# US 2024/0199596 A1 · Diacylglycerol kinase modulating compounds

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- Number: US 2024/0199596 A1
- Document ID: US20240199596A1
- Status: Published application
- Kind: A1
- Application number: 18/413,767
- Filed: 2024-01-16
- Published: 2024-06-20
- Earliest claimed: 2021-06-23
- Assignees: Gilead Sciences, Inc.
- Applicants: Gilead Sciences, Inc.
- Inventors: Michael Graupe; Juan A. Guerrero; Stephen D. Holmbo; Jesse M. Jacobsen; Tetsuya Kobayashi; Leena B. Patel; Heath A. Weaver; Jie Xu; Suet C. Yeung
- Web page: https://patentgrep.com/patent/US20240199596A1

## CPC

- C07D 413/14: containing three or more hetero rings
- A61K 31/517: ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
- A61K 31/55: having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K 31/553: having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
- A61P 31/18: for HIV
- A61P 31/20: for DNA viruses
- A61P 35/00: Antineoplastic agents
- A61P 35/04: specific for metastasis
- C07B 59/002: {Heterocyclic compounds}
- C07D 239/95: with hetero atoms directly attached in positions 2 and 4
- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 401/14: containing three or more hetero rings
- C07D 403/04: directly linked by a ring-member-to-ring-member bond
- C07D 403/12: linked by a chain containing hetero atoms as chain links
- C07D 405/12: linked by a chain containing hetero atoms as chain links
- C07D 413/04: directly linked by a ring-member-to-ring-member bond
- C07D 417/12: linked by a chain containing hetero atoms as chain links
- C07D 471/04: Ortho-condensed systems
- C07D 487/08: Bridged systems
- C07B 2200/05: Isotopically modified compounds, e.g. labelled
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## Abstract

The present disclosure provides diacylglycerol kinase modulating compounds, and pharmaceutical compositions thereof, for treating cancer, including solid tumors, and viral infections, such as HIV or hepatitis B virus infection. The compounds can be used alone or in combination with other agents.

## Claims

### Claim 1

A compound of Formula (I):
or a pharmaceutically acceptable salt thereof, wherein
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)(R2e), —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,
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, each aryl is optionally substituted with 1 to 3 R3f groups 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, R3f, R3g, 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 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(R5a1)(R5a2)(R5a3);
R5a1, R5a2, and R5a3 are each independently C1-6 alkyl; and
R6 is C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C6-12 aryl substituted with 1 to 3 R6a which can be the same or different, or heteroaryl 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, —OC(O)R6b, —C(O)N(R6b)(R6c), —N(R6b)C(O)R6, —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)(R6g2), —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(R6j1)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.

### Claim 2

A compound of Formula (I):
or a pharmaceutically acceptable salt thereof, wherein
R1 is hydrogen, C1-6 alkyl, or halogen;
R2 is hydrogen, C1-6 alkyl, or halogen;
R3 is hydrogen, C1-6 alkyl, or halogen;
R4 is hydrogen, C1-6 alkyl, or halogen;
R7 is hydrogen or C1-6 alkyl optionally substituted with —OH;
R5 is C1-6 alkyl or C1-6 haloalkyl;
R6 is phenyl substituted with 1 to 3 R6a which can be the same or different, or heteroaryl optionally substituted with 1 to 3 R6a which can be the same or different, wherein the heteroaryl is a 5 or 6 membered ring having 1 to 3 heteroatoms each independently N, O or S;
or
X3, X4, X3, and X6 are each independently CH, N, or C—R6a, provided that not more than two of X3, X4, X5, and X6 are N, and not more than two of X3, X4, X5, and X6 are C—R6a, and
Ring A is a 5 to 8 membered heterocycloalkyl optionally having 1 to 2 additional heteroatoms each independently N, O, or S, and optionally Ring A is substituted with 1 or 2 R6g which can be the same or different;
each R6a is independently halogen, C2-8 alkynyl, phenyl, heterocycloalkyl, or heteroaryl, wherein the phenyl, heterocycloalkyl, or heteroaryl is each optionally substituted with 1 to 3 R6e, and the alkynyl is optionally substituted with 1 to 4 R6j which can be the same or different, wherein the heterocycloalkyl is a 3 to 10 membered ring having 1 to 3 heteroatoms each independently N, O or S, the heteroaryl is a 5 or 6 membered ring having 1 to 3 heteroatoms each independently N, O or S;
each R6j is independently halogen, C1-6 haloalkyl, —OR6j1, —CN, —N(R6j1)(R6j2), —N(R6j1)C(O)R6j2, C3-10 cycloalkyl, heteroaryl, or heterocycloalkyl, wherein the cycloalkyl, heteroaryl, or heterocycloalkyl is optionally substituted with 1 to 3 R6p which can be the same or different, the heterocycloalkyl is a 3 to 10 membered ring having 1 to 3 heteroatoms each independently N, O or S; the heteroaryl is a 5 or 6 membered ring having 1 to 3 heteroatoms each independently N, O or S;
each R6j1 and R6j2 is independently hydrogen, C1-6 alkyl, C1-6 haloalkyl, or C3-10 cycloalkyl optionally substituted with C1-6 haloalkyl;
each R6p is independently halogen, C1-6 alkyl, C1-6 haloalkyl, —C(O)R6p1, or heterocycloalkyl, the heterocycloalky is a 3 to 10 membered ring having 1 to 3 heteroatoms each independently N, O or S;
R6p1 is C1-6 alkyl, or C3-10 cycloalkyl;
each R6e is independently C1-6 alkyl, C3-6 cycloalkyl, heterocycloalkyl, halogen, C1-6 haloalkyl, or —CN, wherein the cycloalkyl and heterocycloalkyl are optionally substituted with 1 to 3 R6h which can be the same or different, the heterocycloalkyl is a 3 to 10 membered ring having 1 to 3 heteroatoms each independently N, O or S;
each R6h is independently C1-6 alkyl, C1-6 haloalkyl, ═O, or —OH; and
each R6g is independently C1-6 alkyl, halogen, or C1-6 haloalkyl.

