, C 1 -C 6 alkoxyC 1 -C 6 alkyl, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, amino, CN, OH, and SH;

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

10. The compound of claim 2 , wherein R 3 is

Ring B is a fused C 3 -C 7 cycloalkyl;

X is CR 16 2 , S, or O;

R 13 , R 15 and R 16 are independently haloC 1 -C 6 alkyl, haloC 2 -C 6 alkenyl, halo, haloC 1 -C 6 alkoxy, C 1 -C 6 alkoxy, C 1 -C 6 alkoxyC 1 -C 6 alkyl, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 2 -C 6 alkenyl, amino, CN, OH, or SH;

r is independently 0, 1, 2, 3, 4, 5, 6, 7 or 8; and

j is independently 0, 1, 2, 3, or 4.

11. The compound of claim 2 , wherein R 3 is

X is CH 2 or O;

R 18 and R 20 are independently H, haloC 1 -C 6 alkyl, haloC 2 -C 6 alkenyl, halo, haloC 1 -C 6 alkoxy, C 1 -C 6 alkoxy, C 1 -C 6 alkoxyC 1 -C 6 alkyl, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 2 -C 6 alkenyl, C 3 -C 6 alkyl, amino, CN, OH, or SH; and

f is 0, 1 or 2.

12. The compound of claim 2 , wherein R 4 is —CH 2 -E or —CH 2 (CH 3 )-E, wherein E is phenyl, cyclopentyl, cyclopentenyl, cyclohexyl or cyclohexenyl 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.

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

(R)-6-((1-cyclobutylethyl)amino)-8-(5-(dimethylamino)-2-(trifluoromethoxy)phenyl)-7-(4-(trifluoromethyl)benzyl)-7H-purine-2-carboxylic acid;

(R)-8-(2-chloro-5-ethylphenyl)-6-((1-cyclobutylethyl)amino)-7-(4-(trifluoromethyl) benzyl)-7H-purine-2-carboxylic acid;

(R)-6-((1-cyclobutylethyl)amino)-7-(3-fluoro-4-(trifluoromethyl)benzyl)-8-(5-isopropyl-2-(trifluoromethoxy)phenyl)-7H-purine-2-carb oxylic acid;

(R)-6-((1-cyclobutylethyl)amino)-8-(2-isopropylpyridin-4-yl)-7-(4-(trifluoromethyl)benzyl)-7H-purine-2-carboxylic acid;

(R)-6-((1-cyclobutylethyl)amino)-8-(6-methyl-4-(prop-1-en-2-yl)pyridin-2-yl)-7-(4-(trifluoromethyl)benzyl)-7H-purine-2-carboxylic acid;

7-(4-chloro-3-fluorobenzyl)-6-{[(1R)-1-cyclobutylethyl]amino}-8-[4-(propan-2-yl)pyridin-2-yl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[4-(propan-2-yl)pyridin-2-yl]-7-{[5-(trifluoromethyl)thiophen-2-yl]methyl}-7H-purine-2-carboxylic acid;

6-(((R)-1-cyclobutylethyl)amino)-8-(4-(hydroxy(phenyl)methyl)pyridin-2-yl)-7-(4-(trifluoromethyl)benzyl)-7H-purine-2-carboxylic acid;

(R)-8-(4-benzylpyridin-2-yl)-6-((1-cyclobutylethyl)amino)-7-(4-(trifluoromethyl)benzyl)-7H-purine-2-carboxylic acid;

(R)-6-((1-cyclobutylethyl)amino)-8-(5-fluoro-4-isopropylpyridin-2-yl)-7-(4-(trifluoromethyl)benzyl)-7H-purine-2-carboxylic acid;

(R)-6-((1-cyclobutylethyl)amino)-8-(2-hydroxy-5-isopropylphenyl)-7-(4-(trifluoromethyl)benzyl)-7H-purine-2-carboxylic acid;

(R)-6-((1-cyclobutylethyl)amino)-8-(2-ethoxy-5-isopropylphenyl)-7-(4-(trifluoromethyl)benzyl)-7H-purine-2-carboxylic acid;

(R)-6-((1-cyclobutylethyl)(methyl)amino)-7-(3-fluoro-4-(trifluoromethyl)benzyl)-8-(4-isopropylpyridin-2-yl)-7H-purine-2-carboxylic acid;

