Diacylglycerol kinase modulating compounds

A compound of Formula (I):

• or a pharmaceutically acceptable salt thereof, wherein
• Z1 is N or CR1;
• Z2 is N or CR2;
• R1 is hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, halogen, C1-6 haloalkyl, C1-6 haloalkoxy, or —CN;
• R2 is hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 hydroxyalkyl, C1-6 aminoalkyl, C1-6 alkoxy, C2-6 alkoxyalkyl, halogen, C1-6 haloalkyl, C1-6 haloalkoxy, —CN, —NO, —NO2, —C(O)R2a, —C(O)OR2a, —OC(O)R2a, —C(O)N(R2a)(R2b), —N(R2a)C(O)R2b, —OC(O)N(R2a)(R2b), —N(R2a)C(O)OR2b, —C(═NR2a)N(R2b)(R2c), —N(R2a)(R2b), —N(R2a)N(R2b)(R2c), —N(R2a)N═C(R2b)(OR2c), —OR2a, —SR2a, —S(O)R2a, —S(O)(NR2a)(R2b), —S(NR2a)(NR2b)(R2c), —S(O)2R2a, —S(O)2N(R2a)(R2b), —N(R2a)S(O)2(R2b), —P(R2a)(R2b), —P(O)(R2a)(R2b), —P(O)(OR2a)(R2b), —P(O)(OR2a)(OR2b), C3-10 cycloalkyl, C1-6 alkyl-C3-10 cycloalkyl, C6-12 aryl, C1-6 alkyl-C6-12 aryl, heterocycloalkyl, C1-6 alkyl-(heterocycloalkyl), heteroaryl, or C1-6 alkyl-(heteroaryl), wherein each alkyl, alkenyl or alkynyl is independently optionally substituted with 1 to 3 R2d groups which can be the same or different, each cycloalkyl is optionally substituted with 1 to 3 R2e groups which can be the same or different, each aryl is optionally substituted with 1 to 3 R2f groups which can be the same or different, each heterocycloalkyl is optionally substituted with 1 to 3 R2g groups which can be the same or different, and each heteroaryl is optionally substituted with 1 to 3 R2h groups which can be the same or different;
• each R2a, R2b, and R2c is independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 hydroxyalkyl, C1-6 aminoalkyl, C2-6 alkoxyalkyl, C1-6 haloalkyl, C3-10 cycloalkyl, C1-6 alkyl-C3-10 cycloalkyl, C6-12 aryl, C1-6 alkyl-C6-12 aryl, heterocycloalkyl, C1-6 alkyl-(heterocycloalkyl), heteroaryl, or C1-6 alkyl-(heteroaryl), wherein the aryl or heteroaryl is optionally substituted with 1 to 3 R2j which can be the same or different;
• alternatively, R2a, R2b, and R2c when attached to the same atom can be combined with the atom to which they are attached to form a heterocycloalkyl;
• each R2d is independently —CN, —C(O)R2d1, —C(O)OR2d1, —OC(O)R2d1, —C(O)N(R2d1)(R2d2), —N(R2d1)C(O)R2d2, —OC(O)N(R2d1)(R2d2), —N(R2d1)C(O)OR2d2, —N(R2d1)(R2d2), ═O, —OR2d1, —SR2d1, —S(O)R2d1, —S(O)(NR2d1)(R2d2), —S(O)2R2d1, —S(O)N(R2d1)(R2d2), —N(R2d1)S(O)2R2d2, C3-10 cycloalkyl, C1-6 alkyl-C3-10 cycloalkyl, C6-12 aryl, C1-6 alkyl-C6-12 aryl, heterocycloalkyl, C1-6 alkyl-(heterocycloalkyl), heteroaryl, or C1-6 alkyl-(heteroaryl);
• each R2d1 and R2d2 is independently hydrogen, C1-6 alkyl, C1-6 hydroxyalkyl, C1-6 aminoalkyl, C2-6 alkoxyalkyl, or C1-6 haloalkyl;
