Thienopyrrole compounds

Abstract

The present disclosure relates generally to certain compounds, pharmaceutical compositions comprising said compounds, and methods of making and using said compounds and pharmaceutical compositions. The compounds and compositions provided herein may be used for the treatment or prevention of an autoimmune disease and / or inflammatory condition, including systemic lupus erythematosus and cutaneous lupus erythematosus.

Description

[Technical Field]

[0001] This disclosure generally relates to novel thienopyrrole compounds, pharmaceutical compositions comprising such compounds, and methods of manufacturing and using such compounds and pharmaceutical compositions. In some embodiments, the novel thienopyrrole compounds provided herein may be used to treat certain diseases and conditions, including but not limited to inflammatory conditions, systemic lupus erythematosus, cutaneous lupus erythematosus, or lupus nephritis. [Previous Technology]

[0002] Toll-like receptors (TLRs) are a family of transmembrane immune receptors that sense pathogens, trigger innate immune responses, and induce adaptive immunity. TLR7 / 8 / 9 are endosome-localized TLRs, and they respond to single-stranded RNA (TLR7 / 8) or unmethylated DNA containing the cytosine-phosphate-guanine (CpG) motif (TLR9). Activation of TLR7 / 8 / 9 leads to inflammatory responses, including the production of type I interferon and pro-inflammatory cytokines, B cell activation and antibody production, and neutrophil NETosis. Aberrant activation of TLR7 / 8 / 9 results in increased type I interferon response, increased pro-inflammatory cytokines, and persistent autoantibody production, which may contribute to the chronic progression of various autoimmune diseases and inflammatory conditions, leading to widespread inflammation and tissue damage. (Kawai et al., 2010, Nat Immunol 11, 373; Joosten et al., 2016, Nat Rev Rheomatol 12, 344; Crow et al., 2019, Lupus Sci Med 6, e000336; Garcia-Romo et al., 2011, Sci Transl Med 3, 73ra20; Kono et al., 2009, PNAS 106, 12061; Koh et al., 2013, J Immunol 190, 4982). Therefore, there is a need for compounds that are stable and exhibit effective pharmacokinetic and / or pharmacodynamic profiles, and are effective TLR7, and / or TLR8, and / or TLR9 antagonists. [Summary of the Invention]

[0003] In one embodiment, this document provides compounds of formula I, formula I, or pharmaceutically acceptable salts thereof, wherein R1 is an 8- to 15-member fused tricyclic heterocyclic group or an 8- to 15-member fused tricyclic heteroaryl group, wherein the 8- to 15-member fused tricyclic heterocyclic group and the 8- to 15-member fused tricyclic heteroaryl group are each optionally substituted by 1 to 4 Ra groups; R2 is a C1-6 alkyl group, wherein the C1-6 alkyl group is optionally substituted by 1 to 4 groups independently selected from halogens and C1-6 alkoxy groups, wherein the C1-6 alkoxy group is optionally substituted by 1 to 3 halogen groups; R3 is a H, halogen, -CN, C1-6 alkyl, and C3-7 monocyclic cycloalkyl group, wherein the C1-6 alkyl and C3-7 monocyclic cycloalkyl groups are each optionally substituted by 1 to 3 groups independently selected from the following groups: -OH, halogen, -CN, and C 1-4 alkoxy groups, wherein the C1-4 alkoxy group is optionally substituted with 1 to 3 halogen groups; Z-series C1-6 alkyl, -C(O)R13-C(O)NR6R7, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, 4 to 7-membered monocyclic heterocyclic group, phenyl, 5 to 6-membered monocyclic heteroaryl, 8 to 10-membered fused bicyclic heterocyclic group, 6 to 10-membered bridged bicyclic heterocyclic group, 8 to 10-membered fused bicyclic heteroaryl, or 7 to 10-membered spirocyclic heterocyclic group, wherein the C1-6 alkyl group is optionally substituted with 1 to 4 Rb groups; wherein the C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C The 5-10-membered bridged bicyclic cycloalkyl, 4-7-membered monocyclic heterocyclic, phenyl, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, and 7-10-membered spirocyclic heterocyclic are each optionally substituted with 1-2 R8 groups and each optionally substituted with 1-3 Ra groups; the R6 group consists of C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, 4-7-membered monocyclic heterocyclic, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, or 7-10-membered spirocyclic heterocyclic, wherein the C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5 ... The 5-10-membered bridged bicyclic cycloalkyl, 4-7-membered monocyclic heterocyclic, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, and 7-10-membered spirocyclic heterocyclic groups are each optionally substituted with 1 to 4 Ra groups; the R13 group consists of 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, or 7-10-membered spirocyclic heterocyclic groups.The 4- to 7-membered monocyclic heterocyclic group, the 5- to 6-membered monocyclic heteroaryl group, the 8- to 10-membered fused bicyclic heterocyclic group, the 6- to 10-membered bridged bicyclic heterocyclic group, the 8- to 10-membered fused bicyclic heteroaryl group, and the 7- to 10-membered spirocyclic heterocyclic group are each optionally substituted with 1 to 4 Ra groups; R7 is H, C1-6 alkyl, C3-7 monocyclic cycloalkyl, or 4- to 6-membered monocyclic heterocyclic group, wherein the C1-6 alkyl, C3-7 monocyclic cycloalkyl, and the 4- to 6-membered monocyclic heterocyclic group are each optionally substituted with 1 to 4 groups independently selected from -OH, halogen, -CN, and C1-6 alkoxy; each R8 is independently halogen, -C(O)R9, -NR10R10, C1-6 alkyl, C3-7 monocyclic cycloalkyl, C 7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, 4-7 member monocyclic heterocyclic, phenyl, 5-6 member monocyclic heteroaryl, 8-10 member fused bicyclic heterocyclic, 6-10 member bridged bicyclic heterocyclic, 8-10 member fused bicyclic heteroaryl, 7-10 member spirocyclic heterocyclic, -OR 5, -C(O)N(R 5)(R 5), -N(R 5) 2(R 5) +, -N(R 5)C(O)R 5, -N(R 5)C(O)OR 5, -N(R 5)C(O)N(R 5)(R 5), -N(R 5)S(O) 2(R 5a), -NR 5S(O) 2N(R 5)(R 5), -NR 5S(O) 2O(R 5a), -OC(O)N(R5)(R5), -S(O)R5a, -S(O)(NH)R5, -S(O)2R5a, -S(O)2N(R5)(R5), or -N=S(R5a)(R5a)=O, wherein the C1-6 alkyl group is optionally substituted with 1 to 4 Rb groups, wherein the C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, 4 to 7-membered monocyclic heterocyclic group, phenyl, 5 to 6-membered monocyclic heteroaryl, 8 to 10-membered fused bicyclic heterocyclic group, 6 to 10-membered bridged bicyclic heterocyclic group, 8 to 10-membered fused bicyclic heteroaryl, and 7 to 10-membered spirocyclic heterocyclic group are each independently optionally substituted with 1 to 4 Ra groups; each R9 is independently C 3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7 member monocyclic heterocyclic group, 5-6 member monocyclic heteroaryl, 8-10 member fused bicyclic heterocyclic group, 6-10 member bridged bicyclic heterocyclic group, 8-10 member fused bicyclic heteroaryl, or 7-10 member spirocyclic heterocyclic group, wherein the C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7 member monocyclic heterocyclic group, 5-6 member monocyclic heteroaryl group, C5-10 member spirocyclic heterocyclic group, C5-10 member monocyclic cycloalkyl, C5-10 bridged bi ...The 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, and 7-10-membered spirocyclic heterocyclic groups are each optionally substituted with 1 to 4 Ra groups; each R5 and R10 is independently H, C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, or 7-10-membered spirocyclic heterocyclic, wherein the C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl groups are each optionally substituted by 1 to 4 Rb groups, wherein the C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C The 5-10 bridging bicyclic cycloalkyl, phenyl, naphthyl, 4-7 member monocyclic heterocyclic, 5-6 member monocyclic heteroaryl, 8-10 member fused bicyclic heterocyclic, 6-10 member bridging bicyclic heterocyclic, 8-10 member fused bicyclic heteroaryl, and 7-10 member spirocyclic heterocyclic groups are each optionally substituted with 1 to 4 Ra groups; each R 5a is independently a C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 monocyclic cycloalkyl, C 7-10 fused bicyclic cycloalkyl, C 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, or 7-10-membered spirocyclic heterocyclic, wherein the C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl groups are each optionally substituted by 1 to 4 Rb groups, wherein the C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C The 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, and 7-10-membered spirocyclic heterocyclic groups are each optionally substituted with 1 to 4 Ra groups; each Ra is independently substituted with a side oxygen, imino, halogen, -NO2, -N3, -CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, 7-10-membered spirocyclic heterocyclic, -OR 11, -C(O)R 11, -C(O)OR11. -C(O)N(R 11)(R 11), -NR 11R 11. -N(R 11) 2(R 11) +, -N(R 11)C(O)R 11. -N(R 11)C(O)OR 11. -N(R 11)C(O)N(R 11)(R 11), -N(R 11)S(O) 2(R 11a), -NR 11S(O) 2N(R 11)(R 11), -NR 11S(O) 2O(R 11a), -OC(O)R 11, -OC(O)OR 11, -OC(O)N(R 11)(R 11), -SR 11, -S(O)R 11a, -S(O)(NH)R 11, -S(O) 2R 11a, -S(O)2N(R11)(R11), or -N=S(R11a)(R11a)=O, wherein the C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl groups are each independently and optionally substituted with 1 to 3 Rc groups, wherein the C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4 to 7-membered monocyclic heterocyclic, 5 to 6-membered monocyclic heteroaryl, 8 to 10-membered fused bicyclic heterocyclic, 6 to 10-membered bridged bicyclic heterocyclic, 8 to 10-membered fused bicyclic heteroaryl, and 7 to 10-membered spirocyclic heterocyclic groups are each independently and optionally substituted with 1 to 3 Rd groups, and each Rb is independently a side oxygen group, imine group, halogen, -NO2, -N 3, -CN, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4 to 7 member monocyclic heterocyclic, 5 to 6 member monocyclic heteroaryl, 8 to 10 member fused bicyclic heterocyclic, 8 to 10 member bridged bicyclic heterocyclic, 6 to 10 member bridged bicyclic heterocyclic, 8 to 10 member fused bicyclic heteroaryl, 7 to 10 member spirocyclic heterocyclic, -OR 11, -C(O)R 11, -C(O)OR 11, -C(O)N(R 11)(R 11), -NR 11R 11, -N(R 11) 2(R 11) +, -N(R 11)C(O)R 11, -N(R 11)C(O)OR 11, -N(R 11)C(O)N(R 11)(R 11), -N(R 11)S(O) 2(R 11a), -NR 11S(O) 2N(R 11)(R 11), -NR 11S(O) 2O(R 11a), -OC(O)R 11, -OC(O)OR 11, -OC(O)N(R 11)(R 11), -SR 11, -S(O)R 11a, -S(O)(NH)R 11, -S(O) 2R 11a, -S(O) 2N(R 11)(R 11), or -N=S(R 11a)(R11a)=O, wherein the C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4 to 7-membered monocyclic heterocyclic group, 5 to 6-membered monocyclic heteroaryl, 8 to 10-membered fused bicyclic heterocyclic group, 6 to 10-membered bridged bicyclic heterocyclic group, 8 to 10-membered fused bicyclic heteroaryl, and 7 to 10-membered spirocyclic heterocyclic group are each optionally substituted by 1 to 3 Rd groups; each Rc is independently halogenated, -CN, C7-10 fused bicyclic cycloalkyl, C 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, 7-10-membered spirocyclic heterocyclic, -OR 12, -C(O)R 12, -C(O)OR 12, -C(O)N(R 12)(R 12), -NR 12R 12, -N(R 12) 2(R 12) +, -N(R 12)C(O)R 12, -N(R 12)C(O)OR 12, -N(R 12)C(O)N(R 12)(R 12), -N(R 12)S(O) 2(R 12a), -NR 12S(O) 2N(R 12)(R 12), -NR 12S(O) 2O(R 12a), -OC(O)R 12, -OC(O)OR 12, -OC(O)N(R 12)(R 12), -SR 12, -S(O)R 12a, -S(O)(NH)R 12, -S(O) 2R 12a, -S(O) 2N(R 12)(R 12), or -N=S(R 12a)(R 12a)=O; Each R d is independently associated with a side oxygen group, halogen, -CN, C 1-6 alkyl, C 7-10 fused bicyclic cycloalkyl, C 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, 7-10-membered spirocyclic heterocyclic, -OR 12, -C(O)R 12, -C(O)OR 12, -C(O)N(R 12)(R 12), -NR 12R 12, -N(R 12) 2(R 12) +, -N(R 12)C(O)R 12, -N(R 12)C(O)OR 12, -N(R 12)C(O)N(R 12)(R 12), -N(R 12)S(O) 2(R 12a), -NR 12S(O) 2N(R 12)(R 12), -NR 12S(O) 2O(R 12a), -OC(O)R 12, -OC(O)OR 12, -OC(O)N(R 12)(R 12), -SR12, -S(O)R12a, -S(O)(NH)R12, -S(O)2R12a, -S(O)2N(R12)(R12), or -N=S(R12a)(R12a)=O, wherein the C1-6 alkyl group is optionally substituted by 1 to 3 groups independently selected from the following: -OH, halogen, -CN, and C1-3 alkoxy; each R11 is independently H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C The group comprises 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, or 7-10-membered spirocyclic heterocyclic, wherein each of the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, and 7-10-membered spirocyclic heterocyclic groups is optionally substituted with 1 to 3 Rc groups; each Rc group is substituted with one or more Rc groups. 11a Independently comprises C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4 to 7-membered monocyclic heterocyclic group, 5 to 6-membered monocyclic heteroaryl, 8 to 10-membered fused bicyclic heterocyclic group, 6 to 10-membered bridged bicyclic heterocyclic group, 8 to 10-membered fused bicyclic heteroaryl, or 7 to 10-membered spirocyclic heterocyclic group, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 condensed bicyclic cycloalkyl, C6-6 alkyl, C7-10 condensed bicyclic cyclo ... The 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, and 7-10-membered spirocyclic heterocyclic groups are each optionally substituted with 1 to 3 Rc groups; each R12 is independently H, C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C12 alkyl, C2-6 alkyne, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C12 alkyl, C3-7 cycloalkyl, C7-10 fused bicyclic cycloalkyl, C7 cycloalkyl, C7 cycloalkyl, C8 cycloalkyl, C9 cycloalkyl, C10 cycloalkyl, C9 cycloalkyl, C12 ... 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, or 7-10-membered spirocyclic heterocyclic; each R 12a is independently C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic group, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic group, 6-10-membered bridged bicyclic heterocyclic group, 8-10-membered fused bicyclic heteroaryl, or 7-10-membered spirocyclic heterocyclic group, wherein each 4-membered monocyclic heterocyclic group independently has one cyclic heteroatom selected from N, O, and S; each 5-7-membered monocyclic heterocyclic group independently has one to two cyclic heteroatoms independently selected from N, O, and S; each 6-membered bridged bicyclic heterocyclic group independently has one cyclic heteroatom selected from N, O, and S; and each 7-membered bridged bicyclic heterocyclic group independently has one to two cyclic heteroatoms independently selected from N, O, and S. Each of the 5 to 6 monocyclic heteroaryl groups, 8 to 10 fused bicyclic heteroaryl groups, 8 to 10 bridged bicyclic heteroaryl groups, 8 to 10 fused bicyclic heteroaryl groups, and 7 to 10 spirocyclic heteroaryl groups independently has 1 to 4 cyclic heteroatoms independently selected from N, O, and S; and each of the 8 to 15 fused tricyclic heteroaryl groups and 8 to 15 fused tricyclic heteroaryl groups independently has 1 to 7 cyclic heteroatoms independently selected from N, O, and S.

[0004] In one embodiment, this document provides a pharmaceutical composition comprising a compound provided herein or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient or carrier.

[0005] In one embodiment, this document provides a method for inhibiting the activity of tyrosine receptor 7 and / or 8 in a subject in need, comprising administering to the subject a therapeutically effective amount of a compound provided herein or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of a pharmaceutical composition provided herein.

[0006] In one embodiment, this document provides a method for inhibiting the activity of a tyrosine receptor 7 in a subject in need, comprising administering to the subject a therapeutically effective amount of a compound provided herein or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of a pharmaceutical composition provided herein.

[0007] In one embodiment, this document provides a method for inhibiting the activity of cyclophosphamide receptor 8 in a subject in need, comprising administering to the subject a therapeutically effective amount of a compound provided herein or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of a pharmaceutical composition provided herein.

[0008] In one embodiment, this document provides a method of treating a disease or condition in a subject of need that is associated with elevated activity of troponin receptors 7 and / or 8, comprising administering to the subject a therapeutically effective amount of a compound provided herein or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of a pharmaceutical composition provided herein.

[0009] In one embodiment, this document provides a method of treating a disease or condition associated with elevated tyrosine receptor 7 activity in a subject of need, comprising administering to the subject a therapeutically effective amount of a compound provided herein or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of a pharmaceutical composition provided herein.

[0010] In one embodiment, this document provides a method of treating a disease or condition associated with elevated troponin 8 receptor activity in a subject of need, comprising administering to the subject a therapeutically effective amount of a compound provided herein or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of a pharmaceutical composition provided herein.

[0011] In one embodiment, this document provides a method of treating an inflammatory condition in a subject in need, comprising administering to the subject a therapeutically effective amount of a compound provided herein or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of a pharmaceutical composition provided herein.

[0012] In one embodiment, this document provides a method of treating systemic lupus erythematosus in a subject in need, comprising administering to the subject a therapeutically effective amount of a compound provided herein or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of a pharmaceutical composition provided herein.

[0013] In one embodiment, this document provides a method of treating cutaneous lupus erythematosus in a subject in need, comprising administering to the subject a therapeutically effective amount of a compound provided herein or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of a pharmaceutical composition provided herein.

[0014] In one embodiment, this document provides a method of treating lupus nephritis in a subject in need, comprising administering to the subject a therapeutically effective amount of a compound provided herein or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of a pharmaceutical composition provided herein.

[0015] In one embodiment, this document provides a compound provided herein or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition provided herein, which is used in a therapy.

[0016] In one embodiment, this document provides a compound provided herein or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition provided herein, for use in a method of inhibiting the activity of tyrosine receptor 7 and / or 8 in a subject in need, the method comprising administering to the subject a therapeutically effective amount of the compound or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of the pharmaceutical composition.

[0017] In one embodiment, this document provides a compound provided herein or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition provided herein, for use in a method of inhibiting the activity of a tyrosine receptor 7 in a subject in need, the method comprising administering to the subject a therapeutically effective amount of the compound or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of the pharmaceutical composition.

[0018] In one embodiment, this document provides a compound provided herein or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition provided herein, for use in a method of inhibiting the activity of a tyrosine receptor 8 in a subject of need, the method comprising administering to the subject a therapeutically effective amount of the compound or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of the pharmaceutical composition.

[0019] In one embodiment, this document provides a compound provided herein or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition provided herein, for use in a method of treating a disease or condition associated with elevated tyrosine receptor 7 and / or 8 activity in a subject of need, the method comprising administering to the subject a therapeutically effective amount of the compound or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of the pharmaceutical composition.

[0020] In one embodiment, this document provides a compound provided herein or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition provided herein, for use in a method of treating a disease or condition associated with elevated tyrosine receptor 7 activity in a subject of need, the method comprising administering to the subject a therapeutically effective amount of the compound or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of the pharmaceutical composition.

[0021] In one embodiment, this document provides a compound provided herein or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition provided herein, for use in a method of treating a disease or condition associated with elevated tyrosine receptor 8 activity in a subject of need, the method comprising administering to the subject a therapeutically effective amount of the compound or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of the pharmaceutical composition.

[0022] In one embodiment, this document provides a compound or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, for use in a method of treating an inflammatory condition in a subject in need, the method comprising administering to the subject a therapeutically effective amount of the compound or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of the pharmaceutical composition thereof.

[0023] In one embodiment, this document provides a compound or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, for use in a method of treating systemic lupus erythematosus in a subject of need, the method comprising administering to the subject a therapeutically effective amount of the compound or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of the pharmaceutical composition thereof.

[0024] In one embodiment, this document provides a method of treating cutaneous lupus erythematosus in a subject of need, comprising administering to the subject a therapeutically effective amount of the compound or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of the pharmaceutical composition thereof.

Implementation Method

[0026] Cross-reference to related applications

[0027] This application claims priority to U.S. Provisional Patent Application No. 63 / 242,969, filed September 10, 2021, the entire contents of which are incorporated herein by reference for all purposes. I. Definitions

[0028] The following description is made under the understanding that this disclosure is considered as an example of the claimed subject matter and is not intended to limit the scope of the appended claims to the specific embodiments described. The headings used throughout this disclosure are provided for convenience and should not be construed as limiting the scope of the claims in any way. Embodiments described under any heading may be combined with embodiments described under any other heading.

[0029] 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. It should be noted that, as used herein and in the appended claims, the singular forms "a / an" and "the" include plural references unless the context clearly indicates otherwise. Thus, for example, reference to "the compound" includes a plural of such compounds, and reference to "the assay" includes one or more assays and their equivalents known to one of ordinary skill in the art, etc.

[0030] As used in this disclosure, the following words, phrases and symbols are generally intended to have the meanings set forth below, unless otherwise indicated in the context in which they are used.

[0031] A dash ("-") not between two letters or symbols is used to indicate the attachment point of a substituent. For example, -CONH 2 is attached through a carbon atom. Dashes before or at the end of chemical groups are for convenience; chemical groups may or may not be depicted with one or more dashes without losing their usual meaning. Wavy lines drawn through lines in the structure indicate the attachment point of a group. Unless required by chemical or structural rules, the order in which chemical groups are written or named does not indicate or imply directionality. A solid line emanating from the center of a ring (including fused, bridged, or spirocyclic systems) indicates that the attachment point of a substituent on the ring can be at any ring atom. For example, in the following structures, Raa can be attached to any of the five carbon ring atoms or Raa can replace a hydrogen atom attached to a nitrogen ring atom: As another example, Raa is in the following structures: Raa can be attached to any of the numbered positions shown below:

[0032] A solid line emanating from the center of a ring (including fused, bridged, or spirocyclic systems) indicates that the attachment point of the ring system to the remainder of the compound may be at any ring atom in the fused, bridged, or spirocyclic system. For example, in the following structure: a monocyclic heterocyclic group may be attached to the remainder of the compound at any of the numbered positions shown below: As another example, in the following fused bicyclic heterocyclic structure: a fused bicyclic heterocyclic group may be attached to the remainder of the compound at any of the eight numbered positions shown below:

[0033] Prefixes such as "C uv" indicate that the following groups have u to v carbon atoms. For example, "C 1-6 alkyl" indicates that an alkyl group has 1 to 6 carbon atoms. Similarly, the term "x to y membered" ring, where the values ​​of x and y coefficients range (such as "3 to 12 membered heterocyclic group"), refers to a ring containing x to y atoms (i.e., 3 to 12), of which up to 80% may be heteroatoms such as N, O, S, and P, while the remaining atoms are carbon.

[0034] In addition, certain commonly used alternative chemical names may or may not be used. For example, divalent groups such as divalent "alkyl" and divalent "aryl" may also be referred to as "alkylene / alkylenyl / alkylyl" and "arylene / arylenyl / arylyl", respectively.

[0035] "A compound disclosed herein", "a compound of the present disclosure", "a compound provided herein", or "a compound described herein" refers to a compound of formula I. It also includes specific compounds of Examples 1 to 68.

[0036] The use of the term "about" in this document includes (and describes) embodiments for that value or parameter itself. In some embodiments, the term "about" includes an indication of ±10%. In other embodiments, the term "about" includes an indication of ±5%. In some other embodiments, the term "about" includes an indication of ±1%. Furthermore, the term "about X" includes a description of "X".

[0037] "alkyl" means unbranched or branched saturated hydrocarbon chain. As used herein, an alkyl group has 1 to 20 carbon atoms (i.e., C1-20 alkyl), 1 to 12 carbon atoms (i.e., C1-12 alkyl), 1 to 8 carbon atoms (i.e., C1-8 alkyl), 1 to 6 carbon atoms (i.e., C1-6 alkyl), 1 to 4 carbon atoms (i.e., C1-4 alkyl), 1 to 3 carbon atoms (i.e., C1-3 alkyl), or 1 to 2 carbon atoms (i.e., C1-2 alkyl). Examples of alkyl groups include methyl, ethyl, propyl, isopropyl, n-butyl, dibutyl, isobutyl, terbutyl, pentyl, 2-pentyl, isopentyl, neopentyl, hexyl, 2-hexyl, 3-hexyl, and 3-methylpentyl. When an alkyl residue with a specific number of carbons is named by a chemical name or determined by a molecular formula, it can encompass isomers with all positions having that number of carbons. Thus, for example, "butyl" includes n-butyl (i.e., -(CH2)3CH3), secondary butyl (i.e., -CH(CH3)CH2CH3), isobutyl (i.e., -CH2CH(CH3)2), and tertiary butyl (i.e., -C(CH3)3); and "propyl" includes n-propyl (i.e., -(CH2)2CH3) and isopropyl (i.e., -CH(CH3)2).

[0038] "Alkenyl" refers to an aliphatic group containing at least one carbon-carbon double bond and having 2 to 20 carbon atoms (i.e., C2-20 alkenyl), or 2 to 8 carbon atoms (i.e., C2-8 alkenyl), or 2 to 6 carbon atoms (i.e., C2-6 alkenyl), or 2 to 4 carbon atoms (i.e., C2-4 alkenyl). Examples of alkenyl groups include vinyl, propenyl, and butadienyl (including 1,2-butadienyl and 1,3-butadienyl).

[0039] "alkynyl" refers to an aliphatic group containing at least one carbon-carbon linkage and having 2 to 20 carbon atoms (i.e., C2-20 alkynyl), or 2 to 8 carbon atoms (i.e., C2-8 alkynyl), or 2 to 6 carbon atoms (i.e., C2-6 alkynyl), or 2 to 4 carbon atoms (i.e., C2-4 alkynyl). The term "alkynyl" also includes groups having one linkage and one double bond.

[0040] "alkylene" refers to a divalent and unbranched saturated hydrocarbon chain. As used herein, alkylene has 1 to 20 carbon atoms (i.e., C1-20 alkylene), 1 to 12 carbon atoms (i.e., C1-12 alkylene), 1 to 8 carbon atoms (i.e., C1-8 alkylene), 1 to 6 carbon atoms (i.e., C1-6 alkylene), 1 to 4 carbon atoms (i.e., C1-4 alkylene), 1 to 3 carbon atoms (i.e., C1-3 alkylene), or 1 to 2 carbon atoms (i.e., C1-2 alkylene). Examples of alkylene include methylene, ethylene, propylene, butylene, pentylene, and hexylene. In some embodiments, the alkylene may optionally be alkylated. Examples of substituted alkyl groups include -CH(CH 3)CH 2-, -CH 2CH(CH 3)-, -CH 2CH(CH 2CH 3)-, -CH 2C(CH 3) 2-, -C(CH 3) 2CH 2-, -CH(CH 3)CH(CH 3)-, -CH 2C(CH 2CH 3)(CH 3)-, and -CH 2C(CH 2CH 3) 2.

[0041] "Alkoxy" refers to the group "alkyl-O-". Examples of alkoxy groups include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, secondary-butoxy, n-pentoxy, n-hexoxy, and 1,2-dimethylbutoxy. "Haloalkoxy" refers to an alkoxy group as defined above, wherein one or more hydrogen atoms are replaced by halogens.

[0042] “Acyl” refers to the group -C(=O)R, wherein R is hydrogen, alkyl, cycloalkyl, heterocyclic, aryl, heteroalkyl, or heteroaryl; each of which may optionally be substituted, as defined herein. Examples of acyl include methylacyl, acetylated, cyclohexylcarbonyl, cyclohexylmethyl-carbonyl, and benzoyl.

[0043] “amido” refers to both “C-amido” and “N-amido”, where C-amido refers to the group -C(=O)NR yR z and N-amido refers to the group -NR yC(=O)R z, wherein R y and R z are independently selected from the group consisting of: hydrogen, alkyl, aryl, haloalkyl, heteroaryl, cycloalkyl, or heterocyclic; each of which may be optionally substituted.

[0044] "Amino" refers to -NR yR z, wherein R y and R z are independently selected from the group consisting of: hydrogen, alkyl, haloalkyl, aryl, heteroaryl, cycloalkyl, or heterocyclic; each may be optionally substituted.

[0045] "Aryl" means an aromatic carbocyclic group having a single ring (e.g., monocyclic) or multiple rings (e.g., bicyclic or tricyclic), including fused systems. As used herein, an aryl group has 6 to 20 carbon atoms (i.e., C6-20 aryl), 6 to 12 carbon atoms (i.e., C6-12 aryl), or 6 to 10 carbon atoms (i.e., C6-10 aryl). Examples of aryl groups include phenyl, naphthyl, tyrosyl, and anthracene. However, aryl does not encompass heteroaryl groups as defined below or overlap with them in any way. If one or more aryl groups are fused with a heteroaryl ring, the resulting ring system is a heteroaryl group.

[0046] "Cyano" or "carbonitrile" refers to the group -CN.

[0047] "Cycloalkyl" refers to a saturated or partially saturated cyclic alkyl group having a single ring or multiple rings, including fused, bridged, and spirocyclic systems. The term "cycloalkyl" includes cycloalkenyl (i.e., a cyclic group having at least one double bond). As used herein, cycloalkyl groups have 3 to 20 ring carbon atoms (i.e., C3-20 cycloalkyl), 3 to 12 ring carbon atoms (i.e., C3-12 cycloalkyl), 3 to 10 ring carbon atoms (i.e., C3-10 cycloalkyl), 3 to 8 ring carbon atoms (i.e., C3-8 cycloalkyl), or 3 to 6 ring carbon atoms (i.e., C3-6 cycloalkyl). Examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0048] "Cycloalkoxy" refers to the group "cycloalkyl-O-". Examples of cycloalkoxy groups include, but are not limited to: , , , and .

[0049] "Bridged" refers to a ring fusion in which different atoms on a ring are joined by a divalent substituent (such as a alkyl group, or an alkyl group containing one or two heteroatoms, or a single heteroatom). Examples of pyridyl and adamantyl-based bridged ring systems.

[0050] The term "fused" refers to a ring that is bonded to an adjacent ring.

[0051] "spiro" refers to a cyclic substituent formed by two bonds bonded at the same carbon atom. Examples of spiro groups include 1,1-diethylcyclopentane, dimethyl-di, and 4-benzyl-4-methylpiperidine, wherein cyclopentane and piperidine are spiro substituents.

[0052] "Halogen" or "halo" includes fluorine, chlorine, bromine, and iodine groups.

[0053] "Haloalkyl" means a non-branched or branched alkyl group in which one or more hydrogen atoms have been halogenated as defined above. For example, in the case where the residues are substituted with more than one halogen, it may be designated by using a prefix corresponding to the number of halogen moieties attached. Dihaloalkyl and trihaloalkyl refer to alkyl groups substituted with two ("di") or three ("tri") halogen groups, which may be, but are not required to be, the same halogen. Examples of haloalkyl include difluoromethyl (-CHF2) and trifluoromethyl (-CF3).

[0054] "Heteroalkylene" refers to a divalent and unbranched saturated hydrocarbon chain having one, two, or three heteroatoms selected from NH, O, or S. As used herein, heteroelongyl groups have 1 to 20 carbon atoms and one, two, or three heteroatoms selected from NH, O, and S (i.e., C1-20 heteroelongyl groups); 1 to 8 carbon atoms and one, two, or three heteroatoms selected from NH, O, and S (i.e., C1-8 heteroelongyl groups); 1 to 6 carbon atoms and one, two, or three heteroatoms selected from NH, O, and SS (i.e., C1-6 heteroelongyl groups); 1 to 4 carbon atoms and one, two, or three heteroatoms selected from NH, O, and S (i.e., C1-4 heteroelongyl groups); 1 to 3 carbon atoms and one, two, or three heteroatoms selected from NH, O, and S (i.e., C1-3 heteroelongyl groups); or 1 to 2 carbon atoms and one, two, or three heteroatoms selected from NH, O, and S (i.e., C1-3 heteroelongyl groups); for example, -CH2O- series C 1. A heterodialkyl group, wherein -CH 2SCH 2- is a C 2 heterodialkyl group. Examples of heterodialkyl groups include -CH 2CH 2OCH 2-, -CH 2SCH 2OCH 2-, -CH 2O-, and -CH 2NHCH 2-. In some embodiments, the heterodialkyl group is optionally alkyl-substituted. Examples of substituted heterodialkyl groups include -CH(CH 3)N(CH 3)CH 2-, -CH 2OCH(CH 3)-, -CH 2CH(CH 2CH 3)S-, -CH 2NHC(CH 3) 2-, -C(CH 3) 2SCH 2-, -CH(CH 3)N(CH 3)CH(CH 3)O-, -CH 2SC(CH 2CH 3)(CH 3)-, and -CH 2C(CH 2CH 3) 2NH-.

