Thienopyridine compounds and uses thereof

Abstract

Provided herein are compounds of formula (I) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate of any of the foregoing, wherein R1, R2, Ring A, L, R6, R7, and R8 are as defined elsewhere herein. Also provided are methods of preparing compounds of formula (I). Also provided herein are methods of modulating TDP-43 and methods of treating a disease or condition mediated by TDP-43 in an individual in need thereof.

Description

[0001] Attorney Docket No.: 185992002140 THIENOPYRIDINE COMPOUNDS AND USES THEREOF CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority benefit of United States Provisional PatentApplication No. 63 / 618,195 filed January 5, 2024, which is hereby incorporated herein byreference in its entirety.FIELD OF THE INVENTION Aspects of the invention generally relate to amino thienopyridine compounds,pharmaceutical compositions, kits comprising the same, their use as biomolecular condensate modifying drugs (c-mods), and their use in the treatment of a disease or condition. BACKGROUND OF THE INVENTION TAR DNA-binding protein 43 (TDP-43) is a highly conserved and ubiquitously- expressed RNA / DNA-binding protein involved in RNA processing. Cytoplasmic aggregates of TDP-43 occur in >97% of amyotrophic lateral sclerosis (ALS) cases. Stress-induced formation of cytoplasmic TDP-43 biological condensates represent an intermediate, reversible, pre-pathological state in neurons. Over time, TDP-43-containing condensates losetheir fluid-like properties and potentially convert into irreversible, toxic aggregates [Ling, etal., Neuron 79, 416–438 (2013); Markmiller, et al. Cell Reports 36, 109685 (2021); and Lu etal. Nat Cell Biol 1–16 (2022)].The role of condensate dysfunction in ALS pathogenesis is supported by thediscovery of condensate genes as genetic modifiers of ALS (e.g., TAF15, EWSR1, TIA1,HNRNPA1, HNRNPA2B1), as well as co-localization of C9ORF72 ALS G4C2expansion- derived dipeptide repeats (DPRs) and stress granule proteins with TDP-43 inclusions in preclinical models. Nuclear depletion of TDP-43 into cytoplasmic condensates leads to toxic loss of splicing function in motor neurons. Small molecule condensate modifying drugs (c-mods) that directly modulate TDP-43 condensates can treat diverse forms of ALS [Chew, J.et al., Mol. Neurodegener. 14, 9 (2019); and Taylor, J. P., et al., Nature 539, 197–206(2016)]. Attorney Docket No.: 185992002140 BRIEF SUMMARY OF THE INVENTION In one aspect, provided herein is a compound of formula (I) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, orsolvate of any of the foregoing, whereinR1 and R2 are each independently H, C1-6alkyl, C2-6alkenyl, -C(=O)R12, -C(=O)OR12, - C(=O)N(R11)(R12), -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 12-memberedheterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, whereinthe C1-6alkyl of R1 or R2 is optionally substituted with one or more R1a,the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to10-membered heteroaryl of R1 or R2 is optionally substituted with one or more R1b,and optionally, two substituents of the C1-6alkyl, C2-6alkenyl, -C(=O)R12, -C(=O)OR12, - C(=O)N(R11)(R12), -S(=O)2R12, -S(=O)2N(R11)(R12), or C3-8cycloalkyl group of R1or R2 are taken together with the atoms to which they are attached to form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl,or 5- to 10-membered heteroaryl is optionally substituted with one or moreR1b;or R1 and R2 are taken together with the N to which they are attached to form a 3- to 12-membered heterocyclyl or 5- to 10-membered heteroaryl, wherein3- to 12-membered heterocyclyl or 5- to 10-membered heteroaryl of R1 and R2 isoptionally substituted with one or more R3; each R3is independently halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, oxo, -OR10, -SR10, -SF5, -N(Rx)(Ry), -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, - OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), - Attorney Docket No.: 185992002140 C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, - S(=NR13)N(R11)R12, -S(=NR13)OR13, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R3is optionally substituted with one or more R3a; the C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with one or more R3b; and optionally, two substituents of R3are taken together with the atoms to which they are attached form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10- membered aryl, or 5- to 10-membered heteroaryl is optionally substituted one or more R3b; Ring A is C3-8cycloalkyl, 4- to 12-membered cycloalkenyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 4- to 12-membered cycloalkenyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of Ring A is optionally substituted by one or more R4, and the 3- to 12-membered heterocyclyl or 5- to 10-membered heteroaryl of Ring A comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; each R4is independently halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -OR10, -SR10, -SF5, - N(Rx)(Ry), -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, - OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), - C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, - S(=NR13)N(R11)R12, -S(=NR13)OR13, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R4is optionally substituted by one or more R4a, the C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R4is optionally substituted with one or more R4b, and the 3- to 8-membered heterocyclyl of R4comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; L is a bond, C1-6alkyl, -O-(C1-6alkyl)-, -S-(C1-6alkyl)-, or -N(R5)(C1-6alkyl)-, wherein Attorney Docket No.: 185992002140 the C1-6alkyl, -O-(C1-6alkyl)-, -S-(C1-6alkyl)-, or -N(R5)(C1-6alkyl)- is optionally substituted by one or more RL; each RLis independently halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, -OC(=O)N(R11)R12, - OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, C3-8cycloalkyl, 3- to 8- membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, or two RLare taken together along with the atoms to which they are attached to form a C3-8cycloalkyl or 3- to 8-membered heterocyclyl; R5is H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -C(=O)R12, -S(=O)2R12, -S(=O)2N(R11)(R12), or C3-8cycloalkyl, wherein the C1-6alkyl of R5is optionally substituted with one or more halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, - OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), - C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, - S(=NR13)N(R11)R12, -S(=NR13)OR13, -S(=O)2R12, or -S(=O)2N(R11)(R12), and the C3-8cycloalkyl is optionally substituted with one or more R5b; R6is H, halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -OR9, -OR10, -SR10, -SF5, -N(Rx)(Ry), - NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, - OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, - C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, -N(R11)S(=O)2R12, - S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, -S(=NR13)N(R11)R12, - S(=NR13)OR13, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R6is optionally substituted by one or more R6a, the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R6is optionally substituted with one or more R6b, - C(=O)R12, -C(=O)N(R11)(R12), or -C(=O)OR12, and the 3- to 12-membered heterocyclyl of R6comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S, and optionally, two substituents of R6are taken together with the atoms to which they are attached form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein Attorney Docket No.: 185992002140 the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with one or more R6b; R7and R8are each independently H, halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -OR9, -OR10, - SR10, -SF5, -N(Rx)(Ry), -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, - N(R11)C(=O)OR12, -OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, - C(=O)N(R11)(R12), -C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, - C(=NR13)OR12, -N(R11)S(=O)2R12, -S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, -S(=NR13)N(R13)R12, -S(=NR13)OR12, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R7or R8is optionally substituted by one or more R7a, the 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R7or R8is optionally substituted with one or more R7b, and the 3- to 8-membered heterocyclyl of R7or R8comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S, and optionally, two substituents of R7or R8are taken together with the atoms to which they are attached form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10- membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with one or more R7b; each R1a, R3a, R4a, R6a, or R7ais independently halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -NO2, - CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, - OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, - C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, -N(R11)S(=O)2R12, - S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, -S(=NR13)N(R13)R12, - S(=NR13)OR12, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R1a, R3a, R4a, R6a, or R7ais optionally substituted with one or more R1b, and the 3- to 12-membered heterocyclyl of R1a, R3a, R4a, R6a, or R7acomprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; Attorney Docket No.: 185992002140 each R1b, R3b, R4b, R5b, R6b, or R7bis independently halo, C1-6alkyl, -OR9, -N(Rx)(Ry), oxo, - CN, C3-8cycloalkyl, or 3- to 8-membered heterocyclyl, wherein the C1-6alkyl of R1b, R3b, R4b, R5b, R6b, or R7bis optionally substituted by -OR12, - N(Rx)(Ry), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl; each R9is independently H, C1-6alkyl, C2-6alkenyl, C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R9is optionally substituted with 6- to 10-membered aryl, or 5- to 10- membered heteroaryl wherein the 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, or -N(Rx)(Ry), and the 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R9is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, -N(Rx)(Ry), or 3- to 12-membered heterocyclyl; each R10is independently H, C1-6alkyl, C2-6alkenyl, C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl is optionally substituted with one or more halo, deuterium, C1-6alkoxy, -N(Rx)(Ry), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10- membered aryl, or 5- to 10-membered heteroaryl wherein the C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, or -N(Rx)(Ry); each R11is independently H, C1-6alkyl, or C3-8cycloalkyl; each R12is independently H, C1-6alkyl, C2-6alkenyl, C3-8cycloalkyl, 6- to 10-membered aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1-6alkyl of R12is optionally substituted by one or more halo, -OH, -O(C1-6alkyl), -SH, -S(C1-6alkyl), -(C=O)NH2, -(C=O)OH, -O(C=O)C1-8alkyl), -NH(C=NH)NH2, - N(Rx)(Ry), C3-8cycloalkyl, 6- to 10-membered aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the 6- to 10-membered aryl is optionally substituted by -OH, and the C3-8cycloalkyl, 6- to 10-membered aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl of R12is optionally substituted with halo, C1-6alkyl, or - N(Rx)(Ry); Attorney Docket No.: 185992002140 each R13is independently H or C1-6alkyl; andeach Rx and Ry is independently H, C1-6alkyl, C3-8cycloalkyl, -C(=O)(C1-6alkyl), or -C(=O)O(C1-6alkyl), whereinthe C1-6alkyl of Rx or Ry is optionally substituted with 6- to 10-membered aryl, 5- to10-membered heteroaryl, or -NH2, NH(C1-6alkyl), or -N(C1-6alkyl)(C1-6alkyl), and the C1-6alkyl of -C(=O)(C1-6alkyl) or -C(=O)O(C1-6alkyl) is optionally substituted with-O(C=O)C1-8alkyl); wherein (i) when -(Ring A)-L-R6are taken together to form and R1is H, R8is not optionally substituted pyrazolyl; (ii) when R1and R2are taken together with the N to which they are attached and Ring A is 5-membered N-containing heteroaryl, then L-R6are not taken together to form halo, pyridyl substituted by methyl, or substituted phenyl; and (iii) when -(Ring A)-L-R6are taken together to form , R1is H, and R2is -CH3, R8is not -CH3. In some embodiments, the compound of formula (I) is a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing. Any embodiments provided herein of a compound of formula (I), or a stereoisomer ortautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate of any of theforegoing, apply where applicable to any other formula detailed herein, the same as if each and every embodiment were specifically and individually listed. Thus, it is understood and described that each embodiment provided herein of a compound of formula (I), or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate ofany of the foregoing, such as embodiments related to R1, R2, R3, Ring A, R4, L, R5, R6, R7,R8, R1a, R3a, R6a, R7a, R1b, R3b, R4b, R5b, R6b, R7b, R9, R10, R11, R12, R13, Rx, and Ry, apply toformula (II), (II-A), (II-B), (II-C), (III), (III-A), or (IV) or a stereoisomer or tautomer thereof,or a pharmaceutically acceptable salt, hydrate, or solvate of any of the foregoing, the same as Attorney Docket No.: 185992002140 if each and every embodiment were specifically and individually listed. It is also understood and described that all such embodiments may be used in any of the pharmaceutical compositions, methods, kits, uses, or other aspects detailed herein. In one aspect, provided is a pharmaceutical composition comprising a compound offormula (I) or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, ora pharmaceutically acceptable salt, hydrate, or solvate of any of the foregoing, and one ormore pharmaceutically acceptable excipients. This aspect in some embodiments may employa compound of any of formulas (II), (II-A), (II-B), (II-C), (III), (III-A), or (IV), or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate ofany of the foregoing. In another variation, provided is a pharmaceutical compositioncomprising a compound of formula (I) or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of theforegoing, and one or more pharmaceutically acceptable excipients. This aspect in someembodiments may employ a compound of any of formulas (I), (II), (II-A), (II-B), (II-C), (III),(III-A), or (IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof. In one aspect, provided is a method for treating a disease or condition mediated byTDP-43, comprising administering to an individual in need thereof a compound of formula(I) or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or apharmaceutically acceptable salt, hydrate, or solvate of any of the foregoing, or apharmaceutical composition comprising a compound of formula (I) or any variation orembodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptablesalt, hydrate, or solvate of any of the foregoing, and one or more pharmaceutically acceptableexcipients. This aspect in some embodiments may employ a compound of any of formulas(II), (II-A), (II-B), (II-C), (III), (III-A), or (IV), or a stereoisomer or tautomer thereof, or apharmaceutically acceptable salt, hydrate, or solvate of any of the foregoing. In anothervariation, provided is a method for treating a disease or condition mediated by TDP-43,comprising administering to an individual in need thereof a compound of formula (I) or anyvariation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition comprising acompound of formula (I) or any variation or embodiment thereof, or a stereoisomer ortautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and one ormore pharmaceutically acceptable excipients. This aspect in some embodiments may employ Attorney Docket No.: 185992002140a compound of any of formulas (I), (II), (II-A), (II-B), (II-C), (III), (III-A), or (IV), or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof. In one aspect, provided herein is a method of modulating TDP-43, comprisingcontacting a cell with an effective amount of a compound of formula (I), or a stereoisomer ortautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate of any of theforegoing. This aspect in some embodiments may employ a compound of any of formulas(II), (II-A), (II-B), (II-C), (III), (III-A), or (IV), or a stereoisomer or tautomer thereof, or apharmaceutically acceptable salt, hydrate, or solvate of any of the foregoing. In anothervariation, provided is a method of modulating TDP-43, comprising contacting a cell with aneffective amount of a compound of formula (I) or any variation or embodiment thereof, or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of theforegoing, or a pharmaceutical composition comprising a compound of formula (I) or anyvariation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceuticallyacceptable salt of any of the foregoing, and one or more pharmaceutically acceptableexcipients. This aspect in some embodiments may employ a compound of any of formulas(I), (II), (II-A), (II-B), (II-C), (III), (III-A), or (IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof. In one aspect, provided herein is a method of modulating TDP-43 target geneexpression levels, comprising contacting a cell with an effective amount of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt,hydrate, or solvate of any of the foregoing. This aspect in some embodiments may employ acompound of any of formulas (II), (II-A), (II-B), (II-C), (III), (III-A), or (IV), or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate ofany of the foregoing. In another variation, provided is a method of modulating TDP-43 targetgene expression levels, comprising contacting a cell with an effective amount of a compoundof formula (I) or any variation or embodiment thereof, or a stereoisomer or tautomer thereof,or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceuticalcomposition comprising a compound of formula (I) or any variation or embodiment thereof,or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of theforegoing, and one or more pharmaceutically acceptable excipients. This aspect in someembodiments may employ a compound of any of formulas (I), (II), (II-A), (II-B), (II-C), (III), Attorney Docket No.: 185992002140 (III-A), or (IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof. In one aspect, provided herein is a compound of formula (I), or a stereoisomer ortautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate of any of theforegoing, or a pharmaceutical composition comprising a compound of formula (I) or anyvariation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceuticallyacceptable salt, hydrate, or solvate of any of the foregoing, and one or more pharmaceuticallyacceptable excipients, for use in the treatment of a disease or condition mediated by TDP-43.This aspect in some embodiments may employ a compound of any of formulas (II), (II-A),(II-B), (II-C), (III), (III-A), or (IV), or a stereoisomer or tautomer thereof, or apharmaceutically acceptable salt, hydrate, or solvate of any of the foregoing.In one aspect, provided herein is the use of a compound of formula (I), or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate ofany of the foregoing, or a pharmaceutical composition comprising a compound of formula (I) or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or apharmaceutically acceptable salt, hydrate, or solvate of any of the foregoing, and one or morepharmaceutically acceptable excipients, in the manufacture a medicament for the treatment ofa disease or condition mediated by TDP-43. This aspect in some embodiments may employ acompound of any of formulas (II), (II-A), (II-B), (II-C), (III), (III-A), or (IV), or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate ofany of the foregoing. In another variation, provided is the use of a compound of formula (I)or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical compositioncomprising a compound of formula (I) or any variation or embodiment thereof, or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of theforegoing, and one or more pharmaceutically acceptable excipients, in the manufacture amedicament for the treatment of a disease or condition mediated by TDP-43. This aspect insome embodiments may employ a compound of any of formulas (I), (II), (II-A), (II-B), (II-C), (III), (III-A), or (IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof. In one aspect, provided herein is a kit, comprising (i) a compound of formula (I), or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate ofany of the foregoing, and (ii) instructions for use in treating a TDP-43 mediated disease or Attorney Docket No.: 185992002140 condition in an individual in need thereof. This aspect in some embodiments may employ acompound of any of formulas (II), (II-A), (II-B), (II-C), (III), (III-A), or (IV), or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate ofany of the foregoing. In another variation, provided is a kit, comprising (i) a compound offormula (I) or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, ora pharmaceutically acceptable salt of any of the foregoing, and (ii) instructions for use intreating a TDP-43 mediated disease or condition in an individual in need thereof. This aspectin some embodiments may employ a compound of any of formulas (I), (II), (II-A), (II-B), (II-C), (III), (III-A), or (IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof. All pharmaceutical compositions, methods, kits, uses, or other aspects described herein with reference to formula (I), or stereoisomer or tautomer thereof, or apharmaceutically acceptable salt, hydrate, or solvate of any of the foregoing, are also herebydescribed and embraced for any one of the other formulas detailed herein such as formula (II), (II-A), (II-B), (II-C), (III), (III-A), or (IV), the same as if each and every embodiment were specifically and individually listed. DETAILED DESCRIPTION OF THE INVENTION “Individual” refers to mammals and includes humans and non-human mammals. Examples of individuals include, but are not limited to, mice, rats, hamsters, guinea pigs, pigs, rabbits, cats, dogs, goats, sheep, cows, and humans. In some embodiments, individual refers to a human. As used herein, “about” a parameter or value includes and describes that parameter or value per se. For example, “about X” includes and describes X per se. “Treatment” or “treating” is an approach for obtaining beneficial or desired results including clinical results. Beneficial or desired results may include one or more of the following: decreasing one or more symptom resulting from the disease or condition; diminishing the extent of the disease or condition; slowing or arresting the development of one or more symptom associated with the disease or condition (e.g., stabilizing the disease or condition, preventing or delaying the worsening or progression of the disease or condition); and relieving the disease, such as by causing the regression of clinical symptoms (e.g., ameliorating the disease state, enhancing the effect of another medication, delaying the progression of the disease, increasing the quality of life, and / or prolonging survival). Attorney Docket No.: 185992002140 As used herein, “delaying” development of a disease or condition means to defer, hinder, slow, retard, stabilize and / or postpone development of the disease or condition. Thisdelay can be of varying lengths of time, depending on the history of the disease and / orindividual being treated. As is evident to one skilled in the art, a sufficient or significant delay can, in effect, encompass prevention, in that the individual does not develop the disease or condition. As used herein, the term “therapeutically effective amount” or “effective amount” intends such amount of a compound of the disclosure or a pharmaceutically salt thereof sufficient to effect treatment when administered to an individual. As is understood in the art, an effective amount may be in one or more doses, e.g., a single dose or multiple doses may be required to achieve the desired treatment endpoint. An effective amount may be considered in the context of administering one or more therapeutic agents, and a single agent may be considered to be given in an effective amount if, in conjunction with one or more other agents, a desirable or beneficial result may be or is achieved. As used herein, “unit dosage form” refers to physically discrete units, suitable as unit dosages, each unit containing a predetermined quantity of active ingredient, or compound, which may be in a pharmaceutically acceptable carrier. As used herein, by “pharmaceutically acceptable” is meant a material that is not biologically or otherwise undesirable, e.g., the material may be incorporated into a pharmaceutical composition administered to an individual without causing significant undesirable biological effects. The term “alkyl”, as used herein, refers to an unbranched or branched saturated univalent hydrocarbon chain. As used herein, alkyl has 1-20 carbons (i.e., C1-20alkyl), 1-16 carbons (i.e., C1-16alkyl), 1-12 carbons (i.e., C1-12alkyl), 1-10 carbons (i.e., C1-10alkyl), 1-8 carbons (i.e., C1-8alkyl), 1-6 carbons (i.e., C1-6alkyl), 1-4 carbons (i.e., C1-4alkyl), or 1-3 carbons (i.e., C1-3alkyl). Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl, pentyl, 2-pentyl, iso-pentyl, neo-pentyl, hexyl, 2-hexyl, 3-hexyl, and 3-methylpentyl. When an alkyl residue having a specific number of carbons is named by chemical name or molecular formula, all positional isomers having that number of carbon atoms may be encompassed—for example, “butyl” includes n-butyl, sec-butyl, iso-butyl, and tert-butyl; and “propyl” includes n-propyl and iso- propyl. Certain commonly used alternative names may be used and will be understood by Attorney Docket No.: 185992002140 those of ordinary skill in the art. For instance, a divalent group, such as a divalent “alkyl” group, may be referred to as an “alkylene”. The term “alkenyl”, as used herein, refers to a branched or unbranched univalent hydrocarbon chain comprising at least one carbon-carbon double bond. As used herein, alkenyl has 2-20 carbons (i.e., C2-20alkenyl), 2-16 carbons (i.e., C2-16alkenyl), 2-12 carbons (i.e., C2-12alkenyl), 2-10 carbons (i.e., C2-10alkenyl), 2-8 carbons (i.e., C2-8alkenyl), 2-6 carbons (i.e., C2-6alkenyl), 2-4 carbons (i.e., C2-4alkenyl), or 2-3 carbons (i.e., C2-3alkenyl). Examples of alkenyl include, but are not limited to, ethenyl, prop-1-enyl, prop-2-enyl 1,2- butadienyl, and 1,3-butadienyl. When an alkenyl residue having a specific number of carbons is named by chemical name or molecular formula, all positional isomers having that number of carbon atoms may be encompassed—for example, “propenyl” includes prop-1- enyl and prop-2-enyl. Certain commonly used alternative names may be used and will be understood by those of ordinary skill in the art. For instance, a divalent group, such as a divalent “alkenyl” group, may be referred to as an “alkenylene”. The term “alkynyl”, as used herein, refers to a branched or unbranched univalent hydrocarbon chain comprising at least one carbon-carbon triple bond. As used herein, alkynyl has 2-20 carbons (i.e., C2-20alkynyl), 2-16 carbons (i.e., C2-16alkynyl), 2-12 carbons (i.e., C2-12alkynyl), 2-10 carbons (i.e., C2-10alkynyl), 2-8 carbons (i.e., C2-8alkynyl), 2-6 carbons (i.e., C2-6alkynyl), 2-4 carbons (i.e., C2-4alkynyl), or 2-3 carbons (i.e., C2-3alkynyl). Examples of alkynyl include, but are not limited to, ethynyl, prop-1-ynyl, prop-2-ynyl, but-1- ynyl, but-2-ynyl, and but-3-ynyl. When an alkynyl residue having a specific number of carbons is named by chemical name or molecular formula, all positional isomers having that number of carbon atoms may be encompassed—for example, “propynyl” includes prop-1- ynyl and prop-2-ynyl. Certain commonly used alternative names may be used and will be understood by those of ordinary skill in the art. For instance, a divalent group, such as a divalent “alkynyl” group, may be referred to as an “alkynylene”. The term “alkoxy”, as used herein, refers to an -O-alkyl moiety. Examples of alkoxy groups include, but are not limited to, methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, tert-butoxy, sec-butoxy, n-pentoxy, n-hexoxy, and 1,2-dimethylbutoxy. The term “aryl”, as used herein, refers to a fully unsaturated carbocyclic ring moiety. The term “aryl” encompasses monocyclic and polycyclic fused-ring moieties. As used herein, aryl encompasses ring moieties comprising, for example, 6 to 20 annular carbonatoms (i.e., 6- to 20-membered aryl), 6 to 16 annular carbon atoms (i.e., 6- to 16-membered Attorney Docket No.: 185992002140aryl), 6 to 12 annular carbon atoms (i.e., 6- to 12-membered aryl), or 6 to 10 annular carbonatoms (i.e., 6- to 10-membered aryl). Examples of aryl moieties include, but are not limitedto, phenyl, naphthyl, fluorenyl, and anthryl. The term “cycloalkyl”, as used herein, refers to a saturated or partially unsaturated carbocyclic ring moiety. The term “cycloalkyl” encompasses monocyclic and polycyclic ring moieties, wherein the polycyclic moieties may be fused, branched, or spiro. Cycloalkyl includes cycloalkenyl groups, wherein the ring moiety comprises at least one annular double bond. Cycloalkyl includes any polycyclic carbocyclic ring moiety comprising at least one non-aromatic ring, regardless of the point of attachment to the remainder of the molecule. As used herein, cycloalkyl includes rings comprising, for example, 3 to 20 annular carbon atoms (i.e., a C3-20cycloalkyl), 3 to 16 annular carbon atoms (i.e., a C3-16cycloalkyl), 3 to 12 annular carbon atoms (i.e., a C3-12cycloalkyl), 3 to 10 annular carbon atoms (i.e., a C3-10cycloalkyl), 3 to 8 annular carbon atoms (i.e., a C3-8cycloalkyl), 3 to 6 annular carbon atoms (i.e., a C3-6cycloalkyl), or 3 to 5 annular carbon atoms (i.e., a C3-5cycloalkyl). Monocyclic cycloalkyl ring moieties include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Polycyclic groups include, for example, bicyclo[2.2.1]heptanyl, bicyclo[2.2.2]octanyl, adamantyl, norbonyl, decalinyl, 7,7-dimethyl -bicyclo [2.2.1]heptanyl, and the like. Still further, cycloalkyl also includes spiro cycloalkyl ring moieties, for example, spiro[2.5]octanyl, spiro[4.5]decanyl, or spiro [5.5]undecanyl. The term “halo”, as used herein, refers to atoms occupying groups VIIA of The Periodic Table and includes fluorine (fluoro), chlorine (chloro), bromine (bromo), and iodine (iodo). Additionally, terms such as “haloalkyl” are meant to include monohaloalkyl and polyhaloalkyl. For example, the term “C1-4haloalkyl” is mean to include trifluoromethyl, 2,2,2-trifluoroethyl, 4-chlorobutyl, 3-bromopropyl, difluoromethyl, and the like. The term “heteroaryl”, as used herein, refers to an aromatic (fully unsaturated) ringmoiety that comprises one or more annular heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur. The term “heteroaryl” includes both monocyclic and polycyclic fused-ring moieties. As used herein, a heteroaryl comprises, forexample, 5 to 20 annular atoms (i.e., a 5- to 20-membered heteroaryl), 5 to 16 annular atoms(i.e., a 5- to16-membered heteroaryl), 5 to 12 annular atoms (i.e., a 5- to 12-memberedheteroaryl), 5 to 10 annular atoms (i.e., a 5- to 10-membered heteroaryl), 5 to 8 annular atoms(i.e., a 5- to 8-membered heteroaryl), or 5 to 6 annular atoms (i.e., a 5- to 6-memberedheteroaryl). Any monocyclic or polycyclic aromatic ring moiety comprising one or more Attorney Docket No.: 185992002140 annular heteroatoms is considered a heteroaryl, regardless of the point of attachment to the remainder of the molecule (i.e., the heteroaryl moiety may be attached to the remainder of the molecule through any annular carbon or any annular heteroatom of the heteroaryl moiety). Examples of heteroaryl groups include, but are not limited to, oxazolyl, thiazolyl, pyridinyl, pyrimidinyl, and pyridazinyl. The term “heterocyclyl”, as used herein, refers to a saturated or partially unsaturated cyclic moiety that encompasses one or more annular heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur. The term “heterocyclyl” includes both monocyclic and polycyclic ring moieties, wherein the polycyclic ring moieties may be fused, bridged, or spiro. Any non-aromatic monocyclic or polycyclic ring moiety comprisingat least one annular heteroatom is considered a heterocyclyl, regardless of the point ofattachment to the remainder of the molecule (i.e., the heterocyclyl moiety may be attached to the remainder of the molecule through any annular carbon or any annular heteroatom of the heterocyclyl moiety). Further, the term heterocyclyl is intended to encompass any polycyclic ring moiety comprising at least one annular heteroatom wherein the polycyclic ring moiety comprises at least one non-aromatic ring, regardless of the point of attachment to the remainder of the molecule. As used herein, a heterocyclyl comprises, for example, 3 to 20annular atoms (i.e., a 3- to 20-membered heterocyclyl), 3 to 16 annular atoms (i.e., a 3- to 16-membered heterocyclyl), 3 to 12 annular atoms (i.e., a 3- to 12-membered heterocyclyl), 3 to10 annular atoms (i.e., a 3- to 10-membered heterocyclyl), 3 to 8 annular atoms (i.e., a 3- to8-membered heterocyclyl), 3 to 6 annular atoms (i.e., a 3- to 6-membered heterocyclyl), 3 to5 annular atoms (i.e., a 3- to 5-membered heterocyclyl), 5 to 8 annular atoms (i.e., a 5- to 8-membered heterocyclyl), or 5 to 6 annular atoms (i.e., a 5- to 6-membered heterocyclyl).Examples of heterocyclyl groups include, e.g., azetidinyl, piperidinyl, piperazinyl, pyrrolidinyl, pyrazolidinyl, thiazolidinyl, tetrahydrofuryl, or tetrahydropyranyl. Examples of spiro heterocyclyl rings include, but are not limited to, bicyclic and tricyclic ring systems, such as 2-oxa-7-azaspiro[3.5]nonanyl, 2-oxa-6-azaspiro[3.4]octanyl, and 6-oxa-1-azaspiro[3.3]heptanyl. Examples of fused heterocyclyl rings include, but are not limited to,5,6,7,8-tetrahydropyrido[4,3-d]pyrimidinyl, 6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidinyl, 5,7- dihydrofuro[3,4-d]pyrimidinyl, and 5,7-dihydrothieno[3,4-d]pyrimidinyl, where theheterocyclyl can be bound via either ring of the fused system.The term “oxo”, as used herein, refers to a =O moiety. Attorney Docket No.: 185992002140 The terms “spiro”, “spirocycle” and “spirocyclic”, as used herein, refer to a polycyclic moiety in which two of the rings share one atom in common. The terms “spiro”, “spirocycle”and “spirocyclic” may refer to a saturated or partially unsaturated carbocycle, or a saturatedor partially unsaturated heterocycle.The term “fused”, as used herein, refers to a polycyclic moiety in which two of the rings share two adjacent atoms in common. The term “fused” may refer to a saturated orpartially unsaturated carbocycle, or a saturated or partially unsaturated heterocycle.The term “bridged”, as used herein, refers to a polycyclic moiety in which two of the rings share three or more atoms in common, and the bridgehead atoms are separated by at least one atoms. The term “bridged” may refer to a saturated or partially unsaturatedcarbocycle, or a saturated or partially unsaturated heterocycle.The terms “optional” and “optionally”, as used herein, mean that the subsequently described event or circumstance may or may not occur and that the description includes instances where the event or circumstance occurs and instances where it does not. Accordingly, the term “optionally substituted” infers that any one or more (e.g., 1, 2, 1 to 5, 1 to 3, 1 to 2, etc.) hydrogen atoms on the designated atom or moiety or group may be replaced or not replaced by an atom or moiety or group other than hydrogen. By way of illustration and not limitation, the phrase “methyl optionally substituted with one or more chloro” encompasses -CH3, -CH2Cl, -CHCl2, and -CCl3 moieties. It is understood that aspects and embodiments described herein as “comprising” include “consisting of” and “consisting essentially of” embodiments. The term “pharmaceutically acceptable salt”, as used herein, of a given compound refers to salts that retain the biological effectiveness and properties of the given compound and which are not biologically or otherwise undesirable. “Pharmaceutically acceptable salts” include, for example, salts with inorganic acids, and salts with an organic acid. In addition, if the compounds described herein are obtained as an acid addition salt, the free base can be obtained by basifying a solution of the acid salt. Conversely, if the product is a free base, an addition salt, particularly a pharmaceutically acceptable addition salt, may be produced by dissolving the free base in a suitable organic solvent and treating the solution with an acid, in accordance with conventional procedures for preparing acid addition salts from base compounds. See, e.g., Handbook of Pharmaceutical Salts Properties, Selection, and Use, International Union of Pure and Applied Chemistry, John Wiley & Sons (2008), which isincorporated herein by reference in its entirety. Those skilled in the art will recognize various Attorney Docket No.: 185992002140 synthetic methodologies that may be used to prepare nontoxic pharmaceutically acceptable addition salts. Pharmaceutically acceptable acid addition salts may be prepared from inorganic or organic acids. Salts derived from inorganic acids include, e.g., hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like. Salts derived from organic acids include, e.g., acetic acid, propionic acid, gluconic acid, glycolic acid, pyruvic acid, oxalic acid, malic acid, malonic acid, succinic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluene-sulfonic acid, salicylic acid, trifluoroacetic acid, and the like. Likewise, pharmaceutically acceptable base addition salts can be prepared from inorganic or organic bases. Salts derived from inorganic bases include, by way of example only, sodium, potassium, lithium, aluminum, ammonium, calcium, and magnesium salts. Salts derived from organic bases include, but are not limited to, salts of primary, secondary, and tertiary amines. Specific examples of suitable amines include, by way of example only, isopropylamine, trimethyl amine, diethyl amine, tri(iso-propyl) amine, tri(n-propyl) amine, ethanolamine, 2-dimethylaminoethanol, piperazine, piperidine, morpholine, N- ethylpiperidine, and the like. Isotopically labeled forms of the compounds depicted herein may be prepared. Isotopically labeled compounds have structures depicted herein, except that one or more atoms are replaced by an atom having a selected atomic mass or mass number. Examples of isotopes that can be incorporated into the disclosed compounds include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, fluorine, chlorine, and iodine, such as2H,3H,11C,13C,14C,13N,15N,15O,17O,18O,31P,32P,35S,18F,36Cl,123I, and125I, respectively. In someembodiments, a compound of formula (I) is provided wherein one or more hydrogen isreplaced by deuterium or tritium. Some of the compounds provided herein may exist as tautomers. Tautomers are in equilibrium with one another. By way of illustration, amide containing compounds may exist in equilibrium with imidic acid tautomers. Regardless of which tautomer is shown and regardless of the nature of the equilibrium among tautomers, the compounds of this disclosure are understood by one of ordinary skill in the art to comprise both amide and imidic acid tautomers. Thus, for example, amide-containing compounds are understood to include their imidic acid tautomers. Likewise, imidic-acid containing compounds are understood to include their amide tautomers. Attorney Docket No.: 185992002140 Also provided herein are prodrugs of the compounds depicted herein, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvatethereof. In some embodiments, provided herein are prodrugs of the compounds depictedherein, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof. Prodrugs are compounds that may be administered to an individual and release, in vivo, a compound depicted herein as the parent drug compound. It is understood that prodrugs may be prepared by modifying a functional group on a parent drug compound in such a way thatthe modification is cleaved in vitro or in vivo to release the parent drug compound. See, e.g.,Rautio, J., Kumpulainen, H., Heimbach, T. et al. Prodrugs: design and clinical applications.Nat Rev Drug Discov 7, 255–270 (2008), which is incorporated herein by reference in itsentirety. The compounds of the present disclosure, or their pharmaceutically acceptable salts,hydrates, or solvates may include an asymmetric center and may thus give rise toenantiomers, diastereomers, and other stereoisomeric forms that may be defined, in terms ofabsolute stereochemistry, as (R)- or (S)- (or as (D)- or (L)- for amino acids). The presentdisclosure is meant to include all such possible isomers, as well as their racemic and opticallypure forms and mixtures thereof in any ratio. Optically active (+) and (-), (R)- and (S)-, or(D)- and (L)- isomers may be prepared using chiral synthons or chiral reagents, or may beresolved using conventional techniques, for example, chromatography and / or fractional crystallization. Conventional techniques for the preparation / isolation of individual enantiomers include chiral synthesis from a suitable optically pure precursor or the resolution of the racemate (or the racemate of a salt or derivative) using, for example, chiral high pressure liquid chromatography (HPLC), and chiral supercritical fluid chromatography(SFC). When the compounds described herein contain olefinic double bonds or other centersof geometric asymmetry, unless specified otherwise, it is intended that the present disclosureincludes both E and Z geometric isomers. Likewise, cis- and trans- are used in theirconventional sense to describe relative spatial relationships. A “stereoisomer” refers to a compound made up of the same atoms bonded by the same bonds, but having different three-dimensional structures, which are not interchangeable.The present disclosure contemplates various stereoisomers, or mixtures thereof, and includes“enantiomers,” which refers to two stereoisomers whose structures are non-superimposable mirror images of one another. “Diastereomers” are stereoisomers that have at least two asymmetric atoms, but which are not mirror images of each other. Attorney Docket No.: 185992002140 Where enantiomeric and / or diastereomeric forms exist of a given structure, flat bondsindicate a mixture of stereoisomeric forms of the depicted structure may be present. Wherethe composition is made up of at least 90%, by weight, dashes or wedges with or without thepresence of an “(S)” or “(R)” designation indicate a single enantiomer or diastereomer withknown relative or absolute stereochemistry.COMPOUNDS In one aspect, provided herein is a compound of formula (I) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, orsolvate of any of the foregoing, whereinR1 and R2 are each independently H, C1-6alkyl, C2-6alkenyl, -C(=O)R12, -C(=O)OR12, - C(=O)N(R11)(R12), -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 12-memberedheterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, whereinthe C1-6alkyl of R1 or R2 is optionally substituted with one or more R1a,the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to10-membered heteroaryl of R1 or R2 is optionally substituted with one or more R1b,and optionally, two substituents of the C1-6alkyl, C2-6alkenyl, -C(=O)R12, -C(=O)OR12, - C(=O)N(R11)(R12), -S(=O)2R12, -S(=O)2N(R11)(R12), or C3-8cycloalkyl group of R1or R2 are taken together with the atoms to which they are attached to form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl,or 5- to 10-membered heteroaryl is optionally substituted with one or moreR1b; Attorney Docket No.: 185992002140 or R1and R2are taken together with the N to which they are attached to form a 3- to 12- membered heterocyclyl or 5- to 10-membered heteroaryl, wherein 3- to 12-membered heterocyclyl or 5- to 10-membered heteroaryl of R1and R2is optionally substituted with one or more R3; each R3is independently halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, oxo, -OR10, -SR10, -SF5, - N(Rx)(Ry), -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, - OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), - C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, - S(=NR13)N(R11)R12, -S(=NR13)OR13, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R3is optionally substituted with one or more R3a; the C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with one or more R3b; and optionally, two substituents of R3are taken together with the atoms to which they are attached form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10- membered aryl, or 5- to 10-membered heteroaryl is optionally substituted one or more R3b; Ring A is C3-8cycloalkyl, 4- to 12-membered cycloalkenyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 4- to 12-membered cycloalkenyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of Ring A is optionally substituted by one or more R4, and the 3- to 12-membered heterocyclyl or 5- to 10-membered heteroaryl of Ring A comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; each R4is independently halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -OR10, -SR10, -SF5, - N(Rx)(Ry), -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, - OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), - C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, - Attorney Docket No.: 185992002140 S(=NR13)N(R11)R12, -S(=NR13)OR13, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R4is optionally substituted by one or more R4a, the C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R4is optionally substituted with one or more R4b, and the 3- to 8-membered heterocyclyl of R4comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; L is a bond, C1-6alkyl, -O-(C1-6alkyl)-, -S-(C1-6alkyl)-, or -N(R5)(C1-6alkyl)-, wherein the C1-6alkyl, -O-(C1-6alkyl)-, -S-(C1-6alkyl)-, or -N(R5)(C1-6alkyl)- is optionally substituted by one or more RL; each RLis independently halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, -OC(=O)N(R11)R12, - OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, C3-8cycloalkyl, 3- to 8- membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, or two RLare taken together along with the atoms to which they are attached to form a C3-8cycloalkyl or 3- to 8-membered heterocyclyl; R5is H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -C(=O)R12, -S(=O)2R12, -S(=O)2N(R11)(R12), or C3-8cycloalkyl, wherein the C1-6alkyl of R5is optionally substituted with one or more halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, - OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), - C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, - S(=NR13)N(R11)R12, -S(=NR13)OR13, -S(=O)2R12, or -S(=O)2N(R11)(R12), and the C3-8cycloalkyl is optionally substituted with one or more R5b; R6is H, halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -OR9, -OR10, -SR10, -SF5, -N(Rx)(Ry), - NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, - OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, - C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, -N(R11)S(=O)2R12, - S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, -S(=NR13)N(R11)R12, - S(=NR13)OR13, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R6is optionally substituted by one or more R6a, Attorney Docket No.: 185992002140 the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R6is optionally substituted with one or more R6b, - C(=O)R12, -C(=O)N(R11)(R12), or -C(=O)OR12, and the 3- to 12-membered heterocyclyl of R6comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S, and optionally, two substituents of R6are taken together with the atoms to which they are attached form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with one or more R6b; R7and R8are each independently H, halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -OR9, -OR10, - SR10, -SF5, -N(Rx)(Ry), -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, - N(R11)C(=O)OR12, -OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, - C(=O)N(R11)(R12), -C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, - C(=NR13)OR12, -N(R11)S(=O)2R12, -S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, -S(=NR13)N(R13)R12, -S(=NR13)OR12, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R7or R8is optionally substituted by one or more R7a, the 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R7or R8is optionally substituted with one or more R7b, and the 3- to 8-membered heterocyclyl of R7or R8comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S, and optionally, two substituents of R7or R8are taken together with the atoms to which they are attached form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10- membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with one or more R7b; each R1a, R3a, R4a, R6a, or R7ais independently halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -NO2, - CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, - OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, - C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, -N(R11)S(=O)2R12, - Attorney Docket No.: 185992002140 S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, -S(=NR13)N(R13)R12, - S(=NR13)OR12, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R1a, R3a, R4a, R6a, or R7ais optionally substituted with one or more R1b, and the 3- to 12-membered heterocyclyl of R1a, R3a, R4a, R6a, or R7acomprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; each R1b, R3b, R4b, R5b, R6b, or R7bis independently halo, C1-6alkyl, -OR9, -N(Rx)(Ry), oxo, - CN, C3-8cycloalkyl, or 3- to 8-membered heterocyclyl, wherein the C1-6alkyl of R1b, R3b, R4b, R5b, R6b, or R7bis optionally substituted by -OR12, - N(Rx)(Ry), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl; each R9is independently H, C1-6alkyl, C2-6alkenyl, C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R9is optionally substituted with 6- to 10-membered aryl, or 5- to 10- membered heteroaryl wherein the 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, or -N(Rx)(Ry), and the 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R9is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, -N(Rx)(Ry), or 3- to 12-membered heterocyclyl; each R10is independently H, C1-6alkyl, C2-6alkenyl, C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl is optionally substituted with one or more halo, deuterium, C1- 6alkoxy, -N(Rx)(Ry), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10- membered aryl, or 5- to 10-membered heteroaryl wherein the C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with halo, C1-3alkyl, C1- 3alkoxy, or -N(Rx)(Ry); each R11is independently H, C1-6alkyl, or C3-8cycloalkyl; each R12is independently H, C1-6alkyl, C2-6alkenyl, C3-8cycloalkyl, 6- to 10-membered aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein Attorney Docket No.: 185992002140 the C1-6alkyl of R12is optionally substituted by one or more halo, -OH, -O(C1-6alkyl), -SH, -S(C1-6alkyl), -(C=O)NH2, -(C=O)OH, -O(C=O)C1-8alkyl), -NH(C=NH)NH2, - N(Rx)(Ry), C3-8cycloalkyl, 6- to 10-membered aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the 6- to 10-membered aryl is optionally substituted by -OH, and the C3-8cycloalkyl, 6- to 10-membered aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl of R12is optionally substituted with halo, C1-6alkyl, or - N(Rx)(Ry); each R13is independently H or C1-6alkyl; and each Rxand Ryis independently H, C1-6alkyl, C3-8cycloalkyl, -C(=O)(C1-6alkyl), or - C(=O)O(C1-6alkyl), wherein the C1-6alkyl of Rxor Ryis optionally substituted with 6- to 10-membered aryl, 5- to 10-membered heteroaryl, or -NH2, NH(C1-6alkyl), or -N(C1-6alkyl)(C1-6alkyl), and the C1-6alkyl of -C(=O)(C1-6alkyl) or -C(=O)O(C1-6alkyl) is optionally substituted with -O(C=O)C1-8alkyl); wherein(i) when -(Ring A)-L-R6 are taken together to form , and R1 is H, R8 is not optionallysubstituted pyrazolyl; (ii) when R1and R2are taken together with the N to which they are attached and Ring A is 5-membered N-containing heteroaryl, then L-R6are not taken together to form halo, pyridyl substituted by methyl, or substituted phenyl; and(iii) when -(Ring A)-L-R6 are taken together to form , R1 is H, and R2 is -CH3, R8is not -CH3. In some embodiments of the above, the compound is a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing. Attorney Docket No.: 185992002140 In one aspect, provided herein is a compound of formula (I) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, orsolvate of any of the foregoing, whereinR1 and R2 are each independently H, C1-6alkyl, C2-6alkenyl, -C(=O)R12, -C(=O)OR12, - C(=O)N(R11)(R12), -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 12-memberedheterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, whereinthe C1-6alkyl of R1 or R2 is optionally substituted with one or more R1a,the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to10-membered heteroaryl of R1 or R2 is optionally substituted with one or more R1b,and optionally, two substituents of the C1-6alkyl, C2-6alkenyl, -C(=O)R12, -C(=O)OR12, - C(=O)N(R11)(R12), -S(=O)2R12, -S(=O)2N(R11)(R12), or C3-8cycloalkyl group of R1or R2 are taken together with the atoms to which they are attached to form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl,or 5- to 10-membered heteroaryl is optionally substituted with one or moreR1b;or R1 and R2 are taken together with the N to which they are attached to form a 3- to 12-membered heterocyclyl or 5- to 10-membered heteroaryl, wherein3- to 12-membered heterocyclyl or 5- to 10-membered heteroaryl of R1 and R2 isoptionally substituted with one or more R3; each R3is independently halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, oxo, -OR10, -SR10, -SF5, -N(Rx)(Ry), -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, - OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), - C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - Attorney Docket No.: 185992002140 N(R11)S(=O)2R12, -S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, - S(=NR13)N(R11)R12, -S(=NR13)OR13, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R3is optionally substituted with one or more R3a, and optionally, two substituents of R3are taken together with the atoms to which they are attached form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10- membered aryl, or 5- to 10-membered heteroaryl is optionally substituted one or more R3b; Ring A is C3-8cycloalkyl, 4- to 12-membered cycloalkenyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 4- to 12-membered cycloalkenyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of Ring A is optionally substituted by one or more R4, and the 3- to 12-membered heterocyclyl or 5- to 10-membered heteroaryl of Ring A comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; each R4is independently halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -OR10, -SR10, -SF5, - N(Rx)(Ry), -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, - OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), - C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, - S(=NR13)N(R11)R12, -S(=NR13)OR13, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R4is optionally substituted by one or more R4a, the C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R4is optionally substituted with one or more R4b, and the 3- to 8-membered heterocyclyl of R4comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; L is a bond, C1-6alkyl, -O-(C1-6alkyl)-, -S-(C1-6alkyl)-, or -N(R5)(C1-6alkyl)-, wherein the C1-6alkyl, -O-(C1-6alkyl)-, -S-(C1-6alkyl)-, or -N(R5)(C1-6alkyl)- is optionally substituted by one or more RL; Attorney