### Claim 3 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein
R5 is 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); the heterocycloalkyl is a 5 to 8 membered ring having 1 to 2 heteroatoms each independently N, O, or S, wherein the heteroaryl is a 5 to 6 membered ring having 1 to 2 heteroatoms each independently N, O, or S; and
R6 is phenyl substituted with 1 to 3 R6a which can be the same or different, or heteroaryl optionally substituted with 1 to 3 R6a which can be the same or different, wherein the heteroaryl is a 5 to 6 membered ring having 1 to 2 heteroatoms each independently N, O, or S.

### Claim 4 (depends on 1, 3)

The compound of claim 1 or 3, or a pharmaceutically acceptable salt thereof, wherein R5 is C1-6 alkyl or C1-6 haloalkyl.

### Claim 5

The compound of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein R5 is —CH2CHF2, —CH2CF3, or Me.

### Claim 6

The compound of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein R5 is —CH2CHF2.

### Claim 7

The compound of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein
R6 is phenyl substituted with 1 or 2 R6a, or heteroaryl optionally substituted with 1 or 2 R6a, wherein the heteroaryl is 5 to 6 membered ring having 1 to 2 heteroatoms each independently N, O, or S.

### Claim 8

The compound of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein
R6 is phenyl substituted with 1 or 2 R6a which can be the same or different; or thienyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyrrolyl, pyrazolyl, pyrazinyl, pyridyl, or pyrimidinyl, which are each optionally substituted with 1 or 2 R6a.

### Claim 9

The compound of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein
R6 is phenyl substituted with 1 or 2 R6a which can be the same or different, or, thienyl, thiazolyl, pyridyl, pyrazinyl, or pyrimidinyl, which are each optionally substituted with 1 or 2 R6a.

### Claim 10

The compound of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein
R6 is phenyl substituted with C2-8 alkynyl, the alkynyl is substituted with 1 or 2 R6j which can be the same or different; and
the phenyl is optionally substituted with one additional R6a.

### Claim 11

The compound of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein
R6 is phenyl substituted with F and C2-8 alkynyl, the alkynyl is substituted with 1 or 2 R6j which can be the same or different.

### Claim 12 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9)

The compound of any one of claims 1-9, or a pharmaceutically acceptable salt thereof, wherein
R6 is phenyl substituted with 1 or 2 substituents selected from the group consisting of F, phenyl, pyridyl and pyrazinyl, wherein the phenyl, pyridyl or pyrazinyl is each optionally substituted with 1 or 2 R6e which can be the same or different.

### Claim 13 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9)

The compound of any one of claims 1-9, or a pharmaceutically acceptable salt thereof, wherein
R6 is pyridyl or pyrazinyl, which are each optionally substituted with 1 or 2 R6a which can be the same or different.

### Claim 14 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 13)

The compound of any one of claims 1-9 and 13, or a pharmaceutically acceptable salt thereof, wherein
R6 is pyridyl or pyrazinyl, which are each optionally substituted with C2-8 alkynyl, the alkynyl is substituted with 1 or 2 R6j which can be the same or different.