8-(4-(sec-butyl)pyridin-2-yl)-6-(((R)-1-cyclobutylethyl)amino)-7-(4-(trifluoromethyl)benzyl)-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-pyridin-2-yl-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(4-methylpyridin-2-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(3-methylpyridin-2-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(6-methylpyridin-2-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(5-methoxypyridin-2-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(3,6-dimethylpyridin-2-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[4-(1-methylethyl)pyridin-2-yl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(3-methoxy-6-methylpyridin-2-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[4-(methylsulfonyl)phenyl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-(7-methylquinolin-6-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(4-phenylpyridin-2-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[4-(1-hydroxy-1-methylethyl)pyridin-2-yl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[4-(1-hydroxyethyl)pyridin-2-yl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(5-ethyl-2-hydroxyphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[2-(methoxymethoxy)-5-(1-methylethyl)phenyl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(5-ethyl-2-methoxyphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(2-ethoxy-5-ethylphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[2-ethoxy-5-(trifluoromethyl)phenyl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[2-methoxy-5-(trifluoromethyl)phenyl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[5-ethyl-2-(methoxymethoxy)phenyl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

8-(3-carbamoylphenyl)-6-{[(1R)-1-cyclobutylethyl]amino}-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[2-fluoro-5-(trifluoromethyl)phenyl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[5-(dimethylamino)-2-methylphenyl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(5-ethyl-2-fluorophenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[2-methoxy-5-(1-methylethyl)phenyl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[5-(dimethylamino)-2-hydroxyphenyl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(4-ethoxypyridin-2-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

8-(4-chloropyridin-2-yl)-6-{[(1R)-1-cyclobutylethyl]amino}-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[4-(cyclobutyloxy)pyridin-2-yl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[4-(difluoromethyl)pyridin-2-yl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[4-(dimethylamino)pyridin-2-yl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[4-(3-methyl-1H-pyrazol-1-yl)pyridin-2-yl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-7-[3-fluoro-4-(trifluoromethyl)benzyl]-8-[4-(1-methylethyl)pyridin-2-yl]-7H-purine-2-carboxylic acid;

6-{[(1 S)-1-cyclobutylethyl]amino}-8-[4-(1-methylethyl)pyridin-2-yl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(4-cyclopropylpyridin-2-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[5-(1-methylethyl)-2-(trifluoromethoxy)phenyl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

8-(4-tert-butylpyridin-2-yl)-6-{[(1R)-1-cyclobutylethyl]amino}-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(4-cyclobutylpyridin-2-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(4-cyclopentylpyridin-2-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(4-cyclohexylpyridin-2-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(4-thiophen-2-ylpyridin-2-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[4-(cyclohexyloxy)pyridin-2-yl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[4-(1-methylethoxy)pyridin-2-yl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-7-[4-(trifluoromethyl)benzyl]-8-[4-(trifluoromethyl)pyridin-2-yl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(2,3-dihydro-1H-isoindol-4-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-isoquinolin-3-yl-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(6-phenylpyridin-2-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

8-[4,6-bis(difluoromethyl)pyridin-2-yl]-6-{[(1R)-1-cyclobutylethyl]amino}-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[5-(1,3-dioxolan-2-yl)pyridin-2-yl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[5-(difluoromethoxy)pyridin-2-yl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(4-methoxypyridin-2-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(4-propylpyridin-2-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(4-ethylpyridin-2-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[6-(1-methylethyl)pyridin-2-yl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-7-[3-fluoro-4-(trifluoromethoxy)benzyl]-8-[4-(1-methylethyl)pyridin-2-yl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[4-(1-methylethyl)pyridin-2-yl]-7-[4-(trifluoromethoxy)benzyl]-7H-purine-2-carb oxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-isoquinolin-1-yl-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(4-methoxy-3-methylpyridin-2-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(3-phenylpyridin-2-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