Docket No.: 185992002140 each RLis independently halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, -OC(=O)N(R11)R12, - OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, C3-8cycloalkyl, 3- to 8- membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, or two RLare taken together along with the atoms to which they are attached to form a C3-8cycloalkyl or 3- to 8-membered heterocyclyl; R5is H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -C(=O)R12, -S(=O)2R12, -S(=O)2N(R11)(R12), or C3-8cycloalkyl, wherein the C1-6alkyl of R5is optionally substituted with one or more halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, - OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), - C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, - S(=NR13)N(R11)R12, -S(=NR13)OR13, -S(=O)2R12, or -S(=O)2N(R11)(R12), and the C3-8cycloalkyl is optionally substituted with one or more R5b; R6is H, halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -OR9, -OR10, -SR10, -SF5, -N(Rx)(Ry), - NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, - OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, - C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, -N(R11)S(=O)2R12, - S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, -S(=NR13)N(R11)R12, - S(=NR13)OR13, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R6is optionally substituted by one or more R6a, the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R6is optionally substituted with one or more R6b, - C(=O)R12, -C(=O)N(R11)(R12), or -C(=O)OR12, and the 3- to 12-membered heterocyclyl of R6comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S, and optionally, two substituents of R6are taken together with the atoms to which they are attached form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein Attorney Docket No.: 185992002140 the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with one or more R6b; R7and R8are each independently H, halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -OR9, -OR10, - SR10, -SF5, -N(Rx)(Ry), -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, - N(R11)C(=O)OR12, -OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, - C(=O)N(R11)(R12), -C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, - C(=NR13)OR12, -N(R11)S(=O)2R12, -S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, -S(=NR13)N(R13)R12, -S(=NR13)OR12, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R7or R8is optionally substituted by one or more R7a, the 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R7or R8is optionally substituted with one or more R7b, and the 3- to 8-membered heterocyclyl of R7or R8comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S, and optionally, two substituents of R7or R8are taken together with the atoms to which they are attached form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10- membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with one or more R7b; each R1a, R3a, R4a, R6a, or R7ais independently halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -NO2, - CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, - OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, - C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, -N(R11)S(=O)2R12, - S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, -S(=NR13)N(R13)R12, - S(=NR13)OR12, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R1a, R3a, R4a, R6a, or R7ais optionally substituted with one or more R1b, and the 3- to 12-membered heterocyclyl of R1a, R3a, R4a, R6a, or R7acomprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; Attorney Docket No.: 185992002140 each R1b, R3b, R4b, R5b, R6b, or R7bis independently halo, C1-6alkyl, -OR9, -N(Rx)(Ry), oxo, - CN, C3-8cycloalkyl, or 3- to 8-membered heterocyclyl, wherein the C1-6alkyl of R1b, R3b, R4b, R5b, R6b, or R7bis optionally substituted by -OR12, - N(Rx)(Ry), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl; each R9is independently H, C1-6alkyl, C2-6alkenyl, C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R9is optionally substituted with 6- to 10-membered aryl, or 5- to 10- membered heteroaryl wherein the 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, or -N(Rx)(Ry), and the 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R9is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, -N(Rx)(Ry), or 3- to 12-membered heterocyclyl; each R10is independently H, C1-6alkyl, C2-6alkenyl, C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl is optionally substituted with one or more halo, deuterium, C1-6alkoxy, -N(Rx)(Ry), or 3- to 8-membered heterocyclyl; each R11is independently H, C1-6alkyl, or C3-8cycloalkyl; each R12is independently H, C1-6alkyl, C2-6alkenyl, C3-8cycloalkyl, 6- to 10-membered aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1-6alkyl of R12is optionally substituted by one or more halo, -OH, -O(C1-6alkyl), -SH, -S(C1-6alkyl), -(C=O)NH2, -(C=O)OH, -O(C=O)C1-8alkyl), -NH(C=NH)NH2, - N(Rx)(Ry), C3-8cycloalkyl, 6- to 10-membered aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the 6- to 10-membered aryl is optionally substituted by -OH, and the C3-8cycloalkyl, 6- to 10-membered aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl of R12is optionally substituted with halo, C1-6alkyl, or - N(Rx)(Ry); each R13is independently H or C1-6alkyl; and each Rxand Ryis independently H, C1-6alkyl, C3-8cycloalkyl, -C(=O)(C1-6alkyl), or - C(=O)O(C1-6alkyl), wherein Attorney Docket No.: 185992002140 the C1-6alkyl of Rx or Ry is optionally substituted with 6- to 10-membered aryl, 5- to10-membered heteroaryl, or -NH2, NH(C1-6alkyl), or -N(C1-6alkyl)(C1-6alkyl), and the C1-6alkyl of -C(=O)(C1-6alkyl) or -C(=O)O(C1-6alkyl) is optionally substituted with-O(C=O)C1-8alkyl). In some embodiments of the above, the compound is a compoundof formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt any of the foregoing. In some embodiments of a compound of formula (I), or any variation or embodimentthereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate,or solvate of any of the foregoing,R1 is H, C1-6alkyl, C2-6alkenyl, -C(=O)R12, -C(=O)OR12, -C(=O)N(R11)(R12), -S(=O)2R12, - S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl,or 5- to 10-membered heteroaryl, whereinthe C1-6alkyl of R1is optionally substituted with one or more R1a, the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to10-membered heteroaryl of R1 is optionally substituted with one or more R1b, andoptionally, two substituents of the C1-6alkyl, C2-6alkenyl, -C(=O)R12, -C(=O)OR12, - C(=O)N(R11)(R12), -S(=O)2R12, -S(=O)2N(R11)(R12), or C3-8cycloalkyl group of R1are taken together with the atoms to which they are attached to form a C3-8cycloalkyl, 3-to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-memberedheteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl,or 5- to 10-membered heteroaryl is optionally substituted with one or moreR1b; R2is C1-6alkyl, C2-6alkenyl, -C(=O)R12, -C(=O)OR12, -C(=O)N(R11)(R12), -S(=O)2R12, - S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl,or 5- to 10-membered heteroaryl, whereinthe C1-6alkyl of R2is optionally substituted with one or more R1a, the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to10-membered heteroaryl of R2 is optionally substituted with one or more R1b, andoptionally, two substituents of the C1-6alkyl, C2-6alkenyl, -C(=O)R12, -C(=O)OR12, - C(=O)N(R11)(R12), -S(=O)2R12, -S(=O)2N(R11)(R12), or C3-8cycloalkyl group of R2are taken together with the atoms to which they are attached to form a C3-8cycloalkyl, 3- Attorney Docket No.: 185992002140 to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with one or more R1b; or R1and R2are taken together with the N to which they are attached to form a 3- to 12- membered heterocyclyl or 5- to 10-membered heteroaryl, wherein 3- to 12-membered heterocyclyl or 5- to 10-membered heteroaryl of R1and R2is optionally substituted with one or more R3; each R3is independently halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, oxo, -OR10, -SR10, -SF5, - N(Rx)(Ry), -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, - OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), - C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, - S(=NR13)N(R11)R12, -S(=NR13)OR13, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R3is optionally substituted with one or more R3a, and optionally, two substituents of R3are taken together with the atoms to which they are attached form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10- membered aryl, or 5- to 10-membered heteroaryl is optionally substituted one or more R3b; Ring A is C3-8cycloalkyl, 4- to 12-membered cycloalkenyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 4- to 12-membered cycloalkenyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of Ring A is optionally substituted by one or more R4, and the 3- to 12-membered heterocyclyl or 5- to 10-membered heteroaryl of Ring A comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; each R4is independently halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -OR10, -SR10, -SF5, - N(Rx)(Ry), -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, - OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), - Attorney Docket No.: 185992002140 C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, - S(=NR13)N(R11)R12, -S(=NR13)OR13, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R4is optionally substituted by one or more R4a, the C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R4is optionally substituted with one or more R4b, and the 3- to 8-membered heterocyclyl of R4comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; L is a bond, C1-6alkyl, -O-(C1-6alkyl)-, -S-(C1-6alkyl)-, or -N(R5)(C1-6alkyl)-, wherein the C1-6alkyl, -O-(C1-6alkyl)-, -S-(C1-6alkyl)-, or -N(R5)(C1-6alkyl)- is optionally substituted by one or more RL; each RLis independently halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, -OC(=O)N(R11)R12, - OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, C3-8cycloalkyl, 3- to 8- membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, or two RLare taken together along with the atoms to which they are attached to form a C3-8cycloalkyl or 3- to 8-membered heterocyclyl; R5is H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -C(=O)R12, -S(=O)2R12, -S(=O)2N(R11)(R12), or C3-8cycloalkyl, wherein the C1-6alkyl of R5is optionally substituted with one or more halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, - OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), - C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, - S(=NR13)N(R11)R12, -S(=NR13)OR13, -S(=O)2R12, or -S(=O)2N(R11)(R12), and the C3-8cycloalkyl is optionally substituted with one or more R5b; R6is H, halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -OR9, -OR10, -SR10, -SF5, -N(Rx)(Ry), - NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, - OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, - C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, -N(R11)S(=O)2R12, - S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, -S(=NR13)N(R11)R12, - Attorney Docket No.: 185992002140 S(=NR13)OR13, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R6is optionally substituted by one or more R6a, the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R6is optionally substituted with one or more R6b, - C(=O)R12, -C(=O)N(R11)(R12), or -C(=O)OR12, and the 3- to 12-membered heterocyclyl of R6comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S, and optionally, two substituents of R6are taken together with the atoms to which they are attached form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with one or more R6b; R7is H, halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -OR9, -OR10, -SR10, -SF5, -N(Rx)(Ry), - NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, - OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, - C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, -N(R11)S(=O)2R12, - S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, -S(=NR13)N(R13)R12, - S(=NR13)OR12, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R7is optionally substituted by one or more R7a, the 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R7is optionally substituted with one or more R7b, and the 3- to 8-membered heterocyclyl of R7comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S, and optionally, two substituents of R7are taken together with the atoms to which they are attached form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with one or more R7b; and Attorney Docket No.: 185992002140 R8is halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -OR9, -OR10, -SR10, -SF5, -N(Rx)(Ry), -NO2, - CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, - OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, - C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, -N(R11)S(=O)2R12, - S(=O)R12, -S(=O)2R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, -S(=NR13)N(R13)R12, - S(=NR13)OR12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10- membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R8is optionally substituted by one or more R7a, the 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R8is optionally substituted with one or more R7b, and the 3- to 8-membered heterocyclyl of R8comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S, and optionally, two substituents of R8are taken together with the atoms to which they are attached form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with one or more R7b; each R1a, R3a, R4a, R6a, or R7ais independently halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -NO2, - CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, - OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, - C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, -N(R11)S(=O)2R12, - S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, -S(=NR13)N(R13)R12, - S(=NR13)OR12, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R1a, R3a, R4a, R6a, or R7ais optionally substituted with one or more R1b, and the 3- to 12-membered heterocyclyl of R1a, R3a, R4a, R6a, or R7acomprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; each R1b, R3b, R4b, R5b, R6b, or R7bis independently halo, C1-6alkyl, -OR9, -N(Rx)(Ry), oxo, - CN, C3-8cycloalkyl, or 3- to 8-membered heterocyclyl, wherein Attorney Docket No.: 185992002140 the C1-6alkyl of R1b, R3b, R4b, R5b, R6b, or R7bis optionally substituted by -OR12, - N(Rx)(Ry), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl; each R9is independently H, C1-6alkyl, C2-6alkenyl, C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R9is optionally substituted with 6- to 10-membered aryl, or 5- to 10- membered heteroaryl wherein the 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, or -N(Rx)(Ry), and the 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R9is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, -N(Rx)(Ry), or 3- to 12-membered heterocyclyl; each R10is independently H, C1-6alkyl, C2-6alkenyl, C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl is optionally substituted with one or more halo, deuterium, C1-6alkoxy, -N(Rx)(Ry), or 3- to 8-membered heterocyclyl; each R11is independently H, C1-6alkyl, or C3-8cycloalkyl; each R12is independently H, C1-6alkyl, C2-6alkenyl, C3-8cycloalkyl, 6- to 10-membered aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1-6alkyl of R12is optionally substituted by one or more halo, -OH, -O(C1-6alkyl), -SH, -S(C1-6alkyl), -(C=O)NH2, -(C=O)OH, -O(C=O)C1-8alkyl), -NH(C=NH)NH2, - N(Rx)(Ry), C3-8cycloalkyl, 6- to 10-membered aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the 6- to 10-membered aryl is optionally substituted by -OH, and the C3-8cycloalkyl, 6- to 10-membered aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl of R12is optionally substituted with halo, C1-6alkyl, or - N(Rx)(Ry); each R13is independently H or C1-6alkyl; and each Rxand Ryis independently H, C1-6alkyl, C3-8cycloalkyl, -C(=O)(C1-6alkyl), or - C(=O)O(C1-6alkyl), wherein the C1-6alkyl of Rxor Ryis optionally substituted with 6- to 10-membered aryl, 5- to 10-membered heteroaryl, or -NH2, NH(C1-6alkyl), or -N(C1-6alkyl)(C1-6alkyl), and Attorney Docket No.: 185992002140 the C1-6alkyl of -C(=O)(C1-6alkyl) or -C(=O)O(C1-6alkyl) is optionally substituted with-O(C=O)C1-8alkyl); wherein (i) when -(Ring A)-L-R6 are taken together to form , and R1 is H, R8 is notoptionally substituted pyrazolyl; (ii) when R1and R2are taken together with the N to which they are attached to form ,-(Ring A)-L-R6 are not taken together to form a pyrazolyl substituted by 3-methylphenyl; and (iii) when -(Ring A)-L-R6 are taken together to form , R1 is H, and R2 is -CH3,R8 is not -CH3. In some embodiments of the above, the compound is a compound offormula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt any of the foregoing. In some embodiments of a compound of formula (I), or any variation or embodimentthereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate,or solvate of any of the foregoing,R1 is H, C1-6alkyl, C2-6alkenyl, -C(=O)R12, -C(=O)OR12, -C(=O)N(R11)(R12), or C3-8cycloalkyl, wherein the C1-6alkyl of R1is optionally substituted with one or more R1a, the C3-8cycloalkyl of R1is optionally substituted with one or more R1b, and optionally, two substituents of the C1-6alkyl, C2-6alkenyl, -C(=O)R12, -C(=O)OR12, - C(=O)N(R11)(R12), or C3-8cycloalkyl group of R1are taken together with the atoms to which they are attached to form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6-to 10-membered aryl, or 5- to 10-membered heteroaryl, whereinthe C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl,or 5- to 10-membered heteroaryl is optionally substituted with one or moreR1b; R2is C1-6alkyl, C2-6alkenyl, -C(=O)R12, -C(=O)OR12, -C(=O)N(R11)(R12), or C3-8cycloalkyl, wherein Attorney Docket No.: 185992002140 the C1-6alkyl of R2is optionally substituted with one or more R1a, the C3-8cycloalkyl of R2is optionally substituted with one or more R1b, and optionally, two substituents of the C1-6alkyl, C2-6alkenyl, -C(=O)R12, -C(=O)OR12, - C(=O)N(R11)(R12), or C3-8cycloalkyl group of R2are taken together with the atoms to which they are attached to form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with one or more R1b; or R1and R2are taken together with the N to which they are attached to form a 3- to 12- membered heterocyclyl or 5- to 10-membered heteroaryl, wherein 3- to 12-membered heterocyclyl or 5- to 10-membered heteroaryl of R1and R2is optionally substituted with one or more R3; each R3is independently halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, oxo, -OR10, -SR10, -SF5, - N(Rx)(Ry), -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, - OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), - C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R3is optionally substituted with one or more R3a, and optionally, two substituents of R3are taken together with the atoms to which they are attached form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10- membered aryl, or 5- to 10-membered heteroaryl is optionally substituted one or more R3b; Ring A is C3-8cycloalkyl, 4- to 8-membered cycloalkenyl, 3- to 8-membered heterocyclyl, phenyl, or 5- to 6-membered heteroaryl, wherein the C3-8cycloalkyl, 4- to 8-membered cycloalkenyl, 3- to 8-membered heterocyclyl, phenyl, or 5- to 6-membered heteroaryl of Ring A is optionally substituted by one or more R4, and the 3- to 8-membered heterocyclyl or 5- to 6-membered heteroaryl of Ring A comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; Attorney Docket No.: 185992002140 each R4is independently halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -OR10, -SR10, -SF5, - N(Rx)(Ry), -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, - OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), - C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R4is optionally substituted by one or more R4a, the C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R4is optionally substituted with one or more R4b, and the 3- to 8-membered heterocyclyl of R4comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; L is a bond, C1-6alkyl, -O-(C1-6alkyl)-, -S-(C1-6alkyl)-, or -N(R5)(C1-6alkyl)-, wherein the C1-6alkyl, -O-(C1-6alkyl)-, -S-(C1-6alkyl)-, or -N(R5)(C1-6alkyl)- is optionally substituted by one or more RL; each RLis independently halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, -OC(=O)N(R11)R12, - OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, C3-8cycloalkyl, 3- to 8- membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, or two RLare taken together along with the atoms to which they are attached to form a C3-8cycloalkyl or 3- to 8-membered heterocyclyl; R5is H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -C(=O)R12, -S(=O)2R12, -S(=O)2N(R11)(R12), or C3-8cycloalkyl, wherein the C1-6alkyl of R5is optionally substituted with one or more halo, -N(Rx)(Ry), -OR10, -SR10, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, - OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, - C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)2R12, or -S(=O)2N(R11)(R12), and the C3-8cycloalkyl is optionally substituted with one or more R5b; R6is H, halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -OR9, -OR10, -SR10, -SF5, -N(Rx)(Ry), - NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, - OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, - C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, -N(R11)S(=O)2R12, - Attorney Docket No.: 185992002140 S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10- membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R6is optionally substituted by one or more R6a, the C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R6is optionally substituted with one or more R6b, - C(=O)R12, -C(=O)N(R11)(R12), or -C(=O)OR12, and the 3- to 8-membered heterocyclyl of R6comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S, and optionally, two substituents of R6are taken together with the atoms to which they are attached form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with one or more R6b; R7is H, halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -OR9, -OR10, -SR10, -SF5, -N(Rx)(Ry), - NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, - OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, - C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, -N(R11)S(=O)2R12, - S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10- membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R7is optionally substituted by one or more R7a, the 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R7is optionally substituted with one or more R7b, and the 3- to 8-membered heterocyclyl of R7comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S, and optionally, two substituents of R7are taken together with the atoms to which they are attached form a 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10- membered heteroaryl, wherein the 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10- membered heteroaryl is optionally substituted with one or more R7b; and R8is halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -OR9, -OR10, -SR10, -SF5, -N(Rx)(Ry), -NO2, - CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, - OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, - Attorney Docket No.: 185992002140 C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, -N(R11)S(=O)2R12, - S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10- membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R8is optionally substituted by one or more R7a, the 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R8is optionally substituted with one or more R7b, and the 3- to 8-membered heterocyclyl of R8comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S, and optionally, two substituents of R8are taken together with the atoms to which they are attached form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with one or more R7b; each R1a, R3a, R4a, R6a, or R7ais independently halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -NO2, - CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, - OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, - C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, -N(R11)S(=O)2R12, - S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10- membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R1a, R3a, R4a, R6a, or R7ais optionally substituted with one or more R1b, and the 3- to 12-membered heterocyclyl of R1a, R3a, R4a, R6a, or R7acomprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; each R1b, R3b, R4b, R5b, R6b, or R7bis independently halo, C1-6alkyl, -OR9, -N(Rx)(Ry), oxo, - CN, C3-8cycloalkyl, or 3- to 8-membered heterocyclyl, wherein the C1-6alkyl of R1b, R3b, R4b, R5b, R6b, or R7bis optionally substituted by -OR12, - N(Rx)(Ry), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, phenyl, or 5- to 6- membered heteroaryl; each R9is independently H, C1-6alkyl, C2-6alkenyl, C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein Attorney Docket No.: 185992002140 the C1-6alkyl of R9is optionally substituted with 6- to 10-membered aryl, or 5- to 10- membered heteroaryl wherein the 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, or -N(Rx)(Ry), and the 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R9is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, -N(Rx)(Ry), or 3- to 12-membered heterocyclyl; each R10is independently H, C1-6alkyl, C2-6alkenyl, C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl is optionally substituted with one or more halo, deuterium, C1- 6alkoxy, -N(Rx)(Ry), or 3- to 8-membered heterocyclyl; each R11is independently H, C1-6alkyl, or C3-8cycloalkyl; each R12is independently H, C1-6alkyl, C2-6alkenyl, C3-8cycloalkyl, phenyl, 5- to 6-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1-6alkyl of R12is optionally substituted by one or more halo, -OH, -O(C1-6alkyl), -N(Rx)(Ry), C3-8cycloalkyl, phenyl, 5- to 6-membered heteroaryl, or 3- to 12- membered heterocyclyl, and the C3-8cycloalkyl, phenyl, 5- to 6-membered heteroaryl, or 3- to 12-membered heterocyclyl of R12is optionally substituted with halo, C1-6alkyl, or -N(Rx)(Ry); each R13is independently H or C1-6alkyl; and each Rxand Ryis independently H, C1-6alkyl, C3-8cycloalkyl, -C(=O)(C1-6alkyl), or - C(=O)O(C1-6alkyl), wherein the C1-6alkyl of Rxor Ryis optionally substituted with 6- to 10-membered aryl, 5- to 10-membered heteroaryl, or -NH2, NH(C1-6alkyl), or -N(C1-6alkyl)(C1-6alkyl), and the C1-6alkyl of -C(=O)(C1-6alkyl) or -C(=O)O(C1-6alkyl) is optionally substituted with -O(C=O)C1-8alkyl); wherein (i) when -(Ring A)-L-R6are taken together to form , and R1is H, R8is not optionally substituted pyrazolyl; Attorney Docket No.: 185992002140 (ii) when R1and R2are taken together with the N to which they are attached to form ,-(Ring A)-L-R6 are not taken together to form a pyrazolyl substituted by 3-methylphenyl; and (iii) when -(Ring A)-L-R6are taken together to form , R1is H, and R2is - CH3, R8 is not -CH3. In some embodiments of the above, the compound is acompound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt any of the foregoing. In some embodiments of a compound of formula (I), or any variation or embodimentthereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate,or solvate of any of the foregoing, R1is H or C1-6alkyl; R2is C1-6alkyl or C3-6cycloalkyl, wherein the C1-6alkyl or C3-6cycloalkyl of R2 is optionally substituted with one or more -OH or-N(Rx)(Ry),or R1 and R2 are taken together with the N to which they are attached to form a 3- to 12-membered heterocyclyl, wherein 3- to 12-membered heterocyclyl of R1 and R2 is optionally substituted with one ormore R3; each