### Claim 15 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9)

The compound of any one of claims 1-9, or a pharmaceutically acceptable salt thereof, wherein R6 is

### Claim 16 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 15)

The compound of any one of claims 1-9 and 15, or a pharmaceutically acceptable salt thereof, wherein R6 is

### Claim 17 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 12)

The compound of any one of claims 1-9, 12, and 15, or a pharmaceutically acceptable salt thereof, wherein
R6 is
X1 and X2 are each independently N or CH; and
X7 is CH or CF.

### Claim 18 (depends on 17)

The compound of claim 17, or a pharmaceutically acceptable salt thereof, wherein X1 and X2 are CH.

### Claim 19 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15)

The compound of any one of claims 1-10 and 15, or a pharmaceutically acceptable salt thereof, wherein R6 is

### Claim 20 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 13, 14, 15)

The compound of any one of claims 1-9 and 13-15, or a pharmaceutically acceptable salt thereof, wherein R6 is

### Claim 21 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 12)

The compound of any one of claims 1-9, 12, and 17, or a pharmaceutically acceptable salt thereof, wherein R6 is

### Claim 22 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein
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.

### Claim 23 (depends on 1, 2)

The compound of any one of claims 1, 2, and 22, or a pharmaceutically acceptable salt thereof, wherein
n is 0, 1, or 2; and
Ring A is a 5 to 8 membered heterocycloalkyl optionally having 1 to 2 additional heteroatoms each independently N, O, or S, and optionally Ring A is substituted with 1 or 2 R6g which can be the same or different.

### Claim 24 (depends on 1, 2)

The compound of claim 1 or 2, or a pharmaceutically acceptable salt thereof, having the formula (Ia-1)
wherein X3, X4, and X5 are each independently CH, N, or C—R6a, provided that not more than two of X3, X4, and X5 are N, and not more than one of X3, X4, and X5 is C—R6a.

### Claim 25 (depends on 1, 2, 22)

The compound of any one of claims 1, 2, 22, and 23, or a pharmaceutically acceptable salt thereof, having the formula (Ia-2)
wherein n is 0, 1, or 2; and
Ring A is a 5 to 8 membered heterocycloalkyl optionally having 1 additional heteroatom N, O, or S.

### Claim 26 (depends on 25)

The compound of claim 25, or a pharmaceutically acceptable salt thereof, wherein

### Claim 27 (depends on 1, 2)

The compound of claim 1 or 2, or a pharmaceutically acceptable salt thereof, having the formula (la-3):
wherein X3, X4, X3, and X6 are each independently CH, N, or C—R6a, provided that not more than two of X3, X4, X3, and X6 are N, and not more than two of X3, X4, X3, and X6 are C—R6a.

### Claim 28 (depends on 1, 2, 22, 23)

The compound of any one of claims 1, 2, 22, 23, and 25-27, or a pharmaceutically acceptable salt thereof, having the formula (Ia-4):
wherein n is 0, 1, or 2.

### Claim 29 (depends on 1, 2)

The compound of any one of claims 1, 2, and 22-28, or a pharmaceutically acceptable salt thereof, having the formula (Ia-5):

### Claim 30 (depends on 1, 2)

The compound of any one of claims 1, 2, and 22, or a pharmaceutically acceptable salt thereof, having the formula (la-6):
wherein
X3, X4, X5, and X6 are each independently CH, N, or C—R6a, provided that not more than two of X3, X4, X3, and X6 are N, and not more than two of X3, X4, X3, and X6 are C—R6a.

### Claim 31 (depends on 1, 2, 22, 23, 25, 26)

The compound of any one of claims 1, 2, 22, 23, 25, 26, and 30, or a pharmaceutically acceptable salt thereof, having the formula (Ia-7):
wherein n is 0, 1, or 2.

### Claim 32 (depends on 1, 2, 22, 23, 24, 25, 26, 30)

The compound of any one of claims 1, 2, 22-26, 30, and 31, or a pharmaceutically acceptable salt thereof, having the formula (Ia-8):

### Claim 33 (depends on 1, 2)

The compound of any one of claims 1, 2, and 22-26, or a pharmaceutically acceptable salt thereof, having the formula (Ia-9):

### Claim 34 (depends on 1, 2)

The compound of any one of claims 1, 2, and 22-26, or a pharmaceutically acceptable salt thereof, having the formula (Ia-10):

