Diacylglycerol kinase modulating compounds

Abstract

To provide a compound having diacylglycerol kinase α (DGKα) inhibitory activity and useful for treating cancer including solid tumors and viral infections such as HIV or hepatitis B virus infection.SOLUTION: A compound of formula (I) or a pharmaceutically acceptable salt thereof is provided.SELECTED DRAWING: None

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims the benefit of priority to Japanese Patent Application No. 2019-232938, filed December 24, 2019, and Japanese Patent Application No. 2020-135810, filed August 11, 2020, each of which is incorporated herein in its entirety. [Background technology]

[0002] Diacylglycerol (DAG) is known as a signaling molecule and a second messenger, playing an important role in cell proliferation, differentiation, and / or metabolism (Carrasco, S., Merida, I. Trends Biochem. Sci. 2007, 32, 27-36). The intracellular concentration and localization of DAG are tightly regulated, and diacylglycerol kinase (DGK) is one of the enzymes that regulates them. DGK synthesizes phosphatidic acid (PA) by transferring a phosphoryl group to DAG. Ten human isozymes (α, β, γ, δ, ε, ζ, η, θ, ι, and κ) are known (Joshi, RP, Koretzky, GAINt. J. Mol. Sci. 2013, 14, 6649-6673). Each isozyme is localized and thought to associate with different proteins and / or different cell types. DGK has been reported to be involved in the pathogenesis of multiple diseases, including cancer, immune disorders, neurodegenerative diseases, and diabetes (Sakane, F., et al. Front. Cell Dev. Biol., 2016, 4, 82).

[0003] DGKα has been the subject of research, including studies into its potential therapeutic potential in cancer. For example, inhibitory activity against glioblastoma cell proliferation was reported as a result of knockdown caused by RNA interference targeting DGKα (Dominguez, CL, et al. Cancer Discov., 2013, 782-797). Inhibitory effects have also been reported in human colon cancer cell lines in three-dimensional cell culture, and knockdown of DGKα was further reported to inhibit tumor growth in a mouse model (Torres-Ayuso, P., et al. Oncotarget, 2014, 5, 9710-9726). Inhibition of DGKα has been disclosed in International Publication No. 2007 / 114239. Therefore, compounds with inhibitory activity against DGKα may be useful as therapeutic agents for the treatment of cancers in which DGKα is involved in their proliferation.

[0004] In recent years, cancer immunotherapy has attracted attention as a potential treatment for cancer. Immune checkpoint inhibitors, such as anti-CTLA-4 (cytotoxic T-lymphocyte antigen 4) antibodies, anti-PD-1 (programmed death receptor 1) antibodies, and anti-PD-L1 (programmed death ligand 1) antibodies, can be administered to enhance antitumor immune responses in patients. Several immune checkpoint inhibitors have already been approved as drugs for antitumor therapy. However, the antitumor effect is often limited to a small number of patients. Furthermore, some patients develop resistance to the inhibitors (Spranger, S., Gajewski, T. F., Nat. Rev. Cancer., 2018, 18, 139-147).

[0005] DGKα is expressed in T cells, mediates T cell receptor (TCR) signaling, and is thought to play a role in T cell activation (Joshi et al. (supra) and Merida, I. et al., Adv. Biol. Regul., 2017, 63, 22-31). When T cells are in an immunologically unresponsive state, such as anergy, DGKα expression may increase, and overexpression of DGKα has been reported to induce an anergic state (Zha, Y. et al., Nat. Immunol., 2006, 7, 1166-1173). Furthermore, knockdown of DGKα in T cells by RNA interference has been reported to result in T cell activation (Avila-Flores, A., et al., Immunol. Cell. Biol., 2017, 95, 549-563). Therefore, compounds having activity regulating DGKα may be useful for preventing and / or treating diseases associated with T cells, such as immune diseases or inflammatory diseases.

[0006] Recently, chimeric antigen receptor (CAR) T cell therapy has attracted attention as a promising immunotherapy for cancer. DGKα-deficient CAR T cells have been reported to have high effector function and antitumor efficacy against solid tumors (Riese, MJ et al. Cancer Res., 2013, 73, 3566-3577; Jung, IY, et al. Cancer Res., 2018, 78, 4692-4703). Therefore, the use of compounds with inhibitory effects against DGKα may complement CAR T cell therapy.

[0007] However, there remains a need for, for example, DGKα inhibitors that have desirable pharmaceutical and therapeutic properties. Summary of the Invention

[0008] In one embodiment, the present disclosure provides a compound of formula (I-1): [ka] or a pharmaceutically acceptable salt thereof, wherein: R1 , R 2 , R 3 and R 4 are independently a hydrogen atom, a halogen atom, a hydroxy group, a carboxy group, a formyl group, a cyano group, an amino group, a nitro group, a nitroso group, an alkoxycarbonyl group, an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted cycloalkyl group, an optionally substituted alkoxy group, an optionally substituted alkylamino group, an optionally substituted aryl group, an optionally substituted heteroaryl group, an optionally substituted acyl group, an optionally substituted carbamoyl group, an optionally substituted acylamino group, an optionally substituted saturated heterocyclo group, or an optionally substituted alkylsulfonylamino group; R 5 is a hydrogen atom, an optionally substituted alkyl group, an optionally substituted alkynyl group, or an optionally substituted aryl group; R 6 is an optionally substituted alkyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group, or R 5 and R 6 may be taken together with the nitrogen atom to which they are attached to form a nitrogen-containing saturated heterocyclic ring to which an aryl ring is fused, the fused ring being optionally substituted; However, the compound is [ka] isn't it.

[0009] In another embodiment, the present disclosure provides a compound of formula (I): [ka] or a pharmaceutically acceptable salt thereof, wherein: R 1 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6Alkynyl, C 1~6 Alkoxy, halogen, C 1~6 Haloalkyl, C 1~6 haloalkoxy, or -CN; R 2 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -NO, -NO2, -C(O)R 2a , -C(O)OR 2a , -OC(O)R 2a , -C(O)N(R 2a )(R 2b ), -N(R 2a )C(O)R 2b , -OC(O)N(R 2a )(R 2b ), -N(R 2a )C(O)OR 2b , -C(=NR 2a )N(R 2b )(R 2c ), -N(R 2a )(R 2b ), -N(R 2a )N(R 2b )(R 2c ), -N(R 2a )N=C(R 2b )(OR 2c ), -OR 2a , -SR 2a , -S(O)R 2a , -S(O)(NR 2a )(R 2b ), -S(NR 2a )(NR 2b )(R 2c ), -S(O)R 2a , -S(O)2N(R 2a )(R 2b ), -N(R 2a )S(O)2(R 2b ), -P(R 2a)(R 2b ), -P(O)(R 2a )(R 2b ), -P(O)(OR 2a )(R 2b ), -P(O)(OR 2a )(OR 2b ), C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), where each alkyl, alkenyl, or alkynyl is independently selected from 1 to 3 R 2d groups, each cycloalkyl being optionally substituted with 1 to 3 R 2e and each aryl is optionally substituted with 1 to 3 R 2f groups, and each heterocycloalkyl is optionally substituted with 1 to 3 R 2g and each heteroaryl is optionally substituted with 1 to 3 R 2h and optionally substituted with a group, Each R 2a , R 2b , and R 2c are independently hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6alkyl-(heteroaryl), where the aryl or heteroaryl is selected from 1 to 3 R 2j and optionally substituted with Alternatively, R 2a , R 2b , and R 2c when attached to the same atom, can combine with the atom to which they are attached to form a heterocycloalkyl, Each R 2d are independently -CN, -C(O)R 2d1 , -C(O)OR 2d1 , -OC(O)R 2d1 , -C(O)N(R 2d1 )(R 2d2 ), -N(R 2d1 )C(O)R 2d2 , -OC(O)N(R 2d1 )(R 2d2 ), -N(R 2d1 )C(O)OR 2d2 , -N(R 2d1 )(R 2d2 ), =O, -OR 2d1 , -SR 2d1 , -S(O)R 2d1 , -S(O)(NR 2d1 )(R 2d2 ), -S(O)R 2d1 , -S(O)N(R 2d1 )(R 2d2 ), -N(R 2d1 )S(O)2R 2d2 , C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), Each R 2d1 and R 2d2 are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C2~6 Alkoxyalkyl, or C 1~6 is haloalkyl, Each R 2e , R 2f , R 2g , and R 2h are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 haloalkoxy, -CN, or -OH; Each R 2j independently, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, or C 1~6 haloalkoxy, R 3 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -NO, -NO2, -C(O)R 3a , -C(O)OR 3a , -OC(O)R 3a , -C(O)N(R 3a )(R 3b ), -N(R 3a )C(O)R 3b , -OC(O)N(R 3a )(R 3b ), -N(R 3a )C(O)OR 3b , -C(=NR 3a )N(R 3b )(R3c ), -N(R 3a )(R 3b ), -N(R 3a )N(R 3b )(R 3c ), -N(R 3a )N=C(R 3b )(OR 3c ), -OR 3a , -SR 3a , -S(O)R 3a , -S(O)(NR 3a )(R 3b ), -S(NR 3a )(NR 3b )(R 3c ), -S(O)R 3a , -S(O)2N(R 3a )(R 3b ), -N(R 3a )S(O)2(R 3b ), -P(R 3a )(R 3b ), -P(O)(R 3a )(R 3b ), -P(O)(OR 3a )(R 3b ), -P(O)(OR 3a )(OR 3b ), C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), where each alkenyl or alkynyl independently is selected from 1 to 3 R 3d groups, each cycloalkyl being optionally substituted with 1 to 3 R 3e and each aryl is optionally substituted with 1 to 3 R 3f groups, and each heterocycloalkyl is optionally substituted with 1 to 3 R 3g and each heteroaryl is optionally substituted with 1 to 3 R 3h and optionally substituted with a group, Each R 3a , R 3b , and R 3c are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 aryl, heterocycloalkyl, or heteroaryl; Alternatively, R 3a , R 3b , and R 3c when attached to the same atom, can combine with the atom to which they are attached to form a heterocycloalkyl, Each R 3d are independently -N(R 3d1 )(R 3d2 ), -OR 3d1 , C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 aryl, heterocycloalkyl, or heteroaryl; Each R 3d1 and R 3d2 are independently hydrogen, C 1~6 Alkyl, or -C(O)O-(C 1~6 alkyl), Each R 3e , R 3f , R 3g , and R 3h are independently hydrogen, C 1~6 Alkyl, C 1~6 Alkoxy, halogen, C 1~6 Haloalkyl, or C 1~6 haloalkoxy, R 4 is hydrogen, C 1~6 Alkyl, C 2~6Alkenyl, C 2~6 Alkynyl, C 1~6 Alkoxy, halogen, C 1~6 Haloalkyl, C 1~6 haloalkoxy, or -CN; R 5 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), where alkyl is R 5a and optionally substituted with R 5a is -OSi(R 5a1 )(R 5a2 )(R 5a3 ) and R 5a1 , R 5a2 , and R 5a3 are each independently C 1~6 is alkyl, R 6 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 6~12 aryl or heteroaryl, wherein the aryl or heteroaryl is selected from 1 to 3 R 6a each optionally substituted with Each R 6a independently, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C1~6 Aminoalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -NO2, -C(O)R 6b , -C(O)OR 6b , -OC(O)R 6b , -C(O)N(R 6b )(R 6c ), -N(R 6b )C(O)R 6c , -C(=NR 6b )N(R 6c )(R 6d ), -N(R 6b )(R 6c ), -OR 6b , -SR 6b , -S(O)R 6b , -S(O)2R 6b , -S(NR 6b )(NR 6c )R 6d , -S(O)(NR 6b )(R 6c ), -S(O)2N(R 6b )(R 6c ), -N(R 6b )S(O)2(R 6c ), -P(R 6b )(R 6c ), -P(O)(R 6b )(R 6c ), -P(O)(OR 6b )(R 6c ), -P(O)(OR 6b )(OR 6c ), C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), where cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is selected from 1 to 3 R6e each optionally substituted with alkyl, R 6f and the alkynyl is optionally substituted with 1 to 4 R 6j and optionally substituted with Each R 6b , R 6c and R 6d are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), where cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is selected from 1 to 3 R 6k and optionally substituted by Each R 6k independently, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, heterocycloalkyl, or C 1~6 alkyl-(heterocycloalkyl), Each R 6e independently, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6Aminoalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -NO2, -C(O)R 6e1 , -C(O)OR 6e1 , -OC(O)R 6e1 , -C(O)N(R 6e1 )(R 6e2 ), -N(R 6e1 )C(O)R 6e2 , -OC(O)N(R 6e1 )(R 6e2 ), -N(R 6e1 )C(O)OR 6e2 , -C(=NR 6e1 )N(R 6e2 )(R 6e3 ), -N(R 6e1 )(R 6e2 ), =O, -OR 6e1 , -SR 6e1 , -S(O)R 6e1 , -S(NR 6e1 )(NR 6e2 ), -S(O)(NR 6e1 )(R 6e2 ), -S(O)R 6e1 , -S(O)2N(R 6e1 )(R 6e2 ), -SF5, -N(R 6e1 )S(O)2(R 6e2 ), -P(R 6e1 )(R 6e2 ), -P(O)(R 6e1 )(R 6e2 ), -P(O)(OR 6e1 )(R 6e2 ), -P(O)(OR 6e1 )(OR 6e2 ), -Si(R 6e1 )(R 6e2 )(R 6e3 ), C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 Aryl, heterocycloalkyl, C 1~6Alkyl-heterocycloalkyl, heteroaryl, or C 1~6 alkyl-heteroaryl, where cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is selected from 1 to 3 R 6h each optionally substituted with 1 to 3 R 6m and optionally substituted with Each R 6e1 , R 6e2 , and R 6e3 are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~10 Aryl, C 1~6 Alkyl-C 6~10 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), where cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is selected from 1 to 3 R 6n and optionally substituted with Each R 6n is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -C(O)R 6n1 , -C(O)OR 6n1 , -OC(O)R 6n1 , -C(O)N(R 6n1 )(R 6n2 ), -N(R 6n1 )C(O)R 6n2, -OC(O)N(R 6n1 )(R 6n2 ), -N(R 6n1 )C(O)OR 6n2 , -C(=NR 6n1 )N(R 6n2 )(R 6n3 ), -N(R 6n1 )(R 6n2 ), =O, -OH, -SR 6n1 , -S(O)R 6n1 , -S(NR 6n1 )(NR 6n2 )R 6n3 , -S(O)(NR 6n1 )(R 6n2 ), -S(O)R 6n1 , -S(O)2N(R 6n1 )(R 6n2 ), or -N(R 6n1 )S(O)2(R 6n2 ) and Each R 6n1 , R 6n2 and R 6n3 are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~10 Aryl, C 1~6 Alkyl-C 6~10 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), Each R 6h independently, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6Haloalkyl, C 1~6 Haloalkoxy, -CN, -C(O)R 6h1 , -C(O)OR 6h1 , -OC(O)R 6h1 , -C(O)N(R 6h1 )(R 6h2 ), -N(R 6h1 )C(O)R 6h2 , -OC(O)N(R 6h1 )(R 6h2 ), -N(R 6h1 )C(O)OR 6h2 , -C(=NR 6h1 )N(R 6h2 )(R 6h3 ), -N(R 6h1 )(R 6h2 ), =O, -OH, -SR 6h1 , -S(O)R 6h1 , -S(NR 6h1 )(NR 6h2 )R 6h3 , -S(O)(NR 6h1 )(R 6h2 ), -S(O)R 6h1 , -S(O)2N(R 6h1 )(R 6h2 ), -N(R 6h1 )S(O)2(R 6h2 ), C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, heterocycloalkyl, or C 1~6 alkyl-(heterocycloalkyl), Each R 6h1 , R 6h2 , and R 6h3 are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~10 Aryl, C 1~6 Alkyl-C 6~10 Aryl, heterocycloalkyl, C1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), Each R 6m are independently halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -C(O)R 6m1 , -C(O)OR 6m1 , -OC(O)R 6m1 , -C(O)N(R 6m1 )(R 6m2 ), -N(R 6m3 )C(O)R 6m2 , -OC(O)N(R 6m1 )(R 6m2 ), -N(R 6m1 )C(O)OR 6m2 , -C(=NR 6m3 )N(R 6m1 )(R 6m2 ), -N(R 6m1 )(R 6m2 ), =O, -OH, -SR 6m1 , -S(O)R 6m1 , -S(NR 6m1 )(NR 6m2 )R 6m3 , -S(O)(NR 6m1 )(R 6m2 ), -S(O)R 6m1 , -S(O)2N(R 6m1 )(R 6m2 ), or -N(R 6m3 )S(O)2(R 6m2 ) and Each R 6m1 , R 6m2 , and R 6m3 are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~10 Aryl, C 1~6 Alkyl-C 6~10Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), R 6f is -OSi(R 6f1 )(R 6f2 )(R 6f3 ) and R 6f1 , R 6f2 , and R 6f3 are each independently C 1~6 is alkyl, Each R 6j independently, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -C(O)R 6j1 , -C(O)OR 6j1 , -OC(O)R 6j1 , -C(O)N(R 6j1 )(R 6j2 ), -N(R 6j3 )C(O)R 6j2 , -OC(O)N(R 6j1 )(R 6j2 ), -N(R 6j1 )C(O)OR 6j2 , -C(=NR 6j3 )N(R 6j1 )(R 6j2 ), -N(R 6j1 )(R 6j2 ), =O, -OR 6j1 , -SR 6j1 , -S(O)R 6j1 , -S(NR 6j1 )(NR 6j2 ), -S(NR 6j1 )(NR 6j2 )R 6j3 , -S(O)(NR 6j1 )(R 6j2 ), -S(O)R 6j1 , -S(O)2N(R 6j1 )(R 6j2 ), -N(R 6j1 )S(O)2(R 6j2 ), -Si(R 6j1 )(R 6j2)(R 6j3 ), C 3~10 Cycloalkyl, C 6~12 aryl, heterocycloalkyl, or heteroaryl, wherein the cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is selected from the group consisting of 1 to 3 R 6p and optionally substituted with Each R 6j1 , R 6j2 , and R 6j3 are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~10 Aryl, C 1~6 Alkyl-C 6~10 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), Each R 6p independently, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -C(O)R 6p1 , -C(O)OR 6p1 , -OC(O)R 6p1 , -C(O)N(R 6p1 )(R 6p2 ), -N(R 6p1 )C(O)R 6p2 , -OC(O)N(R 6p1 )(R 6p2 ), -N(R 6p1 )C(O)OR 6p2 , -C(=NR 6p3 )N(R 6p1 )(R6p2 ), -N(R 6p1 )(R 6p2 ), =O, -OH, -SR 6p1 , -S(O)R 6p1 , -S(NR 6p1 )(NR 6p2 )R 6p3 , -S(O)(NR 6p1 )(R 6p2 ), -S(O)R 6p1 , -S(O)2N(R 6p1 )(R 6p2 ), or -N(R 6p1 )S(O)2(R 6p2 ) and Each R 6p1 , R 6p2 , and R 6p3 are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~10 Aryl, C 1~6 Alkyl-C 6~10 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), Or R 5 and one R 6a together with the atoms to which they are attached form a heterocycloalkyl, and one to three R 6g and optionally substituted with Each R 6g independently, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6haloalkoxy, or -CN; R 7 is hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, C 1~6 Alkylthio, halogen, C 1~6 Haloalkyl, -CN, -OH, -NH2, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, heterocycloalkyl, or C 1~6 alkyl-(heterocycloalkyl), each heterocycloalkyl is a 3- to 20-membered ring having 1-4 heteroatoms, each independently N, O, or S; each heteroaryl is a 5- to 18-membered ring having 1-4 heteroatoms, each independently N, O, or S; However, R 5 and R 6 are both C 1~4 R, not alkyl 5 When is hydrogen, R 6 is not isopropyl or phenyl substituted with 2-Me.

[0010] In another embodiment, the present disclosure provides a pharmaceutical composition comprising a pharmaceutically effective amount of a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

[0011] In another embodiment, the present disclosure provides a method for inhibiting DGKα in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of the present disclosure or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of the present disclosure.

[0012] In another embodiment, the present disclosure provides a method of inhibiting DGKα in a subject in need thereof, the method comprising administering a therapeutically effective amount of a compound of formula (I): [ka] or a pharmaceutically acceptable salt thereof to a subject, wherein: R 1 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Alkoxy, halogen, C 1~6 Haloalkyl, C 1~6 haloalkoxy, or -CN; R 2 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -NO, -NO2, -C(O)R 2a , -C(O)OR 2a , -OC(O)R 2a , -C(O)N(R 2a )(R 2b ), -N(R 2a )C(O)R 2b , -OC(O)N(R 2a )(R 2b ), -N(R 2a )C(O)OR 2b , -C(=NR 2a )N(R 2b )(R 2c ), -N(R 2a )(R 2b ), -N(R 2a )N(R 2b )(R 2c ), -N(R 2a )N=C(R 2b )(OR 2c ), -OR 2a , -SR 2a , -S(O)R 2a , -S(O)(NR 2a )(R 2b ), -S(NR2a )(NR 2b )(R 2c ), -S(O)R 2a , -S(O)2N(R 2a )(R 2b ), -N(R 2a )S(O)2(R 2b ), -P(R 2a )(R 2b ), -P(O)(R 2a )(R 2b ), -P(O)(OR 2a )(R 2b ), -P(O)(OR 2a )(OR 2b ), C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), where each alkyl, alkenyl, or alkynyl is independently selected from 1 to 3 R 2d groups, each cycloalkyl being optionally substituted with 1 to 3 R 2e and each aryl is optionally substituted with 1 to 3 R 2f groups, and each heterocycloalkyl is optionally substituted with 1 to 3 R 2g and each heteroaryl is optionally substituted with 1 to 3 R 2h and optionally substituted with a group, Each R 2a , R 2b , and R 2c are independently hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), where the aryl or heteroaryl is selected from 1 to 3 R 2j and optionally substituted with Alternatively, R 2a , R 2b , and R 2c when attached to the same atom, can combine with the atom to which they are attached to form a heterocycloalkyl, Each R 2d are independently -CN, -C(O)R 2d1 , -C(O)OR 2d1 , -OC(O)R 2d1 , -C(O)N(R 2d1 )(R 2d2 ), -N(R 2d1 )C(O)R 2d2 , -OC(O)N(R 2d1 )(R 2d2 ), -N(R 2d1 )C(O)OR 2d2 , -N(R 2d1 )(R 2d2 ), =O, -OR 2d1 , -SR 2d1 , -S(O)R 2d1 , -S(O)(NR 2d1 )(R 2d2 ), -S(O)R 2d1 , -S(O)N(R 2d1 )(R 2d2 ), -N(R 2d1 )S(O)2R 2d2 , C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 Aryl, heterocycloalkyl, C 1~6Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), Each R 2d1 and R 2d2 are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 2~6 Alkoxyalkyl, or C 1~6 is haloalkyl, Each R 2e , R 2f , R 2g , and R 2h are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 haloalkoxy, -CN, or -OH; Each R 2j independently, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, or C 1~6 haloalkoxy, R 3 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -NO, -NO2, -C(O)R 3a , -C(O)OR 3a , -OC(O)R 3a , -C(O)N(R3a )(R 3b ), -N(R 3a )C(O)R 3b , -OC(O)N(R 3a )(R 3b ), -N(R 3a )C(O)OR 3b , -C(=NR 3a )N(R 3b )(R 3c ), -N(R 3a )(R 3b ), -N(R 3a )N(R 3b )(R 3c ), -N(R 3a )N=C(R 3b )(OR 3c ), -OR 3a , -SR 3a , -S(O)R 3a , -S(O)(NR 3a )(R 3b ), -S(NR 3a )(NR 3b )(R 3c ), -S(O)R 3a , -S(O)2N(R 3a )(R 3b ), -N(R 3a )S(O)2(R 3b ), -P(R 3a )(R 3b ), -P(O)(R 3a )(R 3b ), -P(O)(OR 3a )(R 3b ), -P(O)(OR 3a )(OR 3b ), C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), where each alkenyl or alkynyl independently is selected from 1 to 3 R 3dgroups, each cycloalkyl being optionally substituted with 1 to 3 R 3e and each aryl is optionally substituted with 1 to 3 R 3f groups, and each heterocycloalkyl is optionally substituted with 1 to 3 R 3g and each heteroaryl is optionally substituted with 1 to 3 R 3h and optionally substituted with a group, Each R 3a , R 3b , and R 3c are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 aryl, heterocycloalkyl, or heteroaryl; Alternatively, R 3a , R 3b , and R 3c when attached to the same atom, can combine with the atom to which they are attached to form a heterocycloalkyl, Each R 3d are independently -N(R 3d1 )(R 3d2 ), -OR 3d1 , C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 aryl, heterocycloalkyl, or heteroaryl; Each R 3d1 and R 3d2 are independently hydrogen, C 1~6 Alkyl, or -C(O)O-(C 1~6 alkyl), Each R 3e , R 3f , R3g , and R 3h are independently hydrogen, C 1~6 Alkyl, C 1~6 Alkoxy, halogen, C 1~6 Haloalkyl, or C 1~6 haloalkoxy, R 4 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Alkoxy, halogen, C 1~6 Haloalkyl, C 1~6 haloalkoxy, or -CN; R 5 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), where alkyl is R 5a and optionally substituted with R 5a is -OSi(R 5a1 )(R 5a2 )(R 5a3 ) and R 5a1 , R 5a2 , and R 5a3 are each independently C 1~6 is alkyl, R 6 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 6~12aryl or heteroaryl, wherein the aryl or heteroaryl is selected from 1 to 3 R 6a each optionally substituted with Each R 6a independently, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -NO2, -C(O)R 6b , -C(O)OR 6b , -OC(O)R 6b , -C(O)N(R 6b )(R 6c ), -N(R 6b )C(O)R 6c , -C(=NR 6b )N(R 6c )(R 6d ), -N(R 6b )(R 6c ), -OR 6b , -SR 6b , -S(O)R 6b , -S(O)2R 6b , -S(NR 6b )(NR 6c )R 6d , -S(O)(NR 6b )(R 6c ), -S(O)2N(R 6b )(R 6c ), -N(R 6b )S(O)2(R 6c ), -P(R 6b )(R 6c ), -P(O)(R 6b )(R 6c ), -P(O)(OR 6b )(R 6c ), -P(O)(OR 6b )(OR 6c ), C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), where cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is selected from 1 to 3 R 6e each optionally substituted with alkyl, R 6f and the alkynyl is optionally substituted with 1 to 4 R 6j and optionally substituted with Each R 6b , R 6c and R 6d are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), where cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is selected from 1 to 3 R 6k and optionally substituted by Each R 6k independently, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, C 3~10 Cycloalkyl, C 1~6 Alkyl-C3~10 Cycloalkyl, heterocycloalkyl, or C 1~6 alkyl-(heterocycloalkyl), Each R 6e independently, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -NO2, -C(O)R 6e1 , -C(O)OR 6e1 , -OC(O)R 6e1 , -C(O)N(R 6e1 )(R 6e2 ), -N(R 6e1 )C(O)R 6e2 , -OC(O)N(R 6e1 )(R 6e2 ), -N(R 6e1 )C(O)OR 6e2 , -C(=NR 6e1 )N(R 6e2 )(R 6e3 ), -N(R 6e1 )(R 6e2 ), =O, -OR 6e1 , -SR 6e1 , -S(O)R 6e1 , -S(NR 6e1 )(NR 6e2 ), -S(O)(NR 6e1 )(R 6e2 ), -S(O)R 6e1 , -S(O)2N(R 6e1 )(R 6e2 ), -SF5, -N(R 6e1 )S(O)2(R 6e2 ), -P(R 6e1 )(R 6e2 ), -P(O)(R 6e1 )(R 6e2 ), -P(O)(OR 6e1 )(R 6e2 ), -P(O)(OR 6e1 )(OR 6e2), -Si(R 6e1 )(R 6e2 )(R 6e3 ), C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 Aryl, heterocycloalkyl, C 1~6 Alkyl-heterocycloalkyl, heteroaryl, or C 1~6 alkyl-heteroaryl, where cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is selected from 1 to 3 R 6h each optionally substituted with 1 to 3 R 6m and optionally substituted with Each R 6e1 , R 6e2 , and R 6e3 are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~10 Aryl, C 1~6 Alkyl-C 6~10 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), where cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is selected from 1 to 3 R 6n and optionally substituted with Each R 6n is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 2~6Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -C(O)R 6n1 , -C(O)OR 6n1 , -OC(O)R 6n1 , -C(O)N(R 6n1 )(R 6n2 ), -N(R 6n1 )C(O)R 6n2 , -OC(O)N(R 6n1 )(R 6n2 ), -N(R 6n1 )C(O)OR 6n2 , -C(=NR 6n1 )N(R 6n2 )(R 6n3 ), -N(R 6n1 )(R 6n2 ), =O, -OH, -SR 6n1 , -S(O)R 6n1 , -S(NR 6n1 )(NR 6n2 )R 6n3 , -S(O)(NR 6n1 )(R 6n2 ), -S(O)R 6n1 , -S(O)2N(R 6n1 )(R 6n2 ), or -N(R 6n1 )S(O)2(R 6n2 ) and Each R 6n1 , R 6n2 and R 6n3 are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~10 Aryl, C 1~6 Alkyl-C 6~10 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), Each R 6h independently, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -C(O)R 6h1 , -C(O)OR 6h1 , -OC(O)R 6h1 , -C(O)N(R 6h1 )(R 6h2 ), -N(R 6h1 )C(O)R 6h2 , -OC(O)N(R 6h1 )(R 6h2 ), -N(R 6h1 )C(O)OR 6h2 , -C(=NR 6h1 )N(R 6h2 )(R 6h3 ), -N(R 6h1 )(R 6h2 ), =O, -OH, -SR 6h1 , -S(O)R 6h1 , -S(NR 6h1 )(NR 6h2 )R 6h3 , -S(O)(NR 6h1 )(R 6h2 ), -S(O)R 6h1 , -S(O)2N(R 6h1 )(R 6h2 ), -N(R 6h1 )S(O)2(R 6h2 ), C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, heterocycloalkyl, or C 1~6 alkyl-(heterocycloalkyl), Each R 6h1 , R 6h2 , and R 6h3 are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C1~6 Aminoalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~10 Aryl, C 1~6 Alkyl-C 6~10 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), Each R 6m are independently halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -C(O)R 6m1 , -C(O)OR 6m1 , -OC(O)R 6m1 , -C(O)N(R 6m1 )(R 6m2 ), -N(R 6m3 )C(O)R 6m2 , -OC(O)N(R 6m1 )(R 6m2 ), -N(R 6m1 )C(O)OR 6m2 , -C(=NR 6m3 )N(R 6m1 )(R 6m2 ), -N(R 6m1 )(R 6m2 ), =O, -OH, -SR 6m1 , -S(O)R 6m1 , -S(NR 6m1 )(NR 6m2 )R 6m3 , -S(O)(NR 6m1 )(R 6m2 ), -S(O)R 6m1 , -S(O)2N(R 6m1 )(R 6m2 ), or -N(R 6m3 )S(O)2(R 6m2 ) and Each R 6m1 , R 6m2 , and R 6m3 are independently hydrogen, C 1~6 Alkyl, C1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~10 Aryl, C 1~6 Alkyl-C 6~10 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), R 6f is -OSi(R 6f1 )(R 6f2 )(R 6f3 ) and R 6f1 , R 6f2 , and R 6f3 are each independently C 1~6 is alkyl, Each R 6j independently, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -C(O)R 6j1 , -C(O)OR 6j1 , -OC(O)R 6j1 , -C(O)N(R 6j1 )(R 6j2 ), -N(R 6j3 )C(O)R 6j2 , -OC(O)N(R 6j1 )(R 6j2 ), -N(R 6j1 )C(O)OR 6j2 , -C(=NR 6j3 )N(R 6j1 )(R 6j2 ), -N(R 6j1 )(R 6j2 ), =O, -OR 6j1 , -SR 6j1 , -S(O)R 6j1 , -S(NR 6j1 )(NR 6j2 ), -S(NR 6j1 )(NR6j2 )R 6j3 , -S(O)(NR 6j1 )(R 6j2 ), -S(O)R 6j1 , -S(O)2N(R 6j1 )(R 6j2 ), -N(R 6j1 )S(O)2(R 6j2 ), -Si(R 6j1 )(R 6j2 )(R 6j3 ), C 3~10 Cycloalkyl, C 6~12 aryl, heterocycloalkyl, or heteroaryl, wherein the cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is selected from the group consisting of 1 to 3 R 6p and optionally substituted with Each R 6j1 , R 6j2 , and R 6j3 are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~10 Aryl, C 1~6 Alkyl-C 6~10 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), Each R 6p independently, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -C(O)R 6p1 , -C(O)OR 6p1 , -OC(O)R 6p1, -C(O)N(R 6p1 )(R 6p2 ), -N(R 6p1 )C(O)R 6p2 , -OC(O)N(R 6p1 )(R 6p2 ), -N(R 6p1 )C(O)OR 6p2 , -C(=NR 6p3 )N(R 6p1 )(R 6p2 ), -N(R 6p1 )(R 6p2 ), =O, -OH, -SR 6p1 , -S(O)R 6p1 , -S(NR 6p1 )(NR 6p2 )R 6p3 , -S(O)(NR 6p1 )(R 6p2 ), -S(O)R 6p1 , -S(O)2N(R 6p1 )(R 6p2 ), or -N(R 6p1 )S(O)2(R 6p2 ) and Each R 6p1 , R 6p2 , and R 6p3 are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~10 Aryl, C 1~6 Alkyl-C 6~10 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), Or R 5 and one R 6a together with the atoms to which they are attached form a heterocycloalkyl, and one to three R 6g and optionally substituted with Each R 6g independently, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 haloalkoxy, or -CN; R 7 is hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, C 1~6 Alkylthio, halogen, C 1~6 Haloalkyl, -CN, -OH, -NH2, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, heterocycloalkyl, or C 1~6 alkyl-(heterocycloalkyl), each heterocycloalkyl is a 3- to 20-membered ring having 1-4 heteroatoms, each independently N, O, or S; Each heteroaryl is a 5- to 18-membered ring having 1-4 heteroatoms, each independently N, O, or S.

[0013] In another embodiment, the present disclosure provides 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 the present disclosure or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of the present disclosure.

[0014] In another embodiment, the present disclosure provides a method of treating 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 the present disclosure or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of the present disclosure. DETAILED DESCRIPTION OF THE INVENTION

[0015] I. Definition "Alkyl" refers to a straight- or branched-chain saturated monovalent hydrocarbon. For example, an alkyl group may contain 1 to 18 carbon atoms (i.e., C 1~18 alkyl), or 1 to 8 carbon atoms (i.e., C 1~8 alkyl), or 1 to 6 carbons (i.e., C 1~6 alkyl), or 1 to 4 carbon atoms (i.e., C 1~4Examples of alkyl groups include methyl (Me, -CH3), ethyl (Et, -CH2CH3), 1-propyl (n-Pr, n-propyl, -CH2CH2CH3), 2-propyl (i-Pr, i-propyl, -CH(CH3)2), 1-butyl (n-Bu, n-butyl, -CH2CH2CH2CH3), 2-methyl-1-propyl (i-Bu, i-butyl, -CH2CH(CH3)2), 2-butyl (s-Bu, s-butyl, -CH(CH3)CH2CH3), 2-methyl-2-propyl butyl (t-Bu, t-butyl, -C(CH3)3), 1-pentyl (n-pentyl, -CH2CH2CH2CH2CH3), 2-pentyl (-CH(CH3)CH2CH2CH3), 3-pentyl (-CH(CH2CH3)2), 2-methyl-2-butyl (-C(CH3)2CH2CH3), 3-methyl-2-butyl (-CH(CH3)CH(CH3)2), 3-methyl-1-butyl (-CH2CH2CH(CH3)2), 2-methyl-1-butyl (-CH2CH(CH3)CH2 CH3), 1-hexyl (-CH2CH2CH2CH2CH2CH3), 2-hexyl (-CH(CH3)CH2CH2CH2CH3), 3-hexyl (-CH(CH2CH3)(CH2CH2CH3)), 2-methyl-2-pentyl (-C(CH3)2CH2CH2CH3), 3-methyl-2-pentyl (-CH(CH3)CH(CH3)CH2CH3), 4-methyl-2-pentyl (-CH(CH3)CH2CH(CH3)2), 3-methyl-3-pentyl (-C(CH3) (CH2CH3)2), 2-methyl-3-pentyl (-CH(CH2CH3)CH(CH3)2), 2,3-dimethyl-2-butyl (-C(CH3)2CH(CH3)2), and 3,3-dimethyl-2-butyl (-CH(CH3)C(CH3)3). Other alkyl groups include heptyl, octyl, nonyl, decyl, undecyl, dodecyl, pentadecyl, hexadecyl, heptadecyl, and octadecyl.

[0016] "Alkylene" refers to a straight-chain or branched saturated aliphatic radical, i.e., a divalent hydrocarbon radical, having the number of carbon atoms indicated and linking at least two other groups. The two moieties linked to the alkylene can be linked to the same atom or different atoms of the alkylene group. For example, a straight-chain alkylene is -(CH2) n -, where n is 1, 2, 3, 4, 5, or 6. Representative alkylene groups include, but are not limited to, methylene, ethylene, propylene, isopropylene, butylene, isobutylene, sec-butylene, pentylene, and hexylene. Alkylene groups can be substituted or unsubstituted.

[0017] "Alkenyl" refers to a straight or branched chain hydrocarbon having at least two carbon atoms and at least one double bond. Alkenyl can be any number of carbons, e.g., C, C 2~3 , C 2~4 , C 2~5 , C 2~6 , C 2~7 , C 2~8 , C 2~9 , C 2~10 , C3, C 3~4 , C 3~5 , C 3~6 , C4, C 4~5 , C 4~6 , C5, C 5~6 , and C6. Alkenyl groups can have any suitable number of double bonds, including, but not limited to, 1, 2, 3, 4, 5 or more. Examples of alkenyl groups include, but are not limited to, vinyl (ethenyl), propenyl, isopropenyl, 1-butenyl, 2-butenyl, isobutenyl, butadienyl, 1-pentenyl, 2-pentenyl, isopentenyl, 1,3-pentadienyl, 1,4-pentadienyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 1,3-hexadienyl, 1,4-hexadienyl, 1,5-hexadienyl, 2,4-hexadienyl, or 1,3,5-hexatrienyl. Alkenyl groups can be substituted or unsubstituted.

[0018] "Alkynyl" refers to either a straight or branched chain hydrocarbon having at least two carbon atoms and at least one triple bond. Alkynyl can be any number of carbons, e.g., C, C 2~3 , C 2~4 , C 2~5 , C 2~6 , C 2~7 , C 2~8 , C 2~9 , C 2~10 , C3, C 3~4 , C 3~5 , C 3~6 , C4, C 4~5 , C 4~6 , C5, C 5~6 , and C6. Examples of alkynyl groups include, but are not limited to, acetylenyl, propynyl, 1-butynyl, 2-butynyl, butadinyl, 1-pentynyl, 2-pentynyl, isopentynyl, 1,3-pentadiynyl, 1,4-pentadiynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 1,3-hexadiynyl, 1,4-hexadiynyl, 1,5-hexadiynyl, 2,4-hexadiynyl, or 1,3,5-hexatriynyl. Alkynyl groups can be substituted or unsubstituted.

[0019] "Alkoxy" refers to an alkyl group having an oxygen atom connecting the alkyl group to the point of attachment: alkyl-O-. With respect to alkyl groups, alkoxy groups include C 1~6 Alkoxy groups can have any suitable number of carbon atoms, such as , ...

[0020] "Alkoxyalkyl" refers to an alkoxy group linked to an alkyl group which is linked to the rest of the compound, making the alkyl group divalent. The alkoxyalkyl has 2 to 6 (C 2~6 alkoxyalkyl), 2 to 5 (C 2~5alkoxyalkyl), 2 to 4 (C 2~4 alkoxyalkyl), or 2 to 3 (C 2~3 The alkoxy group may have any suitable number of carbons, such as alkoxyalkyl. The number of carbons refers to the total number of carbons in the alkoxy and alkyl groups. For example, C alkoxyalkyl refers to ethoxy (C alkoxy) linked to butyl (C alkyl), and n-propoxy (C alkoxy) linked to isopropyl (C alkyl). Alkoxy and alkyl are as defined above, where alkyl is divalent and may include, but are not limited to, methoxymethyl (CH)OCH—), methoxyethyl (CHOCHCH—), and others.

[0021] "Aminoalkyl" refers to an amino group linked to an alkyl group which is linked to the remainder of the compound, making the alkyl group divalent. The amino group can be unsubstituted amino (-NH2) or substituted with an alkyl group, e.g., monosubstituted amino (e.g., -NHCH3), or disubstituted amino (e.g., -N(CH3)2). An aminoalkyl can have 1 to 8 (C 1~8 aminoalkyl), 1 to 6 (C 1~6 aminoalkyl), 2 to 6 (C 2~6 aminoalkyl), 2 to 4 (C 2~4 aminoalkyl), or 2 to 3 (C 2~3 The amino alkyl may have any suitable number of carbons, such as -N(CH)(Camino) (aminoalkyl). The number of carbons refers to the total number of carbons in the amino and alkyl groups. For example, a C amino alkyl refers to -N(CH)(Camino) linked to butyl (C alkyl) and -NHCHCHCH(Camino) linked to isopropyl (C alkyl). Alkyl is as defined above, where alkyl is divalent. Amino alkyls can include, but are not limited to, aminomethyl (HNCH-), methylaminomethyl (CHNHCH-), dimethylaminomethyl ((CH)NCH-), dimethylaminoethyl ((CH)NCHCH-), and others.

[0022] "Alkoxy-alkoxy" refers to an alkoxy group linked to a second alkoxy group which is linked to the remainder of the compound. Alkoxy is as defined above and can include, but is not limited to, methoxy-methoxy (CH3OCH2O-), methoxy-ethoxy (CHOCH2CHO-), and others.

[0023] "Halo" or "halogen," as used herein, refers to fluoro (-F), chloro (-Cl), bromo (-Br), and iodo (-I).

[0024] As used herein, "haloalkyl" refers to an alkyl, as defined herein, in which one or more hydrogen atoms of the alkyl are independently replaced with halo substituents, which may be the same or different. For example, C 1~4 Haloalkyl is C 1~4 alkyl, C 1~4 One or more of the hydrogen atoms of the alkyl is replaced by a halo substituent. Examples of haloalkyl groups include, but are not limited to, fluoromethyl, fluorochloromethyl, difluoromethyl, difluorochloromethyl, trifluoromethyl, 1,1,1-trifluoroethyl, and pentafluoroethyl.

[0025] "Haloalkoxy" refers to an alkoxy group in which some or all of the hydrogen atoms are replaced with halogen atoms. With respect to alkyl groups, haloalkoxy groups include C 1~6 The alkoxy group can have any suitable number of carbon atoms, such as 1, 2, 3 or more halogens. When all hydrogens are replaced with halogens, such as fluorine, the compound is per-substituted, for example, perfluorinated. Haloalkoxy includes, but is not limited to, trifluoromethoxy, 2,2,2-trifluoroethoxy, perfluoroethoxy, etc.

[0026] "Cycloalkyl" refers to a group of 3 to 20 cyclic carbon atoms (i.e., C 3~20Cycloalkyl) refers to a single saturated or partially unsaturated all-carbocyclic ring, e.g., having 3 to 12 ring atoms, e.g., 3 to 10 ring atoms, or 3 to 8 ring atoms, or 3 to 6 ring atoms, or 3 to 5 ring atoms, or 3 to 4 ring atoms. The term "cycloalkyl" also includes multiple fused, saturated, and partially unsaturated all-carbocyclic ring systems (e.g., ring systems containing 2, 3, or 4 carbocyclic rings). Thus, cycloalkyl includes polycyclic carbocycles, such as bicyclic carbocycles (e.g., bicyclic carbocycles having 6 to 12 ring carbon atoms, such as bicyclo[3.1.0]hexane and bicyclo[2.1.1]hexane), and polycyclic carbocycles (e.g., tricyclic and tetracyclic carbocycles having up to 20 ring carbon atoms). Rings of multiple fused ring systems can be connected to each other through fused, spiro, and bridged bonds, if permitted by valence requirements. Non-limiting examples of monocyclic cycloalkyls include cyclopropyl, cyclobutyl, cyclopentyl, 1-cyclopent-1-enyl, 1-cyclopent-2-enyl, 1-cyclopent-3-enyl, cyclohexyl, 1-cyclohex-1-enyl, 1-cyclohex-2-enyl, and 1-cyclohex-3-enyl.

[0027] "Alkyl-cycloalkyl" refers to a radical having an alkyl component and a cycloalkyl component, where the alkyl component connects the cycloalkyl component to the point of attachment. The alkyl component is as defined above, except that the alkyl component is at least divalent alkylene to connect to the cycloalkyl component and the point of attachment. In some cases, the alkyl component can be absent. The alkyl component can be any number of carbons, e.g., C 1~6 , C 1~2 , C 1~3 , C 1~4 , C 1~5 , C 2~3 , C 2~4 , C 2~5 , C 2~6 , C 3~4 , C 3~5 , C 3~6 , C 4~5 , C 4~6 and C 5~6The cycloalkyl component is as defined herein. Exemplary alkyl-cycloalkyl groups include, but are not limited to, methyl-cyclopropyl, methyl-cyclobutyl, methyl-cyclopentyl, and methyl-cyclohexyl.

[0028] As used herein, "heterocyclyl" or "heterocycle" or "heterocycloalkyl" refers to a single saturated or partially unsaturated non-aromatic ring or multiple ring system having at least one heteroatom (i.e., at least one ring heteroatom selected from oxygen, nitrogen, and sulfur) in the ring, where the multiple ring system includes at least one non-aromatic ring containing at least one heteroatom. The multiple ring system may also include other aromatic and non-aromatic rings. Unless otherwise specified, a heterocyclyl group has 3 to 20 ring atoms, e.g., 3 to 12 ring atoms, e.g., 3 to 10 ring atoms, or 3 to 8 ring atoms, or 3 to 6 ring atoms, or 3 to 5 ring atoms, or 4 to 6 ring atoms, or 4 to 5 ring atoms. Thus, the term includes a single saturated or partially unsaturated ring (e.g., a 3-, 4-, 5-, 6-, or 7-membered ring) having 1 to 6 ring carbon atoms and 1 to 3 ring heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur within the ring. The heteroatoms are optionally oxidized, such as -N(-OH)-, ═N(-O -)-, -S(=O)-, or -S(=O)2-. The rings of multiple fused ring (e.g., bicyclic heterocyclyl) systems can be connected to each other via fused, spiro, and bridged bonds, where permitted by valence requirements. Heterocycles include azetidine, aziridine, imidazolidine, morpholine, oxirane (epoxide), oxetane, thietane, piperazine, piperidine, pyrazolidine, piperidine, pyrrolidine, pyrrolidinone, tetrahydrofuran, tetrahydrothiophene, dihydropyridine, tetrahydropyridine, quinacridine, 2-oxa-6-azaspiro[3.3]heptan-6-yl, 6-oxa-1-azaspiro[3.3]heptan-1-yl , 2-thia-6-azaspiro[3.3]heptan-6-yl, 2,6-diazaspiro[3.3]heptan-2-yl, 2-azabicyclo[3.1.0]hexan-2-yl, 3-azabicyclo[3.1.0]hexanyl, 2-azabicyclo[2.1.1]hexanyl, 2-azabicyclo[2.2.1]heptan-2-yl, 4-azaspiro[2.4]heptanyl, 5-azaspiro[2.4]heptanyl, and the like.