R3is independently halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, oxo, -OR10, -SR10, -SF5, -N(Rx)(Ry), -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, - OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), - C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, -S(=NR13)N(R11)R12, -S(=NR13)OR13, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, whereinthe C1-6alkyl of R3is optionally substituted with one or more R3a, and Attorney Docket No.: 185992002140 optionally, two substituents of R3are taken together with the atoms to which they are attached form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10- membered aryl, or 5- to 10-membered heteroaryl is optionally substituted one or more R3b; Ring A is phenyl or 5- to 6-membered heteroaryl, wherein the phenyl or 5- to 6-membered heteroaryl of Ring A is optionally substituted by one or more R4, and the 5- to 6-membered heteroaryl of Ring A comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; each R4is independently halo or -OR10; L is a bond, C1-6alkyl, -O-(C1-6alkyl)-, -S-(C1-6alkyl)-, or -N(R5)(C1-6alkyl)-, wherein the C1-6alkyl, -O-(C1-6alkyl)-, -S-(C1-6alkyl)-, or -N(R5)(C1-6alkyl)- is optionally substituted by one or more RL; each RLis independently halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, -OC(=O)N(R11)R12, - OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, C3-8cycloalkyl, 3- to 8- membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, or two RLare taken together along with the atoms to which they are attached to form a C3-8cycloalkyl or 3- to 8-membered heterocyclyl; R5is H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -C(=O)R12, -S(=O)2R12, -S(=O)2N(R11)(R12), or C3-8cycloalkyl, wherein the C1-6alkyl of R5is optionally substituted with one or more halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, - OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), - C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, - S(=NR13)N(R11)R12, -S(=NR13)OR13, -S(=O)2R12, or -S(=O)2N(R11)(R12), and the C3-8cycloalkyl is optionally substituted with one or more R5b; R6is H, -OR9, -OR10, -N(Rx)(Ry), -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, - N(R11)C(=O)OR12, -OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, - Attorney Docket No.: 185992002140 C(=O)N(R11)(R12), -C(=O)OR12, 5- to 6-membered heteroaryl, or 3- to 8-membered heterocyclyl, wherein the 3- to 8-membered heterocyclyl is optionally substituted with one or more R6b, - C(=O)R12, -C(=O)N(R11)(R12), or -C(=O)OR12; R7is H; R8is C1-6alkyl, -OR9, -OR10, -N(Rx)(Ry), or -C(=O)R12; each R1a, R3a, R4a, R6a, or R7ais independently halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -NO2, - CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, - OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, - C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, -N(R11)S(=O)2R12, - S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, -S(=NR13)N(R13)R12, - S(=NR13)OR14, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R1a, R3a, R4a, R6a, or R7ais optionally substituted with one or more R1b, and the 3- to 12-membered heterocyclyl of R1a, R3a, R4a, R6a, or R7acomprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; each R1b, R3b, R4b, R5b, R6b, or R7bis independently halo, C1-6alkyl, -OR9, -N(Rx)(Ry), oxo, - CN, C3-8cycloalkyl, or 3- to 8-membered heterocyclyl, wherein the C1-6alkyl of R1b, R3b, R4b, R5b, R6b, or R7bis optionally substituted by -OR12, - N(Rx)(Ry), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl; each R9is independently H, C1-6alkyl, C2-6alkenyl, C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R9is optionally substituted with 6- to 10-membered aryl, or 5- to 10- membered heteroaryl wherein the 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, or -N(Rx)(Ry), and the 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R9is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, -N(Rx)(Ry), or 3- to 12-membered heterocyclyl; each R10is independently H, C1-6alkyl, or C3-8cycloalkyl, Attorney Docket No.: 185992002140 wherein the C1-6alkyl is optionally substituted with one or more halo, deuterium, 3- to 8-membered heterocyclyl; each R11is independently H, C1-6alkyl, or C3-8cycloalkyl; each R12is independently H, C1-6alkyl, C3-8cycloalkyl, phenyl, 5- to 6-membered heteroaryl, or 3- to 8-membered heterocyclyl, wherein the C1-6alkyl of R12is optionally substituted by one or more halo, -OH, -O(C1-6alkyl), -N(Rx)(Ry), C3-8cycloalkyl, phenyl, 5- to 6-membered heteroaryl, or 3- to 12- membered heterocyclyl, and the C3-8cycloalkyl, phenyl, 5- to 6-membered heteroaryl, or 3- to 12-membered heterocyclyl of R12is optionally substituted with halo, C1-6alkyl, or -N(Rx)(Ry); each R13is independently H or C1-6alkyl; and each Rxand Ryis independently H, C1-6alkyl, C3-8cycloalkyl, -C(=O)(C1-6alkyl), or - C(=O)O(C1-6alkyl), wherein the C1-6alkyl of Rxor Ryis optionally substituted with 6- to 10-membered aryl, 5- to 10-membered heteroaryl, or -NH2, NH(C1-6alkyl), or -N(C1-6alkyl)(C1-6alkyl), and the C1-6alkyl of -C(=O)(C1-6alkyl) or -C(=O)O(C1-6alkyl) is optionally substituted with -O(C=O)C1-8alkyl); wherein (i) when -(Ring A)-L-R6 are taken together to form , and R1 is H, R8 is notoptionally substituted pyrazolyl; (ii) when R1and R2are taken together with the N to which they are attached to form , -(Ring A)-L-R6are not taken together to form a pyrazolyl substituted by 3- methylphenyl; and (iii) when -(Ring A)-L-R6 are taken together to form , R1 is H, and R2 is -CH3,R8is not -CH3. In some embodiments of the above, the compound is a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt any of the foregoing. Attorney Docket No.: 185992002140 In some embodiments of a compound of formula (I), or any variation or embodimentthereof, or stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R1is H or C1-6alkyl; R2is C1-6alkyl or C3-6cycloalkyl, wherein the C1-6alkyl or C3-6cycloalkyl of R2 is optionally substituted with one or more -OH or-N(Rx)(Ry),or R1 and R2 are taken together with the N to which they are attached to form a 3- to 12-membered heterocyclyl, wherein 3- to 12-membered heterocyclyl of R1 and R2 is optionally substituted with one ormore R3; each R3is independently halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, oxo, -OR10, -SR10, -SF5, -N(Rx)(Ry), -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, - OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), - C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, -S(=NR13)N(R11)R12, -S(=NR13)OR13, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, whereinthe C1-6alkyl of R3is optionally substituted with one or more R3a; the C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to10-membered heteroaryl is optionally substituted with one or more R3b; andoptionally, two substituents of R3are taken together with the atoms to which they are attached form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-memberedaryl, or 5- to 10-membered heteroaryl,wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted oneor more R3b;Ring A is phenyl or 5- to 6-membered heteroaryl, whereinthe phenyl or 5- to 6-membered heteroaryl of Ring A is optionally substituted by oneor more R4, and the 5- to 6-membered heteroaryl of Ring A comprises 1, 2, or 3 atoms selected fromthe group consisting of N, O, and S;each R4 is independently halo, C1-6alkyl, or -OR10; Attorney Docket No.: 185992002140 L is a bond, C1-6alkyl, -O-(C1-6alkyl)-, -S-(C1-6alkyl)-, or -N(R5)(C1-6alkyl)-, wherein the C1-6alkyl, -O-(C1-6alkyl)-, -S-(C1-6alkyl)-, or -N(R5)(C1-6alkyl)- is optionally substituted by one or more RL; each RLis independently halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, -OC(=O)N(R11)R12, - OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, C3-8cycloalkyl, 3- to 8- membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, or two RLare taken together along with the atoms to which they are attached to form a C3-8cycloalkyl or 3- to 8-membered heterocyclyl; R5is H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -C(=O)R12, -S(=O)2R12, -S(=O)2N(R11)(R12), or C3-8cycloalkyl, wherein the C1-6alkyl of R5is optionally substituted with one or more halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, - OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), - C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, - S(=NR13)N(R11)R12, -S(=NR13)OR13, -S(=O)2R12, or -S(=O)2N(R11)(R12), and the C3-8cycloalkyl is optionally substituted with one or more R5b; R6is H, -OR9, -OR10, -N(Rx)(Ry), -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, - N(R11)C(=O)OR12, -OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, - C(=O)N(R11)(R12), -C(=O)OR12, 5- to 6-membered heteroaryl, or 3- to 8-membered heterocyclyl, wherein the 3- to 8-membered heterocyclyl is optionally substituted with one or more R6b, - C(=O)R12, -C(=O)N(R11)(R12), or -C(=O)OR12; R7is H; R8is halo, C1-6alkyl, C1-6haloalkyl, -OR9, -OR10, -N(Rx)(Ry), -N(R11)C(=O)R12, - N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, -OC(=O)N(R11)R12, - OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, 3- to 8-membered heterocyclyl, wherein the 3- to 8-membered heterocyclyl of R8is optionally substituted with one or more R7b, and the 3- to 8-membered heterocyclyl of R8comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; Attorney Docket No.: 185992002140 each R1a, R3a, R4a, R6a, or R7ais independently halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -NO2, - CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, - OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, - C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, -N(R11)S(=O)2R12, - S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, -S(=NR13)N(R13)R12, - S(=NR13)OR14, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R1a, R3a, R4a, R6a, or R7ais optionally substituted with one or more R1b, and the 3- to 12-membered heterocyclyl of R1a, R3a, R4a, R6a, or R7acomprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; each R1b, R3b, R4b, R5b, R6b, or R7bis independently halo, C1-6alkyl, -OR9, -N(Rx)(Ry), oxo, - CN, C3-8cycloalkyl, or 3- to 8-membered heterocyclyl, wherein the C1-6alkyl of R1b, R3b, R4b, R5b, R6b, or R7bis optionally substituted by -OR12, - N(Rx)(Ry), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl; each R9is independently H, C1-6alkyl, C2-6alkenyl, C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R9is optionally substituted with 6- to 10-membered aryl, or 5- to 10- membered heteroaryl wherein the 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, or -N(Rx)(Ry), and the 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R9is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, -N(Rx)(Ry), or 3- to 12- membered heterocyclyl; each R10is independently H, C1-6alkyl, or C3-8cycloalkyl, wherein the C1-6alkyl is optionally substituted with one or more halo, deuterium, 3- to 8-membered heterocyclyl, phenyl, or 5- to 6-membered heteroaryl, wherein the C3-8cycloalkyl, phenyl, or 5- to 6-membered heteroaryl is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, or -N(Rx)(Ry); each R11is independently H, C1-6alkyl, or C3-8cycloalkyl; Attorney Docket No.: 185992002140each R12 is independently H, C1-6alkyl, C3-8cycloalkyl, phenyl, 5- to 6-membered heteroaryl,or 3- to 8-membered heterocyclyl, whereinthe C1-6alkyl of R12is optionally substituted by one or more halo, -OH, -O(C1-6alkyl), -N(Rx)(Ry), C3-8cycloalkyl, phenyl, 5- to 6-membered heteroaryl, or 3- to 12-membered heterocyclyl, and the C3-8cycloalkyl, phenyl, 5- to 6-membered heteroaryl, or 3- to 12-memberedheterocyclyl of R12is optionally substituted with halo, C1-6alkyl, or -N(Rx)(Ry); each R13is independently H or C1-6alkyl; andeach Rx and Ry is independently H, C1-6alkyl, C3-8cycloalkyl, -C(=O)(C1-6alkyl), or -C(=O)O(C1-6alkyl), whereinthe C1-6alkyl of Rx or Ry is optionally substituted with 6- to 10-membered aryl, 5- to10-membered heteroaryl, or -NH2, NH(C1-6alkyl), or -N(C1-6alkyl)(C1-6alkyl), and the C1-6alkyl of -C(=O)(C1-6alkyl) or -C(=O)O(C1-6alkyl) is optionally substituted with-O(C=O)C1-8alkyl); wherein (i) when R1 and R2 are taken together with the N to which they are attached to form , -(Ring A)-L-R6 are not taken together to form a pyrazolyl substituted by Br; and(ii) when -(Ring A)-L-R6 are taken together to form , R1 is H, and R2 is -CH3, R8is not -CH3. In some embodiments of a compound of formula (I), or any variation or embodimentthereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate,or solvate of any of the foregoing, R1is H or C1-6alkyl; R2is C1-6alkyl or C3-6cycloalkyl, wherein the C1-6alkyl or C3-6cycloalkyl of R2 is optionally substituted with one or more -OH or-N(Rx)(Ry),or R1 and R2 are taken together with the N to which they are attached to form a 3- to 12-membered heterocyclyl, wherein Attorney Docket No.: 185992002140 3- to 12-membered heterocyclyl of R1and R2is optionally substituted with one or more R3; each R3is independently halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, oxo, -OR10, -SR10, -SF5, - N(Rx)(Ry), -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, - OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), - C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R3is optionally substituted with one or more R3a, and optionally, two substituents of R3are taken together with the atoms to which they are attached form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10- membered aryl, or 5- to 10-membered heteroaryl is optionally substituted one or more R3b; Ring A is phenyl or 5- to 6-membered heteroaryl, wherein the phenyl or 5- to 6-membered heteroaryl of Ring A is optionally substituted by one or more R4, and the 5- to 6-membered heteroaryl of Ring A comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; each R4is independently halo or -OR10; L is a bond, C1-6alkyl, -O-(C1-6alkyl)-, -S-(C1-6alkyl)-, or -N(R5)(C1-6alkyl)-, wherein the C1-6alkyl, -O-(C1-6alkyl)-, -S-(C1-6alkyl)-, or -N(R5)(C1-6alkyl)- is optionally substituted by one or more RL; each RLis independently halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, -OC(=O)N(R11)R12, - OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, C3-8cycloalkyl, 3- to 8- membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, or two RLare taken together along with the atoms to which they are attached to form a C3-8cycloalkyl or 3- to 8-membered heterocyclyl; R5is H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -C(=O)R12, -S(=O)2R12, -S(=O)2N(R11)(R12), or C3-8cycloalkyl, wherein Attorney Docket No.: 185992002140 the C1-6alkyl of R5is optionally substituted with one or more halo, -N(Rx)(Ry), -OR10, -SR10, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, - OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, - C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)2R12, or -S(=O)2N(R11)(R12), and the C3-8cycloalkyl is optionally substituted with one or more R5b; R6is H, -OR9, -OR10, -N(Rx)(Ry), -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, - N(R11)C(=O)OR12, -OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, - C(=O)N(R11)(R12), -C(=O)OR12, 5- to 6-membered heteroaryl, or 3- to 8-membered heterocyclyl, wherein the 3- to 8-membered heterocyclyl is optionally substituted with one or more R6b, -C(=O)R12, -C(=O)N(R11)(R12), or -C(=O)OR12; R7is H; R8is C1-6alkyl, -OR9, -OR10, -N(Rx)(Ry), or -C(=O)R12; each R1a, R3a, R4a, R6a, or R7ais independently halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -NO2, - CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, - OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, - C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, -N(R11)S(=O)2R12, - S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10- membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R1a, R3a, R4a, R6a, or R7ais optionally substituted with one or more R1b, and the 3- to 12-membered heterocyclyl of R1a, R3a, R4a, R6a, or R7acomprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; each R1b, R3b, R4b, R5b, R6b, or R7bis independently halo, C1-6alkyl, -OR9, -N(Rx)(Ry), oxo, - CN, C3-8cycloalkyl, or 3- to 8-membered heterocyclyl, wherein the C1-6alkyl of R1b, R3b, R4b, R5b, R6b, or R7bis optionally substituted by -OR12, - N(Rx)(Ry), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, phenyl, or 5- to 6- membered heteroaryl; each R9is independently H, C1-6alkyl, C2-6alkenyl, C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein Attorney Docket No.: 185992002140 the C1-6alkyl of R9is optionally substituted with 6- to 10-membered aryl, or 5- to 10- membered heteroaryl wherein the 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, or -N(Rx)(Ry), and the 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R9is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, -N(Rx)(Ry), or 3- to 12-membered heterocyclyl; each R10is independently H, C1-6alkyl, or C3-8cycloalkyl, wherein the C1-6alkyl is optionally substituted with one or more halo, deuterium, 3- to 8-membered heterocyclyl; each R11is independently H, C1-6alkyl, or C3-8cycloalkyl; each R12is independently H, C1-6alkyl, C3-8cycloalkyl, phenyl, 5- to 6-membered heteroaryl, or 3- to 8-membered heterocyclyl, wherein the C1-6alkyl of R12is optionally substituted by one or more halo, -OH, -O(C1-6alkyl), -N(Rx)(Ry), C3-8cycloalkyl, phenyl, 5- to 6-membered heteroaryl, or 3- to 12- membered heterocyclyl, and the C3-8cycloalkyl, phenyl, 5- to 6-membered heteroaryl, or 3- to 12-membered heterocyclyl of R12is optionally substituted with halo, C1-6alkyl, or -N(Rx)(Ry); each R13is independently H or C1-6alkyl; and each Rxand Ryis independently H, C1-6alkyl, C3-8cycloalkyl, -C(=O)(C1-6alkyl), or - C(=O)O(C1-6alkyl), wherein the C1-6alkyl of Rxor Ryis optionally substituted with 6- to 10-membered aryl, 5- to 10-membered heteroaryl, or -NH2, NH(C1-6alkyl), or -N(C1-6alkyl)(C1-6alkyl), and the C1-6alkyl of -C(=O)(C1-6alkyl) or -C(=O)O(C1-6alkyl) is optionally substituted with -O(C=O)C1-8alkyl); wherein (i) when -(Ring A)-L-R6are taken together to form , and R1is H, R8is not optionally substituted pyrazolyl; Attorney Docket No.: 185992002140 (ii) when R1and R2are taken together with the N to which they are attached to form ,-(Ring A)-L-R6 are not taken together to form a pyrazolyl substituted by 3-methylphenyl; and (iii) when -(Ring A)-L-R6are taken together to form , R1is H, and R2is - CH3, R8 is not -CH3. In some embodiments of the above, the compound is acompound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt any of the foregoing. In some embodiments of a compound of formula (I), or any variation or embodimentthereof, or stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R1is H or C1-6alkyl; R2is C1-6alkyl or C3-6cycloalkyl, wherein the C1-6alkyl or C3-6cycloalkyl of R2 is optionally substituted with one or more -OH or-N(Rx)(Ry),or R1 and R2 are taken together with the N to which they are attached to form a 3- to 12-membered heterocyclyl, wherein 3- to 12-membered heterocyclyl of R1 and R2 is optionally substituted with one ormore R3; each R3is independently halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, oxo, -OR10, -SR10, -SF5, -N(Rx)(Ry), -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, - OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), - C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-memberedheterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, whereinthe C1-6alkyl of R3is optionally substituted with one or more R3a; the C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to10-membered heteroaryl is optionally substituted with one or more R3b; and Attorney Docket No.: 185992002140 optionally, two substituents of R3are taken together with the atoms to which they are attached form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10- membered aryl, or 5- to 10-membered heteroaryl is optionally substituted one or more R3b; Ring A is phenyl or 5- to 6-membered heteroaryl, wherein the phenyl or 5- to 6-membered heteroaryl of Ring A is optionally substituted by one or more R4, and the 5- to 6-membered heteroaryl of Ring A comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; each R4is independently halo, C1-6alkyl, or -OR10; L is a bond, C1-6alkyl, -O-(C1-6alkyl)-, -S-(C1-6alkyl)-, or -N(R5)(C1-6alkyl)-, wherein the C1-6alkyl, -O-(C1-6alkyl)-, -S-(C1-6alkyl)-, or -N(R5)(C1-6alkyl)- is optionally substituted by one or more RL; each RLis independently halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, -OC(=O)N(R11)R12, - OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, C3-8cycloalkyl, 3- to 8- membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, or two RLare taken together along with the atoms to which they are attached to form a C3-8cycloalkyl or 3- to 8-membered heterocyclyl; R5is H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -C(=O)R12, -S(=O)2R12, -S(=O)2N(R11)(R12), or C3-8cycloalkyl, wherein the C1-6alkyl of R5is optionally substituted with one or more halo, -N(Rx)(Ry), -OR10, -SR10, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, - OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, - C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)2R12, or -S(=O)2N(R11)(R12), and the C3-8cycloalkyl is optionally substituted with one or more R5b; R6is H, -OR9, -OR10, -N(Rx)(Ry), -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, - N(R11)C(=O)OR12, -OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, - C(=O)N(R11)(R12), -C(=O)OR12, 5- to 6-membered heteroaryl, or 3- to 8-membered heterocyclyl, wherein Attorney Docket No.: 185992002140 the 3- to 8-membered heterocyclyl is optionally substituted with one or more R6b, -C(=O)R12, -C(=O)N(R11)(R12), or -C(=O)OR12; R7is H; R8is halo, C1-6alkyl, C1-6haloalkyl, -OR9, -OR10, -N(Rx)(Ry), -N(R11)C(=O)R12, - N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, -OC(=O)N(R11)R12, - OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, 3- to 8-membered heterocyclyl, wherein the 3- to 8-membered heterocyclyl of R8is optionally substituted with one or more R7b, and the 3- to 8-membered heterocyclyl of R8comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; each R1a, R3a, R4a, R6a, or R7ais independently halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -NO2, - CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, - OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, - C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, -N(R11)S(=O)2R12, - S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10- membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R1a, R3a, R4a, R6a, or R7ais optionally substituted with one or more R1b, and the 3- to 12-membered heterocyclyl of R1a, R3a, R4a, R6a, or R7acomprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; each R1b, R3b, R4b, R5b, R6b, or R7bis independently halo, C1-6alkyl, -OR9, -N(Rx)(Ry), oxo, - CN, C3-8cycloalkyl, or 3- to 8-membered heterocyclyl, wherein the C1-6alkyl of R1b, R3b, R4b, R5b, R6b, or R7bis optionally substituted by -OR12, - N(Rx)(Ry), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, phenyl, or 5- to 6- membered heteroaryl; each R9is independently H, C1-6alkyl, C2-6alkenyl, C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R9is optionally substituted with 6- to 10-membered aryl, or 5- to 10- membered heteroaryl wherein the 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, or -N(Rx)(Ry), and Attorney Docket No.: 185992002140 the 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R9is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, -N(Rx)(Ry), or 3- to 12-membered heterocyclyl; each R10is independently H, C1-6alkyl, or C3-8cycloalkyl, wherein the C1-6alkyl is optionally substituted with one or more halo, deuterium, 3- to 8-membered heterocyclyl, phenyl, or 5- to 6-membered heteroaryl, wherein the C3-8cycloalkyl, phenyl, or 5- to 6-membered heteroaryl is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, or -N(Rx)(Ry); each R11is independently H, C1-6alkyl, or C3-8cycloalkyl; each R12is independently H, C1-6alkyl, C3-8cycloalkyl, phenyl, 5- to 6-membered heteroaryl, or 3- to 8-membered heterocyclyl, wherein the C1-6alkyl of R12is optionally substituted by one or more halo, -OH, -O(C1-6alkyl), -N(Rx)(Ry), C3-8cycloalkyl, phenyl, 5- to 6-membered heteroaryl, or 3- to 12- membered heterocyclyl, and the C3-8cycloalkyl, phenyl, 5- to 6-membered heteroaryl, or 3- to 12-membered heterocyclyl of R12is optionally substituted with halo, C1-6alkyl, or -N(Rx)(Ry); each R13is independently H or C1-6alkyl; and each Rxand Ryis independently H, C1-6alkyl, C3-8cycloalkyl, -C(=O)(C1-6alkyl), or - C(=O)O(C1-6alkyl), wherein the C1-6alkyl of Rxor Ryis optionally substituted with 6- to 10-membered aryl, 5- to 10-membered heteroaryl, or -NH2, NH(C1-6alkyl), or -N(C1-6alkyl)(C1-6alkyl), and the C1-6alkyl of -C(=O)(C1-6alkyl) or -C(=O)O(C1-6alkyl) is optionally substituted with -O(C=O)C1-8alkyl); wherein (i) when -(Ring A)-L-R6are taken together to form , and R1is H, R8is not optionally substituted pyrazolyl; (ii) when R1and R2are taken together with the N to which they are attached to form , -(Ring A)-L-R6are not taken together to form a pyrazolyl substituted by 3- methylphenyl; and Attorney Docket No.: 185992002140 (iii) when -(Ring A)-L-R6are taken together to form , R1is H, and R2is - CH3, R8is not -CH3. In some embodiments of a compound of formula (I), or any variation or embodimentthereof, or stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R1is H or C1-6alkyl; R2is C1-6alkyl or C3-6cycloalkyl, wherein the C1-6alkyl or C3-6cycloalkyl of R2 is optionally substituted with one or more -OH or-N(Rx)(Ry),or R1 and R2 are taken together with the N to which they are attached to form a 3- to 12-membered heterocyclyl, wherein 3- to 12-membered heterocyclyl of R1 and R2 is optionally substituted with one ormore R3; each R3is independently halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, oxo, -OR10, -SR10, -SF5, -N(Rx)(Ry), -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, - OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), - C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, -S(=NR13)N(R11)R12, -S(=NR13)OR13, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, whereinthe C1-6alkyl of R3is optionally substituted with one or more R3a; the C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to10-membered heteroaryl is optionally substituted with one or more R3b; andoptionally, two substituents of R3are taken together with the atoms to which they are attached form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-memberedaryl, or 5- to 10-membered heteroaryl,wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted oneor more R3b;Ring A is phenyl or 5- to 6-membered heteroaryl, whereinthe phenyl or 5- to 6-membered heteroaryl of Ring A is optionally substituted by oneor more R4, and Attorney Docket No.: 185992002140 the 5- to 6-membered heteroaryl of Ring A comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; each R4is independently halo, C1-6alkyl, or -OR10; L is a bond, C1-6alkyl, -O-(C1-6alkyl)-, -S-(C1-6alkyl)-, or -N(R5)(C1-6alkyl)-, wherein the C1-6alkyl, -O-(C1-6alkyl)-, -S-(C1-6alkyl)-, or -N(R5)(C1-6alkyl)- is optionally substituted by one or more RL; each RLis independently halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, -OC(=O)N(R11)R12, - OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, C3-8cycloalkyl, 3- to 8- membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, or two RLare taken together along with the atoms to which they are attached to form a C3-8cycloalkyl or 3- to 8-membered heterocyclyl; R5is H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -C(=O)R12, -S(=O)2R12, -S(=O)2N(R11)(R12), or C3-8cycloalkyl, wherein