### Claim 35 (depends on 1, 3, 4, 5, 6, 7, 8, 9, 10, 13, 15, 16)

The compound of any one of claims 1, 3-10, 13, 15, 16, and 23-34, or a pharmaceutically acceptable salt thereof, wherein
each R6a is independently C1-6 alkyl, C2-8 alkynyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C2-6 alkoxyalkyl, halogen, C1-6 haloalkyl, C1-6 haloalkoxy, —CN, —NO2, —C(O)R6b, —C(O)N(R6b)(R6c), —N(R6b)(R6c), —OR6b, C3-10 cycloalkyl, C6-12 aryl, heterocycloalkyl, or heteroaryl, wherein the cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is each optionally substituted with 1 to 3 R6e which can be the same or different, and the alkynyl is optionally substituted with 1 to 3 R6j which can be the same or different;
each R6b and R6c is independently hydrogen, C1-6 alkyl, C1-6 haloalkyl, or C3-10 cycloalkyl;
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(R6j1)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 haloalkyl, or C3-10 cycloalkyl optionally substituted with C1-6 haloalkyl;
each R6p is independently C1-6 alkyl, halogen, C1-6 haloalkyl, —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, ═O, —OH, or heterocycloalkyl;
each R6p1 and R6p2 is independently hydrogen, C1-6 alkyl, C1-6 haloalkyl, or C3-10 cycloalkyl;
each R6e is independently C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 hydroxyalkyl, C1-6 alkoxy, C2-6 alkoxyalkyl, halogen, C1-6 haloalkyl, —C(O)OR6e1, —OC(O)R6e1, —C(O)N(R6e1)(R6e2), —N(R6e1)C(O)R6e2, —OR6e1, —S(O)2N(R6e1)(R6e2), —N(R6e1)S(O)2(R6e2), 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, and the alkyl is optionally substituted with 1 to 3 R6m which can be the same or different;
each R6e1 and R6e2 is independently hydrogen or C1-6 alkyl;
each R6m is independently halogen, —CN, or —OH; and
each R6h is independently halogen, C1-6 alkyl, ═O, or C1-6 haloalkyl.

### Claim 36 (depends on 1, 3, 4, 5, 6, 7, 8, 9, 10, 13, 15, 16)

The compound of any one of claims 1, 3-10, 13, 15, 16, and 23-34, or a pharmaceutically acceptable salt thereof, wherein
each R6a is independently C2-8 alkynyl, halogen, C1-6 haloalkyl, C3-10 cycloalkyl, C6-12 aryl, heterocycloalkyl, or heteroaryl, wherein the cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is each optionally substituted with 1 to 3 R6e which can be the same or different, and the alkynyl is optionally substituted with 1 to 3 R6j which can be the same or different;
each R6j is independently halogen, —OR6j1, —CN, —N(R6j1)(R6j2), —N(R6j1)C(O)R6j2, C3-10 cycloalkyl, heteroaryl, heterocycloalkyl, wherein the cycloalkyl, heteroaryl, or heterocycloalkyl is optionally substituted with 1 to 3 R6p which can be the same or different;
each R6j1 and R6j2 is independently hydrogen C1-6 alkyl, C1-6 haloalkyl, or C3-6 cycloalkyl optionally substituted with C1-3 haloalkyl;
each R6p is independently C1-6 alkyl, halogen, C1-6 haloalkyl, ═O, —CN, —OH, C(O)R6p1, or heterocycloalkyl;
R6p1 is C1-6 alkyl, or C3-6 cycloalkyl;
each R6e is independently C1-6 alkyl, halogen, C1-6 haloalkyl, C3-6 cycloalkyl, or heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is optionally substituted with 1 to 3 R6h which can be the same or different; and
each R6h is independently halogen, C1-6 alkyl, ═O, or C1-6 haloalkyl.

### Claim 37 (depends on 1, 3, 4, 5, 6, 7, 8, 9, 10, 13, 15, 16)

The compound of any one of claims 1, 3-10, 13, 15, 16, and 23-34, or a pharmaceutically acceptable salt thereof, wherein
each R6a is independently C2-8 alkynyl, halogen, C6-12 aryl, a 5 to 6 membered heterocycloalkyl ring having 1 to 2 heteroatoms each independently N or O, or a 5 to 6 membered heteroaryl ring having 1 to 2 heteroatoms each independently N, O, or S, wherein the aryl, heterocycloalkyl, or heteroaryl is each optionally substituted with 1 to 3 R6e which can be the same or different, and the alkynyl is optionally substituted with 1 to 3 R6j which can be the same or different;
each R6j is independently halogen, —OR6j1, —CN, C3-10 cycloalkyl, heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is optionally substituted with 1 to 3 R6p which can be the same or different;
R6j1 is hydrogen or C1-6 alkyl;
each R6p is independently C1-6 alkyl, halogen, ═O, —OH, or C1-6 haloalkyl;
each R6e is independently C1-6 alkyl, halogen, C1-6 haloalkyl, cyclopropyl, a heterocycloalkyl ring having 1 to 2 heteroatoms each independently N, O, or S, wherein the cyclopropyl or heterocycloalkyl is optionally substituted with 1 to 3 R6h which can be the same or different; and
each R6h is independently halogen, C1-6 alkyl, ═O, or C1-6 haloalkyl.