[0055] "Heteroaryl" refers to an aromatic group having a single ring, multiple rings, or multiple fused rings, having one or more cyclic heteroatoms independently selected from nitrogen, oxygen, and sulfur. As used herein, heteroaryl includes 1 to 20 carbon ring atoms (i.e., C1-20 heteroaryl), 3 to 12 carbon ring atoms (i.e., C3-12 heteroaryl), or 3 to 8 carbon ring atoms (i.e., C3-8 heteroaryl); and 1 to 5 cyclic heteroatoms, 1 to 4 cyclic heteroatoms, 1 to 3 cyclic heteroatoms, 1 to 2 cyclic heteroatoms, or 1 cyclic heteroatomum independently selected from nitrogen, oxygen, and sulfur. Examples of heteroaryl include pyrimidinyl, purine, pyridinyl, teryl, benzothiazolyl, and pyrazolyl. Heteroaryl does not encompass or overlap with aryl groups as defined above.

[0056] "Heterocyclyl" or "heterocyclic ring / heterocycle" refers to a non-aromatic cycloalkyl group having one or more independent cyclic heteroatoms selected from nitrogen, oxygen, and sulfur. Unless otherwise indicated, as used herein, "heterocyclyl" or "heterocyclic" refers to a saturated or partially saturated ring; for example, in some embodiments, "heterocyclyl" or "heterocyclic" refers to a partially saturated ring in specified cases. The term "heterocyclyl" or "heterocyclic ring / heterocycle" includes heterocyclic alkenyl groups (i.e., heterocyclic groups having at least one double bond). Heterocyclic groups can be monocyclic or polycyclic, wherein polycyclic groups can be fused, bridged, or spirocyclic. As used herein, a heterocyclic group has 2 to 20 carbon ring atoms (i.e., C 2-20 heterocyclic group), 2 to 12 carbon ring atoms (i.e., C 2-12 heterocyclic group), 2 to 10 carbon ring atoms (i.e., C 2-10 heterocyclic group), 2 to 8 carbon ring atoms (i.e., C 2-8 heterocyclic group), 3 to 12 carbon ring atoms (i.e., C 3-12 heterocyclic group), 3 to 8 carbon ring atoms (i.e., C 3-8 heterocyclic group), or 3 to 6 carbon ring atoms (i.e., C 3-6 heterocyclic group); and has 1 to 5 ring heteroatoms, 1 to 4 ring heteroatoms, 1 to 3 ring heteroatoms, 1 to 2 ring heteroatoms, or 1 ring heteroatomum independently selected from nitrogen, sulfur, or oxygen. Examples of heterocyclic groups include pyrrolidinyl, piperidinyl, piperyl, oxetanyl, dioxolanyl, azetidinyl, and linyl. As used herein, the term "bridged-heterocyclyl" refers to a four- to ten-membered ring moiety having at least one or more (e.g., one or two) four- to ten-membered ring moieties connected at two non-adjacent atoms of the heterocyclic group, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur. As used herein, "bridged-heterocyclyl" includes bicyclic and tricyclic ring systems. As used herein, the term "spiro-heterocyclyl" refers to a ring system in which a three- to ten-membered heterocyclyl group has one or more additional rings, wherein the one or more additional rings are three- to ten-membered cycloalkyl groups or three- to ten-membered heterocyclyl groups, and wherein each atom of the one or more additional rings is also an atom of the three- to ten-membered heterocyclyl group. Examples of spiro-heterocyclyl groups include bicyclic and tricyclic ring systems, such as 2-oxa-7-azaspiro[3.5]nonyl, 2-oxa-6-azaspiro[3.4]octyl, and 6-oxa-1-azaspiro[3.3]heptyl.As used herein, the terms "heterocycle," "heterocyclyl," and "heterocyclic ring" are used interchangeably. In some embodiments, the heterocyclyl group is substituted with a side oxygen group.

[0057] “heterocycloxy” refers to the group “-O(heterocyclyl)”. Examples of heterocycloxy groups include, but are not limited to, -O(pyrrolidyl), -O(tetrahydrofuranyl), -O(piperidinyl), -O(linyl), -O(oxo-uryl), and -O(2-oxa-7-azaspiro[3.5]nonyl).

[0058] "hydroxyl" refers to the group -OH.

[0059] "Side group (oxo)" refers to the group (=O) or (O).

[0060] "sulfonyl" refers to the group -S(O)2Rbb, where Rbb is an alkyl, haloalkyl, heterocyclic, cycloalkyl, heteroaryl, or aryl group. Examples of sulfonyl groups are methanesulfonyl, ethanesulfonyl, benzenesulfonyl, and toluenesulfonyl.

[0061] Unless otherwise indicated, whenever the graphical representation of a group ends with a single bonded nitrogen atom, the group represents an -NH group. Similarly, unless otherwise indicated, hydrogen atoms are implied and considered to be present, as required by the knowledge of one of ordinary skill in the art, to complete the valence or to provide stability.

[0062] The terms "optional" or "optionally" mean that the event or situation described below may or may not occur, and the description includes both the occurrence and non-occurrence of the event or situation. In addition, the term "optionally substituted" means that any one or more hydrogen atoms on the specified atom or group may or may not be substituted by any part other than hydrogen.

[0063] The term "substituted" means that one or more hydrogen atoms on a specified atom or group are replaced by one or more substituents other than hydrogen, provided that the substitution does not exceed the normal valence of the specified atom. One or more substituents include, but are not limited to, alkyl, alkenyl, alkynyl, alkoxy, acetyl, amino, acetamyl, formamidinyl, aryl, azide, aminomethyl, carboxyl, carboxyl ester, cyano, guanidinyl, halogen, haloalkyl, heteroalkyl, heteroaryl, heterocyclic, hydroxyl, hydrazyl, imino, serooxy, nitro, alkylsulfinyl, sulfonic acid, alkylsulfonyl, thiocyanate, thiol, thion, or combinations thereof. Polymers or similar infinite structures obtained by defining substituents by an unlimited number of additional substituents (e.g., a substituted aryl group having a substituted alkyl group, the substituted alkyl group itself being substituted with a substituted aryl group, the substituted aryl group being further substituted with a substituted heteroalkyl group, etc.) are not intended to be included herein. Unless otherwise stated, the maximum number of successive substitutions in the compounds described herein is three. For example, a substituted aryl group consecutively substituted with two other substituted aryl groups is limited to an aryl group substituted with ((substituted aryl) substituted) aryl group. Similarly, the above definitions are not intended to include prohibited substitution patterns (e.g., a methyl group substituted with five fluorine atoms or a heteroaryl group having two adjacent oxygen ring atoms). Such prohibited substitution patterns are well known to those skilled in the art. When used to modify chemical groups, the term "substituted" may describe other chemical groups as defined herein. For example, the term "substituted aryl" includes, but is not limited to, "alkylaryl". Unless otherwise stated, when a group is described as optionally substituted, any substituted element of that group is itself unsubstituted.

[0064] In some embodiments, the substituted cycloalkyl, substituted heterocyclic, substituted aryl, and / or substituted heteroaryl comprise cycloalkyl, heterocyclic, aryl, and / or heteroaryl having substituents on the ring atom, which attach the cycloalkyl, heterocyclic, aryl, and / or heteroaryl to the remainder of the compound. For example, in the following portion, the cyclopropyl is substituted with a methyl group:

[0065] The compounds of the embodiments disclosed herein, or their pharmaceutically acceptable salts, may contain one or more asymmetric centers, and thus may produce mirror-image isomers, non-mirror-image isomers, and other stereoisomers, which may be defined by absolute stereochemistry as (R)- or (S)-, or for amino acids as (D)- or (L)-. This disclosure is intended to include all such possible isomers, as well as their racemic and optically pure forms. Optically active (+) and (-), (R)- and (S)-, or (D)- and (L)- isomers may be prepared using a biosynthetic component or a biosynthetic reagent, or resolved using conventional techniques such as chromatography and fractional crystallization. Conventional techniques for preparing / isolating individual mirror-image isomers include biosynthetic synthesis or resolution of racemic products (or racemic products of salts or derivatives) from suitable optically pure precursors using, for example, biosynthetic high-pressure liquid chromatography (HPLC). When the compounds described herein contain olefinic double bonds or other geometrically asymmetric centers, unless otherwise specified, it is intended that such compounds include both E and Z geometric isomers. Similarly, it is intended to include all tautomer forms. When a compound is expressed in its scalemic form, it should be understood that the examples cover, but are not limited to, specific non-mirrormic or mirror-isomer enriched forms. When scalemicity is not specified but present, it should be understood that the examples relate to specific non-mirrormic or mirror-isomer enriched forms; or racemic or non-racemic mixtures of such compounds. As used herein, a "scalemic mixture" is a mixture of stereoisomers in a non-1:1 ratio.

[0066] "Stereoisomer" refers to a compound consisting of identical atoms bonded by the same bonds but with different three-dimensional structures, and such compounds are not interchangeable. This disclosure envisions various stereoisomers and mixtures thereof, including "enantiomers," which refer to two stereoisomers whose molecules are non-overlapping mirror images of each other.

[0067] A "mirror image isomer" is a pair of stereoisomers that are non-overlapping mirror images of each other. A 1:1 mixture of a pair of mirror image isomers is a "racemic" mixture. A mixture of mirror image isomers in a ratio other than 1:1 is a "scalemic" mixture.

[0068] "A non-mirror image isomer" is a stereoisomer that has at least two asymmetric atoms but is not a mirror image of each other.

[0069] "Tautomer" refers to a proton shift from one atom of a molecule to another atom of the same molecule. This disclosure includes tautomers of any compounds provided herein.

[0070] Some of the compounds provided herein exist as tautomers. These tautomers are in equilibrium with each other. For example, compounds containing acetylamines can exist in equilibrium with imine tautomers. Regardless of the type of tautomers exhibited or the equilibrium nature between them, those skilled in the art will understand that a compound comprises both acetylamine and imine tautomers. Therefore, compounds containing acetylamines should be understood to include their imine tautomers. Similarly, compounds containing imines should be understood to include their acetylamine tautomers.

[0071] A "solvate" is formed by the interaction of a solvent and a compound. Solvates of salts of the compounds provided herein are also provided. Hydrates of the compounds provided herein are also provided.

[0072] Any formula or structure provided herein is intended to represent both the unlabeled and isotopically labeled forms of the compounds. Isotopically labeled compounds have the structures illustrated by the formulas given herein, except that one or more atoms are replaced by atoms having selected atomic masses or mass numbers. Examples of isotopes that may be incorporated into the compounds disclosed herein include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, and chlorine, such as, but not limited to, 2H (deuterium, D), 3H (tritium), 11C, 13C, 14C, 15N, 18F, 31P, 32P, 35S, 36Cl, and 125I. Various isotopically labeled compounds disclosed herein are also provided, for example, those incorporating radioactive isotopes (such as 2H, 3H, 13C, and 14C). These isotopically labeled compounds can be used in metabolic studies, reaction kinetic studies, detection or imaging techniques (such as positron emission tomography (PET) or single-photon emission computed tomography (SPECT)), including drug or substrate distribution detection, or for the treatment of patients with radiation.

[0073] This disclosure also includes compounds of Formula I with one to n hydrogen atoms attached to carbon atoms that have been deuterated, wherein n is the number of hydrogen atoms in the molecule. Such compounds exhibit increased resistance to metabolism and can therefore be used to increase the half-life of any Formula I compound when administered to mammals, particularly humans. 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 using starting materials in which one or more hydrogen atoms have been deuterated.

[0074] The deuterium-labeled or substituted therapeutic compounds disclosed herein may possess improved drug metabolism and pharmacokinetic (DMPK) properties, which are related to absorption, distribution, metabolism, and excretion (ADME). Substitution with a heavier isotope (such as deuterium) can provide certain therapeutic advantages due to higher metabolic stability, such as increased in vivo half-life, reduced dose requirement, and / or improved therapeutic index. 18F-labeled compounds can be used in PET or SPECT studies. The isotope-labeled compounds and their prodrugs disclosed herein can generally be prepared by performing the procedures disclosed in the following schemes or examples and preparations, and by replacing unlabeled reagents with readily available isotope-labeled reagents. It should be understood that, in this context, deuterium is considered as a substituent in compounds of Formula I.

[0075] The concentration of this heavier isotope (specifically deuterium) can be defined by the isotope enrichment factor. In the compounds disclosed herein, any atom not specifically designated as a particular isotope is intended to represent any stable isotope of that atom. Unless otherwise stated, when a position is specifically designated as "H" or "hydrogen," that position is understood to have hydrogen in its naturally abundant isotopic composition. Therefore, in the compounds disclosed herein, any atom specifically designated as deuterium (D) is intended to represent deuterium.

[0076] In many cases, the compounds disclosed herein can form acid salts and / or base salts by means of the presence of amine and / or carboxyl groups or similar groups.

[0077] The term "pharmaceutically acceptable salt" as used for a given compound refers to a salt that retains the biological efficacy and properties of the given compound and is not biologically or otherwise undesirable. Medically acceptable base addition salts can be prepared from inorganic and organic bases. Salts derived from inorganic bases include (by example only) sodium, potassium, lithium, ammonium, calcium, and magnesium salts. Salts derived from organic bases include, but are not limited to, the following: primary, secondary, and tertiary amines, such as alkylamines, dialkylamines, trialkylamines, substituted alkylamines, di(substituted alkyl)amines, tri(substituted alkyl)amines, alkenylamines, dienylamines, trienylamines, substituted alkenylamines, di(substituted alkenyl)amines, tri(substituted alkenyl)amines, mono-, di-, or tricycloalkylamines, mono-, di-, or triarylamines, or mixed amines, and the like. Specific examples of suitable amines include (by way of example only) isopropylamine, trimethylamine, diethylamine, tri(isopropyl)amine, tri(n-propyl)amine, ethanolamine, 2-dimethylaminoethanol, piperidine, piperidine, porphyrin, N-ethylpiperidine, and the like.

[0078] Pharmaceutically acceptable acid addition salts can be prepared from inorganic and organic acids. Salts derived from inorganic acids include salts of hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like. Salts derived from organic acids include salts of acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, malic acid, malonic acid, succinic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and the like.

[0079] As used herein, "pharmaceutically acceptable carrier" or "pharmaceutically acceptable excipient" includes any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonics and absorption delay agents, and the like. The use of such media and agents for pharmaceutically active substances is well known in the art. Unless any known media or agent is incompatible with the active ingredient, its use in therapeutic compositions is covered. Additional active ingredients may also be incorporated into the composition.

[0080] "Treatment" is a method for obtaining a beneficial or desired outcome, including clinical outcomes. A beneficial or desired clinical outcome may include one or more of the following: a) suppressing a disease or condition (i.e., reducing one or more symptoms arising from the disease or condition, and / or reducing the severity of the disease or condition); b) slowing or preventing the development of one or more clinical symptoms associated with the disease or condition (i.e., stabilizing the disease or condition, preventing or delaying the deterioration or progression of the disease or condition, and / or preventing or delaying the spread of the disease or condition (i.e., metastasis)); and / or c) alleviating the disease, i.e., the cessation of clinical symptoms (i.e., improving the disease state, providing partial or overall relief of the disease or condition, enhancing the effect of another drug, delaying the progression of the disease, improving the quality of life, and / or prolonging survival).

[0081] "Prevention" means any treatment of a disease or condition that prevents the development of clinical symptoms. In some embodiments, the compound may be administered to a subject (including humans) who is at risk or has a family history of the disease or condition.

[0082] "Subject" means an animal, such as a mammal (including a human), that has become or will become a subject of treatment, observation, or experimentation. The methods described herein can be used for human therapeutics and / or veterinary applications. In some embodiments, the subject is a mammal. In one embodiment, the subject is a human.

[0083] The terms "therapeutically effective amount" or "effective amount" used herein to describe compounds or their pharmaceutically acceptable salts, isomers, or mixtures mean an amount sufficient, when administered to a subject, to achieve therapeutic effect and provide therapeutic benefits (such as improvement of symptoms or slowing of disease progression). For example, a therapeutically effective amount may be an amount sufficient to improve symptoms of a disease or condition that responds to inhibition of receptors 7, 8, and / or 9. Therapeuticly effective amounts can vary depending on the subject being treated and the disease or condition, the subject's weight and age, the severity of the disease or condition, and the method of administration, and can be readily determined by someone skilled in the art. II. Compounds

[0084] In one embodiment, compounds of formula I, formula I, or pharmaceutically acceptable salts thereof are provided herein, wherein R1 is an 8- to 15-member fused tricyclic heterocyclic group or an 8- to 15-member fused tricyclic heteroaryl group, wherein the 8- to 15-member fused tricyclic heterocyclic group and the 8- to 15-member fused tricyclic heteroaryl group are each optionally substituted by 1 to 4 Ra groups; R2 is a C1-6 alkyl group, wherein the C1-6 alkyl group is optionally substituted by 1 to 4 groups independently selected from halogens and C1-6 alkoxy groups, wherein the C1-6 alkoxy group is optionally substituted by 1 to 3 halogen groups; R3 is a H, halogen, -CN, C1-6 alkyl, and C3-7 monocyclic cycloalkyl group, wherein the C1-6 alkyl and C3-7 monocyclic cycloalkyl groups are each optionally substituted by 1 to 3 groups independently selected from the following groups: -OH, halogen, -CN, and C 1-4 alkoxy groups, wherein the C1-4 alkoxy group is optionally substituted with 1 to 3 halogen groups; Z-series C1-6 alkyl, -C(O)R13-C(O)NR6R7, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, 4 to 7-membered monocyclic heterocyclic group, phenyl, 5 to 6-membered monocyclic heteroaryl, 8 to 10-membered fused bicyclic heterocyclic group, 6 to 10-membered bridged bicyclic heterocyclic group, 8 to 10-membered fused bicyclic heteroaryl, or 7 to 10-membered spirocyclic heterocyclic group, wherein the C1-6 alkyl group is optionally substituted with 1 to 4 Rb groups; wherein the C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C The 5-10-membered bridged bicyclic cycloalkyl, 4-7-membered monocyclic heterocyclic, phenyl, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, and 7-10-membered spirocyclic heterocyclic are each optionally substituted with 1-2 R8 groups and each optionally substituted with 1-3 Ra groups; the R6 group consists of C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, 4-7-membered monocyclic heterocyclic, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, or 7-10-membered spirocyclic heterocyclic, wherein the C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5 ... The 5-10-membered bridged bicyclic cycloalkyl, 4-7-membered monocyclic heterocyclic, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, and 7-10-membered spirocyclic heterocyclic groups are each optionally substituted with 1 to 4 Ra groups; the R13 group consists of 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, or 7-10-membered spirocyclic heterocyclic groups.The 4- to 7-membered monocyclic heterocyclic group, the 5- to 6-membered monocyclic heteroaryl group, the 8- to 10-membered fused bicyclic heterocyclic group, the 6- to 10-membered bridged bicyclic heterocyclic group, the 8- to 10-membered fused bicyclic heteroaryl group, and the 7- to 10-membered spirocyclic heterocyclic group are each optionally substituted with 1 to 4 Ra groups; R7 is H, C1-6 alkyl, C3-7 monocyclic cycloalkyl, or 4- to 6-membered monocyclic heterocyclic group, wherein the C1-6 alkyl, C3-7 monocyclic cycloalkyl, and the 4- to 6-membered monocyclic heterocyclic group are each optionally substituted with 1 to 4 groups independently selected from -OH, halogen, -CN, and C1-6 alkoxy; each R8 is independently halogen, -C(O)R9, -NR10R10, C1-6 alkyl, C3-7 monocyclic cycloalkyl, C 7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, 4-7 member monocyclic heterocyclic, phenyl, 5-6 member monocyclic heteroaryl, 8-10 member fused bicyclic heterocyclic, 6-10 member bridged bicyclic heterocyclic, 8-10 member fused bicyclic heteroaryl, 7-10 member spirocyclic heterocyclic, -OR 5, -C(O)N(R 5)(R 5), -N(R 5) 2(R 5) +, -N(R 5)C(O)R 5, -N(R 5)C(O)OR 5, -N(R 5)C(O)N(R 5)(R 5), -N(R 5)S(O) 2(R 5a), -NR 5S(O) 2N(R 5)(R 5), -NR 5S(O) 2O(R 5a), -OC(O)N(R5)(R5), -S(O)R5a, -S(O)(NH)R5, -S(O)2R5a, -S(O)2N(R5)(R5), or -N=S(R5a)(R5a)=O, wherein the C1-6 alkyl group is optionally substituted with 1 to 4 Rb groups, wherein the C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, 4 to 7-membered monocyclic heterocyclic group, phenyl, 5 to 6-membered monocyclic heteroaryl, 8 to 10-membered fused bicyclic heterocyclic group, 6 to 10-membered bridged bicyclic heterocyclic group, 8 to 10-membered fused bicyclic heteroaryl, and 7 to 10-membered spirocyclic heterocyclic group are each independently optionally substituted with 1 to 4 Ra groups; each R9 is independently C 3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7 member monocyclic heterocyclic group, 5-6 member monocyclic heteroaryl, 8-10 member fused bicyclic heterocyclic group, 6-10 member bridged bicyclic heterocyclic group, 8-10 member fused bicyclic heteroaryl, or 7-10 member spirocyclic heterocyclic group, wherein the C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7 member monocyclic heterocyclic group, 5-6 member monocyclic heteroaryl group, C5-10 member spirocyclic heterocyclic group, C5-10 member monocyclic cycloalkyl, C5-10 bridged bi ...The 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, and 7-10-membered spirocyclic heterocyclic groups are each optionally substituted with 1 to 4 Ra groups; each R5 and R10 is independently H, C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, or 7-10-membered spirocyclic heterocyclic, wherein the C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl groups are each optionally substituted by 1 to 4 Rb groups, wherein the C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C The 5-10 bridging bicyclic cycloalkyl, phenyl, naphthyl, 4-7 member monocyclic heterocyclic, 5-6 member monocyclic heteroaryl, 8-10 member fused bicyclic heterocyclic, 6-10 member bridging bicyclic heterocyclic, 8-10 member fused bicyclic heteroaryl, and 7-10 member spirocyclic heterocyclic groups are each optionally substituted with 1 to 4 Ra groups; each R 5a is independently a C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 monocyclic cycloalkyl, C 7-10 fused bicyclic cycloalkyl, C 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, or 7-10-membered spirocyclic heterocyclic, wherein the C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl groups are each optionally substituted by 1 to 4 Rb groups, wherein the C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C The 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, and 7-10-membered spirocyclic heterocyclic groups are each optionally substituted with 1 to 4 Ra groups; each Ra is independently substituted with a side oxygen, imino, halogen, -NO2, -N3, -CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, 7-10-membered spirocyclic heterocyclic, -OR 11, -C(O)R 11, -C(O)OR11. -C(O)N(R 11)(R 11), -NR 11R 11. -N(R 11) 2(R 11) +, -N(R 11)C(O)R 11. -N(R 11)C(O)OR 11. -N(R 11)C(O)N(R 11)(R 11), -N(R 11)S(O) 2(R 11a), -NR 11S(O) 2N(R 11)(R 11), -NR 11S(O) 2O(R 11a), -OC(O)R 11, -OC(O)OR 11, -OC(O)N(R 11)(R 11), -SR 11, -S(O)R 11a, -S(O)(NH)R 11, -S(O) 2R 11a, -S(O)2N(R11)(R11), or -N=S(R11a)(R11a)=O, wherein the C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl groups are each independently and optionally substituted with 1 to 3 Rc groups, wherein the C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4 to 7-membered monocyclic heterocyclic, 5 to 6-membered monocyclic heteroaryl, 8 to 10-membered fused bicyclic heterocyclic, 6 to 10-membered bridged bicyclic heterocyclic, 8 to 10-membered fused bicyclic heteroaryl, and 7 to 10-membered spirocyclic heterocyclic groups are each independently and optionally substituted with 1 to 3 Rd groups, and each Rb is independently a side oxygen group, imine group, halogen, -NO2, -N 3, -CN, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4 to 7 member monocyclic heterocyclic, 5 to 6 member monocyclic heteroaryl, 8 to 10 member fused bicyclic heterocyclic, 8 to 10 member bridged bicyclic heterocyclic, 6 to 10 member bridged bicyclic heterocyclic, 8 to 10 member fused bicyclic heteroaryl, 7 to 10 member spirocyclic heterocyclic, -OR 11, -C(O)R 11, -C(O)OR 11, -C(O)N(R 11)(R 11), -NR 11R 11, -N(R 11) 2(R 11) +, -N(R 11)C(O)R 11, -N(R 11)C(O)OR 11, -N(R 11)C(O)N(R 11)(R 11), -N(R 11)S(O) 2(R 11a), -NR 11S(O) 2N(R 11)(R 11), -NR 11S(O) 2O(R 11a), -OC(O)R 11, -OC(O)OR 11, -OC(O)N(R 11)(R 11), -SR 11, -S(O)R 11a, -S(O)(NH)R 11, -S(O) 2R 11a, -S(O) 2N(R 11)(R 11), or -N=S(R 11a)(R11a)=O, wherein the C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4 to 7-membered monocyclic heterocyclic group, 5 to 6-membered monocyclic heteroaryl, 8 to 10-membered fused bicyclic heterocyclic group, 6 to 10-membered bridged bicyclic heterocyclic group, 8 to 10-membered fused bicyclic heteroaryl, and 7 to 10-membered spirocyclic heterocyclic group are each optionally substituted by 1 to 3 Rd groups; each Rc is independently halogenated, -CN, C7-10 fused bicyclic cycloalkyl, C 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, 7-10-membered spirocyclic heterocyclic, -OR 12, -C(O)R 12, -C(O)OR 12, -C(O)N(R 12)(R 12), -NR 12R 12, -N(R 12) 2(R 12) +, -N(R 12)C(O)R 12, -N(R 12)C(O)OR 12, -N(R 12)C(O)N(R 12)(R 12), -N(R 12)S(O) 2(R 12a), -NR 12S(O) 2N(R 12)(R 12), -NR 12S(O) 2O(R 12a), -OC(O)R 12, -OC(O)OR 12, -OC(O)N(R 12)(R 12), -SR 12, -S(O)R 12a, -S(O)(NH)R 12, -S(O) 2R 12a, -S(O) 2N(R 12)(R 12), or -N=S(R 12a)(R 12a)=O; Each R d is independently associated with a side oxygen group, halogen, -CN, C 1-6 alkyl, C 7-10 fused bicyclic cycloalkyl, C 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, 7-10-membered spirocyclic heterocyclic, -OR 12, -C(O)R 12, -C(O)OR 12, -C(O)N(R 12)(R 12), -NR 12R 12, -N(R 12) 2(R 12) +, -N(R 12)C(O)R 12, -N(R 12)C(O)OR 12, -N(R 12)C(O)N(R 12)(R 12), -N(R 12)S(O) 2(R 12a), -NR 12S(O) 2N(R 12)(R 12), -NR 12S(O) 2O(R 12a), -OC(O)R 12, -OC(O)OR 12, -OC(O)N(R 12)(R 12), -SR12, -S(O)R12a, -S(O)(NH)R12, -S(O)2R12a, -S(O)2N(R12)(R12), or -N=S(R12a)(R12a)=O, wherein the C1-6 alkyl group is optionally substituted by 1 to 3 groups independently selected from the following: -OH, halogen, -CN, and C1-3 alkoxy; each R11 is independently H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C The group comprises 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, or 7-10-membered spirocyclic heterocyclic, wherein each of the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, and 7-10-membered spirocyclic heterocyclic groups is optionally substituted with 1 to 3 Rc groups; each Rc group is substituted with one or more Rc groups. 11a Independently comprises C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4 to 7-membered monocyclic heterocyclic group, 5 to 6-membered monocyclic heteroaryl, 8 to 10-membered fused bicyclic heterocyclic group, 6 to 10-membered bridged bicyclic heterocyclic group, 8 to 10-membered fused bicyclic heteroaryl, or 7 to 10-membered spirocyclic heterocyclic group, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 condensed bicyclic cycloalkyl, C6-6 alkyl, C7-10 condensed bicyclic cyclo ... The 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, and 7-10-membered spirocyclic heterocyclic groups are each optionally substituted with 1 to 3 Rc groups; each R12 is independently H, C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C12 alkyl, C2-6 alkyne, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C12 alkyl, C3-7 cycloalkyl, C7-10 fused bicyclic cycloalkyl, C7 cycloalkyl, C7 cycloalkyl, C8 cycloalkyl, C9 cycloalkyl, C10 cycloalkyl, C9 cycloalkyl, C12 ... 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, or 7-10-membered spirocyclic heterocyclic; each R 12a is independently C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic group, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic group, 6-10-membered bridged bicyclic heterocyclic group, 8-10-membered fused bicyclic heteroaryl, or 7-10-membered spirocyclic heterocyclic group, wherein each 4-membered monocyclic heterocyclic group independently has one cyclic heteroatom selected from N, O, and S; each 5-7-membered monocyclic heterocyclic group independently has one to two cyclic heteroatoms independently selected from N, O, and S; each 6-membered bridged bicyclic heterocyclic group independently has one cyclic heteroatom selected from N, O, and S; and each 7-membered bridged bicyclic heterocyclic group independently has one to two cyclic heteroatoms independently selected from N, O, and S. Each of the 5 to 6 monocyclic heteroaryl groups, 8 to 10 fused bicyclic heteroaryl groups, 8 to 10 bridged bicyclic heteroaryl groups, 8 to 10 fused bicyclic heteroaryl groups, and 7 to 10 spirocyclic heteroaryl groups independently has 1 to 4 cyclic heteroatoms independently selected from N, O, and S; and each of the 8 to 15 fused tricyclic heteroaryl groups and 8 to 15 fused tricyclic heteroaryl groups independently has 1 to 7 cyclic heteroatoms independently selected from N, O, and S.

[0085] In some embodiments of the compounds of formula I or their pharmaceutically acceptable salts, the Z-groups are C7-10 fused bicyclic cycloalkyl, 8-10 fused bicyclic heterocyclic, 6-10 bridging bicyclic heterocyclic, or 8-10 fused bicyclic heteroaryl, wherein the C7-10 fused bicyclic cycloalkyl, 8-10 fused bicyclic heterocyclic, 6-10 bridging bicyclic heterocyclic, and 8-10 fused bicyclic heteroaryl are each optionally substituted with 1 to 2 R8 groups and each optionally substituted with 1 to 3 Ra groups.

