Kv1.3 potassium channel antagonists

Abstract

The present invention relates to KV1.3 potassium channel antagonists and their use in the treatment and management of inflammatory diseases, including neuroinflammatory diseases.

Description

[0001] KV1.3 potassium channel antagonists

[0002] Technical field

[0003] The present invention relates to Kv1.3 potassium channel antagonists and their use in the treatment and management of inflammatory diseases, including neuroinflammatory diseases.

[0004] Background

[0005] The Kv1.3 potassium channel, a voltage-gated potassium channel, is widely expressed in the immune and nervous systems, playing crucial roles in the function of T-cells and microglia.

[0006] The activation, proliferation, and effector functions of T-cells are tightly regulated by the interplay of ion channels, including the Kv1.3 channel. In T-cells, Kv1.3 channels are involved in the modulation of calcium signalling, which is critical for T-cell receptor (TCR) signalling and subsequent activation.

[0007] Upon TCR engagement, the membrane potential of T-cells becomes depolarized, leading to the opening of voltage-gated Kv1.3 channels. This results in the efflux of potassium ions, which stabilizes the membrane potential and promotes the opening of calcium channels. The influx of calcium activates the calcium-dependent signalling pathways that drive T-cell activation, differentiation, and proliferation. Consequently, the inhibition of Kv1.3 channels can prevent the activation and proliferation of T-cells, modulating immune responses and potentially ameliorating autoimmune and inflammatory conditions.

[0008] Microglia are the resident immune cells of the central nervous system (CNS), responsible for maintaining homeostasis and responding to injury or infection. In the context of neuroinflammation and neurodegenerative diseases, microglial activation can contribute to the release of pro-inflammatory cytokines, chemokines, and reactive oxygen species (ROS), ultimately exacerbating neuronal damage.

[0009] The Kv1.3 potassium channel has been found to play a critical role in microglial activation and function. Under resting conditions, microglia express low levels of Kv1.3 channels, but upon stimulation by pro-inflammatory signals, the expression and activity of these channels increase significantly. This upregulation of Kv1.3 channels enhances the production of ROS and pro-inflammatory cytokines, perpetuating the inflammatory response and amplifying neuronal injury.

[0010] The functional involvement of Kv1.3 channels in T-cells and microglia suggests that their selective antagonism could be a promising therapeutic strategy for mitigating inflammation, particularly neuroinflammation associated with neurodegenerative diseases such as Multiple Sclerosis, Parkinson's disease, amyotrophic lateral sclerosis (ALS), and Huntington's disease. In preclinical studies, the use of Kv1.3 channel antagonists has been shown to suppress T-cell activation and proliferation, reduce microglial activation, and decrease the production of pro-inflammatory mediators. These effects translate into reduced neuroinflammation and improved outcomes in animal models of neurodegenerative diseases, such as Alzheimer's and Parkinson's disease.

[0011] Summary

[0012] The present invention relates to Kv1.3 potassium channel antagonists.

[0013] In one aspect, the present invention relates to a compound of Formula (I),

[0014] Formula (I) wherein

[0015] R1is halogen or H;

[0016] R2is halogen;

[0017] R3is halogen;

[0018] R5is H or halogen;

[0019] R6is H or halogen;

[0020] R4is of Formula (II): Formula (II) wherein X1is C(R7)(R8); X2is C(R9)(R10) or a bond; X3is N(C(O)R11), C(R12)(C(O)R13), C(R14)(R15) or N(R16); X4is C(R17)(R18), O or C(O); X5is C(R19)(R20) or a bond; X6is a bond or C(R21)(R22); wherein R9and R11, R9and R13, R10and R11, R10and R13, R13and R17, R13and R18, or R14and R15are optionally joined together to form a ring together with the intervening atom(s); R7is H, C1-3 alkyl optionally substituted with 1 to 3 F or C1-3 alkoxy, or halogen, such as F; R8is H, C1-3alkyl optionally substituted with 1 to 3 F or C1-3alkoxy, or halogen, such as F; R9is H, C1-3alkyl optionally substituted with 1 to 3 halogens, halogen, such as F, or - C(O)N(R31)(R32), wherein R31is H or C1-3alkyl and R32is H or C1-3alkyl, or when R9is linked to R11or R13to form a ring, then R9is a bond, -C(O)- or a C1-3alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl; R10is H, C1-3alkyl optionally substituted with 1 to 3 halogens, halogen, such as F, , or - C(O)N(R31)(R32), wherein R31is H or C1-3alkyl and R32is H or C1-3alkyl, or when R10is linked to R11or R13to form a ring, then R10is a bond, -C(O)- or a C1-3alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl; R11is -X13-R33; X13is a bond, C1-3alkanediyl optionally substituted with C1-3alkyl, -O-, or C1-3alkanediyl- O-; R33is selected from the group consisting of C1-3alkyl, C3-6cycloalkyl, C1-3alkoxy, pyridinyl, azetidinyl, pyrrolidinyl, oxetanyl, tetrahydrofuranyl, and morpholinyl, each of which is optionally substituted with one or more substituents individually selected from halogen; C1-3 alkoxy optionally substituted with one or more F; C1-3 alkyl optionally substituted with one or more F; NH2; N(H)(CH3); and N(CH3)2; or when R11is linked to R9or R10to form a ring, then R11is -O-, -N(R28)-, or C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl, wherein one methylene group of the C1-3 alkanediyl is optionally replaced by -O- or -N(R28)-, wherein R28is H or C1-3 alkyl;

[0021] R12is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F;

[0022] R13is selected from the group consisting of NH2, N(H)(CH3), N(CH3)2, pyrrolidinyl, azetidinyl, and piperazinyl, wherein

[0023] • said pyrrolidinyl is optionally substituted with one or more substituents individually selected from the group consisting of halogen, NH2, N(H)(CH3), N(CH3)2 and azetidinyl, and said azetidinyl is optionally substituted with one or more halogens, and

[0024] • said azetidinyl optionally substituted with NH2; or when R13is linked to R9, R10, R17, or R18to form a ring, then R13is -N(R28)-, wherein R28is H or C1-3 alkyl;

[0025] R14is -X7N(R23)(C(O)R24), wherein

[0026] X7is a bond or C1-3 alkanediyl;

[0027] R24is C1-3 alkyl; and

[0028] R23is H or C1-3 alkyl, and R15is H or C1-3 alkyl, or R23is a bond or C1-3 alkanediyl, and R15is a bond or C1-3 alkanediyl and R23is linked to R15to form a ring; or R14is -X9C(O)X11-, R15is a bond or C1-3 alkanediyl, and X11is linked to R15to form a ring, wherein

[0029] X9is a bond or -N(R29)-;

[0030] R29is C1-3 alkyl;

[0031] X11is -O-, C1-3 alkanediyl, or -N(R30)-; and

[0032] R30is C1-3 alkyl;

[0033] R16is H or C1-3 alkyl;

[0034] R17is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; or when R17is linked to R13to form a ring, then R17is a bond or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl; R18is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; or when R18is linked to R13to form a ring, then R18is a bond or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl;

[0035] R19is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F;

[0036] R20is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F;

[0037] R21is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F;

[0038] R22is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; any two of

[0039] R7, R8, R9, R10, R17, R18, R19, R20, R21, and R22are optionally linked together to form a ring; with the proviso that when X4is O, then X3is C(R12)C(O)R13and R13is NH2, N(H)(CH3) or N(CH3)2; with the proviso that when X3is N(R16), then X4is C(O), with the proviso that when X4is C(O), then X3is N(R16), and with the proviso that when X2is a bond, then X3is C(R12)(C(O)R13) or C(R14)(R15), or a pharmaceutically acceptable salt thereof.

[0040] In one aspect, the present invention relates a compound of Formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, for use in the treatment of a disease or medical condition where inhibition of Kv1.3 potassium channel is beneficial.

[0041] Definitions

[0042] As used herein, the singular forms “a,” “an” and “the” include plural referents unless the content clearly dictates otherwise.

[0043] The terms “approximately” and “about” as referred herein are synonymous. In some embodiments, “about” refer to the recited amount, value, or duration ±20%, ±10%, ± 5%, ± 4%, ±3%, ±2%, ±1 %, or ± 0.5%.

[0044] As used herein, the term “antagonist” refers to any compound which inhibits (e.g., antagonizes, reduces, decreases, blocks, reverses, or alters) the effect of a given agonist of a protein (including the protein itself). More particularly, an antagonist is capable of acting in a manner relative to the activity of the protein, such that the biological activity of the natural agonist, is decreased in a manner that is antagonistic (e.g., against, a reversal of, contrary to) to the natural action of the protein. The terms “antagonist”, “inhibitor” and “blocker” are used herein interchangeably to refer to an agent that decreases or suppresses a biological activity, such as to repress an activity of an ion channel, such as Kv1.3.

[0045] The term, “compound,” as used herein is meant to include all stereoisomers, geometric isomers, tautomers, and isotopes of the structures depicted, unless otherwise specified.

[0046] The terms “C1-3 alkyl” and “C1-6 alkyl” as used herein refer to a straight or branched hydrocarbon chains containing from 1 to 3 and 1 to 6 carbon atoms, respectively. Representative examples of C1-3 alkyl and C1-6 alkyl include, but are not limited to, methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl, pentyl and hexyl.

[0047] The term “C3-6 cycloalkyl” as used herein refers to a saturated carbocyclic molecule wherein the cyclic framework has 3 to 6 carbon atoms. Representative examples of C3- 6 cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0048] The term “C1-3 alkoxy” as used herein refer to -OR#, wherein R#represents a C1-3 alkyl as defined herein. Representative examples of C1-3 alkoxy include methoxy, ethoxy, propoxy, and iso-propoxy.

[0049] The term “halogen” as used herein refers to -F, -Cl, -Br, or -I. In some embodiments, the halogen is F. In some embodiments, the halogen is Cl.

[0050] As used herein, the term “pharmaceutically acceptable salt” refers to those salts which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like, and are commensurate with a reasonable benefit / risk ratio. Pharmaceutically acceptable salts are well known in the art.

[0051] The term “spiro compound” as used herein refers to a compound having one atom (usually a quaternary carbon) as the only common member of two rings. The term “C5-8 spiroalkyl” as used herein refers to a bicyclic ring system comprising 5 to 8 carbon atoms, wherein the two rings are connected through a single common carbon atom. Representative examples of C5-8 spiroalkyl include, but are not limited to, spiro[2.2]pentanyl, spiro[3.2]hexanyl, spiro[3.3]heptanyl, spiro[3.4]octanyl, and spiro[2.5]octanyl.

[0052] As described herein, compounds of the present invention may contain “substituted” moieties. In general, the term “substituted” means that one or more hydrogens of the designated moiety are replaced with a suitable substituent. Unless otherwise indicated, an “optionally substituted” group may have a suitable substituent at one or more substitutable position of the group, and when more than one position in any given structure is substituted with more than one substituent selected from a specified group, the7ubstitutent may be either the same or different at every position, i.e. the substituent may be individually / independently selected from a group of substituents. Combinations of substituents envisioned by the present invention are preferably those that result in the formation of stable or chemically feasible compounds.

[0053] In some embodiments, a chemical group is “a bond”, which may also be referred to as said chemical group is absent. For example, when Rain CH3-Ra-OH is “a bond”, it refers to CH3OH.

[0054] In some embodiments, two R groups are linked together to form a ring, i.e. a ring is formed by the two R groups and the intervening atom(s).

[0055] The term “stable,” as used herein, refers to compounds that are not substantially altered when subjected to conditions to allow for their production, detection, and, in certain embodiments, their recovery, purification, and use for one or more of the purposes disclosed herein.

[0056] Detailed description

[0057] In one aspect, the present invention relates to a compound of Formula (I),

[0058] Formula (I) wherein

[0059] R1is halogen or H;

[0060] R2is halogen;

[0061] R3is H or halogen;

[0062] R5is H or halogen;

[0063] R6is H or halogen;

[0064] R4is of Formula (II):

[0065] Formula (II) wherein

[0066] X1is C(R7)(R8);

[0067] X2is C(R9)(R10) or a bond;

[0068] X3is N(C(O)R11), C(R12)(C(O)R13), C(R14)(R15) or N(R16);

[0069] X4is C(R17)(R18), O or C(O);

[0070] X5is C(R19)(R20) or a bond;

[0071] X6is a bond or C(R21)(R22); wherein R9and R11, R9and R13, R10and R11, R10and R13, R13and R17, R13and R18, or R14and R15are optionally joined together to form a ring together with the intervening atom(s);

[0072] R7is H, C1-3 alkyl optionally substituted with 1 to 3 F or C1-3 alkoxy, or halogen, such as F;

[0073] R8is H, C1-3 alkyl optionally substituted with 1 to 3 F or C1-3 alkoxy, or halogen, such as F;

[0074] R9is H, C1-3 alkyl optionally substituted with 1 to 3 halogens, halogen, such as F, or - C(O)N(R31)(R32), wherein R31is H or C1-3 alkyl and R32is H or C1-3 alkyl, or when R9is linked to R11or R13to form a ring, then R9is a bond, -C(O)- or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and Ci- 3 alkyl;

[0075] R10is H, C1-3 alkyl optionally substituted with 1 to 3 halogens, halogen, such as F, , or - C(O)N(R31)(R32), wherein R31is H or C1-3 alkyl and R32is H or C1-3 alkyl, or when R10is linked to R11or R13to form a ring, then R10is a bond, -C(O)- or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1- 3 alkyl;

[0076] R11is -X13-R33;

[0077] X13is a bond, C1-3 alkanediyl optionally substituted with C1-3 alkyl, -O-, or Ci-3alkanediyl- O-;

[0078] R33is selected from the group consisting of C1-3 alkyl, C3-6 cycloalkyl, C1-3 alkoxy, pyridinyl, azetidinyl, pyrrolidinyl, oxetanyl, tetrahydrofuranyl, and morpholinyl, each of which is optionally substituted with one or more substituents individually selected from halogen; C1-3 alkoxy optionally substituted with one or more F; C1-3 alkyl optionally substituted with one or more F; NH2; N(H)(CH3); and N(CH3)2; or when R11is linked to R9or R10to form a ring, then R11is -O-, -N(R28)-, or C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl, wherein one methylene group of the C1-3 alkanediyl is optionally replaced by -O- or -N(R28)-, wherein R28is H or C1-3 alkyl;

[0079] R12is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F;

[0080] R13is selected from the group consisting of NH2, N(H)(CH3), N(CH3)2, pyrrolidinyl, azetidinyl, and piperazinyl, wherein

[0081] • said pyrrolidinyl is optionally substituted with one or more substituents individually selected from the group consisting of halogen, NH2, N(H)(CH3), N(CH3)2 and azetidinyl, and said azetidinyl is optionally substituted with one or more halogens, and

[0082] • said azetidinyl optionally substituted with NH2; or when R13is linked to R9, R10, R17, or R18to form a ring, then R13is -N(R28)-, wherein R28is H or C1-3 alkyl;

[0083] R14is -X7N(R23)(C(O)R24), wherein

[0084] X7is a bond or C1-3 alkanediyl;

[0085] R24is C1-3 alkyl; and

[0086] R23is H or C1-3 alkyl, and R15is H or C1-3 alkyl, or R23is a bond or C1-3 alkanediyl, and R15is a bond or C1-3 alkanediyl and R23is linked to R15to form a ring; or R14is -X9C(O)X11-, R15is a bond or C1-3 alkanediyl, and X11is linked to R15to form a ring, wherein

[0087] X9is a bond or -N(R29)-;

[0088] R29is C1-3 alkyl;

[0089] X11is -O-, C1-3 alkanediyl, or -N(R30)-; and

[0090] R30is C1-3 alkyl;

[0091] R16is H or C1-3 alkyl;

[0092] R17is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; or when R17is linked to R13to form a ring, then R17is a bond or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl;

[0093] R18is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; or when R18is linked to R13to form a ring, then R18is a bond or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl;

[0094] R19is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F;

[0095] R20is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F;

[0096] R21is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F;

[0097] R22is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; any two of

[0098] R7, R8, R9, R10, R17, R18, R19, R20, R21, and R22are optionally linked together to form a ring; with the proviso that when X4is O, then X3is C(R12)C(O)R13and R13is NH2, N(H)(CH3) or N(CH3)2; with the proviso that when X3is N(R16), then X4is C(O), with the proviso that when X4is C(O), then X3is N(R16), and with the proviso that when X2is a bond, then X3is C(R12)(C(O)R13) or C(R14)(R15), or a pharmaceutically acceptable salt thereof.

[0099] In one aspect, the present invention relates to a compound of Formula (I), Formula (I) wherein

[0100] R1is halogen or H;

[0101] R2is halogen;

[0102] R3is H or halogen;

[0103] R5is H or halogen;

[0104] R6is H or halogen;

[0105] R4is of Formula (II):

[0106] Formula (II) wherein

[0107] X1is C(R7)(R8);

[0108] X2is C(R9)(R10) or a bond;

[0109] X3is N(C(O)R11), C(R12)(C(O)R13), C(R14)(R15) or N(R16);

[0110] X4is C(R17)(R18), O or C(O);

[0111] X5is C(R19)(R20) or a bond;

[0112] X6is a bond or C(R21)(R22); wherein R9and R11, R9and R13, R10and R11, R10and R13, R13and R17, R13and R18, or R14and R15are optionally joined together to form a ring together with the intervening atom(s);

[0113] R7is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F;

[0114] R8is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F;

[0115] R9is H, C1-3 alkyl optionally substituted with 1 to 3 halogens, or halogen, such as F, or when R9is linked to R11or R13to form a ring, then R9is a bond or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1- 3 alkyl;

[0116] R10is H, C1-3 alkyl optionally substituted with 1 to 3 halogens, or halogen, such as F, or when R10is linked to R11or R13to form a ring, then R10is a bond or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1- 3 alkyl;

[0117] R11is selected from the group consisting of C1-3 alkyl, C3-5 cycloalkyl, C1-3 alkoxy, pyridinyl, azetidinyl, pyrrolidinyl, oxetanyl, and morpholinyl, wherein • said C1-3 alkyl is optionally substituted with one or more substituents individually selected from the group consisting of NH2, N(H)(CH3), N(CH3)2, C1-3 alkoxy, morpholinyl, azetidinyl, -O-azetidinyl, and -O- oxetanyl, and said azetidinyl is optionally substituted with one or more substituents selected from halogen, C1-3 alkoxy, and C1-3 alkyl;

[0118] • said C3-5 cycloalkyl is optionally substituted with one or more substituents selected from halogen, and C1-3 alkoxy;

[0119] • said pyridinyl is optionally substituted with one or more NH2;

[0120] • said pyrrolidinyl is optionally substituted with one or more substituents individually selected from the group consisting of C1-3 alkyl, halogen, C1-3 alkoxy, Ci-s haloalkyl, NH2, N(H)(CH3), N(CHs)2 and azetidinyl, and said azetidinyl is optionally substituted with one or more halogens;

[0121] • said azetidinyl optionally substituted with one or more substituents selected from halogen, C1-3 alkyl, and NH2; and

[0122] • said morpholinyl is optionally substituted with C1-3 alkyl; or when R11is linked to R9or R10to form a ring, then R11is -O-, -N(R28)-, or C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl, wherein one methylene group of the C1-3 alkanediyl is optionally replaced by -O- or -N(R28)-, wherein R28is H or C1-3 alkyl;

[0123] R12is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F;

[0124] R13is selected from the group consisting of NH2, N(H)(CH3), N(CH3)2, pyrrolidinyl, azetidinyl, and piperazinyl, wherein

[0125] • said pyrrolidinyl is optionally substituted with one or more substituents individually selected from the group consisting of halogen, NH2, N(H)(CH3), N(CH3)2 and azetidinyl, and said azetidinyl is optionally substituted with one or more halogens, and

[0126] • said azetidinyl optionally substituted with NH2; or when R13is linked to R9, R10, R17, or R18to form a ring, then R13is -N(R28)-, wherein R28is H or C1-3 alkyl;

[0127] R14is -X7N(R23)(C(O)R24), wherein

[0128] X7is a bond or C1-3 alkanediyl;

[0129] R24is C1-3 alkyl; and R23is H or C1-3 alkyl, and R15is H or C1-3 alkyl, or R23is a bond or C1-3 alkanediyl, and R15is a bond or C1-3 alkanediyl and R23is linked to R15to form a ring; or R14is -X9C(O)X11-, R15is a bond or C1-3 alkanediyl, and X11is linked to R15to form a ring, wherein

[0130] X9is a bond or -N(R29)-;

[0131] R29is C1-3 alkyl;

[0132] X11is -O-, C1-3 alkanediyl, or -N(R30)-; and

[0133] R30is C1-3 alkyl;

[0134] R16is H or C1-3 alkyl;

[0135] R17is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; or when R17is linked to R13to form a ring, then R17is a bond or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl; R18is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; or when R18is linked to R13to form a ring, then R18is a bond or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl; R19is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F;

[0136] R20is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F;

[0137] R21is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F;

[0138] R22is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; any two of R7, R8, R9, R10, R17, R18, R19, R20, R21, and R22are optionally linked together to form a ring; with the proviso that when X4is O, then X3is C(R12)C(O)R13and R13is NH2, N(H)(CH3) or N(CH3)2; with the proviso that when X3is N(R16), then X4is C(O), and with the proviso that when X4is C(O), then X3is N(R16), or a pharmaceutically acceptable salt thereof.

[0139] In one aspect, the present invention relates to a compound of Formula (I), Formula (I) wherein

[0140] R1is halogen or H;

[0141] R2is halogen;

[0142] R3is H or halogen;

[0143] R5is H or halogen;

[0144] R6is H or halogen;

[0145] R4is of Formula (II):

[0146] Formula (II) wherein

[0147] X1is C(R7)(R8);

[0148] R7is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F;

[0149] R8is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F;

[0150] X2is C(R9)(R10) or a bond;

[0151] X3is N(C(O)R11), C(R12)(C(O)R13), C(R14)(R15) or N(R16);

[0152] R9is H, C1-3 alkyl optionally substituted with 1 to 3 halogens, or halogen, such as F;

[0153] R10is H, C1-3 alkyl optionally substituted with 1 to 3 halogens, or halogen, such as F;

[0154] R11is selected from the group consisting of C1-3 alkyl, C3-5 cycloalkyl, C1-3 alkoxy, pyridinyl, azetidinyl and pyrrolidinyl, wherein

[0155] • said C1-3 alkyl is optionally substituted with one or more substituents individually selected from the group consisting of NH2, N(H)(CH3), N(CH3)2, C1-3 alkoxy, and morpholinyl,

[0156] • said pyridinyl is optionally substituted with one or more NH2;

[0157] • said pyrrolidinyl is optionally substituted with one or more substituents individually selected from the group consisting of C1-3 alkyl, halogen, C1-3 alkoxy, NH2, N(H)(CH3), N(CH3)2 and azetidinyl, and said azetidinyl is optionally substituted with one or more halogens, and

[0158] • said azetidinyl optionally substituted with NH2; or R11is linked to R9to form a ring and

[0159] R9is a bond or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl, R10is H, C1-3 alkyl optionally substituted with 1 to 3 halogens, or halogen, such as F, and

[0160] R11is C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl, wherein one methylene group of the C1-3 alkanediyl is optionally replaced by -O- or -N(R28)-, wherein R28is H or C1-3 alkyl; or R11is linked to R10to form a ring and

[0161] R9is H, C1-3 alkyl optionally substituted with 1 to 3 halogens, or halogen, such as F,

[0162] R10is a bond or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl, and R11is C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl, wherein one methylene group of the C1-3 alkanediyl is optionally replaced by -O- or -N(R28)-, wherein R28is H or C1-3 alkyl;

[0163] R12is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F;

[0164] R13is selected from the group consisting of NH2, N(H)(CH3), N(CH3)2, pyrrolidinyl, azetidinyl, and piperazinyl, wherein

[0165] • said pyrrolidinyl is optionally substituted with one or more substituents individually selected from the group consisting of halogen, NH2, N(H)(CH3), N(CH3)2 and azetidinyl, and said azetidinyl is optionally substituted with one or more halogens, and

[0166] • said azetidinyl optionally substituted with NH2;

[0167] R14is -X7N(R23)(C(O)R24), wherein

[0168] X7is a bond or C1-3 alkanediyl;

[0169] R24is C1-3 alkyl; and

[0170] R23is H or C1-3 alkyl, and R15is H or C1-3 alkyl, or R23is a bond or C1-3 alkanediyl, and R15is a bond or C1-3 alkanediyl and R23is linked to R15to form a ring; or R14is -X9C(O)X11-, R15is a bond or C1-3 alkanediyl, and X11is linked to R15to form a ring, wherein

[0171] X9is a bond or -N(R29)-;

[0172] R29is C1-3 alkyl; X11is -0-, C1-3 alkanediyl, or -N(R30)-; and

[0173] R30is C1-3 alkyl;

[0174] R16is H or C1-3 alkyl;

[0175] X4is C(R17)(R18), O or C(O);

[0176] R17is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F;

[0177] R18is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F;

[0178] X5is C(R19)(R20) or a bond;

[0179] R19is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F;

[0180] R20is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F;

[0181] X6is a bond or C(R21)(R22);

[0182] R21is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; and

[0183] R22is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; any two of R7, R8, R9, R10, R17, R18, R19, R20, R21, and R22are optionally linked together to form a ring, with the proviso that when X4is O, then X3is C(R12)C(O)R13and R13is NH2, N(H)(CH3) or N(CH3)2; with the proviso that when X3is N(R16), then X4is C(O), and with the proviso that when X4is C(O), then X3is N(R16), or a pharmaceutically acceptable salt thereof.

[0184] In some embodiments, when X3is N(C(O)R11)or N(R16), then X2is not a bond. In some embodiments, when X3is N(C(O)R11)or N(R16), then X5and X6are not both bonds.

[0185] In one aspect, the present invention relates to a compound of Formula (I),

[0186] Formula (I) wherein

[0187] R1is halogen or H;

[0188] R2is halogen;

[0189] R3is H or halogen;

[0190] R5is H or halogen; R6is H or halogen;

[0191] R4is of Formula (II):

[0192] Formula (II) wherein

[0193] X1is C(R7)(R8);

[0194] R7is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F;

[0195] R8is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F;

[0196] X2is C(R9)(R10) or a bond;

[0197] X3is N(C(O)R11), C(R12)(C(O)R13), C(R14)(R15) or N(R16);

[0198] R9is H, C1-3 alkyl optionally substituted with 1 to 3 halogens, or halogen, such as F;

[0199] R10is H, C1-3 alkyl optionally substituted with 1 to 3 halogens, or halogen, such as F;

[0200] R11is selected from the group consisting of C1-3 alkyl, C3-5 cycloalkyl, C1-3 alkoxy, pyridinyl, azetidinyl and pyrrolidinyl, wherein

[0201] • said C1-3 alkyl is optionally substituted with one or more substituents individually selected from the group consisting of NH2, N(H)(CH3), N(CH3)2, C1-3 alkoxy, and morpholinyl,

[0202] • said pyridinyl is optionally substituted with one or more NH2;

[0203] • said pyrrolidinyl is optionally substituted with one or more substituents individually selected from the group consisting of C1-3 alkyl, halogen, C1-3 alkoxy, NH2, N(H)(CH3), N(CH3)2 and azetidinyl, and said azetidinyl is optionally substituted with one or more halogens, and

[0204] • said azetidinyl optionally substituted with NH2; or R11is linked to R9to form a ring and

[0205] R9is a bond or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl,

[0206] R10is H, C1-3 alkyl optionally substituted with 1 to 3 halogens, or halogen, such as F, and

[0207] R11is C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl, wherein one methylene group of the C1-3 alkanediyl is optionally replaced by -O- or -N(R28)-, wherein R28is H or C1-3 alkyl; or R11is linked to R10to form a ring and

[0208] R9is H, C1-3 alkyl optionally substituted with 1 to 3 halogens, or halogen, such as F,

[0209] R10is a bond or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl, and R11is C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl, wherein one methylene group of the C1-3 alkanediyl is optionally replaced by -O- or -N(R28)-, wherein R28is H or C1-3 alkyl;

[0210] R12is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F;

[0211] R13is selected from the group consisting of NH2, N(H)(CH3), N(CH3)2, pyrrolidinyl, azetidinyl, and piperazinyl, wherein

[0212] • said pyrrolidinyl is optionally substituted with one or more substituents individually selected from the group consisting of halogen, NH2, N(H)(CH3), N(CH3)2 and azetidinyl, and said azetidinyl is optionally substituted with one or more halogens, and

[0213] • said azetidinyl optionally substituted with NH2;

[0214] R14is -X7N(R23)(C(O)R24), wherein

[0215] X7is a bond or C1-3 alkanediyl;

[0216] R24is C1-3 alkyl; and

[0217] R23is H or C1-3 alkyl, and R15is H or C1-3 alkyl, or R23is a bond or C1-3 alkanediyl, and R15is a bond or C1-3 alkanediyl and R23is linked to R15to form a ring; or R14is -X9C(O)X11-, R15is a bond or C1-3 alkanediyl, and X11is linked to R15to form a ring, wherein

[0218] X9is a bond or -N(R29)-;

[0219] R29is C1-3 alkyl;

[0220] X11is -O-, C1-3 alkanediyl, or -N(R30)-; and

[0221] R30is C1-3 alkyl;

[0222] R16is H or C1-3 alkyl;

[0223] X4is C(R17)(R18), O or C(O);

[0224] R17is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F;

[0225] R18is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; X5is C(R19)(R20) or a bond;

[0226] R19is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F;

[0227] R20is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F;

[0228] X6is a bond or C(R21)(R22);

[0229] R21is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; and

[0230] R22is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; any two of R7, R8, R9, R10, R17, R18, R19, R20, R21, and R22are optionally linked together to form a ring; with the proviso that when X4is O, then X3is C(R12)(C(O)R13) and R13is NH2, N(H)(CH3) or N(CH3)2; with the proviso that when X3is N(R16), then X4is C(O), with the proviso that when X4is C(O), then X3is N(R16), with the proviso that when X3is N(C(O)R11) or N(R16), then X2is not a bond, and with the proviso that when X3is N(C(O)R11) or N(R16), then X5and X6are not both bonds, or a pharmaceutically acceptable salt thereof.

[0231] In one aspect, the present invention relates to a compound of Formula (I),

[0232] Formula (I) wherein

[0233] R1is halogen or H;

[0234] R2is halogen;

[0235] R3is H or halogen;

[0236] R5is H or halogen;

[0237] R6is H or halogen;

[0238] R4is of Formula (II): Formula (II) wherein

[0239] X1is C(R7)(R8);

[0240] R7is H, C1-3 alkyl optionally substituted with 1 to 3 F, or F;

[0241] R8is H, C1-3 alkyl optionally substituted with 1 to 3 F, or F;

[0242] X2is C(R9)(R10) or a bond;

[0243] R9is H, C1-3 alkyl optionally substituted with 1 to 3 F, or F;

[0244] R10is H, C1-3 alkyl optionally substituted with 1 to 3 F, or F;

[0245] X3is N(C(O)R11), C(R12)(C(O)R13), C(R14)(R15) or N(R16);

[0246] R11is selected from the group consisting of C1-3 alkyl, C3-5 cycloalkyl, C1-3 alkoxy, pyridinyl, azetidinyl and pyrrolidinyl, a. said C1-3 alkyl is optionally substituted with one or more substituents individually selected from the group consisting of NH2, N(H)(CH3), N(CH3)2 and C1-3 alkoxy, b. said pyridinyl is optionally substituted with one or more NH2; c. said pyrrolidinyl is optionally substituted with one or more substituents individually selected from the group consisting of NH2, N(H)(CH3), N(CH3)2 and azetidinyl, and said azetidinyl is optionally substituted with one or more halogens, and d. said azetidinyl optionally substituted with NH2; e. when R11is C1-3 alkyl or C1-3 alkoxy, then R11is optionally linked to R9or R10to form a ring;

[0247] R12is H, C1-3 alkyl optionally substituted with 1 to 3 F, or F;

[0248] R13is selected from the group consisting of NH2, N(H)(CH3), N(CH3)2, pyrrolidinyl, azetidinyl, and piperazinyl, wherein a. said pyrrolidinyl is optionally substituted with one or more substituents individually selected from the group consisting of NH2, N(H)(CH3), N(CH3)2 and azetidinyl, and said azetidinyl is optionally substituted with one or more halogens, and b. said azetidinyl optionally substituted with NH2;

[0249] R14is -X7N(R23)(C(O)R24);

[0250] X7is a bond or CH2;

[0251] R23is H or C1-3 alkyl, or R23is a bond and R15is C1-3 alkanediyl and R23is linked to R15to form a 4 or 5 membered ring;

[0252] R24is C1-3 alkyl; R15is H or C1-3 alkyl;

[0253] R16is H or C1-3 alkyl;

[0254] X4is C(R17)(R18), O or C(O);

[0255] R17is H, C1-3 alkyl optionally substituted with 1 to 3 F, or F;

[0256] R18is H, C1-3 alkyl optionally substituted with 1 to 3 F, or F;

[0257] X5is C(R19)(R20) or a bond;

[0258] R19is H, C1-3 alkyl optionally substituted with 1 to 3 F, or F;

[0259] R20is H, C1-3 alkyl optionally substituted with 1 to 3 F, or F;

[0260] X6is a bond or C(R21)(R22);

[0261] R21is H, C1-3 alkyl optionally substituted with 1 to 3 F, or F; and

[0262] R22is H, C1-3 alkyl optionally substituted with 1 to 3 F, or F; any two of R7, R8, R9, R10, R17, R18, R19, R20, R21, and R22are optionally linked together to form a ring; with the proviso that when X4is O, then X3is C(R12)(C(O)R13) and R13is NH2, N(H)(CH3) or N(CH3)2; with the proviso that when X3is N(R16), then X4is C(O), and with the proviso that when X4is C(O), then X3is N(R16), or a pharmaceutically acceptable salt thereof.

[0263] Thus, in said aspect, the current invention relates to a compound of Formula (XIII):

[0264] Formula (XIII) wherein R1, R2, R3, R5, R6, X1, X2, X3, X4, X5, and X6, are as defined herein, or a pharmaceutically acceptable salt thereof.

[0265] In one aspect, the present invention relates to a compound of Formula (I), wherein R1, R2, R3, R4, R5, and R6are as defined herein, or a pharmaceutically acceptable salt thereof.

[0266] In one aspect, the present invention relates to a compound of Formula (LVII),

[0267] Formula (LVII) wherein

[0268] R1is halogen or H;

[0269] R2is halogen;

[0270] R3is H or halogen;

[0271] R5is H or halogen;

[0272] R6is H or halogen; wherein R9and R11or R10and R11are optionally joined together to form a ring together with the intervening atoms;

[0273] R7is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F;

[0274] R8is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F;

[0275] R9is H, C1-3 alkyl optionally substituted with 1 to 3 halogens, or halogen, such as F, or when R9is linked to R11to form a ring, then R9is a bond or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl;

[0276] R10is H, C1-3 alkyl optionally substituted with 1 to 3 halogens, or halogen, such as F, or when R10is linked to R11to form a ring, then R10is a bond or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1- 3 alkyl;

[0277] R11is selected from the group consisting of C1-3 alkyl, C3-5 cycloalkyl, C1-3 alkoxy, pyridinyl, azetidinyl, pyrrolidinyl, oxetanyl, and morpholinyl, wherein

[0278] • said C1-3 alkyl is optionally substituted with one or more substituents individually selected from the group consisting of NH2, N(H)(CH3), N(CH3)2, C1-3 alkoxy, morpholinyl, azetidinyl, -O-azetidinyl, and -O- oxetanyl, and said azetidinyl is optionally substituted with one or more substituents selected from halogen, C1-3 alkoxy, and C1-3 alkyl;

[0279] • said C3-5 cycloalkyl is optionally substituted with one or more substituents selected from halogen, and C1-3 alkoxy;

[0280] • said pyridinyl is optionally substituted with one or more NH2; ● said pyrrolidinyl is optionally substituted with one or more substituents individually selected from the group consisting of C1-3alkyl, halogen, C1-3alkoxy, C1-3haloalkyl, NH2, N(H)(CH3), N(CH3)2and azetidinyl, and said azetidinyl is optionally substituted with one or more halogens; ● said azetidinyl optionally substituted with one or more substituents selected from halogen, C1-3 alkyl, and NH2; and ● said morpholinyl is optionally substituted with C1-3alkyl; or when R11is linked to R9or R10to form a ring, then R11is -O-, -N(R28)-, or C1-3alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl, wherein one methylene group of the C1-3alkanediyl is optionally replaced by -O- or -N(R28)-, wherein R28is H or C1-3alkyl; R17is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R18is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R19is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R20is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; and any two of R7, R8, R9, R10, R17, R18, R19, and R20, are optionally linked together to form a ring; or a pharmaceutically acceptable salt thereof. In one aspect, the present invention relates to a compound of Formula (LVII), Formula (LVII) wherein R1is halogen or H; R2is halogen; R3is halogen; R5, R6, R8, R17, R18, R19, and R20are H; wherein R9and R11or R10and R11are optionally joined together via R33to form a ring together with the intervening atoms; R7is H or C1-3alkyl optionally substituted with 1 to 3 F; R10is H, or when R10is linked to R11to form a ring, then R10is a bond or a C1-3alkanediyl; R9is H, or when R9is linked to R11to form a ring, then R9is a bond or a C1-3alkanediyl; R11is -X13-R33; X13is a bond, C1-3alkanediyl optionally substituted with C1-3alkyl, -O-, or C1-3alkanediyl- O-; and R33is C1-3alkyl, azetidinyl, pyrrolidinyl, oxetanyl, and tetrahydrofuranyl, each of which is optionally substituted with one or more F; or when R11is linked to R9or R10via R33to form a ring, then R33is a bond or a C1-3alkanediyl, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (LVII) is of Formula LVIIa): . Formula (LVIIa) In one aspect, the present invention relates compound of Formula (I), wherein R1is halogen or H; R2is halogen; R3is H or halogen; R5is H or halogen; R6is H or halogen; R4is of Formula (XXIV), Formula (XXV), Formula (XXVI) or Formula (XXVII): wherein R7is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R8is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; X3is N(C(O)R11), C(R12)(C(O)R13), C(R14)(R15) or N(R16); R9is H, C1-3 alkyl optionally substituted with 1 to 3 halogens, or halogen, such as F; R10is H, C1-3 alkyl optionally substituted with 1 to 3 halogens, or halogen, such as F; R11is selected from the group consisting of C1-3 alkyl, C3-5 cycloalkyl, C1-3 alkoxy, pyridinyl, azetidinyl and pyrrolidinyl, wherein ^ said C1-3alkyl is optionally substituted with one or more substituents individually selected from the group consisting of NH2, N(H)(CH3), N(CH3)2, C1-3alkoxy, and morpholinyl, ^ said pyridinyl is optionally substituted with one or more NH2; ^ said pyrrolidinyl is optionally substituted with one or more substituents individually selected from the group consisting of C1-3 alkyl, halogen, C1-3 alkoxy, NH2, N(H)(CH3), N(CH3)2 and azetidinyl, and said azetidinyl is optionally substituted with one or more halogens, and ^ said azetidinyl optionally substituted with NH2; or R11is linked to R9to form a ring and R9is a bond or a C1-3alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl, R10is H, C1-3alkyl optionally substituted with 1 to 3 halogens, or halogen, such as F, and R11is C1-3alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl, wherein one methylene group of the C1-3alkanediyl is optionally replaced by -O- or -N(R28)-, wherein R28is H or C1-3alkyl; or R11is linked to R10to form a ring and R9is H, C1-3alkyl optionally substituted with 1 to 3 halogens, or halogen, such as F, R10is a bond or a C1-3alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl, and R11is C1-3alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl, wherein one methylene group of the C1-3alkanediyl is optionally replaced by -O- or -N(R28)-, wherein R28is H or C1-3 alkyl; R12is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R13is selected from the group consisting of NH2, N(H)(CH3), N(CH3)2, pyrrolidinyl, azetidinyl, and piperazinyl, wherein ^ said pyrrolidinyl is optionally substituted with one or more substituents individually selected from the group consisting of halogen, NH2, N(H)(CH3), N(CH3)2 and azetidinyl, and said azetidinyl is optionally substituted with one or more halogens, and ^ said azetidinyl optionally substituted with NH2; R14is -X7N(R23)(C(O)R24), wherein X7is a bond or C1-3alkanediyl; R24is C1-3alkyl; and R23is H or C1-3alkyl, and R15is H or C1-3alkyl, or R23is a bond or C1-3alkanediyl, and R15is a bond or C1-3alkanediyl and R23is linked to R15to form a ring; or R14is -X9C(O)X11-, R15is a bond or C1-3alkanediyl, and X11is linked to R15to form a ring, wherein X9is a bond or -N(R29)-; R29is C1-3 alkyl; X11is -O-, C1-3alkanediyl, or -N(R30)-; and R30is C1-3alkyl; R16is H or C1-3alkyl; X4is C(R17)(R18), O or C(O); R17is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R18is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R19is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R20is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R21is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R22is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; and any two of R7, R8, R9, R10, R17, R18, R19, R20, R21, and R22are optionally linked together to form a ring; or a pharmaceutically acceptable salt thereof. In some embodiments, R4is of Formula (XXV), and X3is C(R12)(C(O)R13) or C(R14)(R15). In some embodiments, R4is of Formula (XXVI), and X3is C(R12)(C(O)R13) or C(R14)(R15). In some embodiments, R4is of Formula (XXVII), and X3is C(R12)(C(O)R13) or C(R14)(R15). In some embodiments, R4is of Formula (XXIV), and X4is C(R17)(R18) or C(O). In one aspect, the present invention relates to a compound of Formula (I), Formula (I) wherein R1is halogen or H; R2is halogen; R3is H or halogen; R5is H or halogen; R6is H or halogen; R4is of Formula (III), Formula (XXXIV), Formula (XXXV), Formula (XXXVI), Formula (XXXVII), Formula (XXXVIII), Formula (XXXIX), or Formula (XL):