8-(4-tert-butylpyridin-2-yl)-6-{[(1R)-1-cyclobutylethyl]amino}-7-[3-fluoro-4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(4-cyclopropylpyridin-2-yl)-7-[3-fluoro-4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(4-cyclobutylpyridin-2-yl)-7-[3-fluoro-4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(4-ethylpyridin-2-yl)-7-[3-fluoro-4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-7-[3-fluoro-4-(trifluoromethyl)benzyl]-8-(4-propylpyridin-2-yl)-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[5-(1-methylethyl)pyridin-3-yl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(3-fluoro-4-methylpyridin-2-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-7-[3-fluoro-4-(trifluoromethoxy)benzyl]-8-[5-(1-methylethyl)-2-(trifluoromethoxy)phenyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[5-methyl-2-(trifluoromethoxy)phenyl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[4-(2-methylpropyl)pyridin-2-yl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[5-methyl-4-(1-methylethyl)pyridin-2-yl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[3-methyl-4-(1-methylethyl)pyridin-2-yl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[4-(3,3-dimethylbutyl)pyridin-2-yl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[4-(2-cyclopropylethyl)pyridin-2-yl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-7-[3-fluoro-4-(trifluoromethoxy)benzyl]-8-[5-methyl-4-(1-methylethyl)pyridin-2-yl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-7-[3-fluoro-4-(trifluoromethoxy)benzyl]-8-[3-methyl-4-(1-methylethyl)pyridin-2-yl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-7-[3-fluoro-4-(trifluoromethyl)benzyl]-8-[5-methyl-4-(1-methylethyl)pyridin-2-yl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[6-methyl-4-(1-methylethyl)pyridin-2-yl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(1,3-dimethyl-1H-pyrazol-5-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(1,5-dimethyl-1H-pyrazol-4-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-phenyl-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-(4-morpholin-4-ylphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-[3-(1-methylethoxy)phenyl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(2,5-dimethylphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[4-(difluoromethoxy)phenyl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[4-(1-hydroxyethyl)phenyl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(3-fluoro-4-methylphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(5-fluoro-2-methylphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(3-fluoro-4-methoxyphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(4-methoxy-3-methylphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-quinoxalin-6-yl-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[3-(1H-pyrrol-1-yl)phenyl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(1-methyl-1H-indol-5-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

8-biphenyl-4-yl-6-{[(1R)-1-cyclobutylethyl]amino}-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(4-cyclohexylphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(2-methylquinolin-6-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(2-fluorobiphenyl-4-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[4-(dimethylamino)phenyl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

8-(4-tert-butylphenyl)-6-{[(1R)-1-cyclobutylethyl]amino}-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

8-[4-chloro-3-(trifluoromethyl)phenyl]-6-{[(1R)-1-cyclobutylethyl]amino}-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[4-(cyclopropylcarbonyl)phenyl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

8-(1-benzofuran-5-yl)-6-{[(1R)-1-cyclobutylethyl]amino}-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-(2-methylpyridin-4-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(2-methoxy-5-methylphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

8-(2-chloro-5-methylphenyl)-6-{[(1R)-1-cyclobutylethyl]amino}-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(2,3-dihydro-1-benzofuran-5-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-7-[4-(trifluoromethyl)benzyl]-8-[6-(trifluoromethyl)pyridin-2-yl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(3-methoxy-5-methylphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

8-(4-chloro-3-methoxyphenyl)-6-{[(1R)-1-cyclobutylethyl]amino}-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(4-methyl-3,4-dihydro-2H-1,4-benzoxazin-7-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(2,3-dimethylphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[3-(1-methylethoxy)phenyl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(3,5-di-tert-butylphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[2-methyl-4-(trifluoromethoxy)phenyl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[3-(phenylamino)phenyl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(3,5-dimethylphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

8-(5-chloro-2-methylphenyl)-6-{[(1R)-1-cyclobutylethyl]amino}-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(6-methoxynaphthalen-2-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(4-methoxy-3,5-dimethylphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-7-[4-(trifluoromethyl)benzyl]-8-[3-(trifluoromethyl)pyridin-2-yl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(2-fluoro-4-methoxyphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(4-fluoro-3-methylphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(2-ethoxy-5-methylphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

(R)-6-((1-cyclobutylethyl)amino)-8-(3-methoxyphenyl)-7-(4-(trifluoromethyl)benzyl)-7H-purine-2-carboxylic acid;

(R)-6-((1-cyclobutylethyl)amino)-8-(4-cyclopropyl-2-methylphenyl)-7-(4-(trifluoromethyl)benzyl)-7H-purine-2-carboxylic acid;

(R)-8-benzyl-6-((1-cyclobutylethyl)amino)-7-(4-(trifluoromethyl)benzyl)-7H-purine-2-carboxylic acid;

(R)-6-((1-cyclobutylethyl)amino)-8-cyclohexyl-7-(4-(trifluoromethyl)benzyl)-7H-purine-2-carboxylic acid;

7-(4-chlorobenzyl)-8-(3-chlorophenyl)-6-{[(1R)-1-cyclopropylethyl]amino}-7H-purine-2-carboxylic acid;