[0086] In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, R1 is an 8- to 15-member fused tricyclic heterocyclic group, optionally substituted with 1 to 4 Ra groups; R2 is a C1-6 alkyl group, wherein the C1-6 alkyl group is optionally substituted with 1 to 4 groups independently selected from halogens and C1-6 alkoxy groups, wherein the C1-6 alkoxy group is optionally substituted with 1 to 3 halogen groups; R3 is an H or C1-6 alkyl group, wherein the C1-6 alkyl group is optionally substituted with 1 to 3 groups independently selected from the following groups: -OH, halogen, -CN, and C1-4 alkoxy groups, wherein the C1-4 alkoxy group is optionally substituted with 1 to 3 halogen groups; Z-series 4- to 7-membered monocyclic heterocyclic groups, phenyl groups, 5- to 6-membered monocyclic heteroaryl groups, 8- to 10-membered fused bicyclic heterocyclic groups, 6- to 10-membered bridged bicyclic heterocyclic groups, or 7- to 10-membered spirocyclic heterocyclic groups, wherein each of the 4- to 7-membered monocyclic heterocyclic groups, phenyl groups, 5- to 6-membered monocyclic heteroaryl groups, 8- to 10-membered fused bicyclic heterocyclic groups, 6- to 10-membered bridged bicyclic heterocyclic groups, and 7- to 10-membered spirocyclic heterocyclic groups is independently and optionally substituted with 1 to 2 R8 groups and is independently and optionally substituted with 1 to 3 Ra groups; each R8 is independently -C(O)R9, C1-6 alkyl, 4- to 7-membered monocyclic heterocyclic group, or -S(O)2R5a, wherein the C1-6 alkyl group is optionally substituted with 1 to 4 Rb groups, and wherein the 4- to 7-membered monocyclic heterocyclic group is optionally substituted with 1 to 4 Rb groups. The α group is substituted; each R9 is independently a C3-7 monocyclic cycloalkyl or a 4- to 7-membered monocyclic heterocyclic group, wherein the C3-7 monocyclic cycloalkyl and the 4- to 7-membered monocyclic heterocyclic group are each independently optionally substituted with 1 to 4 Ra groups; R5a is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is optionally substituted with 1 to 4 Ra groups; each Ra is independently a side oxygen group, imino group, halogen, -NO2, -N3, -CN, C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, 7-10-membered spirocyclic heterocyclic, -OR 11, -C(O)R 11, -C(O)OR 11, -C(O)N(R 11)(R 11), -NR 11R 11, -N(R 11) 2(R 11) +, -N(R 11)C(O)R 11, -N(R 11)C(O)OR 11, -N(R 11)C(O)N(R 11)(R 11), -N(R 11)S(O) 2(R 11a), -NR 11S(O) 2N(R 11)(R11) -NR 11S(O) 2O(R 11a), -OC(O)R 11, -OC(O)OR 11, -OC(O)N(R 11)(R 11), -SR 11, -S(O)R 11a, -S(O)(NH)R 11, -S(O) 2R 11a, -S(O) 2N(R 11)(R 11), or -N=S(R 11a)(R 11a)=O, wherein the C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl groups are each optionally substituted by 1 to 3 Rc groups, wherein the C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, and C The 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, and 7-10-membered spirocyclic heterocyclic groups are each optionally substituted by 1 to 3 Rd groups, and each Rb is independently a side oxygen, imino, halogen, -NO2, -N3, -CN, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 8-10-membered bridged bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, 7-10-membered spirocyclic heterocyclic, -OR 11, -C(O)R 11, -C(O)OR 11, -C(O)N(R 11)(R 11), -NR 11R 11, -N(R 11) 2(R 11) +, -N(R 11)C(O)R 11, -N(R 11)C(O)OR 11, -N(R 11)C(O)N(R 11)(R 11), -N(R 11)S(O) 2(R 11a), -NR 11S(O) 2N(R 11)(R 11), -NR 11S(O) 2O(R 11a), -OC(O)R 11, -OC(O)OR 11, -OC(O)N(R 11)(R 11), -SR 11, -S(O)R 11a, -S(O)(NH)R 11, -S(O) 2R 11a, -S(O) 2N(R 11)(R 11), or -N=S(R 11a)(R 11a)=O, wherein the C 3-7 monocyclic cycloalkyl, C 7-10 fused bicyclic cycloalkyl, C The 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, and 7-10-membered spirocyclic heterocyclic groups are each optionally substituted by 1 to 3 Rd groups; each Rc-Independent halogens, -CN, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7 member monocyclic heterocyclic, 5-6 member monocyclic heteroaryl, 8-10 member fused bicyclic heterocyclic, 6-10 member bridged bicyclic heterocyclic, 8-10 member fused bicyclic heteroaryl, 7-10 member spirocyclic heterocyclic, -OR 12, -C(O)R 12, -C(O)OR 12, -C(O)N(R 12)(R 12), -NR 12R 12, -N(R 12) 2(R 12) +, -N(R 12)C(O)R 12, -N(R 12)C(O)OR 12, -N(R 12)C(O)N(R 12)(R 12), -N(R 12) S(O) 2(R 12a), -NR 12S(O) 2N(R 12)(R 12), -NR 12S(O) 2O(R 12a), -OC(O)R 12, -OC(O)OR 12, -OC(O)N(R 12)(R 12), -SR 12, -S(O)R 12a, -S(O)(NH)R 12, -S(O) 2R 12a, -S(O) 2N(R 12)(R 12), or -N=S(R 12a)(R 12a)=O; Each R d is independently associated with a side oxygen group, halogen, -CN, C1-6 alkyl, C7-10 fused bicyclic cycloalkyl, C 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, 7-10-membered spirocyclic heterocyclic, -OR 12, -C(O)R 12, -C(O)OR 12, -C(O)N(R 12)(R 12), -NR 12R 12, -N(R 12) 2(R 12) +, -N(R 12)C(O)R 12, -N(R 12)C(O)OR 12, -N(R 12)C(O)N(R 12)(R 12), -N(R 12)S(O) 2(R 12a), -NR 12S(O) 2N(R 12)(R 12), -NR 12S(O) 2O(R 12a), -OC(O)R 12, -OC(O)OR 12, -OC(O)N(R 12)(R 12), -SR 12, -S(O)R 12a, -S(O)(NH)R 12, -S(O) 2R 12a, -S(O) 2N(R 12)(R 12), or -N=S(R 12a)(R 12a)=O; Each R 11 is independently H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 monocyclic cycloalkyl, C 7-10 fused bicyclic cycloalkyl, CThe group comprises 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, or 7-10-membered spirocyclic heterocyclic, wherein each of the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, and 7-10-membered spirocyclic heterocyclic groups is optionally substituted with 1 to 3 Rc groups; each Rc group is substituted with one or more Rc groups. 11a Independently comprises C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4 to 7-membered monocyclic heterocyclic group, 5 to 6-membered monocyclic heteroaryl, 8 to 10-membered fused bicyclic heterocyclic group, 6 to 10-membered bridged bicyclic heterocyclic group, 8 to 10-membered fused bicyclic heteroaryl, or 7 to 10-membered spirocyclic heterocyclic group, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 condensed bicyclic cycloalkyl, C6-6 alkyl, C7-10 condensed bicyclic cyclo ... The 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, and 7-10-membered spirocyclic heterocyclic groups are each optionally substituted with 1 to 3 Rc groups; each R12 is independently H, C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C12 alkyl, C2-6 alkyne, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C12 alkyl, C3-7 cycloalkyl, C7-10 fused bicyclic cycloalkyl, C7 cycloalkyl, C7 cycloalkyl, C8 cycloalkyl, C9 cycloalkyl, C10 cycloalkyl, C9 cycloalkyl, C12 ... 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, or 7-10-membered spirocyclic heterocyclic; each R 12a is independently a C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 monocyclic cycloalkyl, C 7-10-membered fused bicyclic cycloalkyl, C 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, or 7-10-membered spirocyclic heterocyclic. Each of the four-membered monocyclic heterocyclic groups independently has one cyclic heteroatom selected from N, O, and S; each of the five to seven-membered monocyclic heterocyclic groups independently has one to two cyclic heteroatoms independently selected from N, O, and S; each of the six-membered bridged bicyclic heterocyclic groups independently has one cyclic heteroatom selected from N, O, and S.Each of the 7-membered bridged bicyclic heterocyclic groups independently has 1 to 2 cyclic heteroatoms independently selected from N, O, and S; each of the 5 to 6-membered monocyclic heteroaryl, 8 to 10-membered fused bicyclic heterocyclic groups, 8 to 10-membered bridged bicyclic heterocyclic groups, 8 to 10-membered fused bicyclic heteroaryl, and 7 to 10-membered spirocyclic heterocyclic groups independently has 1 to 4 cyclic heteroatoms independently selected from N, O, and S; and each of the 8 to 15-membered fused tricyclic heterocyclic groups and the 8 to 15-membered fused tricyclic heteroaryl groups independently has 1 to 7 cyclic heteroatoms independently selected from N, O, and S.

[0087] In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, R1 is an 8 to 15-member fused tricyclic heterocyclic group, optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, oxy, -NR11R11, C1-4 alkoxy, C1-6 alkyl, and C3-7 monocyclic cycloalkyl; R2 is a C1-6 alkyl group, wherein the C1-6 alkyl group is optionally substituted with 1 to 4 groups independently selected from halogen and C1-6 alkoxy; R3 is an H or C1-6 alkyl group, wherein the C1-6 alkyl group is optionally substituted with 1 to 3 groups independently selected from -OH, halogen, -CN, and C1-4 alkoxy. Z-groups consisting of 4 to 7-membered monocyclic heterocyclic groups, phenyl groups, 5 to 6-membered monocyclic heteroaryl groups, 8 to 10-membered fused bicyclic heterocyclic groups, 6 to 10-membered bridged bicyclic heterocyclic groups, or 7 to 10-membered spirocyclic heterocyclic groups, wherein each of the 4 to 7-membered monocyclic heterocyclic groups, phenyl groups, 5 to 6-membered monocyclic heteroaryl groups, 8 to 10-membered fused bicyclic heterocyclic groups, 6 to 10-membered bridged bicyclic heterocyclic groups, and 7 to 10-membered spirocyclic heterocyclic groups is optionally substituted with 1 to 2 R8 groups and is optionally substituted with 1 to 3 groups independently selected from the following groups: -OH, halogen, -CN, sideoxy group, -NR 11R 11, C 1-4 alkoxy group, and C 1-5 alkyl group; each R8 group is independently -C(O)R 9, C 1-6 alkyl group, 4 to 7-membered monocyclic heterocyclic group, or -S(O) 2R 5a. The C1-6 alkyl group is optionally substituted with 1 to 3 independently selected groups from the following: -OH, halogen, -CN, oxy group, -NR 11R 11, -C(O)NR 11R 11, C1-4 alkoxy group, and R 8a; the 4 to 7 membered monocyclic heterocyclic group is optionally substituted with 1 to 3 independently selected groups from the following: -OH, halogen, -CN, oxy group, -NR 11R 11, C1-4 alkoxy group, and C1-5 alkyl group; each R 8a is independently a 4 to 7 membered monocyclic heterocyclic group or a 5 to 6 membered monocyclic heteroaryl group, wherein the 4 to 7 membered monocyclic heterocyclic group and the 5 to 6 membered monocyclic heteroaryl group are each independently optionally substituted with 1 to 3 independently selected groups from the following: -OH, halogen, C1-4 alkoxy group, and C1-5 alkyl group; each R 9 is independently a C 3-7 monocyclic cycloalkyl or 4-7 member monocyclic heterocyclic group, wherein the C3-7 monocyclic cycloalkyl and the 4-7 member monocyclic heterocyclic group are each optionally substituted by 1 to 3 groups independently selected from the following groups: -OH, halogen, -CN, sideoxy, -NR11R11, C1-4 alkoxy, C1-5 alkyl, and 4-7 member monocyclic heterocyclic group;R5a is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is optionally substituted by 1 to 3 groups independently selected from the following: -OH, halogen, -CN, side oxygen, -NR11R11, C1-4 alkoxy, and C1-5 alkyl; each R11 is independently H or C1-6 alkyl; each R12 is independently H or C1-4 alkyl; each 4-membered monocyclic heterocyclic group independently has 1 cyclic heteroatom selected from N, O, and S; each 5- to 7-membered monocyclic heterocyclic group independently has 1 to 2 cyclic heteroatoms independently selected from N, O, and S; each 6-membered bridged bicyclic heterocyclic group independently has 1 cyclic heteroatom selected from N, O, and S; each 7-membered bridged bicyclic heterocyclic group independently has 1 to 2 cyclic heteroatoms independently selected from N, O, and S. Each of the 5-6 member monocyclic heteroaryl group, 8-10 member fused bicyclic heterocyclic group, 8-10 member bridged bicyclic heterocyclic group, 8-10 member fused bicyclic heteroaryl group, and 7-10 member spirocyclic heterocyclic group independently has 1 to 4 cyclic heteroatoms independently selected from N, O, and S; and each of the 8-15 member fused tricyclic heterocyclic group and the 8-15 member fused tricyclic heteroaryl group independently has 1 to 7 cyclic heteroatoms independently selected from N, O, and S.

[0088] Unless otherwise specified, each 4-membered monocyclic heterocyclic group used herein has one cyclic heteroatom selected from N, O, and S. Unless otherwise specified, each 5- to 7-membered monocyclic heterocyclic group used herein has one to two cyclic heteroatoms independently selected from N, O, and S. Unless otherwise specified, each 6-membered bridged bicyclic heterocyclic group used herein has one cyclic heteroatom selected from N, O, and S. Unless otherwise specified, each 7-membered bridged bicyclic heterocyclic group used herein has one to two cyclic heteroatoms independently selected from N, O, and S. Unless otherwise specified, each of the 5 to 6 member monocyclic heteroaryl, 8 to 10 member fused bicyclic heteroaryl, 8 to 10 member bridged bicyclic heteroaryl, 8 to 10 member fused bicyclic heteroaryl and 7 to 10 member spirocyclic heteroaryl used herein independently has 1 to 4 cyclic heteroatoms independently selected from N, O and S.

[0089] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R1 is an 8- to 15-member fused tricyclic heterocyclic group, wherein the 8- to 15-member fused tricyclic heterocyclic group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R1 is an 8- to 15-member fused tricyclic heterocyclic group, wherein the 8- to 15-member fused tricyclic heterocyclic group is optionally substituted with 1 to 3 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R1 is an 8- to 15-member fused tricyclic heterocyclic group, wherein the 8- to 15-member fused tricyclic heterocyclic group is optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR11R11, C1-4 alkoxy group, C1-6 alkyl group, and C3-7 monocyclic cycloalkyl group.

[0090] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R1 is an 8- to 15-membered fused tricyclic heterocyclic group, wherein the 8- to 15-membered fused tricyclic heterocyclic group is substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R1 is an 8- to 15-membered fused tricyclic heterocyclic group, wherein the 8- to 15-membered fused tricyclic heterocyclic group is substituted with 1 to 3 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R1 is an 8- to 15-membered fused tricyclic heterocyclic group, wherein the 8- to 15-membered fused tricyclic heterocyclic group is substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR11R11, C1-4 alkoxy group, C1-6 alkyl group, and C3-7 monocyclic cycloalkyl group.

[0091] In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, R1 is an 8 to 15-member fused tricyclic heterocyclic group.

[0092] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R1 is an 8- to 15-member fused tricyclic heteroaryl group, wherein the 8- to 15-member fused tricyclic heteroaryl group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R1 is an 8- to 15-member fused tricyclic heteroaryl group, wherein the 8- to 15-member fused tricyclic heteroaryl group is optionally substituted with 1 to 3 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R1 is an 8- to 15-member fused tricyclic heteroaryl group, wherein the 8- to 15-member fused tricyclic heteroaryl group is optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR11R11, C1-4 alkoxy group, C1-6 alkyl group, and C3-7 monocyclic cycloalkyl group.

[0093] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R1 is an 8- to 15-member fused tricyclic heteroaryl group, wherein the 8- to 15-member fused tricyclic heteroaryl group is substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R1 is an 8- to 15-member fused tricyclic heteroaryl group, wherein the 8- to 15-member fused tricyclic heteroaryl group is substituted with 1 to 3 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R1 is an 8- to 15-member fused tricyclic heteroaryl group, wherein the 8- to 15-member fused tricyclic heteroaryl group is substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR11R11, C1-4 alkoxy group, C1-6 alkyl group, and C3-7 monocyclic cycloalkyl group.

[0094] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, the R1 group is optionally substituted with one to three groups independently selected from halogen, C1-3 alkyl, and C1-3 alkoxy groups, wherein the C1-3 alkyl group is optionally substituted with one to three halogen groups.

[0095] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, R1 is a series.

[0096] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, R1 is a series of H, -CN, C1-6 alkyl, C1-5 alkoxy, or C3-7 monocyclic cycloalkyl, wherein the C1-6 alkyl and C1-5 alkoxy are each optionally substituted with 1 to 3 halogen groups.

[0097] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, each R 1a is independently H, -CN, -CHF 2, -CF 3, methyl, methoxy, or cyclopropyl.

[0098] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, R1 is a series or.

[0099] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R2 is a C1-6 alkyl group, wherein the C1-6 alkyl group is optionally substituted with 1 to 4 groups independently selected from halogens and C1-6 alkoxy groups, wherein the C1-6 alkoxy group is optionally substituted with 1 to 3 halogen groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R2 is a C1-6 alkyl group, wherein the C1-6 alkyl group is optionally substituted with 1 to 3 groups independently selected from halogens and C1-6 alkoxy groups, wherein the C1-6 alkoxy group is optionally substituted with 1 to 3 halogen groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R2 is a C1-6 alkyl group, wherein the C1-6 alkyl group is optionally substituted with 1 to 3 groups independently selected from halogen and C1-3 alkoxy groups, wherein the C1-3 alkoxy group is optionally substituted with 1 to 3 halogen groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R2 is a C1-6 alkyl group, wherein the C1-6 alkyl group is substituted with 1 to 4 groups independently selected from halogen and C1-6 alkoxy groups, wherein the C1-6 alkoxy group is optionally substituted with 1 to 3 halogen groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R2 is a C1-6 alkyl group, wherein the C1-6 alkyl group is substituted with 1 to 3 groups independently selected from halogen and C1-6 alkoxy groups, wherein the C1-6 alkoxy group is optionally substituted with 1 to 3 halogen groups. In some embodiments of compounds of formula I or their pharmaceutically acceptable salts, R2 is a C1-6 alkyl group, wherein the C1-6 alkyl group is substituted with one to three groups independently selected from halogens and C1-3 alkoxy groups, wherein the C1-3 alkoxy group is optionally substituted with one to three halogen groups.

[0100] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R2 is a C1-6 alkyl group, wherein the C1-6 alkyl group is optionally substituted with 1 to 4 independently selected halogen and C1-6 alkoxy groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R2 is a C1-6 alkyl group, wherein the C1-6 alkyl group is optionally substituted with 1 to 3 independently selected halogen and C1-6 alkoxy groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R2 is a C1-6 alkyl group, wherein the C1-6 alkyl group is optionally substituted with 1 to 3 independently selected halogen and C1-3 alkoxy groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R2 is a C1-6 alkyl group, wherein the C1-6 alkyl group is substituted with 1 to 4 independently selected halogen and C1-6 alkoxy groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, R2 is a C1-6 alkyl group, wherein the C1-6 alkyl group is substituted with one to three independently selected groups selected from halogens and C1-6 alkoxy groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, R2 is a C1-6 alkyl group, wherein the C1-6 alkyl group is substituted with one to three independently selected groups selected from halogens and C1-3 alkoxy groups.

[0101] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R2 is a C1-4 alkyl group, wherein the C1-4 alkyl group is optionally substituted with 1 to 4 independently selected halogen and C1-6 alkoxy groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R2 is a C1-4 alkyl group, wherein the C1-4 alkyl group is optionally substituted with 1 to 3 independently selected halogen and C1-6 alkoxy groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R2 is a C1-4 alkyl group, wherein the C1-4 alkyl group is optionally substituted with 1 to 3 independently selected halogen and C1-3 alkoxy groups.

[0102] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R2 is a C1-4 alkyl group, wherein the C1-4 alkyl group is substituted with 1 to 4 groups independently selected from halogens and C1-6 alkoxy groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R2 is a C1-4 alkyl group, wherein the C1-4 alkyl group is substituted with 1 to 3 groups independently selected from halogens and C1-6 alkoxy groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R2 is a C1-4 alkyl group, wherein the C1-4 alkyl group is substituted with 1 to 3 groups independently selected from halogens and C1-3 alkoxy groups.

[0103] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R2 is a C1-6 alkyl group. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R2 is a C1-4 alkyl group. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R2 is a C1-3 alkyl group. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R2 is ethyl or isopropyl. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R2 is methyl. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R2 is ethyl. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R2 is propyl. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R2 is isopropyl.

[0104] In some embodiments of the compounds of formula I or their pharmaceutically acceptable salts, R3 is H, halogen, -CN, C1-6 alkyl, and C3-7 monocyclic cycloalkyl, wherein the C1-6 alkyl and C3-7 monocyclic cycloalkyl groups are each optionally substituted by 1 to 3 groups independently selected from the following groups: -OH, halogen, -CN, and C1-4 alkoxy, wherein the C1-4 alkoxy group is optionally substituted by 1 to 3 halogen groups.

[0105] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, R3 is an H or C1-6 alkyl group, wherein the C1-6 alkyl group is optionally substituted with one to three groups independently selected from the following: -OH, halogen, -CN, and C1-4 alkoxy group, wherein the C1-4 alkoxy group is optionally substituted with one to three halogen groups.

[0106] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R3 is an H or C1-6 alkyl group, wherein the C1-6 alkyl group is optionally substituted with one to three independently selected groups selected from -OH, halogen, -CN, and C1-4 alkoxy groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R3 is an H or C1-6 alkyl group. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R3 is an H or methyl group.

[0107] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R3 is H. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R3 is a halogen. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R3 is -CN.

[0108] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R3 is a C3-7 monocyclic cycloalkyl group, wherein the C3-7 monocyclic cycloalkyl group is optionally substituted with 1 to 3 groups independently selected from -OH, halogen, -CN, and C1-4 alkoxy groups, wherein the C1-4 alkoxy group is optionally substituted with 1 to 3 halogen groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R3 is a C3-7 monocyclic cycloalkyl group, wherein the C3-7 monocyclic cycloalkyl group is substituted with 1 to 3 groups independently selected from -OH, halogen, -CN, and C1-4 alkoxy groups, wherein the C1-4 alkoxy group is optionally substituted with 1 to 3 halogen groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R3 is a C3-7 monocyclic cycloalkyl group.

[0109] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R3 is a C1-6 alkyl group, wherein the C1-6 alkyl group is optionally substituted with one to three groups independently selected from -OH, halogen, -CN, and C1-4 alkoxy groups, wherein the C1-4 alkoxy group is optionally substituted with one to three halogen groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R3 is a C1-6 alkyl group, wherein the C1-6 alkyl group is substituted with one to three groups independently selected from -OH, halogen, -CN, and C1-4 alkoxy groups, wherein the C1-4 alkoxy group is optionally substituted with one to three halogen groups.

[0110] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R3 is a C1-6 alkyl group, wherein the C1-6 alkyl group is optionally substituted with one to three independently selected groups selected from -OH, halogen, -CN, and C1-4 alkoxy groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R3 is a C1-6 alkyl group, wherein the C1-6 alkyl group is substituted with one to three independently selected groups selected from -OH, halogen, -CN, and C1-4 alkoxy groups.

[0111] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R3 is optionally a C1-4 alkyl group substituted with one to three independently selected groups: -OH, halogen, -CN, and C1-3 alkoxy. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R3 is a methyl group substituted with one to three halogen groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R3 is -CHF2.

[0112] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R3 is a C1-6 alkyl group. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R3 is a C1-4 alkyl group. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R3 is a C1-3 alkyl group. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R3 is a methyl group.

[0113] In some embodiments of compounds of formula I or their pharmaceutically acceptable salts, Z-groups include C1-6 alkyl, -C(O)R13, ​​-C(O)NR6R7, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, 4 to 7-membered monocyclic heterocyclic, phenyl, 5 to 6-membered monocyclic heteroaryl, 8 to 10-membered fused bicyclic heterocyclic, 6 to 10-membered bridged bicyclic heterocyclic, 8 to 10-membered fused bicyclic heteroaryl, or 7 to 10-membered spirocyclic heterocyclic, wherein the C1-6 alkyl group is optionally substituted with 1 to 4 Rb groups, wherein the C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C The 5-10-membered bicyclic cycloalkyl, 4-7-membered monocyclic heterocyclic, phenyl, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, and 7-10-membered spirocyclic heterocyclic groups are each optionally substituted with 1-2 R8 groups and are each optionally substituted with 1-3 Ra groups.

[0114] In some embodiments of the compounds of formula I or their pharmaceutically acceptable salts, the Z-groups are C7-10 fused bicyclic cycloalkyl, 8-10 fused bicyclic heterocyclic, 6-10 bridging bicyclic heterocyclic, or 8-10 fused bicyclic heteroaryl, wherein the C7-10 fused bicyclic cycloalkyl, 8-10 fused bicyclic heterocyclic, 6-10 bridging bicyclic heterocyclic, and 8-10 fused bicyclic heteroaryl are each optionally substituted with 1 to 2 R8 groups and each optionally substituted with 1 to 3 Ra groups.

[0115] In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, Z is a 4- to 7-membered monocyclic heterocyclic group, phenyl, 5- to 6-membered monocyclic heteroaryl, 8- to 10-membered fused bicyclic heterocyclic group, 6- to 10-membered bridged bicyclic heterocyclic group, or 7- to 10-membered spirocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group, phenyl, 5- to 6-membered monocyclic heteroaryl, 8- to 10-membered fused bicyclic heterocyclic group, 6- to 10-membered bridged bicyclic heterocyclic group, and 7- to 10-membered spirocyclic heterocyclic group are each independently optionally substituted with 1 to 2 R 8 groups and are each independently optionally substituted with 1 to 3 Ra groups.

[0116] In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, the Z group consists of a 4- to 7-membered monocyclic heterocyclic group, a phenyl group, a 5- to 6-membered monocyclic heteroaryl group, an 8- to 10-membered fused bicyclic heterocyclic group, a 6- to 10-membered bridged bicyclic heterocyclic group, or a 7- to 10-membered spirocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group, the phenyl group, the 5- to 6-membered monocyclic heteroaryl group, the 8- to 10-membered fused bicyclic heterocyclic group, the 6- to 10-membered bridged bicyclic heterocyclic group, and the 7- to 10-membered spirocyclic heterocyclic group are each independently optionally substituted with 1 to 2 R 8 groups and are each independently optionally substituted with 1 to 3 groups independently selected from the following groups: -OH, halogen, -CN, sideoxy group, -NR 11R 11, C 1-4 alkoxy group, and C 1-5 alkyl group.

[0117] In some embodiments of the compounds of formula I or their pharmaceutically acceptable salts, the Z-groups are C7-10 fused bicyclic cycloalkyl, 8-10 fused bicyclic heterocyclic, 6-10 bridging bicyclic heterocyclic, or 8-10 fused bicyclic heteroaryl, wherein the C7-10 fused bicyclic cycloalkyl, 8-10 fused bicyclic heterocyclic, 6-10 bridging bicyclic heterocyclic, and 8-10 fused bicyclic heteroaryl are each optionally substituted with 1 to 2 R8 groups and each optionally substituted with 1 to 3 Ra groups.

[0118] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a C1-6 alkyl group, wherein the C1-6 alkyl group is optionally substituted with 1 to 4 Rb groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a C1-6 alkyl group, wherein the C1-6 alkyl group is optionally substituted with 1 to 3 Rb groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a C1-6 alkyl group, wherein the C1-6 alkyl group is substituted with 1 to 4 Rb groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a C1-6 alkyl group, wherein the C1-10 alkyl group is substituted with 1 to 3 Rb groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a C1-6 alkyl group.

[0119] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a C3-7 monocyclic cycloalkyl group, wherein the C3-7 monocyclic cycloalkyl group is optionally substituted with 1 to 2 R8 groups and optionally substituted with 1 to 3 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a C3-7 monocyclic cycloalkyl group, wherein the C3-7 monocyclic cycloalkyl group is optionally substituted with 1 to 2 R8 groups and optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group.

[0120] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a C3-7 monocyclic cycloalkyl group, wherein the C3-7 monocyclic cycloalkyl group is substituted with 1 to 2 R8 groups and optionally substituted with 1 to 3 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a C3-7 monocyclic cycloalkyl group, wherein the C3-7 monocyclic cycloalkyl group is substituted with 1 to 2 R8 groups and optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group.

[0121] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a C3-7 monocyclic cycloalkyl group, wherein the C3-7 monocyclic cycloalkyl group is substituted with 1 to 2 R8 groups and substituted with 1 to 3 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a C3-7 monocyclic cycloalkyl group, wherein the C3-7 monocyclic cycloalkyl group is substituted with 1 to 2 R8 groups and substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group.

[0122] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a C3-7 monocyclic cycloalkyl group, wherein the C3-7 monocyclic cycloalkyl group is substituted with 1 to 2 R8 groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a C3-7 monocyclic cycloalkyl group, wherein the C3-7 monocyclic cycloalkyl group is optionally substituted with 1 to 3 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a C3-7 monocyclic cycloalkyl group, wherein the C3-7 monocyclic cycloalkyl group is optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a C3-7 monocyclic cycloalkyl group.

[0123] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a cyclobutanyl, cyclopentanyl, or cyclohexanyl group, each optionally substituted with one or two R8 groups and optionally substituted with one or three groups independently selected from the following: -OH, halogen, -CN, oxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a cyclobutanyl, cyclopentanyl, or cyclohexanyl group, each substituted with one or two R8 groups and optionally substituted with one or three groups independently selected from the following: -OH, halogen, -CN, oxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group. In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, Z is a cyclobutenyl, cyclopentenyl, or cyclohexenyl group, each optionally substituted with one to two R 8 groups. In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, Z is a cyclobutenyl, cyclopentenyl, or cyclohexenyl group, each optionally substituted with one to three independently selected groups from the following: -OH, halogen, -CN, syloxy group, -NR 11R 11, C 1-4 alkoxy group, and C 1-5 alkyl group.

[0124] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a C7-10 fused bicyclic cycloalkyl group, wherein the C7-10 fused bicyclic cycloalkyl group is optionally substituted with 1 to 2 R8 groups and optionally substituted with 1 to 3 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a C7-10 fused bicyclic cycloalkyl group, wherein the C7-10 fused bicyclic cycloalkyl group is substituted with 1 to 2 R8 groups and optionally substituted with 1 to 3 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a C7-10 fused bicyclic cycloalkyl group, wherein the C7-10 fused bicyclic cycloalkyl group is substituted with 1 to 2 R8 groups and substituted with 1 to 3 Ra groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, the Z-series consists of C7-10 fused bicyclic cycloalkyl groups, wherein the C7-10 fused bicyclic cycloalkyl group is substituted with 1 to 2 R8 groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, the Z-series consists of C7-10 fused bicyclic cycloalkyl groups, wherein the C7-10 fused bicyclic cycloalkyl group is optionally substituted with 1 to 3 Ra groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, the Z-series consists of C7-10 fused bicyclic cycloalkyl groups.

[0125] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a C5-10 bridged bicyclic cycloalkyl group, wherein the C5-10 bridged bicyclic cycloalkyl group is optionally substituted with 1 to 2 R8 groups and optionally substituted with 1 to 3 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a C5-10 bridged bicyclic cycloalkyl group, wherein the C5-10 bridged bicyclic cycloalkyl group is substituted with 1 to 2 R8 groups and optionally substituted with 1 to 3 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a C5-10 bridged bicyclic cycloalkyl group, wherein the C5-10 bridged bicyclic cycloalkyl group is substituted with 1 to 2 R8 groups and substituted with 1 to 3 Ra groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a C5-10 bridged bicyclic cycloalkyl group, wherein the C5-10 bridged bicyclic cycloalkyl group is substituted with 1 to 2 R8 groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a C5-10 bridged bicyclic cycloalkyl group, wherein the C5-10 bridged bicyclic cycloalkyl group is optionally substituted with 1 to 3 Ra groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a C5-10 bridged bicyclic cycloalkyl group.

[0126] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, Z is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is optionally substituted with 1 to 2 R 8 groups and optionally substituted with 1 to 3 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, Z is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is substituted with 1 to 2 R 8 groups and optionally substituted with 1 to 3 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, Z is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is substituted with 1 to 2 R 8 groups and substituted with 1 to 3 Ra groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is substituted with 1 to 2 R 8 groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is optionally substituted with 1 to 3 Ra groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a 4- to 7-membered monocyclic heterocyclic group.

[0127] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a 5- to 6-membered monocyclic heterocyclic group, wherein the 5- to 6-membered monocyclic heterocyclic group is optionally substituted with 1 to 2 R 8 groups and optionally substituted with 1 to 3 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a 5- to 6-membered monocyclic heterocyclic group, wherein the 5- to 6-membered monocyclic heterocyclic group is optionally substituted with 1 to 2 R 8 groups and optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR 11R 11, C 1-4 alkoxy group, and C 1-5 alkyl group.

[0128] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a 5- to 6-membered monocyclic heterocyclic group, wherein the 5- to 6-membered monocyclic heterocyclic group is substituted with 1 to 2 R 8 groups and optionally substituted with 1 to 3 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a 5- to 6-membered monocyclic heterocyclic group, wherein the 5- to 6-membered monocyclic heterocyclic group is substituted with 1 to 2 R 8 groups and optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR 11R 11, C 1-4 alkoxy group, and C 1-5 alkyl group.

[0129] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a 5- to 6-membered monocyclic heterocyclic group, wherein the 5- to 6-membered monocyclic heterocyclic group is substituted with 1 to 2 R 8 groups and substituted with 1 to 3 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a 5- to 6-membered monocyclic heterocyclic group, wherein the 5- to 6-membered monocyclic heterocyclic group is substituted with 1 to 2 R 8 groups and substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR 11R 11, C 1-4 alkoxy group, and C 1-5 alkyl group.

[0130] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a 5- to 6-membered monocyclic heterocyclic group, wherein the 5- to 6-membered monocyclic heterocyclic group is substituted with 1 to 2 R 8 groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a 5- to 6-membered monocyclic heterocyclic group, wherein the 5- to 6-membered monocyclic heterocyclic group is optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR 11R 11, C 1-4 alkoxy group, and C 1-5 alkyl group. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a 5- to 6-membered monocyclic heterocyclic group.

[0131] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a phenyl group, wherein the phenyl group is optionally substituted with 1 to 2 R 8 groups and optionally substituted with 1 to 3 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a phenyl group, wherein the phenyl group is optionally substituted with 1 to 2 R 8 groups and optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy, -NR 11R 11, C 1-4 alkoxy, and C 1-5 alkyl.

[0132] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a phenyl group, wherein the phenyl group is substituted with 1 to 2 R 8 groups and optionally with 1 to 3 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a phenyl group, wherein the phenyl group is substituted with 1 to 2 R 8 groups and optionally with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy, -NR 11R 11, C 1-4 alkoxy, and C 1-5 alkyl.

[0133] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, Z is a phenyl group, wherein the phenyl group is substituted with 1 to 2 R 8 groups and with 1 to 3 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, Z is a phenyl group, wherein the phenyl group is substituted with 1 to 2 R 8 groups and with 1 to 3 groups independently selected from the following: -OH, halogen, -CN, sideoxy group, -NR 11R 11, C 1-4 alkoxy group, and C 1-5 alkyl group.

[0134] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, Z is a phenyl group, wherein the phenyl group is substituted with 1 to 2 R 8 groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, Z is a phenyl group, wherein the phenyl group is optionally substituted with 1 to 3 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, Z is a phenyl group, wherein the phenyl group is optionally substituted with 1 to 3 groups independently selected from the following: -OH, halogen, -CN, sideoxy, -NR 11R 11, C 1-4 alkoxy, and C 1-5 alkyl. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, Z is a phenyl group.

[0135] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, Z is a 5- to 6-membered monocyclic heteroaryl group, wherein the 5- to 6-membered monocyclic heteroaryl group is optionally substituted with 1 to 2 R 8 groups and optionally substituted with 1 to 3 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, Z is a 5- to 6-membered monocyclic heteroaryl group, wherein the 5- to 6-membered monocyclic heteroaryl group is substituted with 1 to 2 R 8 groups and optionally substituted with 1 to 3 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, Z is a 5- to 6-membered monocyclic heteroaryl group, wherein the 5- to 6-membered monocyclic heteroaryl group is substituted with 1 to 2 R 8 groups and substituted with 1 to 3 Ra groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a 5- to 6-membered monocyclic heteroaryl group, wherein the 5- to 6-membered monocyclic heteroaryl group is substituted with 1 to 2 R 8 groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a 5- to 6-membered monocyclic heteroaryl group, wherein the 5- to 6-membered monocyclic heteroaryl group is optionally substituted with 1 to 3 Ra groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a 5- to 6-membered monocyclic heteroaryl group.