the C1-6alkyl of R5is optionally substituted with one or more halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, - OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), - C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, - S(=NR13)N(R11)R12, -S(=NR13)OR13, -S(=O)2R12, or -S(=O)2N(R11)(R12), and the C3-8cycloalkyl is optionally substituted with one or more R5b; R6is H, -OR9, -OR10, -N(Rx)(Ry), -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, - N(R11)C(=O)OR12, -OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, - C(=O)N(R11)(R12), -C(=O)OR12, 5- to 6-membered heteroaryl, or 3- to 8-membered heterocyclyl, wherein the 3- to 8-membered heterocyclyl is optionally substituted with one or more R6b, - C(=O)R12, -C(=O)N(R11)(R12), or -C(=O)OR12; R7is H; R8is halo, C1-6alkyl, C1-6haloalkyl, -OR9, -OR10, -N(Rx)(Ry), -N(R11)C(=O)R12, - N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, -OC(=O)N(R11)R12, - OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, 3- to 8-membered heterocyclyl, wherein Attorney Docket No.: 185992002140 the 3- to 8-membered heterocyclyl of R8is optionally substituted with one or more R7b, and the 3- to 8-membered heterocyclyl of R8comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; each R1a, R3a, R4a, R6a, or R7ais independently halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -NO2, - CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, - OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, - C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, -N(R11)S(=O)2R12, - S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, -S(=NR13)N(R13)R12, - S(=NR13)OR14, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R1a, R3a, R4a, R6a, or R7ais optionally substituted with one or more R1b, and the 3- to 12-membered heterocyclyl of R1a, R3a, R4a, R6a, or R7acomprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; each R1b, R3b, R4b, R5b, R6b, or R7bis independently halo, C1-6alkyl, -OR9, -N(Rx)(Ry), oxo, - CN, C3-8cycloalkyl, or 3- to 8-membered heterocyclyl, wherein the C1-6alkyl of R1b, R3b, R4b, R5b, R6b, or R7bis optionally substituted by -OR12, - N(Rx)(Ry), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl; each R9is independently H, C1-6alkyl, C2-6alkenyl, C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R9is optionally substituted with 6- to 10-membered aryl, or 5- to 10- membered heteroaryl wherein the 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, or -N(Rx)(Ry), and the 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R9is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, -N(Rx)(Ry), or 3- to 12-membered heterocyclyl; each R10is independently H, C1-6alkyl, or C3-8cycloalkyl, wherein the C1-6alkyl is optionally substituted with one or more halo, deuterium, 3- to 8-membered heterocyclyl, phenyl, or 5- to 6-membered heteroaryl, wherein Attorney Docket No.: 185992002140 the C3-8cycloalkyl, phenyl, or 5- to 6-membered heteroaryl is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, or -N(Rx)(Ry); each R11is independently H, C1-6alkyl, or C3-8cycloalkyl; each R12is independently H, C1-6alkyl, C3-8cycloalkyl, phenyl, 5- to 6-membered heteroaryl, or 3- to 8-membered heterocyclyl, wherein the C1-6alkyl of R12is optionally substituted by one or more halo, -OH, -O(C1-6alkyl), -N(Rx)(Ry), C3-8cycloalkyl, phenyl, 5- to 6-membered heteroaryl, or 3- to 12- membered heterocyclyl, and the C3-8cycloalkyl, phenyl, 5- to 6-membered heteroaryl, or 3- to 12-membered heterocyclyl of R12is optionally substituted with halo, C1-6alkyl, or -N(Rx)(Ry); each R13is independently H or C1-6alkyl; and each Rxand Ryis independently H, C1-6alkyl, C3-8cycloalkyl, -C(=O)(C1-6alkyl), or - C(=O)O(C1-6alkyl), wherein the C1-6alkyl of Rxor Ryis optionally substituted with 6- to 10-membered aryl, 5- to 10-membered heteroaryl, or -NH2, NH(C1-6alkyl), or -N(C1-6alkyl)(C1-6alkyl), and the C1-6alkyl of -C(=O)(C1-6alkyl) or -C(=O)O(C1-6alkyl) is optionally substituted with -O(C=O)C1-8alkyl); wherein (i) when -(Ring A)-L-R6 are taken together to form , and R1 is H, R8 is notoptionally substituted pyrazolyl; (ii) when R1and R2are taken together with the N to which they are attached to form , -(Ring A)-L-R6are not taken together to form a pyrazolyl substituted by 3- methylphenyl; and (iii) when -(Ring A)-L-R6 are taken together to form , R1 is H, and R2 is -CH3,R8is not -CH3. In some embodiments of the above, the compound of formula (I) is a compound, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt any of the foregoing. Attorney Docket No.: 185992002140 In some embodiments of a compound of formula (I), or any variation or embodimentthereof, or stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R1is H or C1-6alkyl; R2is C1-6alkyl or C3-6cycloalkyl, wherein the C1-6alkyl or C3-6cycloalkyl of R2 is optionally substituted with one or more -OH or-N(Rx)(Ry),or R1 and R2 are taken together with the N to which they are attached to form a 3- to 12-membered heterocyclyl, wherein 3- to 12-membered heterocyclyl of R1 and R2 is optionally substituted with one ormore R3; each R3is independently halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, oxo, -OR10, -SR10, -SF5, -N(Rx)(Ry), -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, - OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), - C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-memberedheterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, whereinthe C1-6alkyl of R3is optionally substituted with one or more R3a; the C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to10-membered heteroaryl is optionally substituted with one or more R3b; andoptionally, two substituents of R3are taken together with the atoms to which they are attached form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-memberedaryl, or 5- to 10-membered heteroaryl,wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted oneor more R3b;Ring A is phenyl or 5- to 6-membered heteroaryl, whereinthe phenyl or 5- to 6-membered heteroaryl of Ring A is optionally substituted by oneor more R4, and the 5- to 6-membered heteroaryl of Ring A comprises 1, 2, or 3 atoms selected fromthe group consisting of N, O, and S; each R4 is independently halo, C1-6alkyl, or -OR10; L is a bond, C1-6alkyl, -O-(C1-6alkyl)-, -S-(C1-6alkyl)-, or -N(R5)(C1-6alkyl)-, wherein Attorney Docket No.: 185992002140 the C1-6alkyl, -O-(C1-6alkyl)-, -S-(C1-6alkyl)-, or -N(R5)(C1-6alkyl)- is optionally substituted by one or more RL; each RLis independently halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, -OC(=O)N(R11)R12, - OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, C3-8cycloalkyl, 3- to 8- membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, or two RLare taken together along with the atoms to which they are attached to form a C3-8cycloalkyl or 3- to 8-membered heterocyclyl; R5is H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -C(=O)R12, -S(=O)2R12, -S(=O)2N(R11)(R12), or C3-8cycloalkyl, wherein the C1-6alkyl of R5is optionally substituted with one or more halo, -N(Rx)(Ry), -OR10, -SR10, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, - OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, - C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)2R12, or -S(=O)2N(R11)(R12), and the C3-8cycloalkyl is optionally substituted with one or more R5b; R6is H, -OR9, -OR10, -N(Rx)(Ry), -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, - N(R11)C(=O)OR12, -OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, - C(=O)N(R11)(R12), -C(=O)OR12, 5- to 6-membered heteroaryl, or 3- to 8-membered heterocyclyl, wherein the 3- to 8-membered heterocyclyl is optionally substituted with one or more R6b, -C(=O)R12, -C(=O)N(R11)(R12), or -C(=O)OR12; R7is H; R8is halo, C1-6alkyl, C1-6haloalkyl, -OR9, -OR10, -N(Rx)(Ry), -N(R11)C(=O)R12, - N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, -OC(=O)N(R11)R12, - OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, 3- to 8-membered heterocyclyl, wherein the 3- to 8-membered heterocyclyl of R8is optionally substituted with one or more R7b, and the 3- to 8-membered heterocyclyl of R8comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; each R1a, R3a, R4a, R6a, or R7ais independently halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -NO2, - CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, - Attorney Docket No.: 185992002140 OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, - C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, -N(R11)S(=O)2R12, - S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10- membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R1a, R3a, R4a, R6a, or R7ais optionally substituted with one or more R1b, and the 3- to 12-membered heterocyclyl of R1a, R3a, R4a, R6a, or R7acomprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; each R1b, R3b, R4b, R5b, R6b, or R7bis independently halo, C1-6alkyl, -OR9, -N(Rx)(Ry), oxo, - CN, C3-8cycloalkyl, or 3- to 8-membered heterocyclyl, wherein the C1-6alkyl of R1b, R3b, R4b, R5b, R6b, or R7bis optionally substituted by -OR12, - N(Rx)(Ry), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, phenyl, or 5- to 6- membered heteroaryl; each R9is independently H, C1-6alkyl, C2-6alkenyl, C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R9is optionally substituted with 6- to 10-membered aryl, or 5- to 10- membered heteroaryl wherein the 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, or -N(Rx)(Ry), and the 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R9is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, -N(Rx)(Ry), or 3- to 12-membered heterocyclyl; each R10is independently H, C1-6alkyl, or C3-8cycloalkyl, wherein the C1-6alkyl is optionally substituted with one or more halo, deuterium, 3- to 8-membered heterocyclyl, phenyl, or 5- to 6-membered heteroaryl, wherein the C3-8cycloalkyl, phenyl, or 5- to 6-membered heteroaryl is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, or -N(Rx)(Ry); each R11is independently H, C1-6alkyl, or C3-8cycloalkyl; each R12is independently H, C1-6alkyl, C3-8cycloalkyl, phenyl, 5- to 6-membered heteroaryl, or 3- to 8-membered heterocyclyl, wherein Attorney Docket No.: 185992002140 the C1-6alkyl of R12is optionally substituted by one or more halo, -OH, -O(C1-6alkyl), -N(Rx)(Ry), C3-8cycloalkyl, phenyl, 5- to 6-membered heteroaryl, or 3- to 12-membered heterocyclyl, andthe C3-8cycloalkyl, phenyl, 5- to 6-membered heteroaryl, or 3- to 12-membered heterocyclylof R12is optionally substituted with halo, C1-6alkyl, or -N(Rx)(Ry); each R13is independently H or C1-6alkyl; andeach Rx and Ry is independently H, C1-6alkyl, C3-8cycloalkyl, -C(=O)(C1-6alkyl), or -C(=O)O(C1-6alkyl), whereinthe C1-6alkyl of Rx or Ry is optionally substituted with 6- to 10-membered aryl, 5- to10-membered heteroaryl, or -NH2, NH(C1-6alkyl), or -N(C1-6alkyl)(C1-6alkyl), and the C1-6alkyl of -C(=O)(C1-6alkyl) or -C(=O)O(C1-6alkyl) is optionally substituted with-O(C=O)C1-8alkyl); wherein (i) when -(Ring A)-L-R6are taken together to form , and R1is H, R8is not optionally substituted pyrazolyl; (ii) when R1and R2are taken together with the N to which they are attached to form ,-(Ring A)-L-R6 are not taken together to form a pyrazolyl substituted by 3-methylphenyl; and (iii) when -(Ring A)-L-R6are taken together to form , R1is H, and R2is - CH3, R8is not -CH3. In some embodiments of a compound of formula (I), or any variation or embodimentthereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate,or solvate of any of the foregoing, Lis a bond or -O(C1-6alkyl)-; andR3 is H, -N(Rx)(Ry), or 4- to 12-membered heterocyclyl optionally substituted withone or more R3a. In some embodiments of the above, the compound is a compound offormula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt any of the foregoing. Attorney Docket No.: 185992002140 In some embodiments of a compound of formula (I), or any variation or embodimentthereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate,or solvate of any of the foregoing, R1 and R2 are taken together with the N to which they are attached to form a 4- to 12-membered heterocyclyl optionally substituted with one or more R3; L is a bond; and R6 is 4- to 12-membered heterocyclyl optionally substituted with one or more R6b, -C(=O)R12, -C(=O)N(R11)(R12), or -C(=O)OR12. In some embodiments of the above,the compound is a compound of formula (I), or a stereoisomer or tautomer thereof, ora pharmaceutically acceptable salt any of the foregoing. In some embodiments of a compound of formula (I), or any variation or embodimentthereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate,or solvate of any of the foregoing, R1 and R2 are taken together with the N to which they are attached to form a 4- to 12-membered heterocyclyl optionally substituted with one or more R3; L is a bond; and R6is piperazinyl optionally substituted with one or more R6b, -C(=O)R12, - C(=O)N(R11)(R12), or -C(=O)OR12. In some embodiments of the above, thecompound is a compound of formula (I), or a stereoisomer or tautomer thereof, or apharmaceutically acceptable salt any of the foregoing. In some embodiments of a compound of formula (I), or any variation or embodimentthereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate,or solvate of any of the foregoing, L is -O(C1-6alkyl)-; and R6 is H or -N(Rx)(Ry). In some embodiments of the above, the compound is acompound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt any of the foregoing. In some embodiments of a compound of formula (I), or any variation or embodimentthereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate,or solvate of any of the foregoing, Ring A is phenyl; and Attorney Docket No.: 185992002140 R6 is C1-6alkyl. In some embodiments of the above, the compound is a compound offormula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt any of the foregoing. In some embodiments of formula (I), or any variation or embodiment thereof, or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate ofany of the foregoing (i) when -(Ring A)-L-R6are taken together to form , and R1is H, R8is not optionally substituted pyrazolyl; (ii) when R1and R2are taken together with the N to which they are attached to form , -(Ring A)-L-R6 are not taken together to form a pyrazolyl substituted by 3-methylphenyl; and(iii) when -(Ring A)-L-R6are taken together to form , R1is H, and R2is -CH3, R8isnot -CH3. In some embodiments of the above, the compound is a compound of formula (I), ora stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt any of the foregoing. In some embodiments of formula (I), or any variation or embodiment thereof, or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate ofany of the foregoing (i) when -(Ring A)-L-R6are taken together to form and R1is H, R8is not optionally substituted pyrazolyl; (ii) when R1and R2are taken together with the N to which they are attached to form , and Ring A is 5-membered N-containing heteroaryl, then L-R6are not taken together to formhalo, pyridyl substituted by methyl, or substituted phenyl; and Attorney Docket No.: 185992002140 (iii) when -(Ring A)-L-R6are taken together to form , R1is H, and R2is -CH3, R8isnot -CH3. In some embodiments of the above, the compound is a compound of formula (I), ora stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt any of the foregoing. In some embodiments of formula (I), or any variation or embodiment thereof, or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate ofany of the foregoing(i) when R1 and R2 are taken together with the N to which they are attached to form (Ring A)-L-R6 are not taken together to form a pyrazolyl substituted by Br; and(ii) when -(Ring A)-L-R6 are taken together to form , R1 is H, and R2 is -CH3, R8isnot -CH3. In some embodiments of the above, the compound is a compound of formula (I), ora stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt any of the foregoing. In some embodiments of a compound of formula (I), or any variation or embodimentthereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate,or solvate of any of the foregoing, R1 is H or C1-6alkyl. In some embodiments, R1 is H. Insome embodiments of the above, the compound is a compound of formula (I), or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt any of the foregoing. In some embodiments of a compound of formula (I), or any variation or embodimentthereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate,or solvate of any of the foregoing, R2 is C1-6alkyl or C3-6cycloalkyl, wherein the C1-6alkyl orC3-6cycloalkyl of R2is optionally substituted with one or more -OH or -N(Rx)(Ry). In some embodiments, R2is -(C1-6alkyl)NH2, -(C1-6alkyl)N(C1-6alkyl)(C1-6alkyl), -(C1-6alkyl)NH(C1-6alkyl-NH2), or -(C3-6cycloalkyl)NH2. In some embodiments, R2is selected from the group Attorney Docket No.: 185992002140 compound is a compound of formula (I), or a stereoisomer or tautomer thereof, or apharmaceutically acceptable salt any of the foregoing. In some embodiments of a compound of formula (I), or any variation or embodimentthereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate,or solvate of any of the foregoing, R1and R2are taken together with the N to which they areattached to form a 3- to 12-membered heterocyclyl optionally substituted with one or moreR3. In some embodiments, R1 and R2 are taken together with the N to which they are attachedto form a 3- to 12-membered heterocyclyl optionally substituted with one or more R3,wherein the 3- to 12-membered heterocyclyl comprises a 3- to 8-membered monocyclicheterocyclyl, a 5- to 12-membered fused heterocyclyl, or a 6- to 12-membered spirocyclicheterocyclyl. In some embodiments, R1 and R2 are taken together with the N to which theyare attached to form a saturated 3- to 10-membered heterocyclyl optionally substituted withone or more R3. In some embodiments, R1and R2are taken together with the N to which theyare attached to form a saturated 4- to 6-membered monocyclic heterocyclyl optionallysubstituted with one or more R3. In some embodiments, R1and R2are taken together with the N to which they are attached to form an azetidinyl or pyrrolidinyl, wherein the azetidinyl or pyrrolidinyl is optionally substituted with one or more R3. In some embodiments, R1and R2are taken together with the N to which they are attached to form a saturated 6- to 10-membered fused or bridged heterocyclyl optionally substituted with one or more R3. In some Attorney Docket No.: 185992002140 embodiments, R1and R2are taken together with the N to which they are attached to form asaturated 6- to 10-membered fused heterocyclyl optionally substituted with one or more R3.In some embodiments, R1and R2are taken together with the N to which they are attached toform a saturated 7- to 10-membered spirocyclic heterocyclyl optionally substituted with oneor more R3. In some embodiments of the above, the compound is a compound of formula (I),or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt any of the foregoing. In some embodiments of a compound of formula (I), or any variation or embodimentthereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate,or solvate of any of the foregoing, R1 and R2 are taken together with the N to which they are Attorney Docket No.: 185992002140 some embodiments, R1and R2are taken together with the N to which they are attached to form a heterocyclyl selected from the group consisting of , Attorney Docket No.: 185992002140 embodiments, R1and R2are taken together with the N to which they are attached to form a R1and R2are taken together with the N to which they are attached to form a group selected Attorney Docket No.: 185992002140 together with the N to which they are attached to form a group selected from the group compound is a compound of formula (I), or a stereoisomer or tautomer thereof, or apharmaceutically acceptable salt any of the foregoing. In some embodiments, R1 and R2 are taken together with the N to which they are Attorney Docket No.: 185992002140 , , Attorney Docket No.: 185992002140 some embodiments, R1and R2are taken together with the N to which they are attached to form a heterocyclyl selected from the Attorney Docket No.: 185992002140 some embodiments, R1and R2are taken together with the N to which they are attached to form a group selected from the group consisting of , some embodiments, R1 and R2 are taken togetherwith the N to which they are attached to form a group selected from the group consisting of In some embodiments of a compound of formula (I), or any variation or embodimentthereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate,or solvate of any of the foregoing, Ring A is phenyl or 6-membered heteroaryl, wherein thephenyl or 6-membered heteroaryl is optionally substituted by one or more R4, and the 5- to 6-membered heteroaryl of Ring A comprises 1, 2, or 3 atoms selected from the group consistingof N, O, and S. In some embodiments, Ring A is phenyl or 6-membered heteroaryl, whereinthe phenyl or 6-membered heteroaryl is substituted by 0 or 1 R4, and the 5- to 6-memberedheteroaryl of Ring A comprises 1, 2, or 3 atoms selected from the group consisting of N, O,and S. In some embodiments, Ring A is phenyl substituted by 0 or 1 R4. In some Attorney Docket No.: 185992002140embodiments of the above, the compound is a compound of formula (I), or a stereoisomer ortautomer thereof, or a pharmaceutically acceptable salt any of the foregoing. In some embodiments of a compound of formula (I), or any variation or embodimentthereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate,or solvate of any of the foregoing, each R4 is independently halo, C1-6alkyl, or -OR10. In someembodiments, each R4 is independently chloro, or -OCH3. In some embodiments, R4ischloro, or -OCH3. In some embodiments, R4 is chloro. In some embodiments, R4 is -OCH3. Insome embodiments of the above, the compound is a compound of formula (I), or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt any of the foregoing. In some embodiments of a compound of formula (I), or any variation or embodimentthereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate,or solvate of any of the foregoing, R6 is H, -OR9, -OR10, -N(Rx)(Ry), -N(R11)C(=O)R12, 5- to6-membered heteroaryl, or 3- to 8-membered heterocyclyl, wherein the 3- to 8-memberedheterocyclyl of R6 is optionally substituted with one or more R6b. In some embodiments, R6 isH, -O(5- to 6-membered heteroaryl), -NH(C1-6alkyl), -NH(C3-6cycloalkyl), -NHC(O)(C1-6alkyl), -NHC(O)(C1-6alkyl)NH2, -N(C1-6alkyl)C(O)(C1-6alkyl)NH2, 5-membered heteroaryl,or 4- to 6-membered N-containing heterocyclyl, wherein the 4- to 6-membered N-containingheterocyclyl of R6 is optionally substituted with one or more R6b, -C(=O)R12, -C(=O)N(R11)(R12), or -C(=O)OR12. In some embodiments, R6 is selected from the group some embodiments of the above, thecompound is a compound of formula (I), or a stereoisomer or tautomer thereof, or apharmaceutically acceptable salt any of the foregoing. Attorney Docket No.: 185992002140 In some embodiments of a compound of formula (I), or any variation or embodimentthereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate,or solvate of any of the foregoing, R8 is C1-6alkyl, -(C1-6alkyl)OH, -C1-6alkyl-O(C1-6alkyl), -(C1-6alkyl)(4- to 7-membered heterocyclyl), -O(C1-6alkyl), -O(C1-6alkyl)(4- to 7-memberedheterocyclyl), -N(C1-6alkyl)(C1-6alkyl), or -C(O)(4- to 7-membered heterocyclyl), whereineach 4- to 7-membered heterocyclyl is optionally substituted by C1-6alkyl. In someembodiments, R8 is selected from the group consisting of -CH3, -CH2OH, , - . In some embodiments of the above, the compound is a compound of formula (I), or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt any of the foregoing. In some embodiments, R8is selected from the group consisting of -CH3, -CH2OH, In some embodiments of a compound of formula (I), or any variation or embodimentthereof, or stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, orsolvate of any of the foregoing, R12 is selected from the group consisting Attorney Docket No.: 185992002140 embodiments, the aforementioned R12 groups have the (R)- configuration. In someembodiments, the aforementioned R12 groups have the (S)- configuration. In someembodiments of the above, the compound is a compound of formula (I), or a stereoisomer ortautomer thereof, or a pharmaceutically acceptable salt any of the foregoing. In some embodiments of a compound of formula (I), the compound is a compound ofFormula (II): any variation or embodiment thereof, or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate ofany of the foregoing, wherein X1 is CH or N, and R1, R2, R6, R7, R8 and L are as definedelsewhere herein. In another variation, X1 is CH or N, and R1, R2, R6, R7, R8 and L are asdefined for a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodimentthereof. In some embodiments of a compound of formula (II), or a stereoisomer or tautomerthereof, or a pharmaceutically acceptable salt, hydrate, or solvate of any of the foregoing, the Attorney Docket No.: 185992002140compound is a compound of formula (II), or a stereoisomer or tautomer thereof, or apharmaceutically acceptable salt any of the foregoing. In some embodiments of a compound of formula (I), the compound is a compound ofFormula (II-A): any variation or embodiment thereof, or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate ofany of the foregoing, wherein R1, R2, R6, R7, R8 and L are as defined elsewhere herein. Inanother variation, R1, R2, R6, R7, R8 and L are as defined for a compound of formula (I), or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of theforegoing, or any variation or embodiment thereof. In some embodiments of a compound offormula (II-A), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt,hydrate, or solvate of any of the foregoing, the compound is a compound of formula (II-A),or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt any of the foregoing. In some embodiments of a compound of formula (I), the compound is a compound ofFormula (II-B): any variation or embodiment thereof, or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate ofany of the foregoing, wherein R2, R6, R7, R8 and L are as defined elsewhere herein. In anothervariation, R2, R6, R7, R8and L are as defined for a compound of formula (I), or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of theforegoing, or any variation or embodiment thereof. In some embodiments of a compound offormula (II-B), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, Attorney Docket No.: 185992002140hydrate, or solvate of any of the foregoing, the compound is a compound of formula (II-B), ora stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt any of the foregoing. In some embodiments of a compound of formula (I), the compound is a compound ofFormula (II-C): any variation or embodiment thereof, or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate ofany of the foregoing, wherein R1, R2, R6, R7, R8 and L are as defined elsewhere herein. Inanother variation, R1, R2, R6, R7, R8and L are as defined for a compound of formula (I), or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of theforegoing, or any variation or embodiment thereof. In some embodiments of a compound offormula (II-C), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt,hydrate, or solvate of any of the foregoing, the compound is a compound of formula (II-C), ora stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt any of the foregoing. In some embodiments of a compound of formula (I), the compound is a compound ofFormula (III): any variation or embodiment thereof, or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate ofany of the foregoing, wherein X1is CH or N, and R1, R2, R6, R7, R8and L are as definedelsewhere herein. In