PD-1/PD-L1 inhibitors

1. A compound of Formula (IIId):

wherein:

each Z 1 is independently halo;

each Z 3 is independently halo or —O—C 1-6 alkyl;

each R 1 is independently selected from the group consisting of H, —C 1-8 alkyl, —C 2-6 alkenyl, —C 2-6 alkynyl, —C 3-6 cycloalkyl, aryl, heteroaryl, heterocyclyl, —C 1-6 alkylaryl, —C 1-6 alkylheteroaryl, —C 1-6 alkylheterocyclyl, —C 1-6 alkylC(O)OR a , —C 2-6 alkenylC(O)OR a , —S(O) 2 R a , —S(O) 2 NR a R b , —C(O)NR a S(O) 2 R a , and —C 1-6 alkylC 3-8 cycloalkyl;

wherein each alkyl, alkenyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl group is optionally substituted with 1 to 4 groups independently selected from the group consisting of —OR a , —CN, halo, —C 1-6 alkyl, —C 1-6 alkylOR a , —C 1-6 cyanoalkyl, —C 1-6 haloalkyl, C 3-8 cycloalkyl, —C 1-3 alkylC 3-8 cycloalkyl, —C(O)R a , —C 1-6 alkylC(O)R a , —C(O)OR a , —C 1-6 alkylC(O)OR a , —NR a R b , —OC(O)NR a R b , —NR a C(O)OR b , —C 1-6 alkylNR a R b , —C(O)NR a R b , —C 1-6 alkylC(O)NR a R b , —S(O) 2 R a , —C 1-6 alkylS(O) 2 R a , —S(O) 2 NR a R b , —C 1-6 alkylS(O) 2 NR a R b , —C(O)NR'S(O) 2 R b , —C 1-6 alkylC(O)NR'S(O) 2 R b , —NR a C(O)R b , and —C 1-6 alkylNR a C(O)R b ;

each R 2 is independently selected from the group consisting of H, —C 1-6 alkyl, —C 2-6 alkenyl, —C 2-6 alkynyl, —C 3-6 cycloalkyl, aryl, heteroaryl, heterocyclyl, —C 1-6 alkylaryl, —C 1-6 alkylheteroaryl, —C 1-6 alkylheterocyclyl, —C 2-6 alkylOR a , —C 1-6 alkylC(O)OR a , and —C 2-6 alkenylC(O)OR a ;

wherein each alkyl, alkenyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl group is optionally substituted with 1 to 4 groups independently selected from the group consisting of —OR a , —CN, halo, —C 1-6 alkyl, —C 1-6 alkylOR a , —C 1-6 cyanoalkyl, —C 1-6 haloalkyl, —C 3-8 cycloalkyl, —C 1-3 alkylC 3-8 cycloalkyl, —C(O)R a , —C 1-6 alkylC(O)R a , —C(O)OR a , —C 1-6 alkylC(O)OR a , —NR a R b , —C 1-6 alkylNR a R b , —C(O)NR a R b , C 1-6 alkylC(O)NR a R b , —S(O) 2 R a , —C 1-6 alkyl S(O) 2 R a , —S(O) 2 NR a R b , —C 1-6 alkyl S(O) 2 NR a R b , —C(O)NR a S(O) 2 R b , and —NR a C(O)R b ;

or R 1 and R 2 combine to form a heterocyclyl group optionally containing 1, 2, or 3 additional heteroatoms independently selected from oxygen, sulfur, and nitrogen, and optionally substituted with 1 to 3 groups independently selected from the group consisting of oxo, —C 1-6 alkyl, —C 3-8 cycloalkyl, —C 2-6 alkenyl, —C 2-6 alkynyl, —0R a , —C(O)OR a , —C 1-6 cyanoalkyl, —C 1-6 alkylOR a , —C 1-6 haloalkyl, —Ci-3 alkylC 3-8 cycloalkyl, —C(O)R a , —C 1-6 alkylC(O)R a , —C 1-6 alkylC(O)OR a , —NR a R b , —C 1-6 alkylNR a R b , —C(O)NR a R b , —C 1-6 alkylC(O)NR a R b , —S(O) 2 R a , —C 1-6 alkyl S(O) 2 R a , —S(O) 2 NR a R b , and —C 1-6 alkyl S(O) 2 NR a R b ;