7-(4-chlorobenzyl)-6-{[(1R)-1-cyclopropylethyl]amino}-8-(3-methylphenyl)-7H-purine-2-carboxylic acid;

8-(1-benzothiophen-5-yl)-7-(4-chlorobenzyl)-6-{[(1R)-1-cyclopropylethyl]amino}-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-(3-methylphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

7-(4-chlorobenzyl)-8-(4-chlorophenyl)-6-{[(1R)-1-cyclopropylethyl]amino}-7H-purine-2-carboxylic acid;

8-(1-benzothiophen-5-yl)-7-(4-chlorobenzyl)-6-{[(1R)-1-cyclobutylethyl]amino}-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(3-methylphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

7-(4-chlorobenzyl)-6-{[(1R)-1-cyclopropylethyl]amino}-8-(2,5-dimethylphenyl)-7H-purine-2-carboxylic acid;

7-(4-chlorobenzyl)-6-{[(1R)-1-cyclopropylethyl]amino}-8-(4-fluoro-3-methylphenyl)-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-(3-methoxyphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-(3-ethoxyphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-(3-ethylphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(3-ethoxyphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-[3-(1-methylethyl)phenyl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

8-(3-tert-butylphenyl)-6-{[(1R)-1-cyclopropylethyl]amino}-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino)}-7-[4-(trifluoromethyl)benzyl]-8-[4-(trifluoromethyl)phenyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-(4-methoxyphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

8-(3-chlorophenyl)-6-{[(1R)-1-cyclopropylethyl]amino}-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(3-ethylphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[3-(1-methylethyl)phenyl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

8-(3-tert-butylphenyl)-6-{[(1R)-1-cyclobutylethyl]amino}-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-[3-(trifluoromethoxy)phenyl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-[4-(trifluoromethoxy)phenyl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-(3,5-dimethoxyphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-[3-(dimethylamino)phenyl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-(2-methylphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-(3,4-dichlorophenyl)-7-[4-(trifluorometethyl)benzyl]-7H-purine-2-carboxylic acid;

8-(4-tert-butylphenyl)-6-{[(1R)-1-cyclopropylethyl]amino}-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-(4-methylphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-[2-(trifluoromethoxy)phenyl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-(1-methyl-1H-pyrazol-4-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-(6-methylpyridin-3-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[3-(dimethylamino)phenyl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-7-[4-(trifluoromethyl)benzyl]-8-[3-(trifluoromethyl)phenyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[3-(trifluoromethoxy)phenyl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

8-(3-chlorophenyl)-6-{[(1R)-1-cyclobutylethyl]amino}-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[4-(methylsulfamoyl)phenyl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

7-(4-chlorobenzyl)-8-cyclopropyl-6-{[(1R)-1-cyclopropylethyl]amino}-7H-purine-2-carboxylic acid;

8-benzyl-7-(4-chlorobenzyl)-6-{[(1R)-1-cyclopropylethyl]amino}-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-pyridin-3-yl-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

8-(3-cyanophenyl)-6-{[(1R)-1-cyclobutylethyl]amino}-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

8-(5-chloro-6-methoxypyridin-3-yl)-6-{[(1R)-1-cyclobutylethyl]amino}-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(2-fluorophenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-(6-methoxypyridin-3-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-(5-fluoro-6-methoxypyridin-3-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-(3,5-dimethylphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-(5-fluoro-6-hydroxypyridin-3-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-(2,4-dimethylphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

8-(4-chloro-3-fluorophenyl)-6-{[(1R)-1-cyclopropylethyl]amino}-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-[2-methyl-4-(trifluoromethoxy)phenyl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

8-(2-chlorophenyl)-6-{[(1R)-1-cyclopropylethyl]amino}-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-(3-fluorophenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

8-(4-cyanophenyl)-6-{[(1R)-1-cyclopropylethyl]amino}-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-(2,4-dichlorophenyl)-7-[4-(trifluorometethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-(2,3-dimethylphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-naphthalen-2-yl-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

8-(3-chloro-4-fluorophenyl)-6-{[(1R)-1-cyclobutylethyl]amino}-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-(2,6-dimethylphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(2,5-dichlorophenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

8-(3-cyano-5-methoxyphenyl)-6-{[(1R)-1-cyclobutylethyl]amino}-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-(2-fluoro-3-methylphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