another variation, X1 is CH or N, and R1, R2, R6, R7, R8 and L are asdefined for a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment Attorney Docket No.: 185992002140thereof. In some embodiments of a compound of formula (III), or a stereoisomer or tautomerthereof, or a pharmaceutically acceptable salt, hydrate, or solvate of any of the foregoing, thecompound is a compound of formula (III), or a stereoisomer or tautomer thereof, or apharmaceutically acceptable salt any of the foregoing. In some embodiments of a compound of formula (I), the compound is a compound ofFormula (III-A): any variation or embodiment thereof, or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate ofany of the foregoing, wherein R1, R2, R6, R7, R8 and L are as defined elsewhere herein. Inanother variation, R1, R2, R6, R7, R8and L are as defined for a compound of formula (I), or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of theforegoing, or any variation or embodiment thereof. In some embodiments of a compound offormula (III-A), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt,hydrate, or solvate of any of the foregoing, the compound is a compound of formula (III-A),or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt any of the foregoing. In some embodiments of a compound of formula (I), the compound is a compound ofFormula (IV): any variation or embodiment thereof, or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate ofany of the foregoing, wherein X2, X4 and X5 are each independently C, N, O or S; X3 and X6are each independently C or N; n is 0, 1, 2, or 3; and R1, R2, R6, R7, R8 and L are as defined Attorney Docket No.: 185992002140elsewhere herein. In another variation, X2, X4 and X5 are each independently C, N, O or S; X3and X6are each independently C or N; n is 0, 1, 2, or 3; and R1, R2, R6, R7, R8and L are as defined for a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodimentthereof. In some embodiments of a compound of formula (IV), or a stereoisomer or tautomerthereof, or a pharmaceutically acceptable salt, hydrate, or solvate of any of the foregoing, thecompound is a compound of formula (IV), or a stereoisomer or tautomer thereof, or apharmaceutically acceptable salt any of the foregoing. In some embodiments, the compounds of formula (I), or any variation or embodimentthereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any ofthe foregoing, selectively modulate TDP-43. In some embodiments, the compounds offormula (I), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, ora pharmaceutically acceptable salt of any of the foregoing, reduce TDP-43 cytoplasmicinclusions, improve nuclear TDP-43 function, or reduce neurodegeneration. In someembodiments, the compounds of formula (I), or any variation or embodiment thereof, or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of theforegoing, reduce TDP-43 cytoplasmic inclusions. In some embodiments, the compounds offormula (I), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, ora pharmaceutically acceptable salt of any of the foregoing, improve nuclear TDP-43 function.In some embodiments, the compounds of formula (I), or any variation or embodimentthereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any ofthe foregoing, reduce neurodegeneration. In some embodiments, the compounds of formula(I), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or apharmaceutically acceptable salt of any of the foregoing, mitigate TDP-43 cytoplasmiccondensates in motor neurons. In some embodiments, the motor neurons are iPSC-derivedmotor neurons. In some embodiments, STMN2 and POLDIP3 splicing in iPSC-derivedmotor neurons is restored. In some embodiments of a compound of formula (I), or any variation or embodimentthereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate,or solvate of any of the foregoing, the compound is selected from Table 1. In someembodiments of a compound of formula (I), or any variation or embodiment thereof, or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate ofany of the foregoing, the compound is selected from compounds 1-65 of Table 1. In some Attorney Docket No.: 185992002140 embodiments of a compound of formula (I), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate of any of the foregoing, the compound is selected from Table 1, or a pharmaceutically acceptable salt of any of the foregoing. In some embodiments of a compound of formula (I), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate of any of the foregoing, the compound is selected from compounds 1-65 of Table 1, or a pharmaceutically acceptable salt of any of the foregoing. In some embodiments of a compound of formula (I), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate of any of the foregoing, the compound is selected from compounds 1- 70 of Table 1, or a pharmaceutically acceptable salt of any of the foregoing. Table 1. Attorney Docket No.: 185992002140 Attorney Docket No.: 185992002140 Attorney Docket No.: 185992002140 Attorney Docket No.: 185992002140 Attorney Docket No.: 185992002140 Attorney Docket No.: 185992002140 Attorney Docket No.: 185992002140 Attorney Docket No.: 185992002140 Attorney Docket No.: 185992002140 Attorney Docket No.: 185992002140 Attorney Docket No.: 185992002140 Attorney Docket No.: 185992002140 Attorney Docket No.: 185992002140 In some embodiments, the compound is selected from the group consisting of 2-methyl-7-(pyrrolidin-1-yl)-5-(4-(3-(pyrrolidin-1-yl) propoxy) phenyl) thieno[3,2-b] pyridine; 5-(3-chloro-4-methoxyphenyl)-2-methyl-7-(pyrrolidin-1-yl) thieno[3,2-b] pyridine; 5-(3,4-dimethoxyphenyl)-2-methyl-7-(pyrrolidin-1-yl) thieno[3,2-b] pyridine; 2-methyl-5-(4-(piperazin-1-yl) phenyl)-7-(pyrrolidin-1-yl) thieno[3,2-b] pyridine; N-methyl-2-(4-(2-methyl-7-(pyrrolidin-1-yl) thieno[3,2-b] pyridin-5-yl) phenoxy) ethan- 1-amine; 1-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-3-ol; 7-(3-methoxypyrrolidin-1-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 2-methyl-5-(4-(piperazin-1-yl) phenyl)-7-(3-(trifluoromethyl) pyrrolidin-1-yl) thieno[3,2- b] pyridine; (1-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-3-yl) methanol; 3-methyl-1-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-3-ol; 2-methyl-7-(3-methylpyrrolidin-1-yl)-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; Attorney Docket No.: 185992002140 7-(3-fluoropyrrolidin-1-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; N, N-dimethyl-1-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-3-amine; 1-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-3-amine; N-methyl-1-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-3-amine; (1-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-3-yl) methanamine; 7-(3-cyclopropylpyrrolidin-1-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 2-methyl-7-(3-phenylpyrrolidin-1-yl)-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 7-(3,3-difluoropyrrolidin-1-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 2-methyl-7-(octahydro-2H-isoindol-2-yl)-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 7-(3,3-dimethylpyrrolidin-1-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 3-methyl-1-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-3-amine; 2-methyl-5-(4-(piperazin-1-yl) phenyl)-7-(2,7-diazaspiro [4.4] nonan-2-yl) thieno[3,2-b] pyridine; 2-methyl-5-(4-(piperazin-1-yl) phenyl)-7-(2,8-diazaspiro [4.5] decan-2-yl) thieno[3,2-b] pyridine; 7-(hexahydropyrrolo[3,4-c] pyrrol-2(1H)-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 2-methyl-7-(5-methylhexahydropyrrolo[3,4-c] pyrrol-2(1H)-yl)-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 7-(hexahydropyrrolo[3,4-b] pyrrol-1(2H)-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 7-(2,5-diazabicyclo [2.2.1] heptan-2-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; Attorney Docket No.: 185992002140 1-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidine-3- carbonitrile 5-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) hexahydro-1H- furo[3,4-c] pyrrole; 7-(3-azabicyclo [3.1.0] hexan-3-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 7-(1,1-difluoro-5-azaspiro [2.4] heptan-5-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 1-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl)-3-(trifluoromethyl) pyrrolidin-3-ol; 2-methyl-5-(4-(piperazin-1-yl) phenyl)-7-(2,6-diazaspiro [3.4] octan-6-yl) thieno[3,2-b] pyridine; 2-methyl-5-(4-(piperazin-1-yl) phenyl)-7-(1,7-diazaspiro [4.4] nonan-7-yl) thieno[3,2-b] pyridine; 2-methyl-5-(4-(piperazin-1-yl) phenyl)-7-(2,7-diazaspiro [4.5] decan-2-yl) thieno[3,2-b] pyridine; 2-methyl-7-(2-methylpyrrolidin-1-yl)-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine 2-methyl-5-(4-(piperazin-1-yl) phenyl)-7-(2-(trifluoromethyl) pyrrolidin-1-yl) thieno[3,2- b] pyridine; (1-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-2-yl) methanol; 2-methyl-7-(octahydro-2H-pyrrolo[3,4-c] pyridin-2-yl)-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; (1-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-2-yl) methanamine; 7-(2-(methoxymethyl) pyrrolidin-1-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 2-methyl-5-(4-(piperazin-1-yl) phenyl)-7-(2-(pyrrolidin-1-ylmethyl) pyrrolidin-1-yl) thieno[3,2-b] pyridine; 2-methyl-5-(4-(piperazin-1-yl) phenyl)-7-(2-(pyridin-3-yl) pyrrolidin-1-yl) thieno[3,2-b] pyridine; Attorney Docket No.: 185992002140 7-(2-(4-chlorophenyl) pyrrolidin-1-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2- b] pyridine; 7-(2-(3-fluorophenyl) pyrrolidin-1-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2- b] pyridine; 7-(2-(4-fluorophenyl) pyrrolidin-1-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2- b] pyridine; 3-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl)-3-azabicyclo [3.1.0] hexan-6-amine; 2-methyl-7-(2-phenylpyrrolidin-1-yl)-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 2-methyl-5-(4-(piperazin-1-yl) phenyl)-7-(2-(pyridin-4-yl) pyrrolidin-1-yl) thieno[3,2-b] pyridine; 2-amino-1-[4-[4-[2-methyl-7-[3-(methylaminomethyl) vazetidin-1-yl] thieno[3,2-b] pyridin-5-yl] phenyl] piperazin-1-yl] propan-1-one; 2-[2-methoxy-5-[4-[2-(methylamino) ethoxy] phenyl] thieno[3,2-b] pyridin-7-yl]- 3,3a,4,5,7,7a-hexahydro-1H-pyrrolo[3,4-c] pyridin-6-one; 1-[1-[5-[4-(1H-imidazol-4-yloxy) phenyl]-2-methoxy-thieno[3,2-b] pyridin-7-yl] azetidin-3-yl]-N-methyl-methanamine; 2-[4-[7-(7,7-difluoro-3,3a,4,5,6,7a-hexahydro-1H-pyrrolo[3,4-c] pyridin-2-yl)-2- methoxy-thieno[3,2-b] pyridin-5-yl] phenoxy]-N-methyl-ethanamine; 2-(4-(2-methoxy-7-(octahydro-2H-pyrrolo[3,4-c]pyridin-2-yl)thieno[3,2-b]pyridin-5- yl)phenoxy)-N-methylethan-1-amine; 2-(4-(2-(methoxy-d3)-7-(octahydro-2H-pyrrolo[3,4-c]pyridin-2-yl)thieno[3,2-b]pyridin- 5-yl)phenoxy)-N-methylethan-1-amine; [1-[2-(dimethylamino)-5-(4-piperazin-1-ylphenyl) thieno[3,2-b] pyridin-7- yl] pyrrolidin- 3-yl] methanol; (1-(2-methyl-5-(4-(pyrrolidin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-3-yl) methanol; N,N-dimethyl-5-(4-(2-(methylamino)ethoxy)phenyl)-7-(octahydro-2H-pyrrolo[3,4- c]pyridin-2-yl)thieno[3,2-b]pyridin-2-amine; (1-(2-methoxy-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-3-yl) methanol; Attorney Docket No.: 185992002140 (1-(2-(dimethylamino)-5-(6-(piperazin-1-yl) pyridin-3-yl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-3-yl) methanol; (1-(2-(dimethylamino)-5-(4-(2-(methylamino) ethoxy) phenyl) thieno[3,2-b] pyridin-7- yl) pyrrolidin-3-yl) methanol; [1-[2-methoxy-5-[4-[2-(methylamino) ethoxy] phenyl] thieno[3,2-b] pyridin-7-yl] pyrrolidin-3-yl] methanol; 2-(2-methoxy-5-(4-(2-(methylamino)ethoxy)phenyl)thieno[3,2-b]pyridin-7-yl)octahydro- 4H-pyrrolo[3,4-c]pyridin-4-one; 2-[4-[7-[1,3,3a,4,5,6,7,7a-octahydropyrrolo[3,4-c] pyridin-2-yl]-2-methoxy-thieno[3,2-b] pyridin-5-yl] phenoxy]-N-methyl-ethanamine; N-methyl-N-(7-(6-methyl-2,6-diazaspiro[3.3]heptan-2-yl)-5-(4-(2- (methylamino)ethoxy)phenyl)thieno[3,2-b]pyridin-2-yl)acetamide; 2-(2-(dimethylamino)-5-(4-(2-(methylamino)ethoxy)phenyl)thieno[3,2-b]pyridin-7-yl)-5- methyloctahydro-4H-pyrrolo[3,4-c]pyridin-4-one; 1-(2-(dimethylamino)-5-(4-(2-(methylamino)ethoxy)phenyl)thieno[3,2-b]pyridin-7-yl)- N,N-dimethylpyrrolidine-3-carboxamide; 1-(2-(dimethylamino)-5-(6-(2-(methylamino)ethoxy)pyridin-3-yl)thieno[3,2-b]pyridin-7- yl)-N,N-dimethylpyrrolidine-3-carboxamide; and 5-(4-((1H-imidazol-4-yl)oxy)phenyl)-2-methoxy-7-(5-methyloctahydro-2H-pyrrolo[3,4- c]pyridin-2-yl)thieno[3,2-b]pyridine. In some embodiments, provided herein is a compound of formula (I), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceuticallyacceptable salt, hydrate, or solvate of any of the foregoing, wherein the compound is selectedfrom the group consisting of 2-methyl-7-(pyrrolidin-1-yl)-5-(4-(3-(pyrrolidin-1-yl) propoxy) phenyl) thieno[3,2-b] pyridine; 5-(3-chloro-4-methoxyphenyl)-2-methyl-7-(pyrrolidin-1-yl) thieno[3,2-b] pyridine; 5-(3,4-dimethoxyphenyl)-2-methyl-7-(pyrrolidin-1-yl) thieno[3,2-b] pyridine; 2-methyl-5-(4-(piperazin-1-yl) phenyl)-7-(pyrrolidin-1-yl) thieno[3,2-b] pyridine; N-methyl-2-(4-(2-methyl-7-(pyrrolidin-1-yl) thieno[3,2-b] pyridin-5-yl) phenoxy) ethan- 1-amine; 1-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-3-ol; Attorney Docket No.: 185992002140 7-(3-methoxypyrrolidin-1-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 2-methyl-5-(4-(piperazin-1-yl) phenyl)-7-(3-(trifluoromethyl) pyrrolidin-1-yl) thieno[3,2- b] pyridine; (1-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-3-yl) methanol; 3-methyl-1-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-3-ol; 2-methyl-7-(3-methylpyrrolidin-1-yl)-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 7-(3-fluoropyrrolidin-1-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; N, N-dimethyl-1-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-3-amine; 1-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-3-amine; N-methyl-1-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-3-amine; (1-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-3-yl) methanamine; 7-(3-cyclopropylpyrrolidin-1-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 2-methyl-7-(3-phenylpyrrolidin-1-yl)-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 7-(3,3-difluoropyrrolidin-1-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 2-methyl-7-((cis)-octahydro-2H-isoindol-2-yl)-5-(4-(piperazin-1-yl) phenyl) thieno[3,2- b] pyridine; 7-(3,3-dimethylpyrrolidin-1-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 3-methyl-1-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-3-amine; 2-methyl-5-(4-(piperazin-1-yl) phenyl)-7-(2,7-diazaspiro [4.4] nonan-2-yl) thieno[3,2-b] pyridine; Attorney Docket No.: 185992002140 2-methyl-5-(4-(piperazin-1-yl) phenyl)-7-(2,8-diazaspiro [4.5] decan-2-yl) thieno[3,2-b] pyridine; 7-((cis)-hexahydropyrrolo[3,4-c] pyrrol-2(1H)-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 2-methyl-7-((cis)-5-methylhexahydropyrrolo[3,4-c] pyrrol-2(1H)-yl)-5-(4-(piperazin-1- yl) phenyl) thieno[3,2-b] pyridine; 7-((cis)-hexahydropyrrolo[3,4-b] pyrrol-1(2H)-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 7-(2,5-diazabicyclo [2.2.1] heptan-2-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 1-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidine-3- carbonitrile (cis)-5-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) hexahydro- 1H-furo[3,4-c] pyrrole; 7-((cis)-3-azabicyclo [3.1.0] hexan-3-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 7-(1,1-difluoro-5-azaspiro [2.4] heptan-5-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 1-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl)-3-(trifluoromethyl) pyrrolidin-3-ol; 2-methyl-5-(4-(piperazin-1-yl) phenyl)-7-(2,6-diazaspiro [3.4] octan-6-yl) thieno[3,2-b] pyridine; 2-methyl-5-(4-(piperazin-1-yl) phenyl)-7-(1,7-diazaspiro [4.4] nonan-7-yl) thieno[3,2-b] pyridine; 2-methyl-5-(4-(piperazin-1-yl) phenyl)-7-(2,7-diazaspiro [4.5] decan-2-yl) thieno[3,2-b] pyridine; 2-methyl-7-(2-methylpyrrolidin-1-yl)-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine 2-methyl-5-(4-(piperazin-1-yl) phenyl)-7-(2-(trifluoromethyl) pyrrolidin-1-yl) thieno[3,2- b] pyridine; (1-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-2-yl) methanol; Attorney Docket No.: 185992002140 2-methyl-7-((cis)-octahydro-2H-pyrrolo[3,4-c] pyridin-2-yl)-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; (1-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-2-yl) methanamine; (S)-7-(2-(methoxymethyl) pyrrolidin-1-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 2-methyl-5-(4-(piperazin-1-yl) phenyl)-7-(2-(pyrrolidin-1-ylmethyl) pyrrolidin-1-yl) thieno[3,2-b] pyridine; 2-methyl-5-(4-(piperazin-1-yl) phenyl)-7-(2-(pyridin-3-yl) pyrrolidin-1-yl) thieno[3,2-b] pyridine; 7-(2-(4-chlorophenyl) pyrrolidin-1-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2- b] pyridine; 7-(2-(3-fluorophenyl) pyrrolidin-1-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2- b] pyridine; 7-(2-(4-fluorophenyl) pyrrolidin-1-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2- b] pyridine; (cis)-3-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl)-3-azabicyclo [3.1.0] hexan-6-amine; 2-methyl-7-(2-phenylpyrrolidin-1-yl)-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 2-methyl-5-(4-(piperazin-1-yl) phenyl)-7-(2-(pyridin-4-yl) pyrrolidin-1-yl) thieno[3,2-b] pyridine; 2-amino-1-[4-[4-[2-methyl-7-[3-(methylaminomethyl) vazetidin-1-yl] thieno[3,2-b] pyridin-5-yl] phenyl] piperazin-1-yl] propan-1-one; (cis)-2-[2-methoxy-5-[4-[2-(methylamino) ethoxy] phenyl] thieno[3,2-b] pyridin-7-yl]- 3,3a,4,5,7,7a-hexahydro-1H-pyrrolo[3,4-c] pyridin-6-one; 1-[1-[5-[4-(1H-imidazol-4-yloxy) phenyl]-2-methoxy-thieno[3,2-b] pyridin-7-yl] azetidin-3-yl]-N-methyl-methanamine; 2-[4-[7-((cis)-7,7-difluoro-3,3a,4,5,6,7a-hexahydro-1H-pyrrolo[3,4-c] pyridin-2-yl)-2- methoxy-thieno[3,2-b] pyridin-5-yl] phenoxy]-N-methyl-ethanamine; 2-(4-(2-methoxy-7-((cis)-octahydro-2H-pyrrolo[3,4-c]pyridin-2-yl)thieno[3,2-b]pyridin- 5-yl)phenoxy)-N-methylethan-1-amine; Attorney Docket No.: 185992002140 2-(4-(2-(methoxy-d3)-7-((cis)-octahydro-2H-pyrrolo[3,4-c]pyridin-2-yl)thieno[3,2- b]pyridin-5-yl)phenoxy)-N-methylethan-1-amine; [1-[2-(dimethylamino)-5-(4-piperazin-1-ylphenyl) thieno[3,2-b] pyridin-7- yl] pyrrolidin-3-yl] methanol; (1-(2-methyl-5-(4-(pyrrolidin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-3-yl) methanol; N,N-dimethyl-5-(4-(2-(methylamino)ethoxy)phenyl)-7-((trans)-octahydro-2H- pyrrolo[3,4-c]pyridin-2-yl)thieno[3,2-b]pyridin-2-amine; (1-(2-methoxy-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-3-yl) methanol; (1-(2-(dimethylamino)-5-(6-(piperazin-1-yl) pyridin-3-yl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-3-yl) methanol; (1-(2-(dimethylamino)-5-(4-(2-(methylamino) ethoxy) phenyl) thieno[3,2-b] pyridin-7- yl) pyrrolidin-3-yl) methanol; [1-[2-methoxy-5-[4-[2-(methylamino) ethoxy] phenyl] thieno[3,2-b] pyridin-7-yl] pyrrolidin-3-yl] methanol; (cis)-2-(2-methoxy-5-(4-(2-(methylamino)ethoxy)phenyl)thieno[3,2-b]pyridin-7-yl)octahydro-4H-pyrrolo[3,4-c]pyridin-4-one; and2-[4-[7-[(trans)-1,3,3a,4,5,6,7,7a-octahydropyrrolo[3,4-c] pyridin-2-yl]-2-methoxy- thieno[3,2-b] pyridin-5-yl] phenoxy]-N-methyl-ethanamine. In some embodiments, provided herein is a compound of formula (I), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate of any of the foregoing, wherein the compound is selected from the group consisting of 2-methyl-7-(pyrrolidin-1-yl)-5-(4-(3-(pyrrolidin-1-yl) propoxy) phenyl) thieno[3,2-b] pyridine; 5-(3-chloro-4-methoxyphenyl)-2-methyl-7-(pyrrolidin-1-yl) thieno[3,2-b] pyridine; 5-(3,4-dimethoxyphenyl)-2-methyl-7-(pyrrolidin-1-yl) thieno[3,2-b] pyridine; 2-methyl-5-(4-(piperazin-1-yl) phenyl)-7-(pyrrolidin-1-yl) thieno[3,2-b] pyridine; N-methyl-2-(4-(2-methyl-7-(pyrrolidin-1-yl) thieno[3,2-b] pyridin-5-yl) phenoxy) ethan- 1-amine; 1-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-3-ol; Attorney Docket No.: 185992002140 7-(3-methoxypyrrolidin-1-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 2-methyl-5-(4-(piperazin-1-yl) phenyl)-7-(3-(trifluoromethyl) pyrrolidin-1-yl) thieno[3,2- b] pyridine; (1-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-3-yl) methanol; 3-methyl-1-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-3-ol; 2-methyl-7-(3-methylpyrrolidin-1-yl)-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 7-(3-fluoropyrrolidin-1-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; N, N-dimethyl-1-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-3-amine; 1-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-3-amine; N-methyl-1-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-3-amine; (1-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-3-yl) methanamine; 7-(3-cyclopropylpyrrolidin-1-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 2-methyl-7-(3-phenylpyrrolidin-1-yl)-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 7-(3,3-difluoropyrrolidin-1-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 2-methyl-7-(octahydro-2H-isoindol-2-yl)-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 7-(3,3-dimethylpyrrolidin-1-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 3-methyl-1-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-3-amine; 2-methyl-5-(4-(piperazin-1-yl) phenyl)-7-(2,7-diazaspiro [4.4] nonan-2-yl) thieno[3,2-b] pyridine; Attorney Docket No.: 185992002140 2-methyl-5-(4-(piperazin-1-yl) phenyl)-7-(2,8-diazaspiro [4.5] decan-2-yl) thieno[3,2-b] pyridine; 7-(hexahydropyrrolo[3,4-c] pyrrol-2(1H)-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 2-methyl-7-(5-methylhexahydropyrrolo[3,4-c] pyrrol-2(1H)-yl)-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 7-(hexahydropyrrolo[3,4-b] pyrrol-1(2H)-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 7-(2,5-diazabicyclo [2.2.1] heptan-2-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 1-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidine-3- carbonitrile 5-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) hexahydro-1H- furo[3,4-c] pyrrole; 7-(3-azabicyclo [3.1.0] hexan-3-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 7-(1,1-difluoro-5-azaspiro [2.4] heptan-5-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 1-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl)-3-(trifluoromethyl) pyrrolidin-3-ol; 2-methyl-5-(4-(piperazin-1-yl) phenyl)-7-(2,6-diazaspiro [3.4] octan-6-yl) thieno[3,2-b] pyridine; 2-methyl-5-(4-(piperazin-1-yl) phenyl)-7-(1,7-diazaspiro [4.4] nonan-7-yl) thieno[3,2-b] pyridine; 2-methyl-5-(4-(piperazin-1-yl) phenyl)-7-(2,7-diazaspiro [4.5] decan-2-yl) thieno[3,2-b] pyridine; 2-methyl-7-(2-methylpyrrolidin-1-yl)-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine 2-methyl-5-(4-(piperazin-1-yl) phenyl)-7-(2-(trifluoromethyl) pyrrolidin-1-yl) thieno[3,2- b] pyridine; (1-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-2-yl) methanol; Attorney Docket No.: 185992002140 2-methyl-7-(octahydro-2H-pyrrolo[3,4-c] pyridin-2-yl)-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; (1-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-2-yl) methanamine; 7-(2-(methoxymethyl) pyrrolidin-1-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 2-methyl-5-(4-(piperazin-1-yl) phenyl)-7-(2-(pyrrolidin-1-ylmethyl) pyrrolidin-1-yl) thieno[3,2-b] pyridine; 2-methyl-5-(4-(piperazin-1-yl) phenyl)-7-(2-(pyridin-3-yl) pyrrolidin-1-yl) thieno[3,2-b] pyridine; 7-(2-(4-chlorophenyl) pyrrolidin-1-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2- b] pyridine; 7-(2-(3-fluorophenyl) pyrrolidin-1-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2- b] pyridine; 7-(2-(4-fluorophenyl) pyrrolidin-1-yl)-2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2- b] pyridine; 3-(2-methyl-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl)-3-azabicyclo [3.1.0] hexan-6-amine; 2-methyl-7-(2-phenylpyrrolidin-1-yl)-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridine; 2-methyl-5-(4-(piperazin-1-yl) phenyl)-7-(2-(pyridin-4-yl) pyrrolidin-1-yl) thieno[3,2-b] pyridine; 2-amino-1-[4-[4-[2-methyl-7-[3-(methylaminomethyl) vazetidin-1-yl] thieno[3,2-b] pyridin-5-yl] phenyl] piperazin-1-yl] propan-1-one; 2-[2-methoxy-5-[4-[2-(methylamino) ethoxy] phenyl] thieno[3,2-b] pyridin-7-yl]- 3,3a,4,5,7,7a-hexahydro-1H-pyrrolo[3,4-c] pyridin-6-one; 1-[1-[5-[4-(1H-imidazol-4-yloxy) phenyl]-2-methoxy-thieno[3,2-b] pyridin-7-yl] azetidin-3-yl]-N-methyl-methanamine; 2-[4-[7-(7,7-difluoro-3,3a,4,5,6,7a-hexahydro-1H-pyrrolo[3,4-c] pyridin-2-yl)-2- methoxy-thieno[3,2-b] pyridin-5-yl] phenoxy]-N-methyl-ethanamine; 2-(4-(2-methoxy-7-(octahydro-2H-pyrrolo[3,4-c]pyridin-2-yl)thieno[3,2-b]pyridin-5- yl)phenoxy)-N-methylethan-1-amine; Attorney Docket No.: 185992002140 2-(4-(2-(methoxy-d3)-7-(octahydro-2H-pyrrolo[3,4-c]pyridin-2-yl)thieno[3,2-b]pyridin- 5-yl)phenoxy)-N-methylethan-1-amine; [1-[2-(dimethylamino)-5-(4-piperazin-1-ylphenyl) thieno[3,2-b] pyridin-7- yl] pyrrolidin-3-yl] methanol; (1-(2-methyl-5-(4-(pyrrolidin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-3-yl) methanol; N,N-dimethyl-5-(4-(2-(methylamino)ethoxy)phenyl)-7-(octahydro-2H-pyrrolo[3,4- c]pyridin-2-yl)thieno[3,2-b]pyridin-2-amine; (1-(2-methoxy-5-(4-(piperazin-1-yl) phenyl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-3-yl) methanol; (1-(2-(dimethylamino)-5-(6-(piperazin-1-yl) pyridin-3-yl) thieno[3,2-b] pyridin-7-yl) pyrrolidin-3-yl) methanol; (1-(2-(dimethylamino)-5-(4-(2-(methylamino) ethoxy) phenyl) thieno[3,2-b] pyridin-7- yl) pyrrolidin-3-yl) methanol; [1-[2-methoxy-5-[4-[2-(methylamino) ethoxy] phenyl] thieno[3,2-b] pyridin-7-yl] pyrrolidin-3-yl] methanol; 2-(2-methoxy-5-(4-(2-(methylamino)ethoxy)phenyl)thieno[3,2-b]pyridin-7-yl)octahydro-4H-pyrrolo[3,4-c]pyridin-4-one; and2-[4-[7-[1,3,3a,4,5,6,7,7a-octahydropyrrolo[3,4-c] pyridin-2-yl]-2-methoxy-thieno[3,2-b] pyridin-5-yl] phenoxy]-N-methyl-ethanamine. PHARMACEUTICAL COMPOSITIONS Provided herein are pharmaceutical compositions comprising a compound of formula(I), or any variation or embodiment thereof, such as (II), (II-A), (II-B), (II-C), (III), (III-A), or(IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, orsolvate of any of the foregoing, as described elsewhere herein. In some embodiments, provided herein is a pharmaceutical composition comprising (i) a compound of formula (I),or any variation or embodiment thereof, such as (II), (II-A), (II-B), (II-C), (III), (III-A), or(IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate of any of the foregoing, and (ii) one or more pharmaceutically acceptable excipients.In another variation, provided is a pharmaceutical composition comprising a compound offormula (I) or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and one or more pharmaceuticallyacceptable excipients. This aspect in some embodiments may employ a compound of any of Attorney Docket No.: 185992002140formulas (I), (II), (II-A), (II-B), (II-C), (III), (III-A), or (IV), or a stereoisomer or tautomerthereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation orembodiment thereof. In some embodiments, the composition comprises a therapeuticallyeffective amount of the compound, or a stereoisomer or tautomer thereof, or apharmaceutically acceptable salt, hydrate, or solvate of any of the foregoing. In someembodiments, the composition comprises a therapeutically effective amount of thecompound, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt ofany of the foregoing. In some embodiments, provided herein are pharmaceutical compositions comprising(i) a compound of formula (I), stereoisomer or tautomer thereof, or apharmaceutically acceptable salt thereof, and (ii) one or more pharmaceutically acceptableexcipients, wherein R1is H or C1-6alkyl; R2is C1-6alkyl or C3-6cycloalkyl, wherein the C1-6alkyl or C3-6cycloalkyl of R2 is optionally substituted with one or more -OH or-N(Rx)(Ry),or R1 and R2 are taken together with the N to which they are attached to form