• each R2e, R2f, R2g, and R2h is independently hydrogen, C1-6 alkyl, C1-6 hydroxyalkyl, C1-6 aminoalkyl, C1-6 alkoxy, C2-6 alkoxyalkyl, halogen, C1-6 haloalkyl, C1-6 haloalkoxy, —CN, or —OH;
• each R2j is independently C1-6 alkyl, C1-6 hydroxyalkyl, C1-6 aminoalkyl, C1-6 alkoxy, C2-6 alkoxyalkyl, halogen, C1-6 haloalkyl, or C1-6 haloalkoxy;
• R3 is hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 hydroxyalkyl, C1-6 aminoalkyl, C1-6 alkoxy, C2-6 alkoxyalkyl, halogen, C1-6 haloalkyl, C1-6 haloalkoxy, —CN, —NO, —NO2, —C(O)R3a, —C(O)OR3a, —OC(O)R3a, —C(O)N(R3a)(R3b), —N(R3a)C(O)R3b, —OC(O)N(R3a)(R3b), —N(R3a)C(O)OR3b, —C(═NR3a)N(R3b)(R3c), —N(R3a)(R3b), —N(R3a)N(R3b)(R3c), —N(R3a)N═C(R3b)(OR3c), —OR3a, —SR3a, —S(O)R3a, —S(O)(NR3a)(R3b), —S(NR3a)(NR3b)(R3c), —S(O)2R3a, —S(O)2N(R3a)(R3b), —N(R3a)S(O)2(R3b), —P(R3a)(R3b), —P(O)(R3a)(R3b), —P(O)(OR3a)(R3b), —P(O)(OR3a)(OR3b), C3-10 cycloalkyl, C1-6 alkyl-C3-10 cycloalkyl, C6-12 aryl, C1-6 alkyl-C6-12 aryl, heterocycloalkyl, C1-6 alkyl-(heterocycloalkyl), heteroaryl, or C1-6 alkyl-(heteroaryl), wherein each alkenyl or alkynyl is independently optionally substituted with 1 to 3 R3d groups, each cycloalkyl is optionally substituted with 1 to 3 R3e groups which can be the same or different, each aryl is optionally substituted with 1 to 3 R3fgroups which can be the same or different, each heterocycloalkyl is optionally substituted with 1 to 3 R3g groups which can be the same or different, and each heteroaryl is optionally substituted with 1 to 3 R3h groups which can be the same or different;
• each R3a, R3b, and R3c is independently hydrogen, C1-6 alkyl, C1-6 hydroxyalkyl, C2-6 alkoxyalkyl, C1-6 haloalkyl, C3-10 cycloalkyl, C1-6 alkyl-C3-10 cycloalkyl, C6-12 aryl, C1-6 alkyl-C6-12 aryl, heterocycloalkyl, or heteroaryl;
• alternatively, R3a, R3b, and R3c when attached to the same atom can be combined with the atom to which they are attached to form a heterocycloalkyl;
• each R3d is independently —N(R3d1)(R3d2), —OR3d1, C3-10 cycloalkyl, C1-6 alkyl-C3-10 cycloalkyl, C6-12 aryl, C1-6 alkyl-C6-12 aryl, heterocycloalkyl, or heteroaryl;
• each R3d1 and R3d2 is independently hydrogen, C1-6 alkyl, or —C(O)O—(C1-6 alkyl);
• each R3e, R3, R39, and R3h is independently hydrogen, C1-6 alkyl, C1-6 alkoxy, halogen, C1-6 haloalkyl or C1-6 haloalkoxy;
• R4 is hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, halogen, C1-6 haloalkyl, C1-6 haloalkoxy, or —CN;
• R5 is hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 hydroxyalkyl, C2-6 alkoxyalkyl, C1-6 haloalkyl, C3-10 cycloalkyl, C1-6 alkyl-C3-10 cycloalkyl, C6-12 aryl, C1-6 alkyl-C6-12 aryl, heterocycloalkyl, C1-6 alkyl-(heterocycloalkyl), heteroaryl, or C1-6 alkyl-(heteroaryl), wherein the alkyl is optionally substituted with R5a;