8-(3-chloro-4-methoxyphenyl)-6-{[(1R)-1-cyclopropylethyl]amino}-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[3-(difluoromethoxy)phenyl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(2,4-difluorophenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-quinolin-6-yl-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-[2-(dimethylamino)pyrimidin-5-yl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-(2-methoxypyridin-4-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-(6-ethoxypyridin-3-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-(2,3-difluorophenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-(2,3-dihydro-1H-inden-5-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

8-(4-bromo-2-fluorophenyl)-6-{[(1R)-1-cyclopropylethyl]amino}-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(3,4-dichlorophenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-pyridin-4-yl-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

8-(2-carbamoylphenyl)-6-{[(1R)-1-cyclopropylethyl]amino}-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-7-[4-(trifluoromethyl)benzyl]-8-[2-(trifluoromethyl)phenyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(2-ethyl-5-methoxyphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(2-ethylphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(2-ethyl-5-methylphenyl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(1-methyl-1H-pyrazol-4-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(3,5-dimethylisoxazol-4-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

(R)-6-((1-cyclobutylethyl)amino)-8-(1-methyl-1H-imidazol-2-yl)-7-(4-(trifluoromethyl) benzyl)-7H-purine-2-carboxylic acid;

(R)-6-((1-cyclobutylethyl)amino)-8-(4-isopropylpyrimidin-2-yl)-7-(4-(trifluoromethyl)benzyl)-7H-purine-2-carboxylic acid;

(R)-6-((1-cyclobutylethyl)amino)-8-(5-isopropylthiazol-2-yl)-7-(4-(trifluoromethyl)benzyl)-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-pyrimidin-2-yl-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(1,3-oxazol-2-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(5-methyl-1,3-thiazol-2-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

7-(4-chlorobenzyl)-6-{[(1R)-1-cyclopropylethyl]amino}-8-(1,3-thiazol-2-yl)-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-8-(1,3-thiazol-2-yl)-7-[4-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

(R)-7-(4-chlorobenzyl)-6-((1-cyclobutylethyl)amino)-8-(2-ethoxy-5-methylphenyl)-7H-purine-2-carboxylic acid;

(R)-7-(4-chlorobenzyl)-6-((1-cyclobutylethyl)amino)-8-(2, 5-dimethylphenyl)-7H-purine-2-carboxylic acid;

(R)-8-(2-(but-3-en-1-yloxy)-5-methylphenyl)-7-(4-chlorobenzyl)-6-((1-cyclopropylethyl)amino)-7H-purine-2-carboxylic acid;

(R)-7-(4-chlorobenzyl)-6-((1-cyclobutylethyl)amino)-8-(2-(3-methoxypropoxy)-5-methylphenyl)-7H-purine-2-carboxylic acid;

(R)-7-(4-chlorobenzyl)-6-((1-cyclopropylethyl)amino)-8-(2-(3-methoxypropoxy)-5-methylphenyl)-7H-purine-2-carboxylic acid;

(R)-7-(4-chlorobenzyl)-6-((1-cyclobutylethyl)amino)-8-(2-(3-hydroxypropoxy)-5-methylphenyl)-7H-purine-2-carboxylic acid;

(R)-7-(4-chlorobenzyl)-6-((1-cyclopropylethyl)amino)-8-(2-ethoxy-5-methylphenyl)-7H-purine-2-carboxylic acid;

(R)-7-(4-chlorobenzyl)-6-((1-cyclobutylethyl)amino)-8-(2-(2-methoxyethoxy)-5-methylphenyl)-7H-purine-2-carboxylic acid;

(R)-7-(4-chlorobenzyl)-6-((1-cyclopropylethyl)amino)-8-(2-(2-methoxyethoxy)-5-methylphenyl)-7H-purine-2-carboxylic acid;

(R)-7-(4-chlorobenzyl)-6-((1-cyclopropylethyl)amino)-8-(2-(2-hydroxyethoxy)-5-methylphenyl)-7H-purine-2-carboxylic acid;

(R)-8-(2-(2-carboxyethoxy)-5-methylphenyl)-7-(4-chlorobenzyl)-6-((1-cyclopropylethyl)amino)-7H-purine-2-carboxylic acid;

(R)-7-(4-chlorobenzyl)-6-((1-cyclopropylethyl)amino)-8-(2-(3-((2-hydroxyethyl)amino)-3-oxopropoxy)-5-methylphenyl)-7H-purine-2-carboxylic acid;