a 3- to 12-membered heterocyclyl, wherein 3- to 12-membered heterocyclyl of R1 and R2 is optionally substituted with one ormore R3; each R3is independently halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, oxo, -OR10, -SR10, -SF5, - N(Rx)(Ry), -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, - OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), - C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, - S(=NR13)N(R11)R12, -S(=NR13)OR13, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein Attorney Docket No.: 185992002140 the C1-6alkyl of R3is optionally substituted with one or more R3a; the C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with one or more R3b; and optionally, two substituents of R3are taken together with the atoms to which they are attached form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10- membered aryl, or 5- to 10-membered heteroaryl is optionally substituted one or more R3b; Ring A is phenyl or 5- to 6-membered heteroaryl, wherein the phenyl or 5- to 6-membered heteroaryl of Ring A is optionally substituted by one or more R4, and the 5- to 6-membered heteroaryl of Ring A comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; each R4is independently halo, C1-6alkyl, or -OR10; L is a bond, C1-6alkyl, -O-(C1-6alkyl)-, -S-(C1-6alkyl)-, or -N(R5)(C1-6alkyl)-, wherein the C1-6alkyl, -O-(C1-6alkyl)-, -S-(C1-6alkyl)-, or -N(R5)(C1-6alkyl)- is optionally substituted by one or more RL; each RLis independently halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, -OC(=O)N(R11)R12, - OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, C3-8cycloalkyl, 3- to 8- membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, or two RLare taken together along with the atoms to which they are attached to form a C3-8cycloalkyl or 3- to 8-membered heterocyclyl; R5is H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -C(=O)R12, -S(=O)2R12, -S(=O)2N(R11)(R12), or C3-8cycloalkyl, wherein the C1-6alkyl of R5is optionally substituted with one or more halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, - OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), - C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, - S(=NR13)N(R11)R12, -S(=NR13)OR13, -S(=O)2R12, or -S(=O)2N(R11)(R12), and the C3-8cycloalkyl is optionally substituted with one or more R5b; Attorney Docket No.: 185992002140 R6is H, -OR9, -OR10, -N(Rx)(Ry), -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, - N(R11)C(=O)OR12, -OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, - C(=O)N(R11)(R12), -C(=O)OR12, 5- to 6-membered heteroaryl, or 3- to 8-membered heterocyclyl, wherein the 3- to 8-membered heterocyclyl is optionally substituted with one or more R6b, - C(=O)R12, -C(=O)N(R11)(R12), or -C(=O)OR12; R7is H; R8is halo, C1-6alkyl, C1-6haloalkyl, -OR9, -OR10, -N(Rx)(Ry), -N(R11)C(=O)R12, - N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, -OC(=O)N(R11)R12, - OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, 3- to 8-membered heterocyclyl, wherein the 3- to 8-membered heterocyclyl of R8is optionally substituted with one or more R7b, and the 3- to 8-membered heterocyclyl of R8comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; each R1a, R3a, R4a, R6a, or R7ais independently halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -NO2, - CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, - OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, - C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, -N(R11)S(=O)2R12, - S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, -S(=NR13)N(R13)R12, - S(=NR13)OR12, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R1a, R3a, R4a, R6a, or R7ais optionally substituted with one or more R1b, and the 3- to 12-membered heterocyclyl of R1a, R3a, R4a, R6a, or R7acomprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; each R1b, R3b, R4b, R5b, R6b, or R7bis independently halo, C1-6alkyl, -OR9, -N(Rx)(Ry), oxo, - CN, C3-8cycloalkyl, or 3- to 8-membered heterocyclyl, wherein the C1-6alkyl of R1b, R3b, R4b, R5b, R6b, or R7bis optionally substituted by -OR12, - N(Rx)(Ry), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl; Attorney Docket No.: 185992002140 each R9is independently H, C1-6alkyl, C2-6alkenyl, C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R9is optionally substituted with 6- to 10-membered aryl, or 5- to 10- membered heteroaryl wherein the 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, or -N(Rx)(Ry), and the 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R9is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, -N(Rx)(Ry), or 3- to 12- membered heterocyclyl; each R10is independently H, C1-6alkyl, or C3-8cycloalkyl, wherein the C1-6alkyl is optionally substituted with one or more halo, deuterium, 3- to 8-membered heterocyclyl, phenyl, or 5- to 6-membered heteroaryl, wherein the C3-8cycloalkyl, phenyl, or 5- to 6-membered heteroaryl is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, or -N(Rx)(Ry); each R11is independently H, C1-6alkyl, or C3-8cycloalkyl; each R12is independently H, C1-6alkyl, C3-8cycloalkyl, phenyl, 5- to 6-membered heteroaryl, or 3- to 8-membered heterocyclyl, wherein the C1-6alkyl of R12is optionally substituted by one or more halo, -OH, -O(C1-6alkyl), -N(Rx)(Ry), C3-8cycloalkyl, phenyl, 5- to 6-membered heteroaryl, or 3- to 12- membered heterocyclyl, and the C3-8cycloalkyl, phenyl, 5- to 6-membered heteroaryl, or 3- to 12-membered heterocyclyl of R12is optionally substituted with halo, C1-6alkyl, or -N(Rx)(Ry); each R13is independently H or C1-6alkyl; and each Rxand Ryis independently H, C1-6alkyl, C3-8cycloalkyl, -C(=O)(C1-6alkyl), or - C(=O)O(C1-6alkyl), wherein the C1-6alkyl of Rxor Ryis optionally substituted with 6- to 10-membered aryl, 5- to 10-membered heteroaryl, or -NH2, NH(C1-6alkyl), or -N(C1-6alkyl)(C1-6alkyl), and the C1-6alkyl of -C(=O)(C1-6alkyl) or -C(=O)O(C1-6alkyl) is optionally substituted with -O(C=O)C1-8alkyl); wherein (i) when R1 and R2 are taken together with the N to which they are attached to form , -(Ring A)-L-R6are not taken together to form a pyrazolyl substituted by Br; and Attorney Docket No.: 185992002140(ii) when -(Ring A)-L-R6 are taken together to form , R1 is H, and R2 is -CH3, R8is not -CH3. Suitable pharmaceutically acceptable excipients may include, for example, fillers, diluents, sterile aqueous solutions and various organic solvents, permeation enhancers, solubilizers, and adjuvants. Various substances may be embraced by the term excipient, including without limitation any substance used as a binder, disintegrant, coating, compression / encapsulation aid, cream or lotion, lubricant, solutions for parenteral administration, materials for chewable tablets, sweetener or flavoring, suspending / gelling agent, or wet granulation agent. Examples of suitable excipients are well-known to those skilled in the art. See, e.g., Handbook of Pharmaceutical Excipients, Pharmaceutical Press (2017), which is incorporated herein by reference in its entirety. Such compositions are prepared in a manner well known in the pharmaceutical art. See, e.g., Remington’s Pharmaceutical Sciences, Academic Press, 23rded. (2020), which is incorporated herein byreference in its entirety.METHODS OF TREATMENT Traumatic brain injury (TBI) is a risk factor for ALS as demonstrated by the significantly higher incidence of disease in professional athletes and military veterans [See,e.g., Lehman et al. Neurology 79, 1970-1974 (2012); McKee et al. J. Neuropathol. Exp.Neurol. 69, 989-929 (2010); Chio et al. Brain 128, 472-476 (2005), and Sagiraju et al. Mil.Med. 185 e501-e509 (2020), each of which is incorporated herein by reference in its entirety].Cytoplasmic accumulation of TDP-43 has been shown in ~80% brains of patients withrepeated head traumas [McKee et al. J. Neuropathol. Exp. Neurol. 69, 989-929 (2010), whichis incorporated herein by reference in its entirety]. TDP-43 proteinopathy and loss-of- function has been shown to be a driver of neurodegeneration and pathology in preclinicalmodels of brain injury and ALS [Lai et al. Cell Stem Cell 31, 519-536 (2024); Dogan et al.Acta Neuropathol Commun 11, 206 (2023); and Kahriman et al. Brain 146, 5139-5152(2023), each of which is incorporated herein by reference in its entirety]. Neurofilament lightchain (NfL) and glial fibrillary acid protein (GFAP) are prognostic neurodegeneration biomarkers for both TBI [Shahim et al. Neurology 95, e610-e622 (2020); Shahim et al. SciRep 6, 36791 (2016) and Abdelhak et al. Nat Rev Neuro 18, 158-172 (2022), each of which isincorporated herein by reference in its entirety] and ALS [Lu et al. Neurology 84, 2247- Attorney Docket No.: 1859920021402257); and Benninger et al. J Clin Neurosci 26, 75-78 (2016), each of which is incorporatedherein by reference in its entirety]. In one aspect, provided is a method for treating a disease or condition mediated byTDP-43, comprising administering to an individual in need thereof a compound of formula(I) or any variation or embodiment thereof, such as (II), (II-A), (II-B), (II-C), (III), (III-A), or(IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, orsolvate of any of the foregoing, or a pharmaceutical composition comprising a compound offormula (I) or any variation or embodiment thereof, such as (II), (II-A), (II-B), (II-C), (III),(III-A), or (IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt,hydrate, or solvate of any of the foregoing, and one or more pharmaceutically acceptableexcipients. In some embodiments, provided is a method for treating a disease or conditionmediated by TDP-43, comprising administering to an individual in need thereof a compoundof formula (I) or any variation or embodiment thereof, such as (II), (II-A), (II-B), (II-C), (III),(III-A), or (IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable saltof any of the foregoing, or a pharmaceutical composition comprising a compound of formula(I) or any variation or embodiment thereof, such as (II), (II-A), (II-B), (II-C), (III), (III-A), or(IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any ofthe foregoing, and one or more pharmaceutically acceptable excipients. In someembodiments, a therapeutically effective amount of a compound of formula (I) or anyvariation or embodiment thereof, such as (II), (II-A), (II-B), (II-C), (III), (III-A), or (IV), or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate ofany of the foregoing, or a pharmaceutical composition comprising a compound of formula (I) or any variation or embodiment thereof, such as (II), (II-A), (II-B), (II-C), (III), (III-A), or (IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, orsolvate of any of the foregoing, and one or more pharmaceutically acceptable excipients isadministered. In some embodiments, a therapeutically effective amount of a compound offormula (I) or any variation or embodiment thereof, such as (II), (II-A), (II-B), (II-C), (III),(III-A), or (IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition comprising a compound of formula(I) or any variation or embodiment thereof, such as (II), (II-A), (II-B), (II-C), (III), (III-A), or(IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any ofthe foregoing, and one or more pharmaceutically acceptable excipients is administered. Insome embodiments, the methods selectively modulate TDP-43. In some embodiments, the Attorney Docket No.: 185992002140 methods reduce TDP-43 cytoplasmic inclusions, improve nuclear TDP-43 function, or reduce neurodegeneration. In some embodiments, the methods reduce TDP-43 cytoplasmic inclusions. In some embodiments, the methods improve nuclear TDP-43 function. In some embodiments, the methods reduce neurodegeneration. In some embodiments, the methods mitigate TDP-43 cytoplasmic condensates in motor neurons. In some embodiments, the motor neurons are iPSC-derived motor neurons. In some embodiments, STMN2 andPOLDIP3 splicing in iPSC-derived motor neurons is restored.In some embodiments, provided herein is a method for treating a disease or conditionmediated by TDP-43, comprising administering to an individual in need thereof a compoundof formula (I), stereoisomer or tautomer thereof, or apharmaceutically acceptable salt thereof, and (ii) one or more pharmaceutically acceptableexcipients, wherein R1is H or C1-6alkyl; R2is C1-6alkyl or C3-6cycloalkyl, wherein the C1-6alkyl or C3-6cycloalkyl of R2 is optionally substituted with one or more -OH or-N(Rx)(Ry),or R1 and R2 are taken together with the N to which they are attached to form a 3- to 12-membered heterocyclyl, wherein 3- to 12-membered heterocyclyl of R1 and R2 is optionally substituted with one ormore R3; each R3is independently halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, oxo, -OR10, -SR10, -SF5, - N(Rx)(Ry), -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, - OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), - C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, - S(=NR13)N(R11)R12, -S(=NR13)OR13, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein Attorney Docket No.: 185992002140 the C1-6alkyl of R3is optionally substituted with one or more R3a; the C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with one or more R3b; and optionally, two substituents of R3are taken together with the atoms to which they are attached form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10- membered aryl, or 5- to 10-membered heteroaryl is optionally substituted one or more R3b; Ring A is phenyl or 5- to 6-membered heteroaryl, wherein the phenyl or 5- to 6-membered heteroaryl of Ring A is optionally substituted by one or more R4, and the 5- to 6-membered heteroaryl of Ring A comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; each R4is independently halo, C1-6alkyl, or -OR10; L is a bond, C1-6alkyl, -O-(C1-6alkyl)-, -S-(C1-6alkyl)-, or -N(R5)(C1-6alkyl)-, wherein the C1-6alkyl, -O-(C1-6alkyl)-, -S-(C1-6alkyl)-, or -N(R5)(C1-6alkyl)- is optionally substituted by one or more RL; each RLis independently halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, -OC(=O)N(R11)R12, - OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, C3-8cycloalkyl, 3- to 8- membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, or two RLare taken together along with the atoms to which they are attached to form a C3-8cycloalkyl or 3- to 8-membered heterocyclyl; R5is H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -C(=O)R12, -S(=O)2R12, -S(=O)2N(R11)(R12), or C3-8cycloalkyl, wherein the C1-6alkyl of R5is optionally substituted with one or more halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, - OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), - C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, - S(=NR13)N(R11)R12, -S(=NR13)OR13, -S(=O)2R12, or -S(=O)2N(R11)(R12), and the C3-8cycloalkyl is optionally substituted with one or more R5b; Attorney Docket No.: 185992002140 R6is H, -OR9, -OR10, -N(Rx)(Ry), -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, - N(R11)C(=O)OR12, -OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, - C(=O)N(R11)(R12), -C(=O)OR12, 5- to 6-membered heteroaryl, or 3- to 8-membered heterocyclyl, wherein the 3- to 8-membered heterocyclyl is optionally substituted with one or more R6b, - C(=O)R12, -C(=O)N(R11)(R12), or -C(=O)OR12; R7is H; R8is halo, C1-6alkyl, C1-6haloalkyl, -OR9, -OR10, -N(Rx)(Ry), -N(R11)C(=O)R12, - N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, -OC(=O)N(R11)R12, - OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, 3- to 8-membered heterocyclyl, wherein the 3- to 8-membered heterocyclyl of R8is optionally substituted with one or more R7b, and the 3- to 8-membered heterocyclyl of R8comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; each R1a, R3a, R4a, R6a, or R7ais independently halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -NO2, - CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, - OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, - C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, -N(R11)S(=O)2R12, - S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, -S(=NR13)N(R13)R12, - S(=NR13)OR12, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R1a, R3a, R4a, R6a, or R7ais optionally substituted with one or more R1b, and the 3- to 12-membered heterocyclyl of R1a, R3a, R4a, R6a, or R7acomprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; each R1b, R3b, R4b, R5b, R6b, or R7bis independently halo, C1-6alkyl, -OR9, -N(Rx)(Ry), oxo, - CN, C3-8cycloalkyl, or 3- to 8-membered heterocyclyl, wherein the C1-6alkyl of R1b, R3b, R4b, R5b, R6b, or R7bis optionally substituted by -OR12, - N(Rx)(Ry), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl; Attorney Docket No.: 185992002140 each R9is independently H, C1-6alkyl, C2-6alkenyl, C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R9is optionally substituted with 6- to 10-membered aryl, or 5- to 10- membered heteroaryl wherein the 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, or -N(Rx)(Ry), and the 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R9is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, -N(Rx)(Ry), or 3- to 12- membered heterocyclyl; each R10is independently H, C1-6alkyl, or C3-8cycloalkyl, wherein the C1-6alkyl is optionally substituted with one or more halo, deuterium, 3- to 8-membered heterocyclyl, phenyl, or 5- to 6-membered heteroaryl, wherein the C3-8cycloalkyl, phenyl, or 5- to 6-membered heteroaryl is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, or -N(Rx)(Ry); each R11is independently H, C1-6alkyl, or C3-8cycloalkyl; each R12is independently H, C1-6alkyl, C3-8cycloalkyl, phenyl, 5- to 6-membered heteroaryl, or 3- to 8-membered heterocyclyl, wherein the C1-6alkyl of R12is optionally substituted by one or more halo, -OH, -O(C1-6alkyl), -N(Rx)(Ry), C3-8cycloalkyl, phenyl, 5- to 6-membered heteroaryl, or 3- to 12- membered heterocyclyl, and the C3-8cycloalkyl, phenyl, 5- to 6-membered heteroaryl, or 3- to 12-membered heterocyclyl of R12is optionally substituted with halo, C1-6alkyl, or -N(Rx)(Ry); each R13is independently H or C1-6alkyl; and each Rxand Ryis independently H, C1-6alkyl, C3-8cycloalkyl, -C(=O)(C1-6alkyl), or - C(=O)O(C1-6alkyl), wherein the C1-6alkyl of Rxor Ryis optionally substituted with 6- to 10-membered aryl, 5- to 10-membered heteroaryl, or -NH2, NH(C1-6alkyl), or -N(C1-6alkyl)(C1-6alkyl), and the C1-6alkyl of -C(=O)(C1-6alkyl) or -C(=O)O(C1-6alkyl) is optionally substituted with -O(C=O)C1-8alkyl); wherein (i) when R1 and R2 are taken together with the N to which they are attached to form , -(Ring A)-L-R6are not taken together to form a pyrazolyl substituted by Br; and Attorney Docket No.: 185992002140(ii) when -(Ring A)-L-R6 are taken together to form , R1 is H, and R2 is -CH3, R8is not -CH3. In some embodiments, the disease or condition is a neurological disease or condition.In some embodiments, the disease or condition is selected from the group consisting ofAlzheimer’s disease, Parkinson’s disease, Huntington’s disease, traumatic brain injury (TBI), chronic traumatic encephalopathy (CTE), frontotemporal dementia (FTD), inclusion bodymyositis, Perry syndrome, corticobasal degeneration, spinocerebellar ataxia type 3, andamyotrophic lateral sclerosis (ALS). In some embodiments, the disease or condition is traumatic brain injury (TBI).In some embodiments, the disease or condition is frontotemporal dementia (FTD).In some embodiments, the disease or condition is amyotrophic lateral sclerosis (ALS).In some variations, the amyotrophic lateral sclerosis is sporadic amyotrophic lateral sclerosisor C9ORF72 amyotrophic lateral sclerosis. In some embodiments, the individual is a human.In one aspect, provided herein is a method of reducing neurodegeneration, comprisingadministering to an individual in need thereof a compound of formula (I) or any variation orembodiment thereof, such as (II), (II-A), (II-B), (II-C), (III), (III-A), or (IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate of any of the foregoing, or a pharmaceutical composition comprising a compound of formula (I) or any variation or embodiment thereof, such as (II), (II-A), (II-B), (II-C), (III), (III-A), or (IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, orsolvate of any of the foregoing, and one or more pharmaceutically acceptable excipients. Insome embodiments, provided herein is a method of reducing neurodegeneration, comprisingadministering to an individual in need thereof a compound of formula (I) or any variation orembodiment thereof, such as (II), (II-A), (II-B), (II-C), (III), (III-A), or (IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of theforegoing, or a pharmaceutical composition comprising a compound of formula (I) or anyvariation or embodiment thereof, such as (II), (II-A), (II-B), (II-C), (III), (III-A), or (IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and one or more pharmaceutically acceptable excipients. In some embodiments,the individual has a neurological disease or condition. In some embodiments, the individualhas a disease or condition selected from the group consisting of Alzheimer’s disease, Attorney Docket No.: 185992002140 Parkinson’s disease, Huntington’s disease, traumatic brain injury (TBI), chronic traumatic encephalopathy (CTE), frontotemporal dementia (FTD), inclusion body myositis, Perrysyndrome, corticobasal degeneration, spinocerebellar ataxia type 3, and amyotrophic lateralsclerosis (ALS). In some embodiments, the individual has frontotemporal dementia (FTD).In some embodiments, the individual has a traumatic brain injury or ALS. In someembodiments, the individual has a traumatic brain injury. In some embodiments, theindividual has ALS. In some variations, the amyotrophic lateral sclerosis is sporadicamyotrophic lateral sclerosis or C9ORF72 amyotrophic lateral sclerosis. In one aspect, provided herein is a method of reducing neurodegeneration fromtraumatic brain injury, comprising administering to an individual in need thereof a compoundof formula (I) or any variation or embodiment thereof, such as (II), (II-A), (II-B), (II-C), (III),(III-A), or (IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate of any of the foregoing, or a pharmaceutical composition comprising acompound of formula (I) or any variation or embodiment thereof, such as (II), (II-A), (II-B),(II-C), (III), (III-A), or (IV), or a stereoisomer or tautomer thereof, or a pharmaceuticallyacceptable salt, hydrate, or solvate of any of the foregoing, and one or more pharmaceuticallyacceptable excipients. In some embodiments, provided herein is a method of reducingneurodegeneration from traumatic brain injury, comprising administering to an individual inneed thereof a compound of formula (I) or any variation or embodiment thereof, such as (II),(II-A), (II-B), (II-C), (III), (III-A), or (IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical compositioncomprising a compound of formula (I) or any variation or embodiment thereof, such as (II),(II-A), (II-B), (II-C), (III), (III-A), or (IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and one or more pharmaceutically acceptable excipients. In one aspect, provided herein is a method of modulating TDP-43, comprisingcontacting a cell with an effective amount of a compound of formula (I) or any variation orembodiment thereof, such as (II), (II-A), (II-B), (II-C), (III), (III-A), or (IV), or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate ofany of the foregoing, or a pharmaceutical composition comprising a compound of formula (I) or any variation or embodiment thereof, such as (II), (II-A), (II-B), (II-C), (III), (III-A), or(IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, orsolvate of any of the foregoing, and one or more pharmaceutically acceptable excipients. In Attorney Docket No.: 185992002140 some embodiments, provided herein is a method of modulating TDP-43, comprisingcontacting a cell with an effective amount of a compound of formula (I) or any variation orembodiment thereof, such as (II), (II-A), (II-B), (II-C), (III), (III-A), or (IV), or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of theforegoing, or a pharmaceutical composition comprising a compound of formula (I) or anyvariation or embodiment thereof, such as (II), (II-A), (II-B), (II-C), (III), (III-A), or (IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of theforegoing, and one or more pharmaceutically acceptable excipients. In some embodiments,modulating TDP-43 comprises modulating TDP-43 incorporation into condensates,modulating TDP-43 binding to RNA in condensates, modulating TDP-43 aggregation, ormodulating TDP-43 protein-protein interactions. In some embodiments, modulating TDP-43comprises modulating TDP-43 incorporation into condensates. In some embodiments,modulating TDP-43 comprises modulating TDP-43 aggregation. In some embodiments,modulating TDP-43 comprises modulating TDP-43 binding to RNA in condensates. In someembodiments, modulating TDP-43 comprises modulating TDP-43 protein-proteininteractions. In some embodiments, modulating TDP-43 comprises mitigating TDP-43interaction to RNA condensates, mitigating TDP-43 aggregation, or mitigating TDP-43 protein-protein interactions. In some embodiments, modulating TDP-43 comprises mitigating TDP-43 interaction to RNA condensates. In some embodiments, modulating TDP-43 comprises mitigating TDP-43 aggregation. In some embodiments, modulating TDP-43 comprises mitigating TDP-43 protein-protein interactions. In some embodiments, the methods selectively modulate TDP-43. In some embodiments, the methods reduce TDP-43 cytoplasmic inclusions, improve nuclear TDP-43 function, or reduce neurodegeneration. In some embodiments, the methods reduce TDP-43 cytoplasmic inclusions. In some embodiments, the methods improve nuclear TDP-43 function. In some embodiments, the methods reduce neurodegeneration. In some embodiments, the methods mitigate TDP-43 cytoplasmic condensates in motor neurons. In some embodiments, the motor neurons areiPSC-derived motor neurons. In some embodiments, STMN2 and POLDIP3 splicing iniPSC-derived motor neurons is restored. In one aspect, provided herein is a method of modulating TDP-43 driven geneexpression levels, comprising contacting a cell with an effective amount of a compound offormula (I) or any variation or embodiment thereof, such as (II), (II-A), (II-B), (II-C), (III),(III-A), or (IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, Attorney Docket No.: 185992002140 hydrate, or solvate of any of the foregoing, or a pharmaceutical composition comprising acompound of formula (I) or any variation or embodiment thereof, such as (II), (II-A), (II-B),(II-C), (III), (III-A), or (IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate of any of the foregoing, and one or more pharmaceuticallyacceptable excipients. In some embodiments, provided herein is a method of modulatingTDP-43 driven gene expression levels, comprising contacting a cell with an effective amountof a compound of formula (I) or any variation or embodiment thereof, such as (II), (II-A), (II-B), (II-C), (III), (III-A), or (IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition comprising acompound of formula (I) or any variation or embodiment thereof, such as (II), (II-A), (II-B),(II-C), (III), (III-A), or (IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and one or more pharmaceutically acceptableexcipients. In some embodiments, the gene expression levels are for STMN2 or POLDIP3. Insome embodiments, the gene expression levels are for STMN2. In some embodiments, thegene expression levels are for POLDIP3. In some embodiments, the methods selectivelymodulate TDP-43. In some embodiments, the methods reduce TDP-43 cytoplasmic inclusions, improve nuclear TDP-43 function, or reduce neurodegeneration. In some