• R5a is —OSi(R5a1a(R5a2)(R5a3);
• R5a1, R5a2, and R5a3 are each independently C1-6 alkyl;
• and
• R6 is C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C6-12 aryl, or heteroaryl, wherein the aryl or heteroaryl are each optionally substituted with 1 to 3 R6a which can be the same or different;
• each R6a is independently C1-6 alkyl, C2-6 alkenyl, C2-8 alkynyl, C1-6 hydroxyalkyl, C1-6 aminoalkyl, C1-6 alkoxy, C2-6 alkoxyalkyl, halogen, C1-6 haloalkyl, C1-6 haloalkoxy, —CN, —NO2, —C(O)R6b, —C(O)OR6b, —OC(O)R6b, —C(O)N(R6b)(R6c), —N(R6b)C(O)R6c, —C(═NR6b)N(R6c)(R6d), —N(R6b)(R6c), —OR6b, —SR6b, —S(O)R6b, —S(O)2R6b, —S(NR6b)(NR6c)R6d, —S(O)(NR6b)(R6c), —S(O)2N(R6b)(R6c), —N(R6b)S(O)2(R6c), —P(R6b)(R6c), —P(O)(R6b)(R6c), —P(O)(OR6b)(R6c), —P(O)(OR6b)(OR6c), C3-10 cycloalkyl, C1-6 alkyl-C3-10 cycloalkyl, C6-12 aryl, C1-6 alkyl-C6-12 aryl, heterocycloalkyl, C1-6 alkyl-(heterocycloalkyl), heteroaryl, or C1-6 alkyl-(heteroaryl), wherein the cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is each optionally substituted with 1 to 3 R6e which can be the same or different, the alkyl is optionally substituted with R6f, and the alkynyl is optionally substituted with 1 to 4 R6j which can be the same or different;
• each R6b, R6c and R6d is independently hydrogen, C1-6 alkyl, C1-6 hydroxyalkyl, C1-6 aminoalkyl, C2-6 alkoxyalkyl, C1-6 haloalkyl, C3-10 cycloalkyl, C1-6 alkyl-C3-10 cycloalkyl, C6-12 aryl, C1-6 alkyl-C6-12 aryl, heterocycloalkyl, C1-6 alkyl-(heterocycloalkyl), heteroaryl, or C1-6 alkyl-(heteroaryl), wherein the cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is optionally substituted by 1 to 3 R6k which can be the same or different;
• each R6k is independently C1-6 alkyl, C1-6 hydroxyalkyl, C1-6 aminoalkyl, C1-6 alkoxy, C2-6 alkoxyalkyl, C1-6 haloalkyl, C1-6 haloalkoxy, C3-10 cycloalkyl, C1-6 alkyl-C3-10 cycloalkyl, heterocycloalkyl, or C1-6 alkyl-(heterocycloalkyl);
• each R6e is independently C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 hydroxyalkyl, C1-6 aminoalkyl, C1-6 alkoxy, C2-6 alkoxyalkyl, halogen, C1-6 haloalkyl, C1-6 haloalkoxy, —CN, —NO2, —C(O)R6e1, —C(O)OR6e1, —OC(O)R6e1, —C(O)N(R6e1)(R6e2), —N(R6e1)C(O)R6e2, —OC(O)N(R6e1)(R6e2), —N(R6e1)C(O)OR6e2, —C(═NR6e1)N(R6e2)(R6e3), —N(R6e1)(R6e2), ═O, —OR6e1, —SR6e1—S(O)R6e1, —S(NR6e1)(NR6e2), —S(O)(NR6e1)(R6e2), —S(O)2R6e1, —S(O)2N(R6e1)(R6e2), —SF5, —N(R6e1)S(O)2(R6e2), —P(R6e1)(R6e2), —P(O)(R6e1)(R6e2), —P(O)(OR6e1)(R6e2), —P(O)(OR6e1)(OR6e2), —Si(R6e1)(R6e2)(R6e3), C3-10 cycloalkyl, C1-6 alkyl-C3-10 cycloalkyl, C6-12 aryl, C1-6 alkyl-C6-12 aryl, heterocycloalkyl, C1-6 alkyl-heterocycloalkyl, heteroaryl, or C1-6 alkyl-heteroaryl, wherein the cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is each optionally substituted with 1 to 3 R6h which can be the same or different, and the alkyl is optionally substituted with 1 to 3 R6m which can be the same or different;