[0281] Formula (XXXIX)Formula (XL)wherein R7is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R8is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R9is H, C1-3 alkyl optionally substituted with 1 to 3 halogens, or halogen, such as F; R10is H, C1-3alkyl optionally substituted with 1 to 3 halogens, or halogen, such as F; R11is selected from the group consisting of C1-3alkyl, C3-5cycloalkyl, C1-3alkoxy, pyridinyl, azetidinyl and pyrrolidinyl, wherein ^ said C1-3alkyl is optionally substituted with one or more substituents individually selected from the group consisting of NH2, N(H)(CH3), N(CH3)2, C1-3alkoxy, and morpholinyl, ^ said pyridinyl is optionally substituted with one or more NH2; ^ said pyrrolidinyl is optionally substituted with one or more substituents individually selected from the group consisting of C1-3alkyl, halogen, C1-3alkoxy, NH2, N(H)(CH3), N(CH3)2and azetidinyl, and said azetidinyl is optionally substituted with one or more halogens, and ^ said azetidinyl optionally substituted with NH2; or R11is linked to R9to form a ring and R9is a bond or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl, R10is H, C1-3alkyl optionally substituted with 1 to 3 halogens, or halogen, such as F, and R11is C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl, wherein one methylene group of the C1-3 alkanediyl is optionally replaced by -O- or -N(R28)-, wherein R28is H or C1-3 alkyl; or R11is linked to R10to form a ring and R9is H, C1-3 alkyl optionally substituted with 1 to 3 halogens, or halogen, such as F, R10is a bond or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl, and R11is C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl, wherein one methylene group of the C1-3 alkanediyl is optionally replaced by -O- or -N(R28)-, wherein R28is H or C1-3 alkyl; R12is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R13is selected from the group consisting of NH2, N(H)(CH3), N(CH3)2, pyrrolidinyl, azetidinyl, and piperazinyl, wherein ^ said pyrrolidinyl is optionally substituted with one or more substituents individually selected from the group consisting of halogen, NH2, N(H)(CH3), N(CH3)2and azetidinyl, and said azetidinyl is optionally substituted with one or more halogens, and ^ said azetidinyl optionally substituted with NH2; R14is -X7N(R23)(C(O)R24), wherein X7is a bond or C1-3alkanediyl; R24is C1-3alkyl; and R23is H or C1-3 alkyl, and R15is H or C1-3 alkyl, or R23is a bond or C1-3 alkanediyl, and R15is a bond or C1-3 alkanediyl and R23is linked to R15to form a ring; or R14is -X9C(O)X11-, R15is a bond or C1-3 alkanediyl, and X11is linked to R15to form a ring, wherein X9is a bond or -N(R29)-; R29is C1-3 alkyl; X11is -O-, C1-3 alkanediyl, or -N(R30)-; and R30is C1-3 alkyl; R16is H or C1-3 alkyl; R17is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R18is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R19is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R20is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R21is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; and R22is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; and any two of R7, R8, R9, R10, R17, R18, R19, R20, R21, and R22are optionally linked together to form a ring, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is a KV1.3 potassium channel inhibitor. In some embodiments, R1is halogen. In some embodiments, R1is Cl. In some embodiments, R1is F. In some embodiments, R1is H. In some embodiments, R2is Cl. In some embodiments, R3is halogen. In some embodiments, R3is Cl. In some embodiments, R3is F. In some embodiments, R3is H. In some embodiments, R5is H. In some embodiments, R5is halogen. In some embodiments, R5is F. In some embodiments, R6is H. In some embodiments, R6is halogen. In some embodiments, R6is F. In some embodiments, R1is F or Cl, R2is Cl, R3is Cl, R5is H, and R6is H. In some embodiments, R5is H and R6is H. In some embodiments, R1is halogen, and R2is halogen. In some embodiments, R2is halogen, and R3is halogen. In some embodiments, R1is halogen, R2is halogen, and R3is halogen. In some embodiments, R1is halogen, R2is halogen, R3is halogen, R5is H, and R6is H. In some embodiments, R1is halogen, R2is halogen, R3is H, R5is H, and R6is H. In some embodiments, R1is halogen, R2is halogen, R3is H, R5is halogen, and R6is H. In some embodiments, R1is halogen, R2is halogen, R3is H, R5is H, and R6is halogen. In some embodiments, R1is H, R2is halogen, R3is halogen, R5is H, and R6is H. In some embodiments, R1is F or Cl, R2is Cl or F, and R3is Cl or F. In some embodiments, R1is F, R2is Cl, and R3is Cl. In some embodiments, R1is F, R2is Cl, and R3is F. In some embodiments, R1is Cl, R2is Cl, and R3is Cl. In some embodiments, R1is Cl, R2is Cl, and R3is F. In some embodiments, R1is F or Cl, R2is Cl or F, and R3is Cl or F, R5is H, and R6is H. In some embodiments, R1is F, R2is Cl, R3is Cl, R5is H, and R6is H. In some embodiments, R1is F, R2is Cl, R3is F, R5is H, and R6is H. In some embodiments, R1is Cl, R2is Cl, R3is Cl, R5is H, and R6is H. In some embodiments, R1is Cl, R2is Cl, R3is F, R5is H, and R6is H. In some embodiments, R1is Cl, R2is Cl, R3is H, R5is F, and R6is H. In some embodiments, R1is Cl, R2is Cl, R3is H, R5is H, and R6is F. In some embodiments, R1is Cl, R2is Cl, R3is H, R5is H, and R6is H. In some embodiments, R1is F, R2is Cl, R3is H, R5is H, and R6is H. In some embodiments, R1is H, R2is Cl, R3is Cl, R5is H, and R6is H. In some embodiments, X6is a bond. In some embodiments, X7is a bond. In some embodiments, X7is C1-3 alkanediyl. In some embodiments, X7is CH2. In some embodiments, X2is C(R9)(R10); X5is C(R19)(R20); and X6is a bond. In some embodiments, R4is of Formula (XXIV): , Formula (XXIV) wherein R7, R8, R9, R10, R19, R20, X3, and X4are as defined herein. In some embodiments, R4is of Formula (XXIV), wherein R7, R8, R9, R10, R19, R20, and X3are as defined herein, and X4is C(R17)(R18) or C(O). In some embodiments, X2is C(R9)(R10); X4is C(R17)(R18); X5is C(R19)(R20); and X6is a bond. In some embodiments, R4is of Formula (XXVIII): , Formula (XXVIII) wherein R7, R8, R9, R10, R17, R18, R19, R20, and X3are as defined herein. In some embodiments, X2is C(R9)(R10); X3is N(C(O)R11); X4is C(R17)(R18); X5is C(R19)(R20); and X6is a bond. In some embodiments, R4is of Formula (III): Formula (III) wherein R7, R8, R9, R10, R11, R17, R18, R19, and R20are as defined herein. In some embodiments, R4is of Formula (IV): Formula (IV) wherein R7, R8, R9, R10, R11, R17, R18, R19, and R20are as defined herein. In some embodiments, R7, R8, R9, R10, R17, R18, R19, and R20are H. In some embodiments, R4is of Formula (V): Formula (V) wherein R11is as defined herein. In some embodiments, R7is C1-3alkyl, such as CH3, and R8, R9, R10, R17, R18, R19, and R20are H. In some embodiments, R8is C1-3alkyl, such as CH3, and R7, R9, R10, R17, R18, R19, and R20are H. In some embodiments, R7and R8are C1-3alkyl, such as CH3, and R9, R10, R17, R18, R19, and R20are H. In some embodiments, R17is C1-3alkyl, such as CH3, and R7, R8, R9, R10, R18, R19, and R20are H. In some embodiments, R18is C1-3 alkyl, such as CH3, and R7, R8, R9, R10, R17, R19, and R20are H. In some embodiments, R17and R18are C1-3 alkyl, such as CH3, and R7, R8, R9, R10, R19, and R20are H. In some embodiments, R8and R17are C1-3 alkyl, such as CH3, and R7, R9, R10, R18, R19, and R20are H. In some embodiments, when R11is linked to R9or R10to form a ring, then R9or R10is linked to R33of R11, i.e. R9or R10and R11are joined together via R33to form a ring together with the intervening atoms. In some embodiments, R9is linked to R33to form a ring. In some embodiments, R10is linked to R33to form a ring. In some embodiments, R11is C1-3 alkyl or C1-3 alkoxy; R9is H; R10is a bond; and R11is linked to R10to form a ring. In some embodiments, R11is C1-3 alkyl or C1-3 alkoxy; R10is H; R9is a bond; and R11is linked to R9to form a ring. In some embodiments, X2is C(R9)(R10); X3is N(R16); X4is C(O); X5is C(R19)(R20); and X6is a bond. In some embodiments, R4is of Formula (XXXIV): Formula (XXXIVI) wherein R7, R8, R9, R10, R16, R19, and R20are as defined herein. In some embodiments, R4is of Formula (XLI): Formula (XLI) wherein R7, R8, R9, R10, R16, R19, and R20are as defined herein. In some embodiments, R4is of Formula (VI): , Formula (VI) wherein R16is H or C1-3 alkyl; and R27is H or C1-3 alkyl. In some embodiments, R4is of Formula (VIA-1): , Formula (VIA-1) wherein R16is H or C1-3 alkyl; and R27is H or C1-3 alkyl. In some embodiments, R4is of Formula (VIA-2): , Formula (VIA-2) wherein R16is H or C1-3 alkyl; and R27is H or C1-3 alkyl. In some embodiments, R4is of Formula (VIB-1): , Formula (VIB-1) wherein R16is H or C1-3 alkyl; and R27is H or C1-3 alkyl. In some embodiments, R4is of Formula (VIB-2): , Formula (VIB-2) wherein R16is H or C1-3alkyl; and R27is H or C1-3alkyl. In some embodiments, R7and R19are linked together to form a bridged bicyclic ring. In some embodiments, R8and R20are linked together to form a bridged bicyclic ring. In some embodiments, R9and R17are linked together to form a bridged bicyclic ring. In some embodiments, R10and R18are linked together to form a bridged bicyclic ring. In some embodiments, R9and R19are linked together to form a bridged bicyclic ring. In some embodiments, R10and R20are linked together to form a bridged bicyclic ring. In some embodiments, R7and R17are linked together to form a bridged bicyclic ring. In some embodiments, R8and R18are linked together to form a bridged bicyclic ring. In some embodiments, X2is C(R9)(R10); X3is N(C(O)R11); X4is C(R17)(R18); X5is C(R19)(R20); X6is a bond; and R7and R19are linked together to form a bridged bicyclic ring. In some embodiments, X2is C(R9)(R10); X3is N(C(O)R11); X4is C(R17)(R18); X5is C(R19)(R20); X6is a bond; and R8and R20are linked together to form a bridged bicyclic ring or a pharmaceutically acceptable salt thereof. In some embodiments, X2is C(R9)(R10); X3is N(C(O)R11); X4is C(R17)(R18); X5is C(R19)(R20); X6is a bond; and R9and R17are linked together to form a bridged bicyclic ring or a pharmaceutically acceptable salt thereof. In some embodiments, X2is C(R9)(R10); X3is N(C(O)R11); X4is C(R17)(R18); X5is C(R19)(R20); X6is a bond; and R10and R18are linked together to form a bridged bicyclic ring or a pharmaceutically acceptable salt thereof. In some embodiments, X2is C(R9)(R10); X3is N(C(O)R11); X4is C(R17)(R18); X5is C(R19)(R20); X6is a bond; and R9and R19are linked together to form a bridged bicyclic ring or a pharmaceutically acceptable salt thereof. In some embodiments, X2is C(R9)(R10); X3is N(C(O)R11); X4is C(R17)(R18); X5is C(R19)(R20); X6is a bond; and R10and R20are linked together to form a bridged bicyclic ring or a pharmaceutically acceptable salt thereof. In some embodiments, X2is C(R9)(R10); X3is N(C(O)R11); X4is C(R17)(R18); X5is C(R19)(R20); X6is a bond; and R7and R17are linked together to form a bridged bicyclic ring or a pharmaceutically acceptable salt thereof. In some embodiments, X2is C(R9)(R10); X3is N(C(O)R11); X4is C(R17)(R18); X5is C(R19)(R20); X6is a bond; and R8and R18are linked together to form a bridged bicyclic ring or a pharmaceutically acceptable salt thereof. In some embodiments, R4is of Formula (VII), Formula (VIII) or Formula (IX): wherein R11is as defined herein and w is 1 or 2. In some embodiments, R4is of Formula (VII). In some embodiments, R4is of Formula (VII) and w is 1. In some embodiments, R4is of Formula (VII) and w is 2. In some embodiments, Formula (VIII). In some embodiments, R4is of Formula (VIII) and w is 1. In some embodiments, R4is of Formula (VIII) and w is 2. In some embodiments, R4is of Formula (IX). In some embodiments, R4is of Formula (IX) and w is 2. In some embodiments, X2is a bond; X5is C(R19)(R20); and X6is C(R21)(R22). In some embodiments, R4is of Formula (XXVII): , Formula (XXVII) wherein R7, R8, R19, R20, R21, R22, X3and X4are as defined herein. In some embodiments, R4is of Formula (XXVII), wherein R7, R8, R19, R20, R21, R22, X4are as defined herein, and X3is C(R12)(C(O)R13), or C(R14)(R15). In some embodiments, R4is of Formula (XXXI): , Formula (XXXI) wherein R7, R8, R19, R20, R21, R22, X3and X4are as defined herein. In some embodiments, R4is of Formula (XXXI), wherein R7, R8, R19, R20, R21, R22, X4are as defined herein, and X3is C(R12)(C(O)R13), or C(R14)(R15). In some embodiments, X2is a bond; X4is C(R17)(R18); X5is C(R19)(R20); and X6is C(R21)(R22). In some embodiments, R4is of Formula (XXXII): , Formula (XXXII) wherein R7, R8, R17, R18, R19, R20, R21, R22, and X3are as defined herein. In some embodiments, X2is a bond; X3is C(R12)(C(O)R13); X4is C(R17)(R18); X5is C(R19)(R20); and X6is C(R21)(R22). In some embodiments, R4is of Formula (XXXIX): Formula (XXXIX) wherein R7, R8, R9, R10, R12, R13, R17, and R18are as defined herein. In some embodiments, R4is of Formula ( Formula (XLVII) wherein R7, R8, R9, R10, R12, R13, R17, and R18are as defined herein. In some embodiments, R4is of Formula (XLVIII): Formula (XLVIII) wherein R7, R8, R9, R10, R12, R13, R17, and R18are as defined herein. In some embodiments, X2is C(R9)(R10); X3is C(R14)(R15); X4is C(R17)(R18); X5is C(R19)(R20); and X6is a bond. In some embodiments, R4is of Formula (XXXV): Formula (XXXV) wherein R7, R8, R9, R10, R14, R15, R17, R18, R19, and R20are as defined herein. In some embodiments, R4is of Formula ( Formula (XLII) wherein R7, R8, R9, R10, R14, R15, R17, R18, R19, and R20are as defined herein. In some embodiments, X2is a bond; X4is O; X5is C(R19)(R20); and X6is C(R21)(R22). In some embodiments, R4is of Formula (XXXIII): , Formula (XXXIII) wherein R7, R8, R19, R20, R21, R22, and X3are as defined herein. In some embodiments, R4is of Formula (XXXIII), wherein R7, R8, R19, R20, R21, R22are as defined herein, and X3is C(R12)(C(O)R13) or C(R14)(R15). In some embodiments, X2is a bond; X3is C(R12)(C(O)R13); X4is O; X5is C(R19)(R20); and X6is C(R21)(R22). In some embodiments, R4is of Formula (XL): Formula (XL) wherein R7, R8, R12, R13, R19, R20, R21, and R22are as defined herein. In some embodiments, R4is of Formula (XLIX): Formula (XLIX) wherein R7, R8, R12, R13, R19, R20, R21, and R22are as defined herein. In some embodiments, R4is of Formula (L): Formula (L) wherein R7, R8, R12, R13, R19, R20, R21, and R22are as defined herein. In some embodiments, X2is C(R9)(R10); X4is C(R17)(R18); X5is a bond; and X6is bond. In some embodiments, R4is of Formula (XXVI): , Formula (XXVI) wherein R7, R8, R9, R10, R17, R18, and X3are as defined herein. In some embodiments, R4is of Formula (XXVI), wherein R7, R8, R9, R10, R17, R18are as defined herein, and X3is C(R12)(C(O)R13) or C(R14)(R15). In some embodiments, R4is of Formula (XXX): , Formula (XXX) wherein R7, R8, R9, R10, R17, R18, and X3are as defined herein. In some embodiments, R4is of Formula (XXX), wherein R7, R8, R9, R10, R17, R18are as defined herein, and X3is C(R12)(C(O)R13) or C(R14)(R15). In some embodiments, X2is C(R9)(R10); X3is C(R12)(C(O)R13); X4is C(R17)(R18); X5is a bond; and X6is bond. In some embodiments, R4is of Formula (XXXVIII): Formula (XXXVIII) wherein R7, R8, R9, R10, R12, R13, R17, and R18are as defined herein. In some embodiments, R4is of Formula (XLV): Formula (XLV) wherein R7, R8, R9, R10, R12, R13, R17, and R18are as defined herein. In some embodiments, R4is of Formula (XLVI): Formula (XLVI) wherein R7, R8, R9, R10, R12, R13, R17, and R18are as defined herein. In some embodiments, R4is of Formula (Xa) or Formula (Xb): Formula (Xa)Formula (Xb)wherein R12and R13are as defined herein. In some embodiments, X2is C(R9)(R10); X3is C(R12)(C(O)R13); and R13is linked to R9to form a ring together with the intervening atoms. In some embodiments, X2is C(R9)(R10); X3is C(R12)(C(O)R13); X4is C(R17)(R18); and R13is linked to R9to form a ring together with the intervening atoms. In some embodiments, X2is C(R9)(R10); X3is C(R12)(C(O)R13); X4is C(R17)(R18); X6is a bond; and R13is linked to R9to form a ring together with the intervening atoms. In some embodiments, X2is C(R9)(R10); X3is C(R12)(C(O)R13); X4is C(R17)(R18); X5is a bond; X6is a bond; and R13is linked to R9to form a ring together with the intervening atoms. In some embodiments, R4is of Formula (LIII): Formula (LIII) wherein R7is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R8is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R9is a bond or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl; R10is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R12is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R13is -N(R28)-, wherein R28is H or C1-3 alkyl; R17is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; and R18is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F. In some embodiments, R4is of Formula (LIIIa): Formula (LIIIa) wherein R7, R8, R9, R10, R12, R13, R17, and R18are as defined herein. In some embodiments, the moiety of Formula (LIII) is of Formula (LIIIa). In some embodiments, R4is of Formula (LIII) or Formula (LIIIa) and R7, R8, R10, R12, R17, and R18are H. In some embodiments, R4is of Formula (LIII) or Formula (LIIIa) and R13is -N(CH3)-. In some embodiments, R4is of Formula (LIII) or Formula (LIIIa) and R9is -CH2-. In some embodiments, X2is C(R9)(R10); X3is C(R12)(C(O)R13); and R13is linked to R10to form a ring together with the intervening atoms. In some embodiments, X2is C(R9)(R10); X3is C(R12)(C(O)R13); X4is C(R17)(R18); and R13is linked to R10to form a ring together with the intervening atoms. In some embodiments, X2is C(R9)(R10); X3is C(R12)(C(O)R13); X4is C(R17)(R18); X6is a bond; and R13is linked to R10to form a ring together with the intervening atoms. In some embodiments, X2is C(R9)(R10); X3is C(R12)(C(O)R13); X4is C(R17)(R18); X5is a bond; X6is a bond; and R13is linked to R10to form a ring together with the intervening atoms. In some embodiments, R4is of Formula (LIV): Formula (LIV) wherein R7is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R8is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R9is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R10is a bond or a C1-3alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl; R12is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R13is -N(R28)-, wherein R28is H or C1-3alkyl; R17is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; and R18is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F. In some embodiments, R4is of Formula (LIVa): Formula (LIVa) wherein R7, R8, R9, R10, R12, R13, R17, and R18are as defined herein. In some embodiments, the moiety of Formula (LIV) is of Formula (LIVa). In some embodiments, R4is of Formula (LIV) or Formula (LIVa) and R7, R8, R9, R12, R17, and R18are H. In some embodiments, R4is of Formula (LIV) or Formula (LIVa) and R13is -N(CH3)-. In some embodiments, R4is of Formula (LIV) or Formula (LIVa) and R10is -CH2-. In some embodiments, X2is a bond; X4is C(R17)(R18); X5is C(R19)(R20); and X6is bond. In some embodiments, R4is of Formula (XXV): , Formula (XXV) wherein R7, R8, R17, R18, R19, R20, and X3are as defined herein. In some embodiments, R4is of Formula (XXV), wherein R7, R8, R17, R18, R19, R20are as defined herein, and X3is C(R12)(C(O)R13) or C(R14)(R15). In some embodiments, R4is of Formula (XXIX): , Formula (XXIX) wherein R7, R8, R17, R18, R19, R20, and X3are as defined herein. In some embodiments, R4is of Formula (XXIX), wherein R7, R8, R17, R18, R19, R20are as defined herein, and X3is C(R12)(C(O)R13) or C(R14)(R15). In some embodiments, X3is C(R12)(C(O)R13); X4is C(R17)(R18); and R13is linked to R17to form a ring together with the intervening atoms. In some embodiments, X2is a bond; X3is C(R12)(C(O)R13); X4is C(R17)(R18); and R13is linked to R17to form a ring together with the intervening atoms. In some embodiments, X2is a bond; X3is C(R12)(C(O)R13); X4is C(R17)(R18); X5is C(R19)(R20); X6is C(R21)(R22); and R13is linked to R17to form a ring together with the intervening atoms. In some embodiments, R4is of Formula (LV): Formula (LV) wherein R7is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R8is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R12is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R13is -N(R28)-, wherein R28is H or C1-3alkyl; R17is a bond or a C1-3alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl; R18is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R19is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R20is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R21is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; and R22is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F. In some embodiments, R4is of Formula (LVa): Formula (LVa) wherein R7, R8, R12, R13, R17, R18, R19, R20, R21and R22are as defined herein. In some embodiments, the moiety of formula (LV) is of Formula (LVa). In some embodiments, R4is of Formula (LV) or Formula (LVa) and R7, R8, R12, R18, R19, R20, R21, and R22are H. In some embodiments, R4is of Formula (LV) or Formula (LVa) and R13is -N(CH3)-. In some embodiments, R4is of Formula (LV) or Formula (LVa) and R17is -CH2-. In some embodiments, X3is C(R12)(C(O)R13); X4is C(R17)(R18); and R13is linked to R18to form a ring together with the intervening atoms.In some embodiments, X2is a bond; X3is C(R12)(C(O)R13); X4is C(R17)(R18); and R13is linked to R18to form a ring together with the intervening atoms. In some embodiments, X2is a bond; X3is C(R12)(C(O)R13); X4is C(R17)(R18); X5is C(R19)(R20); X6is C(R21)(R22); and R13is linked to R18to form a ring together with the intervening atoms. In some embodiments, R4is of Formula (LVI): Formula (LVI) wherein R7is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R8is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R12is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R13is -N(R28)-, wherein R28is H or C1-3 alkyl; R17is a bond or a C1-3alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl; R18is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R19is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R20is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R21is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; and R22is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F. In some embodiments, R4is of Formula (LVIa): Formula (LVIa) wherein R7, R8, R12, R13, R17, R18, R19, R20, R21and R22are as defined herein. In some embodiments, the moiety of formula (LV) is of Formula (LVb). In some embodiments, R4is of Formula (LVI) or Formula (LVIa) and R7, R8, R12, R18, R19, R20, R21, and R22are H. In some embodiments, R4is of Formula (LVI) or Formula (LVIa) and R13is -N(CH3)-. In some embodiments, R4is of Formula (LVI) or Formula (LVIa) and R17is -CH2-. In some embodiments, X2is a bond; X3is C(R14)(R15); X4is C(R17)(R18); X5is C(R19)(R20); and X6is bond. In some embodiments, R4is of Formula (XXXVI): Formula (XXXVI) wherein R7, R8, R14, R15, R17, R18, R19, and R20are as defined herein. In some embodiments, R4is of Formula (XLIII): Formula (XLIII) wherein R7, R8, R14, R15, R17, R18, R19, and R20are as defined herein. In some embodiments, X2is C(R9)(R10); X3is C(R14)(R15); X4is C(R17)(R18); X5is a bond; and X6is bond. In some embodiments, R4is of Formula (XI): Formula (XI) wherein R14is -X7N(R23)(C(O)R24); X7is a bond or CH2; R23is H or C1-3alkyl, or R23is a bond and R15is C1-3alkanediyl and R23is linked to R15to form a 4 or 5 membered ring; R24is C1-3alkyl; and R15is H or C1-3alkyl. In some embodiments, X2is a bond; X3is C(R14)(R15); X4is C(R17)(R18); X5is a bond; and X6is bond. In some embodiments, R4is of Formula (XXXVII): Formula (XXXVII) wherein R7, R8, R14, R15, R17, and R18are as defined herein. In some embodiments, R4is of Formula (XLIV): Formula (XLIV) wherein R7, R8, R14, R15, R17, and R18are as defined herein. In some embodiments, R14and R15are linked together to form a 5 membered ring. In some embodiments, R14and R15are linked together to form a 4 membered ring. In some embodiments, R14and R15are linked together to form a ring, and wherein R14is -X9C(O)X11-, wherein X9is a bond or -N(R29)-; R29is C1-3alkyl; X11is -O-, -CH2-, or -N(R30)-; and R30is C1-3alkyl; and R15is a bond or C1-3alkanediyl. In some embodiments, R4is of Formula (XVI): Formula (XVI) wherein R14and R15are linked together to form a ring; R14is -X9C(O)X11-; X9is a bond or -N(R29)-; R29is C1-3 alkyl; X11is -O-, -CH2-, or -N(R30)-; R30is C1-3 alkyl; and R15is a bond or C1-3 alkanediyl. In some embodiments, R4is of Formula (XIX): Formula (XIX) wherein X9is a bond or -N(R29)-; R29is C1-3 alkyl; X10is -C(O)-, -CH2-, or a bond; X11is -O-, -CH2-, or -N(R30)-; R30is C1-3 alkyl; X12is -N(C(O)R24)- or a bond; m is 1 or 2; n is 0 or 1; and z is 1 or 2; with the proviso that when X10is -C(O)-, then X12is a bond; with the proviso that when X10is -CH2- or a bond, then X12is -N(C(O)R24)-; and with the proviso that ring A is a 4 to 6 membered ring. In one aspect, the present invention relates to a compound of Formula (XXII): Formula (XXII) wherein R1, R2, R3, R5, R6, X9, X10, X11, X12, m, n, and z are as defined herein. In some embodiments, X2is C(R9)(R10); X3is C(R14)(R15); X4is C(R17)(R18); X5is C(R19)(R20); and X6is bond and R14and R15are linked together to form a ring. In some embodiments, X7is a bond; R23is H or C1-3alkyl; R24is C1-3alkyl; and R15is H or C1-3alkyl. In some embodiments, X2is a bond; X3is C(R14)(R15); X4is C(R17)(R18); X5is C(R19)(R20); and X6is bond. In some embodiments, R14and R15are linked together to form a ring. In some embodiments, R23is a bond and R15is C1-3alkanediyl and R23is linked to R15to form a 4 or 5 membered ring. In some embodiments, R4is of Formula (XII): Formula (XII) wherein m is 0 or 1; n is 0 or 1; and p is 0, 1 or 2, or a pharmaceutically acceptable salt thereof. In some embodiments, R4is of Formula (XVII): Formula (XVII) wherein X9is a bond or -N(R29)-; R29is C1-3 alkyl; X11is -O-, -CH2-, or -N(R30)-; R30is C1-3 alkyl; m is 1 or 2; n is 0 or 1; and z is 1 or 2. In some embodiments, R4is of Formula (XVIII): Formula (XVIII) wherein X9is a bond or -N(R29)-; R29is C1-3 alkyl; X11is -O-, -CH2-, or -N(R30)-; R30is C1-3alkyl; and m is 1 or 2. In some embodiments, X9is a bond. In some embodiments, X9is -N(R29)-. In some embodiments, R29is CH3. In some embodiments, X11is -O-. In some embodiments, X11is C1-3alkanediyl. In some embodiments, X11is -CH2-. In some embodiments, X11is -N(R30)-. In some embodiments, R30is CH3. In some embodiments, R4is of Formula (XII) and with the proviso that when m is 0 then p is 1 or 2. In some embodiments, R4is of Formula (XII) and with the proviso that when p is 2, then m is 0. In some embodiments, R4is of Formula (XII), with the proviso that when m is 0 then p is 1 or 2 and with the proviso that when p is 2, then m is 0. In some embodiments, R4is of Formula (XII), wherein m is 0 or 1; n is 0 or 1; and p is 0, 1 or 2, with the proviso that when m is 0 then p is 1 or 2, and with the proviso that when p is 2, then m is 0,. In some embodiments, m is 0. In some embodiments, m is 1. In some embodiments, m is 2. In some embodiments, p is 0. In some embodiments, p is 1. In some embodiments, p is 2. In some embodiments, m is 0 and p is 1. In some embodiments, m is 1 and p is 1. In some embodiments, m is 1 and p is 0. In some embodiments, m is 0 and p is 2. In some embodiments, n is 0. In some embodiments, n is 1. In some embodiments, z is 1.In some embodiments, z is 2. In some embodiments, n is 1 and z is 1. In some embodiments, n is 1 and z is 2. In some embodiments, n is 0 and z is 2. In one aspect, the present invention relates to a compound of Formula (I), Formula (I) wherein R1is halogen or H; R2is halogen; R3is H or halogen; R5is H or halogen; R6is H or halogen; R4is of Formula (XIX): Formula (XIX) wherein X9is a bond or -N(R29)-; R29is C1-3 alkyl; X10is -C(O)-, -CH2-, or a bond; X11is -O-, -CH2-, or -N(R30)-; R30is C1-3 alkyl; X12is -N(C(O)R24)- or a bond; m is 1 or 2; n is 0 or 1; and z is 1 or 2; with the proviso that when X10is -C(O)-, then X12is a bond; with the proviso that when X10is -CH2- or a bond, then X12is -N(C(O)R24)-; and with the proviso that ring A is a 4 to 6 membered ring, or a pharmaceutically acceptable salt thereof. In some embodiments, ring A is a 4 membered ring. In some embodiments, ring A is a 5 membered ring. In some embodiments, X2is C(R9)(R10); X3is N(C(O)R11); and R11is linked to R9to form a ring together with the intervening atoms. In some embodiments, R11is linked to R9to form a 6-membered ring. In some embodiments, X2is C(R9)(R10); X3is N(C(O)R11); X4is C(R17)(R18); and R11is linked to R9to form a ring together with the intervening atoms. In some embodiments, X2is C(R9)(R10); X3is N(C(O)R11); X4is C(R17)(R18); X5is C(R19)(R20); X6is a bond; and R11is linked to R9to form a ring together with the intervening atoms.In some embodiments, X2is C(R9)(R10); X3is N(C(O)R11); X4is C(R17)(R18); X5is C(R19)(R20); X6is a bond; and R11is linked to R9to form a 6-membered ring. In some embodiments, R4is of Formula (LI): , Formula (LI) wherein R7is H, C1-3 alkyl optionally substituted with 1 to 3 F or C1-3 alkoxy, or halogen, such as F; R8is H, C1-3 alkyl optionally substituted with 1 to 3 F or C1-3 alkoxy, or halogen, such as F; R9is a bond, -C(O)-, or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl; R10is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R11is -O-, -N(R28)-, or C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl, wherein one methylene group of the C1-3 alkanediyl is optionally replaced by -O- or -N(R28)-, wherein R28is H or C1-3 alkyl; R17is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R18is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R19is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; and R20is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F. In some embodiments, R4is of Formula (LIa): , Formula (LIa) wherein R7, R8, R9, R10, R11, R17, R18, R19,and R20are as defined herein. In some embodiments, the moiety of Formula (LI) is of Formula (Lia). In some embodiments, R4is of Formula (LI) or Formula (LIa) and R7, R8, R10, R17, R18, R19, and R20are H. In some embodiments, R4is of Formula (LI) or Formula (LIa) and R11is -O-. In some embodiments, R4is of Formula (LI) or Formula (LIa) and R11is - CH2-. In some embodiments, R4is of Formula (LI) or Formula (LIa) and R11is -CH2CH2- . In some embodiments, R11is linked to R9to form a ring and R9is a bond or a C1-3alkanediyl optionally substituted with 1 to 3 F, R10is H, and R11is C1-3alkanediyl wherein one methylene group is optionally replaced by -O- or - N(R28)-, wherein R28is H or C1-3alkyl. In some embodiments, R11is linked to R9to form a 5-membered ring. In some embodiments, X2is C(R9)(R10); X3is N(C(O)R11); and R11is linked to R10to form a ring together with the intervening atoms. In some embodiments, R11is linked to R10to form a 6-membered ring. In some embodiments, X2is C(R9)(R10); X3is N(C(O)R11); X4is C(R17)(R18); and R11is linked to R10to form a ring together with the intervening atoms. In some embodiments, X2is C(R9)(R10); X3is N(C(O)R11); X4is C(R17)(R18); X5is C(R19)(R20); X6is a bond; and R11is linked to R10to form a ring together with the intervening atoms. In some embodiments, X2is C(R9)(R10); X3is N(C(O)R11); X4is C(R17)(R18); X5is C(R19)(R20); X6is a bond; and R11is linked to R10to form a 6-membered ring. In some embodiments, R4is of Formula (LII): wherein R7is H, C1-3 alkyl optionally substituted with 1 to 3 F or C1-3 alkoxy, or halogen, such as F; R8is H, C1-3 alkyl optionally substituted with 1 to 3 F or C1-3 alkoxy, or halogen, such as F; R10is a bond, -C(O)-, or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl; R9is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R11is -O-, -N(R28)-, or C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl, wherein one methylene group of the C1-3 alkanediyl is optionally replaced by -O- or -N(R28)-, wherein R28is H or C1-3 alkyl; R17is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R18is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R19is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; and R20is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F. In some embodiments, R4is of Formula (LIIa): , Formula (LIIa) wherein R7, R8, R9, R10, R11, R17, R18, R19,and R20are as defined herein. In some embodiments, the moiety of Formula (LII) is of Formula (LIIa). In some embodiments, R4is of Formula (LII) or Formula (LIIa) and R7, R8, R10, R17, R18, R19, and R20are H. In some embodiments, R4is of Formula (LII) or Formula (LIIa) and R11is -O-. In some embodiments, R4is of Formula (LII) or Formula (LIIa) and R11is - CH2-. In some embodiments, R4is of Formula (LII) or Formula (LIIa) and R11is - CH2CH2-. In some embodiments, R11is linked to R10to form a ring and R9is H, R10is a bond or a C1-3alkanediyl optionally substituted with 1 to 3 F, and R11is C1-3alkanediyl wherein one methylene group is optionally replaced by -O- or - N(R28)-, wherein R28is H or C1-3alkyl. In some embodiments, R11is linked to R10to form a 5-membered ring. In some embodiments, R11is linked to R9or R10to form a ring together with the intervening atoms, and R11is -O-. In some embodiments, R11is linked to R9or R10to form a ring together with the intervening atoms, and R11is C1-3alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl, wherein one methylene group of the C1-3 alkanediyl is optionally replaced by -O- or - N(R28)-, wherein R28is H or C1-3 alkyl. In some embodiments, R11is linked to R9or R10to form a ring together with the intervening atoms, and R11is C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl. In some embodiments, R11is linked to R9or R10to form a ring together with the intervening atoms, and R11is -CH2-. In some embodiments, R11is linked to R9or R10to form a ring together with the intervening atoms, and R11is -CH2CH2-. In some embodiments, R11is linked to R9or R10to form a ring together with the intervening atoms, and R11is -CH2O-. In some embodiments, R11is linked to R9or R10to form a ring together with the intervening atoms, and R11is -N(R28)-. In some embodiments, R11is linked to R9or R10to form a ring together with the intervening atoms, and R11is - N(CH3)-. In some embodiments, R11is linked to R9or R10to form a ring together with the intervening atoms, and R11is -O-. In some embodiments, R11is linked to R9to form a ring together with the intervening atoms, and R11-R9is -(CH2)3-, -(CH2)O-, -(CH2)2O-, - CH2OCH2-, -C(H)(CH3)CH2-, -C(O)N(H)-. In some embodiments, R11is linked to R10to form a ring together with the intervening atoms, and R11-R10is -(CH2)3-, -(CH2)O-, - (CH2)2O-, -CH2OCH2-, -C(H)(CH3)CH2-, -C(O)N(H)-. In some embodiments, X2is C(R9)(R10); X3is N(C(O)R11); X4is C(R17)(R18); X5is C(R19)(R20); X6is a bond; and R11is linked to R9to form a 5-membered ring. In some embodiments, R4is of Formula (XX): , Formula (XX) wherein R7is H, C1-3alkyl optionally substituted with 1 to 3 F or C1-3alkoxy, or halogen, such as F; R8is H, C1-3 alkyl optionally substituted with 1 to 3 F or C1-3 alkoxy, or halogen, such as F; R10is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R17is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R18is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R19is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R20is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R31is individually halogen or C1-3alkyl; r is 0, 1, 2, 3 or 4; X8is -CH2-, -O-, -CH2O-, -OCH2-, -N(R28)-, or -CH2N(R28)-; and R28is H or C1-3alkyl. In some embodiments, the moiety of Formula (XX) is of Formula (XXa): . Formula (XXa) In some embodiments, R4is of Formula (XXa) wherein: R7is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R8is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R10is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R17is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R18is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R19is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R20is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R31is individually halogen or C1-3alkyl; r is 0, 1, 2, 3 or 4; X8is -CH2-, -O- or -N(R28)-; and R28is H or C1-3alkyl. In some embodiments, X2is C(R9)(R10); X3is N(C(O)R11); X4is C(R17)(R18); X5is C(R19)(R20); X6is a bond; and R11is linked to R10to form a 5 membered ring. In some embodiments, the moiety of Formula (XX) is of Formula (XXb): , Formula (XXb) In some embodiments, R4is of Formula (XXb) wherein: R7is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R8is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R9is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R17is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R18is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R19is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R20is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R31is individually halogen or C1-3 alkyl; r is 0, 1, 2, 3 or 4; X8is -CH2-, -O- or -N(R28)-; and R28is H or C1-3 alkyl. In one aspect, the present invention relates to a compound of Formula (I), wherein R1is halogen or H; R2is halogen; R3is H or halogen; R5is H or halogen; R6is H or halogen; R4is of Formula (XXa) or Formula (XXb): Formula (XXa)Formula (XXb)wherein R7is H, C1-3alkyl optionally substituted with 1 to 3 F or C1-3alkoxy, or halogen, such as F; R8is H, C1-3alkyl optionally substituted with 1 to 3 F or C1-3alkoxy, or halogen, such as F; R9is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R10is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R17is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R18is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R19is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R20is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R31is individually halogen or C1-3 alkyl; r is 0, 1, 2, 3 or 4; X8is -CH2-, -O- or -N(R28)-; and R28is H or C1-3alkyl, or a pharmaceutically acceptable salt thereof. In some embodiments, R4is of Formula (XXa) and R7, R8, R10, R17, R18, R19, and R20are H. In some embodiments, R4is of Formula (XXb) and R7, R8, R9, R17, R18, R19, and R20are H. In some embodiments, R4is of Formula (XV): , Formula (XV) wherein X8is -CH2-, -O- or -N(R28)-; and R28is H or C1-3 alkyl. In one aspect, the present invention relates to a compound of Formula (XXIII): Formula (XXIII) wherein R1is halogen or H; R2is halogen; R3is H or halogen; R5is H or halogen; R6is H or halogen; X8is -CH2-, -O- or -N(R28)-; and R28is H or C1-3 alkyl, or a pharmaceutically acceptable salt thereof. In some embodiments, X8is -CH2-. In some embodiments, X8is -O-. In some embodiments, X8is -N(R28)-. In some embodiments, X8is -CH2O-. In some embodiments, X8is -OCH2-.In some embodiments, X8is -CH2N(R28)-. In some embodiments, R28is C1-3alkyl. In some embodiments, R28is CH3. In some embodiments, X8is -N(CH3)-. In some embodiments, R7is H. In some embodiments, R7is C1-3alkyl. In some embodiments, R7is CH3. In some embodiments, R7is C1-3alkyl substituted with 1 to 3 F. In some embodiments, R7is C1-3alkyl substituted with C1-3alkoxy. In some embodiments, R7is CH2OCH3. In some embodiments, R7is halogen, such as F. In some embodiments, R8is H. In some embodiments, R8is C1-3alkyl. In some embodiments, R8is CH3. In some embodiments, R8is C1-3alkyl substituted with C1-3alkoxy. In some embodiments, R8is CH2OCH3. In some embodiments, R8is C1-3alkyl substituted with 1 to 3 F. In some embodiments, R8is halogen, such as F. In some embodiments, R9is H. In some embodiments, R9is C1-3 alkyl. In some embodiments, R9is C1-3 alkyl substituted with 1 to 3 halogens. In some embodiments, R9is C1-3 alkyl substituted with 1 to 3 F. In some embodiments, R9is -C(O)N(R31)(R32), wherein R31is H or C1-3 alkyl and R32is H or C1-3 alkyl. In some embodiments, R9is - C(O)N(H)(CH3). In some embodiments, R9is -C(O)NH2. In some embodiments, R9is - C(O)N(CH3)2. In some embodiments, R9is halogen, such as F. In some embodiments, R9is linked to R11to form a ring, and R9is a bond. In some embodiments, R9is linked to R11to form a ring, and R9is -C(O)-. In some embodiments, R9is linked to R11to form a ring, and R9is C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl. In some embodiments, R9is linked to R11to form a ring, and R9is -CH2-. In some embodiments, R9is linked to R11to form a ring, and R9is -(CH2)2-. In some embodiments, R9is linked to R11to form a ring, and R9is -C(H)(CH3)-. In some embodiments, R9is linked to R11or R13to form a ring, and R9is a bond. In some embodiments, R9is linked to R11or R13to form a ring, and R9is C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl. In some embodiments, R9is linked to R11or R13to form a ring, and R9is -CH2-. In some embodiments, R9is linked to R11or R13to form a ring, and R9is - CH2CH2-. In some embodiments, R31is H. In some embodiments, R31is C1-3alkyl. In some embodiments, R31is CH3. In some embodiments, R32is H. In some embodiments, R32is C1-3alkyl. In some embodiments,R32is CH3. In some embodiments, R10is H. In some embodiments, R10is C1-3alkyl. In some embodiments, R10is C1-3alkyl substituted with 1 to 3 halogens. In some embodiments, R10is C1-3alkyl substituted with 1 to 3 F. In some embodiments, R10is - C(O)N(R31)(R32), wherein R31is H or C1-3alkyl and R32is H or C1-3alkyl. In some embodiments, R10is -C(O)N(H)(CH3). In some embodiments, R10is -C(O)NH2. In some embodiments, R10is -C(O)N(CH3)2. In some embodiments, R10is halogen, such as F. In some embodiments, R10is linked to R11to form a ring, and R9is a bond. In some embodiments, R10is linked to R11to form a ring, and R9is -C(O)-. In some embodiments, R10is linked to R11to form a ring, and R9is C1-3alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl. In some embodiments, R10is linked to R11to form a ring, and R9is -CH2-. In some embodiments, R10is linked to R11to form a ring, and R9is -(CH2)2-. In some embodiments, R10is linked to R11to form a ring, and R9is -C(H)(CH3)-. In some embodiments, R10is linked to R11or R13to form a ring, and R10is a bond. In some embodiments, R10is linked to R11or R13to form a ring, and R10is C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1- 3 alkyl. In some embodiments, R10is linked to R11or R13to form a ring, and R10is -CH2- . In some embodiments, R10is linked to R11or R13to form a ring, and R10is -CH2CH2-. In some embodiments, X13is a bond. Hence, in one emboidment, R11is R33. In some embodiments, X13is C1-3 alkanediyl. In some embodiments, X13is -CH2-. In some embodiments, X13is C1-3 alkanediyl substituted with C1-3 alkyl. In some embodiments, X13is -C(H)(CH3)-. In some embodiments, X13is -O-. In some embodiments, X13is -C1-3 alkanediyl-O-. In some embodiments, X13is -CH2O-. In some embodiments, X13is bond, -CH2-, -C(H)(CH3)-, -O-, or -CH2O-. In some embodiments, when X13is -O- or - C1-3 alkanediyl-O-, then R33is linked to X13via a carbon atom of R33. In some embodiments, R33is azetidinyl optionally substituted with one or more substituents individually selected from halogen; C1-3 alkoxy optionally substituted with one or more F; C1-3 alkyl optionally substituted with one or more F; NH2; N(H)(CH3); and N(CH3)2. In some embodiments, R33is azetidinyl. In some embodiments, R33is . In some embodiments, R11is . In some embodiments, R11is azetidinyl. In some embodiments, R11is . In some embodiments, R11is . n some em o mens, s . In some embodiments, R33is azetidinyl optionally substituted with one or more substituents selected from halogen, C1-3 alkoxy, and C1-3 alkyl. In some embodiments, R11is azetidinyl optionally substituted with one or more substituents selected from halogen, C1-3 alkyl, and NH2. In some embodiments, R11is azetidinyl substituted with one or more substituents selected from halogen, and C1-3 alkyl. In some embodiments, R11is azetidinyl substituted with halogen, such as F. In some embodiments, R33is azetidinyl substituted with one or more substituents halogen(s) and / or one or more C1-3 alkyl. In some embodiments, R33is azetidinyl substituted with one or more halogens. In some embodiments, R33is azetidinyl substituted with one or more F. In some embodiments, R33is azetidinyl substituted with one or two F. In some embodiments, embodiments, , bodiments, R11 is . In some embodiments, R33is azetidinyl substituted with C1-3alkoxy. In some embodiments, R33is azetidinyl substituted with -OCH3. In some embodiments, some embodiments, . In some embodiments, R11is C1-3 alkyl substituted with -O-azetidinyl, wherein the azetidinyl is optionally substituted with CH3. In some embodiments, R33is . In some embodiments, R11is . In some embodiments, R33is . , . In some embodiments, R11is . In some embodiments, R11is azetidinyl substituted with C1-3alkyl, such as CH3. In some embodiments, In some embodiments, R33is , some embodiments, R11is . In some embodiments, R33is azetidinyl optionally substituted with C1-3 alkyl. In some embodiments, R11is . In some embodiments, R11is . In some embodiments, R33is oxetanyl optionally substituted with one or more substituents individually selected from halogen; C1-3 alkoxy optionally substituted with one or more F; C1-3 alkyl optionally substituted with one or more F; NH2; N(H)(CH3); and N(CH3)2. In some embodiments, R33is oxetanyl. In some embodiments, R33is . so e e o e s, s . In some embodiments, R11is . In some embodiments, R33is oxetanyl substituted with one or more C1-3 alkyl. In some embodiments, R33is oxetanyl substituted with one or more - CH3. In some embodiments, some embodiments, R11is . In some embodiments, R11 . In some embodiments, R11is . In some embodiments, R11is . In some embodiments, R33is pyrrolidinyl optionally substituted with one or more substituents individually selected from halogen; C1-3alkoxy optionally substituted with one or more F; C1-3alkyl optionally substituted with one or more F; NH2; N(H)(CH3); and N(CH3)2. In some embodiments, R33is pyrrolidinyl optionally substituted with one or more substituents individually selected from halogen; C1-3alkoxy optionally substituted with one or more F; C1-3alkyl optionally substituted with one or more F. In some embodiments, R33is pyrrolidinyl substituted with one or more F. In some embodiments, R33is pyrrolidinyl substituted with one or more C1-3alkyl optionally substituted with one or more F. In some embodiments, R33is pyrrolidinyl substituted with one or more -CH3. In some embodiments, R33is pyrrolidinyl substituted with one or more -CF3. In some embodiments, R11is pyrrolidinyl is optionally substituted with one or more substituents individually selected from the group consisting of C1-3alkyl, halogen, C1-3alkoxy, C1-3haloalkyl, NH2, N(H)(CH3), N(CH3)2and azetidinyl, and said azetidinyl is optionally substituted with one or more halogens. In some embodiments, R33is of Formula (XIV): Formula (XIV) wherein R25is H or C1-3 alkyl; R26is individually halogen, such as F, C1-3 alkyl, or C1-3 haloalkyl, such as CF3; and q is 0, 1 or 2. In some embodiments, R11is of Formula (XIV): Formula (XIV) wherein R25is H or C1-3 alkyl; R26is individually halogen, such as F, C1-3 alkyl, or C1-3 haloalkyl, such as CF3; and q is 0, 1 or 2. In some embodiments, R11is pyrrolidinyl optionally substituted with one or more substituents individually selected from C1-3 alkyl and halogen.In some embodiments, R11is of Formula (XIV) wherein R25is H or C1-3 alkyl; R26is halogen, such as F, or C1-3 alkyl; and q is 0, 1 or 2. In some embodiments, q is 0. In some embodiments, q is 1. In some embodiments, R33is of Formula (XIVa) or Formula (XIVb): Formula (XIVa) Formula (XIVb) wherein R25is H or C1-3 alkyl; R26ais H or F; and R26bis H or F. In some embodiments, q is 2. In some embodiments, R11is of Formula (XIVa) wherein R25is H or C1-3 alkyl; R26ais H or F; and R26bis H or F. In some embodiments, the moiety of Formula (XIVa) is of Formula (XIVa-1) or Formula (XIVa-2): . Formula (XIVa-1) Formula (XIVa-2) In some embodiments, R11is of Formula (XIVa-1) wherein R25is H or C1-3alkyl; R26ais H or F; and R26bis H or F. In some embodiments, R11is of Formula (XIVa-2) wherein R25is H or C1-3alkyl; R26ais H or F; and R26bis H or F. In some embodiments, R26ais F. In some embodiments, R26bis F. In some embodiments, R26ais F and R26bis F. In some embodiments, R26ais F and R26bis H. In some embodiments, R26ais H and R26bis F. In some embodiments, R11is of Formula (XIVb) wherein R25is H or C1-3alkyl. In some embodiments, the moiety of Formula (XIVb) is of Formula (XIVb-1) or Formula (XIVb- 2): . Formula (XIVb-1) Formula (XIVb-2) In some embodiments, R11is of Formula (XIVb-1) wherein R25is H or C1-3alkyl. In some embodiments, R11is of Formula (XIVb-2) wherein R25is H or C1-3 alkyl. In some embodiments, R25is H. In some embodiments, R25is C1-3alkyl. In some embodiments, R25is CH3. In some embodiments, R11is pyrrolidinyl. In some embodiments, R11is . In some embodiments, R11is . In some embodiments, R11is . In some embodiments, R11is . In some embodiments, . In some embodiments, R11is . In some embodiments, . In some embodiments, some embodiments, some embodiments, . In some embodiments, some embodiments, . In some embodiments, R11is . In some embodiments, some embodiments, . In some embodiments, R33is tetrahydrofuranyl optionally substituted with one or more substituents individually selected from halogen; C1-3 alkoxy optionally substituted with one or more F; C1-3 alkyl optionally substituted with one or more F; NH2; N(H)(CH3); and N(CH3)2. In some embodiments, R33is tetrahydrofuranyl. In some embodiments, R11is tetrahydrofuranyl. In some embodiments, R33is tetrahydrofuran-2-yl. In some embodiments, R33is . In some embodiments, R11is tetrahydrofuran- 2-yl. In some embodiments, R11 . In some embodiments, R11is . In some embodiments, R33is morpholinyl optionally substituted with one or more substituents individually selected from halogen; C1-3 alkoxy optionally substituted with one or more F; C1-3 alkyl optionally substituted with one or more F; NH2; N(H)(CH3); and N(CH3)2. In some embodiments, R33is morpholinyl. In some embodiments, R33is N-morpholinyl. In some embodiments, some embodiments, R11is morpholinyl optionally substituted with C1-3alkyl. In some embodiments, R11is morpholinyl. In some mbodiments, R1is e1. In some embodiments, R11is . In some embodiments, R11is morpholinyl substituted with C alkyl. In some embodim 11 1-3 ents, R is morpholinyl substituted with CH3. In some embodiments, R11is . In some embodiments, . In some embodiments, R33is pyridinyl optionally substituted with one or more substituents individually selected from halogen; C1-3 alkoxy optionally substituted with one or more F; C1-3 alkyl optionally substituted with one or more F; NH2; N(H)(CH3); and N(CH3)2. In some embodiments, R33is pyridinyl optionally substituted with one or more NH2. In some embodiments, R33is pyridinyl substituted with NH2. In some embodiments, R33is . In some embodiments, some embodiments, R33is . In some embodiments, R11is pyridinyl optionally substituted with one or more NH2. In some embodiments, R11is pyridinyl substituted with NH2. In some embodiments, some embodiments, R11is , . In some embodiments, R33is C1-3 alkyl optionally substituted with one or more substituents individually selected from halogen; C1-3 alkoxy optionally substituted with one or more F; C1-3alkyl optionally substituted with one or more F; NH2; N(H)(CH3); and N(CH3)2. In some embodiments, R11is C1-3alkyl optionally substituted with one or more substituents individually selected from the group consisting of NH2, N(H)(CH3), N(CH3)2, C1-3alkoxy, morpholinyl, azetidinyl, -O-azetidinyl, and -O-oxetanyl, and said azetidinyl is optionally substituted with one or more substituents selected from halogen, C1-3alkoxy, and C1-3alkyl. In some embodiments, R11is C1-3alkyl optionally substituted with one or more substituents individually selected from the group consisting of NH2, N(CH3)2, N(H)(CH3), C1-3alkoxy, and morpholinyl. In some embodiments, R11is C1-3alkyl optionally substituted with one or more substituents individually selected from the group consisting of NH2, N(CH3)2, N(H)(CH3) and C1-3alkoxy. In some embodiments, R33is C1-3alkyl. In some embodiments, R33is CH3. In some embodiments, R11is C1-3alkyl. In some embodiments, R11is CH3. In some embodiments, R33is NH2. In some embodiments, R33is N(H)(CH3). In some embodiments, R33is N(CH3)2. In some embodiments, R11is C1-3 alkyl substituted with one or more N(CH3)2. In some embodiments, R11is C1-3 alkyl substituted with one or more NH2. In some embodiments, R11is -CH2NH2. In some embodiments, R11is C1-3 alkyl substituted with one or more N(CH3)2. In some embodiments, R11is -CH2N(CH3)2. In some embodiments, R11is -CH2-N(H)(CH3). In some embodiments, R33is C1-3 alkoxy optionally substituted with one or more substituents individually selected from halogen; C1-3 alkoxy optionally substituted with one or more F; C1-3 alkyl optionally substituted with one or more F; NH2; N(H)(CH3); and N(CH3)2. In some embodiments, R33is C1-3 alkoxy. In some embodiments, R33is -OCH3. In some embodiments, R11is C1-3 alkyl is substituted with one or more C1-3 alkoxy. In some embodiments, R11is -CH2OCH3. In some embodiments, R11is C1-3 alkoxy. In some embodiments, R11is -OCH3. In some embodiments, R33is C1-3 alkyl optionally substituted with one or more F. In some embodiments, R33is CF3. In some embodiments, R33is CHF2. In some embodiments, R11is -CH2-O-CF3. In some embodiments, R11is -CH2-O-CHF2. In some embodiments, R11is CHF2. In some embodiments, R33is C3-6 cycloalkyl optionally substituted with one or more substituents individually selected from halogen; C1-3 alkoxy optionally substituted with one or more F; C1-3 alkyl optionally substituted with one or more F; NH2; N(H)(CH3); and N(CH3)2. In some embodiments, R33is C3-6 cycloalkyl. In some embodiments, R33is C3-6 cycloalkyl substituted with one or more substituents individually selected from halogen; C1-3 alkoxy optionally substituted with one or more F; and C1-3alkyl optionally substituted with one or more F. In some embodiments, R33 is C3-6cycloalkyl substituted with one or more substituents selected from halogen, and C1-3alkoxy. In some embodiments, R33is C3-6cycloalkyl substituted with one or more F. In some embodiments, R11is C3-6cycloalkyl substituted with C1-3alkoxy. In some embodiments, R11is C3-6cycloalkyl substituted with -OCH3. In some embodiments, the C3-6cycloalkyl is C3-5cycloalkyl. In some embodiments, the C3-5cycloalkyl is cyclobutyl. In some embodiments, R33is . In some embodiments, R33is R11is . In some embodiments, R33is C3-6 cycloalkyl. In some embodiments, R33is cyclopropyl. In some embodiments, R11is C3-5cycloalkyl. In some embodiments, R11is cyclopropyl. In some embodiments, R11is C1-3alkyl substituted with morpholinyl. In some embodiments, R11is C1alkyl substituted with morpholinyl. In some embodiments, R11is C1-3alkyl substituted with azetidinyl, wherein the azetidinyl is optionally substituted with one or more substituents selected from halogen, C1-3alkoxy, and C1-3 alkyl. In some embodiments, R11is C1 alkyl substituted with azetidinyl, wherein the azetidinyl is optionally substituted with one or more substituents selected from halogen, C1-3alkoxy, and C1-3alkyl. In some embodiments, R11is C1-3alkyl substituted with azetidinyl. In some embodiments, R11is C1-3alkyl substituted with azetidinyl, wherein the azetidinyl is substituted with one or more halogens.In some embodiments, R11is C1-3alkyl substituted with azetidinyl, wherein the azetidinyl is substituted with one or more F.In some embodiments, R11is C1-3alkyl substituted with azetidinyl, wherein the azetidinyl is substituted with one or two F. In some embodiments, R11is C1-3alkyl substituted with -O-azetidinyl, wherein the azetidinyl is optionally substituted with one or more substituents selected from halogen, C1-3alkoxy, and C1-3alkyl. In some embodiments, R11is C1-3alkyl substituted with -O-azetidinyl. In some embodiments, R11is C1-3alkyl substituted with -O-azetidinyl, wherein the azetidinyl is optionally substituted with C1-3 alkyl. In some embodiments, R11is C1-3 alkyl substituted with -O-azetidinyl, wherein the azetidinyl is optionally substituted with CH3. In some embodiments, R11is C1-3alkyl substituted with -O-oxetanyl. In some embodiments, R11is C3-5cycloalkyl is optionally substituted with one or more substituents selected from halogen, and C1-3alkoxy. In some embodiments, R11is C3-5cycloalkyl is optionally substituted with one or more halogen, such as F. In some embodiments, R11is C3-5cycloalkyl is optionally substituted with C1-3alkoxy, such as - OCH3. In some embodiments, the C3-5cycloalkyl is cyclobutyl. In some embodiments, R11is . In some embodiments, R11is . In some embodiments, R12is H. In some embodiments, R12is C1-3alkyl. In some embodiments, R12is CH3. In some embodiments, R13is selected from the group consisting of NH2, N(H)(CH3), N(CH3)2, pyrrolidinyl, azetidinyl, and piperazinyl, wherein ^ said pyrrolidinyl is optionally substituted with one or more substituents individually selected from the group consisting of halogen, NH2, N(H)(CH3), N(CH3)2 and azetidinyl, and said azetidinyl is optionally substituted with one or more halogens, and ^ said azetidinyl optionally substituted with NH2. In some embodiments, R13is N(H)(CH3). In some embodiments, when R13is pyrrolidinyl, azetidinyl, or piperazinyl, said pyrrolidinyl, azetidinyl, or piperazinyl is attached to the rest of the molecule via an N atom in said pyrrolidinyl, azetidinyl, or piperazinyl. In some embodiments, R13is pyrrolidinyl optionally substituted with one or more substituents individually selected from the group consisting of halogen, NH2, N(H)(CH3), N(CH3)2and azetidinyl, and said azetidinyl is optionally substituted with one or more halogens. In some embodiments, R13is pyrrolidinyl optionally substituted with NH13 2, N(H)(CH3), or N(CH3)2. In some embodiments, R is . In some13 13 embodiments, R is . In some embodiments, R is . In some embodiments, R13is . In some embodiments, R13is pyrrolidinyl substituted with one or more substituents individually selected from the group consisting of halogen, NH2, N(H)( n some embodiments, R13is . In some embodiments, some embodiments, R13is piperazinyl. In some embodiments, R13is . In some embodiments, R13is pyrrolidinyl optionally substituted with azetidinyl, and the azetidinyl is optionally substituted with or more halogens. In some embodiments, R1 one3is . In some embodiments, some embodiments, some embodiments, some embodiments, R13is azetidinyl 2 embodiments, R13 optionally substituted with NH . In some is . In some embodiments, R13is NH2, N(H)(CH3), or N(CH3)2. In some embodiments, R13is linked to R9, R10, R17, or R18to form a ring together with the intervening atoms, and R13is - N(R28)-, wherein R28is H or C1-3 alkyl. In some embodiments, R13is -N(CH3)-. In some embodiments, R14is N(H)(C(O)CH3). In some embodiments, R15is H. In some embodiments, R16is H. In some embodiments, R16is C1-3alkyl. In some embodiments, R16is CH3. In some embodiments, R17is H. In some embodiments, R17is C1-3alkyl. In some embodiments, R17is CH3. In some embodiments, R17is C1-3alkyl substituted with 1 to 3 F. In some embodiments, R17is halogen, such as F. In some embodiments, R18is H. In some embodiments, R18is C1-3alkyl. In some embodiments, R18is CH3. In some embodiments, R18is C1-3alkyl substituted with 1 to 3 F. In some embodiments, R18is halogen, such as F. In some embodiments, R19is H. In some embodiments, R19is C1-3alkyl. In some embodiments, R19is C1-3 alkyl substituted with 1 to 3 F. In some embodiments, R19is halogen, such as F. In some embodiments, R20is H. In some embodiments, R20is C1-3 alkyl. In some embodiments, R20is CH3. In some embodiments, R20is C1-3 alkyl substituted with 1 to 3 F. In some embodiments, R20is halogen, such as F. In some embodiments, R21is H. In some embodiments, R21is C1-3 alkyl. In some embodiments, R21is CH3. In some embodiments, R21is C1-3 alkyl substituted with 1 to 3 F. In some embodiments, R21is halogen, such as F. In some embodiments, R22is H. In some embodiments, R22is C1-3 alkyl. In some embodiments, R22is CH3. In some embodiments, R22is C1-3 alkyl substituted with 1 to 3 F. In some embodiments, R22is halogen, such as F. In some embodiments, R23is H. In some embodiments, R23is C1-3 alkyl. In some embodiments, R23is a bond and R15is C1-3 alkanediyl and R23is linked to R15to form a 4 or 5 membered ring. In some embodiments, R24is CH3. In some embodiments, no more than two of X2, X5and X6are bonds. In some embodiments, the azetidinyl is azetidin-1-yl. In some embodiments, the azetidinyl is azetidin-2-yl. In some embodiments, the azetidinyl is azetidin-3-yl. In some embodiments, the morpholinyl is morpholin-4-yl. In some embodiments, the morpholinyl is morpholin-3-yl. In some embodiments, the pyrrolidinyl is pyrrolidin-1-yl. In some embodiments, the pyrrolidinyl is pyrrolidin-2-yl. In some embodiments, the pyrrolidinyl is pyrrolidin-3-yl. In some embodiments, the oxetanyl is oxetan-2-yl.In some embodiments, the oxetanyl is oxetan-3-yl. embodiments, some embodiments, some embodiments, some embodiments, some embodiments, some embodiments, some embodiments, R4is . , . In some embodiments, n some embodiments, R4 I is . In some embodiments, R4is , some embodiments, some embodiments, some embodiments, R4is . In some embodiments, R4is . In some embodiments, R4is . In some embodiments, R4is . In some embodiments, R4is embodiments, R4is . In some embodiments, R4is . In some embodiments, some embodiments, R4is embodiments, R4is . In some embodiments, R4is . In some embodiments, some embodiments, R4is some embodiments, some embodiments, In some embodiments, In some embodiments, some embodiments, In some embodiments, R4is .. In some embodiments, R4is , . In some embodiments, R4is . In some embodiments, some embodiments, some embodiments, R4is . In some embodiments, R4is . , some embodiments, R4is embodiments, . In some embodiments, R4is