[0029] Heterocycloalkyl rings also include 9-15 membered fused-ring heterocycloalkyls having two, three, or more rings, where at least one ring is an aryl ring and at least one ring is a non-aromatic ring containing at least one heteroatom. Representative fused bicyclic heterocycloalkyls include, but are not limited to, indoline (dihydroindole), isoindoline (dihydroisoindole), indazoline (dihydroindazole), benzo[d]imidazole, dihydroquinoline, dihydroisoquinoline, dihydrobenzofuran, dihydroisobenzofuran, benzo[d][1,3]dioxole, dihydrobenzo[b]dioxin, dihydrobenzo[d]oxazole, dihydrobenzo[b]thiophene, dihydroisobenzo[c]thiophene, dihydrobenzo[d]thiazole, dihydrobenzo[c]isothiazole, and benzo[b][1,4]thiazine, as shown in the following structure: [ka] A fused bicyclic heterocycloalkyl can also be represented by the structure: [ka] In the formula, X 1 , X 2 , X 3 and X 4 are each independently absent, —CH—, —NH—, —O—, or —S—; X 1 , X 2 , X 3 and X 4 At least one of is -NH-, -O-, or -S-, and the dashed circle represents a saturated or partially unsaturated non-aromatic ring. A fused bicyclic heterocycloalkyl is optionally substituted.

[0030] "Alkyl-heterocycloalkyl" refers to a radical having an alkyl component and a heterocycloalkyl component, where the alkyl component connects the heterocycloalkyl component to the point of attachment. The alkyl component is as defined above, except that the alkyl component is at least divalent alkylene to connect to the heterocycloalkyl component and the point of attachment. The alkyl component can be any number of carbons, e.g., C 0~6 , C 1~2 , C 1~3 , C 1~4 , C 1~5 , C 1~6 , C 2~3 , C 2~4 , C 2~5 , C 2~6 , C 3~4 , C 3~5 , C 3~6 , C 4~5 , C 4~6 and C 5~6 In some cases, the alkyl component may be absent. The heterocycloalkyl component is as defined above. The alkyl-heterocycloalkyl group may be substituted or unsubstituted.

[0031] As used herein, "aryl" refers to a single all-carbon aromatic ring or a multiple fused all-carbon ring system, in which at least one of the rings is aromatic. For example, in some embodiments, aryl groups have 6 to 20 carbon atoms, 6 to 14 carbon atoms, or 6 to 12 carbon atoms. Aryl includes phenyl radicals. Aryl also includes multiple fused ring systems (e.g., ring systems containing 2, 3, or 4 rings) having 9 to 20 carbon atoms, e.g., 9 to 16 carbon atoms, in which at least one ring is aromatic and the other rings may or may not be aromatic (i.e., carbocyclic). Such multiple fused ring systems are optionally substituted with one or more (e.g., 1, 2, or 3) oxo groups on any carbocyclic portion of the multiple fused ring system. The rings of multiple fused ring systems can be connected to each other through fused, spiro, and bridged bonds, where permitted by valence requirements. It should also be understood that when referring to a specific atom range-membered aryl (e.g., a 6- to 10-membered aryl), the atom range is based on the total ring atoms of the aryl. For example, a 6-membered aryl includes phenyl, and a 10-membered aryl includes naphthyl and 1,2,3,4-tetrahydronaphthyl. Non-limiting examples of aryl groups include, but are not limited to, phenyl, indenyl, naphthyl, 1,2,3,4-tetrahydronaphthyl, anthracenyl, and the like.

[0032] "Alkyl-aryl" refers to a radical having an alkyl and an aryl component, where the alkyl component links the aryl component to the point of attachment. The alkyl component is as defined above, except that the alkyl component is at least divalent alkylene to connect to the aryl component and the point of attachment. The alkyl component can have any number of carbons, e.g., C 0~6 , C 1~2 , C 1~3 , C 1~4 , C 1~5 , C 1~6 , C 2~3 , C 2~4 , C 2~5 , C 2~6 , C 3~4 , C 3~5 , C 3~6 , C4~5 , C 4~6 and C 5~6 In some cases, the alkyl component may be absent. The aryl component is as defined above. Examples of alkyl-aryl groups include, but are not limited to, benzyl and ethylbenzene. The alkyl-aryl group may be substituted or unsubstituted.

[0033] As used herein, "heteroaryl" refers to a single aromatic ring having at least one atom other than carbon within the ring, the atom being selected from the group consisting of oxygen, nitrogen, and sulfur; "heteroaryl" also includes multiple fused ring systems having at least one such aromatic ring, which multiple fused ring systems are further described below. Thus, "heteroaryl" includes a single aromatic ring of 1 to 6 carbon atoms and 1 to 4 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur. When the ring is aromatic, the sulfur and nitrogen atoms may also be present in oxidized form. Exemplary heteroaryl ring systems include, but are not limited to, pyridyl, pyrimidinyl, oxazolyl, or furyl. "Heteroaryl" also includes multiple fused ring systems (e.g., ring systems containing 2, 3, or 4 rings), where a heteroaryl group as defined above is fused with one or more rings selected from heteroaryl (e.g., to form 1,8-naphthyridinyl), heterocycle (e.g., to form 1,2,3,4-tetrahydro-1,8-naphthyridinyl), carbocycle (e.g., to form 5,6,7,8-tetrahydroquinolyl), and aryl (e.g., to form indazolyl). Thus, a heteroaryl (single aromatic ring or multiple fused ring system) has 1 to 20 carbon atoms and 1 to 6 heteroatoms in the heteroaryl ring. Such multiple fused ring systems can be optionally substituted with one or more (e.g., 1, 2, 3, or 4) oxo groups on the carbocyclic or heterocyclic portions of the fused rings. The rings of multiple fused ring systems can be connected to each other via fused, spiro, and bridged bonds, where permitted by valence requirements. It is understood that the individual rings of a fused ring system can be connected to each other in any order. It is understood that the point of attachment of a heteroaryl or heteroaryl fused ring system can be any suitable atom of the heteroaryl or heteroaryl fused ring system, including carbon atoms and heteroatoms (e.g., nitrogen). When referring to a specific atom range-membered heteroaryl (e.g., a 5- to 10-membered heteroaryl), it is also understood that the atom range is for the total ring atoms of the heteroaryl and includes carbon atoms and heteroatoms.For example, a 5-membered heteroaryl would include thiazolyl and a 10-membered heteroaryl would include quinolinyl. Exemplary heteroaryls include, but are not limited to, pyridyl, pyrrolyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrazolyl, thienyl, indolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, furyl, oxadiazolyl, thiadiazolyl, quinolyl, isoquinolyl, benzothiazolyl, benzoxazolyl, indazolyl, quinoxalyl, quinazolyl, 5,6,7,8-tetrahydroisoquinolinylbenzofuranyl, benzimidazolyl, thianaphthenyl, pyrrolo[2,3-b]pyridinyl, quinazolinyl-4(3H)-one, and triazolyl.

[0034] "Alkyl-heteroaryl" refers to a radical having an alkyl component and a heteroaryl component, where the alkyl component links the heteroaryl component to the point of attachment. The alkyl component is as defined above, except that the alkyl component is at least divalent alkylene to connect to the heteroaryl component and the point of attachment. The alkyl component can have any number of carbons, e.g., C 0~6 , C 1~2 , C 1~3 , C 1~4 , C 1~5 , C 1~6 , C 2~3 , C 2~4 , C 2~5 , C 2~6 , C 3~4 , C 3~5 , C 3~6 , C 4~5 , C 4~6 and C 5~6 In some cases, the alkyl component may be absent. The heteroaryl component is as defined herein. The alkyl-heteroaryl group may be substituted or unsubstituted.

[0035] "Compounds of the present disclosure" include compounds disclosed herein, for example, compounds of the present disclosure include compounds of formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), and (IIc-8), such as the compounds of the Examples.

[0036] As used herein, "composition" is intended to encompass a product containing the specified ingredients in the specified amounts, as well as any product that results, directly or indirectly, from combining the specified amounts of the specified ingredients. "Pharmaceutically acceptable" means the carrier, diluent, or excipient must be compatible with the other ingredients of the formulation and not deleterious to the recipient thereof.

[0037] "Pharmaceutically effective amount" refers to the amount of a compound of the present disclosure or a combination thereof in a formulation that provides the desired therapeutic or pharmaceutical result.

[0038] A "pharmaceutically acceptable excipient" includes any adjuvant, carrier, filler, lubricant, sweetener, diluent, preservative, dye / colorant, flavor enhancer, surfactant, wetting agent, dispersing agent, suspending agent, stabilizer, isotonic agent, solvent, or emulsifier approved by the U.S. Food and Drug Administration as acceptable for human or veterinary use.

[0039] As used herein, "treatment" or "treating" or "treating" refers to an approach for obtaining a beneficial or desired result. For purposes of this disclosure, a beneficial or desired result includes, but is not limited to, alleviating symptoms and / or reducing the severity of symptoms, and / or preventing worsening of symptoms associated with a disease or condition. In some embodiments, "treatment" or "treating" includes one or more of the following: a) inhibiting the disease or condition (e.g., reducing one or more symptoms resulting from the disease or condition and / or reducing the severity of the disease or condition); b) delaying or halting the onset of one or more symptoms associated with the disease or condition (e.g., stabilizing the disease or condition, slowing the worsening or progression of the disease or condition); and c) alleviating the disease or condition, e.g., causing regression of clinical symptoms, improving the disease state, slowing disease progression, increasing quality of life, and / or prolonging survival.

[0040] As used herein, a "therapeutically effective amount" or "effective amount" refers to an amount effective to elicit a desired biological or medical response when administered to a subject for treating a disease, including a sufficient amount of a compound to effect such treatment of the disease. The effective amount may vary depending on the compound, the disease and its severity, and the age, weight, etc., of the subject being treated. An effective amount may include a range of amounts. As understood in the art, an effective amount may be one or more doses, i.e., a single dose or multiple doses may be required to achieve a desired therapeutic endpoint. An effective amount may be considered in the context of administering one or more therapeutic agents, and a single agent may be administered in an effective amount when a desired or beneficial result is achieved, or is achieved, in combination with one or more other agents. The appropriate dose of any co-administered compound may be reduced due to the combined effect (e.g., additive or synergistic) of the compounds.

[0041] "Administration" refers to oral administration, administration as a suppository, topical contact, parenteral, intravenous, intraperitoneal, intramuscular, intralesional, intranasal, or subcutaneous administration, intrathecal administration, or implantation of a sustained release device, e.g., a mini-osmotic pump, to a subject. Administration can be according to a schedule that dictates frequency of administration, dosage, and other factors.

[0042] As used herein, "co-administration" refers to administration of a unit dose of a compound disclosed herein before or after administration of a unit dose of one or more additional therapeutic agents, e.g., administration of a compound disclosed herein within seconds, minutes, or hours of administration of one or more additional therapeutic agents. For example, in some embodiments, a unit dose of a compound disclosed herein is administered first, followed within seconds or minutes by a unit dose of one or more additional therapeutic agents. Alternatively, in other embodiments, a unit dose of one or more additional therapeutic agents is administered first, followed within seconds or minutes by a unit dose of a compound disclosed herein. In some embodiments, a unit dose of a compound disclosed herein is administered first, followed several hours (e.g., 1-12 hours) later by a unit dose of one or more additional therapeutic agents. In other embodiments, a unit dose of one or more additional therapeutic agents is administered first, followed several hours (e.g., 1-12 hours) later by a unit dose of a compound disclosed herein. Co-administration of a compound disclosed herein with one or more additional therapeutic agents generally refers to simultaneous or sequential administration of a compound disclosed herein with one or more additional therapeutic agents such that a therapeutically effective amount of each agent is present in the patient's body.

[0043] "Subject" refers to an animal such as a mammal, including, but not limited to, a primate (e.g., a human), cow, sheep, goat, horse, dog, cat, rabbit, rat, mouse, etc. In some embodiments, the subject is a human.

[0044] "Disease" or "condition" refers to a state or condition of a patient or subject that can be treated with the compounds, pharmaceutical compositions, or methods provided herein. The disease can be an autoimmune, inflammatory, cancer, infectious (e.g., viral infection), metabolic, developmental, cardiovascular, liver, intestinal, endocrine, neurological, or other disease. In some embodiments, the disease is cancer (e.g., lung cancer, ovarian cancer, osteosarcoma, bladder cancer, cervical cancer, liver cancer, kidney cancer, skin cancer (e.g., Merkel cell carcinoma), testicular cancer, leukemia, lymphoma, head and neck cancer, colorectal cancer, prostate cancer, pancreatic cancer, melanoma, breast cancer, neuroblastoma).

[0045] "Cancer" refers to all types of cancer, neoplasm, or malignant tumor found in mammals, including leukemia, lymphoma, melanoma, neuroendocrine tumor, carcinoma, and sarcoma. Exemplary cancers that may be treated with the compounds, pharmaceutical compositions, or methods provided herein include lymphoma, sarcoma, bladder cancer, bone cancer, brain cancer, cervical cancer, colon cancer, esophageal cancer, gastric cancer, head and neck cancer, kidney cancer, myeloma, thyroid cancer, leukemia, prostate cancer, breast cancer (e.g., triple negative, ER positive, ER negative, chemotherapy resistant, Herceptin resistant, HER2 positive, doxorubicin resistant, tamoxifen resistant, ductal carcinoma, lobular carcinoma, primary, metastatic), Examples of cancers that may be included include ovarian cancer, pancreatic cancer, lung cancer (e.g., hepatocellular carcinoma), lung cancer (e.g., non-small cell lung cancer, squamous cell lung cancer, adenocarcinoma, large cell lung cancer, small cell lung cancer, carcinoid, sarcoma), glioblastoma multiforme, glioma, melanoma, prostate cancer, castration-resistant prostate cancer, breast cancer, triple-negative breast cancer, glioblastoma, ovarian cancer, lung cancer, squamous cell carcinoma (e.g., head, neck, or esophageal), colorectal cancer, leukemia, acute myeloid leukemia, lymphoma, B-cell lymphoma, and multiple myeloma.

[0046] Further examples include cancer of the thyroid, endocrine system, brain, breast, cervix, colon, head and neck, esophagus, lung, kidney, pulmonary, non-small cell lung, melanoma, mesothelioma, ovarian, sarcoma, stomach, uterine, or medulloblastoma, Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, neuroblastoma, glioma, glioblastoma multiforme, ovarian cancer, rhabdomyosarcoma, primary thrombocythemia, primary macroglobulinemia, primary brain tumor, cancer, malignant pancreatic insulinoma, malignant carcinoid, bladder cancer, urinary tract ... These include bladder cancer, premalignant skin lesions, testicular cancer, lymphoma, thyroid cancer, neuroblastoma, esophageal cancer, genitourinary tract cancer, malignant hypercalcemia, endometrial cancer, adrenocortical carcinoma, neoplasms of the endocrine or exocrine pancreas, medullary thyroid cancer, medullary thyroid carcinoma, melanoma, colorectal cancer, papillary thyroid cancer, hepatocellular carcinoma, Paget's disease of the breast, phyllodes tumor, lobular carcinoma, ductal carcinoma of the breast, pancreatic stellate cell carcinoma, hepatic stellate cell carcinoma, or prostate cancer.

[0047] "Leukemia" refers broadly to progressive, malignant diseases of the blood-forming organs, generally characterized by the abnormal proliferation and development of white blood cells and their precursors in the blood and bone marrow. Leukemias are generally classified clinically based on: (1) the duration and character of the disease, acute or chronic; (2) the type of cell involved, bone marrow (myeloid), lymphocyte (lymphoid), or monocytic; and (3) the increased or non-increased number of abnormal cells in the blood, leukemic or non-leukemic (subleukemic). Exemplary leukemias that may be treated with the compounds, pharmaceutical compositions, or methods provided herein include, for example, acute nonlymphocytic leukemia, chronic lymphocytic leukemia, acute granulocytic leukemia, chronic granulocytic leukemia, acute promyelocytic leukemia, adult T-cell leukemia, aleukemic leukemia, leukemic leukemia, basophilic leukemia, blast cell leukemia, bovine leukemia, chronic myeloid leukemia, leukemia cutis, embryonic cell leukemia, eosinophilic leukemia, Gross leukemia, hairy cell leukemia, hemoblastic leukemia, hemoblastic cell leukemia, histiocytic leukemia, stem cell leukemia, acute monocytic leukemia, leukopenic leukemia, The present invention includes leukemia, lymphatic leukemia, lymphoblastic leukemia, lymphocytic leukemia, lymphogenous leukemia, lymphoid leukemia, lymphosarcoma cell leukemia, mast cell leukemia, megakaryocytic leukemia, myeloblastic leukemia, monocytic leukemia, myeloblastic leukemia, myelogenous leukemia, myelogranulocytic leukemia, myelomonocytic leukemia, Naegeli leukemia, plasma cell leukemia, multiple myeloma, plasma cell leukemia, promyelocytic leukemia, Leder cell leukemia, Schilling leukemia, stem cell leukemia, subleukemic leukemia, or anaplastic cell leukemia.

[0048] "Sarcoma" generally refers to a tumor composed of a substance like embryonic connective tissue and generally composed of closely packed cells embedded in a fibrous or homogeneous substance. Sarcomas that may be treated with the compounds, pharmaceutical compositions, or methods provided herein include chondrosarcoma, fibrosarcoma, lymphosarcoma, melanosarcoma, myxosarcoma, osteosarcoma, Abemethy's sarcoma, liposarcoma, alveolar soft part sarcoma, ameloblastic sarcoma, botryoid rhabdomyosarcoma, chloroma sarcoma, choriocarcinoma, embryonal sarcoma, Wilms' tumor sarcoma, endometrial sarcoma, stromal sarcoma, Ewing's sarcoma, myosarcoma, and sarcoma. sarcoma, fibroblastic sarcoma, giant cell sarcoma, granulocytic sarcoma, Hodgkin's sarcoma, idiopathic multiple pigmented hemorrhagic sarcoma, immunoblastic sarcoma of B cells, lymphoma, immunoblastic sarcoma of T cells, Jensen's sarcoma, Kaposi's sarcoma, Kupffer's astrocytic sarcoma, angiosarcoma, leukemia sarcoma, malignant mesenchymal sarcoma, parosteal osteosarcoma, reticulum cell sarcoma, Rous sarcoma, serosarcoma cystic sarcoma, synovial sarcoma, or telangiectatic sarcoma.

[0049] "Melanoma" is understood to mean a tumor arising from the melanocytic system of the skin and other organs. Melanomas that may be treated with the compounds, pharmaceutical compositions, or methods provided herein include, for example, acral lentiginous melanoma, amelanotic melanoma, benign juvenile melanoma, Cloudman melanoma, S91 melanoma, Harding-Passey melanoma, melanoma, juvenile melanoma, lentigo maligna melanoma, malignant melanoma, nodular melanoma, subungual melanoma, or superficial spreading melanoma.

[0050] "Carcinoma" refers to a malignant new growth composed of epithelial cells that tend to infiltrate surrounding tissues and give rise to metastases. Exemplary carcinomas that may be treated with the compounds, pharmaceutical compositions, or methods provided herein include, for example, medullary thyroid carcinoma, familial medullary thyroid carcinoma, acinar carcinoma, lobular carcinoma, adenocystic carcinoma, adenomatous carcinoma, adrenal cortical carcinoma, alveolar carcinoma, basal cell carcinoma, basal cell carcinoma, basaloid carcinoma, basosquamous cell carcinoma, bronchoalveolar carcinoma, bronchiolar carcinoma, bronchogenic carcinoma, cerebriform carcinoma, cholangiocarcinoma, choriocarcinoma, mucinous carcinoma, and pulmonary carcinoma. carcinoma), comedo carcinoma, corpus carcinoma, cribriform carcinoma, armor carcinoma, skin cancer, columnar carcinoma, columnar cell carcinoma, ductal carcinoma, ductal carcinoma, durum carcinoma, embryonal carcinoma, medullary carcinoma, epidermoid carcinoma, epithelial tonsillar carcinoma, exophytic carcinoma, ulcer carcinoma, fibrous carcinoma, gelatinous carcinoma, colloid adenocarcinoma, giant cell carcinoma (carcinoma gigantocellulare), giant cell carcinoma, adenocarcinoma, granulosa cell carcinoma, hair matrix carcinoma, blood-like carcinoma, hepatocellular carcinoma, Hurthle cell carcinoma, hyaline carcinoma, adrenal-like carcinoma, childhood embryonal carcinoma, carcinoma in situ, intraepidermal carcinoma, intraepithelial carcinoma, Krompecher carcinoma, Kurticycky cell carcinoma, large cell carcinoma, lenticular carcinoma, lenticular carcinoma lenticulare), lipomatous carcinoma, lobular carcinoma, lymphoepithelial carcinoma, medullary carcinoma, medullary carcinoma, melanoma, soft carcinoma, mucinous carcinoma, mucinous carcinoma, mucocytic carcinoma, mucoepidermoid carcinoma, carcinoma mucosum, mucouscarcinoma), myxomatous carcinoma, nasopharyngeal carcinoma, oat cell carcinoma, ossifying carcinoma, osteoid carcinoma, papillary carcinoma, periportal carcinoma, preinvasive carcinoma, squamous cell carcinoma, medullary carcinoma, renal cell carcinoma, reserve cell carcinoma, sarcomatoid carcinoma, Schneiderian carcinoma, scirrhous carcinoma, scrotal carcinoma, signet ring cell carcinoma, simplex carcinoma, small cell carcinoma, solanoid carcinoma, spheroid cell carcinoma, spindle cell carcinoma, cavernous carcinoma, squamous cell carcinoma, squamous cell carcinoma, cord-like carcinoma, angioectatic carcinoma, telangiectatic carcinoma, transitional cell carcinoma, nodular carcinoma (carcinoma tuberosum), tubular carcinoma, tuberous carcinoma, verrucous carcinoma, or choriocarcinoma (carcinoma villosum).

[0051] The terms "metastasis," "metastatic," and "metastatic cancer" can be used interchangeably and refer to the spread of a proliferative disease or disorder, such as cancer, from one organ to another, non-adjacent organ or body part. Cancer begins at a site of origin, such as the breast, and that site is called a primary tumor, such as primary breast cancer. Some cancer cells in the primary tumor, i.e., the site of origin, acquire the ability to invade and infiltrate surrounding normal tissue in the local area and / or penetrate the walls of the lymphatic or vascular system and circulate through that system to other sites and tissues in the body. A second, clinically detectable tumor formed from cancer cells of the primary tumor is called a metastatic or secondary tumor. When cancer cells metastasize, the metastatic tumor and its cells are presumed to be similar to those of the original tumor. Thus, if lung cancer metastasizes to the breast, the secondary tumor in the breast site will consist of abnormal lung cells, not abnormal breast cells. The secondary tumor in the breast is called metastatic lung cancer. Therefore, the term metastatic cancer refers to a disease in which a subject has or has had a primary tumor, and has one or more secondary tumors.The term non-metastatic cancer or a subject with cancer that has not metastasized refers to a disease in which a subject has a primary tumor but does not have one or more secondary tumors.For example, metastatic lung cancer refers to a disease in a subject who has or has had a primary lung tumor, and has one or more secondary tumors in a second location or multiple locations, such as the breast.

[0052] In the context of a substance or the activity or function of a substance related to a disease (e.g., diabetes, cancer (e.g., prostate cancer, renal cancer, metastatic cancer, melanoma, castration-resistant prostate cancer, breast cancer, triple-negative breast cancer, glioblastoma, ovarian cancer, lung cancer, squamous cell carcinoma (e.g., of the head, neck, or esophagus), colorectal cancer, leukemia, acute myeloid leukemia, lymphoma, B-cell lymphoma, or multiple myeloma)), "related to" or "related to" means that the disease (e.g., lung cancer, ovarian cancer, osteosarcoma, bladder cancer, cervical cancer, liver cancer, renal cancer, skin cancer (e.g., Merkel cell carcinoma), testicular cancer, leukemia, lymphoma, head and neck cancer, colorectal cancer, prostate cancer, pancreatic cancer, melanoma, breast cancer, neuroblastoma) is caused (in whole or in part) by the substance or the activity or function of the substance, or a symptom of the disease is caused (in whole or in part) by the substance or the activity or function of the substance.

[0053] Pharmaceutically acceptable salts, hydrates, solvates, tautomers, polymorphs, and prodrugs of the compounds described herein are also provided. "Pharmaceutically acceptable" or "physiologically acceptable" refers to compounds, salts, compositions, dosage forms, and other materials that are useful in preparing pharmaceutical compositions suitable for veterinary or human medicine.

[0054] The compounds of the present disclosure described herein can be prepared and / or formulated as pharmaceutically acceptable salts, or, where appropriate, as free bases. Pharmaceutically acceptable salts are non-toxic salts of the free base form of a compound that possess the desired pharmacological activity of the free base. These salts can be derived from inorganic or organic acids or bases. Examples of pharmaceutically acceptable salts of compounds of Formula (I) of the present disclosure include inorganic acid salts such as hydrochloride, sulfate, carbonate, and phosphate, as well as organic acid salts such as fumarate, maleate, methanesulfonate, and p-toluenesulfonate. Further examples include salts with alkali metals such as sodium and potassium, alkaline earth metals such as magnesium or calcium, organic amines such as lower alkylamines or lower alcoholamines, basic amino acids such as lysine, arginine, ornithine, or ammonium salts. For example, compounds containing a basic nitrogen can be prepared as pharmaceutically acceptable salts by contacting the compound with an inorganic or organic acid. Non-limiting examples of pharmaceutically acceptable salts include sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, phosphate, monohydrogenphosphate, dihydrogenphosphate, metaphosphate, pyrophosphate, chloride, bromide, iodide, acetate, propionate, decanoate, caprylate, acrylate, formate, isobutyrate, caproate, heptanoate, propiolate, oxalate, malonate, succinate, suberate, sebacate, fumarate, maleate, butyne-1,4-dioate, hexyne, hexyne-1,4-diol, hexyne-2 ... 1,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, hydroxybenzoate, methoxybenzoate, phthalate, sulfonate, methylsulfonate, propylsulfonate, besylate, xylenesulfonate, naphthalene-1-sulfonate, naphthalene-2-sulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, gamma-hydroxybutyrate, glycolate, tartrate, and mandelate. A list of other suitable pharmaceutically acceptable salts can be found in Remington: The Science and Practice of Pharmacy, 21 stEdition, Lippincott Williams and Wilkins, Philadelphia, Pa., 2006.

[0055] Examples of "pharmaceutically acceptable salts" of the compounds disclosed herein also include alkali metal (e.g., sodium, potassium), alkaline earth metal (e.g., magnesium), ammonium, and NX4 salts. + Also included are salts derived from appropriate bases such as: (wherein X is C1-C4 alkyl). Base addition salts such as sodium or potassium salts are also included.

[0056] Also provided are compounds described herein, or pharmaceutically acceptable salts, isomers, or mixtures thereof, in which 1 to n hydrogen atoms bonded to a carbon atom may be replaced with deuterium atoms or D, where n is the number of hydrogen atoms in the molecule. As known in the art, deuterium atoms are non-radioactive isotopes of hydrogen atoms. Such compounds may enhance resistance to metabolism and therefore may be useful for increasing the half-life of the compounds described herein, or their pharmaceutically acceptable salts, isomers, or mixtures, when administered to a mammal. See, for example, Foster, "Deuterium Isotope Effects in Studies of Drug Metabolism," Trends Pharmacol. Sci., 5(12):524-527 (1984). Such compounds are synthesized by means well known in the art, for example, by employing starting materials in which one or more hydrogen atoms have been replaced with deuterium.

[0057] Additionally, examples of isotopes that can be incorporated into the disclosed compounds include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, chlorine, and iodine, such as: 2 H, 3 H, 11 C. 13 C. 14 C. 13 N, 15 N, 15 O.17 O. 18 O. 31 P, 32 P, 35 S, 18 F, 36 Cl, 123 I, and 125 Positron-emitting isotopes, such as 11 C. 18 F, 15 O and 13 Substitution at N may be useful in positron emission topography (PET) studies to examine substrate receptor occupancy. Isotopically labeled compounds of formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8) can generally be prepared by conventional techniques known to those skilled in the art or by processes similar to those illustrated in the Examples set forth below, substituting the appropriate isotopically labeled reagent for the previously employed non-labeled reagent.

[0058] The compounds of the examples disclosed herein, or pharmaceutically acceptable salts thereof, may contain one or more asymmetric centers and thus give rise to enantiomers, diastereomers, and other stereoisomeric forms that can be defined, with respect to absolute stereochemistry, as (R)- or (S)-, or, for amino acids, as (D)- or (L)-. The present disclosure is intended to encompass all such possible isomers, as well as their racemic and optically pure forms. Optically active (+)- and (−), (R)- and (S)-, or (D)- and (L)-isomers can be prepared using chiral synthons or chiral reagents or resolved using conventional techniques, such as chromatography and fractional crystallization. Conventional techniques for the preparation / isolation of individual enantiomers include chiral synthesis from suitable optically pure precursors or resolution of the racemate (or racemate of a salt or derivative) using, for example, chiral high-pressure liquid chromatography (HPLC). When compounds described herein contain olefinic double bonds or other centers of geometric asymmetry, and unless otherwise specified, these compounds are intended to include both E and Z geometric isomers. Likewise, all tautomeric forms are also intended to be included. When compounds are represented in their chiral form, it is understood that embodiments include, but are not limited to, the specific diastereomerically or enantiomerically enriched forms. Where chirality is not specified, it is understood that embodiments are directed to either the specific diastereomerically or enantiomerically enriched forms, or racemic or scalemic mixtures of such compound(s). As used herein, a "scalemic mixture" is a mixture of stereoisomers in a ratio other than 1:1.

[0059] A "racemate" refers to a mixture of enantiomers. The mixture may contain equal or unequal amounts of each enantiomer.

[0060] "Stereoisomer" refers to a compound that differs in the chirality of one or more stereocenters. Stereoisomers include enantiomers and diastereomers. A compound may exist in stereoisomeric forms if it has one or more asymmetric centers or double bonds with asymmetric substitution and can therefore be produced as individual stereoisomers or as mixtures. Unless otherwise indicated, the description is intended to include individual stereoisomers as well as mixtures. Methods for determining stereochemistry and separating stereoisomers are well known in the art (see, for example, Chapter 4 of Advanced Organic Chemistry, 4th ed., J. March, John Wiley and Sons, New York, 1992).

[0061] "Tautomer" refers to alternative forms of a compound that differ in the location of a proton, e.g., enol-keto and imine-enamine tautomers, or tautomers of heteroaryl groups that contain ring atoms bonded to both the -NH- and =N- rings, e.g., pyrazole, imidazole, benzimidazole, triazole, and tetrazole.

[0062] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. Dashes at the front or end of chemical groups are for convenience, and chemical groups can be depicted with or without one or more dashes without losing their ordinary meaning. A wavy line drawn across a line in a structure indicates the point of attachment of the group. A dashed line indicates an optional bond. Unless chemically or structurally required, no directionality is shown or implied by the order in which chemical groups are written or their point of attachment to the rest of the molecule. For example, the group "-SO2CH2-" is equivalent to "-CH2SO2-", and both can be attached in either direction. Similarly, for example, an "arylalkyl" group can be attached to the rest of the molecule at either the aryl or alkyl portion of the group. "C u~v " or (C u ~C v) prefix indicates that the following group has u to v carbon atoms. For example, "C 1~6 Both "alkyl" and "C1-C6 alkyl" indicate that the alkyl group has from 1 to 6 carbon atoms.

[0063] As used herein, "solvate" refers to the result of the interaction of a solvent with a compound. Solvates of salts of the compounds described herein are also provided. Hydrates of the compounds described herein are also provided.

[0064] As used herein, "prodrug" refers to a derivative of a drug that, upon administration to the human body, is converted into the parent drug by following some chemical or enzymatic pathway. II. Compounds

[0065] The present disclosure provides compounds of formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), and (IIc-8), and pharmaceutically acceptable salts thereof.

[0066] In some embodiments, the compound has the structure of formula (I-1) [ka] or a pharmaceutically acceptable salt thereof.

[0067] In some embodiments, the compound of formula (I-1) or a pharmaceutically acceptable salt thereof is a compound, wherein: R 1 , R 2 , R 3 and R 4are independently a hydrogen atom, a halogen atom, a hydroxy group, a carboxy group, a formyl group, a cyano group, an amino group, a nitro group, a nitroso group, an alkoxycarbonyl group, an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted cycloalkyl group, an optionally substituted alkoxy group, an optionally substituted alkylamino group, an optionally substituted aryl group, an optionally substituted heteroaryl group, an optionally substituted acyl group, an optionally substituted carbamoyl group, an optionally substituted acylamino group, an optionally substituted saturated heterocyclo group, or an optionally substituted alkylsulfonylamino group; R 5 is a hydrogen atom, an optionally substituted alkyl group, an optionally substituted alkynyl group, or an optionally substituted aryl group; R 6 is an optionally substituted alkyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group, or R 5 and R 6 may be taken together with the nitrogen atom to which they are attached to form a nitrogen-containing saturated heterocyclic ring to which an aryl ring is fused, the fused ring being optionally substituted; However, the compound is [ka] isn't it.

[0068] R in the compound of formula (I-1) 1 ~R 4 Examples of the substituent include halogen atoms such as fluorine, chlorine, bromine, or iodine atoms; hydroxy groups; carboxy groups; formyl groups; cyano groups; amino groups; nitro groups; nitroso groups; optionally substituted alkyl groups (e.g., optionally substituted C 1~6Examples of the alkyl group include an alkyl group and an optionally substituted aralkyl group. Further, the substituents of the substituted alkyl include a hydroxy group, a methoxy group, a dimethylamino group, a morpholino group, a 4-methylpiperazin-1-yl group, and a piperidin-1-yl group; optionally substituted alkenyl groups (e.g., optionally substituted C groups such as a vinyl group, an allyl group, an isopropenyl group, a butenyl group, and an isobutenyl group) are also included. 2~6 alkenyl), optionally substituted alkynyl groups (e.g., optionally substituted C groups such as ethynyl, 1-propynyl, and propargyl groups); 2~6 Examples of substituted alkynyl groups include amino, cyclopropyl, hydroxy, and phenyl groups. The amino group can also be substituted with an amino-protecting group, an optionally substituted cycloalkyl group (e.g., an optionally substituted C 3~7 cycloalkyl groups are exemplified), optionally substituted alkoxy groups (e.g., optionally substituted C 1~6 alkoxy groups), optionally substituted alkylamino groups (e.g., mono-C 1~6 Alkylamino group, di-C 1~6 Examples of the substituted alkylamino group include an alkylamino group, and the substituents of the substituted alkylamino group include a hydroxy group, a methoxy group, and the like), an optionally substituted acylamino group (for example, an optionally substituted C 1~4 Examples include an aliphatic acylamino group or an arylacylamino group, including an acetylamino group, a benzoylamino group, or a pyridylcarbonylamino group), an alkoxycarbonyl group (e.g., an optionally substituted C 1~4 alkoxycarbonyl groups), optionally substituted acyl groups (examples of which include alkyl- or aryl-substituted carbonyl groups, for example, acetyl or benzoyl groups), optionally substituted carbamoyl groups (for example, optionally substituted C 1~4 alkylcarbamoyl groups), optionally substituted ureido groups (e.g., optionally substituted C 1~4alkylureido groups), optionally substituted aryl groups (e.g., optionally substituted phenyl groups), optionally substituted saturated heterocyclo groups (e.g., optionally substituted morpholinyl, 4-methylpiperazin-1-yl, piperidin-1-yl, or pyrrolidinyl groups), optionally substituted heteroaryl groups (e.g., optionally substituted pyridyl, thienyl, or furanyl groups), optionally substituted thioalkyl groups (e.g., optionally substituted C 1~4 thioalkyl groups), optionally substituted alkylsulfonyl groups (e.g., optionally substituted C 1~4 alkylsulfonyl groups), optionally substituted alkylsulfonylamino groups (e.g., optionally substituted C 1~4 The aryl group can be protected by a group such as an alkylsulfonylamino group.

[0069] R in the compound of formula (I-1) 5 Examples of the alkyl group include a hydrogen atom, an optionally substituted alkyl group (e.g., an optionally substituted C 1~6 Examples include alkyl groups, such as C 3~6 Substituents for the substituted alkyl group include cycloalkyl groups, hydroxy groups, methoxy groups, phenyl groups, and the like. In addition, hydroxy groups can be optionally substituted with OH protecting groups (as described below), optionally substituted alkynyl groups (e.g., optionally substituted C 2~6 The aryl group may be protected by an optionally substituted aryl group (an optionally substituted phenyl group is an example), an optionally substituted aryl group (an optionally substituted phenyl group is an example), or the like.

[0070] R in the compound of formula (I-1) 6 Examples of optionally substituted alkyl groups include optionally substituted C 1~6 Examples include alkyl groups, such as C 3~6Substituents of the substituted alkyl group include a cycloalkyl group, a hydroxy group, a methoxy group, and the like. Furthermore, the hydroxy group can be protected by an OH protecting group (described later), and examples thereof include an optionally substituted alkynyl group, an optionally substituted aryl group (e.g., a phenyl group and a biphenyl group), and the like, and further include a halogen atom, a hydroxy group, a methoxy group, a cyano group, a nitro group, a C 1~4 Included as substituents for these groups are alkyl groups, carboxy groups, carbamoyl groups, amino groups, methoxycarbonyl groups, cyclopropyl groups, formyl groups, fluoromethyl groups, trifluoromethyl groups, hydroxymethyl groups, methoxymethyl groups, acetylamino groups, phenyl groups, 5- or 6-membered saturated or unsaturated heterocyclo groups, etc. Furthermore, hydroxy groups can be protected by OH-protecting groups (described below), optionally substituted heteroaryl groups (including, for example, pyridyl or thienyl groups), etc.

[0071] The compounds of formula (Ic), (IIc), or (IIc-1) are R 5 and R 6a is a nitrogen-containing 5- to 8-membered saturated heterocyclic ring formed together with the nitrogen atom and fused with an aryl ring (e.g., a phenyl group), and examples of this include 1,2,3,4-tetrahydroquinoline, 3,4-dihydro-2H-1,4-benzoxazine, tetrahydrobenzazepine, and hexahydrobenzazocine.

[0072] In some embodiments, the present disclosure provides a compound of formula (I): [ka] or a pharmaceutically acceptable salt thereof, wherein: R 1 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Alkoxy, halogen, C 1~6 Haloalkyl, C 1~6 haloalkoxy, or -CN; R 2is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -NO, -NO2, -C(O)R 2a , -C(O)OR 2a , -OC(O)R 2a , -C(O)N(R 2a )(R 2b ), -N(R 2a )C(O)R 2b , -OC(O)N(R 2a )(R 2b ), -N(R 2a )C(O)OR 2b , -C(=NR 2a )N(R 2b )(R 2c ), -N(R 2a )(R 2b ), -N(R 2a )N(R 2b )(R 2c ), -N(R 2a )N=C(R 2b )(OR 2c ), -OR 2a , -SR 2a , -S(O)R 2a , -S(O)(NR 2a )(R 2b ), -S(NR 2a )(NR 2b )(R 2c ), -S(O)R 2a , -S(O)2N(R 2a )(R 2b ), -N(R 2a )S(O)2(R 2b ), -P(R 2a )(R 2b ), -P(O)(R 2a )(R 2b ), -P(O)(OR 2a )(R 2b ), -P(O)(OR2a )(OR 2b ), C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), where each alkyl, alkenyl, or alkynyl is independently selected from 1 to 3 R 2d groups, each cycloalkyl being optionally substituted with 1 to 3 R 2e and each aryl is optionally substituted with 1 to 3 R 2f groups, and each heterocycloalkyl is optionally substituted with 1 to 3 R 2g and each heteroaryl is optionally substituted with 1 to 3 R 2h and optionally substituted with a group, Each R 2a , R 2b , and R 2c are independently hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), where the aryl or heteroaryl is selected from 1 to 3 R 2j and optionally substituted with Alternatively, R 2a , R2b , and R 2c when attached to the same atom, can combine with the atom to which they are attached to form a heterocycloalkyl, Each R 2d are independently -CN, -C(O)R 2d1 , -C(O)OR 2d1 , -OC(O)R 2d1 , -C(O)N(R 2d1 )(R 2d2 ), -N(R 2d1 )C(O)R 2d2 , -OC(O)N(R 2d1 )(R 2d2 ), -N(R 2d1 )C(O)OR 2d2 , -N(R 2d1 )(R 2d2 ), =O, -OR 2d1 , -SR 2d1 , -S(O)R 2d1 , -S(O)(NR 2d1 )(R 2d2 ), -S(O)R 2d1 , -S(O)N(R 2d1 )(R 2d2 ), -N(R 2d1 )S(O)2R 2d2 , C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), Each R 2d1 and R 2d2 are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 2~6 Alkoxyalkyl, or C 1~6 is haloalkyl, Each R 2e , R 2f , R 2g, and R 2h are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 haloalkoxy, -CN, or -OH; Each R 2j independently, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, or C 1~6 haloalkoxy, R 3 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -NO, -NO2, -C(O)R 3a , -C(O)OR 3a , -OC(O)R 3a , -C(O)N(R 3a )(R 3b ), -N(R 3a )C(O)R 3b , -OC(O)N(R 3a )(R 3b ), -N(R 3a )C(O)OR 3b , -C(=NR 3a )N(R 3b )(R 3c ), -N(R 3a )(R 3b ), -N(R 3a )N(R 3b )(R 3c ), -N(R3a )N=C(R 3b )(OR 3c ), -OR 3a , -SR 3a , -S(O)R 3a , -S(O)(NR 3a )(R 3b ), -S(NR 3a )(NR 3b )(R 3c ), -S(O)R 3a , -S(O)2N(R 3a )(R 3b ), -N(R 3a )S(O)2(R 3b ), -P(R 3a )(R 3b ), -P(O)(R 3a )(R 3b ), -P(O)(OR 3a )(R 3b ), -P(O)(OR 3a )(OR 3b ), C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), where each alkenyl or alkynyl independently is selected from 1 to 3 R 3d groups, each cycloalkyl being optionally substituted with 1 to 3 R 3e and each aryl is optionally substituted with 1 to 3 R 3f groups, and each heterocycloalkyl is optionally substituted with 1 to 3 R 3g and each heteroaryl is optionally substituted with 1 to 3 R 3h and optionally substituted with a group, Each R 3a , R 3b , and R 3c are independently hydrogen, C 1~6 Alkyl, C 1~6Hydroxyalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 aryl, heterocycloalkyl, or heteroaryl; Alternatively, R 3a , R 3b , and R 3c when attached to the same atom, can combine with the atom to which they are attached to form a heterocycloalkyl, Each R 3d are independently -N(R 3d1 )(R 3d2 ), -OR 3d1 , C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 aryl, heterocycloalkyl, or heteroaryl; Each R 3d1 and R 3d2 are independently hydrogen, C 1~6 Alkyl, or -C(O)O-(C 1~6 alkyl), Each R 3e , R 3f , R 3g , and R 3h are independently hydrogen, C 1~6 Alkyl, C 1~6 Alkoxy, halogen, C 1~6 Haloalkyl, or C 1~6 haloalkoxy, R 4 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Alkoxy, halogen, C 1~6 Haloalkyl, C 1~6 haloalkoxy, or -CN; R 5 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), where alkyl is R 5a and optionally substituted with R 5a is -OSi(R 5a1 )(R 5a2 )(R 5a3 ) and R 5a1 , R 5a2 , and R 5a3 are each independently C 1~6 is alkyl, R 6 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 6~12 aryl or heteroaryl, wherein the aryl or heteroaryl is selected from 1 to 3 R 6a each optionally substituted with Each R 6a independently, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6Haloalkoxy, -CN, -NO2, -C(O)R 6b , -C(O)OR 6b , -OC(O)R 6b , -C(O)N(R 6b )(R 6c ), -N(R 6b )C(O)R 6c , -C(=NR 6b )N(R 6c )(R 6d ), -N(R 6b )(R 6c ), -OR 6b , -SR 6b , -S(O)R 6b , -S(O)2R 6b , -S(NR 6b )(NR 6c )R 6d , -S(O)(NR 6b )(R 6c ), -S(O)2N(R 6b )(R 6c ), -N(R 6b )S(O)2(R 6c ), -P(R 6b )(R 6c ), -P(O)(R 6b )(R 6c ), -P(O)(OR 6b )(R 6c ), -P(O)(OR 6b )(OR 6c ), C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), where cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is selected from 1 to 3 R 6e each optionally substituted with alkyl, R 6f and the alkynyl is optionally substituted with 1 to 4 R 6j and optionally substituted with Each R 6b , R 6c and R 6d are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), where cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is selected from 1 to 3 R 6k and optionally substituted by Each R 6k independently, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, heterocycloalkyl, or C 1~6 alkyl-(heterocycloalkyl), Each R 6e independently, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6Haloalkoxy, -CN, -NO2, -C(O)R 6e1 , -C(O)OR 6e1 , -OC(O)R 6e1 , -C(O)N(R 6e1 )(R 6e2 ), -N(R 6e1 )C(O)R 6e2 , -OC(O)N(R 6e1 )(R 6e2 ), -N(R 6e1 )C(O)OR 6e2 , -C(=NR 6e1 )N(R 6e2 )(R 6e3 ), -N(R 6e1 )(R 6e2 ), =O, -OR 6e1 , -SR 6e1 , -S(O)R 6e1 , -S(NR 6e1 )(NR 6e2 ), -S(O)(NR 6e1 )(R 6e2 ), -S(O)R 6e1 , -S(O)2N(R 6e1 )(R 6e2 ), -SF5, -N(R 6e1 )S(O)2(R 6e2 ), -P(R 6e1 )(R 6e2 ), -P(O)(R 6e1 )(R 6e2 ), -P(O)(OR 6e1 )(R 6e2 ), -P(O)(OR 6e1 )(OR 6e2 ), -Si(R 6e1 )(R 6e2 )(R 6e3 ), C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 Aryl, heterocycloalkyl, C 1~6 Alkyl-heterocycloalkyl, heteroaryl, or C 1~6alkyl-heteroaryl, where cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is selected from 1 to 3 R 6h each optionally substituted with 1 to 3 R 6m and optionally substituted with Each R 6e1 , R 6e2 , and R 6e3 are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~10 Aryl, C 1~6 Alkyl-C 6~10 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), where cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is selected from 1 to 3 R 6n and optionally substituted with Each R 6n is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -C(O)R 6n1 , -C(O)OR 6n1 , -OC(O)R 6n1 , -C(O)N(R 6n1 )(R 6n2 ), -N(R 6n1 )C(O)R 6n2 , -OC(O)N(R 6n1 )(R 6n2), -N(R 6n1 )C(O)OR 6n2 , -C(=NR 6n1 )N(R 6n2 )(R 6n3 ), -N(R 6n1 )(R 6n2 ), =O, -OH, -SR 6n1 , -S(O)R 6n1 , -S(NR 6n1 )(NR 6n2 )R 6n3 , -S(O)(NR 6n1 )(R 6n2 ), -S(O)R 6n1 , -S(O)2N(R 6n1 )(R 6n2 ), or -N(R 6n1 )S(O)2(R 6n2 ) and Each R 6n1 , R 6n2 and R 6n3 are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~10 Aryl, C 1~6 Alkyl-C 6~10 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), Each R 6h independently, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -C(O)R6h1 , -C(O)OR 6h1 , -OC(O)R 6h1 , -C(O)N(R 6h1 )(R 6h2 ), -N(R 6h1 )C(O)R 6h2 , -OC(O)N(R 6h1 )(R 6h2 ), -N(R 6h1 )C(O)OR 6h2 , -C(=NR 6h1 )N(R 6h2 )(R 6h3 ), -N(R 6h1 )(R 6h2 ), =O, -OH, -SR 6h1 , -S(O)R 6h1 , -S(NR 6h1 )(NR 6h2 )R 6h3 , -S(O)(NR 6h1 )(R 6h2 ), -S(O)R 6h1 , -S(O)2N(R 6h1 )(R 6h2 ), -N(R 6h1 )S(O)2(R 6h2 ), C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, heterocycloalkyl, or C 1~6 alkyl-(heterocycloalkyl), Each R 6h1 , R 6h2 , and R 6h3 are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~10 Aryl, C 1~6 Alkyl-C 6~10 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C1~6 alkyl-(heteroaryl), Each R 6m are independently halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -C(O)R 6m1 , -C(O)OR 6m1 , -OC(O)R 6m1 , -C(O)N(R 6m1 )(R 6m2 ), -N(R 6m3 )C(O)R 6m2 , -OC(O)N(R 6m1 )(R 6m2 ), -N(R 6m1 )C(O)OR 6m2 , -C(=NR 6m3 )N(R 6m1 )(R 6m2 ), -N(R 6m1 )(R 6m2 ), =O, -OH, -SR 6m1 , -S(O)R 6m1 , -S(NR 6m1 )(NR 6m2 )R 6m3 , -S(O)(NR 6m1 )(R 6m2 ), -S(O)R 6m1 , -S(O)2N(R 6m1 )(R 6m2 ), or -N(R 6m3 )S(O)2(R 6m2 ) and Each R 6m1 , R 6m2 , and R 6m3 are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~10 Aryl, C 1~6 Alkyl-C 6~10 Aryl, heterocycloalkyl, C 1~6Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), R 6f is -OSi(R 6f1 )(R 6f2 )(R 6f3 ) and R 6f1 , R 6f2 , and R 6f3 are each independently C 1~6 is alkyl, Each R 6j independently, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -C(O)R 6j1 , -C(O)OR 6j1 , -OC(O)R 6j1 , -C(O)N(R 6j1 )(R 6j2 ), -N(R 6j3 )C(O)R 6j2 , -OC(O)N(R 6j1 )(R 6j2 ), -N(R 6j1 )C(O)OR 6j2 , -C(=NR 6j3 )N(R 6j1 )(R 6j2 ), -N(R 6j1 )(R 6j2 ), =O, -OR 6j1 , -SR 6j1 , -S(O)R 6j1 , -S(NR 6j1 )(NR 6j2 ), -S(NR 6j1 )(NR 6j2 )R 6j3 , -S(O)(NR 6j1 )(R 6j2 ), -S(O)R 6j1 , -S(O)2N(R 6j1 )(R 6j2 ), -N(R 6j1 )S(O)2(R 6j2 ), -Si(R 6j1 )(R 6j2 )(R 6j3 ), C 3~10Cycloalkyl, C 6~12 aryl, heterocycloalkyl, or heteroaryl, wherein the cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is selected from the group consisting of 1 to 3 R 6p and optionally substituted with Each R 6j1 , R 6j2 , and R 6j3 are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~10 Aryl, C 1~6 Alkyl-C 6~10 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), Each R 6p independently, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -C(O)R 6p1 , -C(O)OR 6p1 , -OC(O)R 6p1 , -C(O)N(R 6p1 )(R 6p2 ), -N(R 6p1 )C(O)R 6p2 , -OC(O)N(R 6p1 )(R 6p2 ), -N(R 6p1 )C(O)OR 6p2 , -C(=NR 6p3 )N(R 6p1 )(R 6p2 ), -N(R 6p1 )(R6p2 ), =O, -OH, -SR 6p1 , -S(O)R 6p1 , -S(NR 6p1 )(NR 6p2 )R 6p3 , -S(O)(NR 6p1 )(R 6p2 ), -S(O)R 6p1 , -S(O)2N(R 6p1 )(R 6p2 ), or -N(R 6p1 )S(O)2(R 6p2 ) and Each R 6p1 , R 6p2 , and R 6p3 are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~10 Aryl, C 1~6 Alkyl-C 6~10 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), Or R 5 and one R 6a together with the atoms to which they are attached form a heterocycloalkyl, and one to three R 6g and optionally substituted with Each R 6g independently, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 haloalkoxy, or -CN; R7 is hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, C 1~6 Alkylthio, halogen, C 1~6 Haloalkyl, -CN, -OH, -NH2, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, heterocycloalkyl, or C 1~6 alkyl-(heterocycloalkyl), each heterocycloalkyl is a 3- to 20-membered ring having 1-4 heteroatoms, each independently N, O, or S; each heteroaryl is a 5- to 18-membered ring having 1-4 heteroatoms, each independently N, O, or S; However, R 5 and R 6 are both C 1~4 R, not alkyl 5 When is hydrogen, R 6 is not isopropyl or phenyl substituted with 2-Me.