• each R6e1, R6e2, and R6e3 is independently hydrogen, C1-6 alkyl, C1-6 hydroxyalkyl, C1-6 aminoalkyl, C1-6 alkoxyalkyl, C1-6 haloalkyl, C3-10 cycloalkyl, C1-6 alkyl-C3-10 cycloalkyl, C6-10 aryl, C1-6 alkyl-C6-10 aryl, heterocycloalkyl, C1-6 alkyl-(heterocycloalkyl), heteroaryl, or C1-6 alkyl-(heteroaryl), wherein the cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is optionally substituted with 1 to 3 R6n which can be the same or different;
• each R6n is C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 hydroxyalkyl, C1-6 aminoalkyl, C1-6 alkoxy, C2-6 alkoxyalkyl, halogen, C1-6 haloalkyl, C1-6 haloalkoxy, —CN, —C(O)R6n1, —C(O)OR6n1, —OC(O)R6n1, —C(O)N(R6n1)(R6n2), —N(R6n1)C(O)R6n2, —OC(O)N(R6n1)(R6n2), —N(R6n1)C(O)OR6n2, —C(═NR6n1)N(R6n2)(R6n3), —N(R6n1)(R6n2), ═O, —OH, —SR6n1, —S(O)R6n1, —S(NR6n1)(NR6n2)R6n3, —S(O)(NR6n1)(R6n2), —S(O)2R6n1, —S(O)2N(R6n1)(R6n2), or —N(R6n1)S(O)2(R6n2);
• each R6n1, R6n2 and R6n3 is independently hydrogen, C1-6 alkyl, C1-6 hydroxyalkyl, C1-6 aminoalkyl, C2-6 alkoxyalkyl, C1-6 haloalkyl, C3-10 cycloalkyl, C1-6 alkyl-C3-10 cycloalkyl, C6-10 aryl, C1-6 alkyl-C6-10 aryl, heterocycloalkyl, C1-6 alkyl-(heterocycloalkyl), heteroaryl, or C1-6 alkyl-(heteroaryl);
• each R6h is independently C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 hydroxyalkyl, C1-6 aminoalkyl, C1-6 alkoxy, C2-6 alkoxyalkyl, halogen, C1-6 haloalkyl, C1-6 haloalkoxy, —CN, —C(O)R6h1, —C(O)OR6h1, —OC(O)R6h1, —C(O)N(R6h1)(R6h2), —N(R6h1)C(O)R6h2, —OC(O)N(R6h1)(R6h2), —N(R6h1)C(O)OR6h2, —C(═NR6h1)N(R6h2)(R6h3), —N(R6h1)(R6h2), ═O, —OH, —SR6h1, —S(O)R6h1, —S(NR6h1)(NR6h2)R6h3, —S(O)(NR6h1)(R6h2), —S(O)2R6h1, —S(O)2N(R6h1)(R6h2), —N(R6h1)S(O)2(R6h2), C3-10 cycloalkyl, C1-6 alkyl-C3-10 cycloalkyl, heterocycloalkyl, or C1-6 alkyl-(heterocycloalkyl);
• each R6h1, R6h2, and R6h3 is independently hydrogen, C1-6 alkyl, C1-6 hydroxyalkyl, C1-6 aminoalkyl, C2-6 alkoxyalkyl, C1-6 haloalkyl, C3-10 cycloalkyl, C1-6 alkyl-C3-10 cycloalkyl, C6-10 aryl, C1-6 alkyl-C6-10 aryl, heterocycloalkyl, C1-6 alkyl-(heterocycloalkyl), heteroaryl, or C1-6 alkyl-(heteroaryl);
• each R6m is independently halogen, C1-6 haloalkyl, C1-6 haloalkoxy, —CN, —C(O)R6m1, —C(O)OR6m1, —OC(O)R6m1, —C(O)N(R6m1)(R6m2), —N(R6m3)C(O)R6m2, —OC(O)N(R6m1)(R6m2), —N(R6m1)C(O)OR6m2, —C(═NR6m3)N(R6m1)(R6m2), —N(R6m1)(R6m2), ═O, —OH, —SR6m1, —S(O)R6m1, —S(NR6m1)(NR6m2)R6m3, —S(O)(NR6m1)(R6m2), —S(O)2R6m1, —S(O)2N(R6m1)(R6m2), or —N(R6m3)S(O)2(R6m2);