### Claim 38 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 13, 15, 16)

The compound of any one of claims 1-10, 13, 15, 16, and 23-34, or a pharmaceutically acceptable salt thereof, wherein
each R6a is independently C2-8 alkynyl or halogen, wherein the alkynyl is optionally substituted with 1 to 3 R6j which can be the same or different.

### Claim 39 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 13, 15, 16)

The compound of any one of claims 1-10, 13, 15, 16, and 23-34, or a pharmaceutically acceptable salt thereof, wherein
each R6a is independently C2-8 alkynyl substituted with 1 to 3 R6j which can be the same or different.

### Claim 40 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 13, 15, 16)

The compound of any one of claims 1-10, 13, 15, 16, and 23-34, or a pharmaceutically acceptable salt thereof, wherein
each R6a is
and
R6j is C1-6 haloalkyl, C3-6 cycloalkyl, 5-6 membered heteroaryl, or 4-6 membered heterocycloalkyl, wherein the cycloalkyl, heteroaryl, or heterocycloalkyl is optionally substituted with 1 to 3 R6p; and
each R6p is independently halogen, C1-6 alkyl, C1-6 haloalkyl, —C(O)R6p1, or heterocycloalkyl;
R6p1 is C1-6 alkyl, or C3-10 cycloalkyl.

### Claim 41 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 13, 15, 16, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 38)

The compound of any one of claims 1-10, 13, 15, 16, 23-35, 38, and 39, or a pharmaceutically acceptable salt thereof, wherein
each R6j is independently halogen, C1-6 haloalkyl, —OR6j1, —CN, —N(R6j1)(R6j2), —N(R6j1)C(O)R6j2, C3-6 cycloalkyl, 5-6 membered heteroaryl, 4-6 membered heterocycloalkyl, wherein the cycloalkyl, heteroaryl, or heterocycloalkyl is optionally substituted with 1 to 3 R6p which can be the same or different;
each R6j1 and R6j2 is independently hydrogen, C1-6 alkyl, C1-6 haloalkyl, or C3-10 cycloalkyl optionally substituted with C1-6 haloalkyl;
each R6p is independently halogen, C1-6 alkyl, C1-6 haloalkyl, —C(O)R6p1, or heterocycloalkyl, the heterocycloalky is a 3 to 10 membered ring having 1 to 2 heteroatoms each independently N, O or S; and
R6p1 is C1-6 alkyl, or C3-6 cycloalkyl.

### Claim 42 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 13, 15, 16)

The compound of any one of claims 1-10, 13, 15, 16, and 23-41, or a pharmaceutically acceptable salt thereof, wherein each R6p is independently Me, —CF3, —CH2F, —CF2CH3, or —CHF2.

### Claim 43 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39)

The compound of any one of claims 1-16, 23-39, and 41, or a pharmaceutically acceptable salt thereof, wherein each R6j is independently halogen, C1-6 haloalkyl, —OH, —OMe, or —CN.

### Claim 44 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 41)

The compound of any one of claims 1-16, 23-39, 41, and 43, or a pharmaceutically acceptable salt thereof, wherein each R6j is independently —OH, —CN, —F, —OMe, —CHF2, or —CF3.

### Claim 45 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 38)

The compound of any one of claims 1-16, 23-35, 38, and 39, or a pharmaceutically acceptable salt thereof, wherein
each R6j is independently C3-6 cycloalkyl, 5-6 membered heteroaryl, or 4-6 membered heterocycloalkyl, the cycloalkyl, heteroaryl, or heterocycloalkyl is optionally substituted with 1 to 3 R6p which can be the same or different; and
each R6p is independently C1-3 alkyl, C1-3 haloalkyl, —C(O)R6p1, or heterocycloalkyl, the heterocycloalky is 3 to 6 membered ring having 1 to 2 heteroatoms each independently N, O or S; and
R6p1 is C1-3 alkyl, or C3-6 cycloalkyl.

### Claim 46 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35)

The compound of any one of claims 1-16, 23-35, and 38-41, or a pharmaceutically acceptable salt thereof, wherein each R6j is independently cyclopropyl,

### Claim 47 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)

The compound of any one of claims 1-16, and 23-34, or a pharmaceutically acceptable salt thereof, wherein
each R6a is independently phenyl or a 5 or 6 membered heteroaryl ring having 1 to 2 heteroatoms each independently N, O, or S, wherein the phenyl or heteroaryl is optionally substituted with 1 to 3 R6e which can be the same or different.