[0073] In some embodiments, the present disclosure provides a compound of formula (I): [ka] or a pharmaceutically acceptable salt thereof, wherein: R 1 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Alkoxy, halogen, C 1~6 Haloalkyl, C 1~6 haloalkoxy, or -CN; R 2 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6Hydroxyalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -NO, -NO2, -C(O)R 2a , -C(O)OR 2a , -OC(O)R 2a , -C(O)N(R 2a )(R 2b ), -N(R 2a )C(O)R 2b , -OC(O)N(R 2a )(R 2b ), -N(R 2a )C(O)OR 2b , -C(=NR 2a )N(R 2b )(R 2c ), -N(R 2a )(R 2b ), -OR 2a , -SR 2a , -S(O)R 2a , -S(O)2R 2a , -S(O)2N(R 2a )(R 2b ), -N(R 2a )S(O)2(R 2b ), -P(O)(R 2a )(R 2b ), -P(O)(OR 2a )(R 2b ), -P(O)(OR 2a )(OR 2b ), C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 aryl, heterocycloalkyl, or heteroaryl, where each alkenyl or alkynyl independently has 1 to 3 R 2d groups, each cycloalkyl being optionally substituted with 1 to 3 R 2e and each aryl is optionally substituted with 1 to 3 R 2fgroups, and each heterocycloalkyl is optionally substituted with 1 to 3 R 2g and each heteroaryl is optionally substituted with 1 to 3 R 2h and optionally substituted with a group, Each R 2a , R 2b , and R 2c are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 aryl, heterocycloalkyl, or heteroaryl; Alternatively, R 2a , R 2b , and R 2c when attached to the same atom, can combine with the atom to which they are attached to form a heterocycloalkyl, Each R 2d are independently -N(R 2d1 )(R 2d2 ), -OR 2d1 , C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 aryl, heterocycloalkyl, or heteroaryl; Each R 2d1 and R 2d2 are independently hydrogen, C 1~6 Alkyl, or -C(O)O-(C 1~6 alkyl), Each R 2e , R 2f , R 2g , and R 2h are independently hydrogen, C 1~6 Alkyl, C 1~6 Alkoxy, halogen, C1~6 Haloalkyl, or C 1~6 haloalkoxy, R 3 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -NO, -NO2, -C(O)R 3a , -C(O)OR 3a , -OC(O)R 3a , -C(O)N(R 3a )(R 3b ), -N(R 3a )C(O)R 3b , -OC(O)N(R 3a )(R 3b ), -N(R 3a )C(O)OR 3b , -C(=NR 3a )N(R 3b )(R 3c ), -N(R 3a )(R 3b ), -OR 3a , -SR 3a , -S(O)R 3a , -S(O)2R 3a , -S(O)2N(R 3a )(R 3b ), -N(R 3a )S(O)2(R 3b ), -P(O)(R 3a )(R 3b ), -P(O)(OR 3a )(R 3b ), -P(O)(OR 3a )(OR 3b ), C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12aryl, heterocycloalkyl, or heteroaryl, where each alkenyl or alkynyl independently has 1 to 3 R 3d groups, each cycloalkyl being optionally substituted with 1 to 3 R 3e and each aryl is optionally substituted with 1 to 3 R 3f groups, and each heterocycloalkyl is optionally substituted with 1 to 3 R 3g and each heteroaryl is optionally substituted with 1 to 3 R 3h and optionally substituted with a group, Each R 3a , R 3b , and R 3c are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 aryl, heterocycloalkyl, or heteroaryl; Alternatively, R 3a , R 3b , and R 3c when attached to the same atom, can combine with the atom to which they are attached to form a heterocycloalkyl, Each R 3d are independently -N(R 3d1 )(R 3d2 ), -OR 3d1 , C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 aryl, heterocycloalkyl, or heteroaryl; Each R 3d1 and R 3d2 are independently hydrogen, C 1~6Alkyl, or -C(O)O-(C 1~6 alkyl), Each R 3e , R 3f , R 3g , and R 3h are independently hydrogen, C 1~6 Alkyl, C 1~6 Alkoxy, halogen, C 1~6 Haloalkyl, or C 1~6 haloalkoxy, R 4 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Alkoxy, halogen, C 1~6 Haloalkyl, C 1~6 haloalkoxy, or -CN; R 5 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), where alkyl is R 5a and optionally substituted with R 5a is -OSi(R 5a1 )(R 5a2 )(R 5a3 ) and R 5a1 , R 5a2 , and R 5a3 are each independently C 1~6 is alkyl, R 6 is C1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 6~12 aryl or heteroaryl, wherein the aryl or heteroaryl is selected from 1 to 3 R 6a each optionally substituted with Each R 6a independently, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -NO2, -C(O)R 6b , -C(O)OR 6b , -OC(O)R 6b , -C(O)N(R 6b )(R 6c ), -N(R 6b )C(O)R 6c , -C(=NR 6b )N(R 6c )(R 6d ), -N(R 6b )(R 6c ), -OR 6b , -SR 6b , -S(O)R 6b , -S(O)2R 6b , -S(O)2N(R 6b )(R 6c ), -N(R 6b )S(O)2(R 6c ), C 3~10 Cycloalkyl, C 6~12 aryl, heterocycloalkyl, or heteroaryl, wherein the cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is selected from the group consisting of 1 to 3 R 6e each optionally substituted with alkyl, R 6f and optionally substituted with Or R 5 and one R 6atogether with the atoms to which they are attached form a heterocycloalkyl, and one to three R 6g and optionally substituted with Each R 6b , R 6c , and R 6d are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 aryl, heterocycloalkyl, or heteroaryl; Each R 6e independently, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -NO2, -C(O)R 6e1 , -C(O)OR 6e1 , -OC(O)R 6e1 , -C(O)N(R 6e1 )(R 6e2 ), -N(R 6e1 )C(O)R 6e2 , -C(=NR 6e1 )N(R 6e2 )(R 6e3 ), -N(R 6e1 )(R 6e2 ), -OR 6e1 , -SR 6e1 , -S(O)R 6e1 , -S(O)2R 6e1 , -S(O)2N(R 6e1 )(R 6e2 ), -N(R 6e1 )S(O)2(R 6e2 ), C3~10 Cycloalkyl, C 6~12 aryl, heterocycloalkyl, or heteroaryl, wherein the cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is selected from the group consisting of 1 to 3 R 6h each optionally substituted with Each R 6e1 , R 6e2 , and R 6e3 are independently hydrogen or C 1~6 is alkyl, R 6f is -OSi(R 6f1 )(R 6f2 )(R 6f3 ) and R 6f1 , R 6f2 , and R 6f3 are each independently C 1~6 is alkyl, Each R 6g independently, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, C 1~6 haloalkoxy, or -CN; Each R 6h independently, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Alkoxy, halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -C(O)R 6h1 , -C(O)OR 6h1 , -OC(O)R 6h1 , -C(O)N(R 6h1 )(R 6h2 ), -N(R 6h1 )C(O)R 6h2 , -C(=NR 6h1 )N(R 6h2 )(R 6h3 ), -N(R 6h1 )(R 6h2 ), -OH, -SR 6h1 , -S(O)R 6h1 , -S(O)2R6h1 , -S(O)2N(R 6h1 )(R 6h2 ), or -N(R 6h1 )S(O)2(R 6h2 ) and Each R 6h1 , R 6h2 , and R 6h3 are independently hydrogen or C 1~6 is alkyl, R 7 is hydrogen, C 1~6 Alkyl, halogen, C 1~6 haloalkyl, -CN, or -OH; each heterocycloalkyl is a 3- to 10-membered ring having 1-4 heteroatoms, each independently N, O, or S; Each heteroaryl is a 5- to 10-membered ring having 1-4 heteroatoms, each independently N, O, or S, with the proviso that R 5 and R 6 are both C 1~4 R, not alkyl 5 When is hydrogen, R 6 is not isopropyl or phenyl substituted with 2-Me.

[0074] In some embodiments, the compound of Formula (I) or (I-1), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 5 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 alkyl-(heteroaryl), where alkyl is R5a and optionally substituted with R 6 is C 6~12 aryl or heteroaryl, wherein the aryl or heteroaryl is selected from 1 to 3 R 6a each optionally substituted with, or R 5 and R 6a together with the atoms to which they are attached form a heterocycloalkyl, and one to three R 6g is optionally substituted with

[0075] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ib), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 1 is hydrogen, C 1~6 Alkyl, C 1~6 Alkoxy, halogen, C 1~6 In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ib), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein R 1 is hydrogen, C 1~3 Alkyl, C 1~3 In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ib), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein R 1 is hydrogen, Me, -OMe, F, or Cl. In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ib), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound of formula (I), wherein R1 is hydrogen, or F. In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ib), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein R 1 In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ib), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein R 1 is F.

[0076] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 2 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -NO, -NO2, -C(O)R 2a , -C(O)OR 2a , -OC(O)R 2a , -C(O)N(R 2a )(R 2b ), -N(R 2a )C(O)R 2b , -OC(O)N(R 2a )(R 2b ), -N(R 2a )C(O)OR 2b , -N(R 2a )(R 2b), -OR 2a , -S(O)2N(R 2a )(R 2b ), -N(R 2a )S(O)2(R 2b ), C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 aryl, C 1~6 Alkyl-C 6~12 aryl, heterocycloalkyl, or heteroaryl, where each alkenyl or alkynyl independently has 1 to 3 R 2d and each aryl is optionally substituted with 1 to 3 R 2f In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 2 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, -CN, -NO, -NO2, -C(O)R 2a , -C(O)OR 2a , -N(R 2a )C(O)R 2b , -N(R 2a )(R 2b ), -OR 2a , -N(R 2a )S(O)2(R 2b ), C 3~10 Cycloalkyl, C 6~10 aryl, heterocycloalkyl, or heteroaryl, where each alkenyl or alkynyl independently has 1 to 3 R 2dand each aryl is optionally substituted with 1 to 3 R 2f In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 2 is hydrogen, C 1~3 Alkyl, C 2~3 Alkenyl, C 2~6 Alkynyl, C 1~3 Hydroxyalkyl, C 1~3 Alkoxy, C 2~3 Alkoxyalkyl, halogen, C 1~3 Haloalkyl, -CN, -NO, -NO2, -C(O)R 2a , -C(O)OR 2a , -N(R 2a )C(O)R 2b , -N(R 2a )(R 2b ), -N(R 2a )S(O)2(R 2b ), C 3~6 cycloalkyl, phenyl, heterocycloalkyl, or heteroaryl, where each alkenyl or alkynyl is independently selected from one R 2d groups, and each phenyl is optionally substituted with one R 2f In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 2 is hydrogen, C 1~3 Alkyl, C 2~3 Alkenyl, C 2~6 Alkynyl, C 1~3 Hydroxyalkyl, C 2~3Alkoxyalkyl, halogen, -CN, -NO, -NO2, -C(O)R 2a , -N(R 2a )C(O)R 2b , -N(R 2a )(R 2b ), -OR 2a or heteroaryl, wherein heteroaryl is a 5-6 membered ring having 1-3 heteroatoms, each independently being N, O, or S.

[0077] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein each R 2a and R 2b are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, or C 2~6 In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein each R 2a and R 2b are independently hydrogen, C 1~3 Alkyl, C 1~3 Hydroxyalkyl, or C 2~3 In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein each R 2a and R 2b are independently hydrogen or C1~3 In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein each R 2a and R 2b are independently hydrogen or Me.

[0078] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein each R 2d are independently -N(R 2d1 )(R 2d2 ), -OR 2d1 , C 3~10 Cycloalkyl, or C 6~12 In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein each R 2d are independently -N(R 2d1 )(R 2d2 ), -OR 2d1 , C 3~8 It is cycloalkyl, or phenyl.

[0079] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein each R 2d1 and R 2d2 are independently hydrogen, C 1~4 Alkyl, or -C(O)O(C 1~4 In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein each R 2d1 and R 2d2 are independently hydrogen or -C(O)O(C 1~4 In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein each R 2d1 and R 2d2 is independently hydrogen or —C(O)OtBu. In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), or (Ic), or a pharmaceutically acceptable salt thereof, is a compound wherein each R 2d1 and R 2d2 is hydrogen.

[0080] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein each R 2f independently, C 1~6 In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein each R 2f independently, C 1~3 In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein each R 2f are independently -OMe or F.

[0081] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 2 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C1~6 Haloalkoxy, -CN, -NO, -NO2, -C(O)R 2a , -C(O)OR 2a , -OC(O)R 2a , -C(O)N(R 2a )(R 2b ), -N(R 2a )C(O)R 2b , -OC(O)N(R 2a )(R 2b ), -N(R 2a )C(O)OR 2b , -N(R 2a )(R 2b ), -OR 2a , -S(O)2N(R 2a )(R 2b ), -N(R 2a )S(O)2(R 2b ), C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 aryl, a 3- to 8-membered heterocycloalkyl ring having 1 to 3 heteroatoms each independently being N, O, or S, or a 5- to 10-membered heteroaryl ring having 1 to 3 heteroatoms each independently being N, O, or S, wherein each alkenyl or alkynyl is independently selected from 1 to 3 R 2d and each aryl is optionally substituted with 1 to 3 R 2f groups, and each R 2a and R 2b are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 2~6 Alkoxyalkyl, or C 1~6 haloalkyl, and each R 2d are independently -N(R 2d1 )(R 2d2 ), -OR 2d1 , C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C1~6 Alkyl-C 6~12 aryl, and each R 2d1 and R 2d2 are independently hydrogen, C 1~6 Alkyl, or -C(O)O-(C 1~6 alkyl), and each R 2f are independently hydrogen, C 1~6 Alkyl, C 1~6 Alkoxy or halogen.

[0082] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 2 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, -CN, -NO, -NO2, -C(O)R 2a , -C(O)OR 2a , -N(R 2a )C(O)R 2b , -N(R 2a )(R 2b ), -OR 2a , -N(R 2a )S(O)2(R 2b ), C 3~10 Cycloalkyl, C 6~10 aryl, a 5- to 8-membered heterocycloalkyl ring having 1 to 2 heteroatoms each independently being N, O, or S, or a 5- to 6-membered heteroaryl ring having 1 to 3 heteroatoms each independently being N, O, or S, wherein each alkenyl or alkynyl is independently selected from 1 to 3 R 2d and each aryl is optionally substituted with 1 to 3 R 2fgroups, and each R 2a and R 2b are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, or C 2~6 alkoxyalkyl, and each R 2d are independently -N(R 2d1 )(R 2d2 ), -OR 2d1 , C 3~10 Cycloalkyl, or C 6~12 aryl, and each R 2d1 and R 2d2 are independently hydrogen, C 1~4 Alkyl, or -C(O)O-(C 1~4 alkyl), and each R 2f independently, C 1~6 It is alkoxy or halogen.

[0083] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 2 is hydrogen, C 1~3 Alkyl, C 2~3 Alkenyl, C 2~6 Alkynyl, C 1~3 Hydroxyalkyl, C 1~3 Alkoxy, C 2~3 Alkoxyalkyl, halogen, C 1~3 Haloalkyl, -CN, -NO, -NO2, -C(O)R 2a , -C(O)OR 2a , -N(R 2a )C(O)R 2b , -N(R 2a )(R 2b ), -N(R 2a )S(O)2(R 2b ), C 3~6cycloalkyl, phenyl, a 5- to 6-membered heterocycloalkyl ring having 1-2 heteroatoms each independently being N or O, or a 5- to 6-membered heteroaryl ring having 1-2 heteroatoms each independently being N, O, or S, wherein each alkenyl or alkynyl is independently selected from one R 2d groups, and each phenyl is optionally substituted with one R 2f groups, and each R 2a and R 2b are independently hydrogen, C 1~3 Alkyl, C 1~3 Hydroxyalkyl, or C 2~3 alkoxyalkyl, and each R 2d are independently -N(R 2d1 )(R 2d2 ), -OR 2d1 , C 3~8 cycloalkyl, or phenyl, and each R 2d1 and R 2d2 are independently hydrogen or —C(O)O—(C 1~4 alkyl), and each R 2f independently, C 1~3 It is alkoxy or halogen.

[0084] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 2is hydrogen, Me, Et, iPr, -CH=CH2, -CH=CHMe, -C(Me)=CH2, -CMe=CHMe, -CH=C(Me)2, -CH=CHEt, -C≡CH, -C≡C-Me, -C≡C-Et, -C≡C-tBu, - C≡C-CH2OH, -C≡C-CMe2(OH), -C≡C-CH2NH2, -C≡C-CH2NHC(O)OtBu, -C≡C-CMe2(SO2Me), -CH2OH, -CH2CH2CH2OH, -CH(OH)CH2CH3, -OMe, -OEt, -OCH2CH=CH2, -CH2OMe, -CH2NHMe, -CH2NMe2, -CH2CH2COOEt, F, Cl, Br, I, -CF3, -CN, -NO, -NO2, -C(O)H, -COOH, -COOMe, -NHCOMe, -NH2, -NHMe, -NMe2, -NHCH2CH2OH, -NHCH2CH2OMe, -NHSO2Me, -OH, -NH-N=CH-OEt, -NH2-NH2, SMe, SO2Me, cyclopropyl, [ka] is.

[0085] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 2 is hydrogen, Me, Et, iPr, -CH=CH2, -C(Me)=CH2, -C≡C-Me, -C≡C-tBu, -C≡C-CH2OH, -C≡C-CH2NH2, -C≡C-CH2NHC(O)OtBu, -CH2OH, -OMe, -CH2OMe, F, Cl, Br, I, -CF3, -CN, -NO, -NO2, -C(O)H, -COOH, -COOMe, -NHCOMe, -NH2, -NHMe, -NMe2, -NHCH2CH2OH, -NHCH2CH2OMe, -NHSO2Me, -OH, cyclopropyl, [ka] is.

[0086] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 3 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -NO, -NO2, -C(O)R 3a , -C(O)OR 3a , -OC(O)R 3a , -C(O)N(R 3a )(R 3b ), -N(R 3a )C(O)R 3b , -OC(O)N(R 3a )(R 3b ), -N(R 3a )C(O)OR 3b , -N(R 3a )(R 3b ), -OR 3a , -S(O)2N(R 3a )(R 3b ), -N(R 3a )S(O)2(R 3b ), C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 aryl, C 1~6 Alkyl-C 6~12aryl, heterocycloalkyl, or heteroaryl, where each alkenyl or alkynyl independently has 1 to 3 R 3d and each aryl is optionally substituted with 1 to 3 R 3f is optionally substituted with a group.

[0087] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 3 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -NO, -NO2, -C(O)R 3a , -C(O)OR 3a , -OC(O)R 3a , -C(O)N(R 3a )(R 3b ), -N(R 3a )C(O)R 3b , -OC(O)N(R 3a )(R 3b ), -N(R 3a )C(O)OR 3b , -N(R 3a )(R 3b ), -OR 3a , -S(O)2N(R 3a )(R 3b ), -N(R 3a )S(O)2(R 3b ), C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 aryl, C 1~6 Alkyl-C 6~12 aryl, a 3- to 8-membered heterocycloalkyl ring having 1 to 3 heteroatoms each independently being N, O, or S, or a 5- to 10-membered heteroaryl ring having 1 to 3 heteroatoms each independently being N, O, or S, wherein each alkenyl or alkynyl is independently selected from 1 to 3 R 3d and each aryl is optionally substituted with 1 to 3 R 3f groups, and each R 3a and R 3b are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, or C 2~6 alkoxyalkyl, and each R 3d are independently -N(R 3d1 )(R 3d2 ), -OR 3d1 , C 3~10 Cycloalkyl, or C 6~12 aryl, and each R 3d1 and R 3d2 are independently hydrogen, C 1~4 Alkyl, or -C(O)O-(C 1~4 alkyl), and each R 3f independently, C 1~6 It is alkoxy or halogen.

[0088] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 3 is hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, -CN, -NO2, -C(O)OR 3a , -C(O)N(R3a )(R 3b ), -N(R 3a )(R 3b ), -N(R 3a )S(O)2(R 3b ), or a 5- to 6-membered heteroaryl ring having 1 to 3 heteroatoms, each of which is independently N, O, or S; 3a and R 3b are independently hydrogen or C 1~6 In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein R 3 is hydrogen, C 1~3 Alkyl, C 1~3 Hydroxyalkyl, C 1~3 Alkoxy, C 2~3 Alkoxyalkyl, halogen, C 1~3 Haloalkyl, -CN, -NO2, -C(O)OR 3a , -C(O)N(R 3a )(R 3b ), -N(R 3a )(R 3b ), -N(R 3a )S(O)2(R 3b ), or a 5-6 membered heteroaryl ring having 1 or 2 heteroatoms, each of which is N; 3a and R 3b are independently hydrogen or C 1~3 In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein R 3is hydrogen, Me, Et, -CH2OH, -OMe, -CH2OMe, F, Cl, Br, -CF3, -CN, -NO2, -COOMe, -CONH2, -NH2, -NHSO2Me, or [ka] is.

[0089] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 3 is hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, -CN, -NO2, -C(O)OR 3a , -C(O)N(R 3a )(R 3b ), -N(R 3a )(R 3b ), -N(R 3a )S(O)2(R 3b ), or a 5- to 6-membered heteroaryl ring having 1 to 3 heteroatoms, each of which is independently N, O, or S; 3a and R 3b are independently hydrogen or C 1~6 In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein R 3 is hydrogen, C 1~3 Alkyl, C 1~3 Hydroxyalkyl, C 1~3 Alkoxy, C 2~3Alkoxyalkyl, halogen, -CN, -NO2, -C(O)OR 3a , -C(O)N(R 3a )(R 3b ), -N(R 3a )(R 3b ), -N(R 3a )S(O)2(R 3b In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein R 3 is hydrogen, C 1~3 Alkyl, C 1~3 Hydroxyalkyl, C 1~3 Alkoxy, C 2~3 Alkoxyalkyl, halogen, -CN, -NO2, -C(O)OR 3a , -C(O)N(R 3a )(R 3b ), -N(R 3a )(R 3b ), -N(R 3a )S(O)2(R 3b ), or a 5-6 membered heteroaryl ring having 1 or 2 heteroatoms, each of which is N; 3a and R 3b are independently hydrogen or C 1~3 It is alkyl.

[0090] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 3 is hydrogen, C 1~3In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein R 3 is hydrogen, Me, Et, -CH2OH, -OMe, -CH2OMe, F, Cl, Br, -CN, -NO2, -COOMe, -CONH2, -NH2, -NHSO2Me, or [ka] is.

[0091] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 2 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, -CN, -NO, -NO2, -C(O)R 2a , -C(O)OR 2a , -N(R 2a )C(O)R 2b , -N(R 2a )(R 2b ), -OR 2a , -N(R 2a )S(O)2(R 2b ), C 3~10 Cycloalkyl, C 6~10aryl, heterocycloalkyl, or heteroaryl, where each alkenyl or alkynyl independently has 1 to 3 R 2d and each aryl is optionally substituted with 1 to 3 R 2f groups, and each R 2a and R 2b are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, or C 2~6 alkoxyalkyl, and each R 2d are independently -N(R 2d1 )(R 2d2 ), -OR 2d1 , C 3~10 Cycloalkyl, or C 6~12 aryl, and each R 2f independently, C 1~6 alkoxy or halogen; heterocycloalkyl is a 5-8 membered ring having 1-2 heteroatoms, each independently N, O, or S; R 3 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -NO, -NO2, -C(O)R 3a , -C(O)OR 3a , -OC(O)R 3a , -C(O)N(R 3a )(R 3b ), -N(R 3a )C(O)R 3b , -OC(O)N(R 3a )(R 3b ), -N(R 3a )C(O)OR 3b , -N(R 3a )(R 3b ), -OR 3a , -S(O)2N(R 3a )(R3b ), -N(R 3a )S(O)2(R 3b ), C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 aryl, heterocycloalkyl, or heteroaryl, where each alkenyl or alkynyl independently has 1 to 3 R 3d and each aryl is optionally substituted with 1 to 3 R 3f The heteroaryl is a 5-6 membered ring having 1-3 heteroatoms, each independently N, O, or S.

[0092] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 2 is hydrogen, C 1~3 Alkyl, C 2~3 Alkenyl, C 2~6 Alkynyl, C 1~3 Hydroxyalkyl, C 1~3 Alkoxy, C 2~3 Alkoxyalkyl, halogen, C 1~3 Haloalkyl, -CN, -NO, -NO2, -C(O)R 2a , -C(O)OR 2a , -N(R 2a )C(O)R 2b , -N(R 2a )(R 2b ), -N(R 2a )S(O)2(R 2b ), C 3~6 cycloalkyl, phenyl, heterocycloalkyl, or heteroaryl, where each alkenyl or alkynyl is independently selected from one R 2dgroups, and each phenyl is optionally substituted with one R 2f groups, and each R 2a and R 2b are independently hydrogen, C 1~3 Alkyl, C 1~3 Hydroxyalkyl, or C 2~3 alkoxyalkyl, and each R 2d are independently -N(R 2d1 )(R 2d2 ), -OR 2d1 , C 3~8 cycloalkyl, or phenyl, and each R 2f independently, C 1~3 alkoxy or halogen, R 3 is hydrogen, C 1~3 Alkyl, C 1~3 Hydroxyalkyl, C 1~3 Alkoxy, C 2~3 Alkoxyalkyl, halogen, -CN, -NO2, -C(O)OR 3a , -C(O)N(R 3a )(R 3b ), -N(R 3a )(R 3b ), -N(R 3a )S(O)2(R 3b ), or heteroaryl, and each R 3a and R 3b are independently hydrogen or C 1~3 The heterocycloalkyl is a 5- to 6-membered ring having 1 to 2 heteroatoms, each independently N or O, and the heteroaryl is a 5- to 6-membered ring having 1 to 2 heteroatoms, each independently N, O, or S.

[0093] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ib), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 2is hydrogen, F, or Cl. In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ib), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein R 2 In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ib), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein R 2 is F. In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ib), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein R 2 is Cl.

[0094] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 2 is hydrogen, Me, Et, iPr, -CH=CH2, -C(Me)=CH2, -C≡C-Me, -C≡C-tBu, -C≡C-CH2OH, -C≡C-CH2NH2, -C≡C-CH2NHC(O)OtBu, -CH2OH , -OMe, -CH2OMe, F, Cl, Br, I, -CF3, -CN, -NO, -NO2, -C(O)H, -COOH, -COOMe, -NHCOMe, -NH2, -NHMe, -NMe2, -NHCH2CH2OH, -NHCH2CH2OMe, -NHSO2Me, -OH, cyclopropyl, [ka] and R 3 are hydrogen, Me, Et, -CH2OH, -OMe, -CH2OMe, F, Cl, Br, -CN, -NO2, -COOMe, -CONH2, -NH2, -NHSO2Me, or [ka] is.

[0095] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ib), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 3 is hydrogen, F, or Cl. In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ib), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein R 3 In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ib), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein R 3 is F.

[0096] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ib), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 4 is hydrogen, C 1~6 Alkyl, C 1~6 Alkoxy, halogen, C 1~6In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ib), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein R 4 is hydrogen, C 1~6 In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ib), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein R 4 is hydrogen, C 1~3 In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ib), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein R 4 is hydrogen, Me, F, Cl, or Br. In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ib), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein R 4 is hydrogen, F, or Cl. In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ib), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein R 4 In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ib), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein R 4is F.

[0097] In some embodiments, the compound of Formula (I), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 1 and R 2 In some embodiments, a compound of Formula (I), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein R 1 and R 3 In some embodiments, a compound of Formula (I), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein R 1 and R 4 In some embodiments, a compound of Formula (I), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein R 2 and R 3 In some embodiments, a compound of Formula (I), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein R 2 and R 4 In some embodiments, a compound of Formula (I), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein R 3 and R 4 are each hydrogen.

[0098] In some embodiments, the compound of Formula (I), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 1 , R 2 , and R 3 In some embodiments, a compound of Formula (I), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein R 1 , R 2 , and R 4 In some embodiments, a compound of Formula (I), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein R 1 , R 3 , and R 4 In some embodiments, a compound of Formula (I), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein R 2 , R 3 , and R 4 are each hydrogen.

[0099] In some embodiments, the compound of Formula (I), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 1 is hydrogen and R 2 is hydrogen, C 1~3 Alkyl, C 2~3 Alkenyl, C 2~6 Alkynyl, C 1~3 Hydroxyalkyl, C 2~3Alkoxyalkyl, halogen, -CN, -NO, -NO2, -C(O)R 2a , -N(R 2a )C(O)R 2b , -N(R 2a )(R 2b ), -OR 2a or a 5- to 6-membered heteroaryl ring having 1 to 2 heteroatoms, each independently being N, O, or S; R 2a and R 2b are each independently hydrogen or C 1~3 alkyl, and R 3 is hydrogen, C 1~3 alkyl, halogen, -CN or -NO2, and R 4 is hydrogen or halogen, and R 7 is hydrogen or C 1~3 It is alkyl.

[0100] In some embodiments, the compound of Formula (I), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 1 is hydrogen and R 2 is hydrogen, C 1~3 Alkyl, C 2~3 Alkenyl, C 2~6 Alkynyl, C 1~3 Hydroxyalkyl, C 2~3 Alkoxyalkyl, halogen, -CN, -NO, -NO2, -C(O)R 2a , -N(R 2a )C(O)R 2b , -N(R 2a )(R 2b ), -OR 2a or a 5- to 6-membered heteroaryl ring having 1 to 2 heteroatoms, each independently being N, O, or S; R 2a and R 2b are each independently hydrogen or C 1~3 alkyl, and R 3 is hydrogen, C 1~3alkyl, halogen, -CN or -NO2, and R 4 is hydrogen and R 7 is hydrogen.

[0101] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ib), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 1 is hydrogen and R 2 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, -CN, -NO, -NO2, -C(O)R 2a , -C(O)OR 2a , -N(R 2a )C(O)R 2b , -N(R 2a )(R 2b ), -OR 2a , -N(R 2a )S(O)2(R 2b ), C 3~10 Cycloalkyl, C 6~10 aryl, heterocycloalkyl, or heteroaryl, where each alkenyl or alkynyl independently has 1 to 3 R 2d and each aryl is optionally substituted with 1 to 3 R 2f groups, and each R 2a and R 2b are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, or C 2~6 alkoxyalkyl, and each R 2d are independently -N(R 2d1 )(R 2d2 ), -OR 2d1 , C 3~10 Cycloalkyl, or C 6~12aryl, and each R 2f independently, C 1~6 alkoxy or halogen; heterocycloalkyl is a 5-8 membered ring having 1-2 heteroatoms, each independently N, O, or S; R 3 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -NO, -NO2, -C(O)R 3a , -C(O)OR 3a , -OC(O)R 3a , -C(O)N(R 3a )(R 3b ), -N(R 3a )C(O)R 3b , -OC(O)N(R 3a )(R 3b ), -N(R 3a )C(O)OR 3b , -N(R 3a )(R 3b ), -OR 3a , -S(O)2N(R 3a )(R 3b ), -N(R 3a )S(O)2(R 3b ), C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 aryl, heterocycloalkyl, or heteroaryl, where each alkenyl or alkynyl independently has 1 to 3 R 3d and each aryl is optionally substituted with 1 to 3 R 3f heteroaryl is a 5- to 6-membered ring having 1-3 heteroatoms, each independently N, O, or S; R 4 is hydrogen.

[0102] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ib), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 1 is hydrogen or F, and R 2 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 2~6 Alkoxyalkyl, halogen, -CN, -NO, -NO2, -C(O)R 2a , -N(R 2a )C(O)R 2b , -N(R 2a )(R 2b ), -OR 2a or a 5- to 6-membered heteroaryl ring having 1 to 2 heteroatoms, each independently being N, O, or S; R 2a and R 2b are each independently hydrogen or C 1~6 alkyl, and R 3 is hydrogen, C 1~6 alkyl, halogen, -CN or -NO2, and R 4 is hydrogen, F, or Cl.

[0103] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ib), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 1 is hydrogen and R 2 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 2~6 Alkoxyalkyl, halogen, -CN, -NO, -NO2, -C(O)R 2a , -N(R2a )C(O)R 2b , -N(R 2a )(R 2b ), -OR 2a or a 5- to 6-membered heteroaryl ring having 1 to 2 heteroatoms, each independently being N, O, or S; R 2a and R 2b are each independently hydrogen or C 1~6 alkyl, and R 3 is hydrogen, C 1~6 alkyl, halogen, -CN or -NO2, and R 4 is hydrogen.

[0104] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ib), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 1 is hydrogen and R 2 is hydrogen, C 1~3 Alkyl, C 2~3 Alkenyl, C 2~6 Alkynyl, C 1~3 Hydroxyalkyl, C 2~3 Alkoxyalkyl, halogen, -CN, -NO, -NO2, -C(O)R 2a , -N(R 2a )C(O)R 2b , -N(R 2a )(R 2b ), -OR 2a or a 5- to 6-membered heteroaryl ring having 1 to 2 heteroatoms, each independently being N, O, or S; R 2a and R 2b are each independently hydrogen or C 1~3 alkyl, and R 3 is hydrogen, C 1~3 alkyl, halogen, -CN or -NO2, and R 4 is hydrogen.

[0105] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ib), (Ic), (IIa), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 1 is hydrogen and R 2 is hydrogen, C 1~3 Alkyl, C 2~3 Alkenyl, C 2~6 Alkynyl, C 1~3 Hydroxyalkyl, C 2~3 Alkoxyalkyl, halogen, -CN, -NO, -NO2, -C(O)R 2a , -N(R 2a )C(O)R 2b , -N(R 2a )(R 2b ), -OR 2a or heteroaryl, and R 2a and R 2b are each independently hydrogen or C 1~3 alkyl, and R 3 is hydrogen and R 4 is hydrogen, and heteroaryl is a 5-6 membered ring having 1-2 heteroatoms, each independently N, O, or S.

[0106] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (IIa), or (IIa-1), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 5 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 Aryl, C 1~6Alkyl-(heterocycloalkyl), or C 1~6 alkyl-(heteroaryl), where alkyl is R 5a and optionally substituted with R 5a is -OSi(R 5a1 )(R 5a2 )(R 5a3 ) and R 5a1 , R 5a2 , and R 5a3 are each independently C 1~4 and heterocycloalkyl is a 5-8 membered ring having 1-2 heteroatoms, each independently N, O, or S. The heteroaryl is a 5-6 membered ring having 1-2 heteroatoms, each independently N, O, or S. In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (IIa), or (IIa-1), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 5 is C 1~6 Alkyl, C 2~6 Alkynyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 Aryl, or C 1~6 alkyl-(heterocycloalkyl), where alkyl is R 5a and optionally substituted with R 5a is -OSi(R 5a1 )(R 5a2 )(R 5a3 ) and R 5a1 , R 5a2 , and R 5a3 are each independently C 1~4 alkyl, where R 5a1 and R 5a2are different and the heterocycloalkyl is a 5-6 membered ring having 1-2 heteroatoms, each independently N or O. In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (IIa), or (IIa-1), or a pharmaceutically acceptable salt thereof, is a compound wherein R 5 is C 1~6 Alkyl, C 2~6 Alkynyl, C 2~3 Alkoxyalkyl, C 1~3 Haloalkyl, C 3~8 Cycloalkyl, C 1~3 Alkyl-C 3~8 Cycloalkyl, phenyl, C 1~3 Alkyl-phenyl, or C 1~3 alkyl-(heterocycloalkyl), where alkyl is R 5a and optionally substituted with R 5a is -OSi(R 5a1 )(R 5a2 )(R 5a3 ) and R 5a1 , R 5a2 , and R 5a3 are each independently Me or tBu, and R 5a1 and R 5a2 are different and heterocycloalkyl is a 6-membered ring having one heteroatom that is N or O. In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (IIa), or (IIa-1), or a pharmaceutically acceptable salt thereof, is a compound wherein R 5 are Me, Et, nPr, nBu, -CH2CMe3, -CH2C≡CMe, -CH2CH2C≡CH, -CH2CH2OMe, -CH2CH2OSi(Me)2(tBu), CF3, -CH2CF2H, -CH2CF3, [ka] is.

[0107] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (IIa), or (IIa-1), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 5 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 Aryl, C 1~6 Alkyl-(heterocycloalkyl), or C 1~6 alkyl-(heteroaryl), where alkyl is R 5a and optionally substituted with R 5a is -OSi(R 5a1 )(R 5a2 )(R 5a3 ) and R 5a1 , R 5a2 , and R 5a3 are each independently C 1~4 and heterocycloalkyl is a 5-8 membered ring having 1-2 heteroatoms, each independently N, O, or S. The heteroaryl is a 5-6 membered ring having 1-2 heteroatoms, each independently N, O, or S. In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (IIa), or (IIa-1), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 5 is C 1~6 Alkyl, C 2~6 Alkynyl, C 2~6 Alkoxyalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~12 Aryl, C 1~6 Alkyl-C 6~12 Aryl, or C 1~6 alkyl-(heterocycloalkyl), where alkyl is R5a and optionally substituted with R 5a is -OSi(R 5a1 )(R 5a2 )(R 5a3 ) and R 5a1 , R 5a2 , and R 5a3 are each independently C 1~4 alkyl, where R 5a1 and R 5a2 are different and the heterocycloalkyl is a 5-6 membered ring having 1-2 heteroatoms, each independently N or O. In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (IIa), or (IIa-1), or a pharmaceutically acceptable salt thereof, is a compound wherein R 5 is C 1~6 Alkyl, C 2~6 Alkynyl, C 2~3 Alkoxyalkyl, C 1~3 Alkyl-C 3~8 Cycloalkyl, phenyl, C 1~3 Alkyl-phenyl, or C 1~3 alkyl-(heterocycloalkyl), where alkyl is R 5a and optionally substituted with R 5a is -OSi(R 5a1 )(R 5a2 )(R 5a3 ) and R 5a1 , R 5a2 , and R 5a3 are each independently Me or tBu, and R 5a1 and R 5a2 are different and heterocycloalkyl is a 6-membered ring with one heteroatom which is N or O.

[0108] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (IIa), or (IIa-1), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 5are Me, Et, nPr, nBu, -CH2CMe3, -CH2C≡CMe, -CH2CH2C≡CH, -CH2CH2OMe, -CH2CH2OSi(Me)2(tBu), [ka] is.

[0109] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (IIa), or (IIa-1), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 5a1 , R 5a2 , and R 5a3 are each independently C 1~4 In some embodiments, the compound of formula (I), (I-1), (Ia), (Ia-1), or (Ib), or a pharmaceutically acceptable salt thereof, is a compound wherein R 5a1 and R 5a2 and R are each Me or tBu. In some embodiments, a compound of formula (I), (I-1), (Ia), (Ia-1), (Ib), (IIa), or (IIa-1), or a pharmaceutically acceptable salt thereof, is a compound of formula (I), (I-1), (Ia), (Ia-1), (Ib), (IIa), or (IIa-1), or a pharmaceutically acceptable salt thereof, wherein R 5a1 and R 5a2 are different.

[0110] In some embodiments, the compound of Formula (I) or (I-1), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 6 is phenyl, naphthyl, thienyl, thiazolyl, pyridyl, pyrazinyl, pyrimidinyl, or dibenzofuryl, and one or two R 6a each optionally substituted with

[0111] In some embodiments, the compound of Formula (I) or (I-1), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 6 is a phenyl or a 5- to 6-membered heteroaryl ring having 1 to 3 heteroatoms, each independently N, O, or S, and one or two R 6aIn some embodiments, the compound of formula (I) or (I-1), or a pharmaceutically acceptable salt thereof, is a compound of formula (I) or (I-1), wherein R 6 is phenyl, thienyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyrrolyl, pyrazolyl, pyridyl, or pyrimidinyl, and one or two R 6a In some embodiments, the compound of formula (I) or (I-1), or a pharmaceutically acceptable salt thereof, is a compound of formula (I) or (I-1), wherein R 6 is phenyl, thienyl, or pyridyl, and one or two R 6a In some embodiments, the compound of formula (I) or (I-1), or a pharmaceutically acceptable salt thereof, is a compound of formula (I) or (I-1), wherein R 6 teeth, [ka] is.

[0112] In some embodiments, the compound of Formula (I) or (I-1), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 6 teeth, [ka] is.

[0113] In some embodiments, the compound of Formula (I) or (I-1), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 6 teeth, [ka] is.

[0114] In some embodiments, the compound of Formula (I), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 7 is hydrogen, Me, Et, OMe, -CH2OH, -CH2OMe, -CH2NMe2, Cl, CHF2, OH, NH2, SMe, or [ka] is. In some embodiments, the compound of Formula (I), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 7 is hydrogen, Me, —CH2OMe, CHF2, or NH2.

[0115] In some embodiments, the compound of Formula (I), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 7 is hydrogen, Me, Et, OMe, -CH2NMe2, Cl, OH, NH2, SMe, or [ka] is. In some embodiments, the compound of Formula (I), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 7is hydrogen or Me. In some embodiments, the compound of Formula (I), (IIa), (IIa-1), (IIc), (IIc-1), or (IIc-2), or a pharmaceutically acceptable salt thereof, is a compound wherein R 7 In some embodiments, the compound of Formula (I), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein R 7 is Me.

[0116] In some embodiments, the compound of formula (I) or a pharmaceutically acceptable salt thereof has the structure of formula (I-1): [ka] or a pharmaceutically acceptable salt thereof.