• each R6m1, R6m2, and R6m3 is independently hydrogen, C1-6 alkyl, C1-6 hydroxyalkyl, C1-6 aminoalkyl, C2-6 alkoxyalkyl, C1-6 haloalkyl, C3-10 cycloalkyl, C1-6 alkyl-C3-10 cycloalkyl, C6-10 aryl, C1-6 alkyl-C6-10 aryl, heterocycloalkyl, C1-6 alkyl-(heterocycloalkyl), heteroaryl, or C1-6 alkyl-(heteroaryl);
• R6f is —OSi(R6f1)(R6f2)(R6f3);
• R6f1, R6f2, and R6f3 are each independently C1-6 alkyl;
• each R6j is independently C2-6 alkoxyalkyl, halogen, C1-6 haloalkyl, C1-6 haloalkoxy, —CN, —C(O)R6j1, —C(O)OR6j1, —OC(O)R6j1, —C(O)N(R6j1)(R6j2), —N(R6j3)C(O)R6j2, —OC(O)N(R6j1)(R6j2), —N(R6j1)C(O)OR6j2, —C(═NR6j3)N(R6j1)(R6j2), —N(R6j1)(R6j2), ═O, —OR6j1, —SR6j1, —S(O)R6j1, —S(NR6j1)(NR6j2), —S(NR6j1)(NR6j2)R6j3, —S(O)(NR6j1)(R6j2), —S(O)2R6j1, —S(O)2N(R6j1)(R6j2), —N(R6j1)S(O)2(R6j2), —Si(R6j1)(R6j2)(R6j3), C3-10 cycloalkyl, C6-12 aryl, heterocycloalkyl, or heteroaryl, wherein the cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is optionally substituted with 1 to 3 R6p which can be the same or different;
• each R6j1, R6j2, and R6j3 is independently hydrogen, C1-6 alkyl, C1-6 hydroxyalkyl, C1-6 aminoalkyl, C2-6 alkoxyalkyl, C1-6 haloalkyl, C3-10 cycloalkyl optionally substituted with C1-6 haloalkyl, C1-6 alkyl-C3-10 cycloalkyl, C6-10 aryl, C1-6 alkyl-C6-10 aryl, heterocycloalkyl, C1-6 alkyl-(heterocycloalkyl), heteroaryl, or C1-6 alkyl-(heteroaryl);
• each R6p is independently C1-6 alkyl, C1-6 hydroxyalkyl, C1-6 aminoalkyl, C1-6 alkoxy, C2-6 alkoxyalkyl, halogen, C1-6 haloalkyl, C1-6 haloalkoxy, —CN, —C(O)R6p1, —C(O)OR6p1, —OC(O)R6p1, —C(O)N(R6p1)(R6p2), —N(R6p1)C(O)R6p2, —OC(O)N(R6p1)(R6p2), —N(R6p1)C(O)OR6p2, —C(═NR6p3)N(R6p1)(R6p2), —N(R6p1)(R6p2), ═O, —OH, —SR6p1, —S(O)R6p1, —S(NR6p1)(NR6p2)R6p3, —S(O)(NR6p1)(R6p2), —S(O)2R6p1, —S(O)2N(R6p1)(R6p2), or —N(R6p1)S(O)2(R6p2);
• each R6p1, R6p2, and R6p3 is independently hydrogen, C1-6 alkyl, C1-6 hydroxyalkyl, C1-6 aminoalkyl, C2-6 alkoxyalkyl, C1-6 haloalkyl, C3-10 cycloalkyl, C1-6 alkyl-C3-10 cycloalkyl, C6-10 aryl, C1-6 alkyl-C6-10 aryl, heterocycloalkyl, C1-6 alkyl-(heterocycloalkyl), heteroaryl, or C1-6 alkyl-(heteroaryl);
• or R5 and one R6a together with the atoms to which they are attached form a heterocycloalkyl, optionally substituted with 1 to 3 R6g which can be the same or different;
• each R6g is independently C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 hydroxyalkyl, C1-6 aminoalkyl, C2-6 alkoxyalkyl, halogen, C1-6 haloalkyl, C1-6 haloalkoxy, or —CN;
• R7 is hydrogen, C1-6 alkyl, C1-6 hydroxyalkyl, C1-6 aminoalkyl, C2-6 alkoxyalkyl, C1-6 haloalkyl, C3-10 cycloalkyl, C1-6 alkyl-C3-10 cycloalkyl, heterocycloalkyl, or C1-6 alkyl-(heterocycloalkyl);
• each heterocycloalkyl is a 3 to 20 membered ring having 1 to 4 heteroatoms each independently N, O or S;
• and
• each heteroaryl is a 5 to 18 membered ring having 1 to 4 heteroatoms each independently N, O or S.