[0282] e . , . In some embodiments, R4is . In some embodiments, R4is . so e e o e s, s . In some embodiments, . In some embodiments, R4is

[0283] ents, R4is embodiments, some embodiments, some embodiments, some embodiments, R4is is . In some embodiments, R4is .In some embodiments, , some embodiments, some embodiments, embodiments, some embodiments, some embodiments, some embodiments, R4is . In some embodiments, . In some embodiments, . In some embodiments, R4is 4 . In some embodiments, wherein R is . In some 4 4 embodiments, R is . In some embodiments, R is . In some embodiments, In some embodiments, R4is . In some embodiments, R4is , In some embodiments, R4is . In some embodiments, R4is . In some embodiments, R4 . In some embodiments, R4is , , . In some embodiments, some embodiments, R4is

[0284] n some embodiments, R4is . In some embodiments, s . In some embodiments, some embodiments, In some embodiments, some embodiments, R4is e embodiments, , some embodiments, some embodiments, some embodiments, In some embodiments, R4is . In some embodiments, some embodiments, R4 In is . In some embodiments, R4is , some embodiments, , embodiments, R4is .In some embodiments, some embodiments, some embodiments, some embodiments, some embodiments, In some embodiments, the compound is not a compound selected from the group consisting of: (3aR,7aR)-2-[(4-Fluoro-1H-indol-2-yl)carbonyl]hexahydropyrano[3,4-c]pyrrole-7a(1H)- carboxamide; (4,5-dichloro-1H-indol-2-yl)(3-(pyrrolidine-1-carbonyl)piperidin-1-yl)methanone; (4aR,7aS)-1-[(4,5-Dichloro-1H-indol-2-yl)carbonyl]octahydro-5H-pyrrolo[3,4-b]pyridin-5- one; (4-chloro-1H-indol-2-yl)(4-(cyclobutanecarbonyl)piperazin-1-yl)methanone; (4-chloro-5-methyl-1H-indol-2-yl)(4-(cyclopropanecarbonyl)-2,2-dimethylpiperazin-1- yl)methanone; (4-fluoro-1H-indol-2-yl)(3-(pyrrolidine-1-carbonyl)piperidin-1-yl)methanone; [2-(cyclopropylcarbonyl)-4-morpholinyl](4,5-dichloro-1H-indol-2-yl)-methanone; [2-(cyclopropylcarbonyl)-4-morpholinyl](4-fluoro-1H-indol-2-yl)-methanone; [4-[(6-bromo-4-fluoro-1H-indol-2-yl)carbonyl]-2-morpholinyl]cyclopropyl-methanone; 1-[(4,5-dichloro-1H-indol-2-yl)carbonyl]-3-methyl-3-pyrrolidinecarboxamide; 1-[(4,5-dichloro-1H-indol-2-yl)carbonyl]-3-piperidinecarboxamide; 1-[(4,5-dichloro-1H-indol-2-yl)carbonyl]-3-pyrrolidinecarboxamide; 1-[(4,5-dichloro-1H-indol-2-yl)carbonyl]-N-methyl-3-piperidinecarboxamide; 1-[(4-bromo-1H-indol-2-yl)carbonyl]-3-methyl-3-pyrrolidinecarboxamide; 1-[(4-bromo-1H-indol-2-yl)carbonyl]-3-piperidinecarboxamide; 1-[(4-bromo-1H-indol-2-yl)carbonyl]-N-methyl-3-piperidinecarboxamide; 1-[(4-fluoro-1H-indol-2-yl)carbonyl]-N-methyl-3-piperidinecarboxamide; 1-[(6-bromo-4-fluoro-1H-indol-2-yl)carbonyl]-3-methyl-3-pyrrolidinecarboxamide; 1-[(6-bromo-4-fluoro-1H-indol-2-yl)carbonyl]-3-piperidinecarboxamide; 1-[(6-bromo-4-fluoro-1H-indol-2-yl)carbonyl]-N-methyl-3-piperidinecarboxamide; 1-[4-[(4,5-dichloro-1H-indol-2-yl)carbonyl]-1-piperazinyl]-2,2-dimethyl-1-propanone; 1-[4-[(4,5-dichloro-1H-indol-2-yl)carbonyl]-1-piperazinyl]-2-methoxyethanone; 1-[4-[(4,5-dichloro-1H-indol-2-yl)carbonyl]-1-piperazinyl]-2-methyl-1-propanone; 1-[4-[(4,5-dichloro-1H-indol-2-yl)carbonyl]-1-piperazinyl]ethanone; 1-[4-[(4,5-dichloro-1H-indol-2-yl)carbonyl]-3,3-dimethyl-1-piperazinyl]ethanone; 1-[4-[(4-chloro-1H-indol-2-yl)carbonyl]-1-piperazinyl]ethanone; 2-[(4,5-dichloro-1H-indol-2-yl)carbonyl]hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one; 2-[(4,5-dichloro-1H-indol-2-yl)carbonyl]hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one; 2-[(4-bromo-1H-indol-2-yl)carbonyl]hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one; 2-[(4-chloro-1H-indol-2-yl)carbonyl]-7-(2-hydroxyethyl)-2,7-diazaspiro[4.5]decan-6-one; 2-[(4-fluoro-1H-indol-2-yl)carbonyl]hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one; 2-[(6-bromo-4-fluoro-1H-indol-2-yl)carbonyl]hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one; 2-amino-1-[4-[(4,5-dichloro-1H-indol-2-yl)carbonyl]-1-piperazinyl]-ethanone; 4-[(4,5-dichloro-1H-indol-2-yl)carbonyl]-1-(1-methylethyl)-2-piperazinone; 4-[(4,5-dichloro-1H-indol-2-yl)carbonyl]-1,6-dimethyl-2-piperazinone; 4-[(4,5-dichloro-1H-indol-2-yl)carbonyl]-2-piperazinone; 4-[(4,5-dichloro-1H-indol-2-yl)carbonyl]-3,3-dimethyl-2-piperazinone; 4-[(4,5-dichloro-1H-indol-2-yl)carbonyl]-3-propyl-2-piperazinone; 4-[(4,5-dichloro-1H-indol-2-yl)carbonyl]-N-methyl-2-morpholinecarboxamide; 4-[(4,5-dichloro-1H-indol-2-yl)carbonyl]octahydro-2(1H)-quinoxalinone; 7-[(4,5-dichloro-1H-indol-2-yl)carbonyl]-2,7-diazaspiro[4.4]nonan-3-one; 7-[(4,5-dichloro-1H-indol-2-yl)carbonyl]hexahydroimidazo[1,5-a]pyrazin-3(2H)-one; 7-[(4-chloro-1H-indol-2-yl)carbonyl]hexahydro-3H-oxazolo[3,4-a]pyrazin-3-one; 7-[(4-chloro-5-fluoro-1H-indol-2-yl)carbonyl]-2,7-diazaspiro[4.4]nonan-3-one; rel-(3aR,7aR)-2-[(4-Fluoro-1H-indol-2-yl)carbonyl]hexahydropyrano[3,4-c]pyrrole- 7a(1H)-carboxamide; rel-(3R,4R)-1-[(4,5-dichloro-1H-indol-2-yl)carbonyl]-4-methyl-3-pyrrolidinecarboxamide; rel-(3R,4R)-1-[(4-bromo-1H-indol-2-yl)carbonyl]-4-methyl-3-pyrrolidinecarboxamide; and rel-(3R,4R)-1-[(6-bromo-4-fluoro-1H-indol-2-yl)carbonyl]-4-methyl-3- pyrrolidinecarboxamide. In some embodiments, the compound is selected from Group A consisting of:

[0285] ,

[0286] acceptable salt thereof. In one aspect, the present invention relates to a compound selected from Group A, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 4-(3,4,5-trichloro-1H-indole-2- carbonyl)piperazin-2-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(4-(4,5-dichloro-1H-indole-2-carbonyl)piperazin-1-yl)- 2-(dimethylamino)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-[(2R)-4-(4,5-dichloro-1H-indole-2-carbonyl)-2-methyl- piperazin-1-yl]ethanone, or a pharmaceutically acceptable salt thereof.1-[(2S)-4-(4,5- dichloro-1H-indole-2-carbonyl)-2-methyl-piperazin-1-yl]ethanone. In some embodiments, the compound is 1-[4-(4,5-dichloro-1H-indole-2-carbonyl)-2,2-dimethyl- piperazin-1-yl]ethanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-[(3S)-4-(4,5-dichloro-1H-indole-2-carbonyl)-3-methyl- piperazin-1-yl]ethanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-[(3R)-4-(4,5-dichloro-1H-indole-2-carbonyl)-3-methyl- piperazin-1-yl]ethanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-[3-(4,5-dichloro-1H-indole-2-carbonyl)-3,8- diazabicyclo[3.2.1]octan-8-yl]ethanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (3R)-1-(4,5-dichloro-1H-indole-2- carbonyl)pyrrolidine-3-carboxamide, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (3S)-1-(4,5-dichloro-1H-indole-2- carbonyl)pyrrolidine-3-carboxamide, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 4-(4,5-dichloro-1H-indole-2-carbonyl)piperazin-2- one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 4-(4,5-dichloro-1H-indole-2-carbonyl)-1-methyl-piperazin-2-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-[4- (4,5-dichloro-1H-indole-2-carbonyl)piperazin-1-yl]ethanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 4-(4,5-dichloro-6- fluoro-1H-indole-2-carbonyl)piperazin-2-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 4-(4-chloro-5-fluoro-1H-indole-2- carbonyl)piperazin-2-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (3R)-1-[(4,5-dichloro-1H-indol-2-yl)carbonyl]-N- methylpyrrolidine-3-carboxamide, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (3S)-1-[(4,5-dichloro-1H-indol-2-yl)carbonyl]-N- methylpyrrolidine-3-carboxamide, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 4-(4-chloro-1H-indole-2-carbonyl)piperazin-2- one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-[4-(4,5-dichloro-1H-indole-2-carbonyl)piperazin-1-yl]-2-methoxy- ethanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(4-(4-chloro-5-fluoro-1H-indole-2-carbonyl)piperazin-1-yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-[4-(4-chloro-5-fluoro-1H-indole-2-carbonyl)piperazin-1-yl]-2- (dimethylamino)ethanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-[4-(4-chloro-5-fluoro-1H-indole-2-carbonyl)piperazin- 1-yl]-2-methoxy-ethanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 4-(4,5-dichloro-7-fluoro-1 H-indole-2- carbonyl)piperazin-2-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 4-(4,5-dichloro-3-fluoro-1 H-indole-2- carbonyl)piperazin-2-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)-(4,5-dichloro-1H-indol-2-yl)(4-(pyrrolidine-3- carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-(4,5-dichloro-1 H-indol-2-yl)(4-(pyrrolidine-3- carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 2-amino-1-[4-(4,5-dichloro-1 H-indole-2- carbonyl)piperazin-1-yl]ethanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is [4-(azetidine-3-carbonyl)piperazin-1-yl]-(4,5- dichloro-1 H-indol-2-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (4,5-dichloro-1 H-indol-2-yl)-[4-[(3R)-pyrrolidine- 3-carbonyl]piperazin-1-yl]methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (4,5-dichloro-1 H-indol-2-yl)-[4-[(3S)-pyrrolidine-3- carbonyl]piperazin-1-yl]methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is [4-[(2S)-azetidine-2-carbonyl]piperazin-1-yl]-(4,5- dichloro-1 H-indol-2-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is [4-[(2R)-azetidine-2-carbonyl]piperazin-1-yl]-(4,5- dichloro-1 H-indol-2-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (4,5-dichloro-1 H-indol-2-yl)-[4-[(2S)-pyrrolidine-2- carbonyl]piperazin-1-yl]methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (4,5-dichloro-1 H-indol-2-yl)-[4-[(2R)-pyrrolidine-

[0287] 2-carbonyl]piperazin-1-yl]methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 2-amino-1-[4-(4-chloro-5-fluoro-1 H-indole-2- carbonyl)piperazin-1-yl]ethanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (4-(cyclopropanecarbonyl)piperazin-1-yl)(4,5- dichloro-1 H-indol-2-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (4-(2-aminoisonicotinoyl)piperazin-1-yl)(4,5- dichloro-1 H-indol-2-yl) methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is ((R)-3-aminopyrrolidin-1-yl)((R)-1-(4,5-dichloro- 1 H-indole-2-carbonyl) pyrrolidin-3-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is ((S)-3-aminopyrrolidin-1-yl)((S)-1-(4,5- dichloro-1 H-indole-2-carbonyl) pyrrolidin-3-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is ((R)-3- aminopyrrolidin-1-yl)((S)-1-(4,5-dichloro-1 H-indole-2-carbonyl) pyrrolidin-3- yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is ((S)-3-aminopyrrolidin-1-yl)((R)-1-(4,5-dichloro-1 H-indole-2-carbonyl) pyrrolidin-3-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is [(3R)-3-(3-aminoazetidine-1-carbonyl)pyrrolidin-1-yl]- (4,5-dichloro-1 H-indol-2-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is [(3S)-3-(3-aminoazetidine-1- carbonyl)pyrrolidin-1-yl]-(4,5-dichloro-1 H-indol-2-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is [(3R)-3-[(3S)-3- aminopyrrolidine-1-carbonyl]pyrrolidin-1-yl]-(4,5-dichloro-1 H-indol-2-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is [(3S)-3-[(3R)-3-aminopyrrolidine-1-carbonyl]pyrrolidin-1-yl]-(4,5-dichloro-1 H-indol-2- yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is [(3R)-3-[(3R)-3-aminopyrrolidine-1-carbonyl]pyrrolidin-1-yl]-(4,5- dichloro-1 H-indol-2-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is [(3S)-3-[(3S)-3-aminopyrrolidine-1- carbonyl]pyrrolidin-1-yl]-(4,5-dichloro-1 H-indol-2-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is N-[1-(4- acetamidophenyl)sulfonyl-4-piperidyl]-3,5-dimethyl-1 H-pyrrole-2-carboxamide, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)- N-(1-(4,5-dichloro-1 H-indole-2-carbonyl)pyrrolidin-3-yl)acetamide, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)- N-(1-(4,5-dichloro-1 H-indole-2-carbonyl)pyrrolidin-3-yl)acetamide, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)- 1-(4,5-dichloro-1 H-indole-2-carbonyl)-3-methylpyrrolidine-3-carboxamide, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)- 1-(4,5-dichloro-1 H-indole-2-carbonyl)-3-methylpyrrolidine-3-carboxamide, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(4- (3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)piperazin-1-yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 2- (3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)hexahydropyrrolo[1 ,2-a]pyrazin-6(2H)-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 7-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)hexahydro-3H-oxazolo[3,4-a]pyrazin-3- one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is methyl 4-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)piperazine-1- carboxylate, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)-1-(4-(4-chloro-5-fluoro-1 H-indole-2-carbonyl)-3-methylpiperazin-1- yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-1-(4-(4-chloro-5-fluoro-1 H-indole-2-carbonyl)-3-methylpiperazin-1- yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 4-(4,5-dichloro-1 H-indole-2-carbonyl)-N-methylmorpholine-2- carboxamide, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(4-(4,5-dichloro-1 H-indole-2-carbonyl)-3,3-dimethylpiperazin-1-yl)ethan- 1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)-1-(4-(4,5-dichloro-1 H-indole-2-carbonyl)-2-methylpiperazin-1-yl)ethan- 1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-1-(4-(4,5-dichloro-1 H-indole-2-carbonyl)-2-methylpiperazin-1-yl)ethan- 1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)-1-(4,5-dichloro-1 H-indole-2-carbonyl)pyrrolidine-3-carboxamide, or a pharmaceutically acceptable salt thereof. . In some embodiments, the compound is (R)-1-(4,5-dichloro-1 H-indole-2-carbonyl)pyrrolidine-3-carboxamide, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)- 1-(4-(4,5-dichloro-1 H-indole-2-carbonyl)-3-methylpiperazin-1-yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)- 1-(4-(4,5-dichloro-1 H-indole-2-carbonyl)-3-methylpiperazin-1-yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(3- (4,5-dichloro-1 H-indole-2-carbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1- (5-(4,5-dichloro-1 H-indole-2-carbonyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1- (6-(4,5-dichloro-1 H-indole-2-carbonyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-((2S,5R)-4-(4,5-dichloro-1 H-indole-2-carbonyl)-2,5-dimethylpiperazin-1-yl)ethan-1- one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-((2R,5S)-4-(4,5-dichloro-1 H-indole-2-carbonyl)-2,5-dimethylpiperazin-1- yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-((2S,5S)-4-(4,5-dichloro-1 H-indole-2-carbonyl)-2,5- dimethylpiperazin-1-yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-((2R,5R)-4-(4,5-dichloro-1 H-indole-2- carbonyl)-2,5-dimethylpiperazin-1-yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-1-(4,5-dichloro-1 H-indole-2- carbonyl)-N,N-dimethylpyrrolidine-3-carboxamide, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)-1-(4,5-dichloro-1 H-indole-2- carbonyl)-N,N-dimethylpyrrolidine-3-carboxamide, or a pharmaceutically acceptable salt thereof. In some embodiment, the compound is 1-(8-(4,5-dichloro-1 H-indole-2- carbonyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)-1-(4-(3,4-dichloro- 5-fluoro-1 H-indole-2-carbonyl)-3-methylpiperazin-1-yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)- 1-(4-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)-3-methylpiperazin-1-yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)-4-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)-1 ,5-dimethylpiperazin-2-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)- 4-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)-1 ,5-dimethylpiperazin-2-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(4- (3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(dimethylamino)ethan-1- one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(4-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2- methoxyethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 2-amino-1-[4-(4-chloro-5-fluoro-1 H-indole-2- carbonyl)piperazin-1-yl]ethanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 2-amino-1-(4-(3,4-dichloro-5-fluoro-1 H-indole-2- carbonyl)piperazin-1-yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-(4,5-dichloro-1 H-indol-2-yl)(4-prolylpiperazin- 1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)-(4,5-dichloro-1 H-indol-2-yl)(4-prolylpiperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)- (4-chloro-5-fluoro-1 H-indol-2-yl)(4-(pyrrolidine-3-carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-(4-chloro-5-fluoro-1 H-indol-2-yl)(4-(pyrrolidine-3-carbonyl)piperazin-1- yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-azetidin-2-yl(4-(4,5-dichloro-1 H-indole-2-carbonyl)piperazin-1- yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)-azetidin-2-yl(4-(4,5-dichloro-1 H-indole-2-carbonyl)piperazin-1- yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is ((R)-3-aminopyrrolidin-1-yl)((R)-1-(3,4-dichloro-5-fluoro-1 H-indole-2- carbonyl)pyrrolidin-3-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is ((S)-3-aminopyrrolidin-1-yl)((R)-1-(3,4-dichloro-5- fluoro-1 H-indole-2-carbonyl)pyrrolidin-3-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (3,4-dichloro-5-fluoro- 1 H-indol-2-yl)((3R)-3-(3-(dimethylamino)pyrrolidine-1-carbonyl)pyrrolidin-1- yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (3,4-dichloro-5-fluoro-1 H-indol-2-yl)((3S)-3-(3- (dimethylamino)pyrrolidine-1-carbonyl)pyrrolidin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is ((R)-3- aminopyrrolidin-1-yl)((R)-1-(4-chloro-5-fluoro-1 H-indole-2-carbonyl)pyrrolidin-3- yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is ((S)-3-aminopyrrolidin-1-yl)((S)-1-(4-chloro-5-fluoro-1 H-indole-2- carbonyl)pyrrolidin-3-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is ((R)-3-aminopyrrolidin-1-yl)((S)-1-(4-chloro-5- fluoro-1 H-indole-2-carbonyl)pyrrolidin-3-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is ((S)-3-aminopyrrolidin- 1-yl)((R)-1-(4-chloro-5-fluoro-1 H-indole-2-carbonyl)pyrrolidin-3-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (3- (azetidin-1-yl)pyrrolidin-1-yl)((R)-1-(3,4-dichloro-5-fluoro-1 H-indole-2- carbonyl)pyrrolidin-3-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (3-(azetidin-1 -yl)pyrrolidin-1 -yl)((S)-1 -(3,4- dichloro-5-fluoro-1 H-indole-2-carbonyl)pyrrolidin-3-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (3,4-dichloro-5-fluoro- 1 H-indol-2-yl)((3R)-3-(3-(3,3-difluoroazetidin-1-yl)pyrrolidine-1-carbonyl)pyrrolidin-1- yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (3,4-dichloro-5-fluoro-1 H-indol-2-yl)((3S)-3-(3-(3,3-difluoroazetidin-1- yl)pyrrolidine-1-carbonyl)pyrrolidin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (2-amino-4-pyridyl)-[4-(4,5- dichloro-1 H-indole-2-carbonyl)piperazin-1-yl]methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(6-(4,5-dichloro-1 H- indole-2-carbonyl)-2,6-diazaspiro[3.4]octan-2-yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(6-(4,5-dichloro-1 H- indole-2-carbonyl)-1 ,6-diazaspiro[3.4]octan-1-yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(7-(4,5-dichloro-1 H- indole-2-carbonyl)-1 ,7-diazaspiro[4.4]nonan-1-yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(2-(4,5-dichloro-1 H- indole-2-carbonyl)-2,6-diazaspiro[3.4]octan-6-yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(7-(4,5-dichloro-1 H- indole-2-carbonyl)-2,7-diazaspiro[4.4]nonan-2-yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 8-(3,4-dichloro-5- fluoro-1 / 7-indole-2-carbonyl)-2-methyl-2,8-diazaspiro[4.5]decan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 8- (3,4-dichloro-5-fluoro-1 / 7-indole-2-carbonyl)-1-methyl-1 ,8-diazaspiro[4.5]decan-2-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 8-(3,4-dichloro-5-fluoro-1 / 7-indole-2-carbonyl)-1-methyl-3-oxa-1 ,8- diazaspiro[4.5]decan-2-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 8-(3,4-dichloro-5-fluoro-1 / 7-indole-2-carbonyl)-1 ,3- dimethyl-1 ,3,8-triazaspiro[4.5]decan-2-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)-4-(3,4-dichloro-5-fluoro-1 / 7-indole- 2-carbonyl)-1,3-dimethylpiperazin-2-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-4-(3,4-dichloro-5-fluoro-1 / 7-indole-2- carbonyl)-1,3-dimethylpiperazin-2-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)-(3,4-dichloro-5-fluoro-1 / 7-indol-2-yl)(4- (pyrrolidine-3-carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-(3,4-dichloro-5-fluoro-1 / 7-indol-2- yl)(4-(pyrrolidine-3-carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (3,4-dichloro-5-fluoro- 1 / 7-indol-2-yl)(4-(methyl-D-prolyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-(3,4-dichloro-5- fluoro-1 / 7-indol-2-yl)(4-(4,4-difluoropyrrolidine-2-carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)-(3,4-dichloro-5-fluoro-1 / 7-indol-2-yl)(4-(4,4-difluoropyrrolidine-2-carbonyl)piperazin- 1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 7-(3,4-dichloro-5-fluoro-1 / 7-indole-2-carbonyl)-2- methylhexahydroimidazo[1,5-a]pyrazin-3(2 / - / )-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-(3,4-dichloro-5-fluoro-1 / 7- indol-2-yl)(4-(4,4-difluoro-1-methylpyrrolidine-2-carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)-(3,4-dichloro-5-fluoro-1 / 7-indol-2-yl)(4-(4,4-difluoro-1 -methylpyrrolidine-2- carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)-(3,4-dichloro-5-fluoro-1 / 7-indol-2-yl)(4-(1- methylpyrrolidine-3-carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-(3,4-dichloro-5- fluoro-1 / 7-indol-2-yl)(4-(1-methylpyrrolidine-3-carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (4- (6-aminonicotinoyl)piperazin-1-yl)(3,4-dichloro-5-fluoro-1 / 7-indol-2-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)- 2-(3,4-dichloro-5-fluoro-1 / 7-indole-2-carbonyl)hexahydropyrrolo[1 ,2-a]pyrazin-6(2 / - / )- one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-2-(3,4-dichloro-5-fluoro-1 / 7-indole-2-carbonyl)hexahydropyrrolo[1 ,2- a]pyrazin-6(2 / - / )-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-7-(3,4-dichloro-5-fluoro-1 H-indole-2- carbonyl)hexahydro-3 / 7-oxazolo[3,4-a]pyrazin-3-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)-7-(3,4-dichloro-5-fluoro-1 H- indole-2-carbonyl)hexahydro-3 / 7-oxazolo[3,4-a]pyrazin-3-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(4-(3,4-dichloro-5- fluoro-1 / 7-indole-2-carbonyl) piperazin-1 -yl)-2-morpholinoethan-1 -one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (4- (2-aminoisonicotinoyl) piperazin-1 -yl) (3,4-dichloro-5-fluoro-1 H-indol-2-yl) methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is