[0117] In some embodiments, the compound of Formula (I) or a pharmaceutically acceptable salt thereof has the structure of Formula (IIa): [ka] wherein n is 0, 1, 2, or 3. In some embodiments, the compound of Formula (IIa) or a pharmaceutically acceptable salt thereof is a compound wherein n is 0. In some embodiments, the compound of Formula (IIa) or a pharmaceutically acceptable salt thereof is a compound wherein n is 1. In some embodiments, the compound of Formula (IIa) or a pharmaceutically acceptable salt thereof is a compound wherein n is 2. In some embodiments, the compound of Formula (IIa) or a pharmaceutically acceptable salt thereof is a compound wherein n is 3.

[0118] In some embodiments, the compound of Formula (I) or (I-1), or a pharmaceutically acceptable salt thereof, has the structure of Formula (Ia): [ka] wherein n is 0, 1, 2, or 3. In some embodiments, the compound of Formula (Ia) or a pharmaceutically acceptable salt thereof is a compound wherein n is 0. In some embodiments, the compound of Formula (Ia) or a pharmaceutically acceptable salt thereof is a compound wherein n is 1. In some embodiments, the compound of Formula (Ia) or a pharmaceutically acceptable salt thereof is a compound wherein n is 2. In some embodiments, the compound of Formula (Ia) or a pharmaceutically acceptable salt thereof is a compound wherein n is 3.

[0119] In some embodiments, the compound of Formula (I) or a pharmaceutically acceptable salt thereof is a compound having the structure of Formula (IIa-1): [ka]

[0120] In some embodiments, the compound of Formula (I), (I-1), or (Ia), or a pharmaceutically acceptable salt thereof, is a compound having the structure of Formula (Ia-1): [ka]

[0121] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), or (Ic), or a pharmaceutically acceptable salt thereof, is a compound, wherein each R 6aare independently a hydrogen atom, an optionally substituted C1 to C6 alkyl group (e.g., a methyl group and an ethyl group), an optionally substituted C2 to C6 alkenyl group, an optionally substituted C2 to C6 alkynyl group (e.g., a 1-propynyl group, and examples of substituents for these alkyl, alkenyl, and alkynyl groups include a halogen atom, a hydroxy group, and a methoxy group), an optionally substituted C1 to C6 alkoxy group (an example of a substituent is a halogen atom), a C3 to C6 cycloalkyl group (e.g., a cyclopropyl group and a cyclohexyl group), a hydroxy group, a halogen atom, a nitro group , cyano group, amino group, acetylamino group, methoxycarbonyl group, carboxy group, carbamoyl group, formyl group, 5- or 6-membered saturated cyclic amino group (examples include morpholino group, pyrrolidyl group, and piperidyl group), 5- or 6-membered heteroaryl group (examples include furanyl group, thienyl group, imidazolyl group, pyrrolyl group, pyrizolyl group, methylpyrazolyl group, pyridyl group, and pyrimidyl group), phenyl group, substituted phenyl group (examples of the substituent include C1-C6 alkyl group, C3-C6 cycloalkyl group, halogen atom, methoxy group, trifluoromethyl group, and acetylamino group).

[0122] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein each R 6a independently, C 1~6 Alkyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -NO2, -C(O)R 6b , -C(O)OR 6b , -C(O)N(R 6b )(R6c ), -N(R 6b )(R 6c ), -OR 6b , C 3~10 Cycloalkyl, C 6~12 aryl, heterocycloalkyl, or heteroaryl, wherein the cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is selected from the group consisting of 1 to 3 R 6e each optionally substituted with alkyl, R 6f is optionally substituted with

[0123] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein each R 6a independently, C 1~6 Alkyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -NO2, -C(O)R 6b , -C(O)OR 6b , -C(O)N(R 6b )(R 6c ), -N(R 6b )(R 6c ), -OR 6b , C 3~10 Cycloalkyl, C 6~12 aryl, heterocycloalkyl, or heteroaryl, wherein the cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is selected from the group consisting of 1 to 3 R 6e each optionally substituted with alkyl, R 6f and each R 6b and R 6c are independently hydrogen or C 1~6 alkyl, and each R6e independently, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, -C(O)OR 6e1 , -OC(O)R 6e1 , -C(O)N(R 6e1 )(R 6e2 ), -N(R 6e1 )C(O)R 6e2 , -OR 6e1 , -S(O)2N(R 6e1 )(R 6e2 ), -N(R 6e1 )S(O)2(R 6e2 ) and each R 6e1 and R 6e2 are independently hydrogen or C 1~6 alkyl, and R 6f is -OSi(R 6f1 )(R 6f2 )(R 6f3 ) and R 6f1 , R 6f2 , and R 6f3 are each independently C 1~6 In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein each R 6a independently, C 1~3 Alkyl, C 2~3 Alkynyl, C 1~3 Hydroxyalkyl, C 1~3 Alkoxy, C 2~3 Alkoxyalkyl, halogen, C 1~3 Haloalkyl, C 1~3 Haloalkoxy, -CN, -NO2, -C(O)R 6b , -C(O)OR 6b , -C(O)N(R6b )(R 6c ), -N(R 6b )(R 6c ), -OR 6b , C 3~8 cycloalkyl, phenyl, a 5- to 6-membered heterocycloalkyl ring having 1 to 2 heteroatoms each independently being N or O, or a 5- to 6-membered heteroaryl ring having 1 to 2 heteroatoms each independently being N, O, or S, wherein the cycloalkyl, phenyl, heterocycloalkyl, or heteroaryl is selected from the group consisting of 1 to 2 R 6e each optionally substituted with alkyl, R 6f and each R 6b and R 6c are independently hydrogen or C 1~3 alkyl, and each R 6e independently, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, -C(O)OR 6e1 , -OC(O)R 6e1 , -N(R 6e1 )C(O)R 6e2 , -OR 6e1 and each R 6e1 and R 6e2 are independently hydrogen or C 1~6 alkyl, and R 6f is -OSi(R 6f1 )(R 6f2 )(R 6f3 ) and R 6f1 , R 6f2 , and R 6f3 are each independently Me or tBu.

[0124] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein each R 6b and R 6c are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, or C 3~10 In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein each R 6b and R 6c are independently hydrogen, C 1~6 Alkyl, or C 1~6 In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein each R 6b and R 6c are independently hydrogen or C 1~6 In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein each R 6b and R 6c are independently hydrogen or C 1~3In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein each R 6b and R 6c are independently hydrogen or Me.

[0125] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein each R 6b , R 6c and R 6d are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, or C 3~10 In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein each R 6b , R 6c and R 6d are independently hydrogen, C 1~6 Alkyl, or C 1~6 In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein each R6b , R 6c and R 6d are independently hydrogen or C 1~6 In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein each R 6b , R 6c and R 6d are independently hydrogen or C 1~3 In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein each R 6b , R 6c and R 6d are independently hydrogen or Me.

[0126] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein each R 6e are independently a hydrogen atom, a C1-C6 alkyl group (examples include a methyl group, an ethyl group, and a tert-butyl group), a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C1-C6 alkoxy group (for example, a methoxy group), a C3-C6 cycloalkyl group, a hydroxy group, a halogen atom, a nitro group, a cyano group, a carbamoyl group, a formyl group, an acetylamino group, or the like.

[0127] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein each R 6e independently, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, -C(O)OR 6e1 , -OC(O)R 6e1 , -C(O)N(R 6e1 )(R 6e2 ), -N(R 6e1 )C(O)R 6e2 , -OR 6e1 , -S(O)2N(R 6e1 )(R 6e2 ), -N(R 6e1 )S(O)2(R 6e2 ) and each R 6e1 and R 6e2 are independently hydrogen or C 1~6 In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein each R 6e independently, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, -C(O)OR 6e1 , -OC(O)R 6e1 , -N(R 6e1 )C(O)R 6e2 , -OR6e1 and each R 6e1 and R 6e2 are independently hydrogen or C 1~6 In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein each R 6e independently, C 1~6 Alkyl, C 1~3 Alkoxy, halogen, C 1~6 Haloalkyl, -N(R 6e1 )C(O)R 6e2 , or -OR 6e1 and each R 6e1 and R 6e2 are independently hydrogen or C 1~3 It is alkyl.

[0128] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein each R 6n is C 1~6 Alkyl, C 1~6 Hydroxyalkyl, -C(O)OR 6n1 , -OC(O)R 6n1 , -C(O)N(R 6n1 )(R 6n2 ), -N(R 6n1 )C(O)R 6n2 , -OC(O)N(R 6n1 )(R 6n2 ), -N(R 6n1 )C(O)OR 6n2 , ═O, or —OH, where each R 6n1 and R 6n2 are independently hydrogen, C 1~6 Alkyl, or C 1~6In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein each R 6n is C 1~6 Alkyl, -C(O)OR 6n1 , or -OC(O)R 6n1 , -C(O)N(R 6n1 )(R 6n2 ), -N(R 6n1 )C(O)R 6n2 , -OC(O)N(R 6n1 )(R 6n2 ), -N(R 6n1 )C(O)OR 6n2 , ═O, or —OH, where each R 6n1 and R 6n2 are independently hydrogen or C 1~6 In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein each R 6n are independently Me or CO2tBu.

[0129] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein each R 6h independently, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, -CN, -C(O)R 6h1 , -C(O)OR 6h1 , -OC(O)R 6h1 , -C(O)N(R 6h1 )(R 6h2 ), -N(R 6h1 )C(O)R 6h2 , -OC(O)N(R 6h1 )(R 6h2 ), -N(R 6h1 )C(O)OR 6h2 , -N(R 6h1 )(R 6h2 ), =O, -OH, -SR 6h1 , -S(O)R 6h1 , -S(O)2R 6h1 , -S(O)2N(R 6h1 )(R 6h2 ), -N(R 6h1 )S(O)2(R 6h2 ), C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, heterocycloalkyl, or C 1~6 alkyl-(heterocycloalkyl), where each R 6h1 and R 6h2 are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, or C 1~6 Alkyl-C 3~10 In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein each R 6h independently, C 1~6 Alkyl, C 1~6Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 1~6 Haloalkyl, -C(O)R 6h1 , -C(O)OR 6h1 , -N(R 6h1 )(R 6h2 ), ═O, or heterocycloalkyl, where each R 6h1 and R 6h2 are independently hydrogen, C 1~6 Alkyl, or C 1~6 In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein each R 6h are independently Me, -CH2OH, -CH2NHMe, OMe, NH2, CF3, CN, -(CO)Me, -(CO)tBu, -(CO)-CH2OH, CO2Me, CO2tBu, =O, or [ka] is.

[0130] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein each R 6m are independently halogen, C 1~6 Haloalkyl, -CN, -C(O)R 6m1 , -C(O)OR 6m1 , -OC(O)R 6m1 , -C(O)N(R 6m1 )(R 6m2 ), -N(R 6m3 )C(O)R 6m2 , -OC(O)N(R6m1 )(R 6m2 ), -N(R 6m1 )C(O)OR 6m2 , -C(=NR 6m3 )N(R 6m1 )(R 6m2 ), -N(R 6m1 )(R 6m2 ), =O, -OH, -SR 6m1 , -S(O)R 6m1 , -S(O)(NR 6m1 )(R 6m2 ), -S(O)R 6m1 , or -S(O)N(R 6m1 )(R 6m2 ) where each R 6m1 and R 6m2 are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Haloalkyl, C 3~10 In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein each R 6m independently, C 1~6 Haloalkyl, -CN, -C(O)R 6m1 , -C(O)OR 6m1 , -C(O)N(R 6m1 )(R 6m2 ), -N(R 6m1 )(R 6m2 ), =O, -OH, or -S(O)R 6m1 At this time, each R 6m1 and R 6m2 are independently hydrogen, C 1~6In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein each R 6m are independently OH, CF3, CN, CO2H, CONH2, NMe2, SO2Me, or [ka] is.

[0131] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein each R 6e are independently Me, Et, iPr, tBu, -CH2OH, -C(OH)Me2, -OMe, -OEt, -OCH2CH2CH3, -CH2OMe, -OCH2CH2NMe2, F, Cl, Br, CHF2, -C F3, -CH2CHF2, -CH2CF3, -CF2CH3, -C(CH3)2CF3, OCF3, -OCH2CF3, -OCH(CH3)CF3, CN, -C(O)Me, -C(O)tBu, CO2H, CO2M e, CO2tBu, C(O)NH2, =O, OH, NH2, NMe2, -NMeCH2CH2OMe, -NHC(O)Me, -NHC(O)tBu, -NHCO2tBu, SO2Me, SO2Et, SO2(iPr ), SO2(iBu), SO2CF3, -CH2SO2Me, SO(N=H)Me, SO2NH2, SO2NHMe, SO2NMe2, -SO2NHCH2CH2OH, -NHSO2Me, SF5, -POMe2, [ka] is.

[0132] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein each R 6e are Me, Et, iPr, tBu, -CH2OH, -C(OH)Me2, -OMe, -OEt, -OCH2CH2CH3, -CH2OMe, -OCH2CH2NMe2, F, Cl, Br, CHF2, -CF3, -CH2CHF2, -CH2CF3, -CF2CH3, -C(CH3)2CF3, OCF3, -OCH2CF3, -OCH(CH3)CF3, CN, -C(O)Me, -C(O)tBu, CO2H, CO2Me, CO2tBu, C(O)NH2, =O, OH, NH2, NMe2, -NMeCH2CH2OMe, -NHC(O)Me, -NHC(O)tBu, -NHCO2tBu, SO2Me, SO2Et, SO2(iPr) , SO2(iBu), SO2CF3, -CH2SO2Me, SO(N=H)Me, SO2NH2, SO2NHMe, SO2NMe2, -SO2NHCH2CH2OH, -NHSO2Me, SF5, -POMe2, [ka] is. In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein each R 6e are independently Me, Et, tBu, -OMe, F, Cl, -CF3, -NHC(O)Me, or -OH.

[0133] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein each R 6e1 , R 6e2 , and R 6e3 are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, heterocycloalkyl, or C 1~6 alkyl-(heterocycloalkyl), where the cycloalkyl or heterocycloalkyl is selected from 1 to 3 R 6n In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein each R 6e1 , R 6e2 , and R 6e3 are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Alkoxyalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 cycloalkyl, or heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is selected from 1 to 3 R 6n is optionally substituted with

[0134] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein each R 6j are independently halogen, C 1~6 Haloalkyl, -C(O)R 6j1 , -C(O)OR 6j1 , -OC(O)R 6j1 , -C(O)N(R 6j1 )(R 6j2 ), -N(R 6j3 )C(O)R 6j2 , -OC(O)N(R 6j1 )(R 6j2 ), -N(R 6j1 )C(O)OR 6j2 , -N(R 6j1 )(R 6j2 ), =O, -OR 6j1 , -S(O)2R 6j1 , -Si(R 6j1 )(R 6j2 )(R 6j3 ), C 3~10 Cycloalkyl, C 6~12 aryl, heterocycloalkyl, or heteroaryl, wherein the cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is selected from the group consisting of 1 to 3 R 6p wherein each R 6j1 , R 6j2 , and R 6j3 are independently hydrogen or C 1~6 It is alkyl.

[0135] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein each R 6jare independently OH, OMe, CHOMe, F, CHF, CF, CN, NH, NH(CO)CF, NH(CO)OtBu, SOMe, Si(iPr), [ka] is.

[0136] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein each R 6j are independently OH, OMe, F, CHF2, CF3, NH2, NH(CO)OtBu, SO2Me, Si(iPr)3, [ka] is.

[0137] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein each R 6p independently, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -C(O)R 6p1 , -C(O)OR 6p1 , -OC(O)R 6p1 , -C(O)N(R 6p1 )(R 6p2 ), -N(R 6p1 )C(O)R6p2 , -OC(O)N(R 6p1 )(R 6p2 ), -N(R 6p1 )C(O)OR 6p2 , -C(=NR 6p3 )N(R 6p1 )(R 6p2 ), -N(R 6p1 )(R 6p2 ), =O, -OH, -SR 6p1 , -S(O)R 6p1 , -S(NR 6p1 )(NR 6p2 )R 6p3 , -S(O)(NR 6p1 )(R 6p2 ), -S(O)R 6p1 , -S(O)2N(R 6p1 )(R 6p2 ), or -N(R 6p1 )S(O)2(R 6p2 ) where each R 6p1 , R 6p2 , and R 6p3 are independently hydrogen, C 1~6 Alkyl, C 1~6 Hydroxyalkyl, C 1~6 Aminoalkyl, C 2~6 Alkoxyalkyl, C 1~6 Haloalkyl, C 3~10 Cycloalkyl, C 1~6 Alkyl-C 3~10 Cycloalkyl, C 6~10 Aryl, C 1~6 Alkyl-C 6~10 Aryl, heterocycloalkyl, C 1~6 Alkyl-(heterocycloalkyl), heteroaryl, or C 1~6 In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein each R 6p independently, C 1~6 Alkyl, C1~6 Hydroxyalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, -CN, -C(O)R 6p1 , -C(O)OR 6p1 , -OC(O)R 6p1 , -C(O)N(R 6p1 )(R 6p2 ), -N(R 6p1 )C(O)R 6p2 , -OC(O)N(R 6p1 )(R 6p2 ), -N(R 6p1 )C(O)OR 6p2 , -N(R 6p1 )(R 6p2 ), =O, -OH, -SR 6p1 , -S(O)R 6p1 , -S(O)2R 6p1 , -S(O)2N(R 6p1 )(R 6p2 ), or -N(R 6p1 )S(O)2(R 6p2 ) where each R 6p1 and R 6p2 are independently hydrogen or C 1~6 It is alkyl.

[0138] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein each R 6p are independently Me, Et, iPr, F, Cl, CHF, CHF, CF, CFCH, CHCF, ═O, or OH.

[0139] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein each R 6p is independently Me, Cl, CF3, ═O, or OH.

[0140] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein each R 6a is, independently, [ka] [ka] [ka] [ka] [ka] is.

[0141] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein each R 6a is, independently, [ka] [ka] [ka] [ka] [ka] is.

[0142] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein each R 6a are independently Me, Et, -C≡CMe, -OMe, -CH2OH, -CH2OMe, -CH2OSi(Me)2(tBu), F, Cl, Br, I, -CH2F, -CF3, -OCF3, -CN, -NO2, -C(O)H, -COOH, -COOMe, -CONH2, -NH2, -OH, cyclopropyl, cyclohexyl, phenyl, [ka] is.

[0143] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (IIa), or (IIa-1), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 5 is C 1~6 Alkyl, C 2~6 Alkynyl, C 2~6 Alkoxyalkyl, C 1~6 Alkyl-C 3~8 Cycloalkyl, phenyl, C 1~6 Alkyl-phenyl, or C 1~6 alkyl-(heterocycloalkyl), and R 6is phenyl, and one or two R 6a and each R 6a independently, C 1~6 Alkyl, C 2~6 Alkynyl, C 1~6 Hydroxyalkyl, C 1~6 Alkoxy, C 2~6 Alkoxyalkyl, halogen, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -CN, -NO2, -C(O)R 6b , -C(O)OR 6b , -C(O)N(R 6b )(R 6c ), -N(R 6b )(R 6c ), -OR 6b or phenyl, wherein the phenyl is selected from the group consisting of one or two R 6e and optionally substituted with R 6b and R 6c are each independently hydrogen or C 1~6 alkyl, and each R 6e independently, C 1~6 Alkyl, halogen, C 1~6 Haloalkyl, -N(R 6e1 )C(O)R 6e2 , or -OR 6e1 and each R 6e1 and R 6e2 are independently hydrogen or C 1~6 and heterocycloalkyl is a 5- or 6-membered ring having one heteroatom that is N or O. In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (IIa), or (IIa-1), or a pharmaceutically acceptable salt thereof, is a compound wherein R 5 is C 1~6 Alkyl, C 2~6 Alkynyl, C 2~3 Alkoxyalkyl, C 1~3 Alkyl-C 3~8 Cycloalkyl, phenyl, C 1~3 Alkyl-phenyl, or C 1~3 alkyl-(heterocycloalkyl), and R 6is phenyl and R 6a and optionally substituted with R 6a independently, C 1~3 Alkyl, C 2~3 Alkynyl, C 1~3 Hydroxyalkyl, C 1~3 Alkoxy, C 2~3 Alkoxyalkyl, halogen, C 1~3 Haloalkyl, C 1~3 Haloalkoxy, -CN, -NO2, -C(O)R 6b , -C(O)OR 6b , -C(O)N(R 6b )(R 6c ), -N(R 6b )(R 6c ), —OH, or phenyl, where phenyl is R 6e and optionally substituted with R 6b and R 6c are each independently hydrogen or C 1~3 alkyl, and R 6e is C 1~6 Alkyl, halogen, C 1~3 Haloalkyl, -N(R 6e1 )C(O)R 6e2 , or -OR 6e1 and R 6e1 and R 6e2 are independently hydrogen or C 1~3 alkyl, and heterocycloalkyl is a 6-membered ring with one heteroatom which is N or O.

[0144] In some embodiments, the compound of Formula (I), (I-1), or (Ia), or a pharmaceutically acceptable salt thereof, has the structure of Formula (Ib): [ka] wherein m is 0, 1, 2, or 3. In some embodiments, the compound of Formula (I), (I-1), or (Ia), or a pharmaceutically acceptable salt thereof, is a compound wherein m is 0. In some embodiments, the compound of Formula (I), (I-1), or (Ia), or a pharmaceutically acceptable salt thereof, is a compound wherein m is 1. In some embodiments, the compound of Formula (I), (I-1), or (Ia), or a pharmaceutically acceptable salt thereof, is a compound wherein m is 2. In some embodiments, the compound of Formula (I), (I-1), or (Ia), or a pharmaceutically acceptable salt thereof, is a compound wherein m is 3.

[0145] In some embodiments, the compound of Formula (I) or (I-1), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 6 teeth, [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] is.

[0146] In some embodiments, the compound of Formula (I) or (I-1), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 6 teeth, [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] is.

[0147] In some embodiments, the compound of Formula (I) or (I-1), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 6 teeth, [ka] [ka] is.

[0148] In some embodiments, the compound of Formula (I) or (I-1), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 5 and R 6 together with the nitrogen to which they are attached have the following structure: [ka] [ka]

[0149] In some embodiments, the compound of Formula (I) or (I-1), or a pharmaceutically acceptable salt thereof, has the structure of Formula (Ic): [ka] wherein ring A is a 5-8 membered heterocycloalkyl optionally having 1-2 additional heteroatoms, each independently N, O, or S; and optionally wherein ring A is a 5-8 membered heterocycloalkyl optionally having 1-2 additional heteroatoms, each independently N, O, or S; and optionally wherein ring A is a 5-8 membered heterocycloalkyl optionally having 1-2 additional heteroatoms, each independently N, O, or S; 6g and n is 0, 1, or 2. In some embodiments, the compound of Formula (Ic) or a pharmaceutically acceptable salt thereof is a compound wherein ring A is a 5-8 membered heterocycloalkyl optionally having 1-2 additional heteroatoms, each independently N, O, or S, and n is 0, 1, or 2. In some embodiments, the compound of Formula (Ic) or a pharmaceutically acceptable salt thereof is a compound wherein n is 0. In some embodiments, the compound of Formula (Ic) or a pharmaceutically acceptable salt thereof is a compound wherein n is 1. In some embodiments, the compound of Formula (Ic) or a pharmaceutically acceptable salt thereof is a compound wherein n is 2. In some embodiments, the compound of Formula (Ic) or a pharmaceutically acceptable salt thereof is a compound wherein ring A is a 5-8 membered heterocycloalkyl. In some embodiments, the compound of Formula (Ic) or a pharmaceutically acceptable salt thereof is a compound of Formula (Ic) or a pharmaceutically acceptable salt thereof, wherein ring A is a 6-membered heterocycloalkyl having one additional heteroatom, O.

[0150] In some embodiments, the compound of Formula (I) or a pharmaceutically acceptable salt thereof has the structure of Formula (IIc): [ka] wherein ring A is a 5-8 membered heterocycloalkyl optionally having 1-2 additional heteroatoms, each independently N, O, or S; and optionally wherein ring A is a 5-8 membered heterocycloalkyl optionally having 1-2 additional heteroatoms, each independently N, O, or S; and optionally wherein ring A is a 5-8 membered heterocycloalkyl optionally having 1-2 additional heteroatoms, each independently N, O, or S; 6g and n is 0, 1, or 2. In some embodiments, the compound of Formula (IIc) or a pharmaceutically acceptable salt thereof is a compound wherein ring A is a 5-8 membered heterocycloalkyl optionally having 1-2 additional heteroatoms, each independently N, O, or S, and n is 0, 1, or 2. In some embodiments, the compound of Formula (IIc) or a pharmaceutically acceptable salt thereof is a compound wherein n is 0. In some embodiments, the compound of Formula (IIc) or a pharmaceutically acceptable salt thereof is a compound wherein n is 1. In some embodiments, the compound of Formula (IIc) or a pharmaceutically acceptable salt thereof is a compound wherein n is 2. In some embodiments, the compound of Formula (IIc) or a pharmaceutically acceptable salt thereof is a compound wherein ring A is a 5-8 membered heterocycloalkyl. In some embodiments, the compound of Formula (IIc) or a pharmaceutically acceptable salt thereof is a compound of Formula (IIc) or a pharmaceutically acceptable salt thereof, wherein ring A is a 6-membered heterocycloalkyl having one additional O heteroatom.

[0151] In some embodiments, the compound of Formula (Ic), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 1 In some embodiments, the compound of Formula (Ic), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein R 1 is hydrogen or F.

[0152] In some embodiments, the compound of Formula (Ic), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 4 is hydrogen, C 1~3 In some embodiments, the compound of Formula (Ic), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein R 4 is hydrogen, Me, or F.

[0153] In some embodiments, the compound of formula (I) or a pharmaceutically acceptable salt thereof has the structure of formula (IIc-1): [ka] wherein ring A is a 5-8 membered heterocycloalkyl optionally having 1-2 additional heteroatoms, each independently N, O, or S; and optionally wherein ring A is a 5-8 membered heterocycloalkyl optionally having 1-2 additional heteroatoms, each independently N, O, or S; and optionally wherein ring A is a 5-8 membered heterocycloalkyl optionally having 1-2 additional heteroatoms, each independently N, O, or S; 6gand n is 0, 1, or 2. In some embodiments, the compound of Formula (IIc-1) or a pharmaceutically acceptable salt thereof is a compound wherein ring A is a 5-8 membered heterocycloalkyl optionally having 1-2 additional heteroatoms, each independently N, O, or S, and n is 0, 1, or 2. In some embodiments, the compound of Formula (IIc-1) or a pharmaceutically acceptable salt thereof is a compound wherein n is 0. In some embodiments, the compound of Formula (IIc-1) or a pharmaceutically acceptable salt thereof is a compound wherein n is 1. In some embodiments, the compound of Formula (IIc-1) or a pharmaceutically acceptable salt thereof is a compound wherein n is 2. In some embodiments, the compound of Formula (IIc-1) or a pharmaceutically acceptable salt thereof is a compound wherein ring A is a 5-8 membered heterocycloalkyl. In some embodiments, the compound of Formula (IIc-1) or a pharmaceutically acceptable salt thereof is a compound of Formula (IIc-1) or a pharmaceutically acceptable salt thereof, wherein ring A is a 6-membered heterocycloalkyl having one additional O heteroatom.

[0154] In some embodiments, the compound of Formula (Ic), (IIc), or (IIc-1), or a pharmaceutically acceptable salt thereof, is [ka] but, [ka] It is a compound having the structure:

[0155] In some embodiments, the compound of Formula (I) or (Ic), or a pharmaceutically acceptable salt thereof, is 6g But independently, C 1~6 Alkyl, halogen, C 1~6 In some embodiments, the compound of Formula (I) or (Ic), or a pharmaceutically acceptable salt thereof, is a compound of Formula (I) or (Ic), wherein each R is -CH, ... 6g But independently, C 1~6In some embodiments, the compound of formula (I) or (Ic), or a pharmaceutically acceptable salt thereof, is a compound of formula (I) or (Ic), wherein each R is alkyl or halogen. 6g are independently methyl.

[0156] In some embodiments, the compound of Formula (Ic), (IIc), or (IIc-1), or a pharmaceutically acceptable salt thereof, is [ka] but, [ka] [ka] It is a compound having the structure:

[0157] In some embodiments, the compound of Formula (Ic), (IIc), or (IIc-1), or a pharmaceutically acceptable salt thereof, is [ka] but, [ka] It is a compound having the structure:

[0158] In some embodiments, the compound of Formula (Ic) or a pharmaceutically acceptable salt thereof is [ka] but, [ka] It is a compound having the structure:

[0159] In some embodiments, the compound of Formula (Ic), (IIc), or (IIc-1), or a pharmaceutically acceptable salt thereof, is [ka] but, [ka] It is a compound having the structure: In some embodiments, the compound of Formula (Ic), (IIc), or (IIc-1), or a pharmaceutically acceptable salt thereof, is [ka] but, [ka] It is a compound having the structure: In some embodiments, the compound of Formula (Ic), (IIc), or (IIc-1), or a pharmaceutically acceptable salt thereof, is [ka] but, [ka] It is a compound having the structure:

[0160] In some embodiments, the compound of formula (I) or a pharmaceutically acceptable salt thereof has the structure of formula (IIc-2): [ka] wherein n is 0, 1, or 2.

[0161] In some embodiments, the compound of Formula (Ic), (IIc), or (IIc-1), or a pharmaceutically acceptable salt thereof, is [ka] but, [ka] It is a compound having the structure:

[0162] In some embodiments, the compound of Formula (I), (IIa), or (IIc), or a pharmaceutically acceptable salt thereof, is a compound having the following structure: [ka]

[0163] In some embodiments, the compound of Formula (IIc) is a compound of Formula (IIc-3), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (IIc) is a compound of Formula (IIc-4), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (IIc) is a compound of Formula (IIc-5), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (IIc) is a compound of Formula (IIc-6), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (IIc) is a compound of Formula (IIc-7), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (IIc) is a compound of Formula (IIc-8), or a pharmaceutically acceptable salt thereof.

[0164] In some embodiments, a compound of Formula (I), (IIa), (IIa-1), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound of Formula (I), wherein R 1 is hydrogen, C 1~3 alkyl or halogen, R 2 is hydrogen, C 1~3 Alkyl, C 1~3 Hydroxyalkyl, C 2~3 alkoxyalkyl, halogen, or -CN; R 3 is hydrogen, C 1~3 alkyl or halogen, R 4 is hydrogen, C 1~3 alkyl, or halogen, and each R 6a independently, C 1~3 Alkyl, C2~3 Alkenyl, or C 2~3 alkynyl, wherein the alkynyl is selected from 1 to 3 R 6j and each R 6j independently, C 2~3 Alkoxyalkyl, halogen, C 1~3 Haloalkyl, C 1~3 Haloalkoxy, -CN, C 3~8 cycloalkyl, or heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is selected from 1 to 3 R 6p and each R 6p independently, C 1~3 Alkyl, C 1~3 Hydroxyalkyl, C 2~3 Alkoxyalkyl, halogen, C 1~3 Haloalkyl, C 1~3 haloalkoxy, or -CN; and R 7 is hydrogen, C 1~3 Alkyl, C 2~3 Alkoxyalkyl, C 1~3 haloalkyl, or -NH2.

[0165] In some embodiments, a compound of Formula (I), (IIa), (IIa-1), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound of Formula (I), wherein R 1 is hydrogen, C 1~3 alkyl or halogen, R 2 is hydrogen, C 1~3 Alkyl, C 1~3 Hydroxyalkyl, C 2~3 alkoxyalkyl, halogen, or -CN; R 3 is hydrogen, C 1~3 alkyl or halogen, R 4 is hydrogen, C 1~3 alkyl, or halogen, and each R 6a independently, C 1~3 Alkyl, C 2~3 Alkenyl, or C 2~3alkynyl, wherein the alkynyl is selected from 1 to 3 R 6j and each R 6j independently, C 2~3 Alkoxyalkyl, halogen, C 1~3 Haloalkyl, C 1~3 Haloalkoxy, -CN, C 3~8 cycloalkyl, or heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is selected from 1 to 3 R 6p and each R 6p independently, C 1~3 Alkyl, C 1~3 Hydroxyalkyl, C 2~3 Alkoxyalkyl, halogen, C 1~3 Haloalkyl, C 1~3 haloalkoxy, or -CN, and R 7 is hydrogen or C 1~3 It is alkyl.

[0166] In some embodiments, the compound of Formula (I), (IIa), (IIa-1), (IIc), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 1 is hydrogen or F, and R 2 is hydrogen, F or Cl, and R 3 is hydrogen or F, and R 4 is hydrogen or F, and each R 6a independently, C 1~3 Alkyl, C 2~3 Alkenyl, or C 2~3 alkynyl, wherein the alkynyl is selected from 1 to 3 R 6j and each R 6j independently, C 2~3 Alkoxyalkyl, halogen, C 1~3 Haloalkyl, C 1~3 Haloalkoxy, -CN, C 3~8 cycloalkyl, or heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is selected from 1 to 3 R6p and each R 6p independently, C 1~3 Alkyl, C 1~3 Hydroxyalkyl, C 2~3 Alkoxyalkyl, halogen, C 1~3 Haloalkyl, C 1~3 haloalkoxy, or -CN, and R 7 is hydrogen or Me.

[0167] In some embodiments, the compound of Formula (Ic), IIc), or (IIc-1), or a pharmaceutically acceptable salt thereof, is a compound, wherein R 2 is hydrogen, C 1~3 Alkyl, C 1~3 Hydroxyalkyl, C 2~3 alkoxyalkyl, halogen, or -CN; R 3 is hydrogen, C 1~3 alkyl, or halogen, and each R 6a independently, C 1~3 Alkyl, C 2~3 Alkenyl, or C 2~3 alkynyl, wherein the alkynyl is selected from 1 to 3 R 6j and each R 6j independently, C 2~3 Alkoxyalkyl, halogen, C 1~3 Haloalkyl, C 1~3 Haloalkoxy, -CN, C 3~8 cycloalkyl, or heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is selected from 1 to 3 R 6p and each R 6p independently, C 1~3 Alkyl, C 1~3 Hydroxyalkyl, C 2~3 Alkoxyalkyl, halogen, C 1~3 Haloalkyl, C 1~3 haloalkoxy, or -CN, and R 7 is hydrogen or C 1~3 is alkyl, [ka] teeth, [ka] It has the following structure.

[0168] In some embodiments, the compound of Formula (Ic), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is 2 In some embodiments, the compound of Formula (Ic), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein R 2 is hydrogen, F, or Cl.

[0169] In some embodiments, the compound of Formula (Ic), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is 3 is hydrogen, F, or Cl.

[0170] In some embodiments, the compound of Formula (Ic), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein each R 6a independently, C 2~3 alkynyl or halogen, where alkynyl is selected from 1 to 3 R 6jIn some embodiments, a compound of Formula (Ic), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein each R 6a teeth, [ka] 1 R 6j is replaced by .

[0171] In some embodiments, the compound of Formula (Ic), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein each R 6j independently, C 2~3 Alkoxyalkyl, halogen, C 1~3 Haloalkyl, -CN, C 3~6 cycloalkyl, or heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is selected from 1 to 3 R 6p wherein each heterocycloalkyl is a 3- to 6-membered ring having 1-2 heteroatoms, each independently N, O, or S. In some embodiments, a compound of Formula (Ic), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein each R 6j are independently halogen, C 1~3 Haloalkyl, C 3~6 cycloalkyl or heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is selected from 1 to 2 R 6pwherein each heterocycloalkyl is a 3- to 6-membered ring having 1-2 heteroatoms, each independently N, O, or S. In some embodiments, a compound of Formula (Ic), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein each R 6j are independently halogen, C 1~3 Haloalkyl, or C 3~6 cycloalkyl, where cycloalkyl is a group selected from the group consisting of one R 6p In some embodiments, a compound of Formula (Ic), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein each R 6j are independently F, CHF, CHF, CF, CHCF, CFCH, or cyclopropyl, where cyclopropyl is selected from one R 6p is optionally substituted with

[0172] In some embodiments, the compound of Formula (Ic), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound, wherein each R 6p independently, C 1~3 Alkyl, C 1~3 Hydroxyalkyl, halogen, C 1~3 In some embodiments, a compound of Formula (Ic), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein each R 6p are independently Me, Et, CHOH, F, CHF, CHF, CF, CHCF, CFCH, or —CN.

[0173] In some embodiments, the compound of Formula (Ic), (IIc), or (IIc-1), or a pharmaceutically acceptable salt thereof, is [ka] but, [ka] It is a compound having the structure:

[0174] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1)(IIc-2), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein heterocycloalkyl is a 5-8 membered ring having 1-2 heteroatoms, each independently N, O, or S. In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1)(IIc-2), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein heterocycloalkyl is a 5- to 6-membered ring having 1 to 2 heteroatoms, each independently being N or O. In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1)(IIc-2), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein heterocycloalkyl is a 6-membered ring having one heteroatom that is N or O.

[0175] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1)(IIc-2), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein heteroaryl is a 5- to 6-membered ring having 1-2 heteroatoms, each independently N, O, or S. In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein heteroaryl is a 6-membered ring having 1 to 2 heteroatoms, each of which is N.

[0176] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound wherein heterocycloalkyl is a 5- to 6-membered ring having 1-2 heteroatoms, each independently N or O, and heteroaryl is a 5- to 6-membered ring having 1-2 heteroatoms, each independently N, O, or S.

[0177] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is Table 1A, Table 1B, Table 1C, Table 1D, Table 1E, Table 1F, Table 1G, Table 1H, Table 1I, Table 1J, Table 2A, Table 2B, Table 2C, Table 2D, Table 2E, Table 2F, Table 2G, Table 2H, Table 2I, A compound having the structure of a compound in Table 2J, Table 2K, Table 2L, Table 3A, Table 3B, Table 3C, Table 3D, Table 3E, Table 3F, Table 3G, Table 3H, Table 3I, Table 3J, or Table 3K. In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is a compound having the structure of a compound in Table 3F, Table 3H, Table 3I, Table 3J, or Table 3K. [Table 1-1] [Table 1-2] [Table 2-1] [Table 2-2] [Table 3-1] [Table 3-2] [Table 4-1] [Table 4-2] [Table 5-1]

Table 5-2

Table 6-1

Table 6-2

Table 7-1

Table 7-2

Table 8-1

Table 8-2

Table 9-1

Table 9-2

Table 10-1

Table 10-2

Table 11-1

Table 11-2

Table 11-3

Table 12-1

Table 12-2

Table 12-3

Table 13-1

Table 13-2

Table 13-3

Table 14-1

Table 14-2

Table 14-3

Table 15-1

Table 15-2

Table 15-3

Table 16-1

Table 16-2

Table 16-3

Table 17-1

Table 17-2

Table 17-3

Table 18-1

Table 18-2

Table 18-3

Table 19-1

Table 19-2

Table 19-3

Table 20-1

Table 20-2

Table 20-3

Table 21-1

Table 21-2

Table 21-3

Table 22-1

Table 22-2

Table 23-1

Table 23-2

Table 23-3

Table 24-1

Table 24-2

Table 25-1

Table 25-2

Table 26-1

Table 26-2

Table 27-1

Table 27-2

Table 27-3

Table 28-1

Table 28-2

Table 28-3

Table 29-1

Table 29-2

Table 29-3

Table 30-1

Table 30-2

Table 30-3

Table 31-1

[0178] Also within the scope of this specification are in vivo metabolic products of the compounds described herein to the extent that such products are novel and unobvious based on the prior art. Such products may result, for example, from the oxidation, reduction, hydrolysis, amidation, esterification, etc., of the administered compound, primarily by enzymatic processes. Thus, included are novel and unobvious compounds produced by a process comprising contacting the compound with a mammal for a period of time sufficient to yield a metabolic product thereof. Such products are typically radiolabeled (e.g., 14 C or 3H) Compounds are prepared and identified by parenteral administration to animals such as rats, mice, guinea pigs, monkeys, or humans at detectable doses (e.g., greater than about 0.5 mg / kg), allowing sufficient time for metabolism to occur (typically about 30 seconds to about 30 hours), and isolating the transformation products from urine, blood, or other biological samples. These products are labeled and therefore easily isolated (others are isolated by the use of antibodies capable of binding to epitopes remaining in the metabolites). The structures of the metabolites are determined in conventional manner, e.g., by MS or NMR analysis. Metabolite analysis is generally performed in the same manner as conventional drug metabolism studies well known to those skilled in the art.

[0179] In some embodiments, compounds of the present disclosure have selectivity for DGKα over one or more of other DGK isoforms, e.g., β, γ, δ, ε, ζ, η, θ, ι, and / or κ. Selectivity can be measured by relative values ​​in corresponding biochemical assays, e.g., inhibitory activity of DGK isoforms. In some embodiments, compounds have activity against DGKβ, DGKγ, DGKδ, DGKε, DGKζ, DGKη, DGKθ, DGKι, and / or DGKκ, and exhibit IC 50 is greater than about 30 μM in biochemical assays.

[0180] In some embodiments, compounds of the present disclosure have at least about 1.2, about 1.5, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 15, about 20, about 30, about 40, about 50, about 60, about 70, about 80, about 90, about 100, about 200, about 300, about 400, about 500, about 1000, about 2000, about 3000, about 4000, about 5000, or about 10,000 times or more selectivity for DGKα over one or more, e.g., 2, 3, 4, 5, 6, 7, 8, or 9 or more, other DGK isoforms, including DGKβ, DGKγ, DGKδ, DGKε, DGKζ, DGKη, DGKθ, DGKι, and / or DGKκ. In some embodiments, the compound has selectivity for DGKα over DGKβ and / or DGKγ that is at least about 1.2, about 1.5, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 15, about 20, about 30, about 40, about 50, about 60, about 70, about 80, about 90, about 100, about 200, about 300, about 400, about 500, about 1000, about 2000, about 3000, about 4000, about 5000, or about 10,000 times or more. In some embodiments, the compound has at least about 1.2, about 1.5, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 15, about 20, about 30, about 40, about 50, about 60, about 70, about 80, about 90, about 100, about 200, about 300, about 400, about 500, about 1000, about 2000, about 3000, about 4000, about 5000, or about 10,000 times or more selectivity for DGKα over DGKβ. In some embodiments, the compound has at least about 1.2, about 1.5, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 15, about 20, about 30, about 40, about 50, about 60, about 70, about 80, about 90, about 100, about 200, about 300, about 400, about 500, about 1000, about 2000, about 3000, about 4000, about 5000, or about 10,000 times or more selectivity for DGKα over DGKγ.In some embodiments, the compound has at least about 1.2, about 1.5, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 15, about 20, about 30, about 40, about 50, about 60, about 70, about 80, about 90, about 100, about 200, about 300, about 400, about 500, about 1000, about 2000, about 3000, about 4000, about 5000, or about 10,000 times or more selectivity for DGKα over DGKδ. In some embodiments, the compound has at least about 1.2, about 1.5, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 15, about 20, about 30, about 40, about 50, about 60, about 70, about 80, about 90, about 100, about 200, about 300, about 400, about 500, about 1000, about 2000, about 3000, about 4000, about 5000, or about 10,000 times or more selectivity for DGKε over DGKδ. In some embodiments, the compound has at least about 1.2, about 1.5, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 15, about 20, about 30, about 40, about 50, about 60, about 70, about 80, about 90, about 100, about 200, about 300, about 400, about 500, about 1000, about 2000, about 3000, about 4000, about 5000, or about 10,000 times or more selectivity for DGKzeta over DGKdelta. In some embodiments, the compound has at least about 1.2, about 1.5, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 15, about 20, about 30, about 40, about 50, about 60, about 70, about 80, about 90, about 100, about 200, about 300, about 400, about 500, about 1000, about 2000, about 3000, about 4000, about 5000, or about 10,000 times or more selectivity for DGKη over DGKδ. In some embodiments, the compound has at least about 1.2, about 1.5, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 15, about 20, about 30, about 40, about 50, about 60, about 70, about 80, about 90, about 100, about 200, about 300, about 400, about 500, about 1000, about 2000, about 3000, about 4000, about 5000, or about 10,000 times or more selectivity for DGKtheta over DGKdelta.In some embodiments, the compound has at least about 1.2, about 1.5, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 15, about 20, about 30, about 40, about 50, about 60, about 70, about 80, about 90, about 100, about 200, about 300, about 400, about 500, about 1000, about 2000, about 3000, about 4000, about 5000, or about 10000 times or more selectivity for DGKι over DGKδ. In some embodiments, the compound has at least about 1.2, about 1.5, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 15, about 20, about 30, about 40, about 50, about 60, about 70, about 80, about 90, about 100, about 200, about 300, about 400, about 500, about 1000, about 2000, about 3000, about 4000, about 5000, or about 10,000 times or more selectivity for DGKκ over DGKδ. III. Pharmaceutical Preparations

[0181] In some embodiments, the present disclosure provides a pharmaceutical formulation comprising a pharmaceutically effective amount of a compound of the present disclosure or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient. Also provided herein is a pharmaceutical formulation comprising a pharmaceutically effective amount of a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt, solvate, and / or ester thereof, and a pharmaceutically acceptable carrier or excipient.

[0182] In some embodiments, the pharmaceutical composition further comprises one or more additional therapeutic agents. Any suitable additional therapeutic agent or combination therapy can be used with a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, such as the agents and therapies described herein.

[0183] In some embodiments, the pharmaceutical composition comprises a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8) and an additional therapeutic agent, wherein the additional therapeutic agent is an anti-cancer agent. In some embodiments, the pharmaceutical composition is a pharmaceutical composition wherein the additional therapeutic agent is independently an anti-neoplastic agent, nivolumab, pembrolizumab, atezolizumab, ipilimumab, chemotherapy, radiation therapy, or ablation therapy. In some embodiments, the pharmaceutical composition is a pharmaceutical composition wherein the additional therapeutic agent is independently Rituxan, doxorubicin, gemcitabine, nivolumab, pembrolizumab, atezolizumab, nivolumab, pembrolizumab, atezolizumab, or ipilimumab. In some embodiments, the pharmaceutical composition is a pharmaceutical composition wherein the additional therapeutic agent is a PD-1 / PD-L1 inhibitor. In some embodiments, the pharmaceutical composition is a pharmaceutical composition wherein the additional therapeutic agent is a vaccine.

[0184] In some embodiments, the pharmaceutical composition is one in which the additional therapeutic agent comprises one or more populations of immune cells, such as natural killer (NK) cells, NK-T cells, T cells, cytokine-induced killer (CIK) cells, macrophage (MAC) cells, tumor-infiltrating lymphocytes (TIL), and dendritic cells (DC).

[0185] In some embodiments, the pharmaceutical composition is one in which the additional therapeutic agent comprises one or more chimeric antigen receptors (CARs).

[0186] In some embodiments, the pharmaceutical composition is one in which the additional therapeutic agent comprises immunotherapy, immunostimulatory therapy, cytokine therapy, chemokine therapy, cell therapy, gene therapy, and combinations thereof.