[0136] In some embodiments of the compounds of formula I or their pharmaceutically acceptable salts, Z is a 5- to 6-membered monocyclic heteroaryl group, wherein the 5- to 6-membered monocyclic heteroaryl group is optionally substituted with 1 to 2 R 8 groups and is optionally substituted with 1 to 3 groups independently selected from the following groups: -OH, halogen, -CN, sideoxy, -NR 11R 11, C 1-4 alkoxy, and C 1-5 alkyl.

[0137] In some embodiments of the compounds of formula I or their pharmaceutically acceptable salts, Z is a 5- to 6-membered monocyclic heteroaryl group, wherein the 5- to 6-membered monocyclic heteroaryl group is substituted with 1 to 2 R 8 groups and optionally substituted with 1 to 3 groups independently selected from the following groups: -OH, halogen, -CN, sideoxy, -NR 11R 11, C 1-4 alkoxy, and C 1-5 alkyl.

[0138] In some embodiments of the compounds of formula I or their pharmaceutically acceptable salts, Z is a 5- to 6-membered monocyclic heteroaryl group, wherein the 5- to 6-membered monocyclic heteroaryl group is substituted with 1 to 2 R 8 groups and is substituted with 1 to 3 groups independently selected from the following groups: -OH, halogen, -CN, sideoxy, -NR 11R 11, C 1-4 alkoxy, and C 1-5 alkyl.

[0139] In some embodiments of the compounds of formula I or pharmaceutically acceptable salts thereof, Z is a 5- to 6-membered monocyclic heteroaryl group, wherein the 5- to 6-membered monocyclic heteroaryl group is optionally substituted by 1 to 3 independently selected groups from the following: -OH, halogen, -CN, sideoxy, -NR11R11, C1-4 alkoxy, and C1-5 alkyl.

[0140] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is an 8- to 10-member fused bicyclic heterocyclic group, wherein the 8- to 10-member fused bicyclic heterocyclic group is optionally substituted with 1 to 2 R 8 groups and optionally substituted with 1 to 3 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is an 8- to 10-member fused bicyclic heterocyclic group, wherein the 8- to 10-member fused bicyclic heterocyclic group is optionally substituted with 1 to 2 R 8 groups and optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR 11R 11, C 1-4 alkoxy group, and C 1-5 alkyl group.

[0141] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is an 8- to 10-member fused bicyclic heterocyclic group, wherein the 8- to 10-member fused bicyclic heterocyclic group is substituted with 1 to 2 R 8 groups and optionally substituted with 1 to 3 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is an 8- to 10-member fused bicyclic heterocyclic group, wherein the 8- to 10-member fused bicyclic heterocyclic group is substituted with 1 to 2 R 8 groups and optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR 11R 11, C 1-4 alkoxy group, and C 1-5 alkyl group.

[0142] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is an 8- to 10-member fused bicyclic heterocyclic group, wherein the 8- to 10-member fused bicyclic heterocyclic group is substituted with 1 to 2 R 8 groups and substituted with 1 to 3 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is an 8- to 10-member fused bicyclic heterocyclic group, wherein the 8- to 10-member fused bicyclic heterocyclic group is substituted with 1 to 2 R 8 groups and substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR 11R 11, C 1-4 alkoxy group, and C 1-5 alkyl group.

[0143] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is an 8- to 10-member fused bicyclic heterocyclic group, wherein the 8- to 10-member fused bicyclic heterocyclic group is substituted with 1 to 2 R 8 groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is an 8- to 10-member fused bicyclic heterocyclic group, wherein the 8- to 10-member fused bicyclic heterocyclic group is optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR 11R 11, C 1-4 alkoxy group, and C 1-5 alkyl group. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is an 8- to 10-member fused bicyclic heterocyclic group.

[0144] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a 6- to 10-membered bridged bicyclic heterocyclic group, wherein the 6- to 10-membered bridged bicyclic heterocyclic group is optionally substituted with 1 to 2 R 8 groups and optionally substituted with 1 to 3 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a 6- to 10-membered bridged bicyclic heterocyclic group, wherein the 6- to 10-membered bridged bicyclic heterocyclic group is optionally substituted with 1 to 2 R 8 groups and optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR 11R 11, C 1-4 alkoxy group, and C 1-5 alkyl group.

[0145] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a 6- to 10-member fused bicyclic heterocyclic group, wherein the 6- to 10-member fused bicyclic heterocyclic group is substituted with 1 to 2 R 8 groups and optionally substituted with 1 to 3 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a 6- to 10-member bridged bicyclic heterocyclic group, wherein the 6- to 10-member bridged bicyclic heterocyclic group is substituted with 1 to 2 R 8 groups and optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR 11R 11, C 1-4 alkoxy group, and C 1-5 alkyl group.

[0146] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a 6- to 10-membered bridged bicyclic heterocyclic group, wherein the 6- to 10-membered bridged bicyclic heterocyclic group is optionally substituted with 1 to 2 R 8 groups and substituted with 1 to 3 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a 6- to 10-membered bridged bicyclic heterocyclic group, wherein the 6- to 10-membered bridged bicyclic heterocyclic group is substituted with 1 to 2 R 8 groups and substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR 11R 11, C 1-4 alkoxy group, and C 1-5 alkyl group.

[0147] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a 6- to 10-membered bridged bicyclic heterocyclic group, wherein the 6- to 10-membered bridged bicyclic heterocyclic group is substituted with 1 to 2 R 8 groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a 6- to 10-membered bridged bicyclic heterocyclic group, wherein the 6- to 10-membered bridged bicyclic heterocyclic group is optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR 11R 11, C 1-4 alkoxy group, and C 1-5 alkyl group. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a 6- to 10-membered bridged bicyclic heterocyclic group.

[0148] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is an 8- to 10-member fused bicyclic heteroaryl group, wherein the 8- to 10-member fused bicyclic heteroaryl group is optionally substituted with 1 to 2 R 8 groups and optionally substituted with 1 to 3 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is an 8- to 10-member fused bicyclic heteroaryl group, wherein the 8- to 10-member fused bicyclic heteroaryl group is optionally substituted with 1 to 2 R 8 groups and optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR 11R 11, C 1-4 alkoxy group, and C 1-5 alkyl group.

[0149] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, the Z-group is an 8- to 10-member fused bicyclic heteroaryl group, wherein the 8- to 10-member fused bicyclic heteroaryl group is substituted with 1 to 2 R 8 groups and optionally substituted with 1 to 3 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, the Z-group is an 8- to 10-member fused bicyclic heteroaryl group, wherein the 8- to 10-member fused bicyclic heteroaryl group is substituted with 1 to 2 R 8 groups and optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR 11R 11, C 1-4 alkoxy group, and C 1-5 alkyl group.

[0150] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, the Z-group is an 8- to 10-member fused bicyclic heteroaryl group, wherein the 8- to 10-member fused bicyclic heteroaryl group is substituted with 1 to 2 R 8 groups and substituted with 1 to 3 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, the Z-group is an 8- to 10-member fused bicyclic heteroaryl group, wherein the 8- to 10-member fused bicyclic heteroaryl group is substituted with 1 to 2 R 8 groups and substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR 11R 11, C 1-4 alkoxy group, and C 1-5 alkyl group.

[0151] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, the Z-group consists of an 8- to 10-member fused bicyclic heteroaryl group, wherein the 8- to 10-member fused bicyclic heteroaryl group is substituted with 1 to 2 R 8 groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, the Z-group consists of an 8- to 10-member fused bicyclic heteroaryl group, wherein the 8- to 10-member fused bicyclic heteroaryl group is optionally substituted with 1 to 3 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, the Z-group consists of an 8- to 10-member fused bicyclic heteroaryl group, wherein the 8- to 10-member fused bicyclic heteroaryl group is optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR 11R 11, C 1-4 alkoxy group, and C 1-5 alkyl group. In some embodiments of compounds of Formula I or their pharmaceutically acceptable salts, Z is an 8 to 10-member fused bicyclic heteroaryl group.

[0152] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a 7- to 10-membered spirocyclic heterocyclic group, wherein the 7- to 10-membered spirocyclic heterocyclic group is optionally substituted with 1 to 2 R 8 groups and optionally substituted with 1 to 3 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a 7- to 10-membered spirocyclic heterocyclic group, wherein the 7- to 10-membered spirocyclic heterocyclic group is optionally substituted with 1 to 2 R 8 groups and optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR 11R 11, C 1-4 alkoxy group, and C 1-5 alkyl group.

[0153] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a 7- to 10-membered spirocyclic heterocyclic group, wherein the 7- to 10-membered spirocyclic heterocyclic group is substituted with 1 to 2 R 8 groups and optionally substituted with 1 to 3 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a 7- to 10-membered spirocyclic heterocyclic group, wherein the 7- to 10-membered spirocyclic heterocyclic group is substituted with 1 to 2 R 8 groups and optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR 11R 11, C 1-4 alkoxy group, and C 1-5 alkyl group.

[0154] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a 7- to 10-membered spirocyclic heterocyclic group, wherein the 7- to 10-membered spirocyclic heterocyclic group is substituted with 1 to 2 R 8 groups and substituted with 1 to 3 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a 7- to 10-membered spirocyclic heterocyclic group, wherein the 7- to 10-membered spirocyclic heterocyclic group is substituted with 1 to 2 R 8 groups and substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR 11R 11, C 1-4 alkoxy group, and C 1-5 alkyl group.

[0155] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a 7- to 10-membered spirocyclic heterocyclic group, wherein the 7- to 10-membered spirocyclic heterocyclic group is substituted with 1 to 2 R 8 groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a 7- to 10-membered spirocyclic heterocyclic group, wherein the 7- to 10-membered spirocyclic heterocyclic group is optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR 11R 11, C 1-4 alkoxy group, and C 1-5 alkyl group. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z is a 7- to 10-membered spirocyclic heterocyclic group.

[0156] In some embodiments of the compounds of formula I or their pharmaceutically acceptable salts, Z is a 4 to 7-membered monocyclic heterocyclic group, wherein the 4 to 7-membered monocyclic heterocyclic group is optionally substituted with an R 8 group and is optionally substituted with 1 to 3 groups independently selected from the following groups: -OH, halogen, -CN, side oxygen, -NR 11R 11, C 1-4 alkoxy, and C 1-5 alkyl.

[0157] In some embodiments of the compounds of formula I or their pharmaceutically acceptable salts, Z is a 4 to 7-membered monocyclic heterocyclic group, wherein the 4 to 7-membered monocyclic heterocyclic group is optionally substituted with an R 8 group and is optionally substituted with 1 to 3 groups independently selected from the following groups: -OH, halogen, -CN, side oxygen, -NR 11R 11, C 1-4 alkoxy, and C 1-5 alkyl, and wherein the 4 to 7-membered monocyclic heterocyclic group has one or two N-type cyclic heteroatoms.

[0158] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, Z is a 5- to 6-membered monocyclic heterocyclic group, wherein the 5- to 6-membered monocyclic heterocyclic group is optionally substituted with an R 8 group and is optionally substituted with one or two groups independently selected from: -OH, halogen, -CN, side oxygen, -NR 11R 11, C 1-4 alkoxy, and C 1-5 alkyl, and wherein the 5- to 6-membered monocyclic heterocyclic group has one or two N-type cyclic heteroatoms.

[0159] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, Z is a piperidinyl group, wherein the piperidinyl group is optionally substituted with an R8 group.

[0160] In some embodiments of the compounds of formula I or their pharmaceutically acceptable salts, the Z-series is a phenyl or a 5- to 6-membered monocyclic heteroaryl group, each of which is optionally substituted with an R 8 group and optionally substituted with one or two groups independently selected from the following: -OH, halogen, -CN, sideoxy, -NR 11R 11, C 1-4 alkoxy, and C 1-5 alkyl.

[0161] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, Z is optionally a phenyl group substituted with an R8 group.

[0162] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, the Z-system is a 5 to 6 member monocyclic heteroaryl group, wherein the 5 to 6 member monocyclic heteroaryl group is optionally substituted with an R 8 group and has one, two, or three N-system cyclic heteroatoms.

[0163] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, Z is a pyridinyl group or, optionally, is substituted with an R8 group.

[0164] In some embodiments of the compounds of formula I or their pharmaceutically acceptable salts, Z is an 8 to 10-member fused bicyclic heterocyclic group, which is optionally substituted with an R 8 group and optionally substituted with 1 to 2 groups independently selected from the following: -OH, halogen, -CN, sideoxy, -NR 11R 11, C 1-4 alkoxy, and C 1-5 alkyl.

[0165] In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, Z is an 8- to 10-member fused bicyclic heterocyclic group, wherein the 8- to 10-member fused bicyclic heterocyclic group is optionally substituted with an R 8 group and is optionally substituted with one or two groups independently selected from: -OH, halogen, -CN, side oxygen, -NR 11R 11, C 1-4 alkoxy, and C 1-5 alkyl; and wherein the 8- to 10-member fused bicyclic heterocyclic group has one or two N-type cyclic heteroatoms.

[0166] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, the Z group or, each of which is optionally substituted with an R8 group.

[0167] In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, Z is a 6 to 10-member bridged bicyclic heterocyclic group, which is optionally substituted with an R 8 group and optionally substituted with 1 to 2 groups independently selected from the following: -OH, halogen, -CN, sideoxy, -NR 11R 11, C 1-4 alkoxy, and C 1-5 alkyl.

[0168] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, Z is a 6- to 10-membered bridged bicyclic heterocyclic group, wherein the 6- to 10-membered bridged bicyclic heterocyclic group is optionally substituted with an R 8 group and is optionally substituted with one or two groups independently selected from the following: -OH, halogen, -CN, side oxygen, -NR 11R 11, C 1-4 alkoxy, and C 1-5 alkyl, and wherein the 6- to 10-membered bridged bicyclic heterocyclic group has one or two N-type cyclic heteroatoms.

[0169] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, the Z group or, each of which is optionally substituted with an R8 group.

[0170] In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, Z is a 7- to 10-membered spirocyclic heterocyclic group, which is optionally substituted with an R 8 group and optionally substituted with one or two groups independently selected from the following: -OH, halogen, -CN, sideoxy, -NR 11R 11, C 1-4 alkoxy, and C 1-5 alkyl.

[0171] In some embodiments of the compounds of formula I or their pharmaceutically acceptable salts, Z is a 7- to 10-membered spirocyclic heterocyclic group, wherein the 7- to 10-membered spirocyclic heterocyclic group is optionally substituted with an R 8 group and is optionally substituted with one or two groups independently selected from the following: -OH, halogen, -CN, side oxygen, -NR 11R 11, C 1-4 alkoxy, and C 1-5 alkyl, and wherein the 7- to 10-membered spirocyclic heterocyclic group has one or two N-type cyclic heteroatoms.

[0172] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, the Z series is optionally substituted with an R8 group.

[0173] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, the Z series is optionally substituted with an R8 group.

[0174] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, the Z series, ... ...

[0175] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, each R8 is independently a halogen, -C(O)R9, -NR10R10, C1-6 alkyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, 4 to 7-membered monocyclic heterocyclic group, phenyl, 5 to 6-membered monocyclic heteroaryl, 8 to 10-membered fused bicyclic heterocyclic group, 6 to 10-membered bridged bicyclic heterocyclic group, 8 to 10-membered fused bicyclic heteroaryl, 7 to 10-membered spirocyclic heterocyclic group, -OR5, -C(O)N(R5)(R5), -N(R5)2(R5)+, -N(R5)C(O)R5, -N(R5)C(O)OR5, -N(R5)C(O)N(R5)+ 5)(R 5), -N(R 5)S(O) 2(R 5a), -NR 5S(O) 2N(R 5)(R 5), -NR 5S(O) 2O(R 5a), -OC(O)N(R 5)(R 5), -S(O)R 5a, -S(O)(NH)R 5, -S(O) 2R 5a, -S(O) 2N(R 5)(R 5), or -N=S(R 5a)(R 5a)=O, wherein the C 1-6 alkyl group is optionally substituted with 1 to 4 R b groups, wherein the C 3-7 monocyclic cycloalkyl, C 7-10 fused bicyclic cycloalkyl, C Each of the 5-10-membered bicyclic cycloalkyl, 4-7-membered monocyclic heterocyclic, phenyl, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, and 7-10-membered spirocyclic heterocyclic groups is optionally substituted by 1 to 4 Ra groups.

[0176] In some embodiments of the compounds of formula I or pharmaceutically acceptable salts thereof, each R8 is independently -C(O)R9, C1-6 alkyl, 4 to 7-membered monocyclic heterocyclic group, or -S(O)2R5a, wherein the C1-6 alkyl group is optionally substituted with 1 to 4 Rb groups, and wherein the 4 to 7-membered monocyclic heterocyclic group is optionally substituted with 1 to 4 Ra groups.

[0177] In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, each R8 is independently -C(O)R9, C1-6 alkyl, 4 to 7-membered monocyclic heterocyclic group, or -S(O)2R5a, wherein the C1-6 alkyl group is optionally substituted by 1 to 3 groups independently selected from the following groups: -OH, halogen, -CN, oxy group, -NR11R11, -C(O)NR11R11, C1-4 alkoxy group, and R8a, and wherein the 4 to 7-membered monocyclic heterocyclic group is optionally substituted by 1 to 3 groups independently selected from the following groups: -OH, halogen, -CN, oxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group.

[0178] In some embodiments of the compound of Formula I or its pharmaceutically acceptable salt, one or both R8s are halogens. In some embodiments of the compound of Formula I or its pharmaceutically acceptable salt, one or both R8s are -OR5. In some embodiments of the compound of Formula I or its pharmaceutically acceptable salt, one or both R8s are -C(O)N(R5)(R5). In some embodiments of the compound of Formula I or its pharmaceutically acceptable salt, one or both R8s are -N(R5)2(R5)+. In some embodiments of the compound of Formula I or its pharmaceutically acceptable salt, one or both R8s are -N(R5)C(O)OR5. In some embodiments of the compound of Formula I or its pharmaceutically acceptable salt, one or both R8s are -N(R5)C(O)OR5. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are -N(R5)C(O)N(R5)(R5). In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are -N(R5)S(O)2(R5a). In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are -NR5S(O)2N(R5)(R5). In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are -NR5S(O)2O(R5a). In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are -OC(O)N(R5)(R5). In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are -S(O)R5a. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R8 are -S(O)(NH)R5. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R8 are -S(O)2N(R5)(R5). In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R8 are -N=S(R5a)(R5a)=O.

[0179] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are C1-6 alkyl groups, wherein the C1-6 alkyl group is optionally substituted with 1 to 4 Rb groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are C1-6 alkyl groups, wherein the C1-6 alkyl group is optionally substituted with 1 to 3 Rb groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are C1-6 alkyl groups, wherein the C1-6 alkyl group is optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, oxy group, -NR11R11, -C(O)N(R11)(R11), C1-4 alkoxy group, and R8a. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R8s are C1-3 alkyl groups, wherein the C1-3 alkyl group is optionally substituted by one to three independently selected groups selected from: -OH, halogen, -CN, oxy group, -NR11R11, -C(O)N(R11)(R11), C1-4 alkoxy group, and R8a. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R8s are C1-3 alkyl groups, wherein the C1-3 alkyl group is optionally substituted by one to two independently selected groups selected from: oxy group, -NR11R11, -C(O)N(R11)(R11), and R8a. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R8s are C1-6 alkyl groups, wherein the C1-6 alkyl group is substituted with 1 to 4 Rb groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R8s are C1-6 alkyl groups, wherein the C1-6 alkyl group is substituted with 1 to 3 Rb groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R8s are C1-6 alkyl groups, wherein the C1-6 alkyl group is substituted with 1 to 3 groups independently selected from the following: -OH, halogen, -CN, oxy group, -NR11R11, -C(O)N(R11)(R11), C1-4 alkoxy group, and R8a. In some embodiments of compounds of formula I or pharmaceutically acceptable salts thereof, one or both R8s are C1-6 alkyl groups, wherein the C1-6 alkyl group is substituted by one to three independently selected groups from the following: -OH, syloxy group, -NH2, -N(CH3)2, -C(O)NH2, -C(O)N(CH3)2, and R8a.In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R8s are C1-6 alkyl groups, wherein the C1-6 alkyl group is substituted by one to three independently selected groups selected from the following: -OH, oxy group, -N(CH3)2, -C(O)NH2, and R8a. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R8s are C1-3 alkyl groups, wherein the C1-3 alkyl group is substituted by one to three independently selected groups selected from the following: -OH, halogen, -CN, oxy group, -NR11R11, -C(O)N(R11)(R11), C1-4 alkoxy group, and R8a. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R8s are C1-3 alkyl groups, wherein the C1-3 alkyl group is substituted by one or two independently selected groups of: oxy group, -NR11R11, -C(O)N(R11)(R11), and R8a. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R8s are C1-6 alkyl groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R8s are C1-3 alkyl groups.

[0180] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are C1-6 alkyl groups, wherein the C1-6 alkyl group is substituted by one to three independently selected groups selected from the following: -OH, oxy group, -N(CH3)2, -C(O)NH2, -C(O)NHCH3, and R8a. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R8s are C1-6 alkyl groups, wherein the C1-6 alkyl group is substituted by one to three independently selected groups selected from the following: -OH, oxy group, -N(CH3)2, -C(O)NH2, -C(O)NHCH3, and R8a.

[0181] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are C3-7 monocyclic cycloalkyl groups, wherein the C3-7 monocyclic cycloalkyl group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are C3-7 monocyclic cycloalkyl groups, wherein the C3-7 monocyclic cycloalkyl group is substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are C3-7 monocyclic cycloalkyl groups.

[0182] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are C7-10 fused bicyclic cycloalkyl groups, wherein the C7-10 fused bicyclic cycloalkyl group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are C7-10 fused bicyclic cycloalkyl groups, wherein the C7-10 fused bicyclic cycloalkyl group is substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are C7-10 fused bicyclic cycloalkyl groups.

[0183] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are C5-10 bridged bicyclic cycloalkyl groups, wherein the C5-10 bridged bicyclic cycloalkyl group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are C5-10 bridged bicyclic cycloalkyl groups, wherein the C5-10 bridged bicyclic cycloalkyl group is substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are C5-10 bridged bicyclic cycloalkyl groups.

[0184] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are 4 to 7-membered monocyclic heterocyclic groups, wherein the 4 to 7-membered monocyclic heterocyclic group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are 4 to 7-membered monocyclic heterocyclic groups, wherein the 4 to 7-membered monocyclic heterocyclic group is optionally substituted with 1 to 3 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are 4 to 7-membered monocyclic heterocyclic groups, wherein the 4 to 7-membered monocyclic heterocyclic group is optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group.

[0185] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8 are 4 to 7-membered monocyclic heterocyclic groups, wherein the 4 to 7-membered monocyclic heterocyclic group is substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8 are 4 to 7-membered monocyclic heterocyclic groups, wherein the 4 to 7-membered monocyclic heterocyclic group is substituted with 1 to 3 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8 are 4 to 7-membered monocyclic heterocyclic groups, wherein the 4 to 7-membered monocyclic heterocyclic group is substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group.

[0186] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, one or both R8 are 4 to 7 member monocyclic heterocyclic groups.

[0187] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are 5- to 6-membered monocyclic heterocyclic groups, wherein the 5- to 6-membered monocyclic heterocyclic group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are 5- to 6-membered monocyclic heterocyclic groups, wherein the 5- to 6-membered monocyclic heterocyclic group is optionally substituted with 1 to 3 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are 5- to 6-membered monocyclic heterocyclic groups, wherein the 5- to 6-membered monocyclic heterocyclic group is optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group.

[0188] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are 5- to 6-membered monocyclic heteroaryl groups, wherein the 5- to 6-membered monocyclic heteroaryl group is substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are 5- to 6-membered monocyclic heterocyclic groups, wherein the 5- to 6-membered monocyclic heterocyclic group is substituted with 1 to 3 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are 5- to 6-membered monocyclic heterocyclic groups, wherein the 5- to 6-membered monocyclic heterocyclic group is substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group.

[0189] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, one or both R8 are 5 to 6 member monocyclic heterocyclic groups.

[0190] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8 are phenyl groups, wherein the phenyl group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8 are phenyl groups, wherein the phenyl group is substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8 are phenyl groups.

[0191] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are 5 to 6-membered monocyclic heteroaryl groups, wherein the 5 to 6-membered monocyclic heteroaryl group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are 5 to 6-membered monocyclic heteroaryl groups, wherein the 5 to 6-membered monocyclic heteroaryl group is substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are 5 to 6-membered monocyclic heteroaryl groups.

[0192] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are 8 to 10 fused bicyclic heterocyclic groups, wherein the 8 to 10 fused bicyclic heterocyclic groups are optionally substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are 8 to 10 fused bicyclic heterocyclic groups, wherein the 8 to 10 fused bicyclic heterocyclic groups are optionally substituted with 1 to 3 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are 8 to 10 fused bicyclic heterocyclic groups, wherein the 8 to 10 fused bicyclic heterocyclic groups are optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group.

[0193] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are 8 to 10 fused bicyclic heterocyclic groups, wherein the 8 to 10 fused bicyclic heterocyclic groups are substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are 8 to 10 fused bicyclic heterocyclic groups, wherein the 8 to 10 fused bicyclic heterocyclic groups are substituted with 1 to 3 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are 8 to 10 fused bicyclic heterocyclic groups, wherein the 8 to 10 fused bicyclic heterocyclic groups are substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group.

[0194] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, one or both R8 are 8 to 10 fused bicyclic heterocyclic groups.

[0195] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are 6 to 10 membered bridged bicyclic heterocyclic groups, wherein the 6 to 10 membered bridged bicyclic heterocyclic groups are optionally substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are 6 to 10 membered bridged bicyclic heterocyclic groups, wherein the 6 to 10 membered bridged bicyclic heterocyclic groups are optionally substituted with 1 to 3 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are 6 to 10 membered bridged bicyclic heterocyclic groups, wherein the 6 to 10 membered bridged bicyclic heterocyclic groups are optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group.

[0196] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8 are 6 to 10 membered bridged bicyclic heterocyclic groups, wherein the 6 to 10 membered bridged bicyclic heterocyclic groups are substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8 are 6 to 10 membered bridged bicyclic heterocyclic groups, wherein the 6 to 10 membered bridged bicyclic heterocyclic groups are substituted with 1 to 3 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8 are 6 to 10 membered bridged bicyclic heterocyclic groups, wherein the 6 to 10 membered bridged bicyclic heterocyclic groups are substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group.

[0197] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, one or both R8 are 6 to 10 members of a bridged bicyclic heterocyclic group.

[0198] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are 7- to 8-membered bridged bicyclic heterocyclic groups, wherein the 7- to 8-membered bridged bicyclic heterocyclic group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are 7- to 8-membered bridged bicyclic heterocyclic groups, wherein the 7- to 8-membered bridged bicyclic heterocyclic group is optionally substituted with 1 to 3 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are 7- to 8-membered bridged bicyclic heterocyclic groups, wherein the 7- to 8-membered bridged bicyclic heterocyclic group is optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group.

[0199] In some embodiments of the compound of Formula I or its pharmaceutically acceptable salt, one or both R8s are 7- to 8-membered bridged bicyclic heterocyclic groups, wherein the 7- to 8-membered bridged bicyclic heterocyclic group is substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or its pharmaceutically acceptable salt, one or both R8s are 7- to 8-membered bridged bicyclic heterocyclic groups, wherein the 7- to 8-membered bridged bicyclic heterocyclic group is substituted with 1 to 3 Ra groups. In some embodiments of the compound of Formula I or its pharmaceutically acceptable salt, one or both R8s are 7- to 8-membered bridged bicyclic heterocyclic groups, wherein the 7- to 8-membered bridged bicyclic heterocyclic group is substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group.

[0200] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, one or both R8 are 7 to 8 members of a bridged bicyclic heterocyclic group.

[0201] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8 are 7- to 10-membered spirocyclic heterocyclic groups, wherein the 7- to 10-membered spirocyclic heterocyclic group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8 are 7- to 10-membered spirocyclic heterocyclic groups, wherein the 7- to 10-membered spirocyclic heterocyclic group is substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8 are 7- to 10-membered spirocyclic heterocyclic groups.

[0202] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R8s are 7 to 10 spirocyclic heterocyclic groups, wherein the 7 to 10 spirocyclic heterocyclic group is optionally substituted by one to three independently selected groups from the following: -OH, halogen, -CN, oxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R8s are 7 to 10 spirocyclic heterocyclic groups, wherein the 7 to 10 spirocyclic heterocyclic group is substituted by one to three independently selected groups from the following: -OH, halogen, -CN, oxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group.

[0203] In some embodiments of the compound of Formula I or its pharmaceutically acceptable salt, one or both R8 are 7- to 10-membered spirocyclic heterocyclic groups, wherein the 7- to 10-membered spirocyclic heterocyclic group is optionally substituted with 1 to 3 groups independently selected from oxy and methyl groups. In some embodiments of the compound of Formula I or its pharmaceutically acceptable salt, one or both R8 are 7- to 10-membered spirocyclic heterocyclic groups, wherein the 7- to 10-membered spirocyclic heterocyclic group is substituted with 1 to 3 groups independently selected from oxy and methyl groups.

[0204] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8 are OR, each of which is optionally substituted with a methyl group. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8 are OR, each of which is substituted with a methyl group.

[0205] In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, R8 is a 4 to 7-membered monocyclic heterocyclic group, wherein the 4 to 7-membered monocyclic heterocyclic group is optionally substituted by 1 to 3 independently selected groups from the following: -OH, halogen, -CN, sideoxy, -NR11R11, C1-4 alkoxy, and C1-5 alkyl.

[0206] In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, R8 is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is optionally substituted by 1 to 3 independently selected groups selected from: -OH, halogen, -CN, sideoxy, -NR11R11, C1-4 alkoxy, and C1-5 alkyl; and wherein the 4- to 7-membered monocyclic heterocyclic group has one or two independently selected ring heteroatoms selected from N and S.

[0207] In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, R8 is a 5- to 6-membered monocyclic heterocyclic group, wherein the 5- to 6-membered monocyclic heterocyclic group is optionally substituted by 1 to 2 independently selected groups from the following: -OH, halogen, -CN, sideoxy, -NR11R11, C1-4 alkoxy, and C1-5 alkyl.

[0208] In some embodiments of the compounds of formula I or their pharmaceutically acceptable salts, R8 is piperidinyl or piperyl, each of which is optionally substituted by one or two independent groups selected from the following: -OH, halogen, -CN, sideoxy, -NR11R11, C1-4 alkoxy, and C1-5 alkyl.

[0209] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, R8 is piperidinyl or piperyl.

[0210] In some embodiments of the compounds of formula I or pharmaceutically acceptable salts thereof, R8 is a C1-6 alkyl group, wherein the C1-6 alkyl group is optionally substituted by one to three independently selected groups from the following: -OH, halogen, -CN, syloxy group, -NR11R11, -C(O)NR11R11, C1-4 alkoxy group, and R8a.

[0211] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, R8 is a C1-6 alkyl group, wherein the C1-6 alkyl group is substituted with one or two groups independently selected from -C(O)NR11R11 and R8a.

[0212] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, R8 is a C1-4 alkyl group, wherein the C1-4 alkyl group is substituted by one or two independently selected groups selected from the following: -C(O)NH2, 4 to 7-membered monocyclic heterocyclic group and 5 to 6-membered monocyclic heteroaryl group, and wherein the 4 to 7-membered monocyclic heterocyclic group and the 5 to 6-membered monocyclic heteroaryl group are each optionally substituted by one independently selected group selected from the following: -OH, halogen, C1-3 alkoxy group and C1-3 alkyl group.

[0213] In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, each R 8a is independently a 4- to 7-membered monocyclic heterocyclic group or a 5- to 6-membered monocyclic heteroaryl group, wherein the 4- to 7-membered monocyclic heterocyclic group and the 5- to 6-membered monocyclic heteroaryl group are each independently optionally substituted by 1 to 3 independently selected groups from the following: -OH, halogen, C1-4 alkoxy, and C1-5 alkyl.

[0214] In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, each R 8a is independently a 4-membered monocyclic heterocyclic group or a 5-membered monocyclic heteroaryl group, each of which is optionally substituted with a C1-3 alkyl group.

[0215] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, each R 8a is independently an oxo group or a 5-membered monocyclic heteroaryl having two N-based cyclic heteroatoms, wherein the oxo group and the 5-membered monocyclic heteroaryl are each optionally substituted with a methyl group.

[0216] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, each R 8a is independently oxo- or pyrazolyl, wherein the oxo- and pyrazolyl groups are optionally substituted with methyl groups.

[0217] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R8s are -C(O)R9. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R8s are -C(O)R9.

[0218] In some embodiments of the compounds of formula I or their pharmaceutically acceptable salts, each R9 is independently a C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4 to 7-membered monocyclic heterocyclic group, 5 to 6-membered monocyclic heteroaryl, 8 to 10-membered fused bicyclic heterocyclic group, 6 to 10-membered bridged bicyclic heterocyclic group, 8 to 10-membered fused bicyclic heteroaryl, or 7 to 10-membered spirocyclic heterocyclic group, wherein the C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5 to 10-membered spirocyclic heterocyclic group ... Each of the 5-10-membered bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, and 7-10-membered spirocyclic heterocyclic groups is optionally substituted with 1 to 4 Ra groups.