[0288] 1-(4-(3,4-dichloro-1 / 7-indole-2-carbonyl) piperazin-1 -yl)-2-methoxyethan-1 -one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)-

[0289] 2-(4-chloro-3,5-difluoro-1 / 7-indole-2-carbonyl) hexahydropyrrolo[1 ,2-a] pyrazin-6(2 / 7)- one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-2-(4-chloro-3,5-difluoro-1 / 7-indole-2-carbonyl) hexahydropyrrolo[1 ,2-a] pyrazin-6(2 / 7)-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (4-(2-aminoisonicotinoyl)piperazin-1-yl)(4,5-dichloro-

[0290] 1 H-indol-2-yl) methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is ((R)-3-aminopyrrolidin-1-yl)((R)-1-(4,5-dichloro-1 H- indole-2-carbonyl) pyrrolidin-3-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 2-amino-1-(4-(4-chloro-3,5-difluoro- 1 H-indole-2-carbonyl)piperazin-1-yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-(3,4-dichloro-5-fluoro-1 H-indol-2- yl)(4-prolylpiperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is ((3S,4R)-3-amino-4-fluoropyrrolidin-1-yl)((R)-1- (3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)pyrrolidin-3-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (3,4- dichloro-5-fluoro-1 H-indol-2-yl)(4-((3S,4S)-4-(trifluoromethyl)pyrrolidine-3- carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is azetidin-3-yl(4-(4-chloro-3,5-difluoro-1 H-indole-2- carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(3- fluoroazetidine-3-carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is ((3S,4S)-3-amino-4- fluoropyrrolidin-1-yl)((R)-1-(3,4-dichloro-5-fluoro-1H-indole-2-carbonyl) yrrolidine-3- yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)-(4-chloro-3,5-difluoro-1 H-indol-2-yl) (4-(morpholine-3-carbonyl) piperazin-1 -yl) methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-(4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(morpholine- 3-carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)-azetidin-2-yl(4-(4-chloro-3,5-difluoro-1 H- indole-2-carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-azetidin-2-yl(4-(4-chloro-3,5- difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (3,4-dichloro-5-fluoro- 1 H-indol-2-yl)(4-((2R,4R)-4-fluoropyrrolidine-2-carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (4- (2-aminoisonicotinoyl) piperazin-1 -yl) (4-chloro-3,5-difluoro-1 H-indol-2-yl) methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)-(4-chloro-3,5-difluoro-1 H-indol-2-yl) (4-(4,4-difluoropyrrolidine-2-carbonyl) piperazin-1 -yl) methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-(4-chloro-3,5-difluoro-1 H-indol-2-yl) (4-(4,4- difluoropyrrolidine-2-carbonyl) piperazin-1 -yl) methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 2-(azetidin-3-yloxy)-1- (4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)- (4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-prolylpiperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)- (4-chloro-3,5-difluoro- 1 H-indol-2-yl)(4-prolylpiperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is ((R)- 3-aminopyrrolidin-1-yl) ((R)-1-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl) pyrrolidin-3- yl) methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(4-(3-chloro-4-fluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2- methoxyethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 4-(4-chloro-3,5-difluoro-1 H-indole-2- carbonyl)piperazin-2-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(4-(4-chloro-3,5-difluoro-1 H-indole-2- carbonyl)piperazin-1-yl)-2-(dimethylamino)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(4-(4-chloro-3,5- difluoro- 1 H-indole-2-carbonyl)piperazin-1-yl)-2-morpholinoethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (4- chloro-3,5-difluoro-1 H-indol-2-yl)(4-(oxetane-3-carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (4- chloro-3,5-difluoro-1 H-indol-2-yl)(4-(3,3-difluorocyclobutane-1-carbonyl)piperazin-1- yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-((1 R,3R)-3- methoxycyclobutane-1-carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(4-(3-chloro-4,5- difluoro- 1 H-indole-2-carbonyl)piperazin-1-yl)-2-methoxyethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)- (4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(oxetane-2-carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-(4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(oxetane-2-carbonyl)piperazin-1- yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 2-(azetidin-1-yl)-1-(4-(4-chloro-3,5-difluoro-1 H-indole-2- carbonyl)piperazin-1-yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(1- methylazetidine-3-carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (3aR,6aR)-5-(3,4- dichloro-5-fluoro-1 H-indole-2-carbonyl)-2-methylhexahydropyrrolo[3,4-c]pyrrol-1 (2H)- one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 2-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)hexahydro-2H,6H- pyrazino[1 ,2-c][1 ,3]oxazin-6-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(methyl-L- prolyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(methyl-D- prolyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(4-(4-chloro-3,5-difluoro-1 H-indole-2- carbonyl)piperazin-1-yl)-2-methoxyethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)-1-(4-(4-chloro-3,5-difluoro-1 H- indole-2-carbonyl)-3-methylpiperazin-1-yl)-2-methoxyethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 2-( zetidine-1-yl)-1-(4-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl) piperazin-1 -yl) ethan-1- one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)-(4-chloro-3,5-difluoro-1 H-indol-2-yl) (4-(4-methylmorpholine-3- carbonyl) piperazin-1 -yl) methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-(4-chloro-3,5-difluoro-1 H-indol-2-yl) (4-(4- methylmorpholine-3-carbonyl) piperazin-1 -yl) methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 2-(3,4-dichloro-5- fluoro-1 H-indole-2-carbonyl)octahydro-6H-pyrido[1 ,2-a]pyrazin-6-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(4- (3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(3-methoxyazetidin-1- yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(4-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(3- fluoroazetidin-1-yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(4-(3,4-dichloro-5-fluoro-1 H-indole-2- carbonyl)piperazin-1-yl)-2-(3,3-difluoroazetidin-1-yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(4-(4-chloro-3,5- difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(3-methoxyazetidin-1-yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1- (4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(3-fluoroazetidin-1- yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(3,3- difluoroazetidin-1-yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(4-(4-chloro-3,5-difluoro-1 H-indole-2- carbonyl)piperazin-1-yl)-2-(oxetan-3-yloxy)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-7-(4-chloro-3,5- difluoro-1 H-indole-2-carbonyl)hexahydro-3H-oxazolo[3,4-a]pyrazin-3-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)- 7-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)hexahydro-3H-oxazolo[3,4-a]pyrazin-3- one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (3,4-dichloro-5-fluoro-1 H-indol-2-yl)(4-((2R,4S)-4-fluoropyrrolidine-2- carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 5-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)-2- methyloctahydro-3H-pyrrolo[3,4-c] yridine-3-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-(3,4-dichloro-5-fluoro-1 H-indol-2- yl)(4-(4,4-difluoro-1-methylpyrrolidine-2-carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (3,4- dichloro-5-fluoro-1 H-indol-2-yl)(4-((3S,4S)-1-methyl-4-(trifluoromethyl)pyrrolidine-3- carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (3,4-dichloro-5-fluoro-1 H-indol-2-yl)(4-((2R,4R)- 4-fluoro-1-methylpyrrolidine-2-carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (4- chloro-3,5-difluoro-1 H-indol-2-yl)(4-(3-fluoro-1-methylazetidine-3-carbonyl)piperazin-1- yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-((1- methylazetidin-3-yl)oxy)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)-(4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(4,4- difluoro-1-methylpyrrolidine-2-carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)- (4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(4,4-difluoro-1-methylpyrrolidine-2- carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (3,4-dichloro-5-fluoro-1 H-indol-2-yl)(4-((2R,4S)- 4-fluoro-1-methylpyrrolidine-2-carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (3- fluoroazetidin-3-yl)methyl 4-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)piperazine-1- carboxylate, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is azetidin-3-yl 4-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl) piperazine-1- carboxylate, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(4-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(oxetan- 3-yloxy)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 8-(3,4-dichloro-5-fluoro-1 H-indole-2- carbonyl)hexahydropyrazino[2,1-c][1 ,4]oxazin-4(3H)-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 7-(3,4-dichloro-5- fluoro-1 H-indole-2-carbonyl)tetrahydroimidazo[1 ,5-a]pyrazine-1 ,3(2H,5H)-dione, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 2- (3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)-8-methylhexahydropyrrolo[1 ,2-a]pyrazin- 6(2H)-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 2-(azetidin-3-yloxy)-1-(4-(3,4-dichloro-5-fluoro-1 H-indole-2- carbonyl)piperazin-1-yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (3aR,6aR)-5-(4-chloro-3,5-difluoro-1 H-indole-2- carbonyl)-2-methylhexahydropyrrolo[3,4-c]pyrrol-1(2H)-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (3aS,6aS)-5-(4-chloro- 3,5-difluoro-1 H-indole-2-carbonyl)-2-methylhexahydropyrrolo[3,4-c]pyrrol-1 (2H)-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 2- (4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)hexahydro-2H,6H-pyrazino[1 ,2- c][1 ,3]oxazin-6-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-2-(3,4-dichloro-5-fluoro-1 H-indole-2- carbonyl)hexahydro-2H,6H-pyrazino[1 ,2-c][1 ,3]oxazin-6-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)-2-(3,4-dichloro-5- fluoro-1 H-indole-2-carbonyl)hexahydro-2H,6H-pyrazino[1 ,2-c][1 ,3]oxazin-6-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(4- (3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-((1-methylazetidin-3- yl)oxy)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 8-(3,4-dichloro-5-fluoro-1 H-indole-2- carbonyl)octahydro-4 H-pyrazino[1 ,2- a]pyrazin-4-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(4-(3,4-dichloro-5- fluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(3-fluoroazetidin-3-yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(4- (4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(3,3-difluoropyrrolidin-1- yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)-1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)-3- methylpiperazin-1-yl)-2-(3,3-difluoroazetidin-1-yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-1-(4-(4-chloro-3,5- difluoro-1 H-indole-2-carbonyl)-3-methylpiperazin-1-yl)-2-(3,3-difluoroazetidin-1- yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(3,3- difluorocyclobutoxy)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-1-(4-(4-chloro-3,5-difluoro-1 H-indole-2- carbonyl)-3-(methoxymethyl)piperazin-1-yl)-2-(3,3-difluoroazetidin-1-yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)-1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(3,3- difluoroazetidin-1-yl)propan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-1-(4-(4-chloro-3,5-difluoro-1 H-indole-2- carbonyl)piperazin-1-yl)-2-(3,3-difluoroazetidin-1-yl)propan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)- 1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(3,3-difluoro-2- methylazetidin-1-yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-1-(4-(4-chloro-3,5-difluoro-1 H-indole-2- carbonyl)piperazin-1-yl)-2-(3,3-difluoro-2-methylazetidin-1-yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 4-(4- chloro-3,5-difluoro-1 H-indole-2-carbonyl)-N,N-dimethylmorpholine-2-carboxamide, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)- (4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(tetrahydrofuran-2-carbonyl)piperazin-1- yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-(4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(tetrahydrofuran-2- carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)- N,N-dimethylpiperazine-2-carboxamide, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(4-(4-chloro-3,5-difluoro-1 H-indole-2- carbonyl)piperazin-1-yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-(4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(4,4- dimethyloxetane-2-carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)-(4-chloro-3,5- difluoro-1 H-indol-2-yl)(4-(4,4-dimethyloxetane-2-carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)-8-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)hexahydropyrazino[2,1-c][1 ,4]oxazin- 4(3H)-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-8-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)hexahydropyrazino[2,1- c][1 ,4]oxazin-4(3H)-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(4-(4-chloro-3,5-difluoro-1 H-indole-2- carbonyl)piperazin-1-yl)-2,2-difluoroethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-(4-chloro-3,5-difluoro-1 H-indol-2- yl)(4-(2-methyloxetane-2-carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)-(4-chloro-3,5- difluoro- 1 H-indol-2-yl)(4-(2-methyloxetane-2-carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(4- (4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(trifluoromethoxy)ethan-1- one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2- (difluoromethoxy)ethan-l-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)-4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)-N- methylpiperazine-2-carboxamide, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-4-(4-chloro-3,5-difluoro-1 H-indole-2- carbonyl)-N-methylpiperazine-2-carboxamide, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)-4-(4-chloro-3,5-difluoro-1 H-indole- 2-carbonyl)-N,N-dimethylpiperazine-2-carboxamide, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-4-(4-chloro-3,5-difluoro-1 H- indole-2-carbonyl)-N,N-dimethylpiperazine-2-carboxamide, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(4-(3,4-dichloro-1 H- indole-2-carbonyl)piperazin-1-yl)-2-(3,3-difluoroazetidin-1-yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)- (4-chloro-3-fluoro-1 H-indol-2-yl)(4-(oxetane-2-carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(4- (4-chloro-3-fluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-methoxyethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is 1-(4- (4-chloro-3-fluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(3,3-difluoroazetidin-1- yl)ethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-(4-chloro-3-fluoro-1 H-indol-2-yl)(4-(tetrahydrofuran-2- carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)-(4-chloro-3-fluoro-1 H-indol-2-yl)(4- (tetrahydrofuran-2-carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-(3,4-dichloro-1 H- indol-2-yl)(4-(oxetane-2-carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)-(3,4-dichloro-1 H- indol-2-yl)(4-(oxetane-2-carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)-1-(4-(3,4-dichloro- 1 H-indole-2-carbonyl)-3-methylpiperazin-1-yl)-2-methoxyethan-1-one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)- 1-(4-(3,4-dichloro-1 H-indole-2-carbonyl)-3-methylpiperazin-1-yl)-2-methoxyethan-1- one, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (R)-(3,4-dichloro-1 H-indol-2-yl)(4-(tetrahydrofuran-2-carbonyl)piperazin-1- yl)methanone, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is (S)-(3,4-dichloro-1 H-indol-2-yl)(4-(tetrahydrofuran-2- carbonyl)piperazin-1-yl)methanone, or a pharmaceutically acceptable salt thereof.

[0291] Compounds of the invention also include tautomeric forms. Tautomeric forms result from the swapping of a single bond with an adjacent double bond together with the concomitant migration of a proton. Tautomeric forms include prototropic tautomers which are isomeric protonation states having the same empirical formula and total charge. Example prototropic tautomers include ketone - enol pairs, amide - imidic acid pairs, lactam - lactim pairs, enamine - imine pairs, and annular forms where a proton can occupy two or more positions of a heterocyclic system, for example, 1 H- and 3H- imidazole, 1 H-, 2H- and 4H- 1 ,2,4-triazole, 1 H- and 2H- isoindole, and 1 H- and 2H- pyrazole. Tautomeric forms can be in equilibrium or sterically locked into one form by appropriate substitution. Tautomeric forms can also include methyltropic tautomers, which result from the swapping of a single bond with an adjacent double bond together with the concomitant migration of a methyl group.

[0292] Compounds of the invention also include all isotopes of atoms occurring in the intermediates or final compounds. Isotopes include those atoms having the same atomic number but different mass numbers. In some embodiments, the compounds of the invention include one or more isotopes of atoms in an amount greater than the natural abundance of the isotope. For example, isotopes of hydrogen include tritium and deuterium. In some embodiments, a compound of the invention includes at least one deuterium atom in an amount that is greater than the natural abundance of deuterium (e.g., the compound is enriched in deuterium).

[0293] All compounds described herein, and pharmaceutically acceptable salts thereof, can be found together with other substances such as water and solvents (e.g., in the form of hydrates and solvates). In one aspect, the present invention is directed to an intermediate compound, or a pharmaceutically acceptable salt thereof, which can be used in the synthesis of the compounds of the present invention. For example, said intermediate compound is in some embodiments one of the intermediate compounds, or a pharmaceutically acceptable salt thereof, of any one of examples 1 to 194 disclosed herein. In some embodiments the compound of the present invention is selected from any of the intermediate compounds, or a pharmaceutically acceptable salt thereof, disclosed in any one of examples 1 to 194 herein.

[0294] The compounds of the present invention may contain, for example, one or more asymmetric carbon atoms, and therefore may exist as stereoisomers, enantiomers and diastereomers. Accordingly, the scope of the instant invention is to be understood to encompass all possible stereoisomers of the illustrated compounds, including the stereoisomerically pure form and stereoisomeric mixtures of any chemical structures disclosed herein, unless the stereochemistry is specifically identified. If the stereochemistry of a structure or a portion of a structure is not indicated with, for example, bold or dashed lines, the structure or portion of the structure is to be interpreted as encompassing all stereoisomers of it. If the stereochemistry of a structure or a portion of a structure is indicated with, for example, bold or dashed lines, the structure or portion of the structure is to be interpreted as encompassing only the stereoisomer indicated.

[0295] The term “stereoisomer” or “stereoisomerically pure” compound as used herein refers to one stereoisomer of a compound that is substantially free of other stereoisomers of that compound. For example, a stereoisomerically pure compound having one chiral center will be substantially free of the mirror image enantiomer of the compound and a stereoisomerically pure compound having two chiral centers will be substantially free of the other enantiomer and diastereomers of the compound. A typical stereoisomerically pure compound comprises greater than about 80% by weight of one stereoisomer of the compound and equal or less than about 20% by weight of other stereoisomers of the compound, greater than about 90% by weight of one stereoisomer of the compound and equal or less than about 10% by weight of the other stereoisomers of the compound, greater than about 95% by weight of one stereoisomer of the compound and equal or less than about 5% by weight of the other stereoisomers of the compound, or greater than about 97% by weight of one stereoisomer of the compound and equal or less than about 3% by weight of the other stereoisomers of the compound.

[0296] In some embodiments, the compound as defined herein is stereoisomerically pure.

[0297] Mixtures of stereoisomers may be resolved using standard techniques, such as chiral columns or chiral resolving agents, for example as outlined in the example section.

[0298] Pharmaceutical composition

[0299] The present invention also relates to a pharmaceutical composition comprising, for example as an active ingredient, a pharmaceutically effective amount of a compound as disclosed herein. In some embodiments, said pharmaceutical composition comprises a therapeutically effective amount of a compound as disclosed herein or a pharmaceutically acceptable salt thereof, together with at least one pharmaceutically acceptable carrier, excipient and / or diluent.

[0300] While a compound as disclosed herein for use in therapy may be administered in the form of the raw chemical compound, it is often preferred to introduce the active ingredient, optionally in the form of a pharmaceutically acceptable salt, in a pharmaceutical composition together with one or more adjuvants, excipients, carriers, buffers, diluents, and / or other customary pharmaceutical auxiliaries.

[0301] In some embodiments, the invention provides pharmaceutical compositions comprising a compound as disclosed herein or a pharmaceutically acceptable salt thereof, together with one or more pharmaceutically acceptable carriers, and, optionally, other therapeutic and / or prophylactic ingredients, known and used in the art. The carrier(s) must be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not harmful to the recipient thereof.

[0302] A therapeutic amount or therapeutically effective amount or dose refers to that amount of active ingredient, i.e. the compounds or compositions as disclosed herein, which treats, alleviates, abates, or reduces the severity of symptoms of a disease in a subject, such as ameliorates one or more symptoms of the condition or the condition itself. A therapeutic amount of a compound as described herein may improve patient survival, increase survival time or rate, diminish symptoms, make an injury, disease, or condition (e.g. a neurodegenerative disease) more tolerable, slow the rate of degeneration or decline, or improve a patient’s physical or mental well-being.

[0303] Therapeutic efficacy and toxicity, e.g. ED50, may be determined by standard pharmacological procedures in cell cultures or experimental animals. The dose ratio between therapeutic and toxic effects is the therapeutic index and may be expressed by ratio between plasma levels resulting in therapeutic effects and plasma ratios resulting in toxic effects. Pharmaceutical compositions exhibiting large therapeutic indexes are preferred. In some embodiments, the therapeutically effective dose of a compound as disclosed herein is in the range of about 0.01 mg / kg to about 100 mg / kg bodyweight / day.

[0304] The dose administered must of course be carefully adjusted to the age, weight and condition of the individual being treated, as well as the route of administration, dosage form and regimen, and the result desired, and the exact dosage should of course be determined by the practitioner.

[0305] To administer refers to a method of delivering agents, compounds, or compositions to the desired site of biological action. These methods include, but are not limited to, enteral delivery, oral delivery, topical delivery, parenteral delivery, intravenous delivery, intradermal delivery, intramuscular delivery, intrathecal delivery, colonic delivery, rectal delivery, or intraperitoneal delivery.

[0306] Biological activity

[0307] As demonstrated in Example 195, compounds of the present invention are Kv1.3 potassium channel antagonists.

[0308] Medical use

[0309] Being Kv1.3 potassium channel antagonists, the compounds of the present invention are of use in the treatment of diseases and disorders of a living body, including human. As used herein, the term “treatment” includes treatment, prevention, and / or alleviation or amelioration of one or more diseases and disorders or one or more symptoms of a disease or disorder. In one aspect, the compound as described herein is for use as a medicament.