[0187] In some embodiments, a pharmaceutical composition comprises a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8) and an additional therapeutic agent, wherein the additional therapeutic agent is an agent effective against a viral infection. In some embodiments, the viral infection is HIV. In some embodiments, the viral infection is hepatitis B virus. In some embodiments, the pharmaceutical composition comprises a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8) and an additional therapeutic agent, wherein the additional therapeutic agent comprises a vaccine.

[0188] In some embodiments, the pharmaceutical composition is for use in the treatment of cancer.

[0189] In some embodiments, the pharmaceutical composition is for use in treating an HIV or Hepatitis B infection.

[0190] In some embodiments, the compounds disclosed herein are formulated with conventional carriers and excipients, which can be selected according to ordinary practice. Tablets may contain excipients, lubricants, fillers, binders, etc. Aqueous formulations can be prepared in sterile form and can be isotonic, for example, if intended for delivery other than oral administration. In some embodiments, formulations can optionally contain excipients such as those described in the "Handbook of Pharmaceutical Excipients" (1986). Excipients can include, for example, ascorbic acid and other antioxidants, chelating agents such as EDTA, carbohydrates such as dextran, hydroxyalkylcellulose, hydroxyalkylmethylcellulose, and stearic acid. The pH of the formulation ranges from about 3 to about 11, e.g., from about 7 to about 10.

[0191] In some embodiments, a compound disclosed herein is administered alone. In some embodiments, a compound disclosed herein is administered in a pharmaceutical formulation. In some embodiments, veterinary and / or human formulations comprise at least one compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt, solvate, and / or ester thereof, together with one or more acceptable carriers and, optionally, other therapeutic components, such as additional therapeutic components discussed herein. In some embodiments, a carrier is "acceptable" in the sense of being compatible with the other components of the formulation and physiologically innocuous to the recipient thereof.

[0192] In some embodiments, formulations of the present disclosure include those suitable for the aforementioned routes of administration. In some embodiments, the formulations are in unit dosage form. The formulations may be prepared by methods known in the art of pharmacy. Techniques and formulations can be found, for example, in Remington's Pharmaceutical Sciences (Mack Publishing Co., Easton, PA). Such methods include, for example, the step of bringing into association the active ingredient with the carrier(s) which comprises one or more accessory ingredients. In some embodiments, the formulations are prepared by bringing the active ingredient(s) into association with liquid carriers or finely divided solid carriers, or both, and then, in some embodiments, shaping the product.

[0193] Formulations suitable for oral administration may be present as discrete units such as capsules, cachets, or tablets, each containing a predetermined amount of the active ingredient, such as a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt, solvate, and / or ester thereof; as a powder or granules; as a solution or suspension in an aqueous or non-aqueous liquid; or as an oil-in-water or water-in-oil liquid emulsion. In some embodiments, the active ingredient is administered as a bolus, electuary, or paste.

[0194] Tablets can be made, for example, by compression or molding, optionally with one or more accessory ingredients. Compressed tablets can be prepared, for example, by compressing the active ingredient in a free-flowing form, such as a powder or granules, in a suitable machine, optionally mixed with a binder, lubricant, inert diluent, preservative, surfactant, or dispersing agent. Molded tablets can be made, for example, by molding a mixture of the powdered active ingredient moistened with an inert liquid diluent in a suitable machine. Tablets can optionally be coated or scored. In some embodiments, tablets are formulated to provide sustained or controlled release of the active ingredient therefrom.

[0195] For infections of the eye or other external tissues, e.g., mouth and skin, the formulation may comprise an ointment comprising a compound of formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc -8) can be applied as a topical ointment or cream containing, for example, about 0.075 to about 20% w / w (including about 0.1% w / w units of active ingredient in the range of about 0.1% to about 20%, e.g., about 0.6% w / w, about 0.7% w / w, etc.), for example, about 0.2 to about 15% w / w, and for example, about 0.5 to about 10% w / w. When formulated as an ointment, the compounds of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8) may be used with either a paraffinic or a water-miscible ointment base. Alternatively, the compounds of formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8) may be formulated in a cream having an oil-in-water cream base.

[0196] Optionally, the aqueous phase of the cream base may contain, for example, at least about 30% w / w of a polyhydric alcohol, i.e., an alcohol having two or more hydroxyl groups, such as propylene glycol, butane 1,3-diol, mannitol, sorbitol, glycerol, and polyethylene glycol (including PEG 400) and mixtures thereof. Topical formulations, in some embodiments, may include compounds that enhance absorption or penetration of active ingredients through the skin or other affected areas. Examples of such skin penetration enhancers include dimethyl sulfoxide and related analogues.

[0197] The oily phase of the emulsion can be composed of known ingredients in a known manner. The phase can include only an emulsifier (otherwise known as an emulgent), but can also include, for example, a mixture of at least one emulsifier with a fat or oil, or with both a fat and an oil. In some embodiments, a hydrophilic emulsifier is included together with a lipophilic emulsifier that functions as a stabilizer. In some embodiments, the emulsion includes both an oil and a fat. The emulsifiers, with or without a stabilizer, together constitute a so-called emulsifying wax, which, together with the oil and fat, constitute a so-called emulsifying ointment base that forms the oily dispersed phase of a cream formulation.

[0198] Suitable emulsifiers and emulsion stabilizers for use in the formulation include, for example, Tween® 60, Span® 80, cetostearyl alcohol, benzyl alcohol, myristyl alcohol, glyceryl monostearate, and sodium lauryl sulfate.

[0199] The selection of suitable oils or fats for the formulation is based on achieving the desired properties. The cream can be a non-greasy, non-staining, and washable product with a suitable consistency to avoid leakage from tubes or other containers. Linear or branched mono- or dibasic alkyl esters can be used, such as diisoadipate, isocetyl stearate, propylene glycol diester of coconut fatty acid, isopropyl myristate, decyl oleate, isopropyl palmitate, butyl stearate, 2-ethylhexyl palmitate, or a blend of branched esters known as Crodamol CAP. These can be used alone or in combination, depending on the desired properties. Alternatively, high-melting lipids such as white soft paraffin and / or liquid paraffin or other mineral oils can be used.

[0200] In some embodiments, the pharmaceutical formulations herein comprise a combination of one or more pharmaceutically acceptable carriers or excipients, and optionally other therapeutic agents. Pharmaceutical formulations containing the active ingredient may be in any form suitable for the intended method of administration. For example, for oral use, tablets, troches, lozenges, aqueous or oil suspensions, dispersible powders or granules, emulsions, hard or soft capsules, solutions, syrups, or elixirs can be prepared. Compositions intended for oral use may be prepared according to any method known in the art for the manufacture of pharmaceutical compositions, and such compositions may contain one or more agents, including sweeteners, flavoring agents, coloring agents, and preservatives, to provide a palatable preparation. Tablets containing the active ingredient in a mixture with non-toxic pharmaceutically acceptable excipients suitable for the manufacture of tablets are acceptable. These excipients may be, for example, inert diluents such as calcium or sodium carbonate, lactose, calcium or sodium phosphate; granulating and disintegrating agents such as corn starch or alginic acid; binders such as starch, gelatin or acacia; and lubricants such as magnesium stearate, stearic acid or talc. The tablets may be uncoated or may be coated by known techniques, including microencapsulation, to delay disintegration and adsorption in the gastrointestinal tract and thereby provide a sustained action over a longer period. For example, a time-delay material such as glyceryl monostearate or glyceryl distearate alone or with a wax may be employed.

[0201] Formulations for oral use may also be presented as hard gelatin capsules in which the active ingredient is mixed with an inert solid diluent, such as calcium carbonate or kaolin, or as soft gelatin capsules in which the active ingredient is mixed with water or an oil medium such as peanut oil, liquid paraffin, or olive oil.

[0202] Aqueous suspensions contain the active substance in admixture with excipients suitable for the manufacture of aqueous suspensions. Such excipients include suspending agents such as carboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose, sodium alginate, polyvinylpyrrolidone, tragacanth gum, and acacia gum, as well as dispersing or wetting agents such as naturally occurring phosphatides (e.g., lecithin), condensation products of alkylene oxides with fatty acids (e.g., polyoxyethylene stearate), condensation products of ethylene oxide with long-chain aliphatic alcohols (e.g., heptadecathyleneoxycetanol), and condensation products of ethylene oxide with partial esters derived from fatty acids and hexitol anhydrides (e.g., polyoxyethylene sorbitan monooleate). Aqueous suspensions may also contain one or more preservatives, such as ethyl p-hydroxybenzoate or n-propyl p-hydroxybenzoate, one or more coloring agents, one or more flavoring agents, and one or more sweeteners, such as sucrose or saccharin.

[0203] Oily suspensions can be formulated by suspending the active ingredient in vegetable oils such as arachis oil, olive oil, sesame oil, or coconut oil, or in mineral oils such as liquid paraffin. Oral suspensions can contain thickening agents such as beeswax, hard paraffin, or cetyl alcohol. Sweeteners and flavoring agents such as those mentioned above can be added to provide a palatable oral preparation. These compositions can be preserved by adding antioxidants such as ascorbic acid.

[0204] Dispersible powders and granules suitable for preparation of an aqueous suspension by adding water provide the active ingredient mixed with a dispersing or wetting agent, a suspending agent, and one or more preservatives. Suitable dispersing or wetting agents and suspending agents are exemplified by those disclosed above. Additional excipients, such as sweeteners, flavorings, and coloring agents, may also be present.

[0205] The pharmaceutical composition can also be in the form of an oil-in-water emulsion. The oil phase can be vegetable oil such as olive oil or arachis oil, mineral oil such as liquid paraffin, or a mixture thereof. Suitable emulsifiers include natural gums such as acacia gum and tragacanth gum, natural phosphatides such as soybean lecithin, esters or partial esters derived from fatty acids and hexitol anhydrides such as sorbitan monooleate, and condensation products of these partial esters with ethylene oxide such as polyoxyethylene sorbitan monooleate. Emulsions can also contain sweeteners and flavoring agents. Syrups and elixirs can be formulated with sweeteners such as glycerol, sorbitol, or sucrose. Such preparations can also contain demulcents, preservatives, flavorings, or coloring agents.

[0206] Pharmaceutical compositions may be in the form of sterile injectable or intravenous preparations, such as sterile injectable aqueous or oleaginous suspensions. Such suspensions can be formulated according to known techniques using suitable dispersing or wetting agents and suspending agents, as described above. Sterile injectable or intravenous preparations can also include sterile injectable solutions or suspensions in non-toxic parenterally acceptable diluents or solvents, such as solutions in 1,3-butanediol or prepared as lyophilized powders. Acceptable vehicles and solvents that can be used include water, Ringer's solution, and isotonic sodium chloride solution. Additionally, sterile, fixed oils can conveniently be used as solvents or suspending media. For this purpose, any sterile, fixed oil, including synthetic mono- or diglycerides, can be used. Additionally, fatty acids, such as oleic acid, can also be used in the preparation of injectable solutions.

[0207] The amount of active ingredient that may be combined with a carrier material to produce a single dosage form will vary depending on the host treated and the particular mode of administration. For example, a sustained-release formulation intended for oral administration to humans may contain from about 1 to about 1000 mg of active ingredient, compounded with an appropriate and convenient amount of carrier material, which may vary from about 5 to about 95% (weight:weight) of the total composition. Pharmaceutical compositions can be prepared to provide easily measurable amounts for administration. For example, an aqueous solution intended for intravenous infusion may contain from about 3 to about 500 μg of active ingredient per milliliter of solution, so that infusion of a suitable volume can occur at a rate of about 30 mL / hour.

[0208] Formulations suitable for topical administration to the eye also include eye drops, in which the active ingredient is dissolved or suspended in a suitable carrier, especially an aqueous solvent for the active ingredient. The active ingredient may be present in such formulations in a concentration of about 0.5 to about 20%, e.g., about 0.5 to about 10%, e.g., about 1.5% w / w.

[0209] Formulations suitable for topical administration in the mouth include lozenges comprising the active ingredient in a flavored base such as sucrose and acacia or tragacanth; pastilles comprising the active ingredient in an inert base such as gelatin and glycerin, or sucrose and acacia; and mouthwashes comprising the active ingredient in a suitable liquid carrier.

[0210] Formulations for rectal administration may be presented as a suppository with a suitable base comprising, for example, cocoa butter or a salicylate.

[0211] Formulations suitable for pulmonary or nasal administration have particle sizes ranging from about 0.1 to about 500 micrometers, e.g., about 0.5, about 1, about 30, or about 35 micrometers, and are administered by rapid inhalation through the nasal passages or by inhalation through the mouth to reach the alveolar sacs. Suitable formulations include aqueous or oily solutions of the active ingredient. Formulations suitable for aerosol or dry powder administration can be prepared according to conventional methods and can be delivered with other therapeutic agents, such as compounds previously used in the treatment of cancer, as described below.

[0212] In some embodiments, the inhalable composition comprises a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof. In some embodiments, the inhalable composition is suitable for treating cancer. In some embodiments, the pharmaceutically acceptable salt is an inorganic acid salt, including hydrochloride, hydrobromide, sulfate, or phosphate. For example, such salts may be less likely to cause pulmonary inflammation compared to other salts. In some embodiments, the inhalable composition is delivered to the endobronchial space in an aerosol comprising particles having a mass median aerodynamic diameter (MMAD) of about 1 to about 5 μm. In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8) is formulated for aerosol delivery using a nebulizer, a pressurized metered dose inhaler (pMDI), or a dry powder inhaler (DPI).

[0213] Non-limiting examples of nebulizers include atomization, jet, ultrasonic, pressurized, vibrating porous plate, or equivalent nebulizers, including those that utilize adaptive aerosol delivery technology (Denyer, J. Aerosol medicine Pulmonary Drug Delivery 2010, 23 Supp 1, S1-S10). Jet nebulizers utilize air pressure to break up liquid solutions into aerosol droplets. Ultrasonic nebulizers work by using piezoelectric crystals to shear liquids into small aerosol droplets. Pressurized nebulization systems force solutions through small pores under pressure to produce aerosol droplets. Vibrating porous plate devices use rapid vibrations to shear a liquid stream into the appropriate droplet size.

[0214] In some embodiments, the formulation for nebulization is delivered to the endobronchial space as an aerosol comprising primarily particles having an MMAD of about 1 μm to about 5 μm using a nebulizer capable of aerosolizing a formulation of a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8) into particles of the required MMAD. For optimal therapeutic effectiveness and to avoid upper respiratory tract and systemic side effects, the majority of the aerosolized particles should not have an MMAD greater than about 5 μm. If the aerosol contains many particles with an MMAD greater than about 5 μm, the particles will be deposited in the upper respiratory tract, reducing the amount of drug delivered to sites of inflammation and bronchoconstriction in the lower respiratory tract. If the MMAD of the aerosol is smaller than about 1 μm, the particles may remain suspended in the inhaled air and may then be exhaled.

[0215] When formulated and delivered in accordance with the methods herein, the nebulized aerosol formulation delivers a therapeutically effective dose of a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8) to a therapeutic target, such as a site of cancer. The amount of drug administered can be adjusted to reflect the efficiency of delivery of a therapeutically effective dose of a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8). In some embodiments, the combination of an aqueous aerosol formulation with a spray, jet, pressurized, vibrating porous plate, or ultrasonic nebulizer allows delivery of about 20 to about 90%, e.g., 70%, of an administered dose of a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8) to the respiratory tract, depending on the nebulizer. In some embodiments, about 30 to about 50% of the active compound is delivered. For example, about 70 to about 90% of the active compound may be delivered.

[0216] In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is delivered as a dry inhalable powder. The compound is administered intrabronchially as a dry powder formulation, and a dry powder inhaler or metered dose inhaler is used to effectively deliver fine particles of the compound to the endobronchial space. For delivery by DPI, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8) is processed by milling, spray drying, critical fluid processing, or precipitation from solution to produce particles of primarily about 1 μm to about 5 μm MMAD. Media milling, jet milling, and spray drying equipment and procedures capable of producing particle sizes of about 1 μm to about 5 μm MMAD are well known in the art. In some embodiments, an excipient is added to a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8) before processing into particles of the desired size. In some embodiments, an excipient is blended with the particles of the desired size to aid in the dispersion of the drug particles, for example, by using lactose as an excipient.

[0217] Particle size measurements are performed using equipment well known in the art, such as a multistage Andersen cascade impactor or other suitable methods such as those specifically cited in U.S. Pharmacopeia Chapter 601, which are devices that characterize aerosols in metered dose inhalers and dry powder inhalers.

[0218] In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8) can be delivered as a dry powder using a device such as a dry powder inhaler or other dry powder dispersion apparatus. Non-limiting examples of dry powder inhalers and devices include those disclosed in U.S. Patent Nos. 5,458,135, 5,740,794, 5,775,320, 5,785,049, 3,906,950, 4,013,075, 4,069,819, 4,995,385, 5,522,385, 4,668,218, 4,667,668, 4,805,811, and 5,388,572. There are two primary designs of dry powder inhalers. The first design is a metered device in which a reservoir for the drug is located within the device and the patient adds a dose of drug to the inhalation chamber. The second design is a factory-metered device, in which individual doses are manufactured in separate containers. Both systems rely on the compounding of drug into small particles of approximately 1 μm to approximately 5 μm MMAD, often co-compounded with larger excipient particles such as, but not limited to, lactose. Drug powder is placed into the inhalation chamber (either by metering with the device or by dividing a factory-metered dose), and the patient's inspiratory airflow accelerates the powder from the device into the oral cavity. The non-laminar flow characteristics of the powder path break up excipient-drug agglomerates, causing large excipient particle clumps to collide with them at the back of the throat, while smaller drug particles are deposited deep in the lungs.In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is delivered as a dry powder using any of the types of dry powder inhalers described herein, and the MMAD of the dry powder, excluding all excipients, is primarily in the range of about 1 μm to about 5 μm.

[0219] In some embodiments, the compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8) is delivered as a dry powder using a metered dose inhaler. Non-limiting examples of metered dose inhalers and devices include those disclosed in U.S. Patent Nos. 5,261,538, 5,544,647, 5,622,163, 4,955,371, 3,565,070, 3,361,306, and 6,116,234. In some embodiments, a compound of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8), or a pharmaceutically acceptable salt thereof, is delivered as a dry powder using a metered dose inhaler, and the MMAD of the dry powder, excluding all excipients, is primarily in the range of about 1 to about 5 μm.

[0220] Formulations suitable for vaginal administration may be presented as pessaries, tampons, creams, gels, pastes, foams, or spray formulations containing, in addition to the active ingredient, such suitable carriers as are known in the art.

[0221] Formulations suitable for parenteral administration include aqueous and non-aqueous sterile injection solutions which may contain antioxidants, buffers, bacteriostats, and solutes which render the formulation isotonic with the blood of the intended recipient, and aqueous and non-aqueous sterile suspensions which may include suspending agents and thickening agents.

[0222] The formulations may be presented in single-dose or multi-dose containers, for example, sealed ampoules and vials, and may be stored in a freeze-dried (lyophilized) condition requiring only the addition of a sterile liquid carrier, for example, water for injections, immediately prior to use. Extemporaneous injection solutions and suspensions are prepared from sterile powders, granules, and tablets of the kind described above. Unit-dose formulations include those containing a daily dose or unit daily sub-dose, as herein above recited, or an appropriate fraction thereof, of the active ingredient.

[0223] It will be understood that in addition to the ingredients specifically mentioned above, the formulations may include other agents conventional in the art having regard to the type of formulation in question, e.g., those suitable for oral administration may include flavoring agents.

[0224] There is further provided a veterinary composition comprising at least one active ingredient as above defined together with a veterinary carrier thereof.

[0225] A veterinary carrier is a substance useful for the purpose of administering the composition and may be a solid, liquid, or gaseous substance that is inert or acceptable in the veterinary art and compatible with the active ingredient. These veterinary compositions may be administered orally, parenterally, or by any other desired route.

[0226] The compounds herein are used to provide controlled release pharmaceutical formulations ("controlled release formulations") containing one or more active ingredients, wherein the release of the active ingredient is controlled and modulated to allow less frequent administration or to improve the pharmacokinetic or toxicity profile of a given active ingredient.

[0227] The effective dose of active ingredient depends at least on the condition being treated, toxicity, delivery method, and the nature of the pharmaceutical formulation, and can be determined by a clinician using conventional dose-escalation studies. It can be expected to be about 0.0001 to about 100 mg / kg body weight per day, typically about 0.01 to about 10 mg / kg body weight per day, more typically about 0.01 to about 5 mg / kg body weight per day, and most typically about 0.05 to about 0.5 mg / kg body weight per day. For example, the daily dose candidate for an adult weighing about 70 kg can range from about 1 mg to about 1000 mg, e.g., about 5 mg to about 500 mg, and can take the form of a single dose or multiple doses. IV. Route of Administration

[0228] One or more compounds of Formula (I), (I-1), (Ia), (Ia-1), (Ib), (Ic), (IIa), (IIa-1), (IIc), (IIc-1), (IIc-2), (IIc-2), (IIc-3), (IIc-4), (IIc-5), (IIc-6), (IIc-7), or (IIc-8) (referred to herein as the active ingredient) are administered by any route appropriate to the condition to be treated. Suitable routes include oral, rectal, nasal, pulmonary, topical (including buccal and sublingual), vaginal, and parenteral (subcutaneous, intramuscular, intravenous, intradermal, intrathecal, and epidural). It will be understood that the route may vary depending, for example, on the condition of the recipient. An advantage of the compounds herein is that they are orally available and can be administered orally.

[0229] The compounds of the present disclosure (also referred to herein as active ingredients) can be administered by any route appropriate to the condition to be treated. Suitable routes include oral, rectal, nasal, topical (including buccal and sublingual), transdermal, vaginal, and parenteral (subcutaneous, intramuscular, intravenous, intradermal, intrathecal, and epidural), etc. It will be understood that the route may vary depending, for example, on the condition of the recipient. An advantage of certain compounds disclosed herein is that they are orally available and can be administered orally.

[0230] The compounds of the present disclosure may be administered to an individual according to an effective dosing regimen for any desired period or duration, such as at least about 1 month, at least about 2 months, at least about 3 months, at least about 6 months, or at least about 12 months or longer, hi some embodiments, the compounds are administered on a daily or intermittent schedule for the duration of the individual's life.

[0231] The dosage or frequency of administration of a compound of the present disclosure may be adjusted over the course of treatment, based on the judgment of the administering physician.

[0232] The compound can be administered to an individual (e.g., a human) in an effective amount. In some embodiments, the compound is administered once daily.

[0233] Compound I can be administered by any useful route and means, such as oral or parenteral (e.g., intravenous) administration. A therapeutically effective amount of the compound can be about 0.00001 mg / kg body weight per day to about 10 mg / kg body weight per day, for example, about 0.0001 mg / kg body weight per day to about 10 mg / kg body weight per day, or for example, about 0.001 mg / kg body weight per day to about 1 mg / kg body weight per day, or for example, about 0.01 mg / kg body weight per day to about 1 mg / kg body weight per day, or for example, about 0.05 mg / kg body weight per day to about 0.5 mg / kg body weight per day, or for example, about 0.3 mg to about 30 mg per day, or about 0.3 mg to about 300 mg per day.

[0234] The compounds of the present disclosure can be combined with one or more additional therapeutic agents at any dosage of the compound of the present disclosure (e.g., about 1 mg to about 1000 mg of compound). Therapeutically effective amounts can include about 1 mg to about 1000 mg per dose, such as about 50 mg to about 500 mg per dose, or about 100 mg to about 400 mg per dose, or about 150 mg to about 350 mg per dose, or about 200 mg to about 300 mg per dose. Other therapeutically effective amounts of the compounds of the present disclosure are about 100, about 125, about 150, about 175, about 200, about 225, about 250, about 275, about 300, about 325, about 350, about 375, about 400, about 425, about 450, about 475, or about 500 mg per dose. Other therapeutically effective amounts of the compounds of the present disclosure are about 100 mg per dose, or about 125, about 150, about 175, about 200, about 225, about 250, about 275, about 300, about 325, about 350, about 375, about 400, about 425, about 450, or about 500 mg per dose. A single dose can be administered hourly, daily, or weekly. For example, a single dose can be administered once every about 1, about 2, about 3, about 4, about 6, about 8, about 12, about 16 hours, or about every 24 hours. A single dose can also be administered once every about 1, about 2, about 3, about 4, about 5, about 6 days, or about every 7 days. A single dose can also be administered once every about 1, about 2, about 3 weeks, or about every 4 weeks. In some embodiments, a single dose can be administered approximately once every week. Single doses can also be administered approximately once every month.

[0235] Other therapeutically effective amounts of the compounds of the present disclosure are about 20, about 25, about 30, about 35, about 40, about 45, about 50, about 55, about 60, about 65, about 70, about 75, about 80, about 85, about 90, about 95, or about 100 mg per dose.

[0236] The frequency of administration of the compounds of the present disclosure is determined by the needs of each individual patient and can be, for example, once per day, twice per day, or more than once per day. Administration of the compounds continues as long as necessary to treat the disease or condition. For example, the compounds can be administered to a human with cancer for a period of about 20 to about 180 days, or for example, for a period of about 20 to about 90 days, or for example, for a period of about 30 to about 60 days.

[0237] Administration can be intermittent, with the patient receiving a daily dose of a compound of the present disclosure for a period of several days or more, followed by a period of several days or more where the patient does not receive a daily dose of the compound. For example, the patient can receive administration of the compound every other day or three times per week. As a further example, the patient can receive administration of the compound daily for a period of about 1 to about 14 days, followed by a period of about 7 to about 21 days where the patient does not receive Compound I, followed by a subsequent period (e.g., about 1 to about 14 days) where the patient again receives a daily dose of the compound. The alternating periods of administration of the compound followed by non-administration of the compound can be repeated as clinically needed to treat the patient.

[0238] In some embodiments, a pharmaceutical composition is provided that includes a compound of the present disclosure or a pharmaceutically acceptable salt thereof in combination with one or more (e.g., 1, 2, 3, 4, 1 or 2, 1 to 3, or 1 to 4) additional therapeutic agents, and a pharmaceutically acceptable excipient.

[0239] In some embodiments, kits are provided that include a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, in combination with one or more (e.g., 1, 2, 3, 4, 1 or 2, 1 to 3, or 1 to 4) additional therapeutic agents.

[0240] In some embodiments, a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, is combined with one, two, three, four, or more additional therapeutic agents. In some embodiments, a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, is combined with two additional therapeutic agents. In some embodiments, a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, is combined with three additional therapeutic agents. In some embodiments, a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, is combined with four additional therapeutic agents. The one, two, three, four, or more additional therapeutic agents may be different therapeutic agents selected from the same class of therapeutic agents and / or may be selected from different classes of therapeutic agents.

[0241] In some embodiments, when a compound of the present disclosure is combined with one or more additional therapeutic agents described herein, the components of the composition are administered simultaneously or as a sequential regimen. When administered sequentially, the combination may be administered in two or more administrations.

[0242] In some embodiments, compounds of the present disclosure are combined with one or more additional therapeutic agents in a unit dosage form for simultaneous administration to a patient, for example, as a solid dosage form for oral administration.

[0243] In some embodiments, a compound of the present disclosure is co-administered with one or more additional therapeutic agents.

[0244] In order to prolong the effect of a compound of the present disclosure, it is often desirable to slow the absorption of the compound from subcutaneous or intramuscular injection. This can be accomplished by using a liquid suspension of crystalline or amorphous material with poor water solubility. The rate of absorption of the compound then depends on its dissolution rate, which in turn may depend on crystal size and crystalline form. Alternatively, delayed absorption of a parenterally administered compound form can be achieved by dissolving or suspending the compound in an oil vehicle. Injectable depot forms are made by forming microencapsule matrices of the compound in biodegradable polymers such as polylactide-polyglycolide. The compound release rate can be controlled depending on the compound to polymer ratio and the nature of the particular polymer used. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides). Depot injectable formulations can also be prepared by entrapping the compound in liposomal or microemulsion formulations that are compatible with body tissues. V. Combination Therapy

[0245] The compounds of the present disclosure and compositions provided herein may also be used in combination with other active therapeutic agents, which may, where appropriate, be anti-cancer or anti-viral agents, such as anti-HIV or anti-hepatitis B virus agents. A. Combination Therapy 1. Cancer

[0246] In some embodiments, the anti-CD47 agents or anti-SIRPα agents described herein can be administered with one or more additional therapeutic agents, such as an inhibitory immune checkpoint blocker or inhibitor, a stimulatory immune checkpoint stimulator, agonist, or activator, a chemotherapeutic agent, an anti-cancer agent, a radiotherapeutic agent, an anti-neoplastic agent, an anti-proliferative agent, an anti-angiogenic agent, an anti-inflammatory agent, an immunotherapeutic agent, a therapeutic antigen binding molecule (mono- and multispecific antibodies and fragments thereof in any format (e.g., DART®, Duobodies®, BiTEs®, BiKEs, TriKEs, XmAbs®, TandAbs®, scFvs, Fabs, Fab derivatives), bispecific antibodies, non-immunoglobulin antibody mimetics (e.g., adnectins, affibody molecules, affilins, affimers, affitins, alphabodies, anticalins, peptide aptamers, armadillo repeat proteins, etc.), or a combination thereof. and nanoCLAMPs), antibody-drug conjugates (ADCs), antibody-peptide conjugates), oncolytic viruses, gene modifiers or editors, cells comprising a chimeric antigen receptor (CAR) (e.g., T-cell immunotherapeutics, NK cell immunotherapeutics, or macrophage immunotherapeutics, cells comprising an engineered T cell receptor (TCR-T), or any combination thereof. Exemplary Targets

[0247] In some embodiments, the one or more additional therapeutic agents include, but are not limited to, an inhibitor, agonist, antagonist, ligand, modulator, stimulator, blocker, activator, or suppressor of interest (e.g., a polypeptide or polynucleotide), including, but not limited to, an Abelson murine leukemia viral oncogene homolog 1 gene (ABL, such as ABL1), acetyl-CoA carboxylase (ACC1 / 2), activated CDC kinase (ACK, such as ACK1), adenosine deaminase, adenosine receptors (ABR, A2aR, A3aR, etc.), adenylate cyclase, ADP-ribosyl cyclase-1, adrenocorticosteroid receptor (ACTH), aerolysin, AKT1 gene, Alk-5 protein kinase, alkaline phosphatase, α1-adrenergic receptor, α2-adrenergic receptor, α-ketoglutarate dehydrogenase (KGDH), aminopeptidase N, AMP-activated protein kinase, anaplastic lymphoma kinase (ALK, such as ALK1), androgen receptor, angiopoietin (ligand-1, ligand-2, etc.), angiotensinogen (AGT) gene, Murine thymoma viral oncogene homolog 1 (AKT) protein kinase (AKT1, AKT2, AKT3, etc.), apolipoprotein AI (APOA1) gene, apoptosis-inducing factor, apoptosis protein (1, 2, etc.), apoptosis signal-regulating kinase (ASK, such as ASK1), arginase (I), arginine deiminase, aromatase, asteroid homolog 1 (ASTE1) gene, ataxia-telangiectasia and Rad3-related (ATR) serine / threonine protein kinase, Aurora protein kinase (1, 2, etc.) , Axl tyrosine kinase receptor, 4-1BB ligand (CD137L), baculovirus IAP repeat containing 5 (BIRC5) gene, basigin, B cell lymphoma 2 (BCL2) gene, Bcl2 binding component 3, Bcl2 protein, BCL2L11 gene, BCR (breakpoint cluster region) protein and gene, beta-adrenergic receptor, beta-catenin, B lymphocyte antigen CD19, B lymphocyte antigen CD20, B lymphocyte cell adhesion molecule, B lymphocyte stimulatory factor ligand, bone morphogenetic protein-10 ligand, bone morphogenetic protein-9 ligand modifier,Brachyury protein, bradykinin receptor, B-Raf proto-oncogene (BRAF), Brc-Abl tyrosine kinase, bromodomain and ectodomain (BET) bromodomain-containing proteins (BRD2, BRD3, BRD4), Bruton's tyrosine kinase (BTK), calmodulin, calmodulin-dependent protein kinase (CaMK such as CAMKII), cancer-testis antigen 2, cancer-testis antigen NY-ESO-1, cancer / testis antigen 1B (CTAG1) gene, cannabinoid receptors (CB1, CB2, etc.) ), carbonic anhydrase, casein kinase (CKs such as CKI and CKII), caspases (caspase-3, caspase-7, caspase-9, etc.), caspase-8 apoptosis-associated cysteine ​​peptidase CASP8-FADD-like regulator, caspase recruitment domain protein-15, cathepsin G, CCR5 gene, CDK-activating kinase (CAK), checkpoint kinases (CHK1, CHK2, etc.), chemokine (CC motif) receptors (CCR2, CCR4, CCR5, CCR8, etc.), chemokines (CX C motif) receptors (such as CXCR1, CXCR2, CXCR3, and CXCR4), chemokine CC21 ligand, cholecystokinin CCK2 receptor, human chorionic gonadotropin, c-Kit (tyrosine-protein kinase Kit or CD117), CISH (cytokine-inducible SH2-containing protein), claudins (such as 6 and 18), CD4, CD27, CD29, CD30, CD33, CD37, CD40, CD40 ligand receptor, CD40 ligand, CD40LG gene, CD44, CD45, CD 47, cluster of differentiation antigens (CDs) such as CD49b, CD51, CD52, CD55, CD58, CD66e (CEACAM6), CD70 gene, CD74, CD79, CD79b, CD79B gene, CD80, CD95, CD99, CD117, CD122, CDw123, CD134, CDw137, CD158a, CD158b1, CD158b2, CD223, and CD276 antigens; clusterin (CLU) gene, clusterin, c-Met (hepatocyte growth factor receptor, HGFR), complement C3, connective tissue growth factor, and COP9 signalosome subunit 5.CSF-1 (colony-stimulating factor 1 receptor), CSF2 gene, CTLA-4 (cytotoxic T-lymphocyte protein 4) receptor, C-type lectin domain protein 9A (CLEC9 A), cyclin D1, cyclin G1, cyclin-dependent kinase (CDK, e.g., COX1, COX2), CYP2B1 gene, cysteine ​​palmitoyltransferase porcupine, cytochrome P450 11B2, cytochrome P450 17, cytochrome P450 17A1, cytochrome P450 2D6, cytochrome P450 3A4, cytochrome P450 reductase, cytokine signaling 1, cytokine signaling 3, cytosolic isocitrate dehydrogenase, cytosine deaminase, cytosine DNA methyltransferase, cytotoxic T lymphocyte protein 4, DDR2 gene, DEAD-box helicase 6 (DDX6), death receptor 5 (DR5, TRAILR2), death receptor 4 (DR4, TRAILR1), delta-like protein ligands (e.g., 3, 4), deoxyribonucleases, deubiquitinating enzymes (DUBs), Dickkopf-1 ligand, dihydrofolate reductase (DHFR), dihydropyrimidine dehydrogenase, dipeptidyl peptidase IV, discoidin domain receptor receptor, DDR (e.g., DDR1), diacylglycerol kinase zeta (DGKZ), DNA-binding proteins (e.g., HU-β), DNA-dependent protein kinase, DNA gyrase, DNA methyltransferase, DNA polymerase (e.g., α), DNA primase, dUTP pyrophosphatase, L-dopachrome tautomerase, E3 ubiquitin-protein ligase (e.g., RNF128, CBL-B), echinoderm microtubule-like protein 4, EGFR tyrosine kinase receptor, elastase, elongation factor 1α2, elongation factor 2, endoglin, endonuclease,Endoplasmic reticulum aminopeptidase (ERAP, e.g., ERAP1, ERAP2, etc.), endoplasmin, endosialin, endostatin, endothelin (ET-A, ET-B, etc.), enhancer of zeste homolog 2 (EZH2), ephrin (EPH) tyrosine kinase (Epha3, Ephb4, etc.), ephrin B2 ligand, epidermal growth factor, epidermal growth factor receptors (EGFR), epidermal growth factor receptor (EGFR) gene, epigen, epithelial cell adhesion molecule molecule (EpCAM), Erb-b2 (v-erb-b2 avian erythroblastic leukemia virus oncogene homolog 2), tyrosine kinase receptor, Erb-b3 tyrosine kinase receptor, Erb-b4 tyrosine kinase receptor, E-selectin, estradiol 17β-dehydrogenase, estrogen receptor (α, β, etc.), estrogen-related receptor, eukaryotic translation initiation factor 5A (EIF5A) gene, exportin 1, extracellular signal-related kinase (1, 2, etc.), extracellular signal-regulated kinase (ERK), hypoxia-inducible factor prolyl hydroxylase (HIF-PH or EGLN), factor (Xa, VIIa, etc.), farnesoid x receptor (FXR), Fas ligand, fatty acid synthase synthase (FASN), ferritin, FGF-2 ligand, FGF-5 ligand, fibroblast growth factor (FGF, e.g., FGF1, FGF2, FGF4, etc.), fibronectin, focal adhesion kinase (FAK, e.g., FAK2, etc.), folate hydrolase prostate-specific membrane antigen 1 (FOLH1), folate receptor (α, etc.), folate, folate transporter 1, FYN tyrosine kinase,Base-pairing amino acid cleaving enzyme (FURIN), β-glucuronidase, galactosyltransferase, galectin-3, ganglioside GD2, glucocorticoid, glucocorticoid-inducible TNFR-related protein (GITR) receptor, glutamate carboxypeptidase II, glutaminase, glutathione S-transferase P, glycogen synthase (GSK, e.g., 3-β), glypican 3 (GPC3), gonadotropin-releasing hormone (GNRH), granulocyte macrophage colony stimulating factor (GM-CSF) receptor, granulocyte-colony stimulating factor (GCSF) ligand, growth factor receptor-bound protein 2 (GFAP), and mitochondrial endothelial growth factor receptor-bound protein 2 (MGF). 2, GRB2), Grp78 (78 kDa glucose-regulated protein), calcium-binding protein, molecular chaperone groEL2 gene, heme oxygenase 1 (HO1), heme oxygenase 2 (HO2), heat shock proteins (27, 70, 90α, β, etc.), heat shock protein genes, heat-stable enterotoxin receptor, hedgehog protein, heparanase, hepatocyte growth factor, HERV-HLTR-associated protein 2, hexose kinase, histamine H2 receptor, histone methyltransferase (DOT1L), histone deacetylase (HDAC, e.g., 1, 2, 3, 6, 10, 11, etc.), histone H1, histone H3, HLA class I antigen (A-2α), HLA class II antigen, HLA class I antigen alpha G (HLA class I antigen alpha G, HLA-G), non-classical HLA, homeobox protein NANOG, HSPB1 gene, human leukocyte antigen (HLA), human papillomavirus (E6, E7, etc.) proteins, hyaluronic acid, hyaluronidase,Hypoxia inducible factor-1 alpha (HIF1α), imprinted maternally expressed transcript (H19) gene, mitogen-activated protein kinase 1 (MAP4K1), tyrosine protein kinase HCK, I-kappa-B kinase (IKK, e.g., IKKbe), IL-1α, IL-1β, IL-12, IL-12 gene, IL-15, IL-17, IL-2 gene, IL-2 receptor α subunit, IL-2, IL-3 receptor, IL-4, IL-6, IL-7, IL-8, immunoglobulins (e.g., G, G1, G2, K, M), immunoglobulin Fc receptor, immunoglobulin gamma Fc receptor (e.g., I, III, IIIA), indoleamine 2,3-dioxygenase 2,3-dioxygenase, IDO (e.g., IDO1, IDO2, etc.), indoleamine pyrrole 2,3-dioxygenase 1 inhibitors, insulin receptor, , insulin-like growth factors (e.g., 1, 2), integrin α-4 / β-1, integrin α-4 / β-7, integrin α-5 / β-1, integrin α-V / β-3, integrin α-V / β-5, integrin α-V / β-6, intercellular adhesion molecule 1 (ICAM-1), interferons (e.g., α, α2, β, γ), interferon-inducible protein absent in melanoma 2 (AIM2), type I interferon receptor, interleukin-1 ligand, interleukin-13 receptor α2, interleukin-2 ligand, interleukin-1 receptor-associated kinase 4 (IRAK4), interleukin-2, interleukin-29 ligand, interleukin-35 (IL-35), isocitrate dehydrogenase (e.g., IDH1, IDH2), Janus kinase (Janus kinase) kinase, JAK (e.g., JAK1, JAK2), Jun N-terminal kinase, kallikrein-related peptidase 3 (KLK3) gene, killer cell Ig-like receptor, kinase insert domain receptor (KDR), kinesin-like protein KIF11, Kirsten rat sarcoma viral oncogene homolog (Kirsten rat sarcoma viral oncogene) homolog (KRAS) gene, kisspeptin (KiSS-1) receptor, KIT gene, v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) tyrosine kinase, lactoferrin, lanosterol-14 demethylase, LDL receptor-related protein-1, leukocyte immunoglobulin-like receptor subfamily B member 1 (ILT2), leukocyte immunoglobulin-like receptor subfamily B member 2 (ILT4), leukotriene A4 hydrolase, listeriolysin, L-selectin, luteinizing hormone receptor, lyase, lymphocyte activation gene 3 protein3, LAG-3), lymphocyte antigen 75, lymphocyte function antigen 3 receptor, lymphocyte-specific protein tyrosine kinase (LCK), lymphotactin, Lyn (Lck / Yes novel) tyrosine kinase, lysine demethylases (KDM1, KDM2, KDM4, KDM5, KDM6, A / B / C / D, etc.), lysophosphatidic acid-1 receptor, lysosomal-associated membrane protein family (LAMP) genes, lysyl oxidase homolog 2, lysyl oxidase protein (LOX), lipoxygenase (5-LOX), hematopoietic progenitor kinase 1 (HPK1), hepatocyte growth factor receptor (MET) gene, macrophage colony-stimulating factor (MCF) MCSF (macrophage migration inhibitory factor) ligand, macrophage migration inhibitory factor, MAGEC1 gene, MAGEC2 gene, major vault protein, MAPK-activated protein kinase (MK2, etc.), Mas-related G protein-coupled receptor, matrix metalloproteinase (MMP, e.g., MMP2, MMP9, etc.), MCL1 differentiation protein, Mdm2 p53-binding protein, Mdm4 protein, Melan-A (MART-1) melanoma antigen, melanocyte protein Pmel17, melanocyte-stimulating hormone ligand, melanoma antigen family A3 (MAGEA3) gene, melanoma-associated antigens (1, 2, 3, 6, etc.), copper membrane amine oxidase, mesothelin, MET tyrosine kinase, metabotropic glutamate receptor 1, metalloreductase STEAP1 (six-transmembrane epithelial antigen of the prostate 1), metastin, methionine aminopeptidase-2, methyltransferase, mitochondrial 3-ketoacyl-CoA thiolase, mitogen-activated protein kinase (MAPK), mitogen-activated protein kinase (MAPK),kinase, MEK (e.g., MEK1, MEK2), mTOR (mechanistic target of rapamycin (serine / threonine kinase)), mTOR complex (e.g., 1, 2), mucins (e.g., 1, 5A, 16), mut T homolog (MTH, e.g., MTH1), Myc proto-oncogene protein, myeloid cell leukemia 1 (MCL1) gene, myristoylated alanine-rich protein kinase C substrate (MARCKS) protein, NAD ADP-ribosyltransferase, natriuretic peptide receptor C, neural cell adhesion molecule 1, neurokinin 1 (NK1) receptor, neurokinin receptor, neuropilin 2, NFκB-activating protein, NIMA-related kinase 9 9, NEK9), nitric oxide synthase, NK cell receptor, NK3 receptor, NKG2AB activating NK receptor, NLRP3 (NACHT LRR PYD domain protein 3) regulator, noradrenaline transporter, Notch (Notch-2 receptor, Notch-3 receptor, Notch-4 receptor, etc.), nuclear erythroid 2-related factor 2, nuclear factor (Nuclear Factor Factor (NF)κB, nucleolin, nucleophosmin, nucleophosmin anaplastid lymphoma kinase (NPM-ALK), 2-oxoglutarate dehydrogenase, 2,5-oligoadenylate synthetase, O-methylguanine DNA methyltransferase, opioid receptors (δ, etc.), ornithine decarboxylase, orotate phosphoribosyltransferase, orphan nuclear hormone receptor NR4A1, osteocalcin, osteoclast differentiation factor, osteopontin, OX-40 (tumor necrosis factor receptor superfamily member 4 TNFRSF4, or CD134) receptor, P3 protein, p38 kinase, p38 MAP kinase, p53 tumor suppressor protein, parathyroid hormone ligand, peroxisome proliferator-activated receptorreceptor, PPAR (e.g., α, β, γ), P-glycoprotein (e.g., 1), phosphatase and tensin (PTEN) homolog, phosphatidylinositol 3-kinase (PI3K), phosphoinositide-3 kinase (PI3K, e.g., α, β, γ), phosphorylase kinase (PK), PKN3 gene, placenta growth factor, platelet-derived growth factor (PDGF, e.g., α, β), platelet-derived growth factor (PDGF, α, β), pleiotropic drug resistance transporter, Plexin B1, PLK1 gene, polo-like kinase (PLK), polo-like kinase 1, poly(ADP-ribose) polymerase polymerase, PARP (e.g., PARP1, 2, and 3), preferentially expressed antigen in melanoma (PRAME) gene, prenyl-binding protein (PrPB), transcriptional promoter PML, progesterone receptor, programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1) inhibitor, prosaposin (PSAP) gene, prostanoid receptor (EP4), prostaglandin E2 synthase, prostate-specific antigen, prostaglandin acid phosphatase, proteasome, protein E7, protein farnesyltransferase, protein kinasekinases, PKs (e.g., A, B, C), protein tyrosine kinases, protein tyrosine phosphatase β, proto-oncogene serine / threonine-protein kinases (PIMs such as PIM-1, PIM-2, and PIM-3), P-selectin, purine nucleoside phosphorylase, purinergic receptor P2X ligand-gated ion channel 7 (P2X7), pyruvate dehydrogenase (PDH), pyruvate dehydrogenase kinase, pyruvate kinase kinase, PYK), 5α-reductase, Raf protein kinase (e.g., 1, B), RAF1 gene, Ras gene, Ras GTPase, RET gene, Ret tyrosine kinase receptor, retinoblastoma-associated protein, retinoic acid receptor (e.g., γ), retinoid X receptor, Rheb (Ras homolog abundant in brain) GTPase, Rho (Ras homolog)-associated protein kinase 2, ribonuclease, ribonucleotide reductase (e.g., M2 subunit), ribosomal protein S6 kinase, RNA polymerase (e.g., I, II), Ron (Recepteur d'Origine Nantais) tyrosine kinase, ROS1 (ROS proto-oncogene 1, receptor tyrosine kinase) gene, Ros1 tyrosine kinase, Runt-related transcription factor 3, γ-secretase, S100 calcium-binding protein A9, sarcoplasmic reticulum calcium ATPase, second mitochondrial-derived caspase activator (Second Mitochondria-derived activator of caspases (SMAC) protein, secreted frizzled-associated protein-2, secreted phospholipase A2, semaphorin-4D, serine proteases, serine / threonine kinases (STK), serine / threonine-protein kinases (TBK, e.g., TBK1), signal transduction and transcription (STAT, e.g., STAT-1, STAT-3, STAT-5), signaling lymphocyte activation molecules (SIGs), andlymphocytic activation molecule (SLAM) family member 7, six-transmembrane epithelial antigen of the prostate (STEAP) gene, SL cytokine ligand, smoothened membrane oxidizer (SMO) receptor, sodium iodide symporter, sodium phosphate symporter 2B, somatostatin receptors (1, 2, 3, 4, 5, etc.), sonic hedgehog protein, Son of sevenless (SOS), specific protein 1 (Sp1) transcription factor, sphingomyelin synthase, sphingosine kinase (1, 2, etc.), sphingosine-1-phosphate receptor-1, spleen tyrosine kinase (SYK), SRC gene, Src tyrosine kinase, stabilin-1 (STAB1), STAT3 gene, steroid sulfatase, Stimulator of interferon (SIFN) gene genes (STING) receptor, stimulator of interferon genes protein, stromal cell-derived factor 1 ligand, SUMO (small ubiquitin-like modifier), superoxide dismutase, suppressor of cytokine signaling modulators (SOCS), survivin protein, synapsin 3, syndecan-1, synuclein α, T cell surface glycoprotein CD28, tank-binding kinase (TBK), TATA box-binding protein-associated factor RNA polymerase I subunit B (TAF1B) gene, T cell CD3 glycoprotein ζ chain, T cell differentiation antigen CD6, T cell immunoglobulin and mucin domain-containing-3 (TIM-3), T cell surface glycoprotein CD8, Tec protein tyrosine kinase, Tek tyrosine kinase receptor, telomerase, telomerase reverse transcriptase (TERT) gene, tenascin, sleep thyme repair exonuclease Three prime repair exonuclease 1 (TREX1), Three prime repair exonuclease 2 (TREX2), thrombopoietin receptor, thymidine kinase, thymidine phosphorylase, thymidylate synthase, thymosin (e.g., α1), thyroid hormone receptor, thyrotropin receptor, tissue factor, TNF-related apoptosis-inducing ligand, TNFR1-associated death domain protein, TNF-related apoptosis-inducing ligand (TRAIL) receptor, TNFSF11 gene, TNFSF9 gene, Toll-like receptor (TLR, e.g., 1-13), topoisomerase (e.g., I, II, III), transcription factor, transferase, transferrin (TF), transforming growth factor alpha (TGFα), transforming growth factor beta (TGFβ), beta (TGFB) and its isoforms, TGF-β2 ligand, transforming growth factor (TGF-β) receptor kinase, transglutaminase, translocation-associated protein, transmembrane glycoprotein NMB, Trop-2 calcium signal transducer, trophoblast glycoprotein (TPBG) gene, trophoblast glycoprotein, tropomyosin receptor kinase (Trk) receptors (TrkA, TrkB, TrkC, etc.), tryptophan 2,3-dioxygenase (TDO), tryptophan 5-hydroxylase, tubulin, tumor necrosis factor (TNF, e.g., α, β), tumor necrosis factor 13C receptor, tumor progression locus 2 (TPL2), tumor protein 53 (TP53) gene, tumor suppressor candidate 22, TUSC2 gene, tumor-specific neoantigen, tyrosinase, tyrosine hydroxylase, tyrosine kinase (TK), tyrosine kinase receptor, tyrosine kinase with immunoglobulin-like and EGF-like domains (TIE) receptor, tyrosine protein kinase ABL1 inhibitor, ubiquitin, ubiquitin carboxylase hydrolase isoenzyme L5, ubiquitin thioesterase-14, ubiquitin-conjugating enzyme E2I (UBE2I, UBC9), ubiquitin-specific-processing protease 7 (USP7), urease, urokinase plasminogen activator, uteroglobin, vanilloid VR1, vascular cell adhesion protein 1, vascular endothelial growth factor receptor (VEGFR), V-domain Ig suppressor of T-cell activation activation (VISTA), VEGF-1 receptor, VEGF-2 receptor, VEGF-3 receptor, VEGF-A, VEGF-B, vimentin, vitamin D3 receptor, proto-oncogene tyrosine-protein kinase, Mer (Tyrosine Kinase Receptor Modulator), YAP (Yes-associated protein modulator), Wee-1 protein kinase, Werner Syndrome RecQ-Like Helicase (WRN), Wilms Tumor Antigen 1, Wilms Tumor Protein, WW Domain-Containing Transcriptional Regulatory Protein 1 (TAZ), X-linked Inhibitor of Apoptosis Protein, zinc finger protein transcription factor, or any combination thereof. Exemplary Mechanisms of Action