### Claim 48 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 13, 15, 16, 17, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37)

The compound of any one of claims 1-10, 12, 13, 15-17, 23-37, and 47, or a pharmaceutically acceptable salt thereof, wherein
each R6e is independently C1-6 haloalkyl, cyclopropyl, 4-6 membered heterocycloalkyl optionally substituted with ═O or C1-6 alkyl.

### Claim 49 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 13, 15, 16, 17, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 47)

The compound of any one of claims 1-10, 12, 13, 15-17, 23-37, 47, and 48, or a pharmaceutically acceptable salt thereof, wherein each R6e is independently —CHF2,

### Claim 50 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 15, 16)

The compound of any one of claims 1-13, 15-16, and 23-34, or a pharmaceutically acceptable salt thereof, wherein each R6a is independently F, Br,

### Claim 51 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 15, 16, 17, 18)

The compound of any one of claims 1-13, 15-18, and 23-34, or a pharmaceutically acceptable salt thereof, wherein each R6a is independently F, Br,

### Claim 52 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 13, 15, 16, 17)

The compound of any one of claims 1-10, 12, 13, 15-17, and 23-34, or a pharmaceutically acceptable salt thereof, wherein each R6a is independently F, Br,

### Claim 53 (depends on 29)

The compound of claim 29, or a pharmaceutically acceptable salt thereof, wherein

### Claim 54 (depends on 1, 2)

The compound of claim 1, 2, or 23, or a pharmaceutically acceptable salt thereof, wherein

### Claim 55 (depends on 1, 2)

The compound of claim 1 or 2, or a pharmaceutically acceptable salt thereof, wherein

### Claim 56 (depends on 33)

The compound of claim 33, or a pharmaceutically acceptable salt thereof, wherein

### Claim 57 (depends on 23, 25)

The compound of any one of claims 23, 25, and 26, or a pharmaceutically acceptable salt thereof, wherein

### Claim 58 (depends on 1, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57)

The compound of any one of claims 1 and 3-57, or a pharmaceutically acceptable salt thereof, wherein R1 is hydrogen, C1-6 alkyl, C1-6 alkoxy, halogen, C1-6 haloalkyl, or —CN.

### Claim 59 (depends on 1, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57)

The compound of any one of claims 1 and 3-57, or a pharmaceutically acceptable salt thereof, wherein R1 is hydrogen, C1-3 alkyl, C1-3 alkoxy, or halogen.

### Claim 60 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57)

The compound of any one of claims 1-57, or a pharmaceutically acceptable salt thereof, wherein R1 is hydrogen, F, or C1.

### Claim 61 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57)

The compound of any one of claims 1-57, or a pharmaceutically acceptable salt thereof, wherein R1 is hydrogen.

### Claim 62 (depends on 1, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61)

The compound of any one of claims 1 and 3-61, or a pharmaceutically acceptable salt thereof, wherein R2 is hydrogen, C1-6 alkyl, C1-6 alkoxy, halogen, C1-6 haloalkyl, or —CN.

### Claim 63 (depends on 1, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61)

The compound of any one of claims 1 and 3-61, or a pharmaceutically acceptable salt thereof, wherein R2 is hydrogen, C1-3 alkyl, halogen, C1-3 haloalkyl, or —CN.

### Claim 64 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61)

The compound of any one of claims 1-61, or a pharmaceutically acceptable salt thereof, wherein R2 is hydrogen, F, or C1.

### Claim 65 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61)

The compound of any one of claims 1-61, or a pharmaceutically acceptable salt thereof, wherein R2 is Cl.

### Claim 66 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61)

The compound of any one of claims 1-61, or a pharmaceutically acceptable salt thereof, wherein R2 is hydrogen.

### Claim 67 (depends on 1, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66)

The compound of any one of claims 1 and 3-66, or a pharmaceutically acceptable salt thereof, wherein R3 is hydrogen, C1-6 alkyl, C1-6 alkoxy, halogen, C1-6 haloalkyl, or —CN.

### Claim 68 (depends on 1, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66)

The compound of any one of claims 1 and 3-66, or a pharmaceutically acceptable salt thereof, wherein R3 is hydrogen, C1-3 alkyl, halogen, C1-3 haloalkyl, or —CN.

### Claim 69 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66)

The compound of any one of claims 1-66, or a pharmaceutically acceptable salt thereof, wherein R3 is hydrogen.

### Claim 70 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66)

The compound of any one of claims 1-66, or a pharmaceutically acceptable salt thereof, wherein R3 is F.

### Claim 71 (depends on 1, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70)

The compound of any one of claims 1 and 3-70, or a pharmaceutically acceptable salt thereof, wherein R4 is hydrogen, C1-6 alkyl, C1-6 alkoxy, halogen, C1-6 haloalkyl, or —CN.