[0310] In one aspect, the present invention relates to a compound of Formula (I), Formula (I) wherein R1is halogen or H; R2is halogen; R3is H or halogen; R5is H or halogen; R6is H or halogen; R4is of Formula (II): Formula (II) wherein X1is C(R7)(R8); X2is C(R9)(R10) or a bond; X3is N(C(O)R11), C(R12)(C(O)R13), C(R14)(R15) or N(R16); X4is C(R17)(R18), O or C(O); X5is C(R19)(R20) or a bond; X6is a bond or C(R21)(R22); wherein R9and R11, R9and R13, R10and R11, R10and R13, R13and R17, R13and R18, or R14and R15are optionally joined together to form a ring together with the intervening atom(s); R7is H, C1-3 alkyl optionally substituted with 1 to 3 F or C1-3 alkoxy, or halogen, such as F; R8is H, C1-3 alkyl optionally substituted with 1 to 3 F or C1-3 alkoxy, or halogen, such as F; R9is H, C1-3 alkyl optionally substituted with 1 to 3 halogens, halogen, such as F, or - C(O)N(R31)(R32), wherein R31is H or C1-3alkyl and R32is H or C1-3alkyl, or when R9is linked to R11or R13to form a ring, then R9is a bond, -C(O)- or a C1-3alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl; R10is H, C1-3alkyl optionally substituted with 1 to 3 halogens, halogen, such as F, , or - C(O)N(R31)(R32), wherein R31is H or C1-3alkyl and R32is H or C1-3alkyl, or when R10is linked to R11or R13to form a ring, then R10is a bond, -C(O)- or a C1-3alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl; R11is -X13-R33; X13is a bond, C1-3alkanediyl optionally substituted with C1-3alkyl, -O-, or C1-3alkanediyl- O-; R33is selected from the group consisting of C1-3alkyl, C3-6cycloalkyl, C1-3alkoxy, pyridinyl, azetidinyl, pyrrolidinyl, oxetanyl, tetrahydrofuranyl, and morpholinyl, each of which is optionally substituted with one or more substituents individually selected from halogen; C1-3alkoxy optionally substituted with one or more F; C1-3alkyl optionally substituted with one or more F; NH2; N(H)(CH3); and N(CH3)2; or when R11is linked to R9or R10to form a ring, then R11is -O-, -N(R28)-, or C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl, wherein one methylene group of the C1-3 alkanediyl is optionally replaced by -O- or -N(R28)-, wherein R28is H or C1-3 alkyl; R12is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R13is selected from the group consisting of NH2, N(H)(CH3), N(CH3)2, pyrrolidinyl, azetidinyl, and piperazinyl, wherein ^ said pyrrolidinyl is optionally substituted with one or more substituents individually selected from the group consisting of halogen, NH2, N(H)(CH3), N(CH3)2 and azetidinyl, and said azetidinyl is optionally substituted with one or more halogens, and ^ said azetidinyl optionally substituted with NH2; or when R13is linked to R9, R10, R17, or R18to form a ring, then R13is -N(R28)-, wherein R28is H or C1-3alkyl; R14is -X7N(R23)(C(O)R24), wherein X7is a bond or C1-3 alkanediyl; R24is C1-3 alkyl; and R23is H or C1-3 alkyl, and R15is H or C1-3 alkyl, or R23is a bond or C1-3alkanediyl, and R15is a bond or C1-3alkanediyl and R23is linked to R15to form a ring; or R14is -X9C(O)X11-, R15is a bond or C1-3alkanediyl, and X11is linked to R15to form a ring, wherein X9is a bond or -N(R29)-; R29is C1-3alkyl; X11is -O-, C1-3alkanediyl, or -N(R30)-; and R30is C1-3alkyl; R16is H or C1-3alkyl; R17is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; or when R17is linked to R13to form a ring, then R17is a bond or a C1-3alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl; R18is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; or when R18is linked to R13to form a ring, then R18is a bond or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl; R19is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R20is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R21is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R22is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; any two of R7, R8, R9, R10, R17, R18, R19, R20, R21, and R22are optionally linked together to form a ring; with the proviso that when X4is O, then X3is C(R12)C(O)R13and R13is NH2, N(H)(CH3) or N(CH3)2; with the proviso that when X3is N(R16), then X4is C(O), with the proviso that when X4is C(O), then X3is N(R16), and with the proviso that when X2is a bond, then X3is C(R12)(C(O)R13) or C(R14)(R15), or a pharmaceutically acceptable salt thereof., or a pharmaceutically acceptable salt thereof, for use in the treatment of a disease or medical condition where inhibition of KV1.3 potassium channel is beneficial. In one aspect, the present invention relates to a compound as defined herein, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition as defined herein, for use in the treatment of a disease or medical condition where inhibition of KV1.3 potassium channel is beneficial. In one aspect, the present invention relates to a method for treatment of a disease or medical condition where inhibition of KV1.3 potassium channel is beneficial comprising administering a compound, or a pharmaceutically acceptable salt thereof, as described herein to a subject in need thereof. In one aspect, the present invention relates to use of a compound, or a pharmaceutically acceptable salt thereof, as described herein for the manufacture of a medicament for treatment of disease or medical condition where inhibition of KV1.3 potassium channel is beneficial. The compounds of the present invention may be utilized in any therapy where it is desired to treat, reduce or alleviate symptoms of KV1.3 mediated diseases such as inflammatory and autoimmune diseases, diabetes, obesity or cancers. In one aspect, the present invention relates to the compound as defined herein, or a pharmaceutically acceptable salt thereof, for use in the prophylaxis and / or treatment of KV1.3 mediated conditions. In one aspect, the present invention relates to the compound, or a pharmaceutically acceptable salt thereof, as defined herein for use in the treatment of a neurodegenerative disease. A "neurodegenerative disease" refers to a central nervous system characterized by progressive, normally gradual, loss of functional neural tissue. In some embodiments, the neurodegenerative disease is a tauopathy. Tauopathies depicts some neurodegenerative disorders characterized by tau deposits in the brain, with symptoms of dementia and parkinsonism. In some embodiments, the neurodegenerative disease is a tauopathy selected from the group consisting of Primary age related tauopathy (PART), globular glial tauopathy, Chronic traumatic encephalopathy (CTE), Progressive supranuclear palsy, Corticobasal degeneration, diffuse neurofibrillary tangles with calcification (DNTC), Frontotemporal dementia (FTD), and FTD with parkinsonism-17 (FTD with parkinsonism linked to chromosome 17; FTDP-17). In some embodiments, the neurodegenerative disease is a neurodegenerative disorders associated with TDP-43 (TDP-43 proteinopathies or TDP-43-opathies). Inclusions of pathogenic deposits containing TAR DNA-binding protein 43 (TDP-43) are evident in the brain and spinal cord of patients that present across a spectrum of neurodegenerative diseases. In some embodiments, the neurodegenerative disease is a TDP-43 proteinopathy selected from the group consisting of amyotrophic lateral sclerosis (ALS), sporadic amyotrophic lateral sclerosis (sALS), familial amyotrophic lateral sclerosis (fALS), frontotemporal lobar degeneration / disease (FTLD), Primary lateral sclerosis (PLS), progressive muscular atrophy (PMA), FTLD-tau, FTLD-FUS (bvFTLD), FTLD-TDP-43 or FTLD-U (types a, b and c), Facial onset sensory and motor neuronopathy (FOSMN), Limbic-predominant age-related TDP-43 encephalopathy (LATE), cerebral age-related TDP-43 with sclerosis (CARTS), Guam Parkinson-dementia complex (G-PDC) and ALS (G-ALS), Kii ALS / PDC, amyotrophic lateral sclerosis / parkinsonism-dementia complex of Guam (ALS-PDC), Multisystem proteinopathy (MSP; also referred to as inclusion body myopathy (IBM) associated with early-onset Paget disease of the bone and FTLD dementia), Perry disease, and disorders with concomitant TDP-43 pathology, including Alzheimer’s disease (AD) and Chronic traumatic encephalopathy (CTE). In one aspect, the present invention relates to the compound, or a pharmaceutically acceptable salt thereof, as defined herein for use in the treatment of muscular dystrophy such as myotonic dystrophy (DM) including Type 1 DM (DM1) and Type 2 DM (DM2). In some embodiments, the neurodegenerative disease is Multisystem proteinopathy (MSP). MSP is a dominantly inherited, pleiotropic, degenerative disorder of humans that can affect muscle, bone, and / or the central nervous system. MSP can manifest clinically as classical amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), inclusion body myopathy (IBM), Paget's disease of bone (PDB), or as a combination of these disorders (IBMPFD, IBMPFD / ALS). In some embodiments, the neurodegenerative disease is a synucleinopathy. Synucleinopathies (also called α-Synucleinopathies) are neurodegenerative diseases characterised by the abnormal accumulation of aggregates of alpha-synuclein protein in neurons, nerve fibres or glial cells. In some embodiments, the neurodegenerative disease is a synucleinopathy selected from the group consisting of Parkinson's disease (PD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), neuroaxonal dystrophies, Alzheimer's Disease with Amygdalar Restricted Lewy Bodies (AD / ALB). In some embodiments, the neurodegenerative disease is cognitive deficit and / or memory loss. In some embodiments, the neurodegenerative disease is dementia. In some embodiments, the neurodegenerative disease is dementia selected from the group consisting of Alzheimer’s disease, Parkinson’s disease dementia, Huntingtons disease dementia, vascular dementia, HIV dementia, frontotemporal dementia, dementia with lewy bodies, prion disease dementia, argyrophilic grain dementia, dementia pugilistica, Guadeloupean parkinsonism with dementia, neurofibrillary tangle- predominant dementia, tangle only dementia, Down’s syndrome, semantic dementia, familial British dementia, familial Danish dementia, and other dementias caused by another medical condition such as brain tumors, subdural hematoma, endocrine disorders, nutritional deficiencies, infections, immune disorders, liver or kidney failure, metabolic disorders such as Kufs disease, some leukodystrophies, some neurological disorders such as epilepsy, and multiple sclerosis. Disorders of peripheral nerves (peripheral neuropathy) are the most common neurological complications of systemic amyloidosis. In some embodiments, the neurodegenerative disease is peripheral amyloidosis (peripheral neuropathy in systemic amyloidosis). In some embodiments, the neurodegenerative disease is a demyelinating disorder. In some embodiments, the neurodegenerative disease is a demyelinating disorder of the central nervous system, CNS. In some embodiments, the demyelinating disorder is a myelinoclastic or demyelinating disorder, such as selected from the group consisting of multiple sclerosis, neuromyelitis optica (Devic’s disease) and idiopathic inflammatorydemyelinating diseases. In some embodiments, the demyelinating disorder is a leukodystrophic or dysmyelinating disorder, such as selected from the group consisting of CNS neuropathies such as vitamin B12 deficiency, central pontine myelinolysis, myelopathies such as tabes dorsalis (syphilitic myelopathy), leukoencephalopathies and leukodystrophies. In some embodiments, the neurodegenerative disease is a demyelinating disorder of the peripheral nervous system, PNS. In some embodiments, the demyelinating disorder is selected from the group consisting of Guillain–Barré syndrome and its chronic counterpart, chronic inflammatory demyelinating polyneuropathy; Anti-MAG peripheral neuropathy; Charcot–Marie–Tooth disease and its counterpart Hereditary neuropathy with liability to pressure palsy; Copper deficiency-associated conditions (peripheral neuropathy, myelopathy, and rarely optic neuropathy); and Progressive inflammatory neuropathy. In some embodiments, the neurodegenerative disease is Alzheimer’s disease (AD). In some embodiments, the neurodegenerative disease is Alzheimer’s disease (AD) with the R47H mutation. In some embodiments, the neurodegenerative disease is early Alzheimer’s disease. In some embodiments, the neurodegenerative disease is Frontotemporal lobar degeneration (FTLD). In some embodiments, the neurodegenerative disease is frontotemporal dementia. In some embodiments, the neurodegenerative disease is Parkinson’s disease. In some embodiments, the neurodegenerative disease is Nasu-Hakola disease (NHD). In some embodiments, the neurodegenerative disease is FTLD-like syndrome. In some embodiments, the neurodegenerative disease is Huntington disease. In some embodiments, the neurodegenerative disease is Amyotrophic lateral sclerosis (ALS). In some embodiments, the neurodegenerative disease is multiple sclerosis (MS). In some embodiments, the neurodegenerative disease is Guillain-Barre syndrome. In some embodiments, the neurodegenerative disease is chronic inflammatory demyelinating polyneuropathies. In some embodiments, the neurodegenerative disease is progressive subcortical gliosis. In some embodiments, the neurodegenerative disease is Charcot-Marie-Tooth disease. In some embodiments, the neurodegenerative disease is prion disease, such as prion protein cerebral amyloid angiopathy. In some embodiments, the neurodegenerative disease is stroke. In some embodiments, the neurodegenerative disease is cerebral amyloid angiopathy (CAA). In some embodiments the neurodegenerative disease is fragile X-associated tremor ataxia syndrome (FXTAS). In some embodiments the neurodegenerative disease is herpes simplex virus (HSV) encephalitis. In some embodiments the neurodegenerative disease is HIV-associated neurocognitive disorders (HAND). In some embodiments the neurodegenerative disease is progressive supranuclear palsy (PSP). In some embodiments the neurodegenerative disease is corticobasal degeneration. In some embodiments the neurodegenerative disease is Hallevorden-Spatz disease. In some embodiments the neurodegenerative disease is pallido-ponto-nigral degeneration. In some embodiments the neurodegenerative disease is postencephalitic parkinsonism. In some embodiments the neurodegenerative disease is subacute sclerosing panencephalitis (SSPE). In some embodiments the neurodegenerative disease is retinal degeneration (e.g., macular degeneration). In some embodiments the neurodegenerative disease is a Leukoencephalopathy. Leukoencephalopathy (leukodystrophy-like diseases) is a term that describes all of the brain white matter diseases, whether their molecular cause is known or unknown. In some embodiments the neurodegenerative disease is a Leukoencephalopathy selected from the group consisting of Progressive multifocal leukoencephalopathy, Toxic leukoencephalopathy, Leukoencephalopathy with vanishing white matter, Leukoencephalopathy with neuroaxonal spheroids, Reversible posterior leukoencephalopathy syndrome, Megalencephalic leukoencephalopathy with subcortical cysts, and Hypertensive leukoencephalopathy. In some embodiments, the neurodegenerative disease is ALSP (Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia). In some embodiments the neurodegenerative disease is selected from the group consisting of cerebral autosomal dominant arteriopathy with subcortical infarcts or leukoencephalopathy; cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy; and retinal vasculopathy with cerebral leukoencephalopathy (or cerebroretinal vasculopathy). In some embodiments the neurodegenerative disease is a leukodystrophy. In some embodiments the neurodegenerative disease is vanishing white matter disease (VWM). Leukodystrophies are a group of rare, genetic disorders that affect the white matter of the brain. In some embodiments the neurodegenerative disease is a leukodystrophy selected from the group consisting of metachromatic leukodystrophy (MLD, also known as globoid cell leukodystrophy), Krabbe disease, Canavan disease, X-linked adrenoleukodystrophy, Alexander disease, hypomyelinating leukodystrophy type 7 (4H syndrome), Pelizaeus-Merzbacher disease, cerebrotendineous xanthomatosis and leukoendephalopathy with vanishing white matter. In some embodiments the neurodegenerative disease is adult-onset autosomal dominant leukodystrophy (ADLD). In some embodiments the neurodegenerative disease is X-linked adrenoleukodystrophy (X-ALD). In some embodiments the neurodegenerative disease is Nasu-Hakola disease also known as polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, PLOSL). In some embodiments, the neurodegenerative disease is a transmissible spongiform encephalopathy (TSE), including Creutzfeldt-Jakob disease, Gerstmann-Straussler- Scheinker disease (GSS), kuru, and fatal familial insomnia. In one aspect, the present invention relates to a method for treatment of a neurodegenerative disease comprising administering a compound, or a pharmaceutically acceptable salt thereof, as described herein to a subject in need thereof. In one aspect, the present invention relates to a method for treatment of a neurodegenerative disease comprising one or more steps of administering a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt thereof, as defined herein to a subject in need thereof. In one aspect, the present invention relates to use of a compound, or a pharmaceutically acceptable salt thereof, as described herein for the manufacture of a medicament for treatment of a neurodegenerative disease. In one aspect, the present invention concerns a compound as defined herein, or pharmaceutically acceptable salt thereof, for use in a method of inhibiting or reducing inflammation. In one aspect, the present invention concerns a compound as defined herein, or pharmaceutically acceptable salt thereof, for use in the treatment of an inflammatory condition or disorder. In some embodiments, said KV1.3 mediated condition is selected from the group consisting of inflammatory conditions, allergies and allergic conditions, hypersensitivity reactions, autoimmune diseases, severe infections, and organ or tissue transplant rejection. Exemplary Kv1.3 mediated conditions include inflammatory conditions, immune and proliferative disorders, including but not limited to rheumatoid arthritis (RA), osteoarthritis, osteoporosis, uveitis, inflammatory fibrosis (e.g., scleroderma, lung fibrosis, and cirrhosis), inflammatory bowel disorders (e.g., Crohn's disease, ulcerative colitis and inflammatory bowel disease), multiple sclerosis, psoriasis, contact-mediated dermatitis, systemic lupus erythematosus (SLE) and other forms of lupus, diabetes, type I diabetes, cancer, lupus, scleroderma, Sjogren syndrome, and vasculitis. In one aspect, the present invention relates to the compound, or a pharmaceutically acceptable salt thereof, as defined herein for use in the treatment of a lysosomal storage disorder (LSD). Most lysosomal storage disorders cause progressive neurodegeneration leading to early death. In some embodiments the LSD is a lipidoses, such as a lipidoses selected from the group consisting of cholesteryl ester storage disease, fucosidosis, Schindler disease and Wolman disease. In some embodiments the LSD is a sphingolipidoses, such as a sphingolipidoses selected from the group consisting of Fabry disease, Gaucher disease, Krabbe disease (globoid cell leukodystrophy), metachromatic leukodystrophy (MLD), Niemann-Pick disease (Types A, B and C), Sandhoff disease, Farmer disease, multiple sulfatase deficiency and Tay- Sachs disease. In some embodiments the LSD is a mucopolysaccharidoses, such as a mucopolysaccharidoses selected from the group consisting of Hunter syndrome, Hurler syndrome, Hurler-Scheie syndrome, Scheie syndrome, Sanfilippo syndrome (A, B, C, D), Morquio syndrome, Maroteaux-Lamy syndrome, Sly syndrome and Natowicz syndrome. In some embodiments the LSD is selected from the group consisting of Batten disease, cyctinosis, Danon disease and Pompe disease. In one aspect, the present invention relates to the compound, or a pharmaceutically acceptable salt thereof, as defined herein for use in the treatment of a disease or disorder of the bones and / or joints. In some embodiments, said disease or disorder is selected from the group consisting of arthritis, rheumatoid arthritis, pyle disease, osteoporosis, osteopetrosis, osteosclerosis, skeletal dysplasia and dysosteoplasia. In one aspect, the present invention relates to the compound, or a pharmaceutically acceptable salt thereof, as defined herein for use in the treatment of traumatic brain injuries (TBI) and spinal cord injuries. Traumatic brain injuries (TBI), may also be known as intracranial injuries. Traumatic brain injuries occur when an external force traumatically injures the brain. Spinal cord injuries (SCI) include any injury to the spinal cord that is caused by trauma instead of disease. In some embodiments the TBI is chronic traumatic encephalopathy (CTE). In one aspect, the present invention relates to the compound, or a pharmaceutically acceptable salt thereof, as defined herein for use in the treatment of inflammation. In some embodiments said inflammation is selected from the group consisting of inclusion-body myositis, systemic lupus erythematosus (SLE), RA, gout, and certain bowel conditions including Inflammatory bowel disease (IBD). In one aspect, the present invention relates to a compound as defined herein, or a pharmaceutically acceptable salt thereof, for use in the treatment of a condition selected from the group consisting of cancer, an immunological disorder, a central nervous system disorder, an inflammatory disorder, a gastroenterological disorder, a metabolic disorder, a cardiovascular disorder, and a kidney disease. KV1.3 channel expression is associated with the control of proliferation in multiple cell types, apoptosis, and cell survival. These processes are crucial for cancer progression. Thus, inhibitors of KV1.3 channels may be used as anticancer agents. In one aspect, the present invention relates to a compound as defined herein, or a pharmaceutically acceptable salt thereof, for use in the treatment of cancer. In some embodiments, the cancer is selected from the group consisting of biliary tract cancer, brain cancer, breast cancer, cervical cancer, choriocarcinoma, colon cancer, endometrial cancer, esophageal cancer, gastric (stomach) cancer, intraepithelial neoplasms, leukemias, lymphomas, liver cancer, lung cancer, melanoma, neuroblastomas, oral cancer, ovarian cancer, pancreatic cancer, prostate cancer, rectal cancer, renal (kidney) cancer, sarcomas, skin cancer, testicular cancer, and thyroid cancer. KV1.3 channel blockers are potential therapeutic agents as immunosuppressants or immune system modulators. The Kv1.3 channel is also considered as a therapeutic target for the treatment of obesity and for enhancing peripheral insulin sensitivity in patients with type II diabetes mellitus. These compounds can also be utilized in the prevention of graft rejection and the treatment of immunological (e.g., autoimmune) and inflammatory disorders. The term "autoimmune diseases" generally refers to diseases in which "self' components undergo attack by the immune system. Such diseases may affect a single organ, as in, for example, multiple sclerosis and type I diabetes mellitus, or may involve multiple organs, as in, for example, rheumatoid arthritis and systemic lupus erythematosus. In one aspect, the present invention relates to a compound as defined herein, or a pharmaceutically acceptable salt thereof, for use in the treatment of an autoimmune disease. In some embodiments, the autoimmune disease is Graves’ disease. In some embodiments, the autoimmune disease is Hashimoto’s thyroiditis. In some embodiments, the autoimmune disease is myasthenia gravis. Autoimmune encephalitis (AIE) is a type of encephalitis (inflammation of the brain) which can result from a number of autoimmune diseases including Rasmussen encephalitis, Systemic lupus erythematosus, Behçet's disease, Hashimoto's encephalopathy, Autoimmune limbic encephalitis, and Sydenham's chorea. In one aspect, the present invention relates to a compound as defined herein, or a pharmaceutically acceptable salt thereof, for use in the treatment of autoimmune encephalitis. In some embodiment, the AIE is selected from the group consisting of Anti-NMDAR encephalitis; Anti-AMPAR encephalitis; Anti-GABA encephalitis, such as Anti-GABA-AR encephalitis and Anti-GABA-BR encephalitis; Anti-LGI1 encephalitis; Anti-CASPR2 encephalitis; Anti-GAD encephalitis; Anti-GlyR encephalitis; Anti-DPPX encephalitis; Encephalopathy associated with anti-IgLON5 antibodies; Anti-mGluR1 encephalitis; and anti-mGluR5 encephalitis. In one aspect, the present invention relates to the compound, or a pharmaceutically acceptable salt thereof, as defined herein for use in the treatment of atopic dermatitis (eczema). In one aspect, the present invention relates to the compound, or a pharmaceutically acceptable salt thereof, as defined herein for use in the treatment of coeliac disease. In one aspect, the present invention relates to a compound as defined herein, or a pharmaceutically acceptable salt thereof, for use in the treatment of an inflammatory disorder. In some embodiments, the inflammatory disorder is an inflammatory skin condition, arthritis, psoriasis, spondylitis, parodontitits, or an inflammatory neuropathy. KV1.3 channels play a role in gastroenterological disorders including, but not limited to, inflammatory bowel diseases, such as, but not limited to, ulcerative colitis and Crohn’s disease. Ulcerative colitis is a chronic inflammatory bowel disease characterized by excessive T cell infiltration and cytokine production. KV1.3 channels are thought to serve as a marker of disease activity and pharmacological blockade might constitute an immunosuppressive strategy in ulcerative colitis. Crohn’s disease is a type of inflammatory bowel disease which may affect any part of the gastrointestinal tract. Crohn’s disease is thought to be the result of intestinal inflammation due to a T cell- driven process initiated by normally safe bacteria. Thus, KV1.3 channel inhibition can be utilized in treating the Crohn’s disease. In one aspect, the present invention relates to a compound as defined herein, or a pharmaceutically acceptable salt thereof, for use in the treatment of a gastroenterological disorder. In some embodiments, the gastroenterological disorder is an inflammatory bowel disease such as Crohn’s disease or ulcerative colitis. In one aspect, the present invention relates to a compound as defined herein, or a pharmaceutically acceptable salt thereof, for use in the treatment of a immunological disorder. In some embodiments, the immunological disorder is transplant rejection or an autoimmune disease (e.g., rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, or type I diabetes mellitus). Expression of Kv1.3 channels is elevated in microglia of human Alzheimer’s disease brains, suggesting that Kv1.3 channel is a pathologically relevant microglial target in Alzheimer’s disease. Thus, the Kv1.3 channel may be a therapeutic target for Alzheimer’s disease. In one aspect, the present invention relates to a compound as defined herein, or a pharmaceutically acceptable salt thereof, for use in the treatment of Alzheimer’s disease. In some embodiments, the central nervous system disorder is Alzheimer’s disease. In some embodiments, the metabolic disorder is obesity or type II diabetes mellitus. In some embodiments, the kidney disease is chronic kidney disease, nephritis, or chronic renal failure. KV1.3 channel blockers can be useful for ameliorating pathology in cardiovascular disorders such as, but not limited to, ischemic stroke, where activated microglia significantly contributes to the secondary expansion of the infarct. In one aspect, the present invention relates to a compound as defined herein, or a pharmaceutically acceptable salt thereof, for use in the treatment of a cardiovascular disorder. In some embodiments, the cardiovascular disorder is an ischemic stroke. In some embodiments, the condition is selected from the group consisting of cancer, transplant rejection, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, type I diabetes mellitus, Alzheimer’s disease, inflammatory skin condition, inflammatory neuropathy, psoriasis, spondylitis, parodontitis, inflammatory bowel disease, obesity, type II diabetes mellitus, ischemic stroke, chronic kidney disease, nephritis, chronic renal failure, and a combination thereof. In one aspect, the present invention relates to the compound, or a pharmaceutically acceptable salt thereof, as defined herein for use in the treatment of bipolar disorder. In one aspect, the present invention relates to the compound, or a pharmaceutically acceptable salt thereof, as defined herein for use in the treatment of Major depressive disorder (MDD, also known as clinical depression). In some embodiments, said MDD is selected from the group consisting of melancholic depression; atypical depression; catatonic depression; depression with anxious distress; depression with peri-partum onset; and seasonal affective disorder. In one aspect, the present invention relates to the compound, or a pharmaceutically acceptable salt thereof, as defined herein for use in the treatment of schizophrenia. In one aspect, the present invention relates to a compound as defined herein, or a pharmaceutically acceptable salt thereof, for use in the treatment of pain, such as neuropathic pain or inflammatory pain. In one aspect, the present invention relates to a compound as defined herein, or a pharmaceutically acceptable salt thereof, for use in the treatment of CNS complications of COVID-19 infection and / or post-COVID-19 conditions (also known as post-COVID syndrome, long COVID-19, long-haul COVID-19, and post acute sequelae of SARS COV-2 infection (PASC)). In one aspect, the present invention relates to a compound as defined herein, or a pharmaceutically acceptable salt thereof, for use in the treatment of epilepsy, such as genetic epilepsy or sporadic epilepsy. The term “compound” as used herein is meant to include all stereoisomers, geometric isomers, tautomers, and isotopes of the structures depicted, unless otherwise specified. Accordingly, the scope of the methods and uses herein is to be understood to encompass methods and uses employing all such forms. Depending upon the particular condition, or disease, to be treated, additional therapeutic agents, which are normally administered to treat that condition, may be administered in combination with compounds and compositions of the present invention. As used herein, additional therapeutic agents that are normally administered to treat a particular disease, or condition, are known as “appropriate for the disease, or condition, being treated.” In some embodiments, a provided combination, or composition thereof, is administered in combination with another therapeutic agent. In some embodiments, the present invention provides a method of treating a disclosed disease or condition comprising administering to a patient in need thereof an effective amount of a compound disclosed herein, or a pharmaceutically acceptable salt thereof, and co-administering simultaneously or sequentially an effective amount of one or more additional therapeutic agents. In some embodiments, the method includes co- administering one or more additional therapeutic agent. Examples of therapeutic agents the combinations of the present invention may also be combined with include, without limitation: treatments for Parkinson’s disease, rheumatoid arthritis, Alzheimer’s disease, Nasu- Hakola disease, frontotemporal dementia, multiple sclerosis, prion disease, or stroke. In some embodiments, the therapeutic agents the combinations of the present invention may also be combined with include, without limitation: treatments for a disease selected from the group consisting of a tauopathy, a TDP-43 proteinopathy, a synucleinopathy, dementia, amyloidosis, a demyelinating disorder of the CNS, a demyelinating disorder of the PNS, a Leukoencephalopathy, a leukodystrophy, a transmissible spongiform encephalopathy (TSE) and a lysosomal storage disorder (LSD). As used herein, the term “combination,” “combined,” and related terms refers to the simultaneous or sequential administration of therapeutic agents in accordance with the present invention. For example, a combination of the present invention may be administered with another therapeutic agent simultaneously or sequentially in separate unit dosage forms or together in a single unit dosage form. The compounds of the present invention may be used to treat an animal patient belonging to any classification. Examples of such animals include mammals such as humans, rodents, dogs, cats, zoo animals and farm animals. In some embodiments, the subject referred to herein is a mammal, such as a human. In one aspect, the present invention concerns a method of blocking KV1.3 potassium channel in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of at least one compound as defined herein. In one aspect, the present invention relates to a method of modulating the activity of KV1.3 in a biological tissue, the method comprising contacting a biological tissue expressing KV1.3 with a KV1.3 modulating amount of a compound as defined herein, or a pharmaceutically acceptable salt thereof. In one aspect, the present invention concerns a method of suppressing T cell activation in a subject having a condition associated with undesired T cell activation. T cell activation can be measured by well-known methods, such as measuring reduction of IL-2 production by T cells. "Suppressing T cell activation" as used herein refers to the ability of the compound as defined herein, or a pharmaceutically acceptable salt thereof, to inhibit and reduce T cell activation by at least 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100%. In some embodiments, the condition associated with undesired T cell activation is an inflammatory condition, an immune and proliferative disorder, including but not limited to rheumatoid arthritis (RA), osteoarthritis, osteoporosis, uveitis, inflammatory fibrosis (e.g., scleroderma, lung fibrosis, and cirrhosis), inflammatory bowel disorders (e.g., Crohn's disease, ulcerative colitis and inflammatory bowel disease), multiple sclerosis, psoriasis, contact-mediated dermatitis, systemic lupus erythematosus (SLE) and other forms of lupus, diabetes, type I diabetes, cancer, lupus, scleroderma, Sjogren syndrome, and vasculitis. Method of manufacturing The compounds of the invention may be prepared by conventional methods for chemical synthesis, e.g. those described in the working examples. The starting materials for the processes described in the present application are known or may readily be prepared by conventional methods from commercially available chemicals. Substituted 2-indole carboxylic acids are made using known literature procedures and in some cases a R3halogen group is introduced via a halogenation reaction using known procedures and reagents such as NCS for chlorination and SelectfluorTMfor fluorination. In some cases an indole protecting group, such as SEM, may be introduced using known procedures, which is then removed later in the sequence using known procedures. In other cases no protecting group is used and the indole NH remains in place during subsequent steps. Scheme 1 The appropriately substituted indole-2-carboxylic acids are coupled with amines using standard procedures and reagents such as EDC & HOBt, HATU, TCFH & NMI and DIPEA & COMU (Scheme 1). In some cases a Y protecting group (e.g. SEM) is in place during amide bond formation, which is then removed using standard procedures to afford the desired product where Y = H. In some cases the amide bond formation is performed without protection, i.e. where Y = H. In some cases the indole amide substituent includes a protected amine (e.g. Boc protected) which is deprotected to afford final products or further modified using standard procedures such as amide formation with the appropriate coupling reagents (Scheme 2). In some cases the R11 group also contains a protecting group (e.g. Boc) which is subsequently deprotected to afford the final products. Scheme 2 All starting materials are either commercially available or known in the art and may be synthesised by using known procedures. Starting materials may also be synthesised using the procedures disclosed herein. Reaction conditions such as reaction temperature, solvent and reagents for the Schemes in this section may be found in the experimental section herein. In one aspect, the present invention relates to a method for manufacturing a compound of Formula (I): Formula (I) wherein R1, R2, R3, R4, R5, and R6are as defined herein. In one aspect, the present invention relates to a method for manufacturing a compound of Formula (I): wherein R1is halogen or H; R2is halogen; R3is H or halogen; R4is as defined herein; R5is H or halogen; R6is H or halogen, said method comprising the steps of: a. providing a compound of Formula (SI), Formula (SI) wherein R1is halogen or H; R2is halogen; R3is H or halogen; R5is H or halogen; R6is H or halogen; and Y is H or a protecting group; b. reacting the compound of step a) with , wherein is R4as defined herein or a precursor for R4as defined herein, to generate the compound of Formula (SII): Formula (SII) wherein R1is halogen or H; R2is halogen; R3is H or halogen; R5is H or halogen; R6is H or halogen; Y is a H or a protecting group; and is R4as defined herein or a precursor for R4as defined herein. In some embodiments, Y is a protecting group (e.g. SEM) and said method for manufacturing a compound of Formula (I) includes a step subsequent to step b) wherein the protecting group is removed. In some embodiments, Y is H. In some embodiments, is R4is as defined herein. In some embodiments, s a precursor or as e ne eren. or exampe, may be R4including a protecting group, such as if R4includes an amine, said amine may be protected (e.g. Boc protected), or if R4includes an acid, said acid may be protected (e.g. by an alkyl ester). Further, a precursor for R4also includes groups that are further modified to afford R4as defined herein, for example using standard procedures such as amide formation with the appropriate coupling reagents. When is a precursor for R4as defined herein, one or more steps are included subsequent to step b) to afford the compound of Formula (I). In some embodiments, Y is a protecting group and is a precursor for R4as defined herein, and step b) is followed by step c-1), wherein the protecting group in position Y is removed to generate the compound of Formula (SIII): . Formula (SIII) Step c-1) is then followed by step c-2), wherein is modified to R4to generate the compound of Formula (I). In some embodiments, step c-1) and step c-2) occur simultaneously. Alternatively, in some embodiments, Y is a protecting group and is a precursor for R4as defined herein, and step b) is followed by step d-1), wherein is modified to R4to generate the compound of Formula (SIV): . Formula (SIV) Step d-1) is then followed by step d-2), wherein the protecting group in position Y is removed, and the compound of Formula (I) is generated. In some embodiments, step d-1) and step d-2) occur simultaneously. In some embodiments, R3in Formula (SI) is H. In some embodiments, R3in Formula (SI) is H and step a) includes introducing a halogen in position R3of the compound of Formula (SI) via a halogenation reaction. In some embodiments, said halogenation reaction includes using known procedures and reagents such as for example NCS for chlorination and SelectfluorTM for fluorination.

[0311] Items 1. A compound of Formula (I), Formula (I) wherein R1is halogen or H; R2is halogen; R3is H or halogen; R5is H or halogen; R6is H or halogen; R4is of Formula (II): Formula (II) wherein X1is C(R7)(R8); X2is C(R9)(R10) or a bond; X3is N(C(O)R11), C(R12)(C(O)R13), C(R14)(R15) or N(R16); X4is C(R17)(R18), O or C(O); X5is C(R19)(R20) or a bond; X6is a bond or C(R21)(R22); wherein R9and R11, R9and R13, R10and R11, R10and R13, R13and R17, R13and R18, or R14and R15are optionally joined together to form a ring together with the intervening atom(s); R7is H, C1-3 alkyl optionally substituted with 1 to 3 F or C1-3 alkoxy, or halogen, such as F; R8is H, C1-3 alkyl optionally substituted with 1 to 3 F or C1-3 alkoxy, or halogen, such as F; R9is H, C1-3alkyl optionally substituted with 1 to 3 halogens, halogen, such as F, or -C(O)N(R31)(R32), wherein R31is H or C1-3alkyl and R32is H or C1-3alkyl, or when R9is linked to R11or R13to form a ring, then R9is a bond, -C(O)- or a C1-3alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl; R10is H, C1-3alkyl optionally substituted with 1 to 3 halogens, halogen, such as F, , or -C(O)N(R31)(R32), wherein R31is H or C1-3alkyl and R32is H or C1-3alkyl, or when R10is linked to R11or R13to form a ring, then R10is a bond, -C(O)- or a C1-3alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl; R11is -X13-R33; X13is a bond, C1-3alkanediyl optionally substituted with C1-3alkyl, -O-, or C1-3alkanediyl-O-; R33is selected from the group consisting of C1-3alkyl, C3-6cycloalkyl, C1-3alkoxy, pyridinyl, azetidinyl, pyrrolidinyl, oxetanyl, tetrahydrofuranyl, and morpholinyl, each of which is optionally substituted with one or more substituents individually selected from halogen; C1-3 alkoxy optionally substituted with one or more F; C1-3 alkyl optionally substituted with one or more F; NH2; N(H)(CH3); and N(CH3)2; or when R11is linked to R9or R10to form a ring, then R11is -O-, -N(R28)-, or C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl, wherein one methylene group of the C1-3 alkanediyl is optionally replaced by -O- or -N(R28)-, wherein R28is H or C1-3 alkyl; R12is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R13is selected from the group consisting of NH2, N(H)(CH3), N(CH3)2, pyrrolidinyl, azetidinyl, and piperazinyl, wherein ^ said pyrrolidinyl is optionally substituted with one or more substituents individually selected from the group consisting of halogen, NH2, N(H)(CH3), N(CH3)2and azetidinyl, and said azetidinyl is optionally substituted with one or more halogens, and ^ said azetidinyl optionally substituted with NH2; or when R13is linked to R9, R10, R17, or R18to form a ring, then R13is -N(R28)-, wherein R28is H or C1-3 alkyl; R14is -X7N(R23)(C(O)R24), wherein X7is a bond or C1-3alkanediyl; R24is C1-3alkyl; and R23is H or C1-3alkyl, and R15is H or C1-3alkyl, or R23is a bond or C1-3alkanediyl, and R15is a bond or C1-3alkanediyl and R23is linked to R15to form a ring; or R14is -X9C(O)X11-, R15is a bond or C1-3alkanediyl, and X11is linked to R15to form a ring, wherein X9is a bond or -N(R29)-; R29is C1-3alkyl; X11is -O-, C1-3alkanediyl, or -N(R30)-; and R30is C1-3alkyl; R16is H or C1-3alkyl; R17is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; or when R17is linked to R13to form a ring, then R17is a bond or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl; R18is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; or when R18is linked to R13to form a ring, then R18is a bond or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl; R19is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R20is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R21is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R22is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; any two of R7, R8, R9, R10, R17, R18, R19, R20, R21, and R22are optionally linked together to form a ring; with the proviso that when X4is O, then X3is C(R12)C(O)R13and R13is NH2, N(H)(CH3) or N(CH3)2; with the proviso that when X3is N(R16), then X4is C(O), with the proviso that when X4is C(O), then X3is N(R16), and with the proviso that when X2is a bond, then X3is C(R12)(C(O)R13) or C(R14)(R15), or a pharmaceutically acceptable salt thereof. 2. A compound of Formula (I), Formula (I) wherein R1is halogen or H; R2is halogen; R3is H or halogen; R5is H or halogen; R6is H or halogen; R4is of Formula (II): Formula (II) wherein X1is C(R7)(R8); X2is C(R9)(R10) or a bond; X3is N(C(O)R11), C(R12)(C(O)R13), C(R14)(R15) or N(R16); X4is C(R17)(R18), O or C(O); X5is C(R19)(R20) or a bond; X6is a bond or C(R21)(R22); wherein R9and R11, R9and R13, R10and R11, R10and R13, R13and R17, R13and R18, or R14and R15are optionally joined together to form a ring together with the intervening atom(s); R7is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R8is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R9is H, C1-3 alkyl optionally substituted with 1 to 3 halogens, or halogen, such as F, or when R9is linked to R11or R13to form a ring, then R9is a bond or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl; R10is H, C1-3alkyl optionally substituted with 1 to 3 halogens, or halogen, such as F, or when R10is linked to R11or R13to form a ring, then R10is a bond or a C1-3alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl; R11is selected from the group consisting of C1-3alkyl, C3-5cycloalkyl, C1-3alkoxy, pyridinyl, azetidinyl, pyrrolidinyl, oxetanyl, and morpholinyl, wherein ^ said C1-3alkyl is optionally substituted with one or more substituents individually selected from the group consisting of NH2, N(H)(CH3), N(CH3)2, C1-3 alkoxy, morpholinyl, azetidinyl, -O-azetidinyl, and -O- oxetanyl, and said azetidinyl is optionally substituted with one or more substituents selected from halogen, C1-3 alkoxy, and C1-3 alkyl; ^ said C3-5 cycloalkyl is optionally substituted with one or more substituents selected from halogen, and C1-3 alkoxy; ^ said pyridinyl is optionally substituted with one or more NH2; ^ said pyrrolidinyl is optionally substituted with one or more substituents individually selected from the group consisting of C1-3alkyl, halogen, C1-3alkoxy, C1-3haloalkyl, NH2, N(H)(CH3), N(CH3)2and azetidinyl, and said azetidinyl is optionally substituted with one or more halogens; ^ said azetidinyl optionally substituted with one or more substituents selected from halogen, C1-3 alkyl, and NH2; and ^ said morpholinyl is optionally substituted with C1-3alkyl; or when R11is linked to R9or R10to form a ring, then R11is -O-, -N(R28)-, or C1-3alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl, wherein one methylene group of the C1-3alkanediyl is optionally replaced by -O- or -N(R28)-, wherein R28is H or C1-3alkyl; R12is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R13is selected from the group consisting of NH2, N(H)(CH3), N(CH3)2, pyrrolidinyl, azetidinyl, and piperazinyl, wherein ^ said pyrrolidinyl is optionally substituted with one or more substituents individually selected from the group consisting of halogen, NH2, N(H)(CH3), N(CH3)2 and azetidinyl, and said azetidinyl is optionally substituted with one or more halogens, and ^ said azetidinyl optionally substituted with NH2; or when R13is linked to R9, R10, R17, or R18to form a ring, then R13is -N(R28)-, wherein R28is H or C1-3alkyl; R14is -X7N(R23)(C(O)R24), wherein X7is a bond or C1-3alkanediyl; R24is C1-3alkyl; and R23is H or C1-3alkyl, and R15is H or C1-3alkyl, or R23is a bond or C1-3alkyl, and R15is a bond or C1-3alkanediyl and R23 is linked to R15to form a ring; or R14is -X9C(O)X11-, R15is a bond or C1-3alkanediyl, and X11is linked to R15to form a ring, wherein X9is a bond or -N(R29)-; R29is C1-3alkyl; X11is -O-, C1-3 alkanediyl, or -N(R30)-; and R30is C1-3 alkyl; R16is H or C1-3 alkyl; R17is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; or when R17is linked to R13to form a ring, then R17is a bond or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl; R18is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; or when R18is linked to R13to form a ring, then R18is a bond or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl; R19is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R20is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R21is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R22is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; any two of R7, R8, R9, R10, R17, R18, R19, R20, R21, and R22are optionally linked together to form a ring; with the proviso that when X4is O, then X3is C(R12)C(O)R13and R13is NH2, N(H)(CH3) or N(CH3)2; with the proviso that when X3is N(R16), then X4is C(O), and with the proviso that when X4is C(O), then X3is N(R16), or a pharmaceutically acceptable salt thereof. 3. A compound of Formula (I), Formula (I) wherein R1is halogen or H; R2is halogen; R3is H or halogen; R5is H or halogen; R6is H or halogen; R4is of Formula (II): Formula (II) wherein X1is C(R7)(R8); R7is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R8is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; X2is C(R9)(R10) or a bond; X3is N(C(O)R11), C(R12)(C(O)R13), C(R14)(R15) or N(R16); R9is H, C1-3 alkyl optionally substituted with 1 to 3 halogens, or halogen, such as F; R10is H, C1-3 alkyl optionally substituted with 1 to 3 halogens, or halogen, such as F; R11is selected from the group consisting of C1-3 alkyl, C3-5 cycloalkyl, C1-3 alkoxy, pyridinyl, azetidinyl and pyrrolidinyl, wherein ^ said C1-3alkyl is optionally substituted with one or more substituents individually selected from the group consisting of NH2, N(H)(CH3), N(CH3)2, C1-3alkoxy, and morpholinyl, ^ said pyridinyl is optionally substituted with one or more NH2; ^ said pyrrolidinyl is optionally substituted with one or more substituents individually selected from the group consisting of C1-3 alkyl, halogen, C1-3 alkoxy, NH2, N(H)(CH3), N(CH3)2 and azetidinyl, and said azetidinyl is optionally substituted with one or more halogens, and ^ said azetidinyl optionally substituted with NH2; or R11is linked to R9to form a ring and R9is a bond or a C1-3alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl, R10is H, C1-3alkyl optionally substituted with 1 to 3 halogens, or halogen, such as F, and R11is C1-3alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl, wherein one methylene group of the C1-3alkanediyl is optionally replaced by -O- or -N(R28)-, wherein R28is H or C1-3alkyl; or R11is linked to R10to form a ring and R9is H, C1-3alkyl optionally substituted with 1 to 3 halogens, or halogen, such as F, R10is a bond or a C1-3alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl, and R11is C1-3alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl, wherein one methylene group of the C1-3alkanediyl is optionally replaced by -O- or -N(R28)-, wherein R28is H or C1-3alkyl; R12is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R13is selected from the group consisting of NH2, N(H)(CH3), N(CH3)2, pyrrolidinyl, azetidinyl, and piperazinyl, wherein ^ said pyrrolidinyl is optionally substituted with one or more substituents individually selected from the group consisting of halogen, NH2, N(H)(CH3), N(CH3)2 and azetidinyl, and said azetidinyl is optionally substituted with one or more halogens, and ^ said azetidinyl optionally substituted with NH2; R14is -X7N(R23)(C(O)R24), wherein X7is a bond or C1-3alkanediyl; R24is C1-3alkyl; and R23is H or C1-3alkyl, and R15is H or C1-3alkyl, or R23is a bond or C1-3alkanediyl, and R15is a bond or C1-3alkanediyl and R23is linked to R15to form a ring; or R14is -X9C(O)X11-, R15is a bond or C1-3alkanediyl, and X11is linked to R15to form a ring, wherein X9is a bond or -N(R29)-; R29is C1-3alkyl; X11is -O-, C1-3alkanediyl, or -N(R30)-; and R30is C1-3alkyl; R16is H or C1-3alkyl; X4is C(R17)(R18), O or C(O); R17is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R18is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; X5is C(R19)(R20) or a bond; R19is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R20is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; X6is a bond or C(R21)(R22); R21is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R22is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; any two of R7, R8, R9, R10, R17, R18, R19, R20, R21, and R22are optionally linked together to form a ring; with the proviso that when X4is O, then X3is C(R12)C(O)R13and R13is NH2, N(H)(CH3) or N(CH3)2; with the proviso that when X3is N(R16), then X4is C(O), and with the proviso that when X4is C(O), then X3is N(R16), or a pharmaceutically acceptable salt thereof. 4. A compound of Formula (I), Formula (I) wherein R1is halogen or H; R2is halogen; R3is H or halogen; R5is H or halogen; R6is H or halogen; R4is of Formula (II): Formula (II) wherein X1is C(R7)(R8); R7is H, C1-3 alkyl optionally substituted with 1 to 3 F, or F; R8is H, C1-3 alkyl optionally substituted with 1 to 3 F, or F; X2is C(R9)(R10) or a bond; R9is H, C1-3alkyl optionally substituted with 1 to 3 F, or F; R10is H, C1-3alkyl optionally substituted with 1 to 3 F, or F; X3is N(C(O)R11), C(R12)(C(O)R13), C(R14)(R15) or N(R16); R11is selected from the group consisting of C1-3alkyl, C3-5cycloalkyl, C1-3alkoxy, pyridinyl, azetidinyl and pyrrolidinyl, wherein ^ said C1-3 alkyl is optionally substituted with one or more substituents individually selected from the group consisting of NH2, N(H)(CH3), N(CH3)2 and C1-3 alkoxy, ^ said pyridinyl is optionally substituted with one or more NH2; ^ said pyrrolidinyl is optionally substituted with one or more substituents individually selected from the group consisting of halogen, NH2, N(H)(CH3), N(CH3)2and azetidinyl, and said azetidinyl is optionally substituted with one or more halogens, and ^ said azetidinyl optionally substituted with NH2; ^ when R11is C1-3 alkyl or C1-3 alkoxy, then R11is optionally linked to R9or R10to form a ring; R12is H, C1-3 alkyl optionally substituted with 1 to 3 F, or F; R13is selected from the group consisting of NH2, N(H)(CH3), N(CH3)2, pyrrolidinyl, azetidinyl, and piperazinyl, wherein ● said pyrrolidinyl is optionally substituted with one or more substituents individually selected from the group consisting of halogen, NH2, N(H)(CH3), N(CH3)2and azetidinyl, and said azetidinyl is optionally substituted with one or more halogens, and ● said azetidinyl optionally substituted with NH2; R14is -X7N(R23)(C(O)R24); X7is a bond or CH2; R23is H or C1-3 alkyl, or R23is a bond and R15is C1-3 alkanediyl and R23is linked to R15to form a 4 or 5 membered ring; R24is C1-3 alkyl; R15is H or C1-3 alkyl; R16is H or C1-3 alkyl; X4is C(R17)(R18), O or C(O); R17is H, C1-3alkyl optionally substituted with 1 to 3 F, or F; R18is H, C1-3alkyl optionally substituted with 1 to 3 F, or F; X5is C(R19)(R20) or a bond; R19is H, C1-3 alkyl optionally substituted with 1 to 3 F, or F; R20is H, C1-3 alkyl optionally substituted with 1 to 3 F, or F; X6is a bond or C(R21)(R22); R21is H, C1-3alkyl optionally substituted with 1 to 3 F, or F; and R22is H, C1-3alkyl optionally substituted with 1 to 3 F, or F; any two of R7, R8, R9, R10, R17, R18, R19, R20, R21, and R22are optionally linked together to form a ring; with the proviso that when X4is O, then X3is C(R12)(C(O)R13) and R13is NH2, N(H)(CH3) or N(CH3)2; with the proviso that when X3is N(R16), then X4is C(O), and with the proviso that when X4is C(O), then X3is N(R16), or a pharmaceutically acceptable salt thereof. 5. A compound of Formula (I), Formula (I) wherein R1is halogen or H; R2is halogen; R3is H or halogen; R5is H or halogen; R6is H or halogen; R4is of Formula (XXIV), Formula (XXV), Formula (XXVI) or Formula (XXVII): Formula (XXVI) Formula (XXVII) wherein R7is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R8is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; X3is N(C(O)R11), C(R12)(C(O)R13), C(R14)(R15) or N(R16); R9is H, C1-3alkyl optionally substituted with 1 to 3 halogens, or halogen, such as F; R10is H, C1-3 alkyl optionally substituted with 1 to 3 halogens, or halogen, such as F; R11is selected from the group consisting of C1-3alkyl, C3-5cycloalkyl, C1-3alkoxy, pyridinyl, azetidinyl and pyrrolidinyl, wherein ^ said C1-3 alkyl is optionally substituted with one or more substituents individually selected from the group consisting of NH2, N(H)(CH3), N(CH3)2, C1-3alkoxy, and morpholinyl, ^ said pyridinyl is optionally substituted with one or more NH2; ^ said pyrrolidinyl is optionally substituted with one or more substituents individually selected from the group consisting of C1-3alkyl, halogen, C1-3alkoxy, NH2, N(H)(CH3), N(CH3)2and azetidinyl, and said azetidinyl is optionally substituted with one or more halogens, and ^ said azetidinyl optionally substituted with NH2; or R11is linked to R9to form a ring and R9is a bond or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl, R10is H, C1-3alkyl optionally substituted with 1 to 3 halogens, or halogen, such as F, and R11is C1-3alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl, wherein one methylene group of the C1-3 alkanediyl is optionally replaced by -O- or -N(R28)-, wherein R28is H or C1-3 alkyl; or R11is linked to R10to form a ring and R9is H, C1-3 alkyl optionally substituted with 1 to 3 halogens, or halogen, such as F, R10is a bond or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl, and R11is C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl, wherein one methylene group of the C1-3 alkanediyl is optionally replaced by -O- or -N(R28)-, wherein R28is H or C1-3 alkyl; R12is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R13is selected from the group consisting of NH2, N(H)(CH3), N(CH3)2, pyrrolidinyl, azetidinyl, and piperazinyl, wherein ^ said pyrrolidinyl is optionally substituted with one or more substituents individually selected from the group consisting of halogen, NH2, N(H)(CH3), N(CH3)2and azetidinyl, and said azetidinyl is optionally substituted with one or more halogens, and ^ said azetidinyl optionally substituted with NH2; R14is -X7N(R23)(C(O)R24), wherein X7is a bond or C1-3alkanediyl; R24is C1-3alkyl; and R23is H or C1-3 alkyl, and R15is H or C1-3 alkyl, or R23is a bond or C1-3 alkanediyl, and R15is a bond or C1-3 alkanediyl and R23is linked to R15to form a ring; or R14is -X9C(O)X11-, R15is a bond or C1-3 alkanediyl, and X11is linked to R15to form a ring, wherein X9is a bond or -N(R29)-; R29is C1-3 alkyl; X11is -O-, C1-3 alkanediyl, or -N(R30)-; and R30is C1-3 alkyl; R16is H or C1-3 alkyl; X4is C(R17)(R18), O or C(O); R17is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R18is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R19is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R20is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R21is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; and R22is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; any two of R7, R8, R9, R10, R17, R18, R19, R20, R21, and R22are optionally linked together to form a ring; with the proviso that when X4is O, then X3is C(R12)C(O)R13and R13is NH2, N(H)(CH3) or N(CH3)2; with the proviso that when X3is N(R16), then X4is C(O), and with the proviso that when X4is C(O), then X3is N(R16), or a pharmaceutically acceptable salt thereof. 6. A compound of Formula (LVII), Formula (LVII) wherein R1is halogen or H; R2is halogen; R3is H or halogen; R5is H or halogen; R6is H or halogen; wherein R9and R11or R10and R11are optionally joined together to form a ring together with the intervening atoms; R7is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R8is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R9is H, C1-3 alkyl optionally substituted with 1 to 3 halogens, or halogen, such as F, or when R9is linked to R11to form a ring, then R9is a bond or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl; R10is H, C1-3alkyl optionally substituted with 1 to 3 halogens, or halogen, such as F, or when R10is linked to R11to form a ring, then R10is a bond or a C1-3alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl; R11is selected from the group consisting of C1-3alkyl, C3-5cycloalkyl, C1-3alkoxy, pyridinyl, azetidinyl, pyrrolidinyl, oxetanyl, and morpholinyl, wherein ● said C1-3alkyl is optionally substituted with one or more substituents individually selected from the group consisting of NH2, N(H)(CH3), N(CH3)2, C1-3 alkoxy, morpholinyl, azetidinyl, -O-azetidinyl, and -O- oxetanyl, and said azetidinyl is optionally substituted with one or more substituents selected from halogen, C1-3 alkoxy, and C1-3 alkyl; ● said C3-5 cycloalkyl is optionally substituted with one or more substituents selected from halogen, and C1-3 alkoxy; ● said pyridinyl is optionally substituted with one or more NH2; ^ said pyrrolidinyl is optionally substituted with one or more substituents individually selected from the group consisting of C1-3alkyl, halogen, C1-3alkoxy, C1-3haloalkyl, NH2, N(H)(CH3), N(CH3)2and azetidinyl, and said azetidinyl is optionally substituted with one or more halogens; ^ said azetidinyl optionally substituted with one or more substituents selected from halogen, C1-3 alkyl, and NH2; and ^ said morpholinyl is optionally substituted with C1-3alkyl; or when R11is linked to R9or R10to form a ring, then R11is -O-, -N(R28)-, or C1-3alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl, wherein one methylene group of the C1-3alkanediyl is optionally replaced by -O- or -N(R28)-, wherein R28is H or C1-3alkyl; R17is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R18is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R19is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R20is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; and any two of R7, R8, R9, R10, R17, R18, R19, and R20, are optionally linked together to form a ring; or a pharmaceutically acceptable salt thereof. 7. A compound of Formula (LVII), Formula (LVII) wherein R1is halogen or H; R2is halogen; R3is halogen; R5, R6, R8, R17, R18, R19, and R20are H; wherein R9and R11or R10and R11are optionally joined together via R33to form a ring together with the intervening atoms; R7is H or C1-3alkyl optionally substituted with 1 to 3 F; R10is H, or when R10is linked to R11to form a ring, then R10is a bond or a C1-3alkanediyl; R9is H, or when R9is linked to R11to form a ring, then R9is a bond or a C1-3alkanediyl; R11is -X13-R33; X13is a bond, C1-3alkanediyl optionally substituted with C1-3alkyl, -O-, or C1-3alkanediyl-O-; and R33is C1-3alkyl, azetidinyl, pyrrolidinyl, oxetanyl, and tetrahydrofuranyl, each of which is optionally substituted with one or more F; or when R11is linked to R9or R10via R33to form a ring, then R33is a bond or a C1-3alkanediyl, or a pharmaceutically acceptable salt thereof. 8. The compound according to any one of the preceding items, wherein the compound of Formula (LVII) is of Formula LVIIa): , Formula (LVIIa) or a pharmaceutically acceptable salt thereof. 9. The compound according to any one of the preceding items, with the proviso that when R4is of Formula (XXV), then X3is C(R12)(C(O)R13) or C(R14)(R15), or a pharmaceutically acceptable salt thereof. 10. The compound according to any one of the preceding items, with the proviso that when R4is of Formula (XXVI), then X3is C(R12)(C(O)R13) or C(R14)(R15), or a pharmaceutically acceptable salt thereof. 11. The compound according to any one of the preceding items, with the proviso that when R4is of Formula (XXVII), then X3is C(R12)(C(O)R13) or C(R14)(R15), or a pharmaceutically acceptable salt thereof. 12. The compound according to any one of the preceding items, with the proviso that when R4is of Formula (XXVII), then of Formula (XXIV), then X4is C(R17)(R18) or C(O), or a pharmaceutically acceptable salt thereof. 13. The compound according to item 4, wherein R4is of Formula (XXVIII): , Formula (XXVIII) or a pharmaceutically acceptable salt thereof. 14. The compound according to item 4, wherein R4is of Formula (XXIX): , Formula (XXIX) or a pharmaceutically acceptable salt thereof. 15. The compound according to any one of the preceding items, wherein R4is of Formula (XXIX), and X3is C(R12)(C(O)R13) or C(R14)(R15), or a pharmaceutically acceptable salt thereof. 16. The compound according to item 4, wherein R4is of Formula (XXX): , Formula (XXX) or a pharmaceutically acceptable salt thereof. 17. The compound according to any one of the preceding items, wherein R4is of Formula (XXX), and X3is C(R12)(C(O)R13) or C(R14)(R15), or a pharmaceutically acceptable salt thereof. 18. The compound according to item 4, wherein R4is of Formula (XXXI): , Formula (XXXI) or a pharmaceutically acceptable salt thereof. 19. The compound according to any one of the preceding items, wherein R4is of Formula (XXXI), and X3is C(R12)(C(O)R13) or C(R14)(R15), or a pharmaceutically acceptable salt thereof. 20. The compound according to item 4, wherein R4is of Formula (XXXII): , Formula (XXXII) or a pharmaceutically acceptable salt thereof. 21. The compound according to item 4, wherein R4is of Formula (XXXIII): , Formula (XXXIII) or a pharmaceutically acceptable salt thereof. 22. The compound according to any one of the preceding items,with the proviso that when X3is N(C(O)R11)or N(R16), then X2is not a bond, or a pharmaceutically acceptable salt thereof. 23. The compound according to any one of the preceding items, with the proviso that when X3is N(C(O)R11)or N(R16), then X5and X6are not both bonds, or a pharmaceutically acceptable salt thereof. 24. A compound of Formula (I), Formula (I) wherein R1is halogen or H; R2is halogen; R3is H or halogen; R5is H or halogen; R6is H or halogen; R4is of Formula (III), Formula (XXXIV), Formula (XXXV), Formula (XXXVI), Formula (XXXVII), Formula (XXXVIII), Formula (XXXIX), or Formula (XL): Formula (XXXV) Formula (XXXVI) Formula (XXXIX)Formula (XL)wherein R7is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R8is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R9is H, C1-3 alkyl optionally substituted with 1 to 3 halogens, or halogen, such as F; R10is H, C1-3 alkyl optionally substituted with 1 to 3 halogens, or halogen, such as F; R11is selected from the group consisting of C1-3 alkyl, C3-5 cycloalkyl, C1-3 alkoxy, pyridinyl, azetidinyl and pyrrolidinyl, wherein ^ said C1-3alkyl is optionally substituted with one or more substituents individually selected from the group consisting of NH2, N(H)(CH3), N(CH3)2, C1-3alkoxy, and morpholinyl, ^ said pyridinyl is optionally substituted with one or more NH2; ^ said pyrrolidinyl is optionally substituted with one or more substituents individually selected from the group consisting of C1-3alkyl, halogen, C1-3 alkoxy, NH2, N(H)(CH3), N(CH3)2 and azetidinyl, and said azetidinyl is optionally substituted with one or more halogens, and ^ said azetidinyl optionally substituted with NH2; or R11is linked to R9to form a ring and R9is a bond or a C1-3alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl, R10is H, C1-3alkyl optionally substituted with 1 to 3 halogens, or halogen, such as F, and R11is C1-3alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl, wherein one methylene group of the C1-3alkanediyl is optionally replaced by -O- or -N(R28)-, wherein R28is H or C1-3alkyl; or R11is linked to R10to form a ring and R9is H, C1-3alkyl optionally substituted with 1 to 3 halogens, or halogen, such as F, R10is a bond or a C1-3alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl, and R11is C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl, wherein one methylene group of the C1-3 alkanediyl is optionally replaced by -O- or -N(R28)-, wherein R28is H or C1-3 alkyl; R12is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R13is selected from the group consisting of NH2, N(H)(CH3), N(CH3)2, pyrrolidinyl, azetidinyl, and piperazinyl, wherein ^ said pyrrolidinyl is optionally substituted with one or more substituents individually selected from the group consisting of halogen, NH2, N(H)(CH3), N(CH3)2 and azetidinyl, and said azetidinyl is optionally substituted with one or more halogens, and ^ said azetidinyl optionally substituted with NH2; R14is -X7N(R23)(C(O)R24), wherein X7is a bond or C1-3alkanediyl; R24is C1-3alkyl; and R23is H or C1-3alkyl, and R15is H or C1-3alkyl, or R23is a bond or C1-3 alkanediyl, and R15is a bond or C1-3 alkanediyl and R23is linked to R15to form a ring; or R14is -X9C(O)X11-, R15is a bond or C1-3 alkanediyl, and X11is linked to R15to form a ring, wherein X9is a bond or -N(R29)-; R29is C1-3alkyl; X11is -O-, C1-3alkanediyl, or -N(R30)-; and R30is C1-3alkyl; R16is H or C1-3alkyl; R17is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R18is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R19is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R20is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R21is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; and R22is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; and any two of R7, R8, R9, R10, R17, R18, R19, R20, R21, and R22are optionally linked together to form a ring, or a pharmaceutically acceptable salt thereof. 25. The compound according to item 22, wherein R4is of Formula (IV), Formula (XLI), Formula (XLII), Formula (XLIII), Formula (XLIV), Formula (XLV), Formula (XLVI), Formula (XLVII), Formula (XLVIII), Formula (XLIX) or Formula (L): Formula (XLIII) Formula (XLII)