[0248] In some embodiments, the one or more additional therapeutic agents may be categorized by their mechanism of action, e.g., into the following groups:

[0249] antimetabolites / anticancer drugs such as the pyrimidine analogue floxuridine, capecitabine, cytarabine, CPX-351 (liposomal cytarabine, daunorubicin), and TAS-118;

[0250] Alpha 1-adrenergic receptor / alpha 2-adrenergic receptor antagonists such as phenoxybenzamine hydrochloride (injectable, pheochromocytoma);

[0251] androgen receptor antagonists such as nilutamide;

[0252] anti-cadherin antibodies such as HKT-288;

[0253] anti-leucine-rich repeat containing 15 (LRRC15) antibodies such as ABBV-085.ARGX-110;

[0254] angiotensin receptor blockers, nitric oxide donors;

[0255] antisense oligonucleotides such as AEG35156, IONIS-KRAS-2.5Rx, EZN-3042, RX-0201, IONIS-AR-2.5Rx, BP-100 (plexigeversen), and IONIS-STAT3-2.5Rx;

[0256] anti-angiopoietin (ANG)-2 antibodies, such as MEDI3617 and LY3127804;

[0257] anti-ANG-1 / ANG-2 antibodies such as AMG-780;

[0258] anti-CSF1R antibodies such as emactuzumab, LY3022855, AMG-820, and FPA-008 (caviralizumab);

[0259] anti-endoglin antibodies such as TRC105 (carotuximab);

[0260] anti-ERBB antibodies such as CDX-3379, HLX-02, and seribantumab;

[0261] anti-HER2 antibodies such as HERCEPTIN® (trastuzumab), trastuzumab biosimilars, margetuximab, MEDI4276, BAT-8001, pertuzumab (Perjeta), RG6264, ZW25 (a bispecific HER2-directed antibody targeting extracellular domains 2 and 4; Cancer Discov. 2019 Jan;9(1):8; PMID:30504239);

[0262] anti-HLA-DR antibodies such as IMMU-114;

[0263] anti-IL-3 antibodies such as JNJ-56022473;

[0264] Anti-TNF receptor superfamily member 18 (TNFRSF18, GITR; NCBI Gene ID: 8784) antibodies (such as MK-4166, MEDI1873, FPA-154, INCAGN-1876, TRX-518, BMS-986156, MK-1248, GWN-323); and those described, for example, in WO 2017 / 096179, WO 2017 / 096276, WO 2017 / 096189, and WO 2018 / 089628;

[0265] anti-EphA3 antibodies such as KB-004;

[0266] anti-CD37 antibodies such as otlertuzumab (TRU-016);

[0267] anti-FGFR-3 antibodies such as LY3076226, B-701;

[0268] anti-FGFR-2 antibodies such as GAL-F2;

[0269] anti-C5 antibodies such as ALXN-1210;

[0270] anti-EpCAM antibodies such as VB4-845;

[0271] anti-CEA antibodies such as RG-7813;

[0272] CD66C) antibodies such as BAY-1834942, NEO-201 (CEACAM5 / 6);

[0273] anti-GD2 antibodies such as APN-301;

[0274] anti-interleukin 17 (IL-17) antibodies such as CJM-112;

[0275] anti-interleukin-1 beta antibodies such as canakinumab (ACZ885) and VPM087;

[0276] anti-carbonic anhydrase 9 (CA9, CAIX) antibodies such as TX-250;

[0277] anti-CD38 antibodies such as isatuximab, MOR-202, and TAK-079;

[0278] anti-CD38-attenukines such as TAK573;

[0279] anti-mucin 1 (MUC1) antibodies such as gatipotuzumab and Mab-AR-20.5;

[0280] anti-CD33 antibodies such as IMGN-779;

[0281] anti-KMA antibodies such as MDX-1097;

[0282] anti-CD55 antibodies such as PAT-SC1;

[0283] anti-c-Met antibodies such as ABBV-399;

[0284] anti-PSMA antibodies such as ATL-101;

[0285] anti-CD100 antibodies such as VX-15;

[0286] anti-EPHA3 antibodies such as fivatuzumab;

[0287] anti-APRIL antibodies such as BION-1301;

[0288] anti-fibroblast activation protein (FAP) / IL-2R antibodies such as RG7461;

[0289] anti-fibroblast activation protein (FAP) / TRAIL-R2 antibodies such as RG7386;

[0290] anti-fucosyl-GM1 antibodies such as BMS-986012;

[0291] anti-IL-8 (interleukin-8) antibodies such as HuMax-Inflam;

[0292] anti-myostatin inhibitors such as landlozumab;

[0293] anti-delta-like protein ligand 3 (DDL3) antibodies, such as rovalpituzumabtesirin;

[0294] anti-DLL4 (delta-like ligand 4) antibodies such as demcizumab;

[0295] anti-clusterin antibodies such as AB-16B5;

[0296] anti-ephrin-A4 (EFNA4) antibodies, such as PF-06647263;

[0297] anti-RANKL antibodies such as denosumab;

[0298] anti-mesothelin antibodies such as BMS-986148, anti-MSLN-MMAE;

[0299] anti-sodium phosphate cotransporter 2B (NaP2B) antibodies, such as rifastuzumab;

[0300] anti-TGFb antibodies such as SAR439459;

[0301] anti-transforming growth factor-beta (TGF-beta) antibodies such as ABBV-151, LY3022859, NIS793, and XOMA089;

[0302] purine analogues, folate antagonists (such as pralatrexate), cladribine, pentostatin, fludarabine, and related inhibitors;

[0303] antiproliferative / antimitotic agents, including microtubule inhibitors such as vinca alkaloids (vinblastine, vincristine) and taxanes (paclitaxel, docetaxel), natural products such as vinblastine, nocodazole, epothilones, vinorelbine (NAVELBINE®), and epipodophyllotoxins (etoposide, teniposide);

[0304] DNA damaging agents such as actinomycin, amsacrine, busulfan, carboplatin, chlorambucil, cisplatin, cyclophosphamide (CYTOXAN®), dactinomycin, daunorubicin, doxorubicin, DEBDOX, epirubicin, ifosfamide, melphalan, mechlorethamine, mitomycin C, mitoxantrone, nitrosoureas, procarbazine, taxol, taxotere, teniposide, etoposide, and triethylenethiophosphoramide;

[0305] DNA hypomethylating agents such as guadecitabine (SGI-110) and ASTX727;

[0306] Antibiotics such as dactinomycin, daunorubicin, doxorubicin, idarubicin, anthracyclines, mitoxantrone, bleomycin, and primycin (mithramycin);

[0307] Enzymes such as L-asparaginase, which metabolize L-asparagine throughout the body, eliminating cells that do not have the ability to synthesize their own asparagine;

[0308] DNAi oligonucleotides that target Bcl-2, such as PNT2258; drugs that activate or reactivate latent human immunodeficiency virus (HIV), such as panobinostat and romidepsin;

[0309] asparaginase stimulators such as crisantaspase (Erwinase®) and GRASPA (ERY-001, ERY-ASP), calaspargase pegol, and pegaspargase;

[0310] pan-Trk, ROS1 and ALK inhibitors such as entrectinib and TPX-0005;

[0311] anaplastic lymphoma kinase (ALK) inhibitors such as alectinib, ceritinib, Alecensa (RG7853), and ALUNBRIG® (brigatinib);

[0312] antiproliferative / antimitotic alkylating agents such as the nitrogen mustard cyclophosphamide and analogs (e.g., melphalan, chlorambucil, hexamethylmelamine, thiotepa), alkylnitrosoureas (e.g., carmustine) and analogs, streptozocin, and triazines (e.g., dacarbazine);

[0313] antiproliferative / antimitotic antimetabolites such as folic acid analogs (methotrexate);

[0314] Platinum coordination complexes (e.g., cisplatin, oxiloplatin, and carboplatin), procarbazine, hydroxyurea, mitotane, and aminoglutethimide;

[0315] Hormones, hormone analogues (e.g., estrogen, tamoxifen, goserelin, bicalutamide, and nilutamide), and aromatase inhibitors (e.g., letrozole and anastrozole);

[0316] antiplatelet agents; anticoagulants such as heparin, synthetic heparin salts, and other inhibitors of thrombin;

[0317] fibrinolytic agents such as tissue plasminogen activator, streptokinase, urokinase, aspirin, dipyridamole, ticlopidine, and clopidogrel;

[0318] Antimigratory agents; antisecretory agents (e.g., breveldin);

[0319] immunosuppressants such as tacrolimus, sirolimus, azathioprine, and mycophenolate;

[0320] growth factor inhibitors and vascular endothelial growth factor inhibitors;

[0321] fibroblast growth factor inhibitors such as FPA14;

[0322] AMP-activated protein kinase stimulators such as metformin hydrochloride;

[0323] ADP-ribosyl cyclase-1 inhibitors, such as daratumumab (DARZALEX®);

[0324] caspase recruitment domain protein-15 stimulators such as mifamurtide (liposomal);

[0325] CCR5 chemokine antagonists such as MK-7690 (Vicriviroc);

[0326] CDC7 protein kinase inhibitors such as TAK-931;

[0327] cholesterol side-chain cleavage enzyme inhibitors such as ODM-209;

[0328] Dihydropyrimidine dehydrogenase / orotate phosphoribosyltransferase inhibitors such as cefezone (tegafur + gimeracil + oteracil potassium);

[0329] DNA polymerase / ribonucleotide reductase inhibitors such as clofarabine;

[0330] DNA interfering oligonucleotides such as PNT2258, AZD-9150;

[0331] estrogen receptor modulators such as bazedoxifene;

[0332] estrogen receptor agonist / progesterone receptor antagonist such as TRI-CYCLEN LO (norethindrone + ethinyl estradiol);

[0333] HLA class I antigen A-2 alpha modulators such as FH-MCVA2TCR;

[0334] HLA class I antigen A-2 alpha / MART-1 melanoma antigen modulators, such as MART-1 F5 TCR-engineered PBMCs;

[0335] human granulocyte colony-stimulating factors, such as PF-06881894;

[0336] GNRH receptor agonists such as leuprorelin acetate, leuprorelin acetate extended-release depot (ATRIGEL), triptorelin pamoate, and goserelin acetate;

[0337] GNRH receptor antagonists such as elagolix, relugolix, and degarelix;

[0338] endoplasmin modulators such as analotinib;

[0339] H+K+ATPase inhibitors such as omeprazole and esomeprazole;

[0340] ICAM-1 / CD55 modulators such as cavatak (V-937);

[0341] IL-15 / IL-12 modulators such as SAR441000;

[0342] interleukin-23A inhibitors such as guselkumab;

[0343] lysine-specific histone demethylase 1 inhibitors such as CC-90011;

[0344] IL-12 mRNAs such as MEDI 1191;

[0345] RIG-I modulators such as RGT-100;

[0346] NOD2 modulators such as SB-9200 and IR-103.

[0347] progesterone receptor agonists such as levonorgestrel;

[0348] protein cereblon modulators such as CC-92480, CC-90009;

[0349] Protein cereblon modulators such as iverdomide / DNA binding protein Ikaros inhibitors / zinc finger binding protein Aiolos inhibitors;

[0350] Retinoid X receptor modulators such as alitretinoin and bexarotene (oral formulations);

[0351] RIP-1 kinase inhibitors such as GSK-3145095;

[0352] selective estrogen receptor degraders such as AZD9833;

[0353] SUMO inhibitors such as TAK-981;

[0354] thrombopoietin receptor agonists such as eltrombopag;

[0355] thyroid hormone receptor agonists, such as levothyroxine sodium;

[0356] TNF agonists such as tasonermin;

[0357] tyrosine phosphatase substrate 1 inhibitors such as CC-95251;

[0358] HER2 inhibitors such as neratinib and tucatinib (ONT-380);

[0359] EGFR / ErbB2 / Ephb4 inhibitors such as tesevatinib;

[0360] EGFR / HER2 inhibitors such as TAK-788;

[0361] EGFR family tyrosine kinase receptor inhibitors such as DZD-9008;

[0362] EGFR / ErbB-2 inhibitors such as valitinib;

[0363] mutation-selective EGFR inhibitors such as PF-06747775, EGF816 (nazartinib), ASP8273, ACEA-0010, and BI-1482694;

[0364] epha2 inhibitors such as MM-310;

[0365] Polycomb protein (EED) inhibitors such as MAK683;

[0366] DHFR inhibitors / folate transporter 1 modulators / folate receptor antagonists such as pralatrexate;

[0367] DHFR / GAR transformylase / thymidylate synthase / transferase inhibitors such as pemetrexed disodium;

[0368] p38 MAP kinase inhibitors such as ralimetinib;

[0369] PRMT inhibitors such as MS203, PF-06939999, GSK3368715, and GSK3326595;

[0370] sphingosine kinase 2 (SK2) inhibitors such as opaganib;

[0371] nuclear erythroid 2-related factor 2 stimulators, such as omaveloxolone (RTA-408);

[0372] tropomyosin receptor kinase (TRK) inhibitors such as LOXO-195 and ONO-7579;

[0373] mucin 1 inhibitors such as GO-203-2C;

[0374] MARCKS protein inhibitors such as BIO-11006;

[0375] folate antagonists such as arfolitixoline;

[0376] galectin-3 inhibitors such as GR-MD-02;

[0377] phospho-P68 inhibitors such as RX-5902;

[0378] CD95 / TNF modulators such as ofranergene obadenovec;

[0379] pan-PIM kinase inhibitors such as INCB-053914;

[0380] IL-12 gene stimulators such as EGEN-001, taboquinogen terce plasmid;

[0381] heat shock protein HSP90 inhibitors such as TAS-116 and PEN-866;

[0382] VEGF / HGF antagonists such as MP-0250;

[0383] VEGF ligand inhibitors, such as bevacizumab biosimilars;

[0384] VEGF receptor antagonists / VEGF ligand inhibitors such as ramucirumab;

[0385] VEGF-1 / VEGF-2 / VEGF-3 receptor antagonists such as fruquintinib;

[0386] VEGF-1 / VEGF-2 receptor modulators, such as HLA-A2402 / HLA-A0201 restricted epitope peptide vaccines;

[0387] placental growth factor ligand inhibitors / VEGF-A ligand inhibitors such as aflibercept;

[0388] SYK tyrosine kinase / JAK tyrosine kinase inhibitors such as ASN-002;

[0389] Trk tyrosine kinase receptor inhibitors such as larotrectinib sulfate;

[0390] JAK3 / JAK1 / TBK1 kinase inhibitors such as CS-12912;

[0391] IL-24 antagonists such as AD-IL24;

[0392] NLRP3 (NACHT LRR PYD domain protein 3) modulators, such as BMS-986299;

[0393] RIG-I agonists such as RGT-100;

[0394] aerolysin stimulators such as topsalisin;

[0395] P-glycoprotein 1 inhibitors such as HM-30181A;

[0396] CSF-1 antagonists such as ARRY-382, BLZ-945;

[0397] CCR8 inhibitors such as I-309, SB-649701, HG-1013, and RAP-310;

[0398] anti-mesothelin antibodies such as SEL-403;

[0399] thymidine kinase stimulators such as agratimagenbesadenovec;

[0400] Polo-like kinase 1 inhibitors such as PCM-075 and onvansertib;

[0401] NAE inhibitors such as pevonedistat (MLN-4924) and TAS-4464;

[0402] multipathway modulators such as avadomide (CC-122);

[0403] amyloid protein binding protein-1 inhibitors / ubiquitin ligase modulators such as pevonedistat;

[0404] FoxM1 inhibitors such as thiostreptomycin;

[0405] UBA1 inhibitors such as TAK-243;

[0406] Src tyrosine kinase inhibitors such as VAL-201;

[0407] VDAC / HK inhibitors such as VDA-1102;

[0408] Elf4a inhibitors such as rohitinib and eFT226;

[0409] TP53 gene stimulators such as ad-p53;

[0410] retinoic acid receptor agonists, such as tretinoin;

[0411] retinoic acid receptor alpha (RARα) inhibitors, such as SY-1425;

[0412] SIRT3 inhibitors such as YC8-02;

[0413] stromal cell-derived factor 1 ligand inhibitors such as Oraptest pegol (NOX-A12);

[0414] IL-4 receptor modulators such as MDNA-55;

[0415] arginase I stimulators such as pegzylariginase;

[0416] Topoisomerase I inhibitors such as irinotecan hydrochloride and Onivyde;

[0417] topoisomerase I inhibitors / hypoxia-inducible factor-1 alpha inhibitors such as PEG-SN38 (filtecampegol);

[0418] hypoxia-inducible factor-1 alpha inhibitors such as PT-2977, PT-2385;

[0419] CD122 (IL-2 receptor) agonists such as Proleukin (aldesleukin, IL-2); pegylated IL-2 (e.g., NKTR-214); modified variants of IL-2 (e.g., THOR-707);

[0420] TLR7 / TLR8 agonists such as NKTR-262;

[0421] TLR7 agonists such as DS-0509, GS-9620, LHC-165, and TMX-101 (imiquimod);

[0422] p53 tumor suppressor protein stimulators such as quevetrin;

[0423] Mdm4 / Mdm2 p53-binding protein inhibitors, such as ALRN-6924;

[0424] kinesin spindle protein (KSP) inhibitors such as filanesib (ARRY-520);

[0425] CD80-fc fusion protein inhibitors such as FPT-155;

[0426] menin and mixed phenotype leukemia (MLL) inhibitors such as KO-539;

[0427] liver x receptor agonists such as RGX-104;

[0428] IL-10 agonists such as pegylodecaquin (AM-0010);

[0429] VEGFR / PDGFR inhibitors such as borolanib;

[0430] IRAK4 inhibitors such as CA-4948;

[0431] anti-TLR-2 antibodies such as OPN-305;

[0432] calmodulin modulators such as CBP-501;

[0433] glucocorticoid receptor antagonists, such as relacorilant (CORT-125134);

[0434] second mitochondrial-derived activator of caspases (SMAC) protein inhibitors, such as BI-891065;

[0435] lactoferrin modulators such as LTX-315;

[0436] KIT proto-oncogene, receptor tyrosine kinase (KIT) inhibitors, such as PLX-9486;

[0437] Platelet-derived growth factor receptor alpha (PDGFRA) / KIT proto-oncogene, receptor tyrosine kinase (KIT) mutant-specific antagonists / inhibitors, such as BLU-285 and DCC-2618;

[0438] exportin 1 inhibitors such as eltanexor;

[0439] CHST15 gene inhibitors such as STNM-01;

[0440] somatostatin receptor antagonists such as OPS-201;

[0441] CEBPA gene stimulators such as MTL-501;

[0442] DKK3 gene modulators such as MTG-201;

[0443] chemokine (CXCR1 / CXCR2) inhibitors such as SX-682;

[0444] p70s6k inhibitors such as MSC2363318A;

[0445] methionine aminopeptidase 2 (MetAP2) inhibitors such as M8891 and APL-1202;

[0446] arginine N-methyltransferase 5 inhibitors such as GSK-3326595;

[0447] CD71 modulators such as CX-2029-ABBV-2029;

[0448] ATM (ataxia telangiectasia) inhibitors such as AZD0156, AZD1390;

[0449] CHK1 inhibitors such as GDC-0575, LY2606368 (prexasertib), SRA737, and RG7741 (CHK1 / 2);

[0450] CXCR4 antagonists such as BL-8040, LY2510924, blixafor (TG-0054), X4P-002, X4P-001-IO, and plerixafor;

[0451] EXH2 inhibitors such as GSK2816126;

[0452] KDM1 inhibitors such as ORY-1001, IMG-7289, INCB-59872, and GSK-2879552;

[0453] CXCR2 antagonists such as AZD-5069;

[0454] GM-CSF antibodies such as lenzilumab;

[0455] DNA-dependent protein kinase inhibitors such as MSC2490484A (nedisertib), VX-984, and AsiDNA (DT-01); protein kinase C (PKC) inhibitors such as LXS-196 and sotrastaurin;

[0456] selective estrogen receptor downregulators (SERDs) such as fulvestrant (Faslodex®), RG6046, RG6047, RG6171, elacestrant (RAD-1901), SAR439859, and AZD9496;

[0457] selective estrogen receptor covalent antagonists (SERCAs), such as H3B-6545;

[0458] selective androgen receptor modulators (SARMs) such as GTX-024 and darolutamide;

[0459] Transforming growth factor-beta (TGF-beta) kinase antagonists such as galunisertib, LY3200882; TGF-beta inhibitors as described in WO 2019 / 103203;

[0460] TGF beta receptor 1 inhibitors such as PF-06952229;

[0461] ABT-165 (DLL4 / VEGF), MM-141 (IGF-1 / ErbB3), MM-111 (Erb2 / Erb3), JNJ-64052781 (CD19 / CD3), PRS-343 (CD-137 / HER2), AFM26 (BCMA / CD16A), JNJ-61186372 (EGFR / cMET), AMG-211 (CEA / CD3), RG7802 (CEA / CD3), ERY-974 (CD3 / GPC3), vancizumab (angiopoietin / VEGF), PF-06671008 (cadherin / CD3), AFM-13 (CD16 / CD30), APVO436 (CD123 / CD3), flotetuzumab (CD123 / CD3), REGN-1979 (CD20 / CD3), MCLA-117 (CD3 / CLEC12A), MCLA-128 (HER2 / HER3), JNJ-0819, JNJ-7564 (CD3 / heme), AMG-757 (DLL3-CD3), MGD-013 (PD-1 / LAG-3), FS-118 (LAG-3 / PD-L1), MGD-019 (PD-1 / CTLA-4), KN-046 (PD-1 / CTLA-4), MEDI-5752 (CTLA-4 / PD-1), RO-7121661(PD-1 / TIM-3), XmAb-20717(PD-1 / CTLA-4), AK-104(CTLA-4 / PD-1), AMG-330(CD33 / CD3), AMG-420(BCMA / CD3), BI-83 6880(VEFG / ANG2), JNJ-63709178(CD123 / CD3), MGD-007(CD3 / gpA33), MGD-009(CD3 / B7H3), AGEN1223, IMCgp100(CD3 / gp100), AGEN-1423, ATOR-10 15 (CTLA-4 / OX40), LY-3415244 (TIM-3 / PDL1), INHIBRX-105 (4-1BB / PDL1), faricimab (VEGF-A / ANG-2), FAP-4-IBBL (4-1BB / FAP), XmAb-13676 (CD3 / CD20), TAK-252 (PD-1 / OX40L), TG-1801 (CD19 / CD47), XmAb-18087 (SSTR2 / CD3), catumaxomab (CD3 / EpCAM), SAR-156597 (IL4 / IL13), EMB-01 (EGFR / cMET),Bispecific antibodies such as REGN-4018 (MUC16 / CD3), REGN-1979 (CD20 / CD3), RG-7828 (CD20 / CD3), CC-93269 (CD3 / BCMA), REGN-5458 (CD3 / BCMA), nabi-ciquizumab (DLL4 / VEGF), GRB-1302 (CD3 / Erbb2), vanucizumab (VEGF-A / ANG-2), GRB-1342 (CD38 / CD3), GEM-333 (CD3 / CD33), IMM-0306 (CD47 / CD20), RG6076, MEDI5752 (PD-1 / CTLA-4), and LY3164530 (MET / EGFR);

[0462] alpha-ketoglutarate dehydrogenase (KGDH) inhibitors such as CPI-613;

[0463] XPO1 inhibitors such as selinexor (KPT-330);

[0464] isocitrate dehydrogenase 2 (IDH2) inhibitors, such as enasidenib (AG-221);

[0465] IDH1 inhibitors such as AG-120 and AG-881 (IDH1 and IDH2), IDH-305, and BAY-1436032;

[0466] IDH1 gene inhibitors such as ivosidenib;

[0467] interleukin-3 receptor (IL-3R) modulators such as SL-401;

[0468] arginine deiminase stimulators such as pegalgiminase (ADI-PEG-20);

[0469] claudin-18 inhibitors such as claudiximab;

[0470] β-catenin inhibitors such as CWP-291;

[0471] chemokine receptor 2 (CCR) inhibitors such as PF-04136309, CCX-872, and BMS-813160 (CCR2 / CCR5);

[0472] thymimidylate synthase inhibitors such as ONX-0801;

[0473] ALK / ROS1 inhibitors such as lorlatinib;

[0474] tankyrase inhibitors such as G007-LK;

[0475] Mdm2 p53-binding protein inhibitors such as CMG-097 and HDM-201; c-PIM inhibitors such as PIM447;

[0476] sphingosine kinase-2 (SK2) inhibitors such as Yeliva® (ABC294640);

[0477] DNA polymerase inhibitors such as sapacitabine;

[0478] cell cycle / microtubule inhibitors such as eribulin mesylate;

[0479] AMG-337, savolitinib, tivantinib (ARQ-197), capmatinib, and c-MET inhibitors such as tepotinib, ABT-700, AG213, AMG-208, JNJ-38877618 (OMO-1), meristinib, and HQP-8361;

[0480] c-Met / VEGFR inhibitors such as BMS-817378 and TAS-115;

[0481] c-Met / RON inhibitors such as BMS-777607;

[0482] BCR / ABL inhibitors such as rebastinib, asciminib, and ponatinib (ICLUSIG®);

[0483] MNK1 / MNK2 inhibitors such as eFT-508;

[0484] cytochrome P450 11B2 / cytochrome P450 17 / AKT protein kinase inhibitors, such as LAE-201;

[0485] cytochrome P450 3A4 stimulators such as mitotane;

[0486] lysine-specific demethylase-1 (LSD1) inhibitors such as CC-90011;

[0487] CSF1R / KIT and FLT3 inhibitors such as pexidartinib (PLX3397);

[0488] Flt3 tyrosine kinase / Kit tyrosine kinase inhibitors, such as quizartinib hydrochloride, and PDGF receptor antagonists;

[0489] kinase inhibitors such as vandetanib;

[0490] E-selectin antagonists such as GMI-1271;

[0491] differentiation inducers such as tretinoin;

[0492] epidermal growth factor receptor (EGFR) inhibitors such as osimertinib (AZD-9291) and cetuximab;

[0493] Topoisomerase inhibitors such as adriamycin, doxorubicin, daunorubicin, dactinomycin, DaunoXome, Caelyx, eniposide, epirubicin, etoposide, idarubicin, irinotecan, mitoxantrone, pixantrone, sobuzoxane, topotecan, irinotecan, MM-398 (liposomal irinotecan), vosaroxin and GPX-150, aldoxorubicin, AR-67, mavereltinib, AST-2818, avitinib (ACEA-0010), irofulven (MGI-114);

[0494] Corticoids such as cortisone, dexamethasone, hydrocortisone, methylprednisolone, prednisone, and prednisolone;

[0495] growth factor signaling kinase inhibitors;

[0496] nucleoside analogues such as DFP-10917;

[0497] Axl inhibitors such as BGB-324 (bemcentinib) and SLC-0211;

[0498] Axl / Flt3 inhibitors such as gilteritinib;

[0499] Inhibitors of bromodomain and extraterminal motif (BET) proteins (including ABBV-744, BRD2 (NCBI Gene ID: 6046), BRD3 (NCBI Gene ID: 8019), BRD4 (NCBI Gene ID: 23476), and bromodomain testis-specific protein (BRDT; NCBI Gene ID: 676)), such as INCB-054329, INCB057643, TEN-010, AZD-5153, AB T-767, BMS-986158, CC-90010, GSK525762 (molybresive), NHWD-870, ODM-207, GSK-2820151, GSK-1210151A, ZBC246, ZBC260, ZEN3694, FT-1101, RG-6146, CC-90010, CC-95775, mibebrexit, BI-894999, PL...

Claims

1. A compound of formula (I), 【Chemical 1】 or a pharmaceutically acceptable salt thereof, wherein: R １ is hydrogen, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Alkoxy, halogen, C １～６ Haloalkyl, C １～６ haloalkoxy, or —CN; R ２ is hydrogen, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C １～６ Alkoxy, C ２～６ Alkoxyalkyl, halogen, C １～６ Haloalkyl, C １～６ Haloalkoxy, -CN, -NO, -NO ２ , -C(O)R ２ａ , -C(O)OR ２ａ , -OC(O)R ２ａ , -C(O)N(R ２ａ ) (R ２ｂ ), -N(R ２ａ ) C(O)R ２ｂ , -OC(O)N(R ２ａ ) (R ２ｂ ), -N(R ２ａ )C(O)OR ２ｂ , -C(=NR ２ａ ) N (R ２ｂ ) (R ２ｃ ), -N(R ２ａ ) (R ２ｂ ), -N(R ２ａ ) N (R ２ｂ ) (R ２ｃ ), -N(R ２ａ ) N=C(R ２ｂ ) (OR ２ｃ ), -OR ２ａ , -SR ２ａ , -S(O)R ２ａ , -S(O)(NR ２ａ ) (R ２ｂ ), -S(NR ２ａ ) (NR ２ｂ ) (R ２ｃ ), -S(O) ２ R ２ａ , -S(O) ２ N (R ２ａ ) (R ２ｂ ), -N(R ２ａ ) S (O) ２ (R ２ｂ ), -P(R ２ａ ) (R ２ｂ ), -P(O)(R ２ａ ) (R ２ｂ ), -P(O)(OR ２ａ ) (R ２ｂ ), -P(O)(OR ２ａ ) (OR ２ｂ ), C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１２ Aryl, C １～６ Alkyl-C ６～１２ Aryl, heterocycloalkyl, C １～６ alkyl-(heterocycloalkyl), heteroaryl, or C １～６ alkyl-(heteroaryl), where each alkyl, alkenyl, or alkynyl is independently selected from 1 to 3 R ２ｄ groups, and each cycloalkyl is optionally substituted with 1 to 3 R ２ｅ groups, and each aryl is optionally substituted with 1 to 3 R ２ｆ groups, and each heterocycloalkyl is optionally substituted with 1 to 3 R ２ｇ groups, and each heteroaryl is optionally substituted with 1 to 3 R ２ｈ and optionally substituted with a group, Each R ２ａ , R ２ｂ , and R ２ｃ are independently hydrogen, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C ２～６ Alkoxyalkyl, C １～６ Haloalkyl, C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１２ Aryl, C １～６ Alkyl-C ６～１２ Aryl, heterocycloalkyl, C １～６ alkyl-(heterocycloalkyl), heteroaryl, or C １～６ alkyl-(heteroaryl), where the aryl or heteroaryl is selected from 1 to 3 R ２ｊ and optionally substituted with Or, R ２ａ , R ２ｂ , and R ２ｃ when attached to the same atom, can combine with the atom to which they are attached to form a heterocycloalkyl, Each R ２ｄ are independently —CN, —C(O)R ２ｄ１ , -C(O)OR ２ｄ１ , -OC(O)R ２ｄ１ , -C(O)N(R ２ｄ１ ) (R ２ｄ２ ), -N(R ２ｄ１ ) C(O)R ２ｄ２ , -OC(O)N(R ２ｄ１ ) (R ２ｄ２ ), -N(R ２ｄ１ )C(O)OR ２ｄ２ , -N(R ２ｄ１ ) (R ２ｄ２ ), =O, -OR ２ｄ１ , -SR ２ｄ１ , -S(O)R ２ｄ１ , -S(O)(NR ２ｄ１ ) (R ２ｄ２ ), -S(O) ２ R ２ｄ１ , -S(O)N(R ２ｄ１ ) (R ２ｄ２ ), -N(R ２ｄ１ ) S (O) ２ R ２ｄ２ , C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１２ Aryl, C １～６ Alkyl-C ６～１２ Aryl, heterocycloalkyl, C １～６ alkyl-(heterocycloalkyl), heteroaryl, or C １～６ alkyl-(heteroaryl), Each R ２ｄ１ and R ２ｄ２ are independently hydrogen, C １～６ Alkyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C ２～６ Alkoxyalkyl, or C １～６ is haloalkyl, Each R ２ｅ , R ２ｆ , R ２ｇ , and R ２ｈ are independently hydrogen, C １～６ Alkyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C １～６ Alkoxy, C ２～６ Alkoxyalkyl, halogen, C １～６ Haloalkyl, C １～６ haloalkoxy, —CN, or —OH; Each R ２ｊ are independently １～６ Alkyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C １～６ Alkoxy, C ２～６ Alkoxyalkyl, halogen, C １～６ haloalkyl, or C １～６ haloalkoxy, R ３ is hydrogen, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C １～６ Alkoxy, C ２～６ Alkoxyalkyl, halogen, C １～６ Haloalkyl, C １～６ Haloalkoxy, -CN, -NO, -NO ２ , -C(O)R ３ａ , -C(O)OR ３ａ , -OC(O)R ３ａ , -C(O)N(R ３ａ ) (R ３ｂ ), -N(R ３ａ ) C(O)R ３ｂ , -OC(O)N(R ３ａ ) (R ３ｂ ), -N(R ３ａ )C(O)OR ３ｂ , -C(=NR ３ａ ) N (R ３ｂ ) (R ３ｃ ), -N(R ３ａ ) (R ３ｂ ), -N(R ３ａ ) N (R ３ｂ ) (R ３ｃ ), -N(R ３ａ ) N=C(R ３ｂ ) (OR ３ｃ ), -OR ３ａ , -SR ３ａ , -S(O)R ３ａ , -S(O)(NR ３ａ ) (R ３ｂ ), -S(NR ３ａ ) (NR ３ｂ ) (R ３ｃ ), -S(O) ２ R ３ａ , -S(O) ２ N (R ３ａ ) (R ３ｂ ), -N(R ３ａ ) S (O) ２ (R ３ｂ ), -P(R ３ａ ) (R ３ｂ ), -P(O)(R ３ａ ) (R ３ｂ ), -P(O)(OR ３ａ ) (R ３ｂ ), -P(O)(OR ３ａ ) (OR ３ｂ ), C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１２ Aryl, C １～６ Alkyl-C ６～１２ Aryl, heterocycloalkyl, C １～６ alkyl-(heterocycloalkyl), heteroaryl, or C １～６ alkyl-(heteroaryl), where each alkenyl or alkynyl is independently selected from 1 to 3 R ３ｄ groups, and each cycloalkyl is optionally substituted with 1 to 3 R ３ｅ groups, and each aryl is optionally substituted with 1 to 3 R ３ｆ groups, and each heterocycloalkyl is optionally substituted with 1 to 3 R ３ｇ groups, and each heteroaryl is optionally substituted with 1 to 3 R ３ｈ and optionally substituted with a group, Each R ３ａ , R ３ｂ , and R ３ｃ are independently hydrogen, C １～６ Alkyl, C １～６ Hydroxyalkyl, C ２～６ Alkoxyalkyl, C １～６ Haloalkyl, C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１２ Aryl, C １～６ Alkyl-C ６～１２ aryl, heterocycloalkyl, or heteroaryl; Or, R ３ａ , R ３ｂ , and R ３ｃ when attached to the same atom, can combine with the atom to which they are attached to form a heterocycloalkyl, Each R ３ｄ are independently —N(R ３ｄ１ ) (R ３ｄ２ ), -OR ３ｄ１ , C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１２ Aryl, C １～６ Alkyl-C ６～１２ aryl, heterocycloalkyl, or heteroaryl; Each R ３ｄ１ and R ３ｄ２ are independently hydrogen, C １～６ Alkyl, or —C(O)O—(C １～６ alkyl), Each R ３ｅ , R ３ｆ , R ３ｇ , and R ３ｈ are independently hydrogen, C １～６ Alkyl, C １～６ Alkoxy, halogen, C １～６ haloalkyl, or C １～６ haloalkoxy, R ４ is hydrogen, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Alkoxy, halogen, C １～６ Haloalkyl, C １～６ haloalkoxy, or —CN; R ５ is hydrogen, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Hydroxyalkyl, C ２～６ Alkoxyalkyl, C １～６ Haloalkyl, C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１２ Aryl, C １～６ Alkyl-C ６～１２ Aryl, heterocycloalkyl, C １～６ alkyl-(heterocycloalkyl), heteroaryl, or C １～６ alkyl-(heteroaryl), where alkyl is R ５ａ and optionally substituted with R ５ａ is -OSi(R ５ａ１ ) (R ５ａ２ ) (R ５ａ３ ) and R ５ａ１ , R ５ａ２ , and R ５ａ３ are each independently C １～６ is alkyl, R ６ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ６～１２ aryl, or heteroaryl, wherein the aryl or heteroaryl is selected from 1 to 3 R ６ａ each optionally substituted with Each R ６ａ are independently １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C １～６ Alkoxy, C ２～６ Alkoxyalkyl, halogen, C １～６ Haloalkyl, C １～６ Haloalkoxy, —CN, —NO ２ , -C(O)R ６ｂ , -C(O)OR ６ｂ , -OC(O)R ６ｂ , -C(O)N(R ６ｂ ) (R ６ｃ ), -N(R ６ｂ ) C(O)R ６ｃ , -C(=NR ６ｂ ) N (R ６ｃ ) (R ６ｄ ), -N(R ６ｂ ) (R ６ｃ ), -OR ６ｂ , -SR ６ｂ , -S(O)R ６ｂ , -S(O) ２ R ６ｂ , -S(NR ６ｂ ) (NR ６ｃ ) R ６ｄ , -S(O)(NR ６ｂ ) (R ６ｃ ), -S(O) ２ N (R ６ｂ ) (R ６ｃ ), -N(R ６ｂ ) S (O) ２ (R ６ｃ ), -P(R ６ｂ ) (R ６ｃ ), -P(O)(R ６ｂ ) (R ６ｃ ), -P(O)(OR ６ｂ ) (R ６ｃ ), -P(O)(OR ６ｂ ) (OR ６ｃ ), C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１２ Aryl, C １～６ Alkyl-C ６～１２ Aryl, heterocycloalkyl, C １～６ alkyl-(heterocycloalkyl), heteroaryl, or C １～６ alkyl-(heteroaryl), where cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is selected from 1 to 3 R ６ｅ each optionally substituted with, and alkyl is R ６ｆ and the alkynyl is optionally substituted with 1 to 4 R ６ｊ and optionally substituted with Each R ６ｂ , R ６ｃ and R ６ｄ are independently hydrogen, C １～６ Alkyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C ２～６ Alkoxyalkyl, C １～６ Haloalkyl, C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１２ Aryl, C １～６ Alkyl-C ６～１２ Aryl, heterocycloalkyl, C １～６ alkyl-(heterocycloalkyl), heteroaryl, or C １～６ alkyl-(heteroaryl), where cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is selected from 1 to 3 R ６ｋ and optionally substituted by Each R ６ｋ are independently １～６ Alkyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C １～６ Alkoxy, C ２～６ Alkoxyalkyl, C １～６ Haloalkyl, C １～６ Haloalkoxy, C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ cycloalkyl, heterocycloalkyl, or C １～６ alkyl-(heterocycloalkyl), Each R ６ｅ are independently １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C １～６ Alkoxy, C ２～６ Alkoxyalkyl, halogen, C １～６ Haloalkyl, C １～６ Haloalkoxy, —CN, —NO ２ , -C(O)R ６ｅ１ , -C(O)OR ６ｅ１ , -OC(O)R ６ｅ１ , -C(O)N(R ６ｅ１ ) (R ６ｅ２ ), -N(R ６ｅ１ ) C(O)R ６ｅ２ , -OC(O)N(R ６ｅ１ ) (R ６ｅ２ ), -N(R ６ｅ１ )C(O)OR ６ｅ２ , -C(=NR ６ｅ１ ) N (R ６ｅ２ ) (R ６ｅ３ ), -N(R ６ｅ１ ) (R ６ｅ２ ), =O, -OR ６ｅ１ , -SR ６ｅ１ , -S(O)R ６ｅ１ , -S(NR ６ｅ１ ) (NR ６ｅ２ ), -S(O)(NR ６ｅ１ ) (R ６ｅ２ ), -S(O) ２ R ６ｅ１ , -S(O) ２ N (R ６ｅ１ ) (R ６ｅ２ ), -SF ５ , -N(R ６ｅ１ ) S (O) ２ (R ６ｅ２ ), -P(R ６ｅ１ ) (R ６ｅ２ ), -P(O)(R ６ｅ１ ) (R ６ｅ２ ), -P(O)(OR ６ｅ１ ) (R ６ｅ２ ), -P(O)(OR ６ｅ１ ) (OR ６ｅ２ ), -Si(R ６ｅ１ ) (R ６ｅ２ ) (R ６ｅ３ ), C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１２ Aryl, C １～６ Alkyl-C ６～１２ Aryl, heterocycloalkyl, C １～６ Alkyl-heterocycloalkyl, heteroaryl, or C １～６ alkyl-heteroaryl, where cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is selected from 1 to 3 R ６ｈ each optionally substituted with 1 to 3 R ６ｍ and optionally substituted with Each R ６ｅ１ , R ６ｅ２ , and R ６ｅ３ are independently hydrogen, C １～６ Alkyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C １～６ Alkoxyalkyl, C １～６ Haloalkyl, C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１０ Aryl, C １～６ Alkyl-C ６～１０ Aryl, heterocycloalkyl, C １～６ alkyl-(heterocycloalkyl), heteroaryl, or C １～６ alkyl-(heteroaryl), where cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is selected from 1 to 3 R ６ｎ and optionally substituted with Each R ６ｎ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C １～６ Alkoxy, C ２～６ Alkoxyalkyl, halogen, C １～６ Haloalkyl, C １～６ Haloalkoxy, —CN, —C(O)R ６ｎ１ , -C(O)OR ６ｎ１ , -OC(O)R ６ｎ１ , -C(O)N(R ６ｎ１ ) (R ６ｎ２ ), -N(R ６ｎ１ ) C(O)R ６ｎ２ , -OC(O)N(R ６ｎ１ ) (R ６ｎ２ ), -N(R ６ｎ１ )C(O)OR ６ｎ２ , -C(=NR ６ｎ１ ) N (R ６ｎ２ ) (R ６ｎ３ ), -N(R ６ｎ１ ) (R ６ｎ２ ), =O, -OH, -SR ６ｎ１ , -S(O)R ６ｎ１ , -S(NR ６ｎ１ ) (NR ６ｎ２ ) R ６ｎ３ , -S(O)(NR ６ｎ１ ) (R ６ｎ２ ), -S(O) ２ R ６ｎ１ , -S(O) ２ N (R ６ｎ１ ) (R ６ｎ２ ), or -N(R ６ｎ１ ) S (O) ２ (R ６ｎ２ ) and Each R ６ｎ１ , R ６ｎ２ and R ６ｎ３ are independently hydrogen, C １～６ Alkyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C ２～６ Alkoxyalkyl, C １～６ Haloalkyl, C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１０ Aryl, C １～６ Alkyl-C ６～１０ Aryl, heterocycloalkyl, C １～６ alkyl-(heterocycloalkyl), heteroaryl, or C １～６ alkyl-(heteroaryl), Each R ６ｈ are independently １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C １～６ Alkoxy, C ２～６ Alkoxyalkyl, halogen, C １～６ Haloalkyl, C １～６ Haloalkoxy, —CN, —C(O)R ６ｈ１ , -C(O)OR ６ｈ１ , -OC(O)R ６ｈ１ , -C(O)N(R ６ｈ１ ) (R ６ｈ２ ), -N(R ６ｈ１ ) C(O)R ６ｈ２ , -OC(O)N(R ６ｈ１ ) (R ６ｈ２ ), -N(R ６ｈ１ )C(O)OR ６ｈ２ , -C(=NR ６ｈ１ ) N (R ６ｈ２ ) (R ６ｈ３ ), -N(R ６ｈ１ ) (R ６ｈ２ ), =O, -OH, -SR ６ｈ１ , -S(O)R ６ｈ１ , -S(NR ６ｈ１ ) (NR ６ｈ２ ) R ６ｈ３ , -S(O)(NR ６ｈ１ ) (R ６ｈ２ ), -S(O) ２ R ６ｈ１ , -S(O) ２ N (R ６ｈ１ ) (R ６ｈ２ ), -N(R ６ｈ１ ) S (O) ２ (R ６ｈ２ ), C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ cycloalkyl, heterocycloalkyl, or C １～６ alkyl-(heterocycloalkyl), Each R ６ｈ１ , R ６ｈ２ , and R ６ｈ３ are independently hydrogen, C １～６ Alkyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C ２～６ Alkoxyalkyl, C １～６ Haloalkyl, C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１０ Aryl, C １～６ Alkyl-C ６～１０ Aryl, heterocycloalkyl, C １～６ alkyl-(heterocycloalkyl), heteroaryl, or C １～６ alkyl-(heteroaryl), Each R ６ｍ are independently halogen, C １～６ Haloalkyl, C １～６ Haloalkoxy, —CN, —C(O)R ６ｍ１ , -C(O)OR ６ｍ１ , -OC(O)R ６ｍ１ , -C(O)N(R ６ｍ１ ) (R ６ｍ２ ), -N(R ６ｍ３ ) C(O)R ６ｍ２ , -OC(O)N(R ６ｍ１ ) (R ６ｍ２ ), -N(R ６ｍ１ )C(O)OR ６ｍ２ , -C(=NR ６ｍ３ ) N (R ６ｍ１ ) (R ６ｍ２ ), -N(R ６ｍ１ ) (R ６ｍ２ ), =O, -OH, -SR ６ｍ１ , -S(O)R ６ｍ１ , -S(NR ６ｍ１ ) (NR ６ｍ２ ) R ６ｍ３ , -S(O)(NR ６ｍ１ ) (R ６ｍ２ ), -S(O) ２ R ６ｍ１ , -S(O) ２ N (R ６ｍ１ ) (R ６ｍ２ ), or -N(R ６ｍ３ ) S (O) ２ (R ６ｍ２ ) and Each R ６ｍ１ , R ６ｍ２ , and R ６ｍ３ are independently hydrogen, C １～６ Alkyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C ２～６ Alkoxyalkyl, C １～６ Haloalkyl, C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１０ Aryl, C １～６ Alkyl-C ６～１０ Aryl, heterocycloalkyl, C １～６ alkyl-(heterocycloalkyl), heteroaryl, or C １～６ alkyl-(heteroaryl), R ６ｆ is -OSi(R ６ｆ１ ) (R ６ｆ２ ) (R ６ｆ３ ) and R ６ｆ１ , R ６ｆ２ , and R ６ｆ３ are each independently C １～６ is alkyl, Each R ６ｊ are independently ２～６ Alkoxyalkyl, halogen, C １～６ Haloalkyl, C １～６ Haloalkoxy, —CN, —C(O)R ６ｊ１ , -C(O)OR ６ｊ１ , -OC(O)R ６ｊ１ , -C(O)N(R ６ｊ１ ) (R ６ｊ２ ), -N(R ６ｊ３ ) C(O)R ６ｊ２ , -OC(O)N(R ６ｊ１ ) (R ６ｊ２ ), -N(R ６ｊ１ )C(O)OR ６ｊ２ , -C(=NR ６ｊ３ ) N (R ６ｊ１ ) (R ６ｊ２ ), -N(R ６ｊ１ ) (R ６ｊ２ ), =O, -OR ６ｊ１ , -SR ６ｊ１ , -S(O)R ６ｊ１ , -S(NR ６ｊ１ ) (NR ６ｊ２ ), -S(NR ６ｊ１ ) (NR ６ｊ２ ) R ６ｊ３ , -S(O)(NR ６ｊ１ ) (R ６ｊ２ ), -S(O) ２ R ６ｊ１ , -S(O) ２ N (R ６ｊ１ ) (R ６ｊ２ ), -N(R ６ｊ１ ) S (O) ２ (R ６ｊ２ ), -Si(R ６ｊ１ ) (R ６ｊ２ ) (R ６ｊ３ ), C ３～１０ Cycloalkyl, C ６～１２ aryl, heterocycloalkyl, or heteroaryl, wherein the cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is selected from 1 to 3 R ６ｐ and optionally substituted with Each R ６ｊ１ , R ６ｊ２ , and R ６ｊ３ are independently hydrogen, C １～６ Alkyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C ２～６ Alkoxyalkyl, C １～６ Haloalkyl, C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１０ Aryl, C １～６ Alkyl-C ６～１０ Aryl, heterocycloalkyl, C １～６ alkyl-(heterocycloalkyl), heteroaryl, or C １～６ alkyl-(heteroaryl), Each R ６ｐ are independently １～６ Alkyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C １～６ Alkoxy, C ２～６ Alkoxyalkyl, halogen, C １～６ Haloalkyl, C １～６ Haloalkoxy, —CN, —C(O)R ６ｐ１ , -C(O)OR ６ｐ１ , -OC(O)R ６ｐ１ , -C(O)N(R ６ｐ１ ) (R ６ｐ２ ), -N(R ６ｐ１ ) C(O)R ６ｐ２ , -OC(O)N(R ６ｐ１ ) (R ６ｐ２ ), -N(R ６ｐ１ )C(O)OR ６ｐ２ , -C(=NR ６ｐ３ ) N (R ６ｐ１ ) (R ６ｐ２ ), -N(R ６ｐ１ ) (R ６ｐ２ ), =O, -OH, -SR ６ｐ１ , -S(O)R ６ｐ１ , -S(NR ６ｐ１ ) (NR ６ｐ２ ) R ６ｐ３ , -S(O)(NR ６ｐ１ ) (R ６ｐ２ ), -S(O) ２ R ６ｐ１ , -S(O) ２ N (R ６ｐ１ ) (R ６ｐ２ ), or -N(R ６ｐ１ ) S (O) ２ (R ６ｐ２ ) and Each R ６ｐ１ , R ６ｐ２ , and R ６ｐ３ are independently hydrogen, C １～６ Alkyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C ２～６ Alkoxyalkyl, C １～６ Haloalkyl, C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１０ Aryl, C １～６ Alkyl-C ６～１０ Aryl, heterocycloalkyl, C １～６ alkyl-(heterocycloalkyl), heteroaryl, or C １～６ alkyl-(heteroaryl), Or, R ５ and one R ６ａ together with the atom to which they are attached form a heterocycloalkyl, and 1 to 3 R ６ｇ and optionally substituted with Each R ６ｇ are independently １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C ２～６ Alkoxyalkyl, halogen, C １～６ Haloalkyl, C １～６ haloalkoxy, or —CN; R ７ is hydrogen, C １～６ Alkyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C １～６ Alkoxy, C ２～６ Alkoxyalkyl, C １～６ Alkylthio, halogen, C １～６ Haloalkyl, —CN, —OH, —NH ２ , C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ cycloalkyl, heterocycloalkyl, or C １～６ alkyl-(heterocycloalkyl), each heterocycloalkyl is a 3- to 20-membered ring having 1 to 4 heteroatoms, each independently N, O, or S; each heteroaryl is a 5- to 18-membered ring having 1-4 heteroatoms, each independently N, O, or S; However, R ５ and R ６ are both C １～４ Not alkyl, R ５ is hydrogen, R ６ is not isopropyl or phenyl substituted with 2-Me, or a pharmaceutically acceptable salt thereof.