[0219] In some embodiments of the compounds of formula I or their pharmaceutically acceptable salts, each R9 is independently a C3-7 monocyclic cycloalkyl or a 4- to 7-membered monocyclic heterocyclic group, wherein the C3-7 monocyclic cycloalkyl and the 4- to 7-membered monocyclic heterocyclic group are each optionally substituted with 1 to 4 Ra groups.

[0220] In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, each R9 is independently a C3-7 monocyclic cycloalkyl or a 4- to 7-membered monocyclic heterocyclic group, wherein the C3-7 monocyclic cycloalkyl and the 4- to 7-membered monocyclic heterocyclic group are each optionally substituted by 1 to 3 groups independently selected from the following groups: -OH, halogen, -CN, sideoxy, -NR11R11, C1-4 alkoxy, C1-5 alkyl, and 4- to 7-membered monocyclic heterocyclic group.

[0221] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R9s are C3-7 monocyclic cycloalkyl groups, wherein the C3-7 monocyclic cycloalkyl group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R9s are C3-7 monocyclic cycloalkyl groups, wherein the C3-7 monocyclic cycloalkyl group is optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, oxy group, -NR11R11, C1-4 alkoxy group, C1-5 alkyl group, and 4 to 7 member monocyclic heterocyclic groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R9s are C3-7 monocyclic cycloalkyl groups, wherein the C3-7 monocyclic cycloalkyl group is substituted with 1 to 4 Ra groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R9s are C3-7 monocyclic cycloalkyl groups, wherein the C3-7 monocyclic cycloalkyl group is substituted by one to three independently selected groups from the following: -OH, halogen, -CN, oxy group, -NR11R11, C1-4 alkoxy group, C1-5 alkyl group, and 4 to 7-membered monocyclic heterocyclic groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R9s are C3-7 monocyclic cycloalkyl groups.

[0222] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R9s are C7-10 fused bicyclic cycloalkyl groups, wherein the C7-10 fused bicyclic cycloalkyl group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R9s are C7-10 fused bicyclic cycloalkyl groups, wherein the C7-10 fused bicyclic cycloalkyl group is substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R9s are C7-10 fused bicyclic cycloalkyl groups.

[0223] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R9s are C5-10 bridged bicyclic cycloalkyl groups, wherein the C5-10 bridged bicyclic cycloalkyl group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R9s are C5-10 bridged bicyclic cycloalkyl groups, wherein the C5-10 bridged bicyclic cycloalkyl group is substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R9s are C5-10 bridged bicyclic cycloalkyl groups.

[0224] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R9 are phenyl groups, wherein the phenyl group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R9 are phenyl groups, wherein the phenyl group is substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R9 are phenyl groups.

[0225] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R9s are naphthyl groups, wherein the naphthyl group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R9s are naphthyl groups, wherein the naphthyl group is substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R9s are naphthyl groups.

[0226] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R9s are 5 to 6-membered monocyclic heteroaryl groups, wherein the 5 to 6-membered monocyclic heteroaryl group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R9s are 5 to 6-membered monocyclic heteroaryl groups, wherein the 5 to 6-membered monocyclic heteroaryl group is substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R9s are 5 to 6-membered monocyclic heteroaryl groups.

[0227] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R9s are 8 to 10 fused bicyclic heterocyclic groups, wherein the 8 to 10 fused bicyclic heterocyclic groups are optionally substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R9s are 8 to 10 fused bicyclic heterocyclic groups, wherein the 8 to 10 fused bicyclic heterocyclic groups are substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R9s are 8 to 10 fused bicyclic heterocyclic groups.

[0228] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R9s are 8 to 10 fused bicyclic heteroaryl groups, wherein the 8 to 10 fused bicyclic heteroaryl groups are optionally substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R9s are 8 to 10 fused bicyclic heteroaryl groups, wherein the 8 to 10 fused bicyclic heteroaryl groups are substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R9s are 8 to 10 fused bicyclic heteroaryl groups.

[0229] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R9s are 7 to 10 membered spirocyclic heterocyclic groups, wherein the 7 to 10 membered spirocyclic heterocyclic group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R9s are 7 to 10 membered spirocyclic heterocyclic groups, wherein the 7 to 10 membered spirocyclic heterocyclic group is substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R9s are 7 to 10 membered spirocyclic heterocyclic groups.

[0230] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, one or both R9 are 7 to 10 spirocyclic heterocyclic groups, wherein the 7 to 10 spirocyclic heterocyclic group has 1 to 2 cyclic heteroatoms independently selected from N and O.

[0231] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, R9 is used.

[0232] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R9s are 4 to 7-membered monocyclic heterocyclic groups, wherein the 4 to 7-membered monocyclic heterocyclic group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R9s are 4 to 7-membered monocyclic heterocyclic groups, wherein the 4 to 7-membered monocyclic heterocyclic group is optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR11R11, C1-4 alkoxy group, C1-5 alkyl group, and 4 to 7-membered monocyclic heterocyclic group. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R9s are 4 to 7-membered monocyclic heterocyclic groups, wherein the 4 to 7-membered monocyclic heterocyclic group is substituted with 1 to 4 Ra groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R9s are 4- to 7-membered monocyclic heterocyclic groups, wherein the 4- to 7-membered monocyclic heterocyclic group is substituted by one to three independently selected groups from: -OH, halogen, -CN, septyl group, -NR11R11, C1-4 alkoxy group, C1-5 alkyl group, and 4- to 7-membered monocyclic heterocyclic groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R9s are 4- to 7-membered monocyclic heterocyclic groups.

[0233] In some embodiments of the compound of Formula I or its pharmaceutically acceptable salt, one or both R9s are 5 to 7-membered monocyclic heterocyclic groups, wherein the 5 to 7-membered monocyclic heterocyclic group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or its pharmaceutically acceptable salt, one or both R9s are 5 to 7-membered monocyclic heterocyclic groups, wherein the 5 to 7-membered monocyclic heterocyclic group is optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, -NR11R11, C1-3 alkoxy, and C1-3 alkyl. In some embodiments of the compound of Formula I or its pharmaceutically acceptable salt, one or both R9s are 5 to 7-membered monocyclic heterocyclic groups, wherein the 5 to 7-membered monocyclic heterocyclic group is substituted with 1 to 4 Ra groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R9s are 5- to 7-membered monocyclic heterocyclic groups, wherein the 5- to 7-membered monocyclic heterocyclic group is substituted by one to three independently selected groups from the following: -OH, halogen, -CN, -NR11R11, C1-3 alkoxy, and C1-3 alkyl. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R9s are 5- to 7-membered monocyclic heterocyclic groups.

[0234] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R9s are 4- to 6-membered monocyclic heterocyclic groups, wherein the 4- to 6-membered monocyclic heterocyclic group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R9s are 4- to 6-membered monocyclic heterocyclic groups, wherein the 4- to 6-membered monocyclic heterocyclic group is optionally substituted with 1 to 3 groups independently selected from the following: -OH, halogen, -CN, -NR11R11, C1-3 alkoxy, and C1-3 alkyl. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R9s are 4- to 6-membered monocyclic heterocyclic groups, wherein the 4- to 6-membered monocyclic heterocyclic group is optionally substituted with 1 to 2 groups independently selected from the following: -OH, halogen, C1-3 alkoxy, and C1-3 alkyl. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R9s are 4- to 6-membered monocyclic heterocyclic groups, wherein the 4- to 6-membered monocyclic heterocyclic groups are substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R9s are 4- to 6-membered monocyclic heterocyclic groups, wherein the 4- to 6-membered monocyclic heterocyclic groups are substituted with 1 to 3 groups independently selected from the following: -OH, halogen, -CN, -NR11R11, C1-3 alkoxy, and C1-3 alkyl. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R9s are 4- to 6-membered monocyclic heterocyclic groups, wherein the 4- to 6-membered monocyclic heterocyclic groups are substituted with 1 to 2 groups independently selected from the following: -OH, halogen, C1-3 alkoxy, and C1-3 alkyl. In some embodiments of compounds of Formula I or their pharmaceutically acceptable salts, one or both R9s are 4 to 6-membered monocyclic heterocyclic groups.

[0235] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R9 are 6 to 10 membered bridged bicyclic heterocyclic groups, wherein the 6 to 10 membered bridged bicyclic heterocyclic groups are optionally substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R9 are 6 to 10 membered bridged bicyclic heterocyclic groups, wherein the 6 to 10 membered bridged bicyclic heterocyclic groups are optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R9s are 6- to 10-membered bridged bicyclic heterocyclic groups, wherein the 6- to 10-membered bridged bicyclic heterocyclic group is optionally substituted by 1 to 3 independently selected groups from: -OH, halogen, -CN, -NR11R11, C1-3 alkoxy, and C1-3 alkyl. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R9s are 6- to 10-membered bridged bicyclic heterocyclic groups, wherein the 6- to 10-membered bridged bicyclic heterocyclic group is substituted by 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R9s are 6- to 10-membered bridged bicyclic heterocyclic groups, wherein the 6- to 10-membered bridged bicyclic heterocyclic group is substituted by one to three independently selected groups selected from: -OH, halogen, -CN, oxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R9s are 6- to 10-membered bridged bicyclic heterocyclic groups, wherein the 6- to 10-membered bridged bicyclic heterocyclic group is substituted by one to three independently selected groups selected from: -OH, halogen, -CN, -NR11R11, C1-3 alkoxy group, and C1-3 alkyl group. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R9s are 6- to 10-membered bridged bicyclic heterocyclic groups.

[0236] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R9 is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is optionally substituted by 1 to 3 independently selected groups from the following: -OH, halogen, -CN, sideoxy group, -NR11R11, C1-4 alkoxy group, C1-5 alkyl group, and 4- to 7-membered monocyclic heterocyclic group.

[0237] In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, R9 is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is optionally substituted by 1 to 3 independently selected groups selected from: -OH, halogen, -CN, sideoxy, -NR11R11, C1-4 alkoxy, and C1-5 alkyl; and wherein the 4- to 7-membered monocyclic heterocyclic group has one or two N-type cyclic heteroatoms.

[0238] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, R9 is a 5- to 6-membered monocyclic heterocyclic group, wherein the 5- to 6-membered monocyclic heterocyclic group is optionally substituted by one or two independently selected groups of -OH, halogen, C1-3 alkoxy, and C1-3 alkyl, and wherein the 5- to 6-membered monocyclic heterocyclic group has one or two N-type cyclic heteroatoms.

[0239] In some embodiments of the compounds of formula I or their pharmaceutically acceptable salts, R9 is a pyrrolidyl or linyl group, each of which is optionally substituted by one or two independent groups selected from the following: -OH, halogen, C1-3 alkoxy, and C1-3 alkyl.

[0240] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R9 is an acrylyl or pyrrolidyl group, each optionally substituted with one or two independently selected groups of -OH, halogen, C1-3 alkoxy, and C1-3 alkyl. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R9 is an acrylyl or pyrrolidyl group, each substituted with one or two independently selected groups of -OH, halogen, C1-3 alkoxy, and C1-3 alkyl.

[0241] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R9 is a group or, each of which may optionally be substituted with one or two independently selected groups selected from -OH, methyl, and trifluoromethyl. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R9 is a group or, each of which may be substituted with one or two independently selected groups selected from -OH, methyl, and trifluoromethyl.

[0242] In some embodiments of the compounds of formula I or their pharmaceutically acceptable salts, R9 is optionally a C3-7 monocyclic cycloalkyl group substituted with one to three independently selected groups from the following: -OH, halogen, -CN, sideoxy group, -NR11R11, C1-4 alkoxy group, C1-5 alkyl group, and 4 to 7 member monocyclic heterocyclic group.

[0243] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, R9 is cyclopropyl, cyclobutyl, or cyclopentyl, each of which is optionally substituted by one or two independently selected groups of -OH, halogen, C1-3 alkoxy, C1-3 alkyl, and 4 to 7 member monocyclic heterocyclic groups.

[0244] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, R9 is cyclopropyl, cyclobutyl, or cyclopentyl, each of which is optionally substituted by one or two independently selected groups of -OH, halogen, C1-3 alkoxy, C1-3 alkyl, and 5 to 7-membered monocyclic heterocyclic group, wherein the 5 to 7-membered monocyclic heterocyclic group has one or two N-type cyclic heteroatoms.

[0245] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, R9 is a cyclopropyl group optionally substituted with a 6-membered monocyclic heterocyclic group, wherein the 6-membered monocyclic heterocyclic group has an N-type cyclic heteroatom.

[0246] In some embodiments of the compound of formula I or a pharmaceutically acceptable salt thereof, R9 is optionally a cyclopropyl group substituted with a linyl group.

[0247] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, one or both R 8 are -NR 10R 10.

[0248] In some embodiments of the compound of formula II or its pharmaceutically acceptable salt, one or both R8 are -S(O)2R5a.

[0249] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, R8 is S(O)2R5a.

[0250] In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, R5a is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is optionally substituted by 1 to 3 independently selected groups from: -OH, halogen, -CN, sideoxy, -NR11R11, C1-4 alkoxy, and C1-5 alkyl; and wherein the 4- to 7-membered monocyclic heterocyclic group has one or two N-type cyclic heteroatoms.

[0251] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, R 5a is a 5- to 6-membered monocyclic heterocyclic group, wherein the 5- to 6-membered heterocyclic group is optionally substituted by one or two independently selected groups of -OH, halogen, -CN, and C1-5 alkyl; and wherein the 5- to 6-membered heterocyclic group has one or two N-type cyclic heteroatoms.

[0252] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, R5a is a piperyl group.

[0253] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z-series -C(O)NR 6R 7. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z-series -C(O)N(H)R 6. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, Z-series -C(O)N(CH 3)R 6.

[0254] In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, R6 is a C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, 4 to 7-membered monocyclic heterocyclic group, 8 to 10-membered fused bicyclic heterocyclic group, 6 to 10-membered bridged bicyclic heterocyclic group, or 7 to 10-membered spirocyclic heterocyclic group, wherein each of the C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, 4 to 7-membered monocyclic heterocyclic group, 8 to 10-membered fused bicyclic heterocyclic group, 6 to 10-membered bridged bicyclic heterocyclic group, and 7 to 10-membered spirocyclic heterocyclic group is optionally substituted with 1 to 4 Ra groups independently.

[0255] In some embodiments of the compounds of formula I or their pharmaceutically acceptable salts, R6 is a 4- to 7-membered monocyclic heterocyclic group, wherein the C1-6 alkyl group is optionally substituted with 1 to 3 Rb groups, wherein the 4- to 7-membered monocyclic heterocyclic group is optionally substituted with 1 to 3 Ra groups.

[0256] In some embodiments of the compounds of formula I or their pharmaceutically acceptable salts, R6 is a 4- to 7-membered monocyclic heterocyclic group, wherein the C1-6 alkyl group is optionally substituted by 1 to 2 groups independently selected from the following groups: -OH, halogen, -NR11R11, and C1-3 alkoxy, wherein the 4- to 7-membered monocyclic heterocyclic group is optionally substituted by 1 to 3 groups independently selected from the following groups: -OH, halogen, -CN, -NR11R11, C1-3 alkoxy, and C1-3 alkyl.

[0257] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R6 is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is optionally substituted by 1 to 3 groups independently selected from the following groups: -OH, halogen, -CN, sideoxy, -NR11R11, C1-4 alkoxy, and C1-5 alkyl, and wherein the C1-4 alkoxy and C1-5 alkyl are each optionally substituted by 1 to 3 groups independently selected from the following groups: -OH, halogen, -CN, and -NR12R12.

[0258] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R6 is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is optionally substituted by 1 to 3 independently selected groups selected from: -OH, halogen, -CN, oxy group, -NR 11R 11, C 1-4 alkoxy group, and C 1-5 alkyl group. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R6 is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is substituted by 1 to 3 independently selected groups selected from: -OH, halogen, -CN, oxy group, -NR 11R 11, C 1-4 alkoxy group, and C 1-5 alkyl group.

[0259] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R6 is a C3-7 monocyclic cycloalkyl group, wherein the C3-7 monocyclic cycloalkyl group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R6 is a C3-7 monocyclic cycloalkyl group, wherein the C3-7 monocyclic cycloalkyl group is substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R6 is a C3-7 monocyclic cycloalkyl group.

[0260] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R6 is a C7-10 fused bicyclic cycloalkyl group, wherein the C7-10 fused bicyclic cycloalkyl group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R6 is a C7-10 fused bicyclic cycloalkyl group, wherein the C7-10 fused bicyclic cycloalkyl group is substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R6 is a C7-10 fused bicyclic cycloalkyl group.

[0261] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R6 is a C5-10 bridged bicyclic cycloalkyl group, wherein the C5-10 bridged bicyclic cycloalkyl group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R6 is a C5-10 bridged bicyclic cycloalkyl group, wherein the C5-10 bridged bicyclic cycloalkyl group is substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R6 is a C5-10 bridged bicyclic cycloalkyl group.

[0262] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R6 is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R6 is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is optionally substituted with 1 to 3 Ra groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, R6 is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is substituted by 1 to 3 independently selected groups selected from the following: -OH, halogen, -CN, sideoxy, -NR 11R 11, C 1-4 alkoxy, and C 1-5 alkyl, wherein the C 1-4 alkoxy and C 1-5 alkyl are each optionally substituted by 1 to 3 independently selected groups selected from the following: -OH, halogen, -CN, and -NR 12R 12. In some embodiments of compounds of Formula I or their pharmaceutically acceptable salts, R6 is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is optionally substituted by 1 to 3 independently selected groups from the following: -OH, halogen, -CN, -NR11R11, C1-3 alkoxy, and C1-3 alkyl, wherein the C1-3 alkoxy and C1-3 alkyl are each optionally substituted by 1 to 3 independently selected groups from the following: -OH, halogen, -CN, and -NR12R12. In some embodiments of compounds of Formula I or their pharmaceutically acceptable salts, R6 is a 5- to 6-membered monocyclic heterocyclic group, wherein the 5- to 6-membered monocyclic heterocyclic group is optionally substituted by 1 to 3 independently selected groups from the following: -OH, halogen, -CN, -NR11R11, C1-3 alkoxy, and C1-3 alkyl, wherein the C1-3 alkoxy and C1-3 alkyl are each optionally substituted by 1 to 3 independently selected groups from the following: -OH, halogen, -CN, and -NR12R12.

[0263] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R6 is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R6 is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is substituted with 1 to 3 Ra groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, R6 is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is substituted by 1 to 3 independently selected groups selected from the following: -OH, halogen, -CN, sideoxy, -NR 11R 11, C 1-4 alkoxy, and C 1-5 alkyl, wherein the C 1-4 alkoxy and C 1-5 alkyl are each optionally substituted by 1 to 3 independently selected groups selected from the following: -OH, halogen, -CN, and -NR 12R 12. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, R6 is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is substituted by 1 to 3 independently selected groups selected from the following: -OH, halogen, -CN, -NR11R11, C1-3 alkoxy, and C1-3 alkyl, wherein the C1-3 alkoxy and C1-3 alkyl are each optionally substituted by 1 to 3 independently selected groups selected from the following: -OH, halogen, -CN, and -NR12R12. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, R6 is a 5- to 6-membered monocyclic heterocyclic group, wherein the 5- to 6-membered monocyclic heterocyclic group is substituted by 1 to 3 independently selected groups selected from the following: -OH, halogen, -CN, -NR11R11, C1-3 alkoxy, and C1-3 alkyl, wherein the C1-3 alkoxy and C1-3 alkyl are each optionally substituted by 1 to 3 independently selected groups selected from the following: -OH, halogen, -CN, and -NR12R12.

[0264] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R6 is a 4- to 7-membered monocyclic heterocyclic group. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R6 is a 5- to 6-membered monocyclic heterocyclic group.

[0265] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R6 is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is optionally substituted by 1 to 3 groups independently selected from the following: -OH, halogen, -CN, sideoxy, -NR 11R 11, C 1-4 alkoxy, and C 1-5 alkyl, wherein the C 1-4 alkoxy and C 1-5 alkyl groups are each independently optionally substituted by 1 to 3 groups independently selected from the following: -OH, halogen, -CN, and -NR 12R 12; and wherein the 4- to 7-membered monocyclic heterocyclic group has one or two N-type cyclic heteroatoms.

[0266] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, R6 is a 5- to 6-membered monocyclic heterocyclic group, wherein the 5- to 6-membered heterocyclic group is optionally substituted by one or two groups independently selected from the following: -OH, halogen, -CN, and C1-5 alkyl; and wherein the C1-5 alkyl group is optionally substituted by one or two groups independently selected from -OH and halogen.

[0267] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, R6 is pyrrolidyl, piperidinyl, or piperyl, each of which is optionally substituted by one or two independently selected groups selected from -OH, halogen, -CN, and C1-5 alkyl, wherein the C1-5 alkyl is optionally substituted by one or two independently selected groups selected from -OH and halogen.

[0268] In some embodiments of the compounds of formula I or their pharmaceutically acceptable salts, R6 is pyrrolidyl, piperidinyl, or piperyl, each of which is optionally substituted with a C1-3 alkyl group, wherein the C1-3 alkyl group is optionally substituted with one or two independent groups selected from -OH and halogens.

[0269] In some embodiments of the compounds of formula I or their pharmaceutically acceptable salts, the R6 series, or each of them is optionally substituted with a C1-3 alkyl group, wherein the C1-3 alkyl group is substituted with a -OH group.

[0270] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, R6 is piperidinyl.

[0271] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R6 is an 8- to 10-member fused bicyclic heterocyclic group, wherein the 8- to 10-member fused bicyclic heterocyclic group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R6 is an 8- to 10-member fused bicyclic heterocyclic group, wherein the 8- to 10-member fused bicyclic heterocyclic group is optionally substituted with 1 to 3 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R6 is an 8- to 10-member fused bicyclic heterocyclic group, wherein the 8- to 10-member fused bicyclic heterocyclic group is optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group.

[0272] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R6 is an 8- to 10-member fused bicyclic heterocyclic group, wherein the 8- to 10-member fused bicyclic heterocyclic group is substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R6 is an 8- to 10-member fused bicyclic heterocyclic group, wherein the 8- to 10-member fused bicyclic heterocyclic group is substituted with 1 to 3 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R6 is an 8- to 10-member fused bicyclic heterocyclic group, wherein the 8- to 10-member fused bicyclic heterocyclic group is substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group.

[0273] In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, R6 is an 8 to 10-member fused bicyclic heterocyclic group.

[0274] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R6 is a 6- to 10-membered bridged bicyclic heterocyclic group, wherein the 6- to 10-membered bridged bicyclic heterocyclic group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R6 is a 6- to 10-membered bridged bicyclic heterocyclic group, wherein the 6- to 10-membered bridged bicyclic heterocyclic group is optionally substituted with 1 to 3 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R6 is a 6- to 10-membered bridged bicyclic heterocyclic group, wherein the 6- to 10-membered bridged bicyclic heterocyclic group is optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group.

[0275] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R6 is a 6- to 10-membered bridged bicyclic heterocyclic group, wherein the 6- to 10-membered bridged bicyclic heterocyclic group is substituted with 1 to 4 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R6 is a 6- to 10-membered bridged bicyclic heterocyclic group, wherein the 6- to 10-membered bridged bicyclic heterocyclic group is substituted with 1 to 3 Ra groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R6 is a 6- to 10-membered bridged bicyclic heterocyclic group, wherein the 6- to 10-membered bridged bicyclic heterocyclic group is substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group.

[0276] In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, R6 is a 6 to 10 member bridging bicyclic heterocyclic group.

[0277] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R6 is a 7- to 10-membered spirocyclic heterocyclic group, wherein the 7- to 10-membered spirocyclic heterocyclic group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R6 is a 7- to 10-membered spirocyclic heterocyclic group, wherein the 7- to 10-membered spirocyclic heterocyclic group is substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R6 is a 7- to 10-membered spirocyclic heterocyclic group.

[0278] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R7 is an H, C1-6 alkyl, C3-7 monocyclic cycloalkyl, or 4- to 6-membered monocyclic heterocyclic group, wherein the C1-6 alkyl, C3-7 monocyclic cycloalkyl, and 4- to 6-membered monocyclic heterocyclic groups are each optionally substituted by 1 to 4 groups independently selected from -OH, halogen, -CN, and C1-6 alkoxy groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R7 is an H or C1-6 alkyl, wherein the C1-6 alkyl group is optionally substituted by 1 to 4 groups independently selected from -OH, halogen, -CN, and C1-6 alkoxy groups.

[0279] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R7 is H or C1-3 alkyl. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R7 is H or methyl.

[0280] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, R7 is H.

[0281] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R7 is a C1-6 alkyl group, wherein the C1-6 alkyl group is optionally substituted with one to four independently selected groups selected from -OH, halogen, -CN, and C1-6 alkoxy groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R7 is a C1-6 alkyl group, wherein the C1-6 alkyl group is substituted with one to four independently selected groups selected from -OH, halogen, -CN, and C1-6 alkoxy groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R7 is a C1-6 alkyl group. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R7 is a C1-3 alkyl group. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, R7 is a methyl group.

[0282] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R7 is a C3-7 monocyclic cycloalkyl group, wherein the C3-7 monocyclic cycloalkyl group is optionally substituted with one to four independently selected groups selected from -OH, halogen, -CN, and C1-6 alkoxy groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R7 is a C3-7 monocyclic cycloalkyl group, wherein the C3-7 monocyclic cycloalkyl group is substituted with one to four independently selected groups selected from -OH, halogen, -CN, and C1-6 alkoxy groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R7 is a C3-7 monocyclic cycloalkyl group.

[0283] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R7 is a 4- to 6-membered monocyclic heterocyclic group, wherein the 4- to 6-membered monocyclic heterocyclic group is optionally substituted with 1 to 4 groups independently selected from -OH, halogen, -CN, and C1-6 alkoxy groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R7 is a 4- to 6-membered monocyclic heterocyclic group, wherein the 4- to 6-membered monocyclic heterocyclic group is substituted with 1 to 4 groups independently selected from -OH, halogen, -CN, and C1-6 alkoxy groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R7 is a 4- to 6-membered monocyclic heterocyclic group. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R7 is an oxo group.

[0284] In some embodiments of the compound of formula I or a pharmaceutically acceptable salt thereof, Z-C(O)R 13.

[0285] In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, R13 is a 4- to 7-membered monocyclic heterocyclic group, a 5- to 6-membered monocyclic heteroaryl group, an 8- to 10-membered fused bicyclic heterocyclic group, a 6- to 10-membered bridged bicyclic heterocyclic group, an 8- to 10-membered fused bicyclic heteroaryl group, or a 7- to 10-membered spirocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group, the 5- to 6-membered monocyclic heteroaryl group, the 8- to 10-membered fused bicyclic heterocyclic group, the 6- to 10-membered bridged bicyclic heterocyclic group, the 8- to 10-membered fused bicyclic heteroaryl group, and the 7- to 10-membered spirocyclic heterocyclic group are each optionally substituted with 1 to 4 Ra groups independently.

[0286] In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, R13 is a 4- to 7-member monocyclic heterocyclic group, an 8- to 10-member fused bicyclic heterocyclic group, a 6- to 10-member bridged bicyclic heterocyclic group, or a 7- to 10-member spirocyclic heterocyclic group, wherein the 4- to 7-member monocyclic heterocyclic group, the 8- to 10-member fused bicyclic heterocyclic group, the 6- to 10-member bridged bicyclic heterocyclic group, and the 7- to 10-member spirocyclic heterocyclic group are each optionally substituted with 1 to 3 Ra groups independently.

[0287] In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, R13 is a 4- to 7-membered monocyclic heterocyclic group, an 8- to 10-membered fused bicyclic heterocyclic group, a 6- to 10-membered bridged bicyclic heterocyclic group, or a 7- to 10-membered spirocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group, the 8- to 10-membered fused bicyclic heterocyclic group, the 6- to 10-membered bridged bicyclic heterocyclic group, and the 7- to 10-membered spirocyclic heterocyclic group are each optionally substituted by 1 to 3 groups independently selected from the following: -OH, halogen, -CN, sideoxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group, wherein the C1-5 alkyl group is optionally substituted by 1 to 3 groups independently selected from the following: -OH, halogen, -CN, sideoxy group, and -NR12R12 group.

[0288] In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, R13 is a 4- to 7-membered monocyclic heterocyclic group, an 8- to 10-membered fused bicyclic heterocyclic group, a 6- to 10-membered bridged bicyclic heterocyclic group, or a 7- to 10-membered spirocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group, the 8- to 10-membered fused bicyclic heterocyclic group, the 6- to 10-membered bridged bicyclic heterocyclic group, and the 7- to 10-membered spirocyclic heterocyclic group are each optionally substituted by 1 to 3 groups independently selected from the following: -OH, halogen, -CN, sideoxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group, wherein the C1-5 alkyl group is optionally substituted by 1 to 2 groups independently selected from the following: -OH, halogen, -CN, and -NR12R12; and wherein each R12 is independently H or C1-3 alkyl group;

[0289] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is optionally substituted with 1 to 3 Ra groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is optionally substituted by 1 to 3 independently selected groups of: -OH, halogen, -CN, oxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group, wherein the C1-5 alkyl group is optionally substituted by 1 to 3 independently selected groups of: -OH, halogen, -CN, oxy group, and -NR12R12 group. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is substituted by 1 to 3 groups independently selected from the following: -OH, halogen, -CN, oxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group, wherein the C1-5 alkyl group is optionally substituted by 1 to 2 groups independently selected from the following: -OH, halogen, -CN, oxy group, and -NR12R12 group, and wherein each R12 is independently H or C1-3 alkyl group. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is optionally substituted by 1 to 3 independently selected groups from the following: -OH, halogen, -CN, sideoxy, -NR11R11, C1-4 alkoxy, and C1-5 alkyl.

[0290] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is substituted with 1 to 3 Ra groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is substituted by 1 to 3 independently selected groups selected from: -OH, halogen, -CN, oxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group, wherein the C1-5 alkyl group is optionally substituted by 1 to 3 independently selected groups selected from: -OH, halogen, -CN, oxy group, and -NR12R12 group. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is substituted by 1 to 3 groups independently selected from the following: -OH, halogen, -CN, oxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group, wherein the C1-5 alkyl group is optionally substituted by 1 to 2 groups independently selected from the following: -OH, halogen, -CN, oxy group, and -NR12R12 group, and wherein each R12 is independently H or C1-3 alkyl group. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is substituted by 1 to 3 independently selected groups from the following: -OH, halogen, -CN, sideoxy, -NR11R11, C1-4 alkoxy, and C1-5 alkyl.

[0291] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is optionally substituted by 1 to 3 independently selected groups selected from: -OH, halogen, -CN, oxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is substituted by 1 to 3 independently selected groups selected from: -OH, halogen, -CN, oxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group.

[0292] In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, R13 is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is optionally substituted by 1 to 3 independently selected groups selected from: -OH, halogen, -CN, sideoxy, -NR11R11, C1-4 alkoxy, and C1-5 alkyl; and wherein the 4- to 7-membered monocyclic heterocyclic group has one or two N-type cyclic heteroatoms.

[0293] In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, R13 is a 5- to 6-membered monocyclic heterocyclic group, wherein the 5- to 6-membered monocyclic heterocyclic group is optionally substituted by 1 to 3 independently selected groups from the following: -OH, halogen, -CN, sideoxy, -NR11R11, C1-4 alkoxy, and C1-5 alkyl.

[0294] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is a 4- to 7-membered monocyclic heterocyclic group. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is a 5- to 6-membered monocyclic heterocyclic group.

[0295] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, R13 is a piperyl group.

[0296] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is a 5- to 6-membered monocyclic heteroaryl group, wherein the 5- to 6-membered monocyclic heteroaryl group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is a 5- to 6-membered monocyclic heteroaryl group, wherein the 5- to 6-membered monocyclic heteroaryl group is substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is a 5- to 6-membered monocyclic heteroaryl group.

[0297] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is an 8- to 10-member fused bicyclic heterocyclic group, wherein the 8- to 10-member fused bicyclic heterocyclic group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is an 8- to 10-member fused bicyclic heterocyclic group, wherein the 8- to 10-member fused bicyclic heterocyclic group is optionally substituted with 1 to 3 Ra groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is an 8- to 10-member fused bicyclic heterocyclic group, wherein the 8- to 10-member fused bicyclic heterocyclic group is optionally substituted by 1 to 3 independently selected groups from the following: -OH, halogen, -CN, oxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group, wherein the C1-5 alkyl group is optionally substituted by 1 to 3 independently selected groups from the following: -OH, halogen, -CN, oxy group, and -NR12R12 group. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is an 8- to 10-member fused bicyclic heterocyclic group, wherein the 8- to 10-member fused bicyclic heterocyclic group is substituted by 1 to 3 independently selected groups from the following: -OH, halogen, -CN, oxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group, wherein the C1-5 alkyl group is optionally substituted by 1 to 2 independently selected groups from the following: -OH, halogen, -CN, oxy group, and -NR12R12 group, and wherein each R12 is independently H or C1-3 alkyl group.

[0298] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is an 8- to 10-member fused bicyclic heterocyclic group, wherein the 8- to 10-member fused bicyclic heterocyclic group is substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is an 8- to 10-member fused bicyclic heterocyclic group, wherein the 8- to 10-member fused bicyclic heterocyclic group is substituted with 1 to 3 Ra groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is an 8- to 10-member fused bicyclic heterocyclic group, wherein the 8- to 10-member fused bicyclic heterocyclic group is substituted by 1 to 3 independently selected groups selected from: -OH, halogen, -CN, oxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group, wherein the C1-5 alkyl group is optionally substituted by 1 to 3 independently selected groups selected from: -OH, halogen, -CN, oxy group, and -NR12R12. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is an 8- to 10-member fused bicyclic heterocyclic group, wherein the 8- to 10-member fused bicyclic heterocyclic group is substituted by 1 to 3 independently selected groups from the following: -OH, halogen, -CN, oxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group, wherein the C1-5 alkyl group is optionally substituted by 1 to 2 independently selected groups from the following: -OH, halogen, -CN, oxy group, and -NR12R12 group, and wherein each R12 is independently H or C1-3 alkyl group.