### Claim 72 (depends on 1, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70)

The compound of any one of claims 1 and 3-70, or a pharmaceutically acceptable salt thereof, wherein R4 is hydrogen, C1-3 alkyl, halogen, C1-3 haloalkyl, or —CN.

### Claim 73 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70)

The compound of any one of claims 1-70, or a pharmaceutically acceptable salt thereof, wherein R4 is hydrogen, C1-3 alkyl, or halogen.

### Claim 74 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70)

The compound of any one of claims 1-70, or a pharmaceutically acceptable salt thereof, wherein R4 is F.

### Claim 75 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70)

The compound of any one of claims 1-70, or a pharmaceutically acceptable salt thereof, wherein R4 is hydrogen.

### Claim 76 (depends on 1, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75)

The compound of any one of claims 1 and 3-75, or a pharmaceutically acceptable salt thereof, wherein R7 is hydrogen or C1-6 alkyl.

### Claim 77 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75)

The compound of any one of claims 1-75, or a pharmaceutically acceptable salt thereof, wherein R7 is hydrogen, Me, or Et.

### Claim 78 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75)

The compound of any one of claims 1-75, or a pharmaceutically acceptable salt thereof, wherein R7 is hydrogen.

### Claim 79 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75)

The compound of any one of claims 1-75, or a pharmaceutically acceptable salt thereof, wherein R7 is Me.

### Claim 80

A compound as shown in Table 1, or a pharmaceutically acceptable salt thereof.

### Claim 81

A compound as shown in Table 1.

### Claim 82

A compound having the structure:
or a pharmaceutically acceptable salt thereof.

### Claim 83

A compound having the structure:
or a pharmaceutically acceptable salt thereof.

### Claim 84

A compound having the structure:
or a pharmaceutically acceptable salt thereof.

### Claim 85

A compound having the structure:
or a pharmaceutically acceptable salt thereof.

### Claim 86

A compound having the structure:
or a pharmaceutically acceptable salt thereof.

### Claim 87

A compound having the structure:
or a pharmaceutically acceptable salt thereof.

### Claim 88

A compound having the structure:
or a pharmaceutically acceptable salt thereof.

### Claim 89

A compound having the structure:
or a pharmaceutically acceptable salt thereof.

### Claim 90 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89)

A pharmaceutical composition comprising a pharmaceutically effective amount of a compound of any one of claims 1-89, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

### Claim 91 (depends on 90)

The pharmaceutical composition of claim 90, further comprising one or more additional therapeutic agents.

### Claim 92 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89)

A pharmaceutical composition for use in treating a cancer, comprising a pharmaceutically effective amount of a compound of any one of claims 1-89, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

### Claim 93 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89)

A pharmaceutical composition for use in treating an HIV or hepatitis B virus infection, comprising a pharmaceutically effective amount of a compound of any one of claims 1-89, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

### Claim 94 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91)

A method of inhibiting DGKα in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of any one of claims 1-89, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of any one of claims 90-91.

### Claim 95 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91)

A method of treating cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of any one of claims 1-89, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of any one of claims 90-91.

### Claim 96 (depends on 95)

The method of claim 95, wherein the cancer is pancreatic cancer, bladder cancer, colorectal cancer, breast cancer, prostate cancer, renal cancer, hepatocellular cancer, lung cancer, ovarian cancer, cervical cancer, gastric cancer, esophageal cancer, head and neck cancer, melanoma, neuroendocrine cancer, CNS cancer, brain cancer, bone cancer, soft tissue sarcoma, non-small cell lung cancer, small-cell lung cancer or colon cancer.

### Claim 97 (depends on 95)

The method of claim 95, wherein the cancer is acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), myelodysplastic syndrome (MDS), myeloproliferative disease (MPD), chronic myeloid leukemia (CML), multiple myeloma (MM), non-Hodgkin's lymphoma (NHL), mantle cell lymphoma (MCL), follicular lymphoma, Waldestrom's macroglobulinemia (WM), T-cell lymphoma, B-cell lymphoma or diffuse large B-cell lymphoma (DLBCL).

### Claim 98 (depends on 94, 95, 96, 97)

The method of any one of claims 94-97, further comprising administering one or more additional therapeutic agents to the subject.

### Claim 99 (depends on 98)

The method of claim 98, wherein the one or more additional therapeutic agents is an inhibitor of a protein that inhibits T cell activation.

### Claim 100 (depends on 98)

The method of claim 98, wherein the one or more additional therapeutic agents is independently an anti-neoplastic agent, PD-1/PD-L1 inhibitor, CTLA-4 inhibitor, LAG-3 inhibitor, TIM-3 inhibitor, or chemotherapy.

### Claim 101 (depends on 94, 95, 96, 97, 98)

The method of any one of claims 94-98, further comprising radiation therapy, or resection therapy.