[0312] Formula (L) or a pharmaceutically acceptable salt thereof. 26. A compound of Formula (I), Formula (I) wherein R1is halogen or H; R2is halogen; R3is H or halogen; R5is H or halogen; R6is H or halogen; R4is of Formula (XXa) or Formula (XXb): Formula (XXa)Formula (XXb)wherein R7is H, C1-3 alkyl optionally substituted with 1 to 3 F or C1-3 alkoxy, or halogen, such as F; R8is H, C1-3 alkyl optionally substituted with 1 to 3 F or C1-3 alkoxy, or halogen, such as F; R9is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R10is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R17is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R18is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R19is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R20is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R31is individually halogen or C1-3 alkyl; r is 0, 1, 2, 3 or 4; X8is -CH2-, -O-, -CH2O-, -OCH2-, -N(R28)-, or -CH2N(R28)-; and R28is H or C1-3 alkyl, or a pharmaceutically acceptable salt thereof. 27. A compound of Formula (XXIII):

[0313] Formula (XXIII) wherein R1is halogen or H; R2is halogen; R3is H or halogen; R5is H or halogen; R6is H or halogen; X8is -CH2-, -O- or -N(R28)-; and R28is H or C1-3 alkyl, or a pharmaceutically acceptable salt thereof. 28. A compound of Formula (I), wherein R1is halogen or H; R2is halogen; R3is H or halogen; R5is H or halogen; R6is H or halogen; R4is of Formula (XIX): Formula (XIX) wherein X9is a bond or -N(R29)-; R29is C1-3 alkyl; X10is -C(O)-, -CH2-, or a bond; X11is -O-, -CH2-, or -N(R30)-; R30is C1-3 alkyl; X12is -N(C(O)R24)- or a bond; m is 1 or 2; n is 0 or 1; and z is 1 or 2; with the proviso that when X10is -C(O)-, then X12is a bond; with the proviso that when X10is -CH2- or a bond, then X12is -N(C(O)R24)-; and with the proviso that ring A is a 4 to 6 membered ring, or a pharmaceutically acceptable salt thereof. 29. The compound according to any one of the preceding items, wherein R1is halogen, or a pharmaceutically acceptable salt thereof. 30. The compound according to any one of the preceding items, wherein R1is Cl, or a pharmaceutically acceptable salt thereof. 31. The compound according to any one of the preceding items, wherein R1is F, or a pharmaceutically acceptable salt thereof. 32. The compound according to any one of the preceding items, wherein R1is H, or a pharmaceutically acceptable salt thereof. 33. The compound according to any one of the preceding items, wherein R2is Cl, or a pharmaceutically acceptable salt thereof. 34. The compound according to any one of the preceding items, wherein R3is halogen, or a pharmaceutically acceptable salt thereof. 35. The compound according to any one of the preceding items, wherein R3is Cl, or a pharmaceutically acceptable salt thereof. 36. The compound according to any one of the preceding items, wherein R3is F, or a pharmaceutically acceptable salt thereof. 37. The compound according to any one of the preceding items, wherein R3is H, or a pharmaceutically acceptable salt thereof. 38. The compound according to any one of the preceding items, wherein R5is H, or a pharmaceutically acceptable salt thereof. 39. The compound according to any one of the preceding items, wherein R5is halogen, or a pharmaceutically acceptable salt thereof. 40. The compound according to any one of the preceding items, wherein R5is F, or a pharmaceutically acceptable salt thereof. 41. The compound according to any one of the preceding items, wherein R6is H, or a pharmaceutically acceptable salt thereof. 42. The compound according to any one of the preceding items, wherein R6is halogen, or a pharmaceutically acceptable salt thereof. 43. The compound according to any one of the preceding items, wherein R6is F, or a pharmaceutically acceptable salt thereof. 44. The compound according to any one of the preceding items, wherein R5is H and R6is H, or a pharmaceutically acceptable salt thereof. 45. The compound according to any one of the preceding items, wherein R1is halogen, and R2is halogen, or a pharmaceutically acceptable salt thereof. 46. The compound according to any one of the preceding items, wherein R2is halogen, and R3is halogen, or a pharmaceutically acceptable salt thereof. 47. The compound according to any one of the preceding items, wherein R1is halogen, R2is halogen, and R3is halogen, or a pharmaceutically acceptable salt thereof. 48. The compound according to any one of the preceding items, wherein R1is F or Cl, R2is Cl or F, and R3is F or Cl, or a pharmaceutically acceptable salt thereof. 49. The compound according to any one of the preceding items, wherein R1is halogen, R2is halogen, R3is halogen, R5is H, and R6is H, or a pharmaceutically acceptable salt thereof. 50. The compound according to any one of the preceding items, wherein R1is F or Cl, R2is Cl or F, and R3is F or Cl, R5is H, and R6is H, or a pharmaceutically acceptable salt thereof. 51. The compound according to any one of the preceding items, wherein R1is halogen, R2is halogen, R3is H, R5is H, and R6is H, or a pharmaceutically acceptable salt thereof. 52. The compound according to any one of the preceding items, wherein R1is halogen, R2is halogen, R3is H, R5is halogen, and R6is H, or a pharmaceutically acceptable salt thereof. 53. The compound according to any one of the preceding items, wherein R1is halogen, R2is halogen, R3is H, R5is H, and R6is halogen, or a pharmaceutically acceptable salt thereof. 54. The compound according to any one of the preceding items, wherein R1is H, R2is halogen, R3is halogen, R5is H, and R6is H, or a pharmaceutically acceptable salt thereof. 55. The compound according to any one of the preceding items, wherein R1is F, R2is Cl, and R3is Cl, or a pharmaceutically acceptable salt thereof. 56. The compound according to any one of the preceding items, wherein R1is F, R2is Cl, and R3is F, or a pharmaceutically acceptable salt thereof. 57. The compound according to any one of the preceding items, wherein R1is Cl, R2is Cl, and R3is Cl, or a pharmaceutically acceptable salt thereof. 58. The compound according to any one of the preceding items, wherein R1is Cl, R2is Cl, and R3is F, or a pharmaceutically acceptable salt thereof. 59. The compound according to any one of the preceding items, wherein R1is F or Cl, R2is Cl, R3is Cl, R5is H, and R6is H, or a pharmaceutically acceptable salt thereof. 60. The compound according to any one of the preceding items, wherein R1is F, R2is Cl, R3is Cl, R5is H, and R6is H, or a pharmaceutically acceptable salt thereof. 61. The compound according to any one of the preceding items, wherein R1is F, R2is Cl, R3is F, R5is H, and R6is H, or a pharmaceutically acceptable salt thereof. 62. The compound according to any one of the preceding items, wherein R1is Cl, R2is Cl, R3is Cl, R5is H, and R6is H, or a pharmaceutically acceptable salt thereof. 63. The compound according to any one of the preceding items, wherein R1is Cl, R2is Cl, R3is F, R5is H, and R6is H, or a pharmaceutically acceptable salt thereof. 64. The compound according to any one of the preceding items, wherein R1is Cl, R2is Cl, R3is H, R5is F, and R6is H, or a pharmaceutically acceptable salt thereof. 65. The compound according to any one of the preceding items, wherein R1is Cl, R2is Cl, R3is H, R5is H, and R6is F, or a pharmaceutically acceptable salt thereof. 66. The compound according to any one of the preceding items, wherein R1is Cl, R2is Cl, R3is H, R5is H, and R6is H, or a pharmaceutically acceptable salt thereof. 67. The compound according to any one of the preceding items, wherein R1is F, R2is Cl, R3is H, R5is H, and R6is H, or a pharmaceutically acceptable salt thereof. 68. The compound according to any one of the preceding items, wherein R1is H, R2is Cl, R3is Cl, R5is H, and R6is H, or a pharmaceutically acceptable salt thereof. 69. The compound according to any one of the preceding items, wherein X6is a bond, or a pharmaceutically acceptable salt thereof. 70. The compound according to any one of the preceding items, wherein X7is a bond, or a pharmaceutically acceptable salt thereof. 71. The compound according to any one of the preceding items, wherein X7is C1-3 alkanediyl, or a pharmaceutically acceptable salt thereof. 72. The compound according to any one of the preceding items, wherein X7is CH2, or a pharmaceutically acceptable salt thereof. 73. The compound according to any one of the preceding items, wherein X2is C(R9)(R10); X3is N(C(O)R11); X4is C(R17)(R18); X5is C(R19)(R20); and X6is a bond, or a pharmaceutically acceptable salt thereof. 74. The compound according to any one of the preceding items, wherein R4is of Formula (III): , Formula (III) or a pharmaceutically acceptable salt thereof. 75. The compound according to any one of the preceding items, wherein R4is of Formula (IV): , Formula (IV) or a pharmaceutically acceptable salt thereof. 76. The compound according to any one of the preceding items, wherein R7, R8, R9, R10, R17, R18, R19, and R20are H, or a pharmaceutically acceptable salt thereof. 77. The compound according to any one of the preceding items, wherein R4is of Formula (V): Formula (V) or a pharmaceutically acceptable salt thereof. 78. The compound according to any one of the preceding items, wherein R7is C1-3 alkyl, such as CH3, and R8, R9, R10, R17, R18, R19, and R20are H, or a pharmaceutically acceptable salt thereof. 79. The compound according to any one of the preceding items, wherein R8is C1-3 alkyl, such as CH3, and R7, R9, R10, R17, R18, R19, and R20are H, or a pharmaceutically acceptable salt thereof. 80. The compound according to any one of the preceding items, wherein R7and R8are C1-3alkyl, such as CH3, and R9, R10, R17, R18, R19, and R20are H, or a pharmaceutically acceptable salt thereof. 81. The compound according to any one of the preceding items, wherein R17is C1-3 alkyl, such as CH3, and R7, R8, R9, R10, R18, R19, and R20are H, or a pharmaceutically acceptable salt thereof. 82. The compound according to any one of the preceding items, wherein R18is C1-3alkyl, such as CH3, and R7, R8, R9, R10, R17, R19, and R20are H, or a pharmaceutically acceptable salt thereof. 83. The compound according to any one of the preceding items, wherein R17and R18are C1-3alkyl, such as CH3, and R7, R8, R9, R10, R19, and R20are H, or a pharmaceutically acceptable salt thereof. 84. The compound according to any one of the preceding items, wherein R8and R17are C1-3alkyl, such as CH3, and R7, R9, R10, R18, R19, and R20are H, or a pharmaceutically acceptable salt thereof. 85. The compound according to any one of the preceding items, wherein when R11is linked to R9or R10to form a ring, then R9or R10is linked to R33of R11, or a pharmaceutically acceptable salt thereof. 86. The compound according to any one of the preceding items, wherein R9is linked to R33to form a ring, or a pharmaceutically acceptable salt thereof. 87. The compound according to any one of the preceding items, wherein R10is linked to R33to form a ring, or a pharmaceutically acceptable salt thereof. 88. The compound according to any one of the preceding items, wherein R11is C1-3alkyl or C1-3 alkoxy; R9is H; R10is a bond; and R11is linked to R10to form a ring, or a pharmaceutically acceptable salt thereof. 89. The compound according to any one of the preceding items, wherein R11is C1-3 alkyl or C1-3 alkoxy; R10is H; R9is a bond; and R11is linked to R9to form a ring, or a pharmaceutically acceptable salt thereof. 90. The compound according to any one of the preceding items, wherein R11is linked to R9to form a ring and R9is a bond or a C1-3 alkanediyl optionally substituted with 1 to 3 F, R10is H, and R11is C1-3 alkanediyl wherein one methylene group is optionally replaced by -O- or -N(R28)-, wherein R28is H or C1-3 alkyl, or a pharmaceutically acceptable salt thereof. 91. The compound according to any one of the preceding items, wherein R11is linked to R10to form a ring and R9is H, R10is a bond or a C1-3 alkanediyl optionally substituted with 1 to 3 F, and R11is C1-3 alkanediyl wherein one methylene group is optionally replaced by -O- or -N(R28)-, wherein R28is H or C1-3 alkyl, or a pharmaceutically acceptable salt thereof. 92. The compound according to any one of the preceding items, wherein R11is linked to R9to form a 5-membered ring, or a pharmaceutically acceptable salt thereof. 93. The compound according to any one of the preceding items, wherein R11is linked to R10to form a 5-membered ring, or a pharmaceutically acceptable salt thereof. 94. The compound according to any one of the preceding items, wherein X2is C(R9)(R10); X3is N(C(O)R11); and R11is linked to R9to form a ring together with the intervening atoms, or a pharmaceutically acceptable salt thereof. 95. The compound according to any one of the preceding items, wherein X2is C(R9)(R10); X3is N(C(O)R11); X4is C(R17)(R18); and R11is linked to R9to form a ring together with the intervening atoms, or a pharmaceutically acceptable salt thereof. 96. The compound according to any one of the preceding items, wherein X2is C(R9)(R10); X3is N(C(O)R11); X4is C(R17)(R18); X5is C(R19)(R20); X6is a bond; and R11is linked to R9to form a ring together with the intervening atoms, or a pharmaceutically acceptable salt thereof. 97. The compound according to any one of the preceding items, wherein X2is C(R9)(R10); X3is N(C(O)R11); X4is C(R17)(R18); X5is C(R19)(R20); X6is a bond; and R11is linked to R9to form a 5-membered ring, or a pharmaceutically acceptable salt thereof. 98. The compound according to any one of the preceding items, wherein X2is C(R9)(R10); X3is N(C(O)R11); and R11is linked to R10to form a ring together with the intervening atoms, or a pharmaceutically acceptable salt thereof. 99. The compound according to any one of the preceding items, wherein X2is C(R9)(R10); X3is N(C(O)R11); X4is C(R17)(R18); and R11is linked to R10to form a ring together with the intervening atoms, or a pharmaceutically acceptable salt thereof. 100. The compound according to any one of the preceding items, wherein X2is C(R9)(R10); X3is N(C(O)R11); X4is C(R17)(R18); X5is C(R19)(R20); X6is a bond; and R11is linked to R10to form a ring together with the intervening atoms, or a pharmaceutically acceptable salt thereof. 101. The compound according to any one of the preceding items, wherein X2is C(R9)(R10); X3is N(C(O)R11); X4is C(R17)(R18); X5is C(R19)(R20); X6is a bond; and R11is linked to R10to form a 5-membered ring, or a pharmaceutically acceptable salt thereof. 102. The compound according to any one of the preceding items, wherein R4is of Formula (LI): , Formula (LI) wherein R7is H, C1-3 alkyl optionally substituted with 1 to 3 F or C1-3 alkoxy, or halogen, such as F; R8is H, C1-3 alkyl optionally substituted with 1 to 3 F or C1-3 alkoxy, or halogen, such as F; R9is a bond, -C(O)- or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl; R10is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R11is -O-, -N(R28)-, or C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl, wherein one methylene group of the C1-3 alkanediyl is optionally replaced by -O- or -N(R28)-, wherein R28is H or C1-3 alkyl; R17is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R18is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R19is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R20is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; and R28is H or C1-3 alkyl, or a pharmaceutically acceptable salt thereof. 103. The compound according to any one of the preceding items, wherein the moiety of Formula (LI) is of Formula (LIa): , Formula (LIa) or a pharmaceutically acceptable salt thereof. 104. The compound according to any one of the preceding items, wherein R4is of Formula (LI) or Formula (LIa) and R7, R8, R10, R17, R18, R19, and R20are H, or a pharmaceutically acceptable salt thereof. 105. The compound according to any one of the preceding items, wherein R4is of Formula (LI) or Formula (LIa) and R11is -O-, or a pharmaceutically acceptable salt thereof. 106. The compound according to any one of the preceding items, wherein R4is of Formula (LI) or Formula (LIa) and R11is -CH2-, or a pharmaceutically acceptable salt thereof. 107. The compound according to any one of the preceding items, wherein R4is of Formula (LI) or Formula (LIa) and R11is -CH2CH2-, or a pharmaceutically acceptable salt thereof. 108. The compound according to any one of the preceding items, wherein R4is of Formula (LII): , Formula (LII) wherein R7is H, C1-3 alkyl optionally substituted with 1 to 3 F or C1-3 alkoxy, or halogen, such as F; R8is H, C1-3alkyl optionally substituted with 1 to 3 F or C1-3alkoxy, or halogen, such as F; R10is a bond, -C(O)-, or a C1-3alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl; R9is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R11is -O-, -N(R28)-, or C1-3alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl, wherein one methylene group of the C1-3alkanediyl is optionally replaced by -O- or -N(R28)-, wherein R28is H or C1-3alkyl; R17is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R18is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R19is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R20is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; and R28is H or C1-3alkyl, or a pharmaceutically acceptable salt thereof. 109. The compound according to any one of the preceding items, wherein the moiety of Formula (LII) is of Formula (LIIa): , Formula (LIIa) or a pharmaceutically acceptable salt thereof. 110. The compound according to any one of the preceding items, wherein R4is of Formula (LII) or Formula (LIIa) and R7, R8, R10, R17, R18, R19, and R20are H, or a pharmaceutically acceptable salt thereof. 111. The compound according to any one of the preceding items, wherein R4is of Formula (LII) or Formula (LIIa) and R11is -O-, or a pharmaceutically acceptable salt thereof. 112. The compound according to any one of the preceding items, wherein R4is of Formula (LII) or Formula (LIIa) and R11is -CH2-, or a pharmaceutically acceptable salt thereof. 113. The compound according to any one of the preceding items, wherein R4is of Formula (LII) or Formula (LIIa) and R11is -CH2CH2-, or a pharmaceutically acceptable salt thereof. 114. The compound according to any one of the preceding items, wherein R4is of Formula (XX): , Formula (XX) wherein R7is H, C1-3 alkyl optionally substituted with 1 to 3 F or C1-3 alkoxy, or halogen, such as F; R8is H, C1-3 alkyl optionally substituted with 1 to 3 F or C1-3 alkoxy, or halogen, such as F; R10is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R17is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R18is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R19is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R20is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R31is individually halogen or C1-3alkyl; r is 0, 1, 2, 3 or 4; X8is -CH2-, -O-, -CH2O-, -OCH2-, -N(R28)-, or -CH2N(R28)-; and R28is H or C1-3alkyl, or a pharmaceutically acceptable salt thereof. 115. The compound according to any one of the preceding items, wherein the moiety of Formula (XX) is of Formula (XXa): , Formula (XXa) or a pharmaceutically acceptable salt thereof. 116. The compound according to any one of the preceding items, wherein R4is of Formula (XXa) and R7, R8, R10, R17, R18, R19, and R20are H, or a pharmaceutically acceptable salt thereof. 117. The compound according to any one of the preceding items, wherein the moiety of Formula (XX) is of Formula (XXb): , Formula (XXb) wherein R9is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F or a pharmaceutically acceptable salt thereof. 118. The compound according to any one of the preceding items, wherein R4is of Formula (XXb) and R7, R8, R9, R17, R18, R19, and R20are H, or a pharmaceutically acceptable salt thereof. 119. The compound according to any one of the preceding items, wherein R4is of Formula (XV): , Formula (XV) wherein X8is -CH2-, -O- or -N(R28)-; and R28is H or C1-3 alkyl, or a pharmaceutically acceptable salt thereof. 120. The compound according to any one of the preceding items, wherein X8is -CH2-, or a pharmaceutically acceptable salt thereof. 121. The compound according to any one of the preceding items, wherein X8is -O-, or a pharmaceutically acceptable salt thereof. 122. The compound according to any one of the preceding items, wherein X8is -N(R28)-, or a pharmaceutically acceptable salt thereof. 123. The compound according to any one of the preceding items, wherein X8is -CH2O-, or a pharmaceutically acceptable salt thereof. 124. The compound according to any one of the preceding items, wherein X8is -OCH2-, or a pharmaceutically acceptable salt thereof. 125. The compound according to any one of the preceding items, wherein X8is -CH2N(R28)-, or a pharmaceutically acceptable salt thereof. 126. The compound according to any one of the preceding items, wherein R11is linked to R9to form a 6-membered ring, or a pharmaceutically acceptable salt thereof. 127. The compound according to any one of the preceding items, wherein R11is linked to R10to form a 6-membered ring, or a pharmaceutically acceptable salt thereof. 128. The compound according to any one of the preceding items, wherein X2is C(R9)(R10); X3is N(C(O)R11); X4is C(R17)(R18); X5is C(R19)(R20); X6is a bond; and R11is linked to R9to form a 6-membered ring, or a pharmaceutically acceptable salt thereof. 129. The compound according to any one of the preceding items, wherein X2is C(R9)(R10); X3is N(C(O)R11); X4is C(R17)(R18); X5is C(R19)(R20); X6is a bond; and R11is linked to R10to form a 6-membered ring, or a pharmaceutically acceptable salt thereof. 130. The compound according to any one of the preceding items, wherein R11is linked to R9or R10to form a ring together with the intervening atoms, and R11is -O-, or a pharmaceutically acceptable salt thereof. 131. The compound according to any one of the preceding items, wherein R11is linked to R9or R10to form a ring together with the intervening atoms, and R11is C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl, wherein one methylene group of the C1-3 alkanediyl is optionally replaced by -O- or -N(R28)-, wherein R28is H or C1-3 alkyl, or a pharmaceutically acceptable salt thereof. 132. The compound according to any one of the preceding items, wherein R11is linked to R9or R10to form a ring together with the intervening atoms, and R11is C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl, or a pharmaceutically acceptable salt thereof. 133. The compound according to any one of the preceding items, wherein R11is linked to R9or R10to form a ring together with the intervening atoms, and R11is -CH2-, or a pharmaceutically acceptable salt thereof. 134. The compound according to any one of the preceding items, wherein R11is linked to R9or R10to form a ring together with the intervening atoms, and R11is - CH2CH2-, or a pharmaceutically acceptable salt thereof. 135. The compound according to any one of the preceding items, wherein R11is linked to R9or R10to form a ring together with the intervening atoms, and R11is -CH2O-, or a pharmaceutically acceptable salt thereof. 136. The compound according to any one of the preceding items, wherein R11is linked to R9or R10to form a ring together with the intervening atoms, and R11is -N(R28)-, or a pharmaceutically acceptable salt thereof. 137. The compound according to any one of the preceding items, wherein R28is C1-3alkyl, or a pharmaceutically acceptable salt thereof. 138. The compound according to any one of the preceding items, wherein R28is CH3, or a pharmaceutically acceptable salt thereof. 139. The compound according to any one of the preceding items, wherein R11is linked to R9or R10to form a ring together with the intervening atoms, and R11is -O-, or a pharmaceutically acceptable salt thereof. 140. The compound according to any one of the preceding items, wherein R11is linked to R9to form a ring together with the intervening atoms, and R11-R9is -(CH2)3-, -(CH2)O-, -(CH2)2O-, -CH2OCH2-, -C(H)(CH3)CH2-, -C(O)N(H)-, or a pharmaceutically acceptable salt thereof. 141. The compound according to any one of the preceding items, wherein R11is linked to R10to form a ring together with the intervening atoms, and R11-R10is -(CH2)3-, -(CH2)O-, -(CH2)2O-, -CH2OCH2-, -C(H)(CH3)CH2-, -C(O)N(H)-, or a pharmaceutically acceptable salt thereof. 142. The compound according to any one of the preceding items, wherein X2is C(R9)(R10); X3is N(R16); X4is C(O); X5is C(R19)(R20); and X6is a bond, or a pharmaceutically acceptable salt thereof. 143. The compound according to any one of the preceding items, wherein R4is of Formula (VI): , Formula (VI) wherein R16is H or C1-3alkyl; and R27is H or C1-3alkyl, or a pharmaceutically acceptable salt thereof. 144. The compound according to any one of the preceding items, wherein R4is of Formula (VIA-1), Formula (VIA-2), Formula (VIB-1), or Formula (VIB-2): Formula (VIA-1) Formula (VIA-2) Formula (VIB-1) Formula (VIB-2) wherein R7is H or C1-3 alkyl; R16is H or C1-3 alkyl; and R20is H or C1-3 alkyl, or a pharmaceutically acceptable salt thereof. 145. The compound according to any one of the preceding items, wherein R7and R19are linked together to form a bridged bicyclic ring, or a pharmaceutically acceptable salt thereof. 146. The compound according to any one of the preceding items, wherein R8and R20are linked together to form a bridged bicyclic ring, or a pharmaceutically acceptable salt thereof. 147. The compound according to any one of the preceding items, wherein R9and R17are linked together to form a bridged bicyclic ring, or a pharmaceutically acceptable salt thereof. 148. The compound according to any one of the preceding items, wherein R10and R18are linked together to form a bridged bicyclic ring, or a pharmaceutically acceptable salt thereof. 149. The compound according to any one of the preceding items, wherein R9and R19are linked together to form a bridged bicyclic ring, or a pharmaceutically acceptable salt thereof. 150. The compound according to any one of the preceding items, wherein R10and R20are linked together to form a bridged bicyclic ring, or a pharmaceutically acceptable salt thereof. 151. The compound according to any one of the preceding items, wherein R7and R17are linked together to form a bridged bicyclic ring, or a pharmaceutically acceptable salt thereof. 152. The compound according to any one of the preceding items, wherein R8and R18are linked together to form a bridged bicyclic ring, or a pharmaceutically acceptable salt thereof. 153. The compound according to any one of the preceding items, wherein X2is C(R9)(R10); X3is N(C(O)R11); X4is C(R17)(R18); X5is C(R19)(R20); X6is a bond; and R7and R19are linked together to form a bridged bicyclic ring, or a pharmaceutically acceptable salt thereof. 154. The compound according to any one of the preceding items, wherein X2is C(R9)(R10); X3is N(C(O)R11); X4is C(R17)(R18); X5is C(R19)(R20); X6is a bond; and R8and R20are linked together to form a bridged bicyclic ring, or a pharmaceutically acceptable salt thereof. 155. The compound according to any one of the preceding items, wherein X2is C(R9)(R10); X3is N(C(O)R11); X4is C(R17)(R18); X5is C(R19)(R20); X6is a bond; and R9and R17are linked together to form a bridged bicyclic ring, or a pharmaceutically acceptable salt thereof. 156. The compound according to any one of the preceding items, wherein X2is C(R9)(R10); X3is N(C(O)R11); X4is C(R17)(R18); X5is C(R19)(R20); X6is a bond; and R10and R18are linked together to form a bridged bicyclic ring, or a pharmaceutically acceptable salt thereof. 157. The compound according to any one of the preceding items, wherein X2is C(R9)(R10); X3is N(C(O)R11); X4is C(R17)(R18); X5is C(R19)(R20); X6is a bond; and R9and R19are linked together to form a bridged bicyclic ring, or a pharmaceutically acceptable salt thereof. 158. The compound according to any one of the preceding items, wherein X2is C(R9)(R10); X3is N(C(O)R11); X4is C(R17)(R18); X5is C(R19)(R20); X6is a bond; and R10and R20are linked together to form a bridged bicyclic ring, or a pharmaceutically acceptable salt thereof. 159. The compound according to any one of the preceding items, wherein X2is C(R9)(R10); X3is N(C(O)R11); X4is C(R17)(R18); X5is C(R19)(R20); X6is a bond; and R7and R17are linked together to form a bridged bicyclic ring, or a pharmaceutically acceptable salt thereof. 160. The compound according to any one of the preceding items, wherein X2is C(R9)(R10); X3is N(C(O)R11); X4is C(R17)(R18); X5is C(R19)(R20); X6is a bond; and R8and R18are linked together to form a bridged bicyclic ring, or a pharmaceutically acceptable salt thereof. 161. The compound according to any one of the preceding items, wherein R4is of Formula (VII), Formula (VIII), or Formula (IX): Formula (VII) Formula (VIII) Formula (IX) wherein w is 1 or 2, or a pharmaceutically acceptable salt thereof. 162. The compound according to any one of the preceding items, wherein R4is of Formula (VII) and w is 1, or a pharmaceutically acceptable salt thereof. 163. The compound according to any one of the preceding items, wherein R4is of Formula (VII) and w is 2, or a pharmaceutically acceptable salt thereof. 164. The compound according to any one of the preceding items, wherein R4is of Formula (VIII) and w is 1, or a pharmaceutically acceptable salt thereof. 165. The compound according to any one of the preceding items, wherein R4is of Formula (VIII) and w is 2, or a pharmaceutically acceptable salt thereof. 166. The compound according to any one of the preceding items, wherein R4is of Formula (IX) and w is 2, or a pharmaceutically acceptable salt thereof. 167. The compound according to any one of the preceding items, wherein X2is C(R9)(R10); X3is C(R12)(C(O)R13); and R13is linked to R9to form a ring together with the intervening atoms, or a pharmaceutically acceptable salt thereof. 168. The compound according to any one of the preceding items, wherein X2is C(R9)(R10); X3is C(R12)(C(O)R13); X4is C(R17)(R18); and R13is linked to R9to form a ring together with the intervening atoms, or a pharmaceutically acceptable salt thereof. 169. The compound according to any one of the preceding items, wherein X2is C(R9)(R10); X3is C(R12)(C(O)R13); X4is C(R17)(R18); X6is a bond; and R13is linked to R9to form a ring together with the intervening atoms, or a pharmaceutically acceptable salt thereof. 170. The compound according to any one of the preceding items, wherein X2is C(R9)(R10); X3is C(R12)(C(O)R13); X4is C(R17)(R18); X5is a bond; X6is a bond; and R13is linked to R9to form a ring together with the intervening atoms, or a pharmaceutically acceptable salt thereof. 171. The compound according to any one of the preceding items, wherein R4is of Formula (LIII): Formula (LIII) wherein R7is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R8is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R9is a bond or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl; R10is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R12is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R13is -N(R28)-, wherein R28is H or C1-3 alkyl; R17is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; and R18is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F, or a pharmaceutically acceptable salt thereof. 172. The compound according to any one of the preceding items, wherein the moiety of Formula (LIII) is of Formula (LIIIa): Formula (LIIIa) or a pharmaceutically acceptable salt thereof. 173. The compound according to any one of the preceding items, wherein R4is of Formula (LIII) or Formula (LIIIa) and R7, R8, R10, R12, R17, and R18are H, or a pharmaceutically acceptable salt thereof. 174. The compound according to any one of the preceding items, wherein R4is of Formula (LIII) or Formula (LIIIa) and R13is -N(CH3)-, or a pharmaceutically acceptable salt thereof. 175. The compound according to any one of the preceding items, wherein R4is of Formula (LIII) or Formula (LIIIa) and R9is -CH2-, or a pharmaceutically acceptable salt thereof. 176. The compound according to any one of the preceding items, wherein X2is C(R9)(R10); X3is C(R12)(C(O)R13); and R13is linked to R10to form a ring together with the intervening atoms, or a pharmaceutically acceptable salt thereof. 177. The compound according to any one of the preceding items, wherein X2is C(R9)(R10); X3is C(R12)(C(O)R13); X4is C(R17)(R18); and R13is linked to R10to form a ring together with the intervening atoms, or a pharmaceutically acceptable salt thereof. 178. The compound according to any one of the preceding items, wherein X2is C(R9)(R10); X3is C(R12)(C(O)R13); X4is C(R17)(R18); X6is a bond; and R13is linked to R10to form a ring together with the intervening atoms, or a pharmaceutically acceptable salt thereof. 179. The compound according to any one of the preceding items, wherein X2is C(R9)(R10); X3is C(R12)(C(O)R13); X4is C(R17)(R18); X5is a bond; X6is a bond; and R13is linked to R10to form a ring together with the intervening atoms, or a pharmaceutically acceptable salt thereof. 180. The compound according to any one of the preceding items, wherein R4is of Formula (LIV): Formula (LIV) wherein R7is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R8is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R9is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R10is a bond or a C1-3alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl; R12is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R13is -N(R28)-, wherein R28is H or C1-3alkyl; R17is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; and R18is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F, or a pharmaceutically acceptable salt thereof. 181. The compound according to any one of the preceding items, wherein the moiety of Formula (LIV) is of Formula (LIVa): Formula (LIVa) or a pharmaceutically acceptable salt thereof. 182. The compound according to any one of the preceding items, wherein R4is of Formula (LIV) or Formula (LIVa) and R7, R8, R9, R12, R17, and R18are H, or a pharmaceutically acceptable salt thereof. 183. The compound according to any one of the preceding items, wherein R4is of Formula (LIV) or Formula (LIVa) and R13is -N(CH3)-, or a pharmaceutically acceptable salt thereof. 184. The compound according to any one of the preceding items, wherein R4is of Formula (LIV) or Formula (LIVa) and R10is -CH2-, or a pharmaceutically acceptable salt thereof. 185. The compound according to any one of the preceding items, wherein X3is C(R12)(C(O)R13); X4is C(R17)(R18); and R13is linked to R17to form a ring together with the intervening atoms, or a pharmaceutically acceptable salt thereof. 186. The compound according to any one of the preceding items, wherein X2is a bond; X3is C(R12)(C(O)R13); X4is C(R17)(R18); and R13is linked to R17to form a ring together with the intervening atoms, or a pharmaceutically acceptable salt thereof. 187. The compound according to any one of the preceding items, wherein X2is a bond; X3is C(R12)(C(O)R13); X4is C(R17)(R18); X5is C(R19)(R20); X6is C(R21)(R22); and R13is linked to R17to form a ring together with the intervening atoms, or a pharmaceutically acceptable salt thereof. 188. The compound according to any one of the preceding items, wherein R4is of Formula (LV): Formula (LV) wherein R7is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R8is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R12is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R13is -N(R28)-, wherein R28is H or C1-3 alkyl; R17is a bond or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl; R18is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R19is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R20is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R21is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; and R22is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F, or a pharmaceutically acceptable salt thereof. 189. The compound according to any one of the preceding items, wherein the moiety of Formula (LV) is of Formula (LVa) or Formula (LVb): Formula (LVa) Formula (LVb) or a pharmaceutically acceptable salt thereof. 190. The compound according to any one of the preceding items, wherein R4is of Formula (LV), Formula (LVa) or Formula (LVb) and R7, R8, R12, R18, R19, R20, R21, and R22are H, or a pharmaceutically acceptable salt thereof. 191. The compound according to any one of the preceding items, wherein R4is of Formula (LV), Formula (LVa) or Formula (LVb) and R13is -N(CH3)-, or a pharmaceutically acceptable salt thereof. 192. The compound according to any one of the preceding items, wherein R4is of Formula (LV), Formula (LVa) or Formula (LVb) and R17is -CH2-, or a pharmaceutically acceptable salt thereof. 193. The compound according to any one of the preceding items, wherein X3is C(R12)(C(O)R13); X4is C(R17)(R18); and R13is linked to R18to form a ring together with the intervening atoms, or a pharmaceutically acceptable salt thereof. 194. The compound according to any one of the preceding items, wherein X2is a bond; X3is C(R12)(C(O)R13); X4is C(R17)(R18); and R13is linked to R18to form a ring together with the intervening atoms, or a pharmaceutically acceptable salt thereof. 195. The compound according to any one of the preceding items, wherein X2is a bond; X3is C(R12)(C(O)R13); X4is C(R17)(R18); X5is C(R19)(R20); X6is C(R21)(R22); and R13is linked to R18to form a ring together with the intervening atoms, or a pharmaceutically acceptable salt thereof. 196. The compound according to any one of the preceding items, wherein X2is a bond; X3is C(R12)(C(O)R13); X4is O; X5is C(R19)(R20); and X6is C(R21)(R22), or a pharmaceutically acceptable salt thereof. 197. The compound according to any one of the preceding items, wherein X2is a bond; X3is C(R12)(C(O)R13); X4is C(R17)(R18); X5is C(R19)(R20); and X6is C(R21)(R22), or a pharmaceutically acceptable salt thereof. 198. The compound according to any one of the preceding items, wherein X2is C(R9)(R10); X3is C(R12)(C(O)R13); X4is C(R17)(R18); X5is a bond; and X6is bond, or a pharmaceutically acceptable salt thereof. 199. The compound according to any one of the preceding items, wherein R4is of Formula (Xa) or Formula (Xb): Formula (Xa)Formula (Xb)or a pharmaceutically acceptable salt thereof. 200. The compound according to any one of the preceding items, wherein X2is C(R9)(R10); X3is C(R14)(R15); X4is C(R17)(R18); X5is a bond; and X6is bond, or a pharmaceutically acceptable salt thereof. 201. The compound according to any one of the preceding items, wherein R4is of Formula (XI): Formula (XI) wherein R14is -X7N(R23)(C(O)R24); X7is a bond or CH2; R23is H or C1-3alkyl, or R23is a bond and R15is C1-3alkanediyl and R23is linked to R15to form a 4 or 5 membered ring; R24is C1-3alkyl; and R15is H or C1-3alkyl; or a pharmaceutically acceptable salt thereof. 202. The compound according to any one of the preceding items, wherein X7is a bond; R23is H or C1-3alkyl; R24is C1-3alkyl; and R15is H or C1-3alkyl, or a pharmaceutically acceptable salt thereof. 203. The compound according to any one of the preceding items, wherein X2is a bond; X3is C(R14)(R15); X4is C(R17)(R18); X5is C(R19)(R20); and X6is bond, or a pharmaceutically acceptable salt thereof. 204. The compound according to any one of the preceding items, wherein X2is a bond; X3is C(R14)(R15); X4is C(R17)(R18); X5is a bond; and X6is bond, or a pharmaceutically acceptable salt thereof. 205. The compound according to any one of the preceding items, wherein R14and R15are linked together to form a ring, or a pharmaceutically acceptable salt thereof. 206. The compound according to any one of the preceding items, wherein R14and R15are linked together to form a 5 membered ring, or a pharmaceutically acceptable salt thereof. 207. The compound according to any one of the preceding items, wherein R14and R15are linked together to form a 4 membered ring, or a pharmaceutically acceptable salt thereof. 208. The compound according to any one of the preceding items, wherein R4is of Formula (XIX): Formula (XIX) wherein X9is a bond or -N(R29)-; R29is C1-3alkyl; X10is -C(O)-, -CH2-, or a bond; X11is -O-, -CH2-, or -N(R30)-; R30is C1-3alkyl; X12is -N(C(O)R24)- or a bond; m is 1 or 2; n is 0 or 1; and z is 1 or 2; with the proviso that when X10is -C(O)-, then X12is a bond; with the proviso that when X10is -CH2- or a bond, then X12is -N(C(O)R24)-; and with the proviso that ring A is a 4 to 6 membered ring, or a pharmaceutically acceptable salt thereof. 209. The compound according to any one of the preceding items, wherein ring A is a 4 membered ring, or a pharmaceutically acceptable salt thereof. 210. The compound according to any one of the preceding items, wherein ring A is a 5 membered ring, or a pharmaceutically acceptable salt thereof. 211. The compound according to any one of the preceding items, wherein R23is a bond and R15is C1-3alkanediyl and R23is linked to R15to form a 4 or 5 membered ring, or a pharmaceutically acceptable salt thereof. 212. The compound according to any one of the preceding items, wherein R4is of Formula (XII): Formula (XII) wherein m is 0 or 1; n is 0 or 1; and p is 0, 1 or 2, or a pharmaceutically acceptable salt thereof. 213. The compound according to any one of the preceding items, wherein R4is of Formula (XII) and with the proviso that when m is 0 then p is 1 or 2, or a pharmaceutically acceptable salt thereof. 214. The compound according to any one of the preceding items, wherein R4is of Formula (XII) and with the proviso that when p is 2, then m is 0, or a pharmaceutically acceptable salt thereof. 215. The compound according to any one of the preceding items, wherein m is 0, or a pharmaceutically acceptable salt thereof. 216. The compound according to any one of the preceding items, wherein m is 1, or a pharmaceutically acceptable salt thereof. 217. The compound according to any one of the preceding items, wherein p is 0, or a pharmaceutically acceptable salt thereof. 218. The compound according to any one of the preceding items, wherein p is 1, or a pharmaceutically acceptable salt thereof. 219. The compound according to any one of the preceding items, wherein p is 2, or a pharmaceutically acceptable salt thereof. 220. The compound according to any one of the preceding items, wherein m is 0 and p is 1, or a pharmaceutically acceptable salt thereof. 221. The compound according to any one of the preceding items, wherein m is 1 and p is 1, or a pharmaceutically acceptable salt thereof. 222. The compound according to any one of the preceding items, wherein m is 1 and p is 0, or a pharmaceutically acceptable salt thereof. 223. The compound according to any one of the preceding items, wherein m is 0 and p is 2, or a pharmaceutically acceptable salt thereof. 224. The compound according to any one of the preceding items, wherein n is 0, or a pharmaceutically acceptable salt thereof. 225. The compound according to any one of the preceding items, wherein n is 1, or a pharmaceutically acceptable salt thereof. 226. The compound according to any one of the preceding items, wherein X2is C(R9)(R10); X3is C(R14)(R15); X4is C(R17)(R18); X5is C(R19)(R20); and X6is bond, or a pharmaceutically acceptable salt thereof. 227. The compound according to any one of the preceding items, wherein R14and R15are linked together to form a ring, or a pharmaceutically acceptable salt thereof. 228. The compound according to any one of the preceding items, wherein R14and R15are linked together to form a ring, and wherein R14is -X9C(O)X11-, wherein X9is a bond or -N(R29)-; R29is C1-3 alkyl; X11is -O-, -CH2-, or -N(R30)-; and R30is C1-3 alkyl; and R15is a bond or C1-3 alkanediyl, or a pharmaceutically acceptable salt thereof. 229. The compound according to any one of the preceding items, wherein R4is of Formula (XVI): Formula (XVI) wherein R14and R15are linked together to form a ring; R14is -X9C(O)X11-; X9is a bond or -N(R29)-; R29is C1-3alkyl; X11is -O-, -CH2-, or -N(R30)-; R30is C1-3alkyl; and R15is a bond or C1-3alkanediyl, or a pharmaceutically acceptable salt thereof. 230. The compound according to any one of the preceding items, wherein R4is of Formula (XVII): Formula (XVII) wherein X9is a bond or -N(R29)-; R29is C1-3 alkyl; X11is -O-, -CH2-, or -N(R30)-; R30is C1-3 alkyl; m is 1 or 2; n is 0 or 1; and z is 1 or 2, or a pharmaceutically acceptable salt thereof. 231. The compound according to any one of the preceding items, wherein R4is of Formula (XVIII): Formula (XVIII) wherein X9is a bond or -N(R29)-; R29is C1-3alkyl; X11is -O-, -CH2-, or -N(R30)-; R30is C1-3alkyl; and m is 1 or 2, or a pharmaceutically acceptable salt thereof. 232. The compound according to any one of the preceding items, wherein X9is a bond, or a pharmaceutically acceptable salt thereof. 233. The compound according to any one of the preceding items, wherein X9is -N(R29)-, or a pharmaceutically acceptable salt thereof. 234. The compound according to any one of the preceding items, wherein R29is CH3, or a pharmaceutically acceptable salt thereof. 235. The compound according to any one of the preceding items, wherein X11is -O-, or a pharmaceutically acceptable salt thereof. 236. The compound according to any one of the preceding items, wherein X11is C1-3alkanediyl, or a pharmaceutically acceptable salt thereof. 237. The compound according to any one of the preceding items, wherein X11is -CH2-, or a pharmaceutically acceptable salt thereof. 238. The compound according to any one of the preceding items, wherein X11is -N(R30)-, or a pharmaceutically acceptable salt thereof. 239. The compound according to any one of the preceding items, wherein R30is CH3, or a pharmaceutically acceptable salt thereof. 240. The compound according to any one of the preceding items, wherein m is 1, or a pharmaceutically acceptable salt thereof. 241. The compound according to any one of the preceding items, wherein m is 2, or a pharmaceutically acceptable salt thereof. 242. The compound according to any one of the preceding items, wherein z is 1, or a pharmaceutically acceptable salt thereof. 243. The compound according to any one of the preceding items, wherein z is 2, or a pharmaceutically acceptable salt thereof. 244. The compound according to any one of the preceding items, wherein n is 1 and z is 1, or a pharmaceutically acceptable salt thereof. 245. The compound according to any one of the preceding items, wherein n is 1 and z is 2, or a pharmaceutically acceptable salt thereof. 246. The compound according to any one of the preceding items, wherein n is 0 and z is 2, or a pharmaceutically acceptable salt thereof. 247. The compound according to any one of the preceding items, wherein R7is H, or a pharmaceutically acceptable salt thereof. 248. The compound according to any one of the preceding items, wherein R7is C1-3 alkyl, or a pharmaceutically acceptable salt thereof. 249. The compound according to any one of the preceding items, wherein R7is CH3, or a pharmaceutically acceptable salt thereof. 250. The compound according to any one of the preceding items, wherein R7is C1-3alkyl substituted with 1 to 3 F, or a pharmaceutically acceptable salt thereof. 251. The compound according to any one of the preceding items, wherein R7is C1-3alkyl substituted with C1-3alkoxy, or a pharmaceutically acceptable salt thereof. 252. The compound according to any one of the preceding items, wherein R7is CH2OCH3, or a pharmaceutically acceptable salt thereof. 253. The compound according to any one of the preceding items, wherein R7is halogen, such as F, or a pharmaceutically acceptable salt thereof. 254. The compound according to any one of the preceding items, wherein R8is H, or a pharmaceutically acceptable salt thereof. 255. The compound according to any one of the preceding items, wherein R8is C1-3 alkyl, or a pharmaceutically acceptable salt thereof. 256. The compound according to any one of the preceding items, wherein R8is CH3, or a pharmaceutically acceptable salt thereof. 257. The compound according to any one of the preceding items, wherein R8is C1-3 alkyl substituted with 1 to 3 F, or a pharmaceutically acceptable salt thereof. 258. The compound according to any one of the preceding items, wherein R8is halogen, such as F, or a pharmaceutically acceptable salt thereof. 259. The compound according to any one of the preceding items, wherein R8is C1-3 alkyl substituted with C1-3 alkoxy, or a pharmaceutically acceptable salt thereof. 260. The compound according to any one of the preceding items, wherein R8is CH2OCH3, or a pharmaceutically acceptable salt thereof. 261. The compound according to any one of the preceding items, wherein R9is H, or a pharmaceutically acceptable salt thereof. 262. The compound according to any one of the preceding items, wherein R9is C1-3 alkyl, or a pharmaceutically acceptable salt thereof. 263. The compound according to any one of the preceding items, wherein R9is C1-3 alkyl substituted with 1 to 3 halogens, or a pharmaceutically acceptable salt thereof. 264. The compound according to any one of the preceding items, wherein R9is C1-3alkyl substituted with 1 to 3 F, or a pharmaceutically acceptable salt thereof. 265. The compound according to any one of the preceding items, wherein R9is -C(O)N(R31)(R32), wherein R31is H or C1-3alkyl and R32is H or C1-3alkyl, or a pharmaceutically acceptable salt thereof. 266. The compound according to any one of the preceding items, wherein R9is -C(O)N(H)(CH3), or a pharmaceutically acceptable salt thereof. 267. The compound according to any one of the preceding items, wherein R9is -C(O)NH2, or a pharmaceutically acceptable salt thereof. 268. The compound according to any one of the preceding items, wherein R9is -C(O)N(CH3)2, or a pharmaceutically acceptable salt thereof. 269. The compound according to any one of the preceding items, wherein R9is halogen, such as F, or a pharmaceutically acceptable salt thereof. 270. The compound according to any one of the preceding items, wherein R9is linked to R11to form a ring, and R9is a bond, or a pharmaceutically acceptable salt thereof. 271. The compound according to any one of the preceding items, wherein R9is linked to R11to form a ring, and R9is -C(O)-, or a pharmaceutically acceptable salt thereof. 272. The compound according to any one of the preceding items, wherein R9is linked to R11to form a ring, and R9is C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl, or a pharmaceutically acceptable salt thereof. 273. The compound according to any one of the preceding items, wherein R9is linked to R11to form a ring, and R9is -CH2-, or a pharmaceutically acceptable salt thereof. 274. The compound according to any one of the preceding items, wherein R9is linked to R11to form a ring, and R9is -(CH2)2-, or a pharmaceutically acceptable salt thereof. 275. The compound according to any one of the preceding items, wherein R9is linked to R11to form a ring, and R9is -C(H)(CH3)-, or a pharmaceutically acceptable salt thereof. 276. The compound according to any one of the preceding items, wherein R9is linked to R11or R13to form a ring, and R9is a bond, or a pharmaceutically acceptable salt thereof. 277. The compound according to any one of the preceding items, wherein R9is linked to R11or R13to form a ring, and R9is C1-3alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl, or a pharmaceutically acceptable salt thereof. 278. The compound according to any one of the preceding items, wherein R9is linked to R11or R13to form a ring, and R9is -CH2-, or a pharmaceutically acceptable salt thereof. 279. The compound according to any one of the preceding items, wherein R9is linked to R11or R13to form a ring, and R9is -CH2CH2-, or a pharmaceutically acceptable salt thereof. 280. The compound according to any one of the preceding items, wherein R10is H, or a pharmaceutically acceptable salt thereof. 281. The compound according to any one of the preceding items, wherein R10is C1-3 alkyl, or a pharmaceutically acceptable salt thereof. 282. The compound according to any one of the preceding items, wherein R10is C1-3 alkyl substituted with 1 to 3 halogens, or a pharmaceutically acceptable salt thereof. 283. The compound according to any one of the preceding items, wherein R10is C1-3 alkyl substituted with 1 to 3 F, or a pharmaceutically acceptable salt thereof. 284. The compound according to any one of the preceding items, wherein R10is -C(O)N(R31)(R32), wherein R31is H or C1-3 alkyl and R32is H or C1-3 alkyl, or a pharmaceutically acceptable salt thereof. 285. The compound according to any one of the preceding items, wherein R10is -C(O)N(H)(CH3), or a pharmaceutically acceptable salt thereof. 286. The compound according to any one of the preceding items, wherein R10is -C(O)NH2, or a pharmaceutically acceptable salt thereof. 287. The compound according to any one of the preceding items, wherein R10is -C(O)N(CH3)2, or a pharmaceutically acceptable salt thereof. 288. The compound according to any one of the preceding items, wherein R31is H, or a pharmaceutically acceptable salt thereof. 289. The compound according to any one of the preceding items, wherein R31is C1-3alkyl, or a pharmaceutically acceptable salt thereof. 290. The compound according to any one of the preceding items, wherein R31is CH3, or a pharmaceutically acceptable salt thereof. 291. The compound according to any one of the preceding items, wherein R32is H, or a pharmaceutically acceptable salt thereof. 292. The compound according to any one of the preceding items, wherein R32is C1-3alkyl, or a pharmaceutically acceptable salt thereof. 293. The compound according to any one of the preceding items, wherein R32is CH3, or a pharmaceutically acceptable salt thereof. 294. The compound according to any one of the preceding items, wherein R10is halogen, such as F, or a pharmaceutically acceptable salt thereof. 295. The compound according to any one of the preceding items, wherein R10is linked to R11to form a ring, and R9is a bond, or a pharmaceutically acceptable salt thereof. 296. The compound according to any one of the preceding items, wherein R10is linked to R11to form a ring, and R9is -C(O)-, or a pharmaceutically acceptable salt thereof. 297. The compound according to any one of the preceding items, wherein R10is linked to R11to form a ring, and R9is C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl, or a pharmaceutically acceptable salt thereof. 298. The compound according to any one of the preceding items, wherein R10is linked to R11to form a ring, and R9is -CH2-, or a pharmaceutically acceptable salt thereof. 299. The compound according to any one of the preceding items, wherein R10is linked to R11to form a ring, and R9is -(CH2)2-, or a pharmaceutically acceptable salt thereof. 300. The compound according to any one of the preceding items, wherein R10is linked to R11to form a ring, and R9is -C(H)(CH3)-, or a pharmaceutically acceptable salt thereof. 301. The compound according to any one of the preceding items, wherein R10is linked to R11or R13to form a ring, and R10is a bond, or a pharmaceutically acceptable salt thereof. 302. The compound according to any one of the preceding items, wherein R10is linked to R11or R13to form a ring, and R10is C1-3alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl, or a pharmaceutically acceptable salt thereof. 303. The compound according to any one of the preceding items, wherein R10is linked to R11or R13to form a ring, and R10is -CH2-, or a pharmaceutically acceptable salt thereof. 304. The compound according to any one of the preceding items, wherein R10is linked to R11or R13to form a ring, and R10is -CH2CH2-, or a pharmaceutically acceptable salt thereof. 305. The compound according to any one of the preceding items, wherein X13is bond, -CH2-, -C(H)(CH3)-, -O-, or -CH2O-, or a pharmaceutically acceptable salt thereof. 306. The compound according to any one of the preceding items, wherein X13is a bond, or a pharmaceutically acceptable salt thereof. 307. The compound according to any one of the preceding items, wherein X13is C1-3 alkanediyl, or a pharmaceutically acceptable salt thereof. 308. The compound according to any one of the preceding items, wherein X13is -CH2-, or a pharmaceutically acceptable salt thereof. 309. The compound according to any one of the preceding items, wherein X13is C1-3 alkanediyl substituted with C1-3 alkyl, or a pharmaceutically acceptable salt thereof. 310. The compound according to any one of the preceding items, wherein X13is -C(H)(CH3)-, or a pharmaceutically acceptable salt thereof. 311. The compound according to any one of the preceding items, wherein X13is -O-, or a pharmaceutically acceptable salt thereof. 312. The compound according to any one of the preceding items, wherein X13is -C1-3 alkanediyl-O-, or a pharmaceutically acceptable salt thereof. 313. The compound according to any one of the preceding items, wherein X13is -CH2O-, or a pharmaceutically acceptable salt thereof. 314. The compound according to any one of the preceding items, wherein R33is azetidinyl optionally substituted with one or more substituents individually selected from halogen; C1-3 alkoxy optionally substituted with one or more F; C1- 3 alkyl optionally substituted with one or more F; NH2; N(H)(CH3); and N(CH3)2, or a pharmaceutically acceptable salt thereof. 315. The compound according to any one of the preceding items, wherein R33is azetidinyl optionally substituted with one or more substituents selected from halogen, C1-3alkoxy, and C1-3alkyl, or a pharmaceutically acceptable salt thereof. 316. The compound according to any one of the preceding items, wherein R11is azetidinyl optionally substituted with one or more substituents selected from halogen, C1-3alkyl, and NH2, or a pharmaceutically acceptable salt thereof. 317. The compound according to any one of the preceding items,...