[0299] In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, R13 is an 8 to 10-member fused bicyclic heterocyclic group.

[0300] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is a 6- to 10-membered bridged bicyclic heterocyclic group, wherein the 6- to 10-membered bridged bicyclic heterocyclic group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is a 6- to 10-membered bridged bicyclic heterocyclic group, wherein the 6- to 10-membered bridged bicyclic heterocyclic group is optionally substituted with 1 to 3 Ra groups. In some embodiments of compounds of Formula I or their pharmaceutically acceptable salts, R13 is a 6- to 10-membered bridged bicyclic heterocyclic group, wherein the 6- to 10-membered bridged bicyclic heterocyclic group is optionally substituted by 1 to 3 independently selected groups from the following: -OH, halogen, -CN, oxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group, wherein the C1-5 alkyl group is optionally substituted by 1 to 3 independently selected groups from the following: -OH, halogen, -CN, oxy group, and -NR12R12. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is a 6- to 10-membered bridged bicyclic heterocyclic group, wherein the 6- to 10-membered bridged bicyclic heterocyclic group is substituted by 1 to 3 independently selected groups selected from: -OH, halogen, -CN, oxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group, wherein the C1-5 alkyl group is optionally substituted by 1 to 2 independently selected groups selected from: -OH, halogen, -CN, oxy group, and -NR12R12 group, and wherein each R12 is independently H or C1-3 alkyl group.

[0301] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is a 6- to 10-membered bridged bicyclic heterocyclic group, wherein the 6- to 10-membered bridged bicyclic heterocyclic group is substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is a 6- to 10-membered bridged bicyclic heterocyclic group, wherein the 6- to 10-membered bridged bicyclic heterocyclic group is substituted with 1 to 3 Ra groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is a 6- to 10-membered bridged bicyclic heterocyclic group, wherein the 6- to 10-membered bridged bicyclic heterocyclic group is substituted by 1 to 3 independently selected groups selected from: -OH, halogen, -CN, oxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group, wherein the C1-5 alkyl group is optionally substituted by 1 to 3 independently selected groups selected from: -OH, halogen, -CN, oxy group, and -NR12R12. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is a 6- to 10-membered bridged bicyclic heterocyclic group, wherein the 6- to 10-membered bridged bicyclic heterocyclic group is substituted by 1 to 3 independently selected groups selected from: -OH, halogen, -CN, oxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group, wherein the C1-5 alkyl group is optionally substituted by 1 to 2 independently selected groups selected from: -OH, halogen, -CN, oxy group, and -NR12R12 group, and wherein each R12 is independently H or C1-3 alkyl group.

[0302] In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, R13 is a 6 to 10 member bridging bicyclic heterocyclic group.

[0303] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is a 7- to 10-membered spirocyclic heterocyclic group, wherein the 7- to 10-membered spirocyclic heterocyclic group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is a 7- to 10-membered spirocyclic heterocyclic group, wherein the 7- to 10-membered spirocyclic heterocyclic group is optionally substituted with 1 to 3 Ra groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is a 7- to 10-membered spirocyclic heterocyclic group, wherein the 7- to 10-membered spirocyclic heterocyclic group is optionally substituted by 1 to 3 independently selected groups from the following: -OH, halogen, -CN, oxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group, wherein the C1-5 alkyl group is optionally substituted by 1 to 3 independently selected groups from the following: -OH, halogen, -CN, oxy group, and -NR12R12 group. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is a 7- to 10-membered spirocyclic heterocyclic group, wherein the 7- to 10-membered spirocyclic heterocyclic group is substituted by 1 to 3 groups independently selected from the following groups: -OH, halogen, -CN, oxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group, wherein the C1-5 alkyl group is optionally substituted by 1 to 2 groups independently selected from the following groups: -OH, halogen, -CN, oxy group, and -NR12R12 group, and wherein each R12 is independently H or C1-3 alkyl group.

[0304] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is a 7- to 10-membered spirocyclic heterocyclic group, wherein the 7- to 10-membered spirocyclic heterocyclic group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is a 7- to 10-membered spirocyclic heterocyclic group, wherein the 7- to 10-membered spirocyclic heterocyclic group is substituted with 1 to 3 Ra groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is a 7- to 10-membered spirocyclic heterocyclic group, wherein the 7- to 10-membered spirocyclic heterocyclic group is substituted by 1 to 3 independently selected groups from the following: -OH, halogen, -CN, oxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group, wherein the C1-5 alkyl group is optionally substituted by 1 to 3 independently selected groups from the following: -OH, halogen, -CN, oxy group, and -NR12R12. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, R13 is a 7- to 10-membered spirocyclic heterocyclic group, wherein the 7- to 10-membered spirocyclic heterocyclic group is substituted by 1 to 3 groups independently selected from the following groups: -OH, halogen, -CN, oxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group, wherein the C1-5 alkyl group is optionally substituted by 1 to 2 groups independently selected from the following groups: -OH, halogen, -CN, oxy group, and -NR12R12 group, and wherein each R12 is independently H or C1-3 alkyl group.

[0305] In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, R13 is a 7- to 10-membered spirocyclic heterocyclic group.

[0306] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, each R5 is independently H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4 to 7-membered monocyclic heterocyclic group, 5 to 6-membered monocyclic heteroaryl, 8 to 10-membered fused bicyclic heterocyclic group, 6 to 10-membered bridged bicyclic heterocyclic group, 8 to 10-membered fused bicyclic heteroaryl, or 7 to 10-membered spirocyclic heterocyclic group, wherein the C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each independently optionally substituted by 1 to 4 Rb groups, wherein the C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 fused bicyclic cycloalkyl, C5-10 phenyl, naphthyl, 4 to 7-membered monocyclic heterocyclic group, 5 to 6-membered monocyclic heterocyclic group, 8 to 10-membered fused bicyclic heterocyclic group, or 7 to 10-membered spirocyclic heterocyclic group, wherein the C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each independently optionally substituted by 1 to 4 Rb groups, wherein the C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 phenyl, C6-6 ... Each of the 5-10-membered bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, and 7-10-membered spirocyclic heterocyclic groups is optionally substituted with 1 to 4 Ra groups.

[0307] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more R5-based H groups are present. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more R5-based C1-6 alkyl groups are present, wherein the C1-6 alkyl group is optionally substituted with 1 to 4 Rb groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more R5-based C2-6 alkenyl groups are present, wherein the C2-6 alkenyl group is optionally substituted with 1 to 4 Rb groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more R5-based C2-6 alkynyl groups are present, wherein the C2-6 alkynyl group is optionally substituted with 1 to 4 Rb groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more R5-based C3-7 monocyclic cycloalkyl groups are present, wherein the C3-7 monocyclic cycloalkyl group is optionally substituted with 1 to 4 Ra groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R5-based C7-10 fused bicyclic cycloalkyl groups, wherein the C7-10 fused bicyclic cycloalkyl group is optionally substituted with 1 to 4 Ra groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R5-based C5-10 bridged bicyclic cycloalkyl groups, wherein the C5-10 bridged bicyclic cycloalkyl group is optionally substituted with 1 to 4 Ra groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R5-based phenyl groups, wherein the phenyl group is optionally substituted with 1 to 4 Ra groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R5-based naphthyl groups, wherein the naphthyl group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R5 groups are 4- to 7-membered monocyclic heterocyclic groups, wherein the 4- to 7-membered monocyclic heterocyclic groups are optionally substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R5 groups are 5- to 6-membered monocyclic heteroaryl groups, wherein the 5- to 6-membered monocyclic heteroaryl groups are optionally substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R5 groups are 8- to 10-membered fused bicyclic heterocyclic groups, wherein the 8- to 10-membered fused bicyclic heterocyclic groups are optionally substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R5 groups are 6- to 10-membered bridged bicyclic heterocyclic groups, wherein the 6- to 10-membered bridged bicyclic heterocyclic groups are optionally substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, one or more R5-based 8 to 10-member fused bicyclic heteroaryl groups are included, wherein the 8 to 10-member fused bicyclic heteroaryl groups are optionally substituted with 1 to 4 Ra groups.In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, one or more R5 groups are 7 to 10 spirocyclic heterocyclic groups, wherein the 7 to 10 spirocyclic heterocyclic groups are optionally substituted with 1 to 4 Ra groups.

[0308] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, each R10 is independently H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4 to 7-membered monocyclic heterocyclic group, 5 to 6-membered monocyclic heteroaryl, 8 to 10-membered fused bicyclic heterocyclic group, 6 to 10-membered bridged bicyclic heterocyclic group, 8 to 10-membered fused bicyclic heteroaryl, or 7 to 10-membered spirocyclic heterocyclic group, wherein the C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each independently optionally substituted with 1 to 4 Rb groups, wherein the C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 fused bicyclic cycloalkyl, C6-6 alkyl, C7-10 ... Each of the 5-10-membered bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, and 7-10-membered spirocyclic heterocyclic groups is optionally substituted with 1 to 4 Ra groups.

[0309] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, each R10 is independently H or C1-6 alkyl. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, each R10 is independently H or C1-3 alkyl.

[0310] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R10 are H. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R10 are C1-6 alkyl, wherein the C1-6 alkyl group is optionally substituted with 1 to 4 Rb groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R10 are C1-3 alkyl, wherein the C1-3 alkyl group is optionally substituted with 1 to 4 Rb groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R10 are C1-3 alkyl. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or both R10 are C2-6 alkenyl, wherein the C2-6 alkenyl group is optionally substituted with 1 to 4 Rb groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R10 are C2-6 ynyl groups, wherein the C2-6 ynyl group is optionally substituted with 1 to 4 Rb groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R10 are C3-7 monocyclic cycloalkyl groups, wherein the C3-7 monocyclic cycloalkyl group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R10 are C7-10 fused bicyclic cycloalkyl groups, wherein the C7-10 fused bicyclic cycloalkyl group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R10 are C5-10 bridged bicyclic cycloalkyl groups, wherein the C5-10 bridged bicyclic cycloalkyl group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R10 are phenyl groups, wherein the phenyl group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R10 are naphthyl groups, wherein the naphthyl group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R10 are 4 to 7-membered monocyclic heterocyclic groups, wherein the 4 to 7-membered monocyclic heterocyclic groups are optionally substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R10 are 5 to 6-membered monocyclic heteroaryl groups, wherein the 5 to 6-membered monocyclic heteroaryl groups are optionally substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, one or both R10 are 8 to 10-membered fused bicyclic heterocyclic groups, wherein the 8 to 10-membered fused bicyclic heterocyclic groups are optionally substituted with 1 to 4 Ra groups.In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R10 are 6 to 10 membered bridged bicyclic heterocyclic groups, wherein the 6 to 10 membered bridged bicyclic heterocyclic groups are optionally substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R10 are 8 to 10 membered fused bicyclic heteroaryl groups, wherein the 8 to 10 membered fused bicyclic heteroaryl groups are optionally substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or both R10 are 7 to 10 membered spirocyclic heterocyclic groups, wherein the 7 to 10 membered spirocyclic heterocyclic groups are optionally substituted with 1 to 4 Ra groups.

[0311] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt, each R 5a is independently a C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4 to 7-membered monocyclic heterocyclic group, 5 to 6-membered monocyclic heteroaryl, 8 to 10-membered fused bicyclic heterocyclic group, 6 to 10-membered bridged bicyclic heterocyclic group, 8 to 10-membered fused bicyclic heteroaryl, or 7 to 10-membered spirocyclic heterocyclic group, wherein the C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each independently optionally substituted by 1 to 4 R b groups, wherein the C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-7 fused bicyclic cycloalkyl, C5-10 ... Each of the 5-10-membered bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, and 7-10-membered spirocyclic heterocyclic groups is optionally substituted with 1 to 4 Ra groups.

[0312] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more R5a-based C1-6 alkyl groups, wherein the C1-6 alkyl group is optionally substituted with 1 to 4 Rb groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more R5a-based C2-6 alkenyl groups, wherein the C2-6 alkenyl group is optionally substituted with 1 to 4 Rb groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more R5a-based C2-6 alkynyl groups, wherein the C2-6 alkynyl group is optionally substituted with 1 to 4 Rb groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more R5a-based C3-7 monocyclic cycloalkyl groups, wherein the C3-7 monocyclic cycloalkyl group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R 5a-based C 7-10 fused bicyclic cycloalkyl groups, wherein the C 7-10 fused bicyclic cycloalkyl group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R 5a-based C 5-10 bridged bicyclic cycloalkyl groups, wherein the C 5-10 bridged bicyclic cycloalkyl group is optionally substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R 5a-based phenyl groups, wherein the phenyl groups are optionally substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R 5a-based naphthyl groups, wherein the naphthyl groups are optionally substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R5a groups are 4 to 7-membered monocyclic heterocyclic groups, wherein the 4 to 7-membered monocyclic heterocyclic groups are optionally substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R5a groups are 5 to 6-membered monocyclic heteroaryl groups, wherein the 5 to 6-membered monocyclic heteroaryl groups are optionally substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R5a groups are 8 to 10-membered fused bicyclic heterocyclic groups, wherein the 8 to 10-membered fused bicyclic heterocyclic groups are optionally substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R5a groups are 6 to 10-membered bridged bicyclic heterocyclic groups, wherein the 6 to 10-membered bridged bicyclic heterocyclic groups are optionally substituted with 1 to 4 Ra groups. In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, one or more R 5a groups are 8 to 10 fused bicyclic heteroaryl groups, wherein the 8 to 10 fused bicyclic heteroaryl groups are optionally substituted with 1 to 4 Ra groups.In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, one or more R5a groups are 7 to 10-membered spirocyclic heterocyclic groups, wherein the 7 to 10-membered spirocyclic heterocyclic groups are optionally substituted with 1 to 4 Ra groups.

[0313] In some embodiments of compounds of formula I or pharmaceutically acceptable salts thereof, each Ra is independently a side-oxygen group, imino group, halogen, -NO2, -N3, -CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4 to 7-membered monocyclic heterocyclic group, 5 to 6-membered monocyclic heteroaryl, 8 to 10-membered fused bicyclic heterocyclic group, 6 to 10-membered bridged bicyclic heterocyclic group, 8 to 10-membered fused bicyclic heteroaryl, 7 to 10-membered spirocyclic heterocyclic group, -OR11, -C(O)R11, -C(O)OR11, -C(O)N(R11)(R11), -NR11R11, -N(R11) 2(R 11) +, -N(R 11)C(O)R 11, -N(R 11)C(O)OR 11, -N(R 11)C(O)N(R 11)(R 11), -N(R 11)S(O) 2(R 11a), -NR 11S(O) 2N(R 11)(R 11), -NR 11S(O) 2O(R 11a), -OC(O)R 11, -OC(O)OR 11, -OC(O)N(R 11)(R 11), -SR 11, -S(O)R 11a, -S(O)(NH)R 11, -S(O) 2R 11a, -S(O) 2N(R 11)(R 11), or -N=S(R 11a)(R 11a)=O, wherein the C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl groups are each optionally substituted with 1 to 3 Rc groups; and wherein the C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4 to 7-membered monocyclic heterocyclic, 5 to 6-membered monocyclic heteroaryl, 8 to 10-membered fused bicyclic heterocyclic, 6 to 10-membered bridged bicyclic heterocyclic, 8 to 10-membered fused bicyclic heteroaryl, and 7 to 10-membered spirocyclic heterocyclic groups are each optionally substituted with 1 to 3 Rd groups.

[0314] In some embodiments of compounds of Formula I or II or pharmaceutically acceptable salts thereof, each Ra is independently -OH, halogen, -CN, syloxy, -NR11R11, C1-4 alkoxy, or C1-5 alkyl. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, each Ra is independently -OH, halogen, -CN, syloxy, -NR11R11, C1-3 alkoxy, or C1-3 alkyl.

[0315] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more Ra-based side-oxygen groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more Ra-based imine groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more Ra-based halogens. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more Ra-based NO₂. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more Ra-based N₃. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more Ra-based CN. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more Ra-based OR₁₁. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more Ra-based C(O)R₁₁. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Ra-based compounds are represented by -C(O)OR11. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Ra-based compounds are represented by -C(O)N(R11)(R11). In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Ra-based compounds are represented by -NR11R11. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Ra-based compounds are represented by -N(R11)2(R11)+. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Ra-based compounds are represented by -N(R11)C(O)R11. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Ra-based compounds are represented by -N(R11)C(O)OR11. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Ra-based compounds are represented by N(R 11)C(O)N(R 11)(R 11). In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Ra-based compounds are represented by N(R 11)S(O) 2(R 11a). In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Ra-based compounds are represented by NR 11S(O) 2N(R 11)(R 11). In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Ra-based compounds are represented by NR 11S(O) 2O(R 11a). In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Ra-based compounds are represented by OC(O)R 11. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Ra-based compounds are represented by OC(O)OR 11. In some embodiments of compounds of formula I or their pharmaceutically acceptable salts, one or more Ra-based -OC(O)N(R 11)(R 11).In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Ra-based compounds are SR 11. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Ra-based compounds are S(O)R 11a. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Ra-based compounds are S(O)(NH)R 11. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Ra-based compounds are S(O) 2R 11a. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Ra-based compounds are S(O) 2N(R 11)(R 11). In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Ra-based compounds are N=S(R 11a)(R 11a)=O.

[0316] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Ra-based C1-6 alkyl groups are present, wherein the C1-6 alkyl group is optionally substituted with 1 to 3 Rc groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Ra-based C2-6 alkenyl groups are present, wherein the C2-6 alkenyl group is optionally substituted with 1 to 3 Rc groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Ra-based C2-6 alkynyl groups are present, wherein the C2-6 alkynyl group is optionally substituted with 1 to 3 Rc groups.

[0317] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Ra-based C3-7 monocyclic cycloalkyl groups, wherein the C3-7 monocyclic cycloalkyl group is optionally substituted with 1 to 3 Rd groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Ra-based C7-10 fused bicyclic cycloalkyl groups, wherein the C7-10 fused bicyclic cycloalkyl group is optionally substituted with 1 to 3 Rd groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Ra-based C5-10 bridged bicyclic cycloalkyl groups, wherein the C5-10 bridged bicyclic cycloalkyl group is optionally substituted with 1 to 3 Rd groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Ra-based phenyl groups, wherein the phenyl group is optionally substituted with 1 to 3 Rd groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Ra-based naphthyl groups are included, wherein the naphthyl group is optionally substituted with 1 to 3 Rd groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Ra-based 4- to 7-membered monocyclic heterocyclic groups are included, wherein the 4- to 7-membered monocyclic heterocyclic groups are optionally substituted with 1 to 3 Rd groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Ra-based 5- to 6-membered monocyclic heteroaryl groups are included, wherein the 5- to 6-membered monocyclic heteroaryl groups are optionally substituted with 1 to 3 Rd groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Ra-based 8- to 10-membered fused bicyclic heterocyclic groups are included, wherein the 8- to 10-membered fused bicyclic heterocyclic groups are optionally substituted with 1 to 3 Rd groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Ra-based 6- to 10-membered bridged bicyclic heterocyclic groups, wherein the 6- to 10-membered bridged bicyclic heterocyclic groups are optionally substituted with 1 to 3 Rd groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Ra-based 8- to 10-membered fused bicyclic heteroaryl groups, wherein the 8- to 10-membered fused bicyclic heteroaryl groups are optionally substituted with 1 to 3 Rd groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Ra-based 7- to 10-membered spirocyclic heterocyclic groups, wherein the 7- to 10-membered spirocyclic heterocyclic groups are optionally substituted with 1 to 3 Rd groups.

[0318] In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, each Rb is independently a side oxygen group, imino group, halogen, -NO2, -N3, -CN, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4 to 7 member monocyclic heterocyclic group, 5 to 6 member monocyclic heteroaryl, 8 to 10 member fused bicyclic heterocyclic group, 6 to 10 member bridged bicyclic heterocyclic group, 8 to 10 member fused bicyclic heteroaryl, 7 to 10 member spirocyclic heterocyclic group, -OR11, -C(O)R11, -C(O)OR11, -C(O)N(R11)(R11), -NR11R11, -N(R11)2(R11)+, -N(R11)C(O)R 11, -N(R 11)C(O)OR 11, -N(R 11)C(O)N(R 11)(R 11), -N(R 11)S(O) 2(R 11a), -NR 11S(O) 2N(R 11)(R 11), -NR 11S(O) 2O(R 11a), -OC(O)R 11, -OC(O)OR 11, -OC(O)N(R 11)(R 11), -SR 11, -S(O)R 11a, -S(O)(NH)R 11, -S(O) 2R 11a, -S(O) 2N(R 11)(R 11), or -N=S(R 11a)(R 11a)=O, wherein the C 3-7 monocyclic cycloalkyl group, C The 7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4 to 7 member monocyclic heterocyclic, 5 to 6 member monocyclic heteroaryl, 8 to 10 member fused bicyclic heterocyclic, 6 to 10 member bridged bicyclic heterocyclic, 8 to 10 member fused bicyclic heteroaryl, and 7 to 10 member spirocyclic heterocyclic groups are each optionally substituted by 1 to 3 Rd groups.

[0319] In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, each Rb is independently -OH, halogen, -CN, lateral oxy group, -NR11R11, C1-4 alkoxy group, C3-7 monocyclic cycloalkyl group, C7-10 fused bicyclic cycloalkyl group, C5-10 bridged bicyclic cycloalkyl group, phenyl group, naphthyl group, 4 to 7-member monocyclic heterocyclic group, 5 to 6-member monocyclic heteroaryl group, 8 to 10-member fused bicyclic heterocyclic group, 8 to 10-member bridged bicyclic heterocyclic group, 6 to 10-member bridged bicyclic heterocyclic group, 8 to 10-member fused bicyclic heteroaryl group, or 7 to 10-member spirocyclic heterocyclic group.

[0320] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, each Rb is independently -OH, halogen, -CN, syloxy group, -NR 11R 11, -C(O)N(R 11)(R 11), C1-4 alkoxy group, or a 4- to 7-membered monocyclic heterocyclic group. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, each Rb is independently -OH, halogen, -CN, syloxy group, -NR 11R 11, or C1-4 alkoxy group. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, each Rb is independently -OH, halogen, -CN, syloxy group, -NR 11R 11, or C1-3 alkoxy group. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, each Rb is independently halogen or C1-3 alkoxy group.

[0321] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, each Rb is independently a 4- to 7-member monocyclic heterocyclic group, an 8- to 10-member fused bicyclic heterocyclic group, or a 6- to 10-member bridged bicyclic heterocyclic group. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rb is a 4- to 7-member monocyclic heterocyclic group. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rb is a 5- to 7-member monocyclic heterocyclic group. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rb is an 8- to 10-member fused bicyclic heterocyclic group. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rb is a 6- to 10-member bridged bicyclic heterocyclic group.

[0322] In some embodiments of the compound of Formula I or its pharmaceutically acceptable salt, one or more Rb-based side-oxygen groups. In some embodiments of the compound of Formula I or its pharmaceutically acceptable salt, one or more Rb-based imine groups. In some embodiments of the compound of Formula I or its pharmaceutically acceptable salt, one or more Rb-based halogens. In some embodiments of the compound of Formula I or its pharmaceutically acceptable salt, one or more Rb-based -NO2. In some embodiments of the compound of Formula I or its pharmaceutically acceptable salt, one or more Rb-based -N3. In some embodiments of the compound of Formula I or its pharmaceutically acceptable salt, one or more Rb-based -CN. In some embodiments of the compound of Formula I or its pharmaceutically acceptable salt, one or more Rb-based -OR11. In some embodiments of the compound of Formula I or its pharmaceutically acceptable salt, one or more Rb-based -C(O)R11. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rb-based compounds are represented by -C(O)OR 11. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rb-based compounds are represented by -C(O)N(R 11)(R 11). In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rb-based compounds are represented by -NR 11R 11. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rb-based compounds are represented by -N(R 11) 2(R 11) +. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rb-based compounds are represented by -N(R 11)C(O)R 11. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rb-based compounds are represented by -N(R 11)C(O)OR 11. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rb-based compounds are represented by -N(R 11)C(O)N(R 11)(R 11). In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rb-based compounds are represented by -N(R 11)S(O) 2(R 11a). In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rb-based compounds are represented by -NR 11S(O) 2N(R 11)(R 11). In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rb-based compounds are represented by -NR 11S(O) 2O(R 11a). In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rb-based compounds are represented by -OC(O)R 11. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rb-based compounds are represented by -OC(O)OR 11. In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, one or more Rb-OC(O)N(R 11)(R 11).In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rb-based compounds are SR 11. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rb-based compounds are S(O)R 11a. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rb-based compounds are S(O)(NH)R 11. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rb-based compounds are S(O) 2R 11a. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rb-based compounds are S(O) 2N(R 11)(R 11). In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rb-based compounds are N=S(R 11a)(R 11a)=O.

[0323] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rb-based C3-7 monocyclic cycloalkyl groups, wherein the C3-7 monocyclic cycloalkyl group is optionally substituted with 1 to 3 Rd groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rb-based C7-10 fused bicyclic cycloalkyl groups, wherein the C7-10 fused bicyclic cycloalkyl group is optionally substituted with 1 to 3 Rd groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rb-based C5-10 bridged bicyclic cycloalkyl groups, wherein the C5-10 bridged bicyclic cycloalkyl group is optionally substituted with 1 to 3 Rd groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rb-based phenyl groups, wherein the phenyl group is optionally substituted with 1 to 3 Rd groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rb-based naphthyl groups are present, wherein the naphthyl group is optionally substituted with 1 to 3 Rd groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rb-based 4- to 7-membered monocyclic heterocyclic groups are present, wherein the 4- to 7-membered monocyclic heterocyclic groups are optionally substituted with 1 to 3 Rd groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rb-based 5- to 6-membered monocyclic heteroaryl groups are present, wherein the 5- to 6-membered monocyclic heteroaryl groups are optionally substituted with 1 to 3 Rd groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rb-based 8- to 10-membered fused bicyclic heterocyclic groups are present, wherein the 8- to 10-membered fused bicyclic heterocyclic groups are optionally substituted with 1 to 3 Rd groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rb groups are 6- to 10-membered bridged bicyclic heterocyclic groups, wherein the 6- to 10-membered bridged bicyclic heterocyclic groups are optionally substituted with 1 to 3 Rd groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rb groups are 8- to 10-membered fused bicyclic heteroaryl groups, wherein the 8- to 10-membered fused bicyclic heteroaryl groups are optionally substituted with 1 to 3 Rd groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rb groups are 7- to 10-membered spirocyclic heterocyclic groups, wherein the 7- to 10-membered spirocyclic heterocyclic groups are optionally substituted with 1 to 3 Rd groups.

[0324] In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, each Rc is independently a halogen, -CN, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4 to 7-membered monocyclic heterocyclic group, 5 to 6-membered monocyclic heteroaryl, 8 to 10-membered fused bicyclic heterocyclic group, 6 to 10-membered bridged bicyclic heterocyclic group, 8 to 10-membered fused bicyclic heteroaryl, 7 to 10-membered spirocyclic heterocyclic group, -OR12, -C(O)R12, -C(O)OR12, -C(O)N(R12)(R12), -NR12R12, -N(R12)2(R12)+, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)OR12, -N(R12)C(O)R ... 12)C(O)N(R 12)(R 12), -N(R 12)S(O) 2(R 12a), -NR 12S(O) 2N(R 12)(R 12), -NR 12S(O) 2O(R 12a), -OC(O)R 12, -OC(O)OR 12, -OC(O)N(R 12)(R 12), -SR 12, -S(O)R 12a, -S(O)(NH)R 12, -S(O) 2R 12a, -S(O) 2N(R 12)(R 12), or -N=S(R 12a)(R 12a)=O.

[0325] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more Rc-based halogens. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more Rc-based -CN. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more Rc-based C7-10 fused bicyclic cycloalkyl groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more Rc-based C5-10 bridged bicyclic cycloalkyl groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more Rc-based phenyl groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more Rc-based naphthyl groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more Rc-based 4- to 7-membered monocyclic heterocyclic groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more Rc-based 5- to 6-membered monocyclic heteroaryl groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rc-based 8- to 10-member fused bicyclic heterocyclic groups are present. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rc-based 6- to 10-member bridged bicyclic heterocyclic groups are present. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rc-based 8- to 10-member fused bicyclic heteroaryl groups are present. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rc-based 7- to 10-member spirocyclic heterocyclic groups are present. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rc-based -OR 12 are present. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rc-based -C(O)R 12 are present. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rc-based -C(O)OR 12 are present. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rc-based compounds are -C(O)N(R 12)(R 12). In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rc-based compounds are -NR 12R 12. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rc-based compounds are -N(R 12) 2(R 12) +. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rc-based compounds are -N(R 12)C(O)R 12. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rc-based compounds are -N(R 12)C(O)OR 12. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rc-based compounds are -N(R 12)C(O)N(R 12)(R 12).In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rc-based compounds are represented by N(R 12)S(O) 2(R 12a). In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rc-based compounds are represented by NR 12S(O) 2N(R 12)(R 12). In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rc-based compounds are represented by NR 12S(O) 2O(R 12a). In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rc-based compounds are represented by OC(O)R 12. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rc-based compounds are represented by OC(O)OR 12. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rc-based compounds are represented by OC(O)N(R 12)(R 12). In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rc-based compounds are SR 12. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rc-based compounds are S(O)R 12a. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rc-based compounds are S(O)(NH)R 12. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rc-based compounds are S(O) 2R 12a. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rc-based compounds are S(O) 2N(R 12)(R 12). In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rc-based compounds are N=S(R 12a)(R 12a)=O.

[0326] In some embodiments of compounds of Formula I or II or pharmaceutically acceptable salts thereof, each Rc is independently -OH, halogen, -CN, lateral oxy group, or -NR 12R 12. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, each Rc is independently -OH, halogen, -CN, or -NR 12R 12. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rcs are -OH. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rcs are halogens.

[0327] In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, each Rd is independently a side-oxygen group, halogen, -CN, C1-6 alkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4 to 7-membered monocyclic heterocyclic group, 5 to 6-membered monocyclic heteroaryl, 8 to 10-membered fused bicyclic heterocyclic group, 6 to 10-membered bridged bicyclic heterocyclic group, 8 to 10-membered fused bicyclic heteroaryl, 7 to 10-membered spirocyclic heterocyclic group, -OR12, -C(O)R12, -C(O)OR12, -C(O)N(R12)(R12), -NR12R12, -N(R12)2(R12)+, -N(R12)C(O)R12 ... 12)C(O)OR 12, -N(R 12)C(O)N(R 12)(R 12), -N(R 12)S(O) 2(R 12a), -NR 12S(O) 2N(R 12)(R 12), -NR 12S(O) 2O(R 12a), -OC(O)R 12. -OC(O)OR 12, -OC(O)N(R 12)(R 12), -SR 12, -S(O)R 12a, -S(O)(NH)R 12, -S(O) 2R 12a, -S(O) 2N(R 12)(R 12), or -N=S(R 12a)(R 12a)=O, where C The 1-6 alkyl groups may optionally be substituted by one to three independently selected groups from the following: -OH, halogen, -CN, and C1-3 alkoxy.

[0328] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more Rd groups are lateral hydroxyl groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more Rd groups are halogens. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more Rd groups are -CN groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more Rd groups are C7-10 fused bicyclic cycloalkyl groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more Rd groups are C5-10 bridged bicyclic cycloalkyl groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more Rd groups are phenyl groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more Rd groups are naphthyl groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more Rd groups are 4 to 7-membered monocyclic heterocyclic groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rd groups are 5- to 6-membered monocyclic heteroaryl groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rd groups are 8- to 10-membered fused bicyclic heterocyclic groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rd groups are 6- to 10-membered bridged bicyclic heterocyclic groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rd groups are 8- to 10-membered fused bicyclic heteroaryl groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rd groups are 7- to 10-membered spirocyclic heterocyclic groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rd groups are -OR 12. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rd groups are -C(O)R 12. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rd series -C(O)OR 12. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rd series -C(O)N(R 12)(R 12). In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rd series -NR 12R 12. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rd series -N(R 12) 2(R 12) +. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rd series -N(R 12)C(O)R 12. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rd series -N(R 12)C(O)OR 12. In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, one or more Rd series -N(R 12)C(O)N(R 12)(R 12).In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rd-based compounds are denoted as -N(R12)S(O)2(R12a). In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rd-based compounds are denoted as -NR12S(O)2N(R12)(R12). In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rd-based compounds are denoted as -NR12S(O)2O(R12a). In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rd-based compounds are denoted as -OC(O)R12. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rd-based compounds are denoted as -OC(O)OR12. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rd-based compounds are denoted as -OC(O)N(R12)(R12). In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rd series -SR 12. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rd series -S(O)R 12a. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rd series -S(O)(NH)R 12. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rd series -S(O) 2R 12a. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rd series -S(O) 2N(R 12)(R 12). In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more Rd series -N=S(R 12a)(R 12a)=O.

[0329] In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, one or more Rd systems are optionally substituted with one to three C1-6 alkyl groups independently selected from the following groups: -OH, halogen, -CN, and C1-3 alkoxy.