each R a is independently selected from the group consisting of H, —C 1-6 alkyl, —C 3-8 cycloalkyl, aryl, heteroaryl, heterocyclyl, —C 1-3 alkylC 3-8 cycloalkyl, —C 1-6 alkylaryl, —C 1-6 alkylheteroaryl, and —C 1-6 alkylheterocyclyl;

each R b is independently selected from the group consisting of H, —C 1-6 alkyl, —C 3-8 cycloalkyl, aryl, heteroaryl, heterocyclyl, —C 1-3 alkylC 3-8 cycloalkyl, —C 1-6 alkylaryl, —C 1-6 alkylheteroaryl, and —C 1-6 alkylheterocyclyl;

or R a and R b may combine together to form a ring consisting of 3-8 ring atoms that are C, N, O, or S; wherein the ring is optionally substituted with 1 to 4 groups independently selected from the group consisting of —OR f , —CN, halo, —C 1-6 alkylOR f , —C 1-6 cyanoalkyl, —C 1-6 haloalkyl, —C 3-8 cycloalkyl, —C 1-3 alkylC 3-8 cycloalkyl, —C(O)R f , —C 1-6 alkylC(O)R f , —C(O)OR f , —C 1-6 alkylC(O)OR f , —NR f R g , —C 1-6 alkylNR f R g , —C(O)NR f R g , C 1-6 alkylC(O)NR f R g , —S(O) 2 R f , —C 1-6 alkylS(O) 2 R f , —S(O) 2 NR f R g , —C 1-6 alkyl S(O) 2 NR f R g , —C(O)NR f S(O) 2 R g , and —NR f C(O)R g ;

each R f is independently selected from the group consisting of H, —C 1-6 alkyl, —C 3-8 cycloalkyl, aryl, heteroaryl, heterocyclyl, —C 1-3 alkylC 3-8 cycloalkyl, —C 1-6 alkylaryl, —C 1-6 alkylheteroaryl, and -C 1-6 alkylheterocyclyl; and

each R g is independently selected from the group consisting of H, —C 1-6 alkyl, —C 3-8 cycloalkyl, aryl, heteroaryl, heterocyclyl, —C 1-3 alkylC 3-8 cycloalkyl, —C 1-6 alkylaryl, —C 1-6 alkylheteroaryl, and —C 1-6 alkylheterocyclyl;

or a pharmaceutically acceptable salt thereof.

2. A compound selected from:

and

or a pharmaceutically acceptable salt thereof.

3. A pharmaceutical composition comprising a compound according to claim 1 or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

4. The pharmaceutical composition according to claim 3 , further comprising at least one additional anticancer agent or therapy selected from rituxan, doxorubicin, gemcitabine, nivolumab, pembrolizumab, and ipilimumab, and at least one pharmaceutically acceptable excipient.

5. The pharmaceutical composition according to claim 3 , further comprising an additional anticancer agent selected from nivolumab, pembrolizumab, atezolizumab, and ipilimumab, and at least one pharmaceutically acceptable excipient.

6. The compound of claim 1 , wherein each Z 1 is chloro.

7. The compound of claim 1 , wherein Z 3 is —O—C 1-3 alkyl.

8. The compound of claim 1 , wherein Z 3 is —OCH 3 .

9. The compound of claim 1 , wherein R 1 and R 2 combine to form a heterocyclyl group optionally containing 1, 2, or 3 additional heteroatoms independently selected from oxygen, sulfur, and nitrogen, and optionally substituted with 1 to 3 groups independently selected from the group consisting of oxo, —C 1-6 alkyl, —C 3-8 cycloalkyl, —C 2-6 alkenyl, —C 2-6 alkynyl, —OR a , —C(O)OR a , —C 1-6 cyanoalkyl, —C 1-6 alkylOR a , —C 1-6 haloalkyl, —C 1-3 alkylC 3-8 cycloalkyl, —C(O)R a , —C 1-6 alkylC(O)R a , —C 1-6 alkylC(O)OR a , —NR a R b , —C 1-6 alkylNR a R b , —C(O)NR a R b , —C 1-6 alkylC(O)NR a R b , —S(O) 2 R a , —C 1-6 alkyl S(O) 2 R a , —S(O) 2 NR a R b , and —C 1-6 alkyl S(O) 2 NR a R b .