Claims

Claims 1. A compound of Formula (I),Formula (I) wherein R1is halogen or H; R2is halogen; R3is halogen; R5is H or halogen; R6is H or halogen; R4is of Formula (II):Formula (II) wherein X1is C(R7)(R8); X2is C(R9)(R10) or a bond; X3is N(C(O)R11), C(R12)(C(O)R13), C(R14)(R15) or N(R16); X4is C(R17)(R18), O or C(O); X5is C(R19)(R20) or a bond; X6is a bond or C(R21)(R22); wherein R9and R11, R9and R13, R10and R11, R10and R13, R13and R17, R13and R18, or R14and R15are optionally joined together to form a ring together with the intervening atom(s); R7is H, C1-3 alkyl optionally substituted with 1 to 3 F or C1-3 alkoxy, or halogen, such as F; R8is H, C1-3 alkyl optionally substituted with 1 to 3 F or C1-3 alkoxy, or halogen, such as F;R9is H, C1-3alkyl optionally substituted with 1 to 3 halogens, halogen, such as F, or -C(O)N(R31)(R32), wherein R31is H or C1-3alkyl and R32is H or C1-3alkyl, or when R9is linked to R11or R13to form a ring, then R9is a bond, -C(O)- or a C1-3alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl; R10is H, C1-3alkyl optionally substituted with 1 to 3 halogens, halogen, such as F, , or -C(O)N(R31)(R32), wherein R31is H or C1-3alkyl and R32is H or C1-3alkyl, or when R10is linked to R11or R13to form a ring, then R10is a bond, -C(O)- or a C1-3alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3alkyl; R11is -X13-R33; X13is a bond, C1-3alkanediyl optionally substituted with C1-3alkyl, -O-, or C1-3alkanediyl-O-; R33is selected from the group consisting of C1-3alkyl, C3-6cycloalkyl, C1-3alkoxy, pyridinyl, azetidinyl, pyrrolidinyl, oxetanyl, tetrahydrofuranyl, and morpholinyl, each of which is optionally substituted with one or more substituents individually selected from halogen; C1-3 alkoxy optionally substituted with one or more F; C1-3 alkyl optionally substituted with one or more F; NH2; N(H)(CH3); and N(CH3)2; or when R11is linked to R9or R10to form a ring, then R11is -O-, -N(R28)-, or C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl, wherein one methylene group of the C1-3 alkanediyl is optionally replaced by -O- or -N(R28)-, wherein R28is H or C1-3 alkyl; R12is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R13is selected from the group consisting of NH2, N(H)(CH3), N(CH3)2, pyrrolidinyl, azetidinyl, and piperazinyl, wherein ● said pyrrolidinyl is optionally substituted with one or more substituents individually selected from the group consisting of halogen, NH2, N(H)(CH3), N(CH3)2and azetidinyl, and said azetidinyl is optionally substituted with one or more halogens, and ● said azetidinyl optionally substituted with NH2; or when R13is linked to R9, R10, R17, or R18to form a ring, then R13is -N(R28)-, wherein R28is H or C1-3 alkyl; R14is -X7N(R23)(C(O)R24), whereinX7is a bond or C1-3alkanediyl; R24is C1-3alkyl; and R23is H or C1-3alkyl, and R15is H or C1-3alkyl, or R23is a bond or C1-3alkanediyl, and R15is a bond or C1-3alkanediyl and R23is linked to R15to form a ring; or R14is -X9C(O)X11-, R15is a bond or C1-3alkanediyl, and X11is linked to R15to form a ring, wherein X9is a bond or -N(R29)-; R29is C1-3alkyl; X11is -O-, C1-3alkanediyl, or -N(R30)-; and R30is C1-3alkyl; R16is H or C1-3alkyl; R17is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen, such as F; or when R17is linked to R13to form a ring, then R17is a bond or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl; R18is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; or when R18is linked to R13to form a ring, then R18is a bond or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl; R19is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R20is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R21is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R22is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; any two of R7, R8, R9, R10, R17, R18, R19, R20, R21, and R22are optionally linked together to form a ring; with the proviso that when X4is O, then X3is C(R12)C(O)R13and R13is NH2, N(H)(CH3) or N(CH3)2; with the proviso that when X3is N(R16), then X4is C(O), with the proviso that when X4is C(O), then X3is N(R16), and with the proviso that when X2is a bond, then X3is C(R12)(C(O)R13) or C(R14)(R15), or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1, wherein R1is halogen, or a pharmaceutically acceptable salt thereof.

3. The compound according to any one of the preceding claims, wherein R5is H and R6is H, or a pharmaceutically acceptable salt thereof.

4. The compound according to any one of the preceding claims, wherein R1is F or Cl, R2is F or Cl, R3is F or Cl, R5is H, and R6is H, or a pharmaceutically acceptable salt thereof.

5. The compound according to any one of the preceding claims, wherein R4is of Formula (XXIV), Formula (XXV), Formula (XXVI) or Formula (XXVII):Formula (XXVI) Formula (XXVII) or a pharmaceutically acceptable salt thereof.

6. The compound according to any one of the preceding claims, wherein R4is of Formula (III):Formula (III) or a pharmaceutically acceptable salt thereof.

7. The compound according to claim 1, wherein the compound is of Formula (LVII),Formula (LVII) wherein R1is halogen or H; R2is halogen; R3is halogen; R5, R6, R8, R17, R18, R19, and R20are H; wherein R9and R11or R10and R11are optionally joined together via R33to form a ring together with the intervening atoms; R7is H or C1-3 alkyl optionally substituted with 1 to 3 F; R10is H, or when R10is linked to R11to form a ring, then R10is a bond or a C1-3 alkanediyl; R9is H, or when R9is linked to R11to form a ring, then R9is a bond or a C1-3alkanediyl; R11is -X13-R33; X13is a bond, C1-3alkanediyl optionally substituted with C1-3alkyl, -O-, or C1-3alkanediyl-O-; and R33is C1-3alkyl, azetidinyl, pyrrolidinyl, oxetanyl, and tetrahydrofuranyl, each of which is optionally substituted with one or more F; or when R11is linked to R9or R10via R33to form a ring, then R33is a bond or a C1-3alkanediyl, or a pharmaceutically acceptable salt thereof.

8. The compound according to any one of claims 1 to 6, wherein R33is azetidinyl optionally substituted with one or more substituents selected from halogen, C1-3alkoxy, and C1-3alkyl, or a pharmaceutically acceptable salt thereof.

9. The compound according to any one of claims 1 to 6, wherein R33is oxetanyl, or a pharmaceutically acceptable salt thereof.

10. The compound according to any one of claims 1 to 6, wherein R33is pyrrolidinyl optionally substituted with one or more substituents individually selected fromhalogen; C1-3alkoxy optionally substituted with one or more F; C1-3alkyl optionally substituted with one or more F, or a pharmaceutically acceptable salt thereof.

11. The compound according to any one of claims 1 to 6, wherein R33is tetrahydrofuranyl, or a pharmaceutically acceptable salt thereof.

12. The compound according to any one of claims 1 to 6, wherein R33is morpholinyl optionally substituted with C1-3alkyl, or a pharmaceutically acceptable salt thereof.

13. The compound according to any one of claims 1 to 6, wherein R33is pyridinyl optionally substituted with one or more substituents individually selected from NH2; N(H)(CH3); and N(CH3)2, or a pharmaceutically acceptable salt thereof.

14. The compound according to any one of claims 1 to 6, wherein R33is C1-3alkyl optionally substituted with one or more substituents individually selected from halogen; C1-3alkoxy optionally substituted with one or more F; C1-3alkyl optionally substituted with one or more F; NH2; N(H)(CH3); and N(CH3)2, or a pharmaceutically acceptable salt thereof.

15. The compound according to any one of claims 1 to 6, wherein R33is C1-3 alkoxy, or a pharmaceutically acceptable salt thereof.

16. The compound according to any one of claims 1 to 6, wherein R33is C3-6 cycloalkyl optionally substituted with one or more substituents individually selected from halogen; C1-3 alkoxy optionally substituted with one or more F; C1- 3 alkyl optionally substituted with one or more F; NH2; N(H)(CH3); and N(CH3)2, or a pharmaceutically acceptable salt thereof.

17. The compound according to any one of the preceding claims, wherein X13is bond, -CH2-, -C(H)(CH3)-, -O-, or -CH2O-, or a pharmaceutically acceptable salt thereof.

18. The compound according to any one of claims 1 to 7, wherein R11is,acceptable salt thereof.

19. The compound according to any one of claims 1 to 7, wherein R11is, ,20. The compound according to any one of claims 1 to 7, wherein R11ispharmaceutically acceptable salt thereof.

21. The compound according to any one of claims 1 to 7, wherein R11isor, or a pharmaceutically acceptable salt thereof.

22. The compound according to any one of claims 1 to 7, wherein,pharmaceutically acceptable salt thereof.

23. The compound according to any one of claims 1 to 7, whereinpharmaceutically acceptable salt thereof.

24. The compound according to any one of claims 1 to 7, wherein R11is CH3, - CH2NH2, -CH2-N(H)(CH3), -CH2N(CH3)2, is -OCH3, -CH2-O-CF3, -CH2-O-CHF2, or CHF2, or a pharmaceutically acceptable salt thereof.

25. The compound according to any one of claims 1 to 7, wherein R11is -OCH3, or a pharmaceutically acceptable salt thereof.

26. The compound according to any one of claims 1 to 7, wherein R11is cyclopropyl, cyclobutyl,pharmaceutically acceptable salt thereof.

27. The compound according to any one of claims 1 to 4, wherein R4is of Formula (LI):, Formula (LI) wherein R7is H, C1-3alkyl optionally substituted with 1 to 3 F or C1-3alkoxy, or halogen, such as F; R8is H, C1-3alkyl optionally substituted with 1 to 3 F or C1-3alkoxy, or halogen, such as F; R9is a bond, -C(O)- or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl; R10is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R11is -O-, -N(R28)-, or C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl, wherein one methylene group of the C1-3 alkanediyl is optionally replaced by -O- or -N(R28)-, wherein R28is H or C1-3 alkyl; R17is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R18is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R19is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; R20is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; and R28is H or C1-3 alkyl, or a pharmaceutically acceptable salt thereof.

28. The compound according to any one of claims 1 to 4, wherein R4is of Formula (XX):Formula (XX) whereinR7is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen; R8is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen; R10is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen; R17is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen; R18is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen; R19is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen; R20is H, C1-3alkyl optionally substituted with 1 to 3 F, or halogen,; R31is individually halogen or C1-3alkyl; r is 0, 1, 2, 3 or 4; X8is -CH2-, -O- or -N(R28)-; and R28is H or C1-3alkyl, or a pharmaceutically acceptable salt thereof.

29. The compound according to any one of claims 1 to 5, wherein R4is of Formula (XXXIV):Formula (XXXIV) or a pharmaceutically acceptable salt thereof.

30. The compound according to any one of claims 1 to 5, wherein R4is of Formula (XXXV), Formula (XXXVI), Formula (XXXVII):Formula (XXXVI)Formula (XXXVII)Formula (XXXV) or a pharmaceutically acceptable salt thereof.

31. The compound according to any one of any one of claims 1 to 5, wherein R4is of Formula (XIX):Formula (XIX) wherein X9is a bond or -N(R29)-; R29is C1-3 alkyl; X10is -C(O)-, -CH2-, or a bond; X11is -O-, -CH2-, or -N(R30)-; R30is C1-3 alkyl; X12is -N(C(O)R24)- or a bond; m is 1 or 2; n is 0 or 1; and z is 1 or 2; with the proviso that when X10is -C(O)-, then X12is a bond; with the proviso that when X10is -CH2- or a bond, then X12is -N(C(O)R24)-; and with the proviso that ring A is a 4 to 6 membered ring, or a pharmaceutically acceptable salt thereof.

32. The compound according to any one of claims 1 to 5, wherein R4is of Formula (XXXVIII), Formula (XXXIX), or Formula (XL):Formula (XXXVIII)Formula (XXXIX)Formula (XL)or a pharmaceutically acceptable salt thereof.

33. The compound according to claim 32, wherein R13is selected from the group consisting of:● pyrrolidinyl optionally substituted with NH2, N(H)(CH3), or N(CH3)2, such as ●● pyrrolidinyl optionally substituted with azetidinyl, wherein the azetidinyl isoptionally substituted with one or more halogens, such as ,● azetidinyl optionally substituted with NH2, such as ; ● NH2; ● N(H)(CH3); and ● N(CH3)2, or a pharmaceutically acceptable salt thereof.