[0330] In some embodiments of the compounds of formula I or their pharmaceutically acceptable salts, each R11 is independently H, C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4 to 7 membered monocyclic heterocyclic group, 5 to 6 membered monocyclic heteroaryl, 8 to 10 membered fused bicyclic heterocyclic group, 6 to 10 membered bridged bicyclic heterocyclic group, 8 to 10 membered fused bicyclic heteroaryl, or 7 to 10 membered spirocyclic heterocyclic group, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 fused bicyclic cycloalkyl, C6-6 alkyl, C7-10 ... Each of the 5-10-membered bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, and 7-10-membered spirocyclic heterocyclic groups is optionally substituted by 1 to 3 Rc groups.

[0331] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, each R11 is independently H, C1-6 alkyl, C3-7 monocyclic cycloalkyl, or 4 to 7-membered monocyclic heterocyclic group. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, each R11 is independently H or C1-4 alkyl, wherein the C1-4 alkyl group is optionally substituted with a group selected from -OH and -NR12R12. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, each R11 is independently H or C1-4 alkyl. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, each R11 is independently H or C1-3 alkyl. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, each R11 is independently H or methyl.

[0332] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, each R11 is independently H or C1-6 alkyl. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, each R11 is independently H or C1-3 alkyl.

[0333] In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, each R11 of -NR 11R 11 and -C(O)NR 11R 11 is independently H or C 1-3 alkyl.

[0334] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R11-based C1-6 alkyl groups are present, wherein the C1-6 alkyl group is optionally substituted with 1 to 3 Rc groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R11-based C1-4 alkyl groups are present, wherein the C1-4 alkyl group is optionally substituted with 1 to 3 Rc groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R11-based methyl groups are present.

[0335] In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more R11-based H groups are present. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more R11-based C2-6 alkenyl groups are present, wherein the C2-6 alkenyl group is optionally substituted with 1 to 3 Rc groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more R11-based C2-6 alkynyl groups are present, wherein the C2-6 alkynyl group is optionally substituted with 1 to 3 Rc groups. In some embodiments of the compound of Formula I or a pharmaceutically acceptable salt thereof, one or more R11-based C3-7 monocyclic cycloalkyl groups are present, wherein the C3-7 monocyclic cycloalkyl group is optionally substituted with 1 to 3 Rc groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R11-based C7-10 fused bicyclic cycloalkyl groups, wherein the C7-10 fused bicyclic cycloalkyl group is optionally substituted with 1 to 3 Rc groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R11-based C5-10 bridged bicyclic cycloalkyl groups, wherein the C5-10 bridged bicyclic cycloalkyl group is optionally substituted with 1 to 3 Rc groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R11-based phenyl groups, wherein the phenyl group is optionally substituted with 1 to 3 Rc groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R11-based naphthyl groups, wherein the naphthyl group is optionally substituted with 1 to 3 Rc groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R11 groups are 4- to 7-membered monocyclic heterocyclic groups, wherein the 4- to 7-membered monocyclic heterocyclic groups are optionally substituted with 1 to 3 Rc groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R11 groups are 5- to 6-membered monocyclic heteroaryl groups, wherein the 5- to 6-membered monocyclic heteroaryl groups are optionally substituted with 1 to 3 Rc groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R11 groups are 8- to 10-membered fused bicyclic heterocyclic groups, wherein the 8- to 10-membered fused bicyclic heterocyclic groups are optionally substituted with 1 to 3 Rc groups. In some embodiments of compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R11 groups are 6- to 10-membered bridged bicyclic heterocyclic groups, wherein the 6- to 10-membered bridged bicyclic heterocyclic groups are optionally substituted with 1 to 3 Rc groups. In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, one or more R11 groups are 8 to 10-member fused bicyclic heteroaryl groups, wherein the 8 to 10-member fused bicyclic heteroaryl groups are optionally substituted with 1 to 3 Rc groups. In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, one or more R11 groups are 7 to 10-member spirocyclic heterocyclic groups, wherein the 7 to 10-member spirocyclic heterocyclic groups are optionally substituted with 1 to 3 Rc groups.

[0336] In some embodiments of the compounds of formula I or their pharmaceutically acceptable salts, each R 11a is independently a C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4 to 7 membered monocyclic heterocyclic group, 5 to 6 membered monocyclic heteroaryl, 8 to 10 membered fused bicyclic heterocyclic group, 6 to 10 membered bridged bicyclic heterocyclic group, 8 to 10 membered fused bicyclic heteroaryl, or 7 to 10 membered spirocyclic heterocyclic group, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 fused bicyclic cycloalkyl, C6-6 alkyl, C7-10 ... Each of the 5-10-membered bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, and 7-10-membered spirocyclic heterocyclic groups is optionally substituted by 1 to 3 Rc groups.

[0337] In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R11a are C1-6 alkyl groups, wherein the C1-6 alkyl group is optionally substituted with 1 to 3 Rc groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R11a are C2-6 alkenyl groups, wherein the C2-6 alkenyl group is optionally substituted with 1 to 3 Rc groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R11a are C2-6 ynyl groups, wherein the C2-6 ynyl group is optionally substituted with 1 to 3 Rc groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R11a are C3-7 monocyclic cycloalkyl groups, wherein the C3-7 monocyclic cycloalkyl group is optionally substituted with 1 to 3 Rc groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R11a are C7-10 fused bicyclic cycloalkyl groups, wherein the C7-10 fused bicyclic cycloalkyl group is optionally substituted with 1 to 3 Rc groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R11a are C5-10 bridged bicyclic cycloalkyl groups, wherein the C5-10 bridged bicyclic cycloalkyl group is optionally substituted with 1 to 3 Rc groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R11a are phenyl groups, wherein the phenyl group is optionally substituted with 1 to 3 Rc groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R11a are naphthyl groups, wherein the naphthyl group is optionally substituted with 1 to 3 Rc groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R 11a are 4- to 7-membered monocyclic heterocyclic groups, wherein the 4- to 7-membered monocyclic heterocyclic groups are optionally substituted with 1 to 3 R c groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R 11a are 5- to 6-membered monocyclic heteroaryl groups, wherein the 5- to 6-membered monocyclic heteroaryl groups are optionally substituted with 1 to 3 R c groups. In some embodiments of the compounds of Formula I or pharmaceutically acceptable salts thereof, one or more R 11a are 8- to 10-membered fused bicyclic heterocyclic groups, wherein the 8- to 10-membered fused bicyclic heterocyclic groups are optionally substituted with 1 to 3 R c groups. In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, one or more R11a groups are 6 to 10-membered bridged bicyclic heterocyclic groups, wherein the 6 to 10-membered bridged bicyclic heterocyclic groups are optionally substituted with 1 to 3 Rc groups. In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, one or more R11a groups are 8 to 10-membered fused bicyclic heteroaryl groups, wherein the 8 to 10-membered fused bicyclic heteroaryl groups are optionally substituted with 1 to 3 Rc groups.In some embodiments of the compounds of Formula I or their pharmaceutically acceptable salts, one or more R11a are 7 to 10-membered spirocyclic heterocyclic groups, wherein the 7 to 10-membered spirocyclic heterocyclic group is optionally substituted with 1 to 3 Rc groups.

[0338] In some embodiments of the compound of formula I or its pharmaceutically acceptable salt,...

Claims

1. A compound of formula I, or a pharmaceutically acceptable salt thereof, wherein R1 is an 8- to 15-member fused tricyclic heterocyclic group or an 8- to 15-member fused tricyclic heteroaryl group, wherein the 8- to 15-member fused tricyclic heterocyclic group and the 8- to 15-member fused tricyclic heteroaryl group are each optionally substituted by 1 to 4 Ra groups; R2 is a C1-6 alkyl group, wherein the C1-6 alkyl group is optionally substituted by 1 to 4 groups independently selected from halogens and C1-6 alkoxy groups, wherein the C1-6 alkoxy group is optionally substituted by 1 to 3 halogen groups; R3 is a H, halogen, -CN, C1-6 alkyl group, and C3-7 monocyclic cycloalkyl group, wherein the C1-6 alkyl group and the C3-7 monocyclic cycloalkyl group are each optionally substituted by 1 to 3 groups independently selected from the following groups: -OH, halogen, -CN, and C1-4 alkoxy group. The C1-4 alkoxy group may optionally be substituted with 1 to 3 halogen groups; Z-series C1-6 alkyl, -C(O)R13-C(O)NR6R7, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, 4 to 7-membered monocyclic heterocyclic, phenyl, 5 to 6-membered monocyclic heteroaryl, 8 to 10-membered fused bicyclic heterocyclic, 6 to 10-membered bridged bicyclic heterocyclic, 8 to 10-membered fused bicyclic heteroaryl, or 7 to 10-membered spirocyclic heterocyclic, wherein the C1-6 alkyl group may optionally be substituted with 1 to 4 Rb groups; wherein the C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C The 5-10-membered bridged bicyclic cycloalkyl, 4-7-membered monocyclic heterocyclic, phenyl, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, and 7-10-membered spirocyclic heterocyclic are each optionally substituted with 1-2 R8 groups and each optionally substituted with 1-3 Ra groups; the R6 group consists of C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, 4-7-membered monocyclic heterocyclic, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, or 7-10-membered spirocyclic heterocyclic, wherein the C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5 ... The 5-10-membered bridged bicyclic cycloalkyl, 4-7-membered monocyclic heterocyclic, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, and 7-10-membered spirocyclic heterocyclic groups are each optionally substituted with 1 to 4 Ra groups; the R13 group consists of 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, or 7-10-membered spirocyclic heterocyclic groups.The 4- to 7-membered monocyclic heterocyclic group, the 5- to 6-membered monocyclic heteroaryl group, the 8- to 10-membered fused bicyclic heterocyclic group, the 6- to 10-membered bridged bicyclic heterocyclic group, the 8- to 10-membered fused bicyclic heteroaryl group, and the 7- to 10-membered spirocyclic heterocyclic group are each optionally substituted with 1 to 4 Ra groups; R7 is H, C1-6 alkyl, C3-7 monocyclic cycloalkyl, or 4- to 6-membered monocyclic heterocyclic group, wherein the C1-6 alkyl, C3-7 monocyclic cycloalkyl, and the 4- to 6-membered monocyclic heterocyclic group are each optionally substituted with 1 to 4 groups independently selected from -OH, halogen, -CN, and C1-6 alkoxy; each R8 is independently halogen, -C(O)R9, -NR10R10, C1-6 alkyl, C3-7 monocyclic cycloalkyl, C 7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, 4-7 member monocyclic heterocyclic, phenyl, 5-6 member monocyclic heteroaryl, 8-10 member fused bicyclic heterocyclic, 6-10 member bridged bicyclic heterocyclic, 8-10 member fused bicyclic heteroaryl, 7-10 member spirocyclic heterocyclic, -OR 5, -C(O)N(R 5)(R 5), -N(R 5) 2(R 5) +, -N(R 5)C(O)R 5, -N(R 5)C(O)OR 5, -N(R 5)C(O)N(R 5)(R 5), -N(R 5)S(O) 2(R 5a), -NR 5S(O) 2N(R 5)(R 5), -NR 5S(O) 2O(R 5a), -OC(O)N(R5)(R5), -S(O)R5a, -S(O)(NH)R5, -S(O)2R5a, -S(O)2N(R5)(R5), or -N=S(R5a)(R5a)=O, wherein the C1-6 alkyl group is optionally substituted with 1 to 4 Rb groups, wherein the C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, 4 to 7-membered monocyclic heterocyclic group, phenyl, 5 to 6-membered monocyclic heteroaryl, 8 to 10-membered fused bicyclic heterocyclic group, 6 to 10-membered bridged bicyclic heterocyclic group, 8 to 10-membered fused bicyclic heteroaryl, and 7 to 10-membered spirocyclic heterocyclic group are each independently optionally substituted with 1 to 4 Ra groups; each R9 is independently C 3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7 member monocyclic heterocyclic group, 5-6 member monocyclic heteroaryl, 8-10 member fused bicyclic heterocyclic group, 6-10 member bridged bicyclic heterocyclic group, 8-10 member fused bicyclic heteroaryl, or 7-10 member spirocyclic heterocyclic group, wherein the C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7 member monocyclic heterocyclic group, 5-6 member monocyclic heteroaryl group, C5-10 member spirocyclic heterocyclic group, C5-10 member monocyclic cycloalkyl, C5-10 bridged bi ...The 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, and 7-10-membered spirocyclic heterocyclic groups are each optionally substituted with 1 to 4 Ra groups; each R5 and R10 is independently H, C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, or 7-10-membered spirocyclic heterocyclic, wherein the C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl groups are each optionally substituted by 1 to 4 Rb groups, wherein the C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C The 5-10 bridging bicyclic cycloalkyl, phenyl, naphthyl, 4-7 member monocyclic heterocyclic, 5-6 member monocyclic heteroaryl, 8-10 member fused bicyclic heterocyclic, 6-10 member bridging bicyclic heterocyclic, 8-10 member fused bicyclic heteroaryl, and 7-10 member spirocyclic heterocyclic groups are each optionally substituted with 1 to 4 Ra groups; each R 5a is independently a C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 monocyclic cycloalkyl, C 7-10 fused bicyclic cycloalkyl, C 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, or 7-10-membered spirocyclic heterocyclic, wherein the C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl groups are each optionally substituted by 1 to 4 Rb groups, wherein the C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C The 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, and 7-10-membered spirocyclic heterocyclic groups are each optionally substituted with 1 to 4 Ra groups; each Ra is independently substituted with a side oxygen, imino, halogen, -NO2, -N3, -CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, 7-10-membered spirocyclic heterocyclic, -OR 11, -C(O)R 11, -C(O)OR11. -C(O)N(R 11)(R 11), -NR 11R 11. -N(R 11) 2(R 11) +, -N(R 11)C(O)R 11. -N(R 11)C(O)OR 11. -N(R 11)C(O)N(R 11)(R 11), -N(R 11)S(O) 2(R 11a), -NR 11S(O) 2N(R 11)(R 11), -NR 11S(O) 2O(R 11a), -OC(O)R 11, -OC(O)OR 11, -OC(O)N(R 11)(R 11), -SR 11, -S(O)R 11a, -S(O)(NH)R 11, -S(O) 2R 11a, -S(O)2N(R11)(R11), or -N=S(R11a)(R11a)=O, wherein the C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl groups are each independently and optionally substituted with 1 to 3 Rc groups, wherein the C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4 to 7-membered monocyclic heterocyclic, 5 to 6-membered monocyclic heteroaryl, 8 to 10-membered fused bicyclic heterocyclic, 6 to 10-membered bridged bicyclic heterocyclic, 8 to 10-membered fused bicyclic heteroaryl, and 7 to 10-membered spirocyclic heterocyclic groups are each independently and optionally substituted with 1 to 3 Rd groups, and each Rb is independently a side oxygen group, imine group, halogen, -NO2, -N 3, -CN, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4 to 7 member monocyclic heterocyclic, 5 to 6 member monocyclic heteroaryl, 8 to 10 member fused bicyclic heterocyclic, 8 to 10 member bridged bicyclic heterocyclic, 6 to 10 member bridged bicyclic heterocyclic, 8 to 10 member fused bicyclic heteroaryl, 7 to 10 member spirocyclic heterocyclic, -OR 11, -C(O)R 11, -C(O)OR 11, -C(O)N(R 11)(R 11), -NR 11R 11, -N(R 11) 2(R 11) +, -N(R 11)C(O)R 11, -N(R 11)C(O)OR 11, -N(R 11)C(O)N(R 11)(R 11), -N(R 11)S(O) 2(R 11a), -NR 11S(O) 2N(R 11)(R 11), -NR 11S(O) 2O(R 11a), -OC(O)R 11, -OC(O)OR 11, -OC(O)N(R 11)(R 11), -SR 11, -S(O)R 11a, -S(O)(NH)R 11, -S(O) 2R 11a, -S(O) 2N(R 11)(R 11), or -N=S(R 11a)(R11a)=O, wherein the C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4 to 7-membered monocyclic heterocyclic group, 5 to 6-membered monocyclic heteroaryl, 8 to 10-membered fused bicyclic heterocyclic group, 6 to 10-membered bridged bicyclic heterocyclic group, 8 to 10-membered fused bicyclic heteroaryl, and 7 to 10-membered spirocyclic heterocyclic group are each optionally substituted by 1 to 3 Rd groups; each Rc is independently halogenated, -CN, C7-10 fused bicyclic cycloalkyl, C 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, 7-10-membered spirocyclic heterocyclic, -OR 12, -C(O)R 12, -C(O)OR 12, -C(O)N(R 12)(R 12), -NR 12R 12, -N(R 12) 2(R 12) +, -N(R 12)C(O)R 12, -N(R 12)C(O)OR 12, -N(R 12)C(O)N(R 12)(R 12), -N(R 12)S(O) 2(R 12a), -NR 12S(O) 2N(R 12)(R 12), -NR 12S(O) 2O(R 12a), -OC(O)R 12, -OC(O)OR 12, -OC(O)N(R 12)(R 12), -SR 12, -S(O)R 12a, -S(O)(NH)R 12, -S(O) 2R 12a, -S(O) 2N(R 12)(R 12), or -N=S(R 12a)(R 12a)=O; Each R d is independently associated with a side oxygen group, halogen, -CN, C 1-6 alkyl, C 7-10 fused bicyclic cycloalkyl, C 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, 7-10-membered spirocyclic heterocyclic, -OR 12, -C(O)R 12, -C(O)OR 12, -C(O)N(R 12)(R 12), -NR 12R 12, -N(R 12) 2(R 12) +, -N(R 12)C(O)R 12, -N(R 12)C(O)OR 12, -N(R 12)C(O)N(R 12)(R 12), -N(R 12)S(O) 2(R 12a), -NR 12S(O) 2N(R 12)(R 12), -NR 12S(O) 2O(R 12a), -OC(O)R 12, -OC(O)OR 12, -OC(O)N(R 12)(R 12), -SR12, -S(O)R12a, -S(O)(NH)R12, -S(O)2R12a, -S(O)2N(R12)(R12), or -N=S(R12a)(R12a)=O, wherein the C1-6 alkyl group is optionally substituted by 1 to 3 groups independently selected from the following: -OH, halogen, -CN, and C1-3 alkoxy; each R11 is independently H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C The group comprises 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, or 7-10-membered spirocyclic heterocyclic, wherein each of the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, and 7-10-membered spirocyclic heterocyclic groups is optionally substituted with 1 to 3 Rc groups; each Rc group is substituted with one or more Rc groups. 11a Independently comprises C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4 to 7-membered monocyclic heterocyclic group, 5 to 6-membered monocyclic heteroaryl, 8 to 10-membered fused bicyclic heterocyclic group, 6 to 10-membered bridged bicyclic heterocyclic group, 8 to 10-membered fused bicyclic heteroaryl, or 7 to 10-membered spirocyclic heterocyclic group, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 condensed bicyclic cycloalkyl, C6-6 alkyl, C7-10 condensed bicyclic cyclo ... The 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, and 7-10-membered spirocyclic heterocyclic groups are each optionally substituted with 1 to 3 Rc groups; each R12 is independently H, C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C12 alkyl, C2-6 alkyne, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C12 alkyl, C3-7 cycloalkyl, C7-10 fused bicyclic cycloalkyl, C7 cycloalkyl, C7 cycloalkyl, C8 cycloalkyl, C9 cycloalkyl, C10 cycloalkyl, C9 cycloalkyl, C12 ... 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, or 7-10-membered spirocyclic heterocyclic; each R 12a is independently C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic group, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic group, 6-10-membered bridged bicyclic heterocyclic group, 8-10-membered fused bicyclic heteroaryl, or 7-10-membered spirocyclic heterocyclic group, wherein each 4-membered monocyclic heterocyclic group independently has one cyclic heteroatom selected from N, O, and S; each 5-7-membered monocyclic heterocyclic group independently has one to two cyclic heteroatoms independently selected from N, O, and S; each 6-membered bridged bicyclic heterocyclic group independently has one cyclic heteroatom selected from N, O, and S; and each 7-membered bridged bicyclic heterocyclic group independently has one to two cyclic heteroatoms independently selected from N, O, and S. Each of the 5 to 6 monocyclic heteroaryl groups, 8 to 10 fused bicyclic heteroaryl groups, 8 to 10 bridged bicyclic heteroaryl groups, 8 to 10 fused bicyclic heteroaryl groups, and 7 to 10 spirocyclic heteroaryl groups independently has 1 to 4 cyclic heteroatoms independently selected from N, O, and S; and each of the 8 to 15 fused tricyclic heteroaryl groups and 8 to 15 fused tricyclic heteroaryl groups independently has 1 to 7 cyclic heteroatoms independently selected from N, O, and S.

2. A compound of any one of claims 1, or a pharmaceutically acceptable salt thereof, wherein the Z-membered C7-10 fused bicyclic cycloalkyl, 8-10 fused bicyclic heterocyclic, 6-10 bridging bicyclic heterocyclic, or 8-10 fused bicyclic heteroaryl, wherein the C7-10 fused bicyclic cycloalkyl, 8-10 fused bicyclic heterocyclic, 6-10 bridging bicyclic heterocyclic, and 8-10 fused bicyclic heteroaryl are each optionally substituted with 1-2 R8 groups and each optionally substituted with 1-3 Ra groups.

3. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is an 8- to 15-member fused tricyclic heterocyclic group, optionally substituted with 1 to 4 Ra groups; R2 is a C1-6 alkyl group, wherein the C1-6 alkyl group is optionally substituted with 1 to 4 groups independently selected from halogens and C1-6 alkoxy groups, wherein the C1-6 alkoxy group is optionally substituted with 1 to 3 halogen groups; R3 is an H or C1-6 alkyl group, wherein the C1-6 alkyl group is optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, and C1-4 alkoxy groups, wherein the C1-4 alkoxy group is optionally substituted with 1 to 3 halogen groups; Z-series 4- to 7-membered monocyclic heterocyclic groups, phenyl groups, 5- to 6-membered monocyclic heteroaryl groups, 8- to 10-membered fused bicyclic heterocyclic groups, 6- to 10-membered bridged bicyclic heterocyclic groups, or 7- to 10-membered spirocyclic heterocyclic groups, wherein each of the 4- to 7-membered monocyclic heterocyclic groups, phenyl groups, 5- to 6-membered monocyclic heteroaryl groups, 8- to 10-membered fused bicyclic heterocyclic groups, 6- to 10-membered bridged bicyclic heterocyclic groups, and 7- to 10-membered spirocyclic heterocyclic groups is independently and optionally substituted with 1 to 2 R8 groups and is independently and optionally substituted with 1 to 3 Ra groups; each R8 is independently -C(O)R9, C1-6 alkyl, 4- to 7-membered monocyclic heterocyclic group, or -S(O)2R5a, wherein the C1-6 alkyl group is optionally substituted with 1 to 4 Rb groups, and wherein the 4- to 7-membered monocyclic heterocyclic group is optionally substituted with 1 to 4 Rb groups. The α group is substituted; each R9 is independently a C3-7 monocyclic cycloalkyl or a 4- to 7-membered monocyclic heterocyclic group, wherein the C3-7 monocyclic cycloalkyl and the 4- to 7-membered monocyclic heterocyclic group are each independently optionally substituted with 1 to 4 Ra groups; R5a is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is optionally substituted with 1 to 4 Ra groups; each Ra is independently a side oxygen group, imino group, halogen, -NO2, -N3, -CN, C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, 7-10-membered spirocyclic heterocyclic, -OR 11, -C(O)R 11, -C(O)OR 11, -C(O)N(R 11)(R 11), -NR 11R 11, -N(R 11) 2(R 11) +, -N(R 11)C(O)R 11, -N(R 11)C(O)OR 11, -N(R 11)C(O)N(R 11)(R 11), -N(R 11)S(O) 2(R 11a), -NR 11S(O) 2N(R 11)(R11) -NR 11S(O) 2O(R 11a), -OC(O)R 11, -OC(O)OR 11, -OC(O)N(R 11)(R 11), -SR 11, -S(O)R 11a, -S(O)(NH)R 11, -S(O) 2R 11a, -S(O) 2N(R 11)(R 11), or -N=S(R 11a)(R 11a)=O, wherein the C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl groups are each optionally substituted by 1 to 3 Rc groups, wherein the C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, and C The 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, and 7-10-membered spirocyclic heterocyclic groups are each optionally substituted by 1 to 3 Rd groups, and each Rb is independently a side oxygen, imino, halogen, -NO2, -N3, -CN, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 8-10-membered bridged bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, 7-10-membered spirocyclic heterocyclic, -OR 11, -C(O)R 11, -C(O)OR 11, -C(O)N(R 11)(R 11), -NR 11R 11, -N(R 11) 2(R 11) +, -N(R 11)C(O)R 11, -N(R 11)C(O)OR 11, -N(R 11)C(O)N(R 11)(R 11), -N(R 11)S(O) 2(R 11a), -NR 11S(O) 2N(R 11)(R 11), -NR 11S(O) 2O(R 11a), -OC(O)R 11, -OC(O)OR 11, -OC(O)N(R 11)(R 11), -SR 11, -S(O)R 11a, -S(O)(NH)R 11, -S(O) 2R 11a, -S(O) 2N(R 11)(R 11), or -N=S(R 11a)(R 11a)=O, wherein the C 3-7 monocyclic cycloalkyl, C 7-10 fused bicyclic cycloalkyl, C The 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, and 7-10-membered spirocyclic heterocyclic groups are each optionally substituted by 1 to 3 Rd groups; each Rc-Independent halogens, -CN, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7 member monocyclic heterocyclic, 5-6 member monocyclic heteroaryl, 8-10 member fused bicyclic heterocyclic, 6-10 member bridged bicyclic heterocyclic, 8-10 member fused bicyclic heteroaryl, 7-10 member spirocyclic heterocyclic, -OR 12, -C(O)R 12, -C(O)OR 12, -C(O)N(R 12)(R 12), -NR 12R 12, -N(R 12) 2(R 12) +, -N(R 12)C(O)R 12, -N(R 12)C(O)OR 12, -N(R 12)C(O)N(R 12)(R 12), -N(R 12) S(O) 2(R 12a), -NR 12S(O) 2N(R 12)(R 12), -NR 12S(O) 2O(R 12a), -OC(O)R 12, -OC(O)OR 12, -OC(O)N(R 12)(R 12), -SR 12, -S(O)R 12a, -S(O)(NH)R 12, -S(O) 2R 12a, -S(O) 2N(R 12)(R 12), or -N=S(R 12a)(R 12a)=O; Each R d is independently associated with a side oxygen group, halogen, -CN, C1-6 alkyl, C7-10 fused bicyclic cycloalkyl, C 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, 7-10-membered spirocyclic heterocyclic, -OR 12, -C(O)R 12, -C(O)OR 12, -C(O)N(R 12)(R 12), -NR 12R 12, -N(R 12) 2(R 12) +, -N(R 12)C(O)R 12, -N(R 12)C(O)OR 12, -N(R 12)C(O)N(R 12)(R 12), -N(R 12)S(O) 2(R 12a), -NR 12S(O) 2N(R 12)(R 12), -NR 12S(O) 2O(R 12a), -OC(O)R 12, -OC(O)OR 12, -OC(O)N(R 12)(R 12), -SR 12, -S(O)R 12a, -S(O)(NH)R 12, -S(O) 2R 12a, -S(O) 2N(R 12)(R 12), or -N=S(R 12a)(R 12a)=O; Each R 11 is independently H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 monocyclic cycloalkyl, C 7-10 fused bicyclic cycloalkyl, CThe group comprises 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, or 7-10-membered spirocyclic heterocyclic, wherein each of the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, and 7-10-membered spirocyclic heterocyclic groups is optionally substituted with 1 to 3 Rc groups; each Rc group is substituted with one or more Rc groups. 11a Independently comprises C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 bridged bicyclic cycloalkyl, phenyl, naphthyl, 4 to 7-membered monocyclic heterocyclic group, 5 to 6-membered monocyclic heteroaryl, 8 to 10-membered fused bicyclic heterocyclic group, 6 to 10-membered bridged bicyclic heterocyclic group, 8 to 10-membered fused bicyclic heteroaryl, or 7 to 10-membered spirocyclic heterocyclic group, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C5-10 condensed bicyclic cycloalkyl, C6-6 alkyl, C7-10 condensed bicyclic cyclo ... The 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, and 7-10-membered spirocyclic heterocyclic groups are each optionally substituted with 1 to 3 Rc groups; each R12 is independently H, C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C12 alkyl, C2-6 alkyne, C3-7 monocyclic cycloalkyl, C7-10 fused bicyclic cycloalkyl, C12 alkyl, C3-7 cycloalkyl, C7-10 fused bicyclic cycloalkyl, C7 cycloalkyl, C7 cycloalkyl, C8 cycloalkyl, C9 cycloalkyl, C10 cycloalkyl, C9 cycloalkyl, C12 ... 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, or 7-10-membered spirocyclic heterocyclic; each R 12a is independently a C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 monocyclic cycloalkyl, C 7-10-membered fused bicyclic cycloalkyl, C 5-10-membered bridged bicyclic cycloalkyl, phenyl, naphthyl, 4-7-membered monocyclic heterocyclic, 5-6-membered monocyclic heteroaryl, 8-10-membered fused bicyclic heterocyclic, 6-10-membered bridged bicyclic heterocyclic, 8-10-membered fused bicyclic heteroaryl, or 7-10-membered spirocyclic heterocyclic. Each of the four-membered monocyclic heterocyclic groups independently has one cyclic heteroatom selected from N, O, and S; each of the five to seven-membered monocyclic heterocyclic groups independently has one to two cyclic heteroatoms independently selected from N, O, and S; each of the six-membered bridged bicyclic heterocyclic groups independently has one cyclic heteroatom selected from N, O, and S.Each of the 7-membered bridged bicyclic heterocyclic groups independently has 1 to 2 cyclic heteroatoms independently selected from N, O, and S; each of the 5 to 6-membered monocyclic heteroaryl, 8 to 10-membered fused bicyclic heterocyclic groups, 8 to 10-membered bridged bicyclic heterocyclic groups, 8 to 10-membered fused bicyclic heteroaryl, and 7 to 10-membered spirocyclic heterocyclic groups independently has 1 to 4 cyclic heteroatoms independently selected from N, O, and S; and each of the 8 to 15-membered fused tricyclic heterocyclic groups and the 8 to 15-membered fused tricyclic heteroaryl groups independently has 1 to 7 cyclic heteroatoms independently selected from N, O, and S.

4. The compound of claim 1 or 3, or a pharmaceutically acceptable salt thereof, wherein R1 is an 8- to 15-member fused tricyclic heterocyclic group, optionally substituted by 1 to 3 independently selected groups from: -OH, halogen, -CN, syloxy, -NR11R11, C1-4 alkoxy, C1-6 alkyl, and C3-7 monocyclic cycloalkyl; R2 is a C1-6 alkyl group, wherein the C1-6 alkyl group is optionally substituted by 1 to 4 independently selected groups from halogen and C1-6 alkoxy; R3 is a C1-6 alkyl group, wherein the C1-6 alkyl group is optionally substituted by 1 to 3 independently selected groups from -OH, halogen, -CN, and C1-4 alkoxy; Z-groups consisting of 4 to 7-membered monocyclic heterocyclic groups, phenyl groups, 5 to 6-membered monocyclic heteroaryl groups, 8 to 10-membered fused bicyclic heterocyclic groups, 6 to 10-membered bridged bicyclic heterocyclic groups, or 7 to 10-membered spirocyclic heterocyclic groups, wherein each of the 4 to 7-membered monocyclic heterocyclic groups, phenyl groups, 5 to 6-membered monocyclic heteroaryl groups, 8 to 10-membered fused bicyclic heterocyclic groups, 6 to 10-membered bridged bicyclic heterocyclic groups, and 7 to 10-membered spirocyclic heterocyclic groups is optionally substituted with 1 to 2 R8 groups and is optionally substituted with 1 to 3 groups independently selected from the following groups: -OH, halogen, -CN, sideoxy group, -NR 11R 11, C 1-4 alkoxy group, and C 1-5 alkyl group; each R8 group is independently -C(O)R 9, C 1-6 alkyl group, 4 to 7-membered monocyclic heterocyclic group, or -S(O) 2R 5a. The C1-6 alkyl group is optionally substituted with 1 to 3 independently selected groups from the following: -OH, halogen, -CN, oxy group, -NR 11R 11, -C(O)NR 11R 11, C1-4 alkoxy group, and R 8a; the 4 to 7 membered monocyclic heterocyclic group is optionally substituted with 1 to 3 independently selected groups from the following: -OH, halogen, -CN, oxy group, -NR 11R 11, C1-4 alkoxy group, and C1-5 alkyl group; each R 8a is independently a 4 to 7 membered monocyclic heterocyclic group or a 5 to 6 membered monocyclic heteroaryl group, wherein the 4 to 7 membered monocyclic heterocyclic group and the 5 to 6 membered monocyclic heteroaryl group are each independently optionally substituted with 1 to 3 independently selected groups from the following: -OH, halogen, C1-4 alkoxy group, and C1-5 alkyl group; each R 9 is independently a C 3-7 monocyclic cycloalkyl or 4-7 member monocyclic heterocyclic group, wherein the C3-7 monocyclic cycloalkyl and the 4-7 member monocyclic heterocyclic group are each optionally substituted by 1 to 3 groups independently selected from the following groups: -OH, halogen, -CN, sideoxy, -NR11R11, C1-4 alkoxy, C1-5 alkyl, and 4-7 member monocyclic heterocyclic group;R5a is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is optionally substituted by 1 to 3 groups independently selected from the following: -OH, halogen, -CN, side oxygen, -NR11R11, C1-4 alkoxy, and C1-5 alkyl; each R11 is independently H or C1-6 alkyl; each R12 is independently H or C1-4 alkyl; each 4-membered monocyclic heterocyclic group independently has 1 cyclic heteroatom selected from N, O, and S; each 5- to 7-membered monocyclic heterocyclic group independently has 1 to 2 cyclic heteroatoms independently selected from N, O, and S; each 6-membered bridged bicyclic heterocyclic group independently has 1 cyclic heteroatom selected from N, O, and S; each 7-membered bridged bicyclic heterocyclic group independently has 1 to 2 cyclic heteroatoms independently selected from N, O, and S. Each of the 5-6 member monocyclic heteroaryl group, 8-10 member fused bicyclic heterocyclic group, 8-10 member bridged bicyclic heterocyclic group, 8-10 member fused bicyclic heteroaryl group, and 7-10 member spirocyclic heterocyclic group independently has 1 to 4 cyclic heteroatoms independently selected from N, O, and S; and each of the 8-15 member fused tricyclic heterocyclic group and the 8-15 member fused tricyclic heteroaryl group independently has 1 to 7 cyclic heteroatoms independently selected from N, O, and S.