2. During the ceremony, R １ is hydrogen, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Alkoxy, halogen, C １～６ Haloalkyl, C １～６ haloalkoxy, or —CN; R ２ is hydrogen, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Hydroxyalkyl, C １～６ Alkoxy, C ２～６ Alkoxyalkyl, halogen, C １～６ Haloalkyl, C １～６ Haloalkoxy, -CN, -NO, -NO ２ , -C(O)R ２ａ 、-C(O)OR ２ａ 、-OC(O)R ２ａ 、-C(O)N(R ２ａ )(R ２ｂ )、-N(R ２ａ )C(O)R ２ｂ 、 -OC(O)N(R ２ａ )(R ２ｂ )、-N(R ２ａ )C(O)OR ２ｂ 、-C(=NR ２ａ )N(R ２ｂ )(R ２ｃ )、-N(R ２ａ )(R ２ｂ )、 -OR ２ａ 、-SR ２ａ 、-S(O)R ２ａ 、-S(O) ２ R ２ａ 、-S(O) ２ N(R ２ａ )(R ２ｂ )、-N(R ２ａ )S(O) ２ (R ２ｂ )、 -P(O)(R ２ａ ) (R ２ｂ ), -P(O)(OR ２ａ ) (R ２ｂ ), -P(O)(OR ２ａ ) (OR ２ｂ ), C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１２ Aryl, C １～６ Alkyl-C ６～１２ aryl, heterocycloalkyl, or heteroaryl, where each alkenyl or alkynyl is independently selected from 1 to 3 R ２ｄ groups, and each cycloalkyl is optionally substituted with 1 to 3 R ２ｅ groups, and each aryl is optionally substituted with 1 to 3 R ２ｆ groups, and each heterocycloalkyl is optionally substituted with 1 to 3 R ２ｇ groups, and each heteroaryl is optionally substituted with 1 to 3 R ２ｈ and optionally substituted with a group, Each R ２ａ , R ２ｂ , and R ２ｃ are independently hydrogen, C １～６ Alkyl, C １～６ Hydroxyalkyl, C ２～６ Alkoxyalkyl, C １～６ Haloalkyl, C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１２ Aryl, C １～６ Alkyl-C ６～１２ aryl, heterocycloalkyl, or heteroaryl; Or, R ２ａ , R ２ｂ , and R ２ｃ when attached to the same atom, can combine with the atom to which they are attached to form a heterocycloalkyl, Each R ２ｄ are independently —N(R ２ｄ１ ) (R ２ｄ２ ), -OR ２ｄ１ , C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１２ Aryl, C １～６ Alkyl-C ６～１２ aryl, heterocycloalkyl, or heteroaryl; Each R ２ｄ１ and R ２ｄ２ are independently hydrogen, C １～６ Alkyl, or —C(O)O—(C １～６ alkyl), Each R ２ｅ , R ２ｆ , R ２ｇ , and R ２ｈ are independently hydrogen, C １～６ Alkyl, C １～６ Alkoxy, halogen, C １～６ Haloalkyl or C １～６ haloalkoxy, R ３ is hydrogen, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Hydroxyalkyl, C １～６ Alkoxy, C ２～６ Alkoxyalkyl, halogen, C １～６ Haloalkyl, C １～６ Haloalkoxy, -CN, -NO, -NO ２ , -C(O)R ３ａ 、-C(O)OR ３ａ 、-OC(O)R ３ａ 、-C(O)N(R ３ａ )(R ３ｂ )、-N(R ３ａ )C(O)R ３ｂ 、 -OC(O)N(R ３ａ )(R ３ｂ )、-N(R ３ａ )C(O)OR ３ｂ 、-C(=NR ３ａ )N(R ３ｂ )(R ３ｃ )、-N(R ３ａ )(R ３ｂ )、 -OR ３ａ 、-SR ３ａ 、-S(O)R ３ａ 、-S(O) ２ R ３ａ 、-S(O) ２ N(R ３ａ )(R ３ｂ )、-N(R ３ａ )S(O) ２ (R ３ｂ )、 -P(O)(R ３ａ ) (R ３ｂ ), -P(O)(OR ３ａ ) (R ３ｂ ), -P(O)(OR ３ａ ) (OR ３ｂ ), C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１２ Aryl, C １～６ Alkyl-C ６～１２ aryl, heterocycloalkyl, or heteroaryl, where each alkenyl or alkynyl is independently selected from 1 to 3 R ３ｄ groups, and each cycloalkyl is optionally substituted with 1 to 3 R ３ｅ groups, and each aryl is optionally substituted with 1 to 3 R ３ｆ groups, and each heterocycloalkyl is optionally substituted with 1 to 3 R ３ｇ groups, and each heteroaryl is optionally substituted with 1 to 3 R ３ｈ and optionally substituted with a group, Each R ３ａ , R ３ｂ , and R ３ｃ are independently hydrogen, C １～６ Alkyl, C １～６ Hydroxyalkyl, C ２～６ Alkoxyalkyl, C １～６ Haloalkyl, C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１２ Aryl, C １～６ Alkyl-C ６～１２ aryl, heterocycloalkyl, or heteroaryl; Or, R ３ａ , R ３ｂ , and R ３ｃ when attached to the same atom, can combine with the atom to which they are attached to form a heterocycloalkyl, Each R ３ｄ are independently —N(R ３ｄ１ ) (R ３ｄ２ ), -OR ３ｄ１ , C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１２ Aryl, C １～６ Alkyl-C ６～１２ aryl, heterocycloalkyl, or heteroaryl; Each R ３ｄ１ and R ３ｄ２ are independently hydrogen, C １～６ Alkyl, or —C(O)O—(C １～６ alkyl), Each R ３ｅ , R ３ｆ , R ３ｇ , and R ３ｈ are independently hydrogen, C １～６ Alkyl, C １～６ Alkoxy, halogen, C １～６ haloalkyl, or C １～６ haloalkoxy, R ４ is hydrogen, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Alkoxy, halogen, C １～６ Haloalkyl, C １～６ haloalkoxy, or —CN; R ５ is hydrogen, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Hydroxyalkyl, C ２～６ Alkoxyalkyl, C １～６ Haloalkyl, C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１２ Aryl, C １～６ Alkyl-C ６～１２ Aryl, heterocycloalkyl, C １～６ alkyl-(heterocycloalkyl), heteroaryl, or C １～６ alkyl-(heteroaryl), where alkyl is R ５ａ and optionally substituted with R ５ａ is -OSi(R ５ａ１ ) (R ５ａ２ ) (R ５ａ３ ) and R ５ａ１ , R ５ａ２ , and R ５ａ３ are each independently C １～６ is alkyl, R ６ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ６～１２ aryl, or heteroaryl, wherein the aryl or heteroaryl is selected from 1 to 3 R ６ａ each optionally substituted with Each R ６ａ are independently １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Hydroxyalkyl, C １～６ Alkoxy, C ２～６ Alkoxyalkyl, halogen, C １～６ Haloalkyl, C １～６ haloalkoxy, —CN, -NO ２ 、-C(O)R ６ｂ 、-C(O)OR ６ｂ 、-OC(O)R ６ｂ 、-C(O)N(R ６ｂ )(R ６ｃ )、-N(R ６ｂ )C(O)R ６ｃ 、 -C(=NR ６ｂ )N(R ６ｃ )(R ６ｄ )、-N(R ６ｂ )(R ６ｃ )、-OR ６ｂ 、-SR ６ｂ 、-S(O)R ６ｂ 、-S(O) ２ R ６ｂ 、 -S(O) ２ N (R ６ｂ ) (R ６ｃ ), -N(R ６ｂ ) S (O) ２ (R ６ｃ ), C ３～１０ Cycloalkyl, C ６～１２ aryl, heterocycloalkyl, or heteroaryl, wherein the cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is selected from 1 to 3 R ６ｅ each optionally substituted with, and alkyl is R ６ｆ and optionally substituted with Or, R ５ and one R ６ａ together with the atom to which they are attached form a heterocycloalkyl, and 1 to 3 R ６ｇ and optionally substituted with Each R ６ｂ , R ６ｃ , and R ６ｄ are independently hydrogen, C １～６ Alkyl, C １～６ Hydroxyalkyl, C ２～６ Alkoxyalkyl, C １～６ Haloalkyl, C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１２ Aryl, C １～６ Alkyl-C ６～１２ aryl, heterocycloalkyl, or heteroaryl; Each R ６ｅ are independently １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Hydroxyalkyl, C １～６ Alkoxy, C ２～６ Alkoxyalkyl, halogen, C １～６ Haloalkyl, C １～６ haloalkoxy, —CN, -NO ２ 、-C(O)R ６ｅ１ 、-C(O)OR ６ｅ１ 、-OC(O)R ６ｅ１ 、-C(O)N(R ６ｅ１ )(R ６ｅ２ )、 -N(R ６ｅ１ )C(O)R ６ｅ２ 、-C(=NR ６ｅ１ )N(R ６ｅ２ )(R ６ｅ３ )、-N(R ６ｅ１ )(R ６ｅ２ )、-OR ６ｅ１ 、-SR ６ｅ１ 、 -S(O)R ６ｅ１ , -S(O) ２ R ６ｅ１ , -S(O) ２ N (R ６ｅ１ ) (R ６ｅ２ ), -N(R ６ｅ１ ) S (O) ２ (R ６ｅ２ ), C ３～１０ Cycloalkyl, C ６～１２ aryl, heterocycloalkyl, or heteroaryl, wherein the cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is selected from 1 to 3 R ６ｈ each optionally substituted with Each R ６ｅ１ , R ６ｅ２ , and R ６ｅ３ are independently hydrogen or C １～６ is alkyl, R ６ｆ is -OSi(R ６ｆ１ ) (R ６ｆ２ ) (R ６ｆ３ ) and R ６ｆ１ , R ６ｆ２ , and R ６ｆ３ are each independently C １～６ is alkyl, Each R ６ｇ are independently １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, halogen, C １～６ Haloalkyl, C １～６ haloalkoxy, or —CN; Each R ６ｈ are independently １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Alkoxy, halogen, C １～６ Haloalkyl, C １～６ Haloalkoxy, —C(O)R ６ｈ１ , -C(O)OR ６ｈ１ , -OC(O)R ６ｈ１ , -C(O)N(R ６ｈ１ )(R ６ｈ２ )、-N(R ６ｈ１ )C(O)R ６ｈ２ 、-C(=NR ６ｈ１ )N(R ６ｈ２ )(R ６ｈ３ )、 -N(R ６ｈ１ )(R ６ｈ２ ), -OH, -SR ６ｈ１ , -S(O)R ６ｈ１ , -S(O) ２ R ６ｈ１ , -S(O) ２ N(R ６ｈ１ )(R ６ｈ２ ), or -N(R ６ｈ１ ) S (O) ２ (R ６ｈ２ ) and Each R ６ｈ１ , R ６ｈ２ , and R ６ｈ３ are independently hydrogen or C １～６ is alkyl, R ７ is hydrogen, C １～６ Alkyl, halogen, C １～６ haloalkyl, —CN, or —OH; each heterocycloalkyl is a 3- to 10-membered ring having 1 to 4 heteroatoms, each independently N, O, or S; each heteroaryl is a 5-10 membered ring having 1-4 heteroatoms, each independently N, O, or S; However, R ５ and R ６ are both C １～４ Not alkyl, R ５ is hydrogen, R ６ The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein is not isopropyl or phenyl substituted with 2-Me.

3. During the ceremony, R ５ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Hydroxyalkyl, C ２～６ Alkoxyalkyl, C １～６ Haloalkyl, C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１２ aryl, C １～６ Alkyl-C ６～１２ Aryl, heterocycloalkyl, C １～６ alkyl-(heterocycloalkyl), heteroaryl, or C １～６ alkyl-(heteroaryl), where alkyl is R ５ａ and optionally substituted with R ６ is C ６～１２ aryl, or heteroaryl, wherein the aryl or heteroaryl is selected from 1 to 3 R ６ａ each optionally substituted with Or, R ５ and R ６ａ together with the atom to which they are attached form a heterocycloalkyl, and 1 to 3 R ６ｇ 3. The compound of claim 1 or 2, or a pharmaceutically acceptable salt thereof, optionally substituted with:

4. In the formula, R １ is hydrogen, C １～６ Alkyl, C １～６ Alkoxy, halogen, C １～６ The compound according to any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, which is haloalkyl, or -CN.

5. In the formula, R １ is hydrogen, C １～３ Alkyl, C １～３ The compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof, wherein R is alkoxy or halogen.

6. In the formula, R １ The compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, wherein - is hydrogen, Me, -OMe, F, or Cl.

7. In the formula, R １ The compound according to any one of claims 1 to 6, or a pharmaceutically acceptable salt thereof, wherein is hydrogen.

8. During the ceremony, R ２ is hydrogen, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Hydroxyalkyl, C １～６ Alkoxy, C ２～６ Alkoxyalkyl, halogen, C １～６ Haloalkyl, C １～６ Haloalkoxy, -CN, -NO, -NO ２ , -C(O)R ２ａ 、-C(O)OR ２ａ 、-OC(O)R ２ａ 、-C(O)N(R ２ａ )(R ２ｂ )、-N(R ２ａ )C(O)R ２ｂ 、 -OC(O)N(R ２ａ )(R ２ｂ )、-N(R ２ａ )C(O)OR ２ｂ 、-N(R ２ａ )(R ２ｂ )、-OR ２ａ 、 -S(O) ２ N (R ２ａ ) (R ２ｂ ), -N(R ２ａ ) S (O) ２ (R ２ｂ ), C ３～１０ cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１２ Aryl, C １～６ Alkyl-C ６～１２ aryl, a 3- to 8-membered heterocycloalkyl ring having 1-3 heteroatoms each independently being N, O, or S, or a 5- to 10-membered heteroaryl ring having 1-3 heteroatoms each independently being N, O, or S, wherein each alkenyl or alkynyl is independently selected from 1-3 R ２ｄ groups, and each aryl is optionally substituted with 1 to 3 R ２ｆ and optionally substituted with a group, Each R ２ａ and R ２ｂ are independently hydrogen, C １～６ Alkyl, C １～６ Hydroxyalkyl, C ２～６ Alkoxyalkyl, or C １～６ is haloalkyl, Each R ２ｄ are independently —N(R ２ｄ１ ) (R ２ｄ２ ), -OR ２ｄ１ , C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１２ Aryl, C １～６ Alkyl-C ６～１２ is aryl, Each R ２ｄ１ and R ２ｄ２ are independently hydrogen, C １～６ Alkyl, or —C(O)O—(C １～６ alkyl), Each R ２ｆ are independently hydrogen, C １～６ Alkyl, C １～６ The compound according to any one of claims 1 to 7, or a pharmaceutically acceptable salt thereof, wherein R is alkoxy or halogen.

9. During the ceremony, R ２ is hydrogen, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Hydroxyalkyl, C １～６ Alkoxy, C ２～６ Alkoxyalkyl, halogen, C １～６ Haloalkyl, —CN, —NO, —NO ２ , -C(O)R ２ａ 、-C(O)OR ２ａ 、-N(R ２ａ )C(O)R ２ｂ 、-N(R ２ａ )(R ２ｂ )、-OR ２ａ 、 -N(R ２ａ ) S (O) ２ (R ２ｂ ), C ３～１０ Cycloalkyl, C ６～１０ aryl, a 5-8 membered heterocycloalkyl ring having 1-2 heteroatoms each independently being N, O, or S, or a 5-6 membered heteroaryl ring having 1-3 heteroatoms each independently being N, O, or S, wherein each alkenyl or alkynyl is independently selected from 1-3 R ２ｄ groups, and each aryl is optionally substituted with 1 to 3 R ２ｆ and optionally substituted with a group, Each R ２ａ and R ２ｂ are independently hydrogen, C １～６ Alkyl, C １～６ Hydroxyalkyl, or C ２～６ is an alkoxyalkyl; Each R ２ｄ are independently —N(R ２ｄ１ ) (R ２ｄ２ ), -OR ２ｄ１ , C ３～１０ cycloalkyl, or C ６～１２ is aryl, Each R ２ｄ１ and R ２ｄ２ are independently hydrogen, C １～４ Alkyl, or —C(O)O—(C １～４ alkyl), Each R ２ｆ are independently １～６ The compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt thereof, which is alkoxy or halogen.

10. During the ceremony, R ２ is hydrogen, C １～３ Alkyl, C ２～３ Alkenyl, C ２～６ Alkynyl, C １～３ Hydroxyalkyl, C １～３ Alkoxy, C ２～３ Alkoxyalkyl, halogen, C １～３ Haloalkyl, —CN, —NO, —NO ２ , -C(O)R ２ａ , -C(O)OR ２ａ , -N(R ２ａ ) C(O)R ２ｂ , -N(R ２ａ ) (R ２ｂ ), -N(R ２ａ ) S (O) ２ (R ２ｂ ), C ３～６ cycloalkyl, phenyl, a 5- to 6-membered heterocycloalkyl ring having 1-2 heteroatoms each independently being N or O, or a 5- to 6-membered heteroaryl ring having 1-2 heteroatoms each independently being N, O, or S, wherein each alkenyl or alkynyl is independently selected from one R ２ｄ groups, and each phenyl is optionally substituted with one R ２ｆ and optionally substituted with a group, Each R ２ａ and R ２ｂ are independently hydrogen, C １～３ Alkyl, C １～３ Hydroxyalkyl, or C ２～３ is an alkoxyalkyl; Each R ２ｄ are independently —N(R ２ｄ１ ) (R ２ｄ２ ), -OR ２ｄ１ , C ３～８ cycloalkyl, or phenyl; Each R ２ｄ１ and R ２ｄ２ are independently hydrogen or —C(O)O—(C １～４ alkyl), Each R ２ｆ are independently １～３ The compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof, which is alkoxy or halogen.

11. During the ceremony, ( ２ は、Newspaper | ２ 、a||||||| ２ 、a|||||||||、|||| ２ The . ２ ﯨ、!C≡C||| ２ ( ２ . ２ 、!C≡!\H ２ ! ２ (3) ２ *|)、|| ２ !!、CH ２ ヨ ２ ヨ ２ !!. ２ ヨ ３ 、. ２ !!||| ２ 、!| ２ |||、||| ２ !!|||、|| ２ !*| ２ 、!| ２ ヨ ２ .................................... ３ 、!!!!!O ２ The ２ 、!\\e、N\e ２ 、!\H ２ ヨ ２ !!、!HHH ２ ヨ ２ ! ２ [||、!!HQ\\foQB4、BB ２ H ２ 、+]、S- ２ ||、シクロプロピル、 【Chemistry 2】 The compound according to any one of claims 1 to 10, or a pharmaceutically acceptable salt thereof, wherein:

12. During the ceremony, R ３ is hydrogen, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Hydroxyalkyl, C １～６ Alkoxy, C ２～６ Alkoxyalkyl, halogen, C １～６ Haloalkyl, C １～６ Haloalkoxy, -CN, -NO, -NO ２ , -C(O)R ３ａ 、-C(O)OR ３ａ 、-OC(O)R ３ａ 、-C(O)N(R ３ａ )(R ３ｂ )、-N(R ３ａ )C(O)R ３ｂ 、 -OC(O)N(R ３ａ )(R ３ｂ )、-N(R ３ａ )C(O)OR ３ｂ 、-N(R ３ａ )(R ３ｂ )、-OR ３ａ 、 -S(O) ２ N (R ３ａ ) (R ３ｂ ), -N(R ３ａ ) S (O) ２ (R ３ｂ ), C ３～１０ cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１２ Aryl, C １～６ Alkyl-C ６～１２ aryl, a 3- to 8-membered heterocycloalkyl ring having 1-3 heteroatoms each independently being N, O, or S, or a 5- to 10-membered heteroaryl ring having 1-3 heteroatoms each independently being N, O, or S, wherein each alkenyl or alkynyl is independently selected from 1-3 R ３ｄ groups, and each aryl is optionally substituted with 1 to 3 R ３ｆ and optionally substituted with a group, Each R ３ａ and R ３ｂ are independently hydrogen, C １～６ Alkyl, C １～６ Hydroxyalkyl, or C ２～６ is an alkoxyalkyl; Each R ３ｄ are independently —N(R ３ｄ１ ) (R ３ｄ２ ), -OR ３ｄ１ , C ３～１０ cycloalkyl, or C ６～１２ is aryl, Each R ３ｄ１ and R ３ｄ２ are independently hydrogen, C １～４ Alkyl, or —C(O)O—(C １～４ alkyl), Each R ３ｆ are independently １～６ The compound according to any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof, which is alkoxy or halogen.

13. During the ceremony, R ３ is hydrogen, C １～６ Alkyl, C １～６ Hydroxyalkyl, C １～６ Alkoxy, C ２～６ Alkoxyalkyl, halogen, C １～６ Haloalkyl, —CN, —NO ２ , -C(O)OR ３ａ , -C(O)N(R ３ａ ) (R ３ｂ ), -N(R ３ａ ) (R ３ｂ ), -N(R ３ａ ) S (O) ２ (R ３ｂ ), or a 5-6 membered heteroaryl ring having 1-3 heteroatoms, each independently N, O, or S; Each R ３ａ and R ３ｂ are independently hydrogen or C １～６ The compound according to any one of claims 1 to 12, or a pharmaceutically acceptable salt thereof, wherein R is alkyl.

14. During the ceremony, R ３ is hydrogen, C １～３ Alkyl, C １～３ Hydroxyalkyl, C １～３ Alkoxy, C ２～３ Alkoxyalkyl, halogen, C １～３ Haloalkyl, —CN, —NO ２ , -C(O)OR ３ａ , -C(O)N(R ３ａ ) (R ３ｂ ), -N(R ３ａ ) (R ３ｂ ), -N(R ３ａ ) S (O) ２ (R ３ｂ ), or a 5-6 membered heteroaryl ring having 1-2 heteroatoms, each of which is N; Each R ３ａ and R ３ｂ are independently hydrogen or C １～３ The compound according to any one of claims 1 to 13, or a pharmaceutically acceptable salt thereof, wherein R is alkyl.

15. During the ceremony, R ３ is hydrogen, Me, Et, -CH ２ OH, -OMe, -CH ２ OMe, F, Cl, Br, -CF ３ , -CN, -NO ２ , -COOMe、-CONH ２ , -NH ２ ,-NHSO ２ Me, again 【Chemistry 3】 The compound according to any one of claims 1 to 14, or a pharmaceutically acceptable salt thereof, wherein:

16. During the ceremony, R ３ is hydrogen, C １～６ Alkyl, C １～６ Hydroxyalkyl, C １～６ Alkoxy, C ２～６ Alkoxyalkyl, halogen, -CN, -NO ２ , -C(O)OR ３ａ , -C(O)N(R ３ａ ) (R ３ｂ ), -N(R ３ａ ) (R ３ｂ ), -N(R ３ａ ) S (O) ２ (R ３ｂ ), or a 5-6 membered heteroaryl ring having 1-3 heteroatoms, each independently N, O, or S; Each R ３ａ and R ３ｂ are independently hydrogen or C １～６ The compound according to any one of claims 1 to 12, or a pharmaceutically acceptable salt thereof, wherein R is alkyl.

17. During the ceremony, R ３ is hydrogen, C １～３ Alkyl, C １～３ Hydroxyalkyl, C １～３ Alkoxy, C ２～３ Alkoxyalkyl, halogen, -CN, -NO ２ , -C(O)OR ３ａ , -C(O)N(R ３ａ ) (R ３ｂ ), -N(R ３ａ ) (R ３ｂ ), -N(R ３ａ ) S (O) ２ (R ３ｂ ), or a 5-6 membered heteroaryl ring having 1-2 heteroatoms, each of which is N; Each R ３ａ and R ３ｂ are independently hydrogen or C １～３ The compound according to any one of claims 1 to 16, or a pharmaceutically acceptable salt thereof, which is alkyl.

18. During the ceremony, R ３ is hydrogen, Me, Et, -CH ２ OH, -OMe, -CH ２ OMe, F, Cl, Br, -CN, -NO ２ , -COOMe、-CONH ２ , -NH ２ ,-NHSO ２ Me, and は, 【Chemistry 4】 18. The compound according to any one of claims 1 to 17, or a pharmaceutically acceptable salt thereof, wherein:

19. In the formula, R ４ is hydrogen, C １～６ Alkyl, C １～６ Alkoxy, halogen, C １～６ The compound according to any one of claims 1 to 18, or a pharmaceutically acceptable salt thereof, which is haloalkyl, or -CN.

20. In the formula, R ４ is hydrogen, C １～６ 20. The compound according to any one of claims 1 to 19, or a pharmaceutically acceptable salt thereof, wherein R is alkyl, or halogen.

21. In the formula, R ４ The compound according to any one of claims 1 to 20, or a pharmaceutically acceptable salt thereof, wherein is hydrogen, Me, F, Cl, or Br.

22. In the formula, R ４ The compound according to any one of claims 1 to 21, or a pharmaceutically acceptable salt thereof, wherein is hydrogen.

23. During the ceremony, R １ is hydrogen, R ２ is hydrogen, C １～３ Alkyl, C ２～３ Alkenyl, C ２～６ Alkynyl, C １～３ hydroxyalkyl, C ２～３ Alkoxyalkyl, halogen, -CN, -NO, -NO ２ , -C(O)R ２ａ , -N(R ２ａ ) C(O)R ２ｂ , -N(R ２ａ ) (R ２ｂ ), -OR ２ａ or a 5-6 membered heteroaryl ring having 1-2 heteroatoms, each independently N, O, or S; R ２ａ and R ２ｂ are each independently hydrogen or C １～３ is alkyl, R ３ is hydrogen, C １～３ Alkyl, halogen, —CN or —NO ２ and R ４ The compound according to any one of claims 1 to 22, or a pharmaceutically acceptable salt thereof, wherein is hydrogen.

24. During the ceremony, R １ is hydrogen, R ２ is hydrogen, C １～３ Alkyl, C ２～３ Alkenyl, C ２～６ Alkynyl, C １～３ hydroxyalkyl, C ２～３ Alkoxyalkyl, halogen, -CN, -NO, -NO ２ , -C(O)R ２ａ , -N(R ２ａ ) C(O)R ２ｂ , -N(R ２ａ ) (R ２ｂ ), -OR ２ａ or a 5-6 membered heteroaryl ring having 1-2 heteroatoms, each independently N, O, or S; R ２ａ and R ２ｂ are each independently hydrogen or C １～３ is alkyl, R ３ is hydrogen, R ４ The compound according to any one of claims 1 to 22, or a pharmaceutically acceptable salt thereof, wherein is hydrogen.

25. During the ceremony, R ５ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Hydroxyalkyl, C ２～６ Alkoxyalkyl, C １～６ Haloalkyl, C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１２ Aryl, C １～６ Alkyl-C ６～１２ Aryl, C １～６ alkyl-(heterocycloalkyl), or C １～６ alkyl-(heteroaryl), where alkyl is R ５ａ and optionally substituted with R ５ａ is -OSi(R ５ａ１ ) (R ５ａ２ ) (R ５ａ３ ) and R ５ａ１ , R ５ａ２ , and R ５ａ３ are each independently C １～４ is alkyl, heterocycloalkyl is a 5-8 membered ring having 1-2 heteroatoms, each independently N, O, or S; 25. The compound according to any one of claims 1 to 24, or a pharmaceutically acceptable salt thereof, wherein heteroaryl is a 5- to 6-membered ring having 1 to 2 heteroatoms, each independently being N, O, or S.

26. During the ceremony, R ５ is C １～６ Alkyl, C ２～６ Alkynyl, C ２～６ Alkoxyalkyl, C １～６ Haloalkyl, C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１２ Aryl, C １～６ Alkyl-C ６～１２ Aryl, or C １～６ alkyl-(heterocycloalkyl), where alkyl is R ５ａ and optionally substituted with R ５ａ is -OSi(R ５ａ１ ) (R ５ａ２ ) (R ５ａ３ ) and R ５ａ１ , R ５ａ２ , and R ５ａ３ are each independently C １～４ alkyl, where R ５ａ１ and R ５ａ２ are different, 26. The compound of any one of claims 1 to 25, or a pharmaceutically acceptable salt thereof, wherein the heterocycloalkyl is a 5- to 6-membered ring having 1 to 2 heteroatoms, each independently being N or O.

27. During the ceremony, R ５ is C １～６ Alkyl, C ２～６ Alkynyl, C ２～３ Alkoxyalkyl, C １～３ Haloalkyl, C ３～８ Cycloalkyl, C １～３ Alkyl-C ３～８ Cycloalkyl, phenyl, C １～３ alkyl-phenyl, or C １～３ alkyl-(heterocycloalkyl), where alkyl is R ５ａ and optionally substituted with R ５ａ is -OSi(R ５ａ１ ) (R ５ａ２ ) (R ５ａ３ ) and R ５ａ１ , R ５ａ２ , and R ５ａ３ are each independently Me or tBu, ５ａ１ and R ５ａ２ are different, 26. The compound of any one of claims 1 to 25, wherein the heterocycloalkyl is a 6-membered ring having one heteroatom which is N or O, or a pharmaceutically acceptable salt thereof.

28. During the ceremony, 2 ５ . ２ 3ｭe ３ 、-32 ２ C≡CMe、-CH ２ 38 ２ C≡CH、-CH ２ 38 ２ 9e、 -CH ２ CH ２ OSi(Me) ２ (tBu)、CF ３ 、-CH ２ CF ２ H、-CH ２ CF ３ 、 【Chemistry 5】 27. The compound according to any one of claims 1 to 26, or a pharmaceutically acceptable salt thereof, wherein:

29. During the ceremony, R ５ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Hydroxyalkyl, C ２～６ Alkoxyalkyl, C １～６ Haloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１２ Aryl, C １～６ Alkyl-C ６～１２ Aryl, C １～６ alkyl-(heterocycloalkyl), or C １～６ alkyl-(heteroaryl), where alkyl is R ５ａ and optionally substituted with R ５ａ is -OSi(R ５ａ１ ) (R ５ａ２ ) (R ５ａ３ ) and R ５ａ１ , R ５ａ２ , and R ５ａ３ are each independently C １～４ is alkyl, heterocycloalkyl is a 5-8 membered ring having 1-2 heteroatoms, each independently N, O, or S; 25. The compound according to any one of claims 1 to 24, or a pharmaceutically acceptable salt thereof, wherein heteroaryl is a 5- to 6-membered ring having 1 to 2 heteroatoms, each independently being N, O, or S.

30. During the ceremony, R ５ is C １～６ Alkyl, C ２～６ Alkynyl, C ２～６ Alkoxyalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１２ Aryl, C １～６ Alkyl-C ６～１２ Aryl, or C １～６ alkyl-(heterocycloalkyl), where alkyl is R ５ａ and optionally substituted with R ５ａ is -OSi(R ５ａ１ ) (R ５ａ２ ) (R ５ａ３ ) and R ５ａ１ , R ５ａ２ , and R ５ａ３ are each independently C １～４ alkyl, where R ５ａ１ and R ５ａ２ are different, 25. The compound of any one of claims 1 to 24, or a pharmaceutically acceptable salt thereof, wherein the heterocycloalkyl is a 5- to 6-membered ring having 1 to 2 heteroatoms, each independently being N or O.

31. During the ceremony, R ５ is C １～６ Alkyl, C ２～６ Alkynyl, C ２～３ Alkoxyalkyl, C １～３ Alkyl-C ３～８ Cycloalkyl, phenyl, C １～３ alkyl-phenyl, or C １～３ alkyl-(heterocycloalkyl), where alkyl is R ５ａ and optionally substituted with R ５ａ is -OSi(R ５ａ１ ) (R ５ａ２ ) (R ５ａ３ ) and R ５ａ１ , R ５ａ２ , and R ５ａ３ are each independently Me or tBu, ５ａ１ and R ５ａ２ are different, 25. The compound of any one of claims 1 to 24, wherein the heterocycloalkyl is a 6-membered ring having one heteroatom which is N or O, or a pharmaceutically acceptable salt thereof.

32. During the ceremony, 2 ５ . ２ 3ｭe ３ 、-32 ２ C≡CMe、-CH ２ 38 ２ C≡CH、-CH ２ 38 ２ 9e、 -CH ２ CH ２ OSi(Me) ２ (tBu)、 【Chemistry 6】 25. The compound according to any one of claims 1 to 24, wherein:

33. During the ceremony, R ６ is phenyl, naphthyl, thienyl, thiazolyl, pyridyl, pyrazinyl, pyrimidinyl, or dibenzofuryl, and one or two R ６ａ or a pharmaceutically acceptable salt thereof, wherein each of the following is optionally substituted:

34. During the ceremony, R ６ is a phenyl or a 5- to 6-membered heteroaryl ring having 1 to 3 heteroatoms, each independently N, O, or S, and one or two R ６ａ or a pharmaceutically acceptable salt thereof, wherein each of the following is optionally substituted:

35. During the ceremony, R ６ is phenyl, thienyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyrrolyl, pyrazolyl, pyridyl, or pyrimidinyl, and one or two R ６ａ or a pharmaceutically acceptable salt thereof, each of which is optionally substituted with

36. In the formula, R ６ teeth, 【Chemistry 7】 34. The compound according to any one of claims 1 to 33, or a pharmaceutically acceptable salt thereof, wherein:

37. In the formula, R ６ teeth, 【Chemistry 8】 34. The compound according to any one of claims 1 to 33, or a pharmaceutically acceptable salt thereof, wherein:

38. In the formula, R ７ is hydrogen, Me, Et, OMe, -CH ２ OH, -CH ２ OMe, -CH ２ NMe ２ , Cl, CHF ２ , OH, NH ２ , SMe, or 【Chemistry 9】 37. The compound according to any one of claims 1 to 36, or a pharmaceutically acceptable salt thereof, wherein:

39. In the formula, R ７ is hydrogen, Me, Et, OMe, -CH ２ NMe ２ , Cl, OH, NH ２ , SMe, or 【Chemistry 10】 37. The compound according to any one of claims 1 to 36, or a pharmaceutically acceptable salt thereof, wherein:

40. having the formula (IIa): 【Chemistry 11】 40. The compound according to any one of claims 1 to 39, wherein n is 0, 1, 2, or 3, or a pharmaceutically acceptable salt thereof.

41. The compound according to any one of claims 1 to 39, having the formula (I-1), or a pharmaceutically acceptable salt thereof: 【Chemistry 12】

42. 40. The compound of claims 1 to 39, having the formula (IIa-1): or a pharmaceutically acceptable salt thereof. 【Chemistry 13】

43. During the ceremony, Each R ６ａ are independently １～６ Alkyl, C ２～６ Alkynyl, C １～６ Hydroxyalkyl, C １～６ Alkoxy, C ２～６ Alkoxyalkyl, halogen, C １～６ Haloalkyl, C １～６ Haloalkoxy, —CN, —NO ２ , -C(O)R ６ｂ , -C(O)OR ６ｂ , -C(O)N(R ６ｂ ) (R ６ｃ ), -N(R ６ｂ ) (R ６ｃ ), -OR ６ｂ , C ３～１０ Cycloalkyl, C ６～１２ aryl, heterocycloalkyl, or heteroaryl, wherein the cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is selected from 1 to 3 R ６ｅ each optionally substituted with, and alkyl is R ６ｆ and optionally substituted with Each R ６ｂ and R ６ｃ are independently hydrogen or C １～６ is alkyl, Each R ６ｅ are independently １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Hydroxyalkyl, C １～６ Alkoxy, C ２～６ Alkoxyalkyl, halogen, C １～６ Haloalkyl, —C(O)OR ６ｅ１ , -OC(O)R ６ｅ１ , -C(O)N(R ６ｅ１ )(R ６ｅ２ )、-N(R ６ｅ１ )C(O)R ６ｅ２ 、-OR ６ｅ１ 、-S(O) ２ N(R ６ｅ１ )(R ６ｅ２ )、 -N(R ６ｅ１ ) S (O) ２ (R ６ｅ２ ) and Each R ６ｅ１ and R ６ｅ２ are independently hydrogen or C １～６ is alkyl, R ６ｆ is -OSi(R ６ｆ１ ) (R ６ｆ２ ) (R ６ｆ３ ) and R ６ｆ１ , R ６ｆ２ , and R ６ｆ３ are each independently C １～６ 43. The compound of any one of claims 1 to 42, or a pharmaceutically acceptable salt thereof, which is alkyl.

44. During the ceremony, Each R ６ａ are independently １～３ Alkyl, C ２～３ Alkynyl, C １～３ Hydroxyalkyl, C １～３ Alkoxy, C ２～３ Alkoxyalkyl, halogen, C １～３ Haloalkyl, C １～３ Haloalkoxy, —CN, —NO ２ , -C(O)R ６ｂ , -C(O)OR ６ｂ , -C(O)N(R ６ｂ ) (R ６ｃ ), -N(R ６ｂ ) (R ６ｃ ), -OR ６ｂ , C ３～８ cycloalkyl, phenyl, a 5- to 6-membered heterocycloalkyl ring having 1-2 heteroatoms each independently being N or O, or a 5- to 6-membered heteroaryl ring having 1-2 heteroatoms each independently being N, O, or S, wherein the cycloalkyl, phenyl, heterocycloalkyl, or heteroaryl is selected from the group consisting of 1-2 R ６ｅ and alkyl is R ６ｆ and optionally substituted with Each R ６ｂ and R ６ｃ are independently hydrogen or C １～３ is alkyl, Each R ６ｅ are independently １～６ Alkyl, C １～６ Hydroxyalkyl, C １～６ Alkoxy, C ２～６ Alkoxyalkyl, halogen, C １～６ Haloalkyl, —C(O)OR ６ｅ１ , -OC(O)R ６ｅ１ , -N(R ６ｅ１ ) C(O)R ６ｅ２ , -OR ６ｅ１ and Each R ６ｅ１ and R ６ｅ２ are independently hydrogen or C １～６ is alkyl, R ６ｆ is -OSi(R ６ｆ１ ) (R ６ｆ２ ) (R ６ｆ３ ) and R ６ｆ１ , R ６ｆ２ , and R ６ｆ３ The compound according to any one of claims 1 to 43, or a pharmaceutically acceptable salt thereof, wherein each of

45. During the ceremony, Each R ６ｅ are independently １～６ Alkyl, C １～３ Alkoxy, halogen, C １～６ haloalkyl, -N(R ６ｅ１ ) C(O)R ６ｅ２ , or -OR ６ｅ１ and Each R ６ｅ１ and R ６ｅ２ are independently hydrogen or C １～３ 45. The compound of any one of claims 1 to 44, or a pharmaceutically acceptable salt thereof, which is alkyl.

46. In the formula, each R ６ｎ are independently Me or CO ２ 43. The compound of any one of claims 1 to 42, or a pharmaceutically acceptable salt thereof, which is tBu.