(R)-7-(4-chlorobenzyl)-6-((1-cyclopropylethyl)amino)-8-(5-methyl-2-(3-(methylamino)-3-oxopropoxy)phenyl)-7H-purine-2-carboxylic acid;

(R)-7-(4-chlorobenzyl)-6-((1-cyclopropylethyl)amino)-8-(5-methyl-2-(3-morpholinopropoxy)phenyl)-7H-purine-2-carboxylic acid;

(R)-8-(2-(3-(bis(2-methoxyethyl)amino)propoxy)-5-methylphenyl)-7-(4-chlorobenzyl)-6-((1-cyclopropylethyl)amino)-7H-purine-2-carboxylic acid;

(R)-7-(4-cyanobenzyl)-6-((1-cyclopropylethyl)amino)-8-(2-(3-hydroxypropoxy)-5-methylphenyl)-7H-purine-2-carboxylic acid;

(R)-7-(4-chlorobenzyl)-6-(1-cyclopropylethylamino)-8-(5-methyl-2-(3-(4-methylpiperazin-1-yl)propoxy)phenyl)-7H-purine-2-carboxylic acid;

(R)-7-(4-chlorobenzyl)-6-((1-cyclopropylethyl)amino)-8-(2-hydroxy-5-methylphenyl)-7H-purine-2-carboxylic acid;

7-(4-chlorobenzyl)-6-(((R)-1-cyclopropylethyl)amino)-8-(2-(2,3-dihydroxypropoxy)-5-methylphenyl)-7H-purine-2-carboxylic acid;

(R)-7-(4-chlorobenzyl)-6-((1-cyclopropylethyl)amino)-8-(2-(3-hydroxypropoxy)-5-methylphenyl)-7H-purine-2-carboxylic acid;

7-[1-(4-chlorophenyl)ethyl]-6-{[(1R)-1-cyclopropylethyl]amino}-8-(3-methylphenyl)-7H-purine-2-carboxylic acid;

7-[1-(4-chlorophenyl)ethyl]-6-[(cyclopropylmethyl)amino]-8-(3-methylphenyl)-7H-purine-2-carboxylic acid;

7-[1-(4-chlorophenyl)ethyl]-6-{[(1S)-1-cyclopropylethyl]amino}-8-(3-methylphenyl)-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-7-[4-fluoro-3-(trifluoromethyl)benzyl]-8-(3-methylphenyl)-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-7-(2-ethoxy-5-(trifluoromethyl)benzyl)-8-(3-methylphenyl)-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-7-(2-ethoxybenzyl)-8-(3-methylphenyl)-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-7-[4-(1-methylethyl)benzyl]-8-(3-methylphenyl)-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-(3-methylphenyl)-7-[4-(trifluoromethoxy)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-7-[3-fluoro-4-(trifluoromethyl)benzyl]-8-(3-methylphenyl)-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-7-(4-cyclopropylbenzyl)-8-(3-methylphenyl)-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-7-(2,4-dichlorobenzyl)-8-(3-methylphenyl)-7H-purine-2-carboxylic acid;

7-[2-chloro-4-(trifluoromethyl)benzyl]-6-{[(1R)-1-cyclobutylethyl]amino}-8-(3-methylphenyl)-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-7-[4-(difluoromethoxy)benzyl]-8-(3-methylphenyl)-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-7-[3-fluoro-4-(trifluoromethoxy)benzyl]-8-(3-methylphenyl)-7H-purine-2-carboxylic acid;

7-[3-chloro-4-(trifluoromethyl)benzyl]-6-{[(1R)-1-cyclopropylethyl]amino}-8-(3-methylphenyl)-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-8-(3-methylphenyl)-7-[2-(trifluoromethyl)benzyl]-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-7-[2-fluoro-4-(trifluoromethyl)benzyl]-8-(3-methylphenyl)-7H-purine-2-carb oxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-7-[2-ethoxy-4-(trifluoromethyl)benzyl]-8-(3-methylphenyl)-7H-purine-2-carb oxylic acid;

6-{[(1R)-1-cyclobutylethyl]amino}-7-(4-methoxybenzyl)-8-(3-methylphenyl)-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-7-(4-ethylbenzyl)-8-(3-methylphenyl)-7H-purine-2-carboxylic acid;

6-{[(1R)-1-cyclopropylethyl]amino}-7-(4-methylbenzyl)-8-(3-methylphenyl)-7H-purine-2-carboxylic acid;