5. A compound of any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof, wherein R1 is optionally substituted with one to three groups independently selected from halogen, C1-3 alkyl, and C1-3 alkoxy groups, wherein the C1-3 alkyl group is optionally substituted with one to three halogen groups.

6. The compound of any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, wherein R 1 is:

7. The compound of any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof, wherein R 1 is: or.

8. A compound of any one of claims 1 to 7, or a pharmaceutically acceptable salt thereof, wherein R2 is a C1-6 alkyl group.

9. A compound of any one of claims 1 to 8, or a pharmaceutically acceptable salt thereof, wherein R2 is a C1-3 alkyl group.

10. The compound of any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof, wherein R2 is isopropyl.

11. A compound of any one of claims 1 to 10, or a pharmaceutically acceptable salt thereof, wherein R3 is a C1-6 alkyl group.

12. The compound of any one of claims 1 to 10, or a pharmaceutically acceptable salt thereof, wherein R3 is optionally substituted with one to three C1-4 alkyl groups independently selected from -OH, halogen, -CN, and C1-3 alkoxy groups.

13. The compound of any one of claims 1 to 12, or a pharmaceutically acceptable salt thereof, wherein R3 is a methyl group.

14. A compound of any one of claims 1 and 3 to 13, or a pharmaceutically acceptable salt thereof, wherein Z is a 4 to 7-membered monocyclic heterocyclic group, wherein the 4 to 7-membered monocyclic heterocyclic group is optionally substituted with an R 8 group and is optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR 11R 11, C 1-4 alkoxy group, and C 1-5 alkyl group.

15. A compound of any one of claims 1 and 3 to 14, or a pharmaceutically acceptable salt thereof, wherein Z is a 4 to 7-membered monocyclic heterocyclic group, wherein the 4 to 7-membered monocyclic heterocyclic group is optionally substituted with an R 8 group and is optionally substituted with 1 to 3 groups independently selected from: -OH, halogen, -CN, side oxygen, -NR 11R 11, C 1-4 alkoxy, and C 1-5 alkyl, and wherein the 4 to 7-membered monocyclic heterocyclic group has one or two N-type cyclic heteroatoms.

16. A compound of any one of claims 1 and 3 to 15, or a pharmaceutically acceptable salt thereof, wherein Z is a 5- or 6-membered monocyclic heterocyclic group, wherein the 5- or 6-membered monocyclic heterocyclic group is optionally substituted with an R 8 group and is optionally substituted with one or two groups independently selected from: -OH, halogen, -CN, side oxygen, -NR 11R 11, C 1-4 alkoxy, and C 1-5 alkyl, and wherein the 5- or 6-membered monocyclic heterocyclic group has one or two N-type cyclic heteroatoms.

17. A compound of any one of claims 1 and 3 to 16, or a pharmaceutically acceptable salt thereof, wherein Z is a piperidinyl group, wherein the piperidinyl group is optionally substituted with an R 8 group.

18. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 and 3 to 13, wherein the Z-series phenyl or 5 to 6-membered monocyclic heteroaryl group is optionally substituted with an R 8 group and optionally substituted with one or two groups independently selected from the following: -OH, halogen, -CN, syloxy, -NR 11R 11, C 1-4 alkoxy, and C 1-5 alkyl.

19. A compound of any one of claims 1, 3 to 13 and 18, or a pharmaceutically acceptable salt thereof, wherein Z is a phenyl group optionally substituted with an R 8 group.

20. A compound or a pharmaceutically acceptable salt thereof, as claimed in any one of claims 1, 3 to 13 and 18, wherein the Z-membered 5- to 6-membered monocyclic heteroaryl group is optionally substituted with an R 8 group and has one, two or three N-membered cyclic heteroatoms.

21. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1, 3 to 13, 18 and 20, wherein Z is a pyridyl group or, optionally, is substituted with an R8 group.

22. A compound of any one of claims 1 to 13, or a pharmaceutically acceptable salt thereof, wherein Z is an 8 to 10-member fused bicyclic heterocyclic group, optionally substituted with an R 8 group and optionally substituted with one or two groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR 11R 11, C 1-4 alkoxy group, and C 1-5 alkyl group.

23. A compound of any one of claims 1 to 13, or a pharmaceutically acceptable salt thereof, wherein the Z-group is an 8 to 10-membered fused bicyclic heterocyclic group, wherein the 8 to 10-membered fused bicyclic heterocyclic group is optionally substituted with an R 8 group and is optionally substituted with one or two groups independently selected from: -OH, halogen, -CN, side oxygen, -NR 11R 11, C 1-4 alkoxy, and C 1-5 alkyl; and wherein the 8 to 10-membered fused bicyclic heterocyclic group has one or two N-type cyclic heteroatoms.

24. The compound of any one of claims 1 to 13 and 22 to 23, or a pharmaceutically acceptable salt thereof, wherein the Z-series or, each of which is optionally substituted with an R 8 group.

25. A compound of any one of claims 1 to 13, or a pharmaceutically acceptable salt thereof, wherein Z is a 6 to 10-membered bridged bicyclic heterocyclic group, which is optionally substituted with an R 8 group and optionally substituted with one or two groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR 11R 11, C 1-4 alkoxy group, and C 1-5 alkyl group.

26. A compound of any one of claims 1 to 13 and 25, or a pharmaceutically acceptable salt thereof, wherein the Z group is a 6 to 10-membered bridged bicyclic heterocyclic group, wherein the 6 to 10-membered bridged bicyclic heterocyclic group is optionally substituted with an R 8 group and is optionally substituted with one or two groups independently selected from: -OH, halogen, -CN, side oxygen, -NR 11R 11, C 1-4 alkoxy, and C 1-5 alkyl, and wherein the 6 to 10-membered bridged bicyclic heterocyclic group has one or two N-type cyclic heteroatoms.

27. The compound of any one of claims 1 to 13 and 25 to 26, or a pharmaceutically acceptable salt thereof, wherein the Z-series or, each of which is optionally substituted with an R 8 group.

28. A compound of any one of claims 1 to 13, or a pharmaceutically acceptable salt thereof, wherein the Z group is a 7 to 10-membered spirocyclic heterocyclic group, optionally substituted with an R 8 group and optionally substituted with one or two groups independently selected from: -OH, halogen, -CN, sideoxy group, -NR 11R 11, C 1-4 alkoxy group, and C 1-5 alkyl group.

29. A compound or a pharmaceutically acceptable salt thereof, as claimed in any one of claims 1 to 13 and 28, wherein Z is a 7 to 10-membered spirocyclic heterocyclic group, wherein the 7 to 10-membered spirocyclic heterocyclic group is optionally substituted with an R 8 group and is optionally substituted with one or two groups independently selected from: -OH, halogen, -CN, side oxygen, -NR 11R 11, C 1-4 alkoxy, and C 1-5 alkyl, and wherein the 7 to 10-membered spirocyclic heterocyclic group has one or two N-type cyclic heteroatoms.

30. A compound of any one of claims 1 to 13 and 28 to 29, or a pharmaceutically acceptable salt thereof, wherein the Z series is optionally substituted with an R 8 group.

31. The compound of any one of claims 1 to 13 and 28 to 29, or a pharmaceutically acceptable salt thereof, wherein the Z series is optionally substituted with an R 8 group.

32. A compound of any one of claims 1 to 13, or a pharmaceutically acceptable salt thereof, wherein a Z-series compound, ... ...

33. A compound of any one of claims 1 to 32, or a pharmaceutically acceptable salt thereof, wherein R8 is a 4 to 7-membered monocyclic heterocyclic group, wherein the 4 to 7-membered monocyclic heterocyclic group is optionally substituted by 1 to 3 independently selected from the following groups: -OH, halogen, -CN, sideoxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group.

34. A compound of any one of claims 1 to 33, or a pharmaceutically acceptable salt thereof, wherein R8 is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is optionally substituted by 1 to 3 independently selected groups selected from: -OH, halogen, -CN, sideoxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group; and wherein the 4- to 7-membered monocyclic heterocyclic group has one or two independently selected ring heteroatoms selected from N and S.

35. A compound of any one of claims 1 to 34, or a pharmaceutically acceptable salt thereof, wherein R8 is a 5- or 6-membered monocyclic heterocyclic group, wherein the 5- or 6-membered monocyclic heterocyclic group is optionally substituted by one or two independently selected groups from the following: -OH, halogen, -CN, sideoxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group.

36. A compound of any one of claims 1 to 35, or a pharmaceutically acceptable salt thereof, wherein R8 is piperidinyl or piperyl, each of which is optionally substituted by one or two independently selected groups from: -OH, halogen, -CN, syloxy, -NR11R11, C1-4 alkoxy, and C1-5 alkyl.

37. A compound of any one of claims 1 to 36, or a pharmaceutically acceptable salt thereof, wherein R 8 is piperidinyl or piperyl.

38. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 2 and 5 to 32, wherein each R 8 is independently a 7 to 10-membered spirocyclic heterocyclic group, wherein the 7 to 10-membered spirocyclic heterocyclic group is optionally substituted by 1 to 3 independently selected from the following groups: -OH, halogen, -CN, sideoxy group, -NR 11R 11, C 1-4 alkoxy group, and C 1-5 alkyl group.

39. A compound or a pharmaceutically acceptable salt thereof, as claimed in any one of claims 1 to 2, 5 to 32 and 38, wherein each R 8 is independently a 7 to 10-membered spirocyclic heterocyclic group, wherein the 7 to 10-membered spirocyclic heterocyclic group is optionally substituted by 1 to 3 groups independently selected from the side oxygen and methyl groups.

40. The compound of any one of claims 1 to 2, 5 to 32, and 38 to 39, or a pharmaceutically acceptable salt thereof, wherein each R8 is independently or, optionally, substituted with a methyl group.

41. A compound of any one of claims 1 to 32, or a pharmaceutically acceptable salt thereof, wherein R8 is a C1-6 alkyl group, wherein the C1-6 alkyl group is optionally substituted by one to three independently selected groups from the following: -OH, halogen, -CN, syloxy group, -NR11R11, -C(O)NR11R11, C1-4 alkoxy group, and R8a.

42. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 32 and 41, wherein R8 is a C1-6 alkyl group, wherein the C1-6 alkyl group is substituted by one or two groups independently selected from -C(O)NR11R11 and R8a.

43. A compound or a pharmaceutically acceptable salt thereof, as claimed in any one of claims 1 to 32 and 41 to 42, wherein R8 is a C1-4 alkyl group, wherein the C1-4 alkyl group is substituted by one or two groups independently selected from -C(O)NH2, 4 to 7-membered monocyclic heterocyclic groups, and 5 to 6-membered monocyclic heteroaryl groups, and wherein the 4 to 7-membered monocyclic heterocyclic groups and the 5 to 6-membered monocyclic heteroaryl groups are each optionally substituted by a group independently selected from -OH, halogen, C1-3 alkoxy, and C1-3 alkyl.

44. The compound of any one of claims 1 to 32 and 41 to 42, or a pharmaceutically acceptable salt thereof, wherein each R 8a is independently a 4-membered monocyclic heterocyclic group or a 5-membered monocyclic heteroaryl group, each of which may optionally be substituted with a C1-3 alkyl group.

45. A compound or a pharmaceutically acceptable salt thereof, as claimed in any one of claims 1 to 32, 41 to 42 and 44, wherein each R 8a is independently an oxo group or a 5-membered monocyclic heteroaryl having two N-based cyclic heteroatoms, and wherein the oxo group and the 5-membered monocyclic heteroaryl are optionally substituted with methyl groups.

46. ​​A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 32, 41 to 42 and 44 to 45, wherein each R 8a is independently oxo- or pyrazolyl, wherein the oxo- or pyrazolyl group is optionally substituted with a methyl group.

47. The compound of any one of claims 1 to 32, or a pharmaceutically acceptable salt thereof, wherein R 8 is -C(O)R 9.

48. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 32 and 47, wherein R 9 is a 4 to 7-membered monocyclic heterocyclic group, wherein the 4 to 7-membered monocyclic heterocyclic group is optionally substituted by 1 to 3 independently selected groups from: -OH, halogen, -CN, sideoxy group, -NR 11R 11, C 1-4 alkoxy group, C 1-5 alkyl group, and 4 to 7-membered monocyclic heterocyclic group.

49. A compound of any one of claims 1 to 32 and 47 to 48, or a pharmaceutically acceptable salt thereof, wherein R 9 is a 4 to 7-membered monocyclic heterocyclic group, wherein the 4 to 7-membered monocyclic heterocyclic group is optionally substituted by 1 to 3 independently selected from the group consisting of -OH, halogen, -CN, septyl group, -NR 11R 11, C 1-4 alkoxy group, and C 1-5 alkyl group; and wherein the 4 to 7-membered monocyclic heterocyclic group has one or two N-type cyclic heteroatoms.

50. A compound of any one of claims 1 to 32 and 47 to 49, or a pharmaceutically acceptable salt thereof, wherein R 9 is a 5- or 6-membered monocyclic heterocyclic group, wherein the 5- or 6-membered monocyclic heterocyclic group is optionally substituted by one or two independently selected groups of -OH, halogen, C1-3 alkoxy, and C1-3 alkyl, and wherein the 5- or 6-membered monocyclic heterocyclic group has one or two N-type cyclic heteroatoms.

51. A compound or a pharmaceutically acceptable salt thereof, as claimed in any one of claims 1 to 32 and 47 to 50, wherein R9 is a pyrrolidyl or linyl group, each of which may optionally be substituted by one or two independent groups selected from the following: -OH, halogen, C1-3 alkoxy, and C1-3 alkyl.

52. A compound or a pharmaceutically acceptable salt thereof, as claimed in any one of claims 1 to 32 and 47 to 49, wherein each R9 is independently acryl or pyrrolidinyl, each of which is optionally substituted by one or two independently selected groups of -OH, halogen, C1-3 alkoxy, and C1-3 alkyl.

53. The compound of any one of claims 1 to 32, 47 to 49 and 52, or a pharmaceutically acceptable salt thereof, wherein each R9 is independently or, optionally, substituted with one or two independently selected groups selected from -OH, methyl, and trifluoromethyl.

54. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 2, 5 to 32 and 47, wherein R 9 is a 7 to 10-membered spirocyclic heterocyclic group having 1 to 2 independently selected cyclic heteroatoms chosen from N and O.

55. The compound of any one of claims 1 to 2, 5 to 32, 47 and 54, or a pharmaceutically acceptable salt thereof, wherein R 9 is a series.

56. The compound of any one of claims 1 to 32 and 47, or a pharmaceutically acceptable salt thereof, wherein R9 is optionally substituted by one to three independently selected groups from the following: -OH, halogen, -CN, sideoxy, -NR11R11, C1-4 alkoxy, C1-5 alkyl, and 4 to 7 member monocyclic heterocyclic groups.

57. A compound or a pharmaceutically acceptable salt thereof, as claimed in any one of claims 1 to 32, 47 and 56, wherein R9 is cyclopropyl, cyclobutyl or cyclopentyl, each of which may optionally be substituted by one or two independently selected groups of -OH, halogen, C1-3 alkoxy, C1-3 alkyl and 4 to 7-membered monocyclic heterocyclic groups.

58. A compound or a pharmaceutically acceptable salt thereof, as claimed in any one of claims 1 to 32, 47 and 56 to 57, wherein R9 is cyclopropyl, cyclobutyl or cyclopentyl, each of which is optionally substituted by one or two independently selected groups of: -OH, halogen, C1-3 alkoxy, C1-3 alkyl and 5 to 7-membered monocyclic heterocyclic group, wherein the 5 to 7-membered monocyclic heterocyclic group has one or two N-type cyclic heteroatoms.

59. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 32, 47 and 56 to 58, wherein R 9 is a cyclopropyl group optionally substituted with a 6-membered monocyclic heterocyclic group having an N-type cyclic heteroatom.

60. The compound of any one of claims 1 to 32, 47 and 56 to 59, or a pharmaceutically acceptable salt thereof, wherein R9 is optionally a cyclopropyl group substituted with a linyl group.

61. The compound of any one of claims 1 to 32, or a pharmaceutically acceptable salt thereof, wherein R 8 is -S(O) 2R 5a.

62. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 32 and 61, wherein R 5a is a 4 to 7-membered monocyclic heterocyclic group, wherein the 4 to 7-membered monocyclic heterocyclic group is optionally substituted by 1 to 3 independently selected groups from: -OH, halogen, -CN, sideoxy group, -NR 11R 11, C 1-4 alkoxy group, and C 1-5 alkyl group; and wherein the 4 to 7-membered monocyclic heterocyclic group has one or two N-type cyclic heteroatoms.

63. A compound of any one of claims 1 to 32 and 61 to 62, or a pharmaceutically acceptable salt thereof, wherein R 5a is a 5- or 6-membered monocyclic heterocyclic group, wherein the 5- or 6-membered heterocyclic group is optionally substituted by one or two independently selected groups of -OH, halogen, -CN, and C1-5 alkyl; and wherein the 5- or 6-membered heterocyclic group has one or two N-type cyclic heteroatoms.

64. The compound of any one of claims 1 to 32 and 61 to 63, or a pharmaceutically acceptable salt thereof, wherein R 5a is a piperyl group.

65. The compound of any one of claims 1 and 5 to 13, or a pharmaceutically acceptable salt thereof, wherein the Z-series is -C(O)NR 6R 7.

66. A compound or a pharmaceutically acceptable salt thereof, as claimed in any one of claims 1, 5 to 13 and 65, wherein R6 is a 4- to 7-membered monocyclic heterocyclic group, wherein the 4- to 7-membered monocyclic heterocyclic group is optionally substituted by 1 to 3 independently selected from the following groups: -OH, halogen, -CN, sideoxy group, -NR11R11, C1-4 alkoxy group, and C1-5 alkyl group.

67. The compound of any one of claims 1, 5 to 13 and 65 to 66, or a pharmaceutically acceptable salt thereof, wherein R 6 is piperidinyl.

68. The compound of any one of claims 1, 5 to 13 and 65 to 67, or a pharmaceutically acceptable salt thereof, wherein R7 is H or methyl.

69. The compound of any one of claims 1 and 5 to 13, or a pharmaceutically acceptable salt thereof, wherein the Z-series is -C(O)R 13.

70. A compound or a pharmaceutically acceptable salt thereof, as claimed in any one of claims 1, 5 to 13 and 69, wherein R 13 is a 4 to 7-membered monocyclic heterocyclic group, wherein the 4 to 7-membered monocyclic heterocyclic group is optionally substituted by 1 to 3 independently selected from the group consisting of -OH, halogen, -CN, septyl group, -NR 11R 11, C 1-4 alkoxy group, and C 1-5 alkyl group; and wherein the 4 to 7-membered monocyclic heterocyclic group has one or two N-type cyclic heteroatoms.

71. A compound of any one of claims 1, 5 to 13, and 69 to 70, or a pharmaceutically acceptable salt thereof, wherein R 13 is a 5- or 6-membered monocyclic heterocyclic group, wherein the 5- or 6-membered monocyclic heterocyclic group is optionally substituted by 1 to 3 independently selected from the following groups: -OH, halogen, -CN, sideoxy group, -NR 11R 11, C 1-4 alkoxy group, and C 1-5 alkyl group.

72. The compound of any one of claims 1, 5 to 13 and 69 to 71, or a pharmaceutically acceptable salt thereof, wherein R 13 is a 5- to 6-membered monocyclic heterocyclic group.

73. The compound of any one of claims 1, 5 to 13 and 69 to 72, or a pharmaceutically acceptable salt thereof, wherein R 13 is a piperyl group.

74. A compound of any one of claims 1 to 73, or a pharmaceutically acceptable salt thereof, wherein R11 is an H or C1-3 alkyl group.

75. A compound selected from the group consisting of: , , , , , and , or a medicinally acceptable salt thereof.

76. A compound selected from the group consisting of: , , and , or a pharmaceutically acceptable salt thereof.

77. A compound selected from the group consisting of: , , , , , , , and , or a pharmaceutically acceptable salt thereof.

78. A compound selected from the group consisting of: , , , , , , and , or a pharmaceutically acceptable salt thereof.

79. A compound selected from the group consisting of: , , , , , and , or a pharmaceutically acceptable salt thereof.

80. A compound selected from the group consisting of: , , and , or a pharmaceutically acceptable salt thereof.

81. A compound selected from the group consisting of: , , , and , or a medicinally acceptable salt thereof.

82. A compound selected from the group consisting of: , , , , , , , , and , or a medicinally acceptable salt thereof.

83. A compound selected from the group consisting of: , , and , or a medicinally acceptable salt thereof.

84. A compound selected from the group consisting of: , , , and , or a medicinally acceptable salt thereof.

85. A compound selected from the group consisting of: and, or a pharmaceutically acceptable salt thereof.

86. A pharmaceutical composition comprising a compound of any one of claims 1 to 85 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient or carrier.

87. A pharmaceutical composition as claimed in claim 86, further comprising one or more additional therapeutic agents or pharmaceutically acceptable salts thereof.

88. A pharmaceutical composition as claimed in claim 87, wherein the one or more additional therapeutic agents contain an antimalarial agent.

89. The pharmaceutical composition of claim 88, wherein the antimalarial agent is selected from chloroquine and hydroxychloroquine, or pharmaceutically acceptable salts thereof.

90. A method for inhibiting the activity of troponin receptor 7 and / or 8 in a subject in need, comprising administering to the subject a therapeutically effective amount of a compound of any one of claims 1 to 85 or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of a pharmaceutical composition of any one of claims 86 to 89.

91. A method for inhibiting the activity of a tyrosine receptor 7 in a subject in need, comprising administering to the subject a therapeutically effective amount of a compound of any one of claims 1 to 85 or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of a pharmaceutical composition of any one of claims 86 to 89.

92. A method for inhibiting the activity of troponin receptor 8 in a subject in need, comprising administering to the subject a therapeutically effective amount of a compound of any one of claims 1 to 85 or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of a pharmaceutical composition of any one of claims 86 to 89.

93. A method of treating in a subject a disease or condition associated with elevated activity of troponin receptor 7 and / or 8, comprising administering to the subject a therapeutically effective amount of a compound of any one of claims 1 to 85 or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of a pharmaceutical composition of any one of claims 86 to 89.

94. A method of treating a disease or condition associated with elevated troponin 7 activity in a subject of need, comprising administering to the subject a therapeutically effective amount of a compound of any one of claims 1 to 85 or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of a pharmaceutical composition of any one of claims 86 to 89.

95. A method of treating a disease or condition associated with elevated troponin 8 receptor activity in a subject in need, comprising administering to the subject a therapeutically effective amount of a compound of any one of claims 1 to 85 or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of a pharmaceutical composition of any one of claims 86 to 89.

96. A method of treating an inflammatory condition in a subject in need, comprising administering to the subject a therapeutically effective amount of a compound of any one of claims 1 to 85 or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of a pharmaceutical composition of any one of claims 86 to 89.

97. The method of claim 96, wherein the inflammatory condition is selected from inflammatory bowel disease, psoriasis, psoriatic arthritis, rheumatoid arthritis, glomerulonephritis, mixed connective tissue disease (MCTD), dermatomyositis, polymyositis, systemic sclerosis, antineutrophil-associated vasculitis, antiphospholipid syndrome, autoimmune hemolytic anemia, macrophage activation syndrome-driven inflammatory anemia, IgA nephropathy, type I diabetes, non-alcoholic steatohepatitis, and Sjogren's syndrome.

98. A method of treating systemic lupus erythematosus in a subject in need, comprising administering to the subject a therapeutically effective amount of a compound of any one of claims 1 to 85 or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of a pharmaceutical composition of any one of claims 86 to 89.

99. A method of treating cutaneous lupus erythematosus in a subject in need, comprising administering to the subject a therapeutically effective amount of a compound of any one of claims 1 to 85 or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of a pharmaceutical composition of any one of claims 86 to 89.

100. A method of treating lupus nephritis in a subject in need, comprising administering to the subject a therapeutically effective amount of a compound of any one of claims 1 to 85 or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of a pharmaceutical composition of any one of claims 86 to 89.

101. The method of any of claims 90 to 100 further comprises administering a therapeutically effective amount of one or more additional therapeutic agents or a pharmaceutically acceptable salt thereof.

102. The method of claim 101, wherein the one or more additional therapeutic agents are selected from the group consisting of: veltuzumab, PF-06835375, eculizumab, milatuzumab, SM-06, SM-03, BT-063, QX-006-N, BOS-161721, AK-101, TNX-1500, theralizumab, daxdilimab, TAK-079, felzartamab, itolizumab, anifrolumab, iscalimab, pegylated dapirolizumab pegol), lanalumab, LY-3361237, JNJ-55920839, UBP-1213, DS-7011, PFI-102, BIIB-059, obexelimab, talacotuzumab, vobarilizumab, TE-2324, PRV-3279, chloroquine, hydroxychloroquine, hydroxychloroquine sulfate, COV-08-0064; GNKS-356, AVO-101, rozibafusp alfa, VRN-02, annexuzlimab, ALPN-101, bendamustine hydrochloride hydrochloride), BMS-986256, NKTR-35, atacicept, telitacicept, BMS-986256, M-5049, KZR-616, KPG-818, verdinexor, ALPN-303, valziflocept, LA-1, cenerimod, prednisone, corticotropin, deucravacitinib, CPL-409116, CS-12192, tofacitinib citrate, ISB-830, DV-1079, julemic acidacid), iberdomide, TAM-01, BML-258, brepocitinib, SDC-1801, SDC-1802, ICP-330, NTR-441, dalazatide, GSK-2646264, SKI-O-703, lanraplenib (GS-9876), GNS-1653, HMPL-523, RSLV-132, interleukin-2 follow-on biologic, interleukin-2 Anteluke, interking recombinant human interleukin-2, ILT-101, CUG-252, DZ-2002, polyethylene glycolated HLA-x (SLE), AC-0058, fenebrutinib, XNW-1011, tirabrutinib hydrochloride, branebrutinib, elsubrutinib, orelabrutinib, DWP-213388, INV-103, R-salbutamol sulfate, anchorin, NIK-SMI1, X-6, INV-17, Oshadi D. Baricitinib, Upadacitinib, Filgotinib, Itacitinib, INCB-54707, Delgocitinib, DWP-212525, CKD-971, Mometasone, Betamethasone, Forigerimod, Anandamide, DCB-SLE1, Dichloroethane Arsenic, tairuimide, TV-4710 (edratide), allogeneic human umbilical cord-derived mesenchymal stem cell therapy (hUC-MSC), LC-200, BI-705564, SM-934, GX-101, TXR-712, TXR-711, CIT-013, MHV-370, Panzyga®, TPX-6001, TPX-7001, artenimol, and AMG-592, or any of the aforementioned pharmaceutically acceptable salts, or any combination thereof.

103. The method of any of the requests 90 to 102, wherein the object is a human.

104. The compound of any one of claims 1 to 85 or its pharmaceutically acceptable salt, or the pharmaceutical composition of any one of claims 86 to 89, is used in a therapeutic manner.

105. A compound of any one of claims 1 to 85 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of any one of claims 86 to 89, used in a method for inhibiting the activity of tyrosine receptor 7 and / or 8 in a subject in need, the method comprising administering to the subject a therapeutically effective amount of the compound or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of the pharmaceutical composition.

106. A compound of any one of claims 1 to 85 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of any one of claims 86 to 89, used in a method for inhibiting the activity of a tyrosine receptor 7 in a subject in need, the method comprising administering to the subject a therapeutically effective amount of the compound or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of the pharmaceutical composition.

107. A compound of any one of claims 1 to 85 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of any one of claims 86 to 89, used in a method for inhibiting the activity of tyrosine receptor 8 in a subject in need, the method comprising administering to the subject a therapeutically effective amount of the compound or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of the pharmaceutical composition.

108. A method of treating a disease or condition associated with elevated tyrosine receptor 7 and / or 8 activity in a subject of need, comprising administering to the subject a therapeutically effective amount of the compound or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of the pharmaceutical composition thereof.

109. A method of treating a disease or condition associated with elevated troponin receptor 7 activity in a subject of need, comprising administering to the subject a therapeutically effective amount of the compound or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of the pharmaceutical composition thereof.

110. A method of treating a disease or condition associated with elevated troponin receptor 8 activity in a subject of need, comprising administering to the subject a therapeutically effective amount of the compound or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of the pharmaceutical composition thereof.

111. A method of treating an inflammatory condition in a subject in need of any of claims 1 to 85, comprising administering to the subject a therapeutically effective amount of the compound or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of the pharmaceutical composition thereof.

112. As claimed in claim 111, wherein the inflammatory condition is selected from inflammatory bowel disease, psoriasis, psoriatic arthritis, rheumatoid arthritis, glomerulonephritis, mixed connective tissue disease (MCTD), dermatomyositis, polymyositis, systemic sclerosis, antineutrophil-associated vasculitis, antiphospholipid syndrome, autoimmune hemolytic anemia, macrophage activation syndrome-induced inflammatory anemia, IgA nephropathy, type I diabetes, non-alcoholic steatohepatitis, and Hugh Grant's syndrome.

113. A method of treating systemic lupus erythematosus in a subject in need of any of claims 1 to 85, comprising administering to the subject a therapeutically effective amount of the compound or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of the pharmaceutical composition thereof.

114. A method of treating cutaneous lupus erythematosus in a subject in need of any of claims 1 to 85, comprising administering to the subject a therapeutically effective amount of the compound or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of the pharmaceutical composition thereof.

115. A method of treating lupus nephritis in a subject in need of any of claims 1 to 85, comprising administering to the subject a therapeutically effective amount of the compound or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of the pharmaceutical composition thereof.

116. The use of any of claims 105 to 115 further includes administering one or more additional therapeutic agents.

117. As claimed in claim 116, wherein the one or more additional therapeutic agents are selected from the group consisting of: vetocilizumab, PF-06835375, eculizumab, mirtizumab, SM-06, SM-03, BT-063, QX-006-N, BOS-161721, AK-101, TNX-1500, zeplizumab, dastacilinumab, TAK-079, fenzalumab, etanercept. Icalcitazol, alivrumab, icalimab, pegylated dapizumab, lanrarumab, LY-3361237, JNJ-55920839, UBP-1213, DS-7011, PFI-102, BIIB-059, obbelimumab, talacomab, vobalizumab, TE-2324, PRV-3279, chloroquine, hydroxychloroquine, hydroxychloroquine sulfate, COV-08-0064;GNKS-356, AVO-101, Lobivop α, VRN-02, Anezimumab, ALPN-101, Bendamustine Hydrochloride, BMS-986256, NKTR-35, Asexip, Telitacicept, BMS-986256, M-5049, KZR-616, KPG-818, Vandinisole, ALPN-303, Vasilosip, LA-1, Celimod, Prednisone, Corticotropin, Declavatinib, CPL-409116, CS-12192, Tofacitinib Citrate, ISB-830, DV-1079. Chulaminic acid, Ibmet, TAM-01, BML-258, Brabotinib, SDC-1801, SDC-1802, ICP-330, NTR-441, Darazatide, GSK-2646264, SKI-O-703, Lanlaprilini (GS-9876), GNS-1653, HMPL-523, RSLV-132, Interleukin-2 follow-up biologics, Interleukin-2 Antruk, Interken recombinant human interleukin-2, ILT-101, CUG-252, DZ-2002, Polyvinyl glycolated HLA-x (SLE), AC-0058, Finatinib, XNW-1011, Tiratitinib Hydrochloride, Buritinib, Aishutinib, Olabutinib, DWP-213388, INV-103, R-Salbutamol Sulfate, Anchor Protein, NIK-SMI1, X-6, INV-17, Oshadi D. Baricitinib, Upatinib, Figotinib, Etatinib, INCB-54707, Degatinib, DWP-212525, CKD-971, Mometasone, Betamethasone, Vergimod, Cannabinoids, DCB-SLE1, Arsenic Trioxide, Terainmi, TV-4710 (Ailatide), Allogeneic Human Umbilical Cord-Derived Mesenchymal Stem Cell Therapy (hUC-MSC), LC-200, BI-705564, SM-934, GX-101, TXR-712, TXR-711, CIT-013, MHV-370, Panzyga®, TPX-6001, TPX-7001, Dihydroartemisinin, and AMG-592, or pharmaceutically acceptable salts thereof.

118. The use of any of the requests 104 to 117, wherein the object is a human being.