### Claim 102 (depends on 98)

The method of claim 98, wherein the one or more additional therapeutic agents is a PD-1/PD-L1 inhibitor.

### Claim 103 (depends on 102)

The method of claim 102, wherein the PD-1/PD-L1 inhibitor is selected from the group consisting of nivolumab, pembrolizumab, cemiplimab, atezolizumab, avelumab, and durvalumab.

### Claim 104 (depends on 98)

The method of claim 98, wherein the one or more additional therapeutic agents is a CTLA-4 inhibitor.

### Claim 105 (depends on 104)

The method of claim 104, wherein the CTLA-4 inhibitor is selected from the group consisting of ipilimumab and tremelimumab.

### Claim 106 (depends on 98)

The method of claim 98, wherein the one or more additional therapeutic agents comprises one or more populations of immune cells selected from the group consisting of: natural killer (NK) cells, NK-T cells, T cells, cytokine-induced killer (CIK) cells, macrophage (MAC) cells, tumor infiltrating lymphocytes (TILs) and dendritic cell (DCs).

### Claim 107 (depends on 98)

The method of claim 98, wherein the one or more additional therapeutic agents comprises a population of T cells selected from the group consisting of: alpha/beta TCR T cells, gamma/delta TCR T cells, regulatory T (Treg) cells and TRuC™ T cells.

### Claim 108 (depends on 98)

The method of claim 98, wherein the one or more additional therapeutic agents comprises a population of NK-92 cells.

### Claim 109 (depends on 106)

The method of claim 106, wherein the one or more populations of immune cells comprise one or more chimeric antigen receptors (CARs).

### Claim 110 (depends on 106, 107, 108, 109)

The method of any one of claims 106-109, wherein the cells are allogeneic to an intended recipient.

### Claim 111 (depends on 98)

The method of claim 98, wherein the one or more additional therapeutic agents comprises an immunotherapy, an immunostimulatory therapy, a cytokine therapy, a chemokine therapy, a cellular therapy, a gene therapy, or combinations thereof.

### Claim 112 (depends on 111)

The method of claim 111, wherein the immunotherapy comprises co-administering one or more antibodies or antigen-binding antibody fragments thereof, or antibody-drug conjugates thereof, CD3-targeting multi-specific molecules, CD16-targeting multi-specific molecules, or non-immunoglobulin antigen-binding domains or antibody mimetic proteins directed against one or more targets or tumor associated antigens (TAAs).

### Claim 113 (depends on 98)

The method of claim 98, wherein the one or more additional therapeutic agents comprises a vaccine.

### Claim 114 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91)

A method of treating an HIV or hepatitis B virus infection in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of any one of claims 1-89, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of any one of claims 90-91.

### Claim 115 (depends on 114)

The method of claim 114, further comprising one or more additional therapeutic agents.

### Claim 116 (depends on 115)

The method of claim 115, wherein the one or more additional therapeutic agents comprises a vaccine.

### Claim 117 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89)

A method for manufacturing a medicament for treating cancer in a subject in need thereof, characterized in that a compound of any one of claims 1-89, or a pharmaceutically acceptable salt thereof, is used.

### Claim 118 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89)

A method for manufacturing a medicament for inhibiting cancer metastasis in a subject in need thereof, characterized in that a compound of any one of claims 1-89, or a pharmaceutically acceptable salt thereof, is used.

### Claim 119 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89)

A method for manufacturing a medicament for treating an HIV or hepatitis B virus infection in a subject in need thereof, characterized in that a compound of any one of claims 1-89, or a pharmaceutically acceptable salt thereof, is used.

### Claim 120 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89)

Use of the compound of any one of claims 1-89, or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for the treatment of cancer in a subject.

### Claim 121 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89)

Use of the compound of any one of claims 1-89, or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for inhibiting cancer metastasis in a subject.

### Claim 122 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89)

Use of the compound of any one of claims 1-89, or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for the treatment of an HIV or hepatitis B virus infection in a subject.

### Claim 123 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89)

The compound of any one of claims 1-89, or a pharmaceutically acceptable salt thereof, for use in the treatment of cancer in a subject in need thereof.

### Claim 124 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89)

The compound of any one of claims 1-89, or a pharmaceutically acceptable salt thereof, for use in inhibiting cancer metastasis in a subject in need thereof.

### Claim 125 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89)

The compound of any one of claims 1-89, or a pharmaceutically acceptable salt thereof, for use in the treatment of an HIV or hepatitis B virus infection in a subject in need thereof.

### Claim 126 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89)

The compound of any one of claims 1-89, or a pharmaceutically acceptable salt thereof, for use in therapy.