34. The compound according to claim 1, wherein the compound is: 4-(3,4,5-trichloro-1H-indole-2-carbonyl)piperazin-2-one; 4-(4,5-dichloro-3-fluoro-1H-indole-2-carbonyl)piperazin-2-one; 1-(4-(3,4-dichloro-5-fluoro-1H-indole-2-carbonyl)piperazin-1-yl)ethan-1-one; 2-(3,4-dichloro-5-fluoro-1H-indole-2-carbonyl)hexahydropyrrolo[1,2-a]pyrazin-6(2H)- one; 7-(3,4-dichloro-5-fluoro-1H-indole-2-carbonyl)hexahydro-3H-oxazolo[3,4-a]pyrazin-3- one; methyl 4-(3,4-dichloro-5-fluoro-1H-indole-2-carbonyl)piperazine-1-carboxylate; 1-(4-(4,5-dichloro-1H-indole-2-carbonyl)-3,3-dimethylpiperazin-1yl)ethan-1-one; (S)-1-(4-(3,4-dichloro-5-fluoro-1H-indole-2-carbonyl)-3-methylpiperazin-1-yl)ethan-1- one; (S)-4-(3,4-dichloro-5-fluoro-1H-indole-2-carbonyl)-1,5-dimethylpiperazin-2-one;1-(4-(3,4-dichloro-5-fluoro-1H-indole-2-carbonyl)piperazin-1-yl)-2- (dimethylamino)ethan-1-one; 1-(4-(3,4-dichloro-5-fluoro-1H-indole-2-carbonyl)piperazin-1-yl)-2-methoxyethan-1-one; 2-amino-1-(4-(3,4-dichloro-5-fluoro-1H-indole-2-carbonyl)piperazin-1-yl)ethan-1-one; ((R)-3-aminopyrrolidin-1-yl)((R)-1-(3,4-dichloro-5-fluoro-1H-indole-2-carbonyl)pyrrolidin- 3-yl)methanone; (3,4-dichloro-5-fluoro-1H-indol-2-yl)((3R)-3-(3-(dimethylamino)pyrrolidine-1- carbonyl)pyrrolidin-1-yl)methanone; (3-(azetidin-1-yl)pyrrolidin-1-yl)((R)-1-(3,4-dichloro-5-fluoro-1H-indole-2- carbonyl)pyrrolidin-3-yl)methanone; (3,4-dichloro-5-fluoro-1H-indol-2-yl)((3R)-3-(3-(3,3-difluoroazetidin-1-yl)pyrrolidine-1- carbonyl)pyrrolidin-1-yl)methanone; (2-amino-4-pyridyl)-[4-(4,5-dichloro-1H-indole-2-carbonyl)piperazin-1-yl]methanone; 8-(3,4-dichloro-5-fluoro-1H-indole-2-carbonyl)-2-methyl-2,8-diazaspiro[4.5]decan-1- one; 8-(3,4-dichloro-5-fluoro-1H-indole-2-carbonyl)-1-methyl-1,8-diazaspiro[4.5]decan-2- one; 8-(3,4-dichloro-5-fluoro-1H-indole-2-carbonyl)-1-methyl-3-oxa-1,8- diazaspiro[4.5]decan-2-one; 8-(3,4-dichloro-5-fluoro-1H-indole-2-carbonyl)-1,3-dimethyl-1,3,8-triazaspiro[4.5]decan- 2-one; (S)-4-(3,4-dichloro-5-fluoro-1H-indole-2-carbonyl)-1,3-dimethylpiperazin-2-one; (S)-(3,4-dichloro-5-fluoro-1H-indol-2-yl)(4-(pyrrolidine-3-carbonyl)piperazin-1- yl)methanone; (3,4-dichloro-5-fluoro-1H-indol-2-yl)(4-(methyl-D-prolyl)piperazin-1-yl)methanone; (R)-(3,4-dichloro-5-fluoro-1H-indol-2-yl)(4-(4,4-difluoropyrrolidine-2-carbonyl)piperazin- 1-yl)methanone; 7-(3,4-dichloro-5-fluoro-1H-indole-2-carbonyl)-2-methylhexahydroimidazo[1,5- a]pyrazin-3(2H)-one; (R)-(3,4-dichloro-5-fluoro-1H-indol-2-yl)(4-(4,4-difluoro-1-methylpyrrolidine-2- carbonyl)piperazin-1-yl)methanone; (S)-(3,4-dichloro-5-fluoro-1H-indol-2-yl)(4-(1-methylpyrrolidine-3-carbonyl)piperazin-1- yl)methanone; (4-(6-aminonicotinoyl)piperazin-1-yl)(3,4-dichloro-5-fluoro-1H-indol-2-yl)methanone;(S)-2-(3,4-dichloro-5-fluoro-1H-indole-2-carbonyl)hexahydropyrrolo[1,2-a]pyrazin- 6(2H)-one; (R)-2-(3,4-dichloro-5-fluoro-1H-indole-2-carbonyl)hexahydropyrrolo[1,2-a]pyrazin- 6(2H)-one; (R)-7-(3,4-dichloro-5-fluoro-1H-indole-2-carbonyl)hexahydro-3H-oxazolo[3,4-a]pyrazin- 3-one; (S)-7-(3,4-dichloro-5-fluoro-1H-indole-2-carbonyl)hexahydro-3H-oxazolo[3,4-a]pyrazin- 3-one; 1-(4-(3,4-dichloro-5-fluoro-1H-indole-2-carbonyl) piperazin-1-yl)-2-morpholinoethan-1- one; (4-(2-aminoisonicotinoyl) piperazin-1-yl) (3,4-dichloro-5-fluoro-1H-indol-2-yl) methanone; 1-(4-(3,4-dichloro-1H-indole-2-carbonyl) piperazin-1-yl)-2-methoxyethan-1-one; (S)-2-(4-chloro-3,5-difluoro-1H-indole-2-carbonyl) hexahydropyrrolo[1,2-a] pyrazin- 6(2H)-one; (R)-2-(4-chloro-3,5-difluoro-1H-indole-2-carbonyl) hexahydropyrrolo[1,2-a] pyrazin- 6(2H)-one; 2-amino-1-(4-(4-chloro-3,5-difluoro-1H-indole-2-carbonyl)piperazin-1-yl)ethan-1-one; (R)-(3,4-dichloro-5-fluoro-1H-indol-2-yl)(4-prolylpiperazin-1-yl)methanone; ((3S,4R)-3-amino-4-fluoropyrrolidin-1-yl)((R)-1-(3,4-dichloro-5-fluoro-1H-indole-2- carbonyl)pyrrolidin-3-yl)methanone; (3,4-dichloro-5-fluoro-1H-indol-2-yl)(4-((3S,4S)-4-(trifluoromethyl)pyrrolidine-3- carbonyl)piperazin-1-yl)methanone; azetidin-3-yl(4-(4-chloro-3,5-difluoro-1H-indole-2-carbonyl)piperazin-1-yl)methanone; (4-chloro-3,5-difluoro-1H-indol-2-yl)(4-(3-fluoroazetidine-3-carbonyl)piperazin-1- yl)methanone; ((3S,4S)-3-amino-4-fluoropyrrolidin-1-yl)(®-1-(3,4-dichloro-5-fluoro-1H-indole-2- carbonyl) yrrolidine-3-yl)methanone; (S)-(4-chloro-3,5-difluoro-1H-indol-2-yl) (4-(morpholine-3-carbonyl) piperazin-1-yl) methanone; (R)-(4-chloro-3,5-difluoro-1H-indol-2-yl)(4-(morpholine-3-carbonyl)piperazin-1- yl)methanone; (S)-azetidin-2-yl(4-(4-chloro-3,5-difluoro-1H-indole-2-carbonyl)piperazin-1- yl)methanone;(R)-azetidin-2-yl(4-(4-chloro-3,5-difluoro-1H-indole-2-carbonyl)piperazin-1- yl)methanone; (3,4-dichloro-5-fluoro-1H-indol-2-yl)(4-((2R,4R)-4-fluoropyrrolidine-2- carbonyl)piperazin-1-yl)methanone; (4-(2-aminoisonicotinoyl) piperazin-1-yl) (4-chloro-3,5-difluoro-1H-indol-2-yl) methanone; (S)-(4-chloro-3,5-difluoro-1H-indol-2-yl) (4-(4,4-difluoropyrrolidine-2-carbonyl) piperazin-1-yl) methanone; (R)-(4-chloro-3,5-difluoro-1H-indol-2-yl) (4-(4,4-difluoropyrrolidine-2-carbonyl) piperazin-1-yl) methanone; 2-(azetidin-3-yloxy)-1-(4-(4-chloro-3,5-difluoro-1H-indole-2-carbonyl)piperazin-1- yl)ethan-1-one; (S)-(4-chloro-3,5-difluoro-1H-indol-2-yl)(4-prolylpiperazin-1-yl)methanone; (R)-(4-chloro-3,5-difluoro-1H-indol-2-yl)(4-prolylpiperazin-1-yl)methanone; ((R)-3-aminopyrrolidin-1-yl) ((R)-1-(4-chloro-3,5-difluoro-1H-indole-2-carbonyl) pyrrolidin-3-yl) methanone; 1-(4-(3-chloro-4-fluoro-1H-indole-2-carbonyl)piperazin-1-yl)-2-methoxyethan-1-one; 4-(4-chloro-3,5-difluoro-1H-indole-2-carbonyl)piperazin-2-one; 1-(4-(4-chloro-3,5-difluoro-1H-indole-2-carbonyl)piperazin-1-yl)-2- (dimethylamino)ethan-1-one; 1-(4-(4-chloro-3,5-difluoro-1H-indole-2-carbonyl)piperazin-1-yl)-2-morpholinoethan-1- one; (4-chloro-3,5-difluoro-1H-indol-2-yl)(4-(oxetane-3-carbonyl)piperazin-1-yl)methanone; (4-chloro-3,5-difluoro-1H-indol-2-yl)(4-(3,3-difluorocyclobutane-1-carbonyl)piperazin-1- yl)methanone; (4-chloro-3,5-difluoro-1H-indol-2-yl)(4-((1R,3R)-3-methoxycyclobutane-1- carbonyl)piperazin-1-yl)methanone; 1-(4-(3-chloro-4,5-difluoro-1H-indole-2-carbonyl)piperazin-1-yl)-2-methoxyethan-1-one; (S)-(4-chloro-3,5-difluoro-1H-indol-2-yl)(4-(oxetane-2-carbonyl)piperazin-1- yl)methanone; (R)-(4-chloro-3,5-difluoro-1H-indol-2-yl)(4-(oxetane-2-carbonyl)piperazin-1- yl)methanone; 2-(azetidin-1-yl)-1-(4-(4-chloro-3,5-difluoro-1H-indole-2-carbonyl)piperazin-1-yl)ethan- 1-one;(4-chloro-3,5-difluoro-1H-indol-2-yl)(4-(1-methylazetidine-3-carbonyl)piperazin-1- yl)methanone; (3aR,6aR)-5-(3,4-dichloro-5-fluoro-1H-indole-2-carbonyl)-2- methylhexahydropyrrolo[3,4-c]pyrrol-1(2H)-one; 2-(3,4-dichloro-5-fluoro-1H-indole-2-carbonyl)hexahydro-2H,6H-pyrazino[1,2- c][1,3]oxazin-6-one; (4-chloro-3,5-difluoro-1H-indol-2-yl)(4-(methyl-L-prolyl)piperazin-1-yl)methanone; (4-chloro-3,5-difluoro-1H-indol-2-yl)(4-(methyl-D-prolyl)piperazin-1-yl)methanone; 1-(4-(4-chloro-3,5-difluoro-1H-indole-2-carbonyl)piperazin-1-yl)-2-methoxyethan-1-one; (S)-1-(4-(4-chloro-3,5-difluoro-1H-indole-2-carbonyl)-3-methylpiperazin-1-yl)-2- methoxyethan-1-one; 2-( zetidine-1-yl)-1-(4-(3,4-dichloro-5-fluoro-1H-indole-2-carbonyl) piperazin-1-yl) ethan- 1-one; (S)-(4-chloro-3,5-difluoro-1H-indol-2-yl) (4-(4-methylmorpholine-3-carbonyl) piperazin- 1-yl) methanone; (R)-(4-chloro-3,5-difluoro-1H-indol-2-yl) (4-(4-methylmorpholine-3-carbonyl) piperazin- 1-yl) methanone; 2-(3,4-dichloro-5-fluoro-1H-indole-2-carbonyl)octahydro-6H-pyrido[1,2-a]pyrazin-6-one; 1-(4-(3,4-dichloro-5-fluoro-1H-indole-2-carbonyl)piperazin-1-yl)-2-(3-methoxyazetidin-1- yl)ethan-1-one; 1-(4-(3,4-dichloro-5-fluoro-1H-indole-2-carbonyl)piperazin-1-yl)-2-(3-fluoroazetidin-1- yl)ethan-1-one; 1-(4-(3,4-dichloro-5-fluoro-1H-indole-2-carbonyl)piperazin-1-yl)-2-(3,3-difluoroazetidin- 1-yl)ethan-1-one; 1-(4-(4-chloro-3,5-difluoro-1H-indole-2-carbonyl)piperazin-1-yl)-2-(3-methoxyazetidin-1- yl)ethan-1-one; 1-(4-(4-chloro-3,5-difluoro-1H-indole-2-carbonyl)piperazin-1-yl)-2-(3-fluoroazetidin-1- yl)ethan-1-one; 1-(4-(4-chloro-3,5-difluoro-1H-indole-2-carbonyl)piperazin-1-yl)-2-(3,3-difluoroazetidin- 1-yl)ethan-1-one; 1-(4-(4-chloro-3,5-difluoro-1H-indole-2-carbonyl)piperazin-1-yl)-2-(oxetan-3- yloxy)ethan-1-one; (R)-7-(4-chloro-3,5-difluoro-1H-indole-2-carbonyl)hexahydro-3H-oxazolo[3,4-a]pyrazin- 3-one;(S)-7-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)hexahydro-3H-oxazolo[3,4-a]pyrazin- 3-one;(3,4-dichloro-5-fluoro-1 H-indol-2-yl)(4-((2R,4S)-4-fluoropyrrolidine-2- carbonyl)piperazin-1-yl)methanone;5-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)-2-methyloctahydro-3H-pyrrolo[3,4-c] yridine-3-one;(3,4-dichloro-5-fluoro-1 H-indol-2-yl)(4-((3S,4S)-1-methyl-4-(trifluoromethyl)pyrrolidine-3-carbonyl)piperazin-1-yl)methanone;(3,4-dichloro-5-fluoro-1 H-indol-2-yl)(4-((2R,4R)-4-fluoro-1-methylpyrrolidine-2- carbonyl)piperazin-1-yl)methanone;(4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(3-fluoro-1-methylazetidine-3-carbonyl)piperazin- 1-yl)methanone;1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-((1-methylazetidin-3- yl)oxy)ethan-1-one;(S)-(4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(4,4-difluoro-1-methylpyrrolidine-2- carbonyl)piperazin-1-yl)methanone;(R)-(4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(4,4-difluoro-1-methylpyrrolidine-2- carbonyl)piperazin-1-yl)methanone;(3,4-dichloro-5-fluoro-1 H-indol-2-yl)(4-((2R,4S)-4-fluoro-1-methylpyrrolidine-2- carbonyl)piperazin-1-yl)methanone;(3-fluoroazetidin-3-yl)methyl 4-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)piperazine-1- carboxylate; azetidin-3-yl 4-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl) piperazine-1 -carboxylate;1-(4-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(oxetan-3- yloxy)ethan-1-one;8-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)hexahydropyrazino[2,1-c][1 ,4]oxazin-4(3H)-one;7-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)tetrahydroimidazo[1,5-a]pyrazine- 1 ,3(2H,5H)-dione;2-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)-8-methylhexahydropyrrolo[1,2-a]pyrazin- 6(2H)-one;2-(azetidin-3-yloxy)-1-(4-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)piperazin-1- yl)ethan-1-one;(3aR,6aR)-5-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)-2- methylhexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;2-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)hexahydro-2H,6H-pyrazino[1,2- c][1 ,3]oxazin-6-one;(R)-2-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)hexahydro-2H,6H-pyrazino[1,2- c][1 ,3]oxazin-6-one;(S)-2-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)hexahydro-2H,6H-pyrazino[1,2- c][1 ,3]oxazin-6-one;1-(4-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-((1-methylazetidin-3- yl)oxy)ethan-1-one;8-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)octahydro-4 H-pyrazino[1,2- a]pyrazin-4- one;1-(4-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(3-fluoroazetidin-3- yl)ethan-1-one;1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(3,3-difluoropyrrolidin-1-yl)ethan-1-one;(S)-1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)-3-methylpiperazin-1-yl)-2-(3,3- difluoroazetidin-1-yl)ethan-1-one;1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(3,3- difluorocyclobutoxy)ethan-1-one;(R)-1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)-3-(methoxymethyl)piperazin-1-yl)-2-(3,3-difluoroazetidin-1-yl)ethan-1-one;(S)-1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(3,3- difluoroazetidin-1-yl)propan-1-one;(R)-1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(3,3- difluoroazetidin-1-yl)propan-1-one;(S)-1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(3,3-difluoro-2- methylazetidin-1-yl)ethan-1-one;(R)-1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(3,3-difluoro-2- methylazetidin-1-yl)ethan-1-one;4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)-N,N-dimethylmorpholine-2-carboxamide;(S)-(4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(tetrahydrofuran-2-carbonyl)piperazin-1- yl)methanone;(R)-(4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(tetrahydrofuran-2-carbonyl)piperazin-1- yl)methanone;4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)-N,N-dimethylpiperazine-2-carboxamide;1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)ethan-1-one;(R)-(4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(4,4-dimethyloxetane-2-carbonyl)piperazin-1- yl)methanone;(S)-(4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(4,4-dimethyloxetane-2-carbonyl)piperazin-1- yl)methanone;(S)-8-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)hexahydropyrazino[2,1-c][1 ,4]oxazin-4(3H)-one;(R)-8-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)hexahydropyrazino[2,1-c][1 ,4]oxazin-4(3H)-one;1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2,2-difluoroethan-1- one;(R)-(4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(2-methyloxetane-2-carbonyl)piperazin-1- yl)methanone;1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(trifluoromethoxy)ethan-l-one;1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(difluoromethoxy)ethan-l -one;(S)-4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)-N-methylpiperazine-2-carboxamide;(S)-4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)-N,N-dimethylpiperazine-2- carboxamide;1-(4-(3,4-dichloro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(3,3-difluoroazetidin-1- yl)ethan-1-one;(R)-(4-chloro-3-fluoro-1 H-indol-2-yl)(4-(oxetane-2-carbonyl)piperazin-1-yl)methanone;1-(4-(4-chloro-3-fluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-methoxyethan-1-one;1-(4-(4-chloro-3-fluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(3,3-difluoroazetidin-1- yl)ethan-1-one;(R)-(4-chloro-3-fluoro-1 H-indol-2-yl)(4-(tetrahydrofuran-2-carbonyl)piperazin-1- yl)methanone;(R)-(3,4-dichloro-1 H-indol-2-yl)(4-(oxetane-2-carbonyl)piperazin-1-yl)methanone;(S)-1-(4-(3,4-dichloro-1 H-indole-2-carbonyl)-3-methylpiperazin-1-yl)-2-methoxyethan-1- one; and(R)-(3,4-dichloro-1 H-indol-2-yl)(4-(tetrahydrofuran-2-carbonyl)piperazin-1- yl)methanone, or a pharmaceutically acceptable salt thereof.

35. The compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein the compound is a Kv1 .3 potassium channel inhibitor.

36. A pharmaceutical composition comprising a compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers, excipients and / or diluents.

37. The compound according to any one of claims 1 to 36, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition according to claim 36, for use as a medicament.

38. The compound according to any one of claims 1 to 36, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition according to claim 36, for use in the treatment of a disease or medical condition where inhibition of Kv1.3 potassium channel is beneficial.

39. A compound of Formula (I):Formula (I) whereinR1is halogen or H;R2is halogen;R3is H or halogen;R5is H or halogen;R6is H or halogen;R4is of Formula (II):Formula (II) whereinX1is C(R7)(R8);X2is C(R9)(R10) or a bond;X3is N(C(O)R11), C(R12)(C(O)R13), C(R14)(R15) or N(R16);X4is C(R17)(R18), O or C(O);X5is C(R19)(R20) or a bond;X6is a bond or C(R21)(R22); wherein R9and R11, R9and R13, R10and R11, R10and R13, R13and R17, R13and R18, or R14and R15are optionally joined together to form a ring together with the intervening atom(s);R7is H, C1-3 alkyl optionally substituted with 1 to 3 F or C1-3 alkoxy, or halogen, such as F;R8is H, C1-3 alkyl optionally substituted with 1 to 3 F or C1-3 alkoxy, or halogen, such as F;R9is H, C1-3 alkyl optionally substituted with 1 to 3 halogens, halogen, such as F, or -C(O)N(R31)(R32), wherein R31is H or C1-3 alkyl and R32is H or C1-3 alkyl, or when R9is linked to R11or R13to form a ring, then R9is a bond, -C(O)- or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl;R10is H, C1-3 alkyl optionally substituted with 1 to 3 halogens, halogen, such as F, , or -C(O)N(R31)(R32), wherein R31is H or C1-3 alkyl and R32is H or C1-3 alkyl, or when R10is linked to R11or R13to form a ring, then R10is a bond, -C(O)- or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl;R11is -X13-R33;X13is a bond, C1-3 alkanediyl optionally substituted with C1-3 alkyl, -O-, or C1-3 alkanediyl-O-;R33is selected from the group consisting of C1-3 alkyl, C3-6 cycloalkyl, C1-3 alkoxy, pyridinyl, azetidinyl, pyrrolidinyl, oxetanyl, tetrahydrofuranyl, and morpholinyl, each of which is optionally substituted with one or more substituents individually selected from halogen; C1-3 alkoxy optionally substituted with one or more F; C1-3 alkyl optionally substituted with one or more F; NH2; N(H)(CH3); and N(CH3)2; or when R11is linked to R9or R10to form a ring, then R11is -O-, -N(R28)-, or C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl, wherein one methylene group of the C1-3 alkanediyl is optionally replaced by -O- or -N(R28)-, wherein R28is H or C1-3 alkyl;R12is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F;R13is selected from the group consisting of NH2, N(H)(CH3), N(CHa)2, pyrrolidinyl, azetidinyl, and piperazinyl, wherein• said pyrrolidinyl is optionally substituted with one or more substituents individually selected from the group consisting of halogen, NH2, N(H)(CH3), N(CHS)2 and azetidinyl, and said azetidinyl is optionally substituted with one or more halogens, and• said azetidinyl optionally substituted with NH2; or when R13is linked to R9, R10, R17, or R18to form a ring, then R13is -N(R28)-, wherein R28is H or C1-3 alkyl;R14is -X7N(R23)(C(O)R24), whereinX7is a bond or C1-3 alkanediyl;R24is C1-3 alkyl; andR23is H or C1-3 alkyl, and R15is H or C1-3 alkyl, or R23is a bond or C1-3 alkanediyl, and R15is a bond or C1-3 alkanediyl and R23is linked to R15to form a ring; or R14is -X9C(O)X11-, R15is a bond or C1-3 alkanediyl, and X11is linked to R15to form a ring, whereinX9is a bond or -N(R29)-;R29is C1-3 alkyl;X11is -O-, C1-3 alkanediyl, or -N(R30)-; andR30is C1-3 alkyl;R16is H or C1-3 alkyl;R17is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; or when R17is linked to R13to form a ring, then R17is a bond or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl;R18is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; or when R18is linked to R13to form a ring, then R18is a bond or a C1-3 alkanediyl optionally substituted with 1 to 3 substituents individually selected from halogen and C1-3 alkyl;R19is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F;R20is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F;R21is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F;R22is H, C1-3 alkyl optionally substituted with 1 to 3 F, or halogen, such as F; any two of R7, R8, R9, R10, R17, R18, R19, R20, R21, and R22are optionally linked together to form a ring; with the proviso that when X4is O, then X3is C(R12)C(O)R13and R13is NH2, N(H)(CH3) or N(CH3)2; with the proviso that when X3is N(R16), then X4is C(O), with the proviso that when X4is C(O), then X3is N(R16), and with the proviso that when X2is a bond, then X3is C(R12)(C(O)R13) or C(R14)(R15), or a pharmaceutically acceptable salt thereof, for use in the treatment of a disease or medical condition where inhibition of Kv1.3 potassium channel is beneficial.

40. The compound for use according to claim 39, wherein R1is halogen, and R3is halogen.

41. The compound for use according to claim 39, wherein the compound is: 4-(3,4,5-trichloro-1 H-indole-2-carbonyl)piperazin-2-one;1-(4-(4,5-dichloro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(dimethylamino)ethan-1-one; 1-[(2R)-4-(4,5-dichloro-1 H-indole-2-carbonyl)-2-methyl-piperazin-1-yl]ethanone; 1-[4-(4,5-dichloro-1 H-indole-2-carbonyl)-2,2-dimethyl-piperazin-1-yl]ethanone;1-[3-(4,5-dichloro-1 H-indole-2-carbonyl)-3,8-diazabicyclo[3.2.1]octan-8-yl]ethanone; 1-[4-(4,5-dichloro-1 H-indole-2-carbonyl)piperazin-1-yl]ethanone;1-[(3S)-4-(4,5-dichloro-1 H-indole-2-carbonyl)-3-methyl-piperazin-1-yl]ethanone;1-[4-(4-chloro-5-fluoro-1 H-indole-2-carbonyl)piperazin-1-yl]-2- (dimethylamino)ethanone;1-(4-(4,5-dichloro-1 H-indole-2-carbonyl)-3,3-dimethylpiperazin-1-yl)ethan-1-one;2-amino-1-[4-(4-chloro-5-fluoro-1 H-indole-2-carbonyl)piperazin-1-yl]ethanone;2-amino-1-[4-(4,5-dichloro-1 H-indole-2-carbonyl)piperazin-1-yl]ethanone;(3R)-1-(4,5-dichloro-1 H-indole-2-carbonyl)pyrrolidine-3-carboxamide;4-(4,5-dichloro-1 H-indole-2-carbonyl)piperazin-2-one;4-(4,5-dichloro-1 H-indole-2-carbonyl)-1-methyl-piperazin-2-one;4-(4,5-dichloro-6-fluoro-1 H-indole-2-carbonyl)piperazin-2-one;4-(4-chloro-5-fluoro-1 H-indole-2-carbonyl)piperazin-2-one;(3R)-1-[(4,5-dichloro-1 H-indol-2-yl)carbonyl]-N-methylpyrrolidine-3-carboxamide;4-(4-chloro-1 H-indole-2-carbonyl)piperazin-2-one;1-[4-(4,5-dichloro-1 H-indole-2-carbonyl)piperazin-1-yl]-2-methoxy-ethanone;1-(4-(4-chloro-5-fluoro-1 H-indole-2-carbonyl)piperazin-1-yl)ethan-1-one;1-[4-(4-chloro-5-fluoro-1 H-indole-2-carbonyl)piperazin-1-yl]-2-methoxy-ethanone;4-(4,5-dichloro-7-fluoro-1 H-indole-2-carbonyl)piperazin-2-one;4-(4,5-dichloro-3-fluoro-1 H-indole-2-carbonyl)piperazin-2-one;(S)-(4,5-dichloro-1 H-indol-2-yl)(4-(pyrrolidine-3-carbonyl)piperazin-1-yl)methanone;[4-(azetidine-3-carbonyl)piperazin-1-yl]-(4,5-dichloro-1 H-indol-2-yl)methanone;(4,5-dichloro-1 H-indol-2-yl)-[4-[(3R)-pyrrolidine-3-carbonyl]piperazin-1-yl]methanone;[4-[(2S)-azetidine-2-carbonyl]piperazin-1-yl]-(4,5-dichloro-1 H-indol-2-yl)methanone;(4,5-dichloro-1 H-indol-2-yl)-[4-[(2S)-pyrrolidine-2-carbonyl]piperazin-1-yl]methanone;(4-(cyclopropanecarbonyl)piperazin-1-yl)(4,5-dichloro-1 H-indol-2-yl)methanone;(4-(2-aminoisonicotinoyl)piperazin-1-yl)(4,5-dichloro-1 H-indol-2-yl) methanone;((R)-3-aminopyrrolidin-1-yl)((R)-1-(4,5-dichloro-1 H-indole-2-carbonyl) pyrrolidin-3- yl)methanone;[(3R)-3-(3-aminoazetidine-1-carbonyl)pyrrolidin-1-yl]-(4,5-dichloro-1 H-indol-2- yl)methanone;[(3R)-3-[(3S)-3-aminopyrrolidine-1-carbonyl]pyrrolidin-1-yl]-(4,5-dichloro-1 H-indol-2- yl)methanone;N-[1-(4-acetamidophenyl)sulfonyl-4-piperidyl]-3,5-dimethyl-1 H-pyrrole-2-carboxamide;(R)-N-(1-(4,5-dichloro-1 H-indole-2-carbonyl)pyrrolidin-3-yl)acetamide;(R)-1-(4,5-dichloro-1 H-indole-2-carbonyl)-3-methylpyrrolidine-3-carboxamide;1-(4-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)piperazin-1-yl)ethan-1-one;2-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)hexahydropyrrolo[1,2-a]pyrazin-6(2H)- one;7-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)hexahydro-3H-oxazolo[3,4-a]pyrazin-3- one; methyl 4-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)piperazine-1 -carboxylate;(S)-1-(4-(4-chloro-5-fluoro-1 H-indole-2-carbonyl)-3-methylpiperazin-1-yl)ethan-1-one;4-(4,5-dichloro-1 H-indole-2-carbonyl)-N-methylmorpholine-2-carboxamide;1-(4-(4,5-dichloro-1 H-indole-2-carbonyl)-3,3-dimethylpiperazin-1yl)ethan-1-one;(S)-1-(4-(4,5-dichloro-1 H-indole-2-carbonyl)-2-methylpiperazin-1-yl)ethan-1-one;(S)-1-(4,5-dichloro-1 H-indole-2-carbonyl)pyrrolidine-3-carboxamide;(R)-1-(4-(4,5-dichloro-1 H-indole-2-carbonyl)-3-methylpiperazin-1-yl)ethan-1-one;1-(3-(4,5-dichloro-1 H-indole-2-carbonyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)ethan-1- one;1-(5-(4,5-dichloro-1 H-indole-2-carbonyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)ethan-1-one;1-(6-(4,5-dichloro-1 H-indole-2-carbonyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)ethan-1- one;1-((2S,5R)-4-(4,5-dichloro-1 H-indole-2-carbonyl)-2,5-dimethylpiperazin-1-yl)ethan-1- one;(R)-1-(4,5-dichloro-1 H-indole-2-carbonyl)-N,N-dimethylpyrrolidine-3-carboxamide;1-(8-(4,5-dichloro-1 H-indole-2-carbonyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)ethan-1-one;(S)-1-(4-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)-3-methylpiperazin-1-yl)ethan-1- one;(S)-4-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)-1 ,5-dimethylpiperazin-2-one;1-(4-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(dimethylamino)ethan-l -one;1-(4-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-methoxyethan-1-one;2-amino-1-(4-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)piperazin-1-yl)ethan-1-one;(R)-(4,5-dichloro-1 H-indol-2-yl)(4-prolylpiperazin-1-yl)methanone;(S)-(4-chloro-5-fluoro-1 H-indol-2-yl)(4-(pyrrolidine-3-carbonyl)piperazin-1- yl)methanone;(R)-azetidin-2-yl(4-(4,5-dichloro-1 H-indole-2-carbonyl)piperazin-1-yl)methanone;((R)-3-aminopyrrolidin-1-yl)((R)-1-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)pyrrolidin-3-yl)methanone;(3,4-dichloro-5-fluoro-1 H-indol-2-yl)((3R)-3-(3-(dimethylamino)pyrrolidine-1- carbonyl)pyrrolidin-1-yl)methanone;((R)-3-aminopyrrolidin-1-yl)((R)-1-(4-chloro-5-fluoro-1 H-indole-2-carbonyl)pyrrolidin-3- yl)methanone;(3-(azetidin-1-yl)pyrrolidin-1-yl)((R)-1-(3,4-dichloro-5-fluoro-1 H-indole-2- carbonyl)pyrrolidin-3-yl)methanone;(3,4-dichloro-5-fluoro-1 H-indol-2-yl)((3R)-3-(3-(3,3-difluoroazetidin-1-yl)pyrrolidine-1- carbonyl)pyrrolidin-1-yl)methanone;(2-amino-4-pyridyl)-[4-(4,5-dichloro-1 H-indole-2-carbonyl)piperazin-1-yl]methanone;1-(6-(4,5-dichloro-1 H-indole-2-carbonyl)-2,6-diazaspiro[3.4]octan-2-yl)ethan-1-one;1-(6-(4,5-dichloro-1 H-indole-2-carbonyl)-1,6-diazaspiro[3.4]octan-1-yl)ethan-1-one;1-(7-(4,5-dichloro-1 H-indole-2-carbonyl)-1,7-diazaspiro[4.4]nonan-1-yl)ethan-1-one;1-(2-(4,5-dichloro-1 H-indole-2-carbonyl)-2,6-diazaspiro[3.4]octan-6-yl)ethan-1-one;1-(7-(4,5-dichloro-1 H-indole-2-carbonyl)-2,7-diazaspiro[4.4]nonan-2-yl)ethan-1-one;8-(3,4-dichloro-5-fluoro-1 / 7-indole-2-carbonyl)-2-methyl-2,8-diazaspiro[4.5]decan-1- one;8-(3,4-dichloro-5-fluoro-1 / 7-indole-2-carbonyl)-1-methyl-1 ,8-diazaspiro[4.5]decan-2- one;8-(3,4-dichloro-5-fluoro-1 / 7-indole-2-carbonyl)-1-methyl-3-oxa-1 ,8- diazaspiro[4.5]decan-2-one;8-(3,4-dichloro-5-fluoro-1 / 7-indole-2-carbonyl)-1 ,3-dimethyl-1 ,3,8-triazaspiro[4.5]decan-2-one;(S)-4-(3,4-dichloro-5-fluoro-1 / 7-indole-2-carbonyl)-1 ,3-dimethylpiperazin-2-one;(S)-(3,4-dichloro-5-fluoro-1 / 7-indol-2-yl)(4-(pyrrolidine-3-carbonyl)piperazin-1- yl)methanone;(3,4-dichloro-5-fluoro-1 / 7-indol-2-yl)(4-(methyl-D-prolyl)piperazin-1-yl)methanone;(R)-(3,4-dichloro-5-fluoro-1 / 7-indol-2-yl)(4-(4,4-difluoropyrrolidine-2-carbonyl)piperazin- 1-yl)methanone;7-(3,4-dichloro-5-fluoro-1 / 7-indole-2-carbonyl)-2-methylhexahydroimidazo[1 ,5- a]pyrazin-3(2 / - / )-one;(R)-(3,4-dichloro-5-fluoro-1 / 7-indol-2-yl)(4-(4,4-difluoro-1-methylpyrrolidine-2- carbonyl)piperazin-1-yl)methanone;(S)-(3,4-dichloro-5-fluoro-1 / 7-indol-2-yl)(4-(1-methylpyrrolidine-3-carbonyl)piperazin-1- yl)methanone;(4-(6-aminonicotinoyl)piperazin-1-yl)(3,4-dichloro-5-fluoro-1 / 7-indol-2-yl)methanone;(S)-2-(3,4-dichloro-5-fluoro-1 / 7-indole-2-carbonyl)hexahydropyrrolo[1 ,2-a]pyrazin-6(2 / - / )-one;(R)-2-(3,4-dichloro-5-fluoro-1 / 7-indole-2-carbonyl)hexahydropyrrolo[1 ,2-a]pyrazin-6(2 / - / )-one;(R)-7-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)hexahydro-3 / 7-oxazolo[3,4-a]pyrazin-3-one;(S)-7-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)hexahydro-3 / 7-oxazolo[3,4-a]pyrazin- 3-one;1-(4-(3,4-dichloro-5-fluoro-1 / 7-indole-2-carbonyl) piperazin-1 -yl)-2-morpholinoethan-1- one;(4-(2-aminoisonicotinoyl) piperazin-1 -yl) (3,4-dichloro-5-fluoro-1 H-indol-2-yl) methanone;1-(4-(3,4-dichloro-1 / 7-indole-2-carbonyl) piperazin-1 -yl)-2-methoxyethan-1 -one;(S)-2-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl) hexahydropyrrolo[1 ,2-a] pyrazin- 6(2 / - / )-one;(R)-2-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl) hexahydropyrrolo[1 ,2-a] pyrazin- 6(2 / - / )-one;2-amino-1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)ethan-1-one;(R)-(3,4-dichloro-5-fluoro-1 H-indol-2-yl)(4-prolylpiperazin-1-yl)methanone;((3S,4R)-3-amino-4-fluoropyrrolidin-1-yl)((R)-1-(3,4-dichloro-5-fluoro-1 H-indole-2- carbonyl)pyrrolidin-3-yl)methanone;(3,4-dichloro-5-fluoro-1 H-indol-2-yl)(4-((3S,4S)-4-(trifluoromethyl)pyrrolidine-3- carbonyl)piperazin-1-yl)methanone; azetidin-3-yl(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)methanone;(4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(3-fluoroazetidine-3-carbonyl)piperazin-1- yl)methanone;((3S,4S)-3-amino-4-fluoropyrrolidin-1-yl)(®-1-(3,4-dichloro-5-fluoro-1 H-indole-2- carbonyl) yrrolidine-3-yl)methanone;(S)-(4-chloro-3,5-difluoro-1 H-indol-2-yl) (4-(morpholine-3-carbonyl) piperazin-1 -yl) methanone;(R)-(4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(morpholine-3-carbonyl)piperazin-1- yl)methanone;(S)-azetidin-2-yl(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1- yl)methanone;(R)-azetidin-2-yl(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1- yl)methanone;(3,4-dichloro-5-fluoro-1 H-indol-2-yl)(4-((2R,4R)-4-fluoropyrrolidine-2- carbonyl)piperazin-1-yl)methanone;(4-(2-aminoisonicotinoyl) piperazin-1 -yl) (4-chloro-3,5-difluoro-1 H-indol-2-yl) methanone;(S)-(4-chloro-3,5-difluoro-1 H-indol-2-yl) (4-(4,4-difluoropyrrolidine-2-carbonyl) piperazin-1 -yl) methanone;(R)-(4-chloro-3,5-difluoro-1 H-indol-2-yl) (4-(4,4-difluoropyrrolidine-2-carbonyl) piperazin-1 -yl) methanone;2-(azetidin-3-yloxy)-1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1- yl)ethan-1-one;(S)-(4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-prolylpiperazin-1-yl)methanone;(R)-(4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-prolylpiperazin-1-yl)methanone;((R)-3-aminopyrrolidin-1 -yl) ((R)-1-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl) pyrrolidin-3-yl) methanone;1-(4-(3-chloro-4-fluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-methoxyethan-1-one;4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-2-one;1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(dimethylamino)ethan-l -one;1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-morpholinoethan-1- one;(4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(oxetane-3-carbonyl)piperazin-1-yl)methanone;(4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(3,3-difluorocyclobutane-1-carbonyl)piperazin-1- yl)methanone;(4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-((1 R,3R)-3-methoxycyclobutane-1- carbonyl)piperazin-1-yl)methanone;1-(4-(3-chloro-4,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-methoxyethan-1-one;(S)-(4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(oxetane-2-carbonyl)piperazin-1- yl)methanone;(R)-(4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(oxetane-2-carbonyl)piperazin-1- yl)methanone;2-(azetidin-1-yl)-1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)ethan-1-one;(4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(1-methylazetidine-3-carbonyl)piperazin-1- yl)methanone;(3aR,6aR)-5-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)-2- methylhexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;2-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)hexahydro-2H,6H-pyrazino[1 ,2- c][1 ,3]oxazin-6-one;(4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(methyl-L-prolyl)piperazin-1-yl)methanone;(4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(methyl-D-prolyl)piperazin-1-yl)methanone;1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-methoxyethan-1-one;(S)-1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)-3-methylpiperazin-1-yl)-2- methoxyethan-1-one;2-( zetidine-1-yl)-1-(4-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl) piperazin-1 -yl) ethan- 1-one;(S)-(4-chloro-3,5-difluoro-1 H-indol-2-yl) (4-(4-methylmorpholine-3-carbonyl) piperazin- 1-yl) methanone;(R)-(4-chloro-3, 5-difl uoro- 1 H-indol-2-yl) (4-(4-methylmorpholine-3-carbonyl) piperazin-1-yl) methanone;2-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)octahydro-6H-pyrido[1,2-a]pyrazin-6-one;1-(4-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(3-methoxyazetidin-1- yl)ethan-1-one;1-(4-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(3-fluoroazetidin-1- yl)ethan-1-one;1-(4-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(3,3-difluoroazetidin- 1-yl)ethan-1-one;1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(3-methoxyazetidin-1- yl)ethan-1-one;1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(3-fluoroazetidin-1- yl)ethan-1-one;1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(3,3-difluoroazetidin-1-yl)ethan-1-one;1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(oxetan-3- yloxy)ethan-1-one;(R)-7-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)hexahydro-3H-oxazolo[3,4-a]pyrazin-3-one;(S)-7-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)hexahydro-3H-oxazolo[3,4-a]pyrazin- 3-one;(3,4-dichloro-5-fluoro-1 H-indol-2-yl)(4-((2R,4S)-4-fluoropyrrolidine-2- carbonyl)piperazin-1-yl)methanone;5-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)-2-methyloctahydro-3H-pyrrolo[3,4-c] yridine-3-one;(3,4-dichloro-5-fluoro-1 H-indol-2-yl)(4-((3S,4S)-1-methyl-4-(trifluoromethyl)pyrrolidine-3-carbonyl)piperazin-1-yl)methanone;(3,4-dichloro-5-fluoro-1 H-indol-2-yl)(4-((2R,4R)-4-fluoro-1-methylpyrrolidine-2- carbonyl)piperazin-1-yl)methanone;(4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(3-fluoro-1-methylazetidine-3-carbonyl)piperazin- 1-yl)methanone;1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-((1-methylazetidin-3- yl)oxy)ethan-1-one;(S)-(4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(4,4-difluoro-1-methylpyrrolidine-2- carbonyl)piperazin-1-yl)methanone;(R)-(4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(4,4-difluoro-1 -methylpyrrolidine-2- carbonyl)piperazin-1-yl)methanone;(3,4-dichloro-5-fluoro-1 H-indol-2-yl)(4-((2R,4S)-4-fluoro-1-methylpyrrolidine-2- carbonyl)piperazin-1-yl)methanone;(3-fluoroazetidin-3-yl)methyl 4-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)piperazine-1- carboxylate; azetidin-3-yl 4-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl) piperazine-1 -carboxylate;1-(4-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(oxetan-3- yloxy)ethan-1-one;8-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)hexahydropyrazino[2,1-c][1 ,4]oxazin-4(3H)-one;7-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)tetrahydroimidazo[1,5-a]pyrazine- 1 ,3(2H,5H)-dione;2-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)-8-methylhexahydropyrrolo[1,2-a]pyrazin- 6(2H)-one;2-(azetidin-3-yloxy)-1-(4-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)piperazin-1- yl)ethan-1-one;(3aR,6aR)-5-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)-2- methylhexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;2-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)hexahydro-2H,6H-pyrazino[1,2- c][1 ,3]oxazin-6-one;(R)-2-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)hexahydro-2H,6H-pyrazino[1,2- c][1 ,3]oxazin-6-one;(S)-2-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)hexahydro-2H,6H-pyrazino[1,2- c][1 ,3]oxazin-6-one;1-(4-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-((1-methylazetidin-3- yl)oxy)ethan-1-one;8-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)octahydro-4 H-pyrazino[1,2- a]pyrazin-4- one;1-(4-(3,4-dichloro-5-fluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(3-fluoroazetidin-3- yl)ethan-1-one;1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(3,3-difluoropyrrolidin- 1-yl)ethan-1-one;(S)-1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)-3-methylpiperazin-1-yl)-2-(3,3- difluoroazetidin-1-yl)ethan-1-one;1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(3,3- difluorocyclobutoxy)ethan-1-one;(R)-1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)-3-(methoxymethyl)piperazin-1-yl)-2-(3,3-difluoroazetidin-1-yl)ethan-1-one;(S)-1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(3,3- difluoroazetidin-1-yl)propan-1-one;(R)-1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(3,3- difluoroazetidin-1-yl)propan-1-one;(S)-1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(3,3-difluoro-2- methylazetidin-1-yl)ethan-1-one;(R)-1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(3,3-difluoro-2- methylazetidin-1-yl)ethan-1-one;4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)-N,N-dimethylmorpholine-2-carboxamide;(S)-(4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(tetrahydrofuran-2-carbonyl)piperazin-1- yl)methanone;(R)-(4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(tetrahydrofuran-2-carbonyl)piperazin-1- yl)methanone;4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)-N,N-dimethylpiperazine-2-carboxamide;1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)ethan-1-one;(R)-(4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(4,4-dimethyloxetane-2-carbonyl)piperazin-1- yl)methanone;(S)-(4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(4,4-dimethyloxetane-2-carbonyl)piperazin-1- yl)methanone;(S)-8-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)hexahydropyrazino[2,1-c][1 ,4]oxazin-4(3H)-one;(R)-8-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)hexahydropyrazino[2,1-c][1 ,4]oxazin-4(3H)-one;1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2,2-difluoroethan-1- one;(R)-(4-chloro-3,5-difluoro-1 H-indol-2-yl)(4-(2-methyloxetane-2-carbonyl)piperazin-1- yl)methanone;1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(trifluoromethoxy)ethan-l-one;1-(4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(difluoromethoxy)ethan-l -one;(S)-4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)-N-methylpiperazine-2-carboxamide;(S)-4-(4-chloro-3,5-difluoro-1 H-indole-2-carbonyl)-N,N-dimethylpiperazine-2- carboxamide;1-(4-(3,4-dichloro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(3,3-difluoroazetidin-1- yl)ethan-1-one;(R)-(4-chloro-3-fluoro-1 H-indol-2-yl)(4-(oxetane-2-carbonyl)piperazin-1-yl)methanone; 1-(4-(4-chloro-3-fluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-methoxyethan-1-one; 1-(4-(4-chloro-3-fluoro-1 H-indole-2-carbonyl)piperazin-1-yl)-2-(3,3-difluoroazetidin-1- yl)ethan-1-one;(R)-(4-chloro-3-fluoro-1 H-indol-2-yl)(4-(tetrahydrofuran-2-carbonyl)piperazin-1- yl)methanone;(R)-(3,4-dichloro-1 H-indol-2-yl)(4-(oxetane-2-carbonyl)piperazin-1-yl)methanone;(S)-1-(4-(3,4-dichloro-1 H-indole-2-carbonyl)-3-methylpiperazin-1-yl)-2-methoxyethan-1- one; or(R)-(3,4-dichloro-1 H-indol-2-yl)(4-(tetrahydrofuran-2-carbonyl)piperazin-1- yl)methanone, or a pharmaceutically acceptable salt thereof.

42. The compound for use according to any one of claims 38 to 41 , wherein the disease or medical condition is a neurodegenerative disease.

43. The compound for use according to any one of claims 38 to 41 , wherein the disease or medical condition is Multiple Sclerosis, Parkinson's disease, amyotrophic lateral sclerosis (ALS), and Huntington's disease44. The compound for use according to claim 42, wherein the neurodegenerative disease is a tauopathy, a TDP-43 proteinopathy, a synucleinopathy, dementia, amyloidosis, a demyelinating disorder of the CNS, a demyelinating disorder of the PNS, a Leukoencephalopathy, a leukodystrophy, a transmissible spongiform encephalopathy (TSE), or a lysosomal storage disorder (LSD).

45. The compound for use according to claim 42, wherein the neurodegenerative disease is Alzheimer’s disease, Frontotemporal lobar degeneration (FTLD), frontotemporal dementia (FTD), Parkinson’s disease, Nasu-Hakola disease, FTLD-like syndrome, Huntington disease, Amyotrophic lateral sclerosis, multiple sclerosis, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathies, Charcot-Marie-Tooth disease, prion disease or stroke.

46. The compound for use according to any one of claims 38 to 41 , wherein the disease or medical condition is rheumatoid arthritis (RA), neuropathic pain,inflammatory pain, CNS complications of COVID-19 infection, post-COVID-19 conditions, Chronic Traumatic Encephalopathy, HIV-Associated Neurocognitive Disorder (HAND), Traumatic Brain Injury, Epilepsy, Autoimmune Encephalitis, Bipolar disorder, major depression disorder(MDD) or Schizophrenia.

47. The compound for use according to any one of claims 38 to 41, wherein the disease or medical condition is Psoriasis, Atopic dermatitis, Celiac Disease, Lupus, Type 1 diabetes, Sjogren’s syndrome, Vasculitis, IBD, Crohn’s disease, Graves’ disease, Hashimoto’s thyroiditis, Myasthenia gravis or Scleroderma.

48. The compound for use according to any one of claims 38 to 41, wherein the disease or medical condition is cancer; an immunological disorder, such as transplant rejection or an autoimmune disease, for example rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, or type I diabetes mellitus; a central nervous system disorder, such as Alzheimer’s disease; an inflammatory disorder, such as an inflammatory skin condition, arthritis, psoriasis, spondylitis, parodontitits, or an inflammatory neuropathy; a gastroenterological disorder, such as an inflammatory bowel disease; a metabolic disorder, such as obesity or type II diabetes mellitus; a cardiovascular disorder; or a kidney disease, such as chronic kidney disease, nephritis, or chronic renal failure.

49. The compound for use according to any one of claims 38 to 41, wherein the condition is selected from the group consisting of cancer, transplant rejection, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, type I diabetes mellitus, Alzheimer’s disease, inflammatory skin condition, inflammatory neuropathy, psoriasis, spondylitis, parodontitis, Crohn’s disease, ulcerative colitis, obesity, type II diabetes mellitus, ischemic stroke, chronic kidney disease, nephritis, chronic renal failure, and a combination thereof.

50. Use of a compound, or a pharmaceutically acceptable salt thereof, as defined in any one of claims 20 to 22 for the manufacture of a medicament for treatment of disease or medical condition where inhibition of Kv1.3 potassium channel is beneficial.

51. A method for treatment of a disease or medical condition where inhibition of Kv1.3 potassium channel is beneficial comprising administering a compound, or a pharmaceutically acceptable salt thereof, as defined in any one of claims 38 to 41 to a subject in need thereof.

52. A method of blocking Kv1.3 potassium channel in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of at least one as defined in any one of claims 38 to 41 , or a pharmaceutically acceptable salt thereof.

53. The method according to any one of claims 52 or 53, wherein the subject is a mammal, such as human.

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