47. In the formula, each R ６ｈ are independently Me, —CH ２ OH, -CH ２ NHMe, OMe, NH ２ , C.F. ３ , CN, -(CO)Me, -(CO)tBu, -(CO)-CH ２ OH, CO ２ Me, CO ２ tBu, =O, or 【Chemistry 14】 43. The compound according to any one of claims 1 to 42, or a pharmaceutically acceptable salt thereof, wherein:

48. In the formula, each R ６ｍ are independently OH, CF ３ , C.N., C.O. ２ H, CONH ２ , NMe ２ , S.O. ２ Me, or 【Chemistry 15】 43. The compound according to any one of claims 1 to 42, or a pharmaceutically acceptable salt thereof, wherein:

49. During the ceremony, Each ６ｅ は、independently、Me、Et、iPr、tBu、-CH ２ OH、-C (OH)Me ２ 、-OMe、-OEt、-OCH ２ CH ２ CH ３ ,-CH ２ OME, -OCH ２ CH ２ NME ２ 、F、*-、Br、CHF ２ ,-CF ３ ,-CH ２ CHF ２ ,-CH ２ CF ３ ,-CF ２ CH ３ , -C (CH) ３ ) ２ CF ３ ,OCF ３ ,-OCH ２ CF ３ , -OCH (CH ３ )CF ３ 、&N、-C(O)Me、-C(O)tB5、CO ２ H, CO ２ Me, CO ２ tBu、C(O)NH ２ ,=O, OH, NH ２ ,NMe ２ ,-NMeCH ２ CH ２ OMe、-NFC(O)Me、-NFC(O)~B--NGA ２ tBu, SO ２ Me, SO ２ Et, SO ２ (iPr), SO ２ (iBu), SO ２ CF ３ ,-CH ２ SO ２ Me、SO(N=H)Me、SO ２ NH ２ ,SO ２ NHMe, SO ２ NME ２ ,-E ２ NHCHH ２ CH ２ OH, -NHSO ２ Me、SF ５ 、-POMe ２ 、 【Chemistry 16】 43. The compound according to any one of claims 1 to 42, or a pharmaceutically acceptable salt thereof, wherein:

50. During the ceremony, Each ６ｅ は、independently、Me、Et、iPr、tBu、-CH ２ OH、-C (OH)Me ２ 、-OMe、-OEt、-OCH ２ CH ２ CH ３ ,-CH ２ OME, -OCH ２ CH ２ NME ２ 、F、*-、Br、CHF ２ ,-CF ３ ,-CH ２ CHF ２ ,-CH ２ CF ３ ,-CF ２ CH ３ , -C (CH) ３ ) ２ CF ３ ,OCF ３ ,-OCH ２ CF ３ , -OCH (CH ３ )CF ３ 、&N、-C(O)Me、-C(O)tB5、CO ２ H, CO ２ Me, CO ２ tBu、C(O)NH ２ ,=O, OH, NH ２ ,NMe ２ ,-NMeCH ２ CH ２ OMe、-NFC(O)Me、-NFC(O)~B--NGA ２ tBu, SO ２ Me, SO ２ Et, SO ２ (iPr), SO ２ (iBu), SO ２ CF ３ ,-CH ２ SO ２ Me、SO(N=H)Me、SO ２ NH ２ ,SO ２ NHMe, SO ２ NME ２ ,-E ２ NHCHH ２ CH ２ OH, -NHSO ２ Me、SF ５ 、-POMe ２ 、 【Chemistry 17】 43. The compound according to any one of claims 1 to 42, or a pharmaceutically acceptable salt thereof, wherein:

51. During the ceremony, Each R ６ｅ are independently Me, Et, tBu, -OMe, F, Cl, -CF ３ , -NHC(O)Me, or -OH, or a pharmaceutically acceptable salt thereof.

52. In the formula, each R ６ｊ are independently OH, OMe, CH ２ OMe, F, CHF ２ , C.F. ３ , C.N., N.H. ２ , NH(CO)CF ３ ,NH(CO)OtBu,SO ２ Me, Si (iPr) ３ , 【Chemistry 18】 43. The compound according to any one of claims 1 to 42, or a pharmaceutically acceptable salt thereof, wherein:

53. In the formula, each R ６ｊ are independently OH, OMe, F, CHF ２ , C.F. ３ , N.H. ２ ,NH(CO)OtBu,SO ２ Me, Si (iPr) ３ , 【Chemistry 19】 43. The compound according to any one of claims 1 to 42, or a pharmaceutically acceptable salt thereof, wherein:

54. In the formula, each R ６ｐ are independently Me, Et, iPr, F, Cl, CH ２ F, CHF ２ , C.F. ３ , C.F. ２ CH ３ , C.H. ２ CF ３ 43. The compound of any one of claims 1 to 42, or a pharmaceutically acceptable salt thereof, wherein R is ═O, ═O, or OH.

55. In the formula, each R ６ｐ are independently Me, Cl, CF ３ 43. The compound of any one of claims 1 to 42, or a pharmaceutically acceptable salt thereof, wherein R is ═O, ═O, or OH.

56. During the ceremony, Each R ６ａ is, independently, 【Chemistry 20】 【Chemical 21】 【Chemical 22】 【Chemical 23】 【Chemistry 24】 43. The compound according to any one of claims 1 to 42, or a pharmaceutically acceptable salt thereof, wherein:

57. During the ceremony, Each R ６ａ are independently Me, Et, —C≡CMe, —OMe, —CH ２ OH, -CH ２ OMe, -CH ２ OSi(Me) ２ (tBu)、F、Cl、Br、I、-CH ２ F、-CF ３ 、-OCF ３ 、-CN、-NO ２ 、-C(O)H、 -COOH, -COOMe, -CONH ２ , -NH ２ , —OH, cyclopropyl, cyclohexyl, phenyl, 【Chemistry 25】 45. The compound according to any one of claims 1 to 44, or a pharmaceutically acceptable salt thereof, wherein:

58. During the ceremony, R ５ is C １～６ Alkyl, C ２～６ Alkynyl, C ２～３ Alkoxyalkyl, C １～３ Alkyl-C ３～８ Cycloalkyl, phenyl, C １～３ alkyl-phenyl, or C １～３ alkyl-(heterocycloalkyl), R ６ is phenyl, and R ６ａ and optionally substituted with R ６ａ are independently １～３ Alkyl, C ２～３ Alkynyl, C １～３ Hydroxyalkyl, C １～３ Alkoxy, C ２～３ Alkoxyalkyl, halogen, C １～３ Haloalkyl, C １～３ Haloalkoxy, —CN, —NO ２ , -C(O)R ６ｂ , -C(O)OR ６ｂ , -C(O)N(R ６ｂ ) (R ６ｃ ), -N(R ６ｂ ) (R ６ｃ ), —OH, or phenyl, where phenyl is R ６ｅ and optionally substituted with R ６ｂ and R ６ｃ are each independently hydrogen or C １～３ is alkyl, R ６ｅ is C １～６ Alkyl, halogen, C １～３ haloalkyl, —N(R ６ｅ１ ) C(O)R ６ｅ２ , or -OR ６ｅ１ and R ６ｅ１ and R ６ｅ２ are independently hydrogen or C １～３ is alkyl, 58. The compound of any one of claims 1 to 57, or a pharmaceutically acceptable salt thereof, wherein the heterocycloalkyl is a 6-membered ring having one heteroatom which is N or O.

59. having the formula (Ib): 【Chemical 26】 59. The compound according to any one of claims 1 to 58, wherein m is 0, 1, 2, or 3, or a pharmaceutically acceptable salt thereof.

60. In the formula, R ６ teeth, 【Chemical 27】 【Chemical Formula 28】 【Chemical 29】 【Chemistry 30】 【Chemical 31】 【Chemical 32】 【Chemical 33】 【Chemical 34】 【Chemistry 35】 【Chemical 36】 【Chemical 37】 59. The compound according to any one of claims 1 to 58, or a pharmaceutically acceptable salt thereof, wherein:

61. In the formula, R ６ teeth, 【Chemical Formula 38】 【Chemical 39】 42. The compound according to any one of claims 1 to 41, or a pharmaceutically acceptable salt thereof, wherein:

62. having the formula (Ic): 【Chemistry 40】 During the ceremony, Ring A is a 5-8 membered heterocycloalkyl optionally having 1-2 additional heteroatoms, each independently N, O, or S; optionally, wherein Ring A is selected from the group consisting of 1 or 2 R ６ｇ is replaced by 25. The compound according to any one of claims 1 to 24, or a pharmaceutically acceptable salt thereof, wherein n is 0, 1, or 2.

63. In the formula, each R ６ｇ The compound according to any one of claims 1 to 24, or a pharmaceutically acceptable salt thereof, wherein is methyl.

64. having the structure of formula (IIc): 【Chemistry 41】 During the ceremony, Ring A is a 5-8 membered heterocycloalkyl optionally having 1-2 additional heteroatoms, each independently N, O, or S; optionally, wherein Ring A is selected from the group consisting of 1 or 2 R ６ｇ is replaced by 40. The compound according to any one of claims 1 to 24, 33 to 35, and 38, wherein n is 0, 1, or 2, or a pharmaceutically acceptable salt thereof.

65. During the ceremony, R １ is hydrogen, C １～３ alkyl, or halogen; R ２ is hydrogen, C １～３ Alkyl, C １～３ Hydroxyalkyl, C ２～３ alkoxyalkyl, halogen, or —CN; R ３ is hydrogen, C １～３ alkyl, or halogen; R ４ is hydrogen, C １～３ alkyl, or halogen; Each R ６ａ are independently １～３ Alkyl, C ２～３ Alkenyl, or C ２～３ alkynyl, wherein the alkynyl is selected from 1 to 3 R ６ｊ and optionally substituted with Each R ６ｊ are independently ２～３ Alkoxyalkyl, halogen, C １～３ Haloalkyl, C １～３ Haloalkoxy, -CN, C ３～８ cycloalkyl, or heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is selected from 1 to 3 R ６ｐ and optionally substituted with Each R ６ｐ are independently １～３ Alkyl, C １～３ Hydroxyalkyl, C ２～３ Alkoxyalkyl, halogen, C １～３ Haloalkyl, C １～３ haloalkoxy, or —CN; R ７ is hydrogen, C １～３ Alkyl, C ２～３ Alkoxyalkyl, C １～３ Haloalkyl, or —NH ２ 65. The compound of claim 64, wherein:

66. During the ceremony, R １ 66. The compound of claim 64 or 65, wherein is hydrogen or halogen.

67. During the ceremony, R １ is hydrogen or F.

68. During the ceremony, R ４ is hydrogen, C １～３ 67. The compound of any one of claims 64 to 66, wherein the aryl group is alkyl or halogen.

69. During the ceremony, R ４ is hydrogen, Me, or F.

70. having the structure of formula (IIc-1): 【Chemistry 42】 During the ceremony, Ring A is a 5-8 membered heterocycloalkyl optionally having 1-2 additional heteroatoms, each independently N, O, or S; optionally, wherein Ring A is selected from the group consisting of 1 or 2 R ６ｇ is replaced by 40. The compound according to any one of claims 1 to 24, 33 to 35, and 38, wherein n is 0, 1, or 2, or a pharmaceutically acceptable salt thereof.

71. During the ceremony, 【Chemistry 43】 but, 【Chemical Formula 44】 71. The compound of any one of claims 62 and 64 to 70, having the structure: or a pharmaceutically acceptable salt thereof.

72. having the structure of formula (IIc-2): 【Chemistry 45】 40. The compound according to any one of claims 1 to 24, 33 to 35, and 38, wherein n is 0, 1, or 2, or a pharmaceutically acceptable salt thereof.

73. During the ceremony, 【Chemistry 46】 but, 【Chemistry 47】 【Chemistry 48】 71. The compound according to any one of claims 1 to 24 and 62 to 70, having the structure: or a pharmaceutically acceptable salt thereof.

74. During the ceremony, 【Chemistry 49】 but, 【Chemistry 50】 The compound according to any one of claims 1 to 24, having the structure: or a pharmaceutically acceptable salt thereof.

75. During the ceremony, R ２ is hydrogen, C １～３ Alkyl, C １～３ Hydroxyalkyl, C ２～３ alkoxyalkyl, halogen, or —CN; R ３ is hydrogen, C １～３ alkyl, or halogen; Each R ６ａ are independently １～３ Alkyl, C ２～３ Alkenyl, or C ２～３ alkynyl, wherein the alkynyl is selected from 1 to 3 R ６ｊ and optionally substituted with Each R ６ｊ are independently ２～３ Alkoxyalkyl, halogen, C １～３ Haloalkyl, C １～３ Haloalkoxy, -CN, C ３～８ cycloalkyl, or heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is selected from 1 to 3 R ６ｐ and optionally substituted with Each R ６ｐ are independently １～３ Alkyl, C １～３ Hydroxyalkyl, C ２～３ Alkoxyalkyl, halogen, C １～３ Haloalkyl, C １～３ haloalkoxy, or —CN; R ７ is hydrogen or C １～３ is alkyl, 【Chemistry 51】 but, 【Chemistry 52】 71. The compound of claim 64 or 70, having the structure: or a pharmaceutically acceptable salt thereof.

76. In the formula, R ２ 76. The compound of claim 75, or a pharmaceutically acceptable salt thereof, wherein is hydrogen, halogen, or -CN.

77. In the formula, R ２ 77. The compound of claim 75 or 76, or a pharmaceutically acceptable salt thereof, wherein is hydrogen, F, or Cl.

78. In the formula, R ３ 78. The compound according to any one of claims 75 to 77, or a pharmaceutically acceptable salt thereof, wherein is hydrogen, F, or Cl.

79. In the formula, each R ６ａ are independently ２～３ alkynyl or halogen, where alkynyl is selected from 1 to 3 R ６ｊ 79. The compound of any one of claims 75 to 78, or a pharmaceutically acceptable salt thereof, optionally substituted with:

80. In the formula, each R ６ａ teeth, 【Chemistry 53】 1 R ６ｊ 80. The compound of any one of claims 75 to 79, or a pharmaceutically acceptable salt thereof, substituted with:

81. In the formula, each R ６ｊ are independently ２～３ Alkoxyalkyl, halogen, C １～３ Haloalkyl, -CN, C ３～６ cycloalkyl, or heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is selected from 1 to 3 R ６ｐ and each heterocycloalkyl is a 3-6 membered ring having 1-2 heteroatoms which are each independently N, O, or S; or a pharmaceutically acceptable salt thereof.

82. In the formula, each R ６ｊ are independently halogen, C １～３ Haloalkyl, C ３～６ cycloalkyl, or heterocycloalkyl, wherein the cycloalkyl or heterocycloalkyl is selected from 1 to 2 R ６ｐ and each heterocycloalkyl is a 3-6 membered ring having 1-2 heteroatoms which are each independently N, O, or S; or a pharmaceutically acceptable salt thereof.

83. In the formula, each R ６ｊ are independently halogen, C １～３ haloalkyl, or C ３～６ cycloalkyl, where cycloalkyl is one R ６ｐ 83. The compound of any one of claims 75 to 82, or a pharmaceutically acceptable salt thereof, optionally substituted with:

84. In the formula, each R ６ｊ are independently F, CH ２ F, CHF ２ , C.F. ３ , C.H. ２ CF ３ , C.F. ２ CH ３ or cyclopropyl, where cyclopropyl is selected from one R ６ｐ 84. The compound of any one of claims 75 to 83, or a pharmaceutically acceptable salt thereof, optionally substituted with:

85. In the formula, each R ６ｐ are independently １～３ Alkyl, C １～３ Hydroxyalkoxy, halogen, C １～３ 85. The compound of any one of claims 75 to 84, or a pharmaceutically acceptable salt thereof, which is haloalkyl, or -CN.

86. In the formula, each R ６ｐ are independently Me, Et, CH ２ OH, F, CH ２ F, CHF ２ , C.F. ３ , C.H. ２ CF ３ , C.F. ２ CH ３ 86. The compound according to any one of claims 75 to 85, or a pharmaceutically acceptable salt thereof, wherein:

87. During the ceremony, 【Chemical 54】 but, 【Chemistry 55】 87. The compound of any one of claims 75 to 86, having the structure: or a pharmaceutically acceptable salt thereof.

88. 75. The compound of any one of claims 1 to 74, having the structure of a compound in Table 1A, Table 1B, Table 1C, Table 1D, Table 1E, Table 1F, Table 1G, Table 1H, Table 1I, Table 1J, Table 2A, Table 2B, Table 2C, Table 2D, Table 2E, Table 2F, Table 2G, Table 2H, Table 2I, Table 2J, Table 2K, Table 2L, Table 3A, Table 3B, Table 3C, Table 3D, Table 3E, Table 3F, Table 3G, Table 3H, Table 3I, Table 3J, or Table 3K, or a pharmaceutically acceptable salt thereof.

89. 89. The compound of any one of claims 1 to 88, having the structure: or a pharmaceutically acceptable salt thereof. 【Chemical Formula 56】

90. 89. The compound of any one of claims 1 to 88, having the structure: 【Chemical 57】

91. 89. The compound of any one of claims 1 to 88, having the structure: or a pharmaceutically acceptable salt thereof. 【Chemistry 58】

92. 89. The compound of any one of claims 1 to 88, having the structure: 【Chemical 59】

93. 89. The compound of any one of claims 1 to 88, having the structure: or a pharmaceutically acceptable salt thereof. 【Chemistry 60】

94. 89. The compound of any one of claims 1 to 88, having the structure: 【Hua 61】

95. 89. The compound of any one of claims 1 to 88, having the structure: or a pharmaceutically acceptable salt thereof. 【Hua 62】

96. 89. The compound of any one of claims 1 to 88, having the structure: 【Chemistry 63】

97. 89. The compound of any one of claims 1 to 88, having the structure: or a pharmaceutically acceptable salt thereof. 【Hua 64】

98. 89. The compound of any one of claims 1 to 88, having the structure: 【Chemistry 65】

99. 89. The compound of any one of claims 1 to 88, having the structure: or a pharmaceutically acceptable salt thereof. 【Hua 66】

100. 89. The compound of any one of claims 1 to 88, having the structure: 【Hua 67】

101. A pharmaceutical composition comprising a pharmaceutically effective amount of a compound according to any one of claims 1 to 100 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

102. 102. The pharmaceutical composition of claim 101, further comprising one or more additional therapeutic agents.

103. 103. The pharmaceutical composition of claim 102, wherein the one or more additional therapeutic agents are independently an anti-neoplastic agent, nivolumab, pembrolizumab, atezolizumab, ipilimumab, chemotherapy, radiation therapy, or ablation therapy.

104. 103. The pharmaceutical composition of claim 102, wherein the one or more additional therapeutic agents are independently rituximab, doxorubicin, gemcitabine, nivolumab, pembrolizumab, atezolizumab, nivolumab, pembrolizumab, atezolizumab, or ipilimumab.

105. 103. The pharmaceutical composition of claim 102, wherein the one or more additional therapeutic agents is a PD-1 / PD-L1 inhibitor.

106. 103. The pharmaceutical composition of claim 102, wherein the one or more additional therapeutic agents is a vaccine.

107. 101. A pharmaceutical composition for use in the treatment of cancer, comprising a pharmaceutically effective amount of a compound according to any one of claims 1 to 100 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

108. 101. A pharmaceutical composition for use in treating HIV or Hepatitis B virus infection, comprising a pharmaceutically effective amount of a compound according to any one of claims 1 to 100, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

109. 107. A method of inhibiting DGKα in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound according to any one of claims 1 to 100 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to any one of claims 101 to 106.

110. 107. A method of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound according to any one of claims 1 to 100 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to any one of claims 101 to 106.

111. 111. The method of claim 110, wherein the cancer is pancreatic cancer, bladder cancer, colorectal cancer, breast cancer, prostate cancer, renal cancer, hepatocellular carcinoma, 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.

112. 111. The method of claim 110, wherein the cancer is acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), myelodysplastic syndromes (MDS), myeloproliferative disorders (MPD), chronic myelogenous leukemia (CML), multiple myeloma (MCL), non-Hodgkin's lymphoma (NHL), mantle cell lymphoma (MCL), follicular lymphoma, Waldenstrom's macroglobulinemia (WM), T-cell lymphoma, B-cell lymphoma, or diffuse large B-cell lymphoma (DLBCL).

113. 113. The method of any one of claims 110 to 112, further comprising administering one or more additional therapeutic agents to the subject.

114. 114. The method of claim 113, wherein the one or more additional therapeutic agents are, independently, an anti-neoplastic agent, nivolumab, pembrolizumab, atezolizumab, ipilimumab, chemotherapy, radiation therapy, or ablation therapy.

115. 114. The method of claim 113, wherein the one or more additional therapeutic agents are independently rituximab, doxorubicin, gemcitabine, nivolumab, pembrolizumab, atezolizumab, nivolumab, pembrolizumab, atezolizumab, or ipilimumab.

116. 114. The method of claim 113, wherein the one or more additional therapeutic agents are PD-1 / PD-L1 inhibitors.

117. 114. The method of claim 113, wherein the one or more additional therapeutic agents comprise one or more immune cell populations 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 (TIL), and dendritic cells (DC).

118. 114. The method of claim 113, wherein the one or more additional therapeutic agents comprise a T cell population selected from the group consisting of α / β TCR T cells, γ / δ TCR T cells, regulatory T (Treg) cells, and TRuC™ T cells.

119. 114. The method of claim 113, wherein the one or more additional therapeutic agents comprise a population of NK-92 cells.

120. 120. The method of any one of claims 117-119, wherein the one or more immune cell populations comprise one or more chimeric antigen receptors (CARs).

121. 121. The method of any one of claims 117 to 120, wherein the cells are allogeneic to the intended recipient.

122. 114. The method of claim 113, wherein the one or more additional therapeutic agents comprise immunotherapy, immunostimulatory therapy, cytokine therapy, chemokine therapy, cell therapy, gene therapy, and combinations thereof.

123. 123. The method of claim 122, wherein the immunotherapy comprises co-administration of one or more antibodies or antigen-binding antibody fragments thereof, or antibody-drug conjugates thereof, CD3-targeting multispecific molecules, CD16-targeting multispecific molecules, or non-immunoglobulin antigen-binding domain or antibody mimetic proteins targeted to one or more targets or tumor-associated antigens (TAAs).

124. 114. The method of claim 113, wherein the one or more additional therapeutic agents comprises a vaccine.

125. 104. A method of treating HIV or Hepatitis B virus infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound according to any one of claims 1 to 100 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to any one of claims 101 to 105.

126. 126. The method of claim 125, further comprising one or more additional therapeutic agents.

127. 127. The method of claim 126, wherein the one or more additional therapeutic agents comprises a vaccine.

128. 101. A method for the manufacture of a medicament for the treatment of cancer in a subject in need thereof, comprising using a compound according to any one of claims 1 to 100 or a pharmaceutically acceptable salt thereof.

129. 101. A method for manufacturing a medicament for inhibiting cancer metastasis in a subject in need thereof, comprising using a compound according to any one of claims 1 to 100 or a pharmaceutically acceptable salt thereof.

130. 100. A method for the manufacture of a medicament for the treatment of HIV or Hepatitis B virus infection in a subject in need thereof, comprising using a compound according to any one of claims 1 to 100 or a pharmaceutically acceptable salt thereof.

131. 101. Use of a compound according to any one of claims 1 to 100, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment of cancer in a subject.

132. 101. Use of a compound according to any one of claims 1 to 100, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for inhibiting cancer metastasis in a subject.

133. 101. Use of a compound according to any one of claims 1 to 100, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment of an HIV or Hepatitis B virus infection in a subject.

134. 101. A compound according to any one of claims 1 to 100, or a pharmaceutically acceptable salt thereof, for use in the treatment of cancer in a subject in need thereof.

135. 101. A compound according to any one of claims 1 to 100, or a pharmaceutically acceptable salt thereof, for use in inhibiting cancer metastasis in a subject in need thereof.

136. 101. A compound according to any one of claims 1 to 100, or a pharmaceutically acceptable salt thereof, for use in treating HIV or Hepatitis B virus infection in a subject in need thereof.

137. 101. A compound according to any one of claims 1 to 100, or a pharmaceutically acceptable salt thereof, for use in therapy.

138. 1. A method of inhibiting DGKα in a subject in need thereof, comprising administering to a subject a therapeutically effective amount of a compound of formula (I): 【Chemistry 68】 or a pharmaceutically acceptable salt thereof to said subject, wherein: R １ is hydrogen, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Alkoxy, halogen, C １～６ Haloalkyl, C １～６ haloalkoxy, or —CN; R ２ is hydrogen, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C １～６ Alkoxy, C ２～６ Alkoxyalkyl, halogen, C １～６ Haloalkyl, C １～６ Haloalkoxy, -CN, -NO, -NO ２ , -C(O)R ２ａ , -C(O)OR ２ａ , -OC(O)R ２ａ , -C(O)N(R ２ａ ) (R ２ｂ ), -N(R ２ａ ) C(O)R ２ｂ , -OC(O)N(R ２ａ ) (R ２ｂ ), -N(R ２ａ )C(O)OR ２ｂ , -C(=NR ２ａ ) N (R ２ｂ ) (R ２ｃ ), -N(R ２ａ ) (R ２ｂ ), -N(R ２ａ ) N (R ２ｂ ) (R ２ｃ ), -N(R ２ａ ) N=C(R ２ｂ ) (OR ２ｃ ), -OR ２ａ , -SR ２ａ , -S(O)R ２ａ , -S(O)(NR ２ａ ) (R ２ｂ ), -S(NR ２ａ ) (NR ２ｂ ) (R ２ｃ ), -S(O) ２ R ２ａ , -S(O) ２ N (R ２ａ ) (R ２ｂ ), -N(R ２ａ ) S (O) ２ (R ２ｂ ), -P(R ２ａ ) (R ２ｂ ), -P(O)(R ２ａ ) (R ２ｂ ), -P(O)(OR ２ａ ) (R ２ｂ ), -P(O)(OR ２ａ ) (OR ２ｂ ), C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１２ Aryl, C １～６ Alkyl-C ６～１２ Aryl, heterocycloalkyl, C １～６ alkyl-(heterocycloalkyl), heteroaryl, or C １～６ alkyl-(heteroaryl), where each alkyl, alkenyl, or alkynyl is independently selected from 1 to 3 R ２ｄ groups, and each cycloalkyl is optionally substituted with 1 to 3 R ２ｅ groups, and each aryl is optionally substituted with 1 to 3 R ２ｆ groups, and each heterocycloalkyl is optionally substituted with 1 to 3 R ２ｇ groups, and each heteroaryl is optionally substituted with 1 to 3 R ２ｈ and optionally substituted with a group, Each R ２ａ , R ２ｂ , and R ２ｃ are independently hydrogen, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C ２～６ Alkoxyalkyl, C １～６ Haloalkyl, C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１２ Aryl, C １～６ Alkyl-C ６～１２ Aryl, heterocycloalkyl, C １～６ alkyl-(heterocycloalkyl), heteroaryl, or C １～６ alkyl-(heteroaryl), where the aryl or heteroaryl is selected from 1 to 3 R ２ｊ and optionally substituted with Or, R ２ａ , R ２ｂ , and R ２ｃ when attached to the same atom, can combine with the atom to which they are attached to form a heterocycloalkyl, Each R ２ｄ are independently —CN, —C(O)R ２ｄ１ , -C(O)OR ２ｄ１ , -OC(O)R ２ｄ１ , -C(O)N(R ２ｄ１ ) (R ２ｄ２ ), -N(R ２ｄ１ ) C(O)R ２ｄ２ , -OC(O)N(R ２ｄ１ ) (R ２ｄ２ ), -N(R ２ｄ１ )C(O)OR ２ｄ２ , -N(R ２ｄ１ ) (R ２ｄ２ ), =O, -OR ２ｄ１ , -SR ２ｄ１ , -S(O)R ２ｄ１ , -S(O)(NR ２ｄ１ ) (R ２ｄ２ ), -S(O) ２ R ２ｄ１ , -S(O)N(R ２ｄ１ ) (R ２ｄ２ ), -N(R ２ｄ１ ) S (O) ２ R ２ｄ２ , C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１２ Aryl, C １～６ Alkyl-C ６～１２ Aryl, heterocycloalkyl, C １～６ alkyl-(heterocycloalkyl), heteroaryl, or C １～６ alkyl-(heteroaryl), Each R ２ｄ１ and R ２ｄ２ are independently hydrogen, C １～６ Alkyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C ２～６ Alkoxyalkyl, or C １～６ is haloalkyl, Each R ２ｅ , R ２ｆ , R ２ｇ , and R ２ｈ are independently hydrogen, C １～６ Alkyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C １～６ Alkoxy, C ２～６ Alkoxyalkyl, halogen, C １～６ Haloalkyl, C １～６ haloalkoxy, —CN, or —OH; Each R ２ｊ are independently １～６ Alkyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C １～６ Alkoxy, C ２～６ Alkoxyalkyl, halogen, C １～６ haloalkyl, or C １～６ haloalkoxy, R ３ is hydrogen, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C １～６ Alkoxy, C ２～６ Alkoxyalkyl, halogen, C １～６ Haloalkyl, C １～６ Haloalkoxy, -CN, -NO, -NO ２ , -C(O)R ３ａ , -C(O)OR ３ａ , -OC(O)R ３ａ , -C(O)N(R ３ａ ) (R ３ｂ ), -N(R ３ａ ) C(O)R ３ｂ , -OC(O)N(R ３ａ ) (R ３ｂ ), -N(R ３ａ )C(O)OR ３ｂ , -C(=NR ３ａ ) N (R ３ｂ ) (R ３ｃ ), -N(R ３ａ ) (R ３ｂ ), -N(R ３ａ ) N (R ３ｂ ) (R ３ｃ ), -N(R ３ａ ) N=C(R ３ｂ ) (OR ３ｃ ), -OR ３ａ , -SR ３ａ , -S(O)R ３ａ , -S(O)(NR ３ａ ) (R ３ｂ ), -S(NR ３ａ ) (NR ３ｂ ) (R ３ｃ ), -S(O) ２ R ３ａ , -S(O) ２ N (R ３ａ ) (R ３ｂ ), -N(R ３ａ ) S (O) ２ (R ３ｂ ), -P(R ３ａ ) (R ３ｂ ), -P(O)(R ３ａ ) (R ３ｂ ), -P(O)(OR ３ａ ) (R ３ｂ ), -P(O)(OR ３ａ ) (OR ３ｂ ), C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１２ Aryl, C １～６ Alkyl-C ６～１２ Aryl, heterocycloalkyl, C １～６ alkyl-(heterocycloalkyl), heteroaryl, or C １～６ alkyl-(heteroaryl), where each alkenyl or alkynyl is independently selected from 1 to 3 R ３ｄ groups, and each cycloalkyl is optionally substituted with 1 to 3 R ３ｅ groups, and each aryl is optionally substituted with 1 to 3 R ３ｆ groups, and each heterocycloalkyl is optionally substituted with 1 to 3 R ３ｇ groups, and each heteroaryl is optionally substituted with 1 to 3 R ３ｈ and optionally substituted with a group, Each R ３ａ , R ３ｂ , and R ３ｃ are independently hydrogen, C １～６ Alkyl, C １～６ Hydroxyalkyl, C ２～６ Alkoxyalkyl, C １～６ Haloalkyl, C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１２ Aryl, C １～６ Alkyl-C ６～１２ aryl, heterocycloalkyl, or heteroaryl; Or, R ３ａ , R ３ｂ , and R ３ｃ when attached to the same atom, can combine with the atom to which they are attached to form a heterocycloalkyl, Each R ３ｄ are independently —N(R ３ｄ１ ) (R ３ｄ２ ), -OR ３ｄ１ , C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１２ Aryl, C １～６ Alkyl-C ６～１２ aryl, heterocycloalkyl, or heteroaryl; Each R ３ｄ１ and R ３ｄ２ are independently hydrogen, C １～６ Alkyl, or —C(O)O—(C １～６ alkyl), Each R ３ｅ , R ３ｆ , R ３ｇ , and R ３ｈ are independently hydrogen, C １～６ Alkyl, C １～６ Alkoxy, halogen, C １～６ haloalkyl, or C １～６ haloalkoxy, R ４ is hydrogen, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Alkoxy, halogen, C １～６ Haloalkyl, C １～６ haloalkoxy, or —CN; R ５ is hydrogen, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Hydroxyalkyl, C ２～６ Alkoxyalkyl, C １～６ Haloalkyl, C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１２ Aryl, C １～６ Alkyl-C ６～１２ Aryl, heterocycloalkyl, C １～６ alkyl-(heterocycloalkyl), heteroaryl, or C １～６ alkyl-(heteroaryl), where alkyl is R ５ａ and optionally substituted with R ５ａ is -OSi(R ５ａ１ ) (R ５ａ２ ) (R ５ａ３ ) and R ５ａ１ , R ５ａ２ , and R ５ａ３ are each independently C １～６ is alkyl, R ６ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ６～１２ aryl, or heteroaryl, wherein the aryl or heteroaryl is selected from 1 to 3 R ６ａ each optionally substituted with Each R ６ａ are independently １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C １～６ Alkoxy, C ２～６ Alkoxyalkyl, halogen, C １～６ Haloalkyl, C １～６ Haloalkoxy, —CN, —NO ２ , -C(O)R ６ｂ , -C(O)OR ６ｂ , -OC(O)R ６ｂ , -C(O)N(R ６ｂ ) (R ６ｃ ), -N(R ６ｂ ) C(O)R ６ｃ , -C(=NR ６ｂ ) N (R ６ｃ ) (R ６ｄ ), -N(R ６ｂ ) (R ６ｃ ), -OR ６ｂ , -SR ６ｂ , -S(O)R ６ｂ , -S(O) ２ R ６ｂ , -S(NR ６ｂ ) (NR ６ｃ ) R ６ｄ , -S(O)(NR ６ｂ ) (R ６ｃ ), -S(O) ２ N (R ６ｂ ) (R ６ｃ ), -N(R ６ｂ ) S (O) ２ (R ６ｃ ), -P(R ６ｂ ) (R ６ｃ ), -P(O)(R ６ｂ ) (R ６ｃ ), -P(O)(OR ６ｂ ) (R ６ｃ ), -P(O)(OR ６ｂ ) (OR ６ｃ ), C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１２ Aryl, C １～６ Alkyl-C ６～１２ Aryl, heterocycloalkyl, C １～６ alkyl-(heterocycloalkyl), heteroaryl, or C １～６ alkyl-(heteroaryl), where cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is selected from 1 to 3 R ６ｅ each optionally substituted with, and alkyl is R ６ｆ and the alkynyl is optionally substituted with 1 to 4 R ６ｊ and optionally substituted with Each R ６ｂ , R ６ｃ and R ６ｄ are independently hydrogen, C １～６ Alkyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C ２～６ Alkoxyalkyl, C １～６ Haloalkyl, C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１２ Aryl, C １～６ Alkyl-C ６～１２ Aryl, heterocycloalkyl, C １～６ alkyl-(heterocycloalkyl), heteroaryl, or C １～６ alkyl-(heteroaryl), where cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is selected from 1 to 3 R ６ｋ and optionally substituted by Each R ６ｋ are independently １～６ Alkyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C １～６ Alkoxy, C ２～６ Alkoxyalkyl, C １～６ Haloalkyl, C １～６ Haloalkoxy, C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ cycloalkyl, heterocycloalkyl, or C １～６ alkyl-(heterocycloalkyl), Each R ６ｅ are independently １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C １～６ Alkoxy, C ２～６ Alkoxyalkyl, halogen, C １～６ Haloalkyl, C １～６ Haloalkoxy, —CN, —NO ２ , -C(O)R ６ｅ１ , -C(O)OR ６ｅ１ , -OC(O)R ６ｅ１ , -C(O)N(R ６ｅ１ ) (R ６ｅ２ ), -N(R ６ｅ１ ) C(O)R ６ｅ２ , -OC(O)N(R ６ｅ１ ) (R ６ｅ２ ), -N(R ６ｅ１ )C(O)OR ６ｅ２ , -C(=NR ６ｅ１ ) N (R ６ｅ２ ) (R ６ｅ３ ), -N(R ６ｅ１ ) (R ６ｅ２ ), =O, -OR ６ｅ１ , -SR ６ｅ１ , -S(O)R ６ｅ１ , -S(NR ６ｅ１ ) (NR ６ｅ２ ), -S(O)(NR ６ｅ１ ) (R ６ｅ２ ), -S(O) ２ R ６ｅ１ , -S(O) ２ N (R ６ｅ１ ) (R ６ｅ２ ), -SF ５ , -N(R ６ｅ１ ) S (O) ２ (R ６ｅ２ ), -P(R ６ｅ１ ) (R ６ｅ２ ), -P(O)(R ６ｅ１ ) (R ６ｅ２ ), -P(O)(OR ６ｅ１ ) (R ６ｅ２ ), -P(O)(OR ６ｅ１ ) (OR ６ｅ２ ), -Si(R ６ｅ１ ) (R ６ｅ２ ) (R ６ｅ３ ), C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１２ Aryl, C １～６ Alkyl-C ６～１２ Aryl, heterocycloalkyl, C １～６ Alkyl-heterocycloalkyl, heteroaryl, or C １～６ alkyl-heteroaryl, where cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is selected from 1 to 3 R ６ｈ each optionally substituted with 1 to 3 R ６ｍ and optionally substituted with Each R ６ｅ１ , R ６ｅ２ , and R ６ｅ３ are independently hydrogen, C １～６ Alkyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C １～６ Alkoxyalkyl, C １～６ Haloalkyl, C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１０ Aryl, C １～６ Alkyl-C ６～１０ Aryl, heterocycloalkyl, C １～６ alkyl-(heterocycloalkyl), heteroaryl, or C １～６ alkyl-(heteroaryl), where cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is selected from 1 to 3 R ６ｎ and optionally substituted with Each R ６ｎ is C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C １～６ Alkoxy, C ２～６ Alkoxyalkyl, halogen, C １～６ Haloalkyl, C １～６ Haloalkoxy, —CN, —C(O)R ６ｎ１ , -C(O)OR ６ｎ１ , -OC(O)R ６ｎ１ , -C(O)N(R ６ｎ１ ) (R ６ｎ２ ), -N(R ６ｎ１ ) C(O)R ６ｎ２ , -OC(O)N(R ６ｎ１ ) (R ６ｎ２ ), -N(R ６ｎ１ )C(O)OR ６ｎ２ , -C(=NR ６ｎ１ ) N (R ６ｎ２ ) (R ６ｎ３ ), -N(R ６ｎ１ ) (R ６ｎ２ ), =O, -OH, -SR ６ｎ１ , -S(O)R ６ｎ１ , -S(NR ６ｎ１ ) (NR ６ｎ２ ) R ６ｎ３ , -S(O)(NR ６ｎ１ ) (R ６ｎ２ ), -S(O) ２ R ６ｎ１ , -S(O) ２ N (R ６ｎ１ ) (R ６ｎ２ ), or -N(R ６ｎ１ ) S (O) ２ (R ６ｎ２ ) and Each R ６ｎ１ , R ６ｎ２ and R ６ｎ３ are independently hydrogen, C １～６ Alkyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C ２～６ Alkoxyalkyl, C １～６ Haloalkyl, C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１０ Aryl, C １～６ Alkyl-C ６～１０ Aryl, heterocycloalkyl, C １～６ alkyl-(heterocycloalkyl), heteroaryl, or C １～６ alkyl-(heteroaryl), Each R ６ｈ are independently １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C １～６ Alkoxy, C ２～６ Alkoxyalkyl, halogen, C １～６ Haloalkyl, C １～６ Haloalkoxy, —CN, —C(O)R ６ｈ１ , -C(O)OR ６ｈ１ , -OC(O)R ６ｈ１ , -C(O)N(R ６ｈ１ ) (R ６ｈ２ ), -N(R ６ｈ１ ) C(O)R ６ｈ２ , -OC(O)N(R ６ｈ１ ) (R ６ｈ２ ), -N(R ６ｈ１ )C(O)OR ６ｈ２ , -C(=NR ６ｈ１ ) N (R ６ｈ２ ) (R ６ｈ３ ), -N(R ６ｈ１ ) (R ６ｈ２ ), =O, -OH, -SR ６ｈ１ , -S(O)R ６ｈ１ , -S(NR ６ｈ１ ) (NR ６ｈ２ ) R ６ｈ３ , -S(O)(NR ６ｈ１ ) (R ６ｈ２ ), -S(O) ２ R ６ｈ１ , -S(O) ２ N (R ６ｈ１ ) (R ６ｈ２ ), -N(R ６ｈ１ ) S (O) ２ (R ６ｈ２ ), C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ cycloalkyl, heterocycloalkyl, or C １～６ alkyl-(heterocycloalkyl), Each R ６ｈ１ , R ６ｈ２ , and R ６ｈ３ are independently hydrogen, C １～６ Alkyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C ２～６ Alkoxyalkyl, C １～６ Haloalkyl, C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１０ Aryl, C １～６ Alkyl-C ６～１０ Aryl, heterocycloalkyl, C １～６ alkyl-(heterocycloalkyl), heteroaryl, or C １～６ alkyl-(heteroaryl), Each R ６ｍ are independently halogen, C １～６ Haloalkyl, C １～６ Haloalkoxy, —CN, —C(O)R ６ｍ１ , -C(O)OR ６ｍ１ , -OC(O)R ６ｍ１ , -C(O)N(R ６ｍ１ ) (R ６ｍ２ ), -N(R ６ｍ３ ) C(O)R ６ｍ２ , -OC(O)N(R ６ｍ１ ) (R ６ｍ２ ), -N(R ６ｍ１ )C(O)OR ６ｍ２ , -C(=NR ６ｍ３ ) N (R ６ｍ１ ) (R ６ｍ２ ), -N(R ６ｍ１ ) (R ６ｍ２ ), =O, -OH, -SR ６ｍ１ , -S(O)R ６ｍ１ , -S(NR ６ｍ１ ) (NR ６ｍ２ ) R ６ｍ３ , -S(O)(NR ６ｍ１ ) (R ６ｍ２ ), -S(O) ２ R ６ｍ１ , -S(O) ２ N (R ６ｍ１ ) (R ６ｍ２ ), or -N(R ６ｍ３ ) S (O) ２ (R ６ｍ２ ) and Each R ６ｍ１ , R ６ｍ２ , and R ６ｍ３ are independently hydrogen, C １～６ Alkyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C ２～６ Alkoxyalkyl, C １～６ Haloalkyl, C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１０ Aryl, C １～６ Alkyl-C ６～１０ Aryl, heterocycloalkyl, C １～６ alkyl-(heterocycloalkyl), heteroaryl, or C １～６ alkyl-(heteroaryl), R ６ｆ is -OSi(R ６ｆ１ ) (R ６ｆ２ ) (R ６ｆ３ ) and R ６ｆ１ , R ６ｆ２ , and R ６ｆ３ are each independently C １～６ is alkyl, Each R ６ｊ are independently ２～６ Alkoxyalkyl, halogen, C １～６ Haloalkyl, C １～６ Haloalkoxy, —CN, —C(O)R ６ｊ１ , -C(O)OR ６ｊ１ , -OC(O)R ６ｊ１ , -C(O)N(R ６ｊ１ ) (R ６ｊ２ ), -N(R ６ｊ３ ) C(O)R ６ｊ２ , -OC(O)N(R ６ｊ１ ) (R ６ｊ２ ), -N(R ６ｊ１ )C(O)OR ６ｊ２ , -C(=NR ６ｊ３ ) N (R ６ｊ１ ) (R ６ｊ２ ), -N(R ６ｊ１ ) (R ６ｊ２ ), =O, -OR ６ｊ１ , -SR ６ｊ１ , -S(O)R ６ｊ１ , -S(NR ６ｊ１ ) (NR ６ｊ２ ), -S(NR ６ｊ１ ) (NR ６ｊ２ ) R ６ｊ３ , -S(O)(NR ６ｊ１ ) (R ６ｊ２ ), -S(O) ２ R ６ｊ１ , -S(O) ２ N (R ６ｊ１ ) (R ６ｊ２ ), -N(R ６ｊ１ ) S (O) ２ (R ６ｊ２ ), -Si(R ６ｊ１ ) (R ６ｊ２ ) (R ６ｊ３ ), C ３～１０ Cycloalkyl, C ６～１２ aryl, heterocycloalkyl, or heteroaryl, wherein the cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is selected from 1 to 3 R ６ｐ and optionally substituted with Each R ６ｊ１ , R ６ｊ２ , and R ６ｊ３ are independently hydrogen, C １～６ Alkyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C ２～６ Alkoxyalkyl, C １～６ Haloalkyl, C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１０ Aryl, C １～６ Alkyl-C ６～１０ Aryl, heterocycloalkyl, C １～６ alkyl-(heterocycloalkyl), heteroaryl, or C １～６ alkyl-(heteroaryl), Each R ６ｐ are independently １～６ Alkyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C １～６ Alkoxy, C ２～６ Alkoxyalkyl, halogen, C １～６ Haloalkyl, C １～６ Haloalkoxy, —CN, —C(O)R ６ｐ１ , -C(O)OR ６ｐ１ , -OC(O)R ６ｐ１ , -C(O)N(R ６ｐ１ ) (R ６ｐ２ ), -N(R ６ｐ１ ) C(O)R ６ｐ２ , -OC(O)N(R ６ｐ１ ) (R ６ｐ２ ), -N(R ６ｐ１ )C(O)OR ６ｐ２ , -C(=NR ６ｐ３ ) N (R ６ｐ１ ) (R ６ｐ２ ), -N(R ６ｐ１ ) (R ６ｐ２ ), =O, -OH, -SR ６ｐ１ , -S(O)R ６ｐ１ , -S(NR ６ｐ１ ) (NR ６ｐ２ ) R ６ｐ３ , -S(O)(NR ６ｐ１ ) (R ６ｐ２ ), -S(O) ２ R ６ｐ１ , -S(O) ２ N (R ６ｐ１ ) (R ６ｐ２ ), or -N(R ６ｐ１ ) S (O) ２ (R ６ｐ２ ) and Each R ６ｐ１ , R ６ｐ２ , and R ６ｐ３ are independently hydrogen, C １～６ Alkyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C ２～６ Alkoxyalkyl, C １～６ Haloalkyl, C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ Cycloalkyl, C ６～１０ Aryl, C １～６ Alkyl-C ６～１０ Aryl, heterocycloalkyl, C １～６ alkyl-(heterocycloalkyl), heteroaryl, or C １～６ alkyl-(heteroaryl), Or, R ５ and one R ６ａ together with the atom to which they are attached form a heterocycloalkyl, and 1 to 3 R ６ｇ and optionally substituted with Each R ６ｇ are independently １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C ２～６ Alkoxyalkyl, halogen, C １～６ Haloalkyl, C １～６ haloalkoxy, or —CN; R ７ is hydrogen, C １～６ Alkyl, C １～６ Hydroxyalkyl, C １～６ Aminoalkyl, C １～６ Alkoxy, C ２～６ Alkoxyalkyl, C １～６ Alkylthio, halogen, C １～６ Haloalkyl, —CN, —OH, —NH ２ , C ３～１０ Cycloalkyl, C １～６ Alkyl-C ３～１０ cycloalkyl, heterocycloalkyl, or C １～６ alkyl-(heterocycloalkyl), each heterocycloalkyl is a 3- to 20-membered ring having 1 to 4 heteroatoms, each independently N, O, or S; each heteroaryl is a 5-18 membered ring having 1-4 heteroatoms which are each independently N, O, or S;

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