embodiments, the methods reduce TDP-43 cytoplasmic inclusions. In some embodiments, the methods improve nuclear TDP-43 function. In some embodiments, the methods reduce neurodegeneration. In some embodiments, the methods mitigate TDP-43 cytoplasmic condensates in motor neurons. In some embodiments, the motor neurons are iPSC-derivedmotor neurons. In some embodiments, STMN2 and POLDIP3 splicing in iPSC-derivedmotor neurons is restored. In one aspect, provided herein is a compound of formula (I), or any variation orembodiment thereof, such as (II), (II-A), (II-B), (II-C), (III), (III-A), or (IV), or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate ofany of the foregoing, or a pharmaceutical composition comprising a compound of formula (I) or any variation or embodiment thereof, such as (II), (II-A), (II-B), (II-C), (III), (III-A), or(IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, orsolvate of any of the foregoing, and one or more pharmaceutically acceptable excipients, foruse in the treatment of a disease or condition mediated by TDP-43. In some embodiments,provided herein is a compound of formula (I), or any variation or embodiment thereof, suchas (II), (II-A), (II-B), (II-C), (III), (III-A), or (IV), or a stereoisomer or tautomer thereof, or a Attorney Docket No.: 185992002140 pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical compositioncomprising a compound of formula (I), or any variation or embodiment thereof, such as (II),(II-A), (II-B), (II-C), (III), (III-A), or (IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and one or more pharmaceutically acceptable excipients, for use in the treatment of a disease or condition mediated by TDP-43. In one aspect, provided herein is the use of a compound of formula (I) or anyvariation or embodiment thereof, such as (II), (II-A), (II-B), (II-C), (III), (III-A), or (IV), or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate ofany of the foregoing, or a pharmaceutical composition comprising a compound of formula (I) or any variation or embodiment thereof, such as (II), (II-A), (II-B), (II-C), (III), (III-A), or(IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, orsolvate of any of the foregoing, and one or more pharmaceutically acceptable excipients, inthe manufacture a medicament for the treatment of a disease or condition mediated by TDP-43. In some embodiments, provided herein is the use of a compound of formula (I) or anyvariation or embodiment thereof, such as (II) or (III), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceuticalcomposition comprising a compound of formula (I) or any variation or embodiment thereof,such as (II) or (III), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and one or more pharmaceutically acceptable excipients, in the manufacture a medicament for the treatment of a disease or condition mediated by TDP-43. KITS The present disclosure further provides kits for carrying out the methods disclosedherein. The kits may comprise a compound, or stereoisomer or tautomer thereof, orpharmaceutically acceptable salt, hydrate, or solvate thereof as described herein and suitablepackaging. The kits may comprise one or more containers comprising any compounddescribed herein. In one aspect, a kit includes a compound of the disclosure, or stereoisomeror tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate thereof, and alabel and / or instructions for use of the compound in the treatment of a disease or disorderdescribed herein. The kits may comprise a unit dosage form of the compound. In someembodiments, the kits may comprise a compound, or stereoisomer or tautomer thereof, orpharmaceutically acceptable salt thereof. Provided herein are kits, comprising (i) an effective amount of a compound offormula (I) or any variation or embodiment thereof, such as (II), (II-A), (II-B), (II-C), (III), Attorney Docket No.: 185992002140(III-A), or (IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt,hydrate, or solvate of any of the foregoing, and (ii) instructions for use in treating a TDP-43mediated disease, disorder, or condition in an individual in need thereof. In someembodiments, the kits comprise (i) an effective amount of a compound of formula (I) or anyvariation or embodiment thereof, such as (II), (II-A), (II-B), (II-C), (III), (III-A), or (IV), or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of theforegoing, and (ii) instructions for use in treating a TDP-43 mediated disease, disorder, orcondition in an individual in need thereof. Also provided herein are kits, comprising (i) apharmaceutical composition comprising an effective amount of a compound of formula (I) orany variation or embodiment thereof, such as (II), (II-A), (II-B), (II-C), (III), (III-A), or (IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, orsolvate of any of the foregoing, and one or more pharmaceutically acceptable excipients; and(ii) instructions for use in treating a TDP-43 mediated disease, disorder, or condition in anindividual in need thereof. In some embodiments, the kits comprise (i) a pharmaceuticalcomposition comprising an effective amount of a compound of formula (I) or any variation orembodiment thereof, such as (II), (II-A), (II-B), (II-C), (III), (III-A), or (IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and one or more pharmaceutically acceptable excipients; and (ii) instructions foruse in treating a TDP-43 mediated disease, disorder, or condition in an individual in needthereof. In some embodiments, the individual is a human. Articles of manufacture are also provided, wherein the article of manufacturecomprises a compound of formula (I) or any variation or embodiment thereof, such as (II),(II-A), (II-B), (II-C), (III), (III-A), or (IV), or a stereoisomer or tautomer thereof, or apharmaceutically acceptable salt, hydrate, or solvate of any of the foregoing, in a suitablecontainer. In some embodiments, the article of manufacture comprises a compound offormula (I) or any variation or embodiment thereof, such as (II), (II-A), (II-B), (II-C), (III),(III-A), or (IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable saltof any of the foregoing, in a suitable container. Also provided herein are articles ofmanufacture, comprising a pharmaceutical composition comprising a compound of formula(I) or any variation or embodiment thereof, such as (II), (II-A), (II-B), (II-C), (III), (III-A), or(IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, orsolvate of any of the foregoing, in a suitable container. In some embodiments, the articles of Attorney Docket No.: 185992002140manufacture comprise a pharmaceutical composition comprising a compound of formula (I)or any variation or embodiment thereof, such as (II), (II-A), (II-B), (II-C), (III), (III-A), or (IV), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any ofthe foregoing, in a suitable container. The container may be a vial, jar, ampoule, preloadedsyringe, or intravenous bag. METHODS OF PREPARING The present disclosure further provides processes for preparing the compounds of present invention. In some aspects, provided herein are processes of preparing a compound offormula (I), or any variation or embodiment thereof or a stereoisomer or tautomer thereof, ora pharmaceutically acceptable salt, hydrate, or solvate of any of the foregoing. In someembodiments, provided herein are processes of preparing a compound of formula (I), or anyvariation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceuticallyacceptable salt of any of the foregoing. In some embodiments, provided herein are processesof preparing a compound of formula (I), or any variation or embodiment thereof, or astereoisomer or tautomer thereof. The following synthetic reaction schemes, which are detailed in the Schemes and Examples, are merely illustrative of some of the methods by which the compounds of the present disclosure, or an embodiment or aspect thereof, can be synthesized. Various modifications to these synthetic reaction schemes can be made, as will be apparent to those of ordinary skill in the art. As depicted in the Schemes and Examples below, in certain exemplary embodiments, compounds of formula (I), or any variation or embodiment thereof, as described elsewhere herein, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate,or solvate of any of the foregoing, are prepared according to the general procedures. Thegeneral methods below, and other methods known to synthetic chemists of ordinary skill in the art, can be applied to all formulae, embodiments, and species described herein. The starting materials and the intermediates of the synthetic reaction schemes can be isolated and purified if desired using conventional techniques, including, but not limited to, filtration, distillation, crystallization, chromatography, and the like. Such materials can be characterized using conventional means, including physical constants and spectral data. Although certain exemplary embodiments are depicted and described herein, the compounds of the present disclosure, or any variation or embodiment thereof, may be Attorney Docket No.: 185992002140 prepared using appropriate starting materials according to the methods described generally herein and / or by methods available to one of ordinary skill in the art. All the products generated from the following reactions can be isolated and purified employing standard techniques, such as extraction, ion exchange chromatography, chromatography on silica gel, prep-HPLC. Specific purification steps and methods were set up and will be referred to in the text as follows. Compounds may be prepared by methods known in the art of organic chemistry as set forth in part by the following synthesis schemes. In all the schemes described below, it is well understood that protecting groups for sensitive or reactive groups are employed where necessary in accordance with general principles of chemistry. Protecting groups are manipulated according to standard methods of organic synthesis (T. W. Green and P.G.M. Wuts (1991) Protecting Groups in Organic Synthesis, John Wiley et Sons, hereby incorporated by reference in its entirety). These groups are removed at a convenient stage of the compound synthesis using methods that are readily apparent to those skilled in the art. The compound may be represented as a mixture of enantiomers, which may be resolved intothe individual pure R- or S-enantiomers.The substituted 2,4-dichloro (methyl)thienopyridine A.1 were used as startingmaterial of FP (Final Product) synthetic sequence (Schemes 1 to 3). 2,4-Dichlorothienopyridine A.1 underwent a Suzuki cross coupling (Scheme 1) withcommercially available or synthesized boronic acid or ester derivatives bor. (see sectionSynthesis of non-commercially available reagents). Thienopyridine A.1 were selectivelysubstituted in position 2 to give compounds A.2. The substitution of position 4 of compoundA.2 was realized by Buchwald cross coupling or by aromatic nucleophilic substitution (SNAr)with amines to afford FP.SCHEME 1. In some cases, the substituted (hetero)aromatic ring added during the Suzuki couplingon thienopyridines A.1 contained a PG (Protecting Group, Scheme 2). In these cases, FP wasobtained after an additional step of deprotection. Scheme 2 describes the synthetic sequence Attorney Docket No.: 185992002140 similar to Scheme 1, with a Suzuki cross coupling realized first on thienopyridines A.1,followed by the substitution of thienopyridine B.1 using a Buchwald reaction or a SNAr toafford compounds B2. Compound B.2 underwent then a deprotection step to give FP.SCHEME 2. Scheme 3 describes a synthetic sequence where both boronic ester derivatives used for the Suzuki coupling and the amine used for the Buchwald coupling or aromaticsubstitution held a protecting group, PG and PG’ respectively. Compound C.1 was then fullydeprotected to give FP. SCHEME 3.

[0002] Attorney Docket No.: 185992002140 Enumerated Embodiments Enumerated Embodiment 1. A compound of Formula (I): or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, orsolvate of any of the foregoing, wherein:R1 and R2 are each independently H, C1-6alkyl, C2-6alkenyl, -C(=O)R12, -C(=O)OR12, - C(=O)N(R11)(R12), -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 12-memberedheterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, whereinthe C1-6alkyl of R1 or R2 is optionally substituted with one or more R1a,the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to10-membered heteroaryl of R1 or R2 is optionally substituted with one or more R1b,and optionally, two substituents of the C1-6alkyl, C2-6alkenyl, -C(=O)R12, -C(=O)OR12, - C(=O)N(R11)(R12), -S(=O)2R12, -S(=O)2N(R11)(R12), or C3-8cycloalkyl group of R1or R2 are taken together with the atoms to which they are attached to form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl,or 5- to 10-membered heteroaryl is optionally substituted with one or moreR1b;or R1 and R2 are taken together with the N to which they are attached to form a 3- to 12-membered heterocyclyl or 5- to 10-membered heteroaryl, whereinthe 3- to 12-membered heterocyclyl or 5- to 10-membered heteroaryl of R1 and R2 isoptionally substituted with one or more R3; each R3is independently halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, oxo, -OR10, -SR10, -SF5, -N(Rx)(Ry), -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, - Attorney Docket No.: 185992002140 OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), - C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, - S(=NR13)N(R11)R12, -S(=NR13)OR13, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R3is optionally substituted with one or more R3a, and optionally, two substituents of R3are taken together with the atoms to which they are attached form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10- membered aryl, or 5- to 10-membered heteroaryl is optionally substituted one or more R3b; Ring A is C3-8cycloalkyl, 4- to 12-membered cycloalkenyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 4- to 12-membered cycloalkenyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of Ring A is optionally substituted by one or more R4, and the 3- to 12-membered heterocyclyl or 5- to 10-membered heteroaryl of Ring A comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; each R4is independently halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -OR10, -SR10, -SF5, - N(Rx)(Ry), -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, - OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), - C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, - S(=NR13)N(R11)R12, -S(=NR13)OR13, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R4is optionally substituted by one or more R4a, the C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R4is optionally substituted with one or more R4b, and the 3- to 8-membered heterocyclyl of R4comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; L is a bond, C1-6alkyl, -O-(C1-6alkyl)-, -S-(C1-6alkyl)-, or -N(R5)(C1-6alkyl)-, wherein Attorney Docket No.: 185992002140 the C1-6alkyl, -O-(C1-6alkyl)-, -S-(C1-6alkyl)-, or -N(R5)(C1-6alkyl)- is optionally substituted by one or more RL; each RLis independently halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, -OC(=O)N(R11)R12, - OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, C3-8cycloalkyl, 3- to 8- membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, or two RLare taken together along with the atoms to which they are attached to form a C3-8cycloalkyl or 3- to 8-membered heterocyclyl; R5is H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -C(=O)R12, -S(=O)2R12, -S(=O)2N(R11)(R12), or C3-8cycloalkyl, wherein the C1-6alkyl of R5is optionally substituted with one or more halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, - OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), - C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, - S(=NR13)N(R11)R12, -S(=NR13)OR13, -S(=O)2R12, or -S(=O)2N(R11)(R12), and the C3-8cycloalkyl is optionally substituted with one or more R5b; R6is H, halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -OR9, -OR10, -SR10, -SF5, -N(Rx)(Ry), - NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, - OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, - C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, -N(R11)S(=O)2R12, - S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, -S(=NR13)N(R11)R12, - S(=NR13)OR13, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R6is optionally substituted by one or more R6a, the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R6is optionally substituted with one or more R6b, - C(=O)R12, -C(=O)N(R11)(R12), or -C(=O)OR12, and the 3- to 12-membered heterocyclyl of R6comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S, and optionally, two substituents of R6are taken together with the atoms to which they are attached form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein Attorney Docket No.: 185992002140 the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with one or more R6b; R7and R8are each independently H, halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -OR9, -OR10, - SR10, -SF5, -N(Rx)(Ry), -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, - N(R11)C(=O)OR12, -OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, - C(=O)N(R11)(R12), -C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, - C(=NR13)OR12, -N(R11)S(=O)2R12, -S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, -S(=NR13)N(R13)R12, -S(=NR13)OR12, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R7or R8is optionally substituted by one or more R7a, the 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R7or R8is optionally substituted with one or more R7b, and the 3- to 8-membered heterocyclyl of R7or R8comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S, and optionally, two substituents of R7or R8are taken together with the atoms to which they are attached form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10- membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with one or more R7b; each R1a, R3a, R4a, R6a, or R7ais independently halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -NO2, - CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, - OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, - C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, -N(R11)S(=O)2R12, - S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, -S(=NR13)N(R13)R12, - S(=NR13)OR12, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R1a, R3a, R4a, R6a, or R7ais optionally substituted with one or more R1b, and the 3- to 12-membered heterocyclyl of R1a, R3a, R4a, R6a, or R7acomprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; Attorney Docket No.: 185992002140 each R1b, R3b, R4b, R5b, R6b, or R7bis independently halo, C1-6alkyl, -OR9, -N(Rx)(Ry), oxo, - CN, C3-8cycloalkyl, or 3- to 8-membered heterocyclyl, wherein the C1-6alkyl of R1b, R3b, R4b, R5b, R6b, or R7bis optionally substituted by -OR12, - N(Rx)(Ry), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl; each R9is independently H, C1-6alkyl, C2-6alkenyl, C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R9is optionally substituted with 6- to 10-membered aryl, or 5- to 10- membered heteroaryl wherein the 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, or -N(Rx)(Ry), and the 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R9is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, -N(Rx)(Ry), or 3- to 12-membered heterocyclyl; each R10is independently H, C1-6alkyl, C2-6alkenyl, C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl is optionally substituted with one or more halo, deuterium, C1-6alkoxy, -N(Rx)(Ry), or 3- to 8-membered heterocyclyl; each R11is independently H, C1-6alkyl, or C3-8cycloalkyl; each R12is independently H, C1-6alkyl, C2-6alkenyl, C3-8cycloalkyl, 6- to 10-membered aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the C1-6alkyl of R12is optionally substituted by one or more halo, -OH, -O(C1-6alkyl), -SH, -S(C1-6alkyl), -(C=O)NH2, -(C=O)OH, -O(C=O)C1-8alkyl), -NH(C=NH)NH2, - N(Rx)(Ry), C3-8cycloalkyl, 6- to 10-membered aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein the 6- to 10-membered aryl is optionally substituted by -OH, and the C3-8cycloalkyl, 6- to 10-membered aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocyclyl of R12is optionally substituted with halo, C1- 6alkyl, or -N(Rx)(Ry); each R13is independently H or C1-6alkyl; and each Rxand Ryis independently H, C1-6alkyl, C3-8cycloalkyl, -C(=O)(C1-6alkyl), or - C(=O)O(C1-6alkyl), wherein Attorney Docket No.: 185992002140 the C1-6alkyl of Rx or Ry is optionally substituted with 6- to 10-membered aryl, 5- to10-membered heteroaryl, or -NH2, NH(C1-6alkyl), or -N(C1-6alkyl)(C1-6alkyl), and the C1-6alkyl of -C(=O)(C1-6alkyl) or -C(=O)O(C1-6alkyl) is optionally substituted with-O(C=O)C1-8alkyl). Enumerated Embodiment 2. The compound of Enumerated Embodiment 1, or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate ofany of the foregoing, wherein:R1 is H, C1-6alkyl, C2-6alkenyl, -C(=O)R12, -C(=O)OR12, -C(=O)N(R11)(R12), -S(=O)2R12, - S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl,or 5- to 10-membered heteroaryl, whereinthe C1-6alkyl of R1is optionally substituted with one or more R1a, the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to10-membered heteroaryl of R1 is optionally substituted with one or more R1b, andoptionally, two substituents of the C1-6alkyl, C2-6alkenyl, -C(=O)R12, -C(=O)OR12, - C(=O)N(R11)(R12), -S(=O)2R12, -S(=O)2N(R11)(R12), or C3-8cycloalkyl group of R1are taken together with the atoms to which they are attached to form a C3-8cycloalkyl, 3-to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-memberedheteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl,or 5- to 10-membered heteroaryl is optionally substituted with one or moreR1b; R2is C1-6alkyl, C2-6alkenyl, -C(=O)R12, -C(=O)OR12, -C(=O)N(R11)(R12), -S(=O)2R12, - S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl,or 5- to 10-membered heteroaryl, whereinthe C1-6alkyl of R2is optionally substituted with one or more R1a, the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to10-membered heteroaryl of R2 is optionally substituted with one or more R1b, andoptionally, two substituents of the C1-6alkyl, C2-6alkenyl, -C(=O)R12, -C(=O)OR12, - C(=O)N(R11)(R12), -S(=O)2R12, -S(=O)2N(R11)(R12), or C3-8cycloalkyl group of R2are taken together with the atoms to which they are attached to form a C3-8cycloalkyl, 3-to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-memberedheteroaryl, wherein Attorney Docket No.: 185992002140 the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with one or more R1b; or R1and R2are taken together with the N to which they are attached to form a 3- to 12- membered heterocyclyl or 5- to 10-membered heteroaryl, wherein the 3- to 12-membered heterocyclyl or 5- to 10-membered heteroaryl of R1and R2is optionally substituted with one or more R3; R7is H, halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -OR9, -OR10, -SR10, -SF5, -N(Rx)(Ry), - NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, - OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, - C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, -N(R11)S(=O)2R12, - S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, -S(=NR13)N(R13)R12, - S(=NR13)OR12, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R7is optionally substituted by one or more R7a, the 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R7is optionally substituted with one or more R7b, and the 3- to 8-membered heterocyclyl of R7comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S, and optionally, two substituents of R7are taken together with the atoms to which they are attached form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with one or more R7b; and R8is halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -OR9, -OR10, -SR10, -SF5, -N(Rx)(Ry), -NO2, - CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, - OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, - C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, -N(R11)S(=O)2R12, - S(=O)R12, -S(=O)2R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, -S(=NR13)N(R13)R12, - S(=NR13)OR12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10- membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R8is optionally substituted by one or more R7a, Attorney Docket No.: 185992002140 the 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-memberedheteroaryl of R8is optionally substituted with one or more R7b, and the 3- to 8-membered heterocyclyl of R8 comprises 1, 2, or 3 atoms selected from thegroup consisting of N, O, and S, and optionally, two substituents of R8are taken together with the atoms to which they are attached form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-memberedaryl, or 5- to 10-membered heteroaryl, whereinthe C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl,or 5- to 10-membered heteroaryl is optionally substituted with one or moreR7b; wherein (i) when -(Ring A)-L-R6 are taken together to form , and R1 is H, R8 is notoptionally substituted pyrazolyl; (ii) when R1and R2are taken together with the N to which they are attached to form ,-(Ring A)-L-R6 are not taken together to form a pyrazolyl substituted by 3-methylphenyl; and (iii) when -(Ring A)-L-R6 are taken together to form , R1 is H, and R2 is -CH3, R6is not -CH3. Enumerated Embodiment 3. The compound of Enumerated Embodiment 1 or 2, or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate ofany of the foregoing, wherein:R1 is H, C1-6alkyl, C2-6alkenyl, -C(=O)R12, -C(=O)OR12, -C(=O)N(R11)(R12), or C3-8cycloalkyl, wherein the C1-6alkyl of R1is optionally substituted with one or more R1a, the C3-8cycloalkyl of R1is optionally substituted with one or more R1b, and Attorney Docket No.: 185992002140 optionally, two substituents of the C1-6alkyl, C2-6alkenyl, -C(=O)R12, -C(=O)OR12, - C(=O)N(R11)(R12), or C3-8cycloalkyl group of R1are taken together with the atoms to which they are attached to form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with one or more R1b; R2is C1-6alkyl, C2-6alkenyl, -C(=O)R12, -C(=O)OR12, -C(=O)N(R11)(R12), or C3-8cycloalkyl, wherein the C1-6alkyl of R2is optionally substituted with one or more R1a, the C3-8cycloalkyl of R2is optionally substituted with one or more R1b, and optionally, two substituents of the C1-6alkyl, C2-6alkenyl, -C(=O)R12, -C(=O)OR12, - C(=O)N(R11)(R12), or C3-8cycloalkyl group of R2are taken together with the atoms to which they are attached to form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with one or more R1b; or R1and R2are taken together with the N to which they are attached to form a 3- to 12- membered heterocyclyl or 5- to 10-membered heteroaryl, wherein the 3- to 12-membered heterocyclyl or 5- to 10-membered heteroaryl of R1and R2is optionally substituted with one or more R3; each R3is independently halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, oxo, -OR10, -SR10, -SF5, - N(Rx)(Ry), -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, - OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), - C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R3is optionally substituted with one or more R3a, and optionally, two substituents of R3are taken together with the atoms to which they are attached form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, Attorney Docket No.: 185992002140 wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10- membered aryl, or 5- to 10-membered heteroaryl is optionally substituted one or more R3b; Ring A is C3-8cycloalkyl, 4- to 8-membered cycloalkenyl, 3- to 8-membered heterocyclyl, phenyl, or 5- to 6-membered heteroaryl, wherein the C3-8cycloalkyl, 4- to 8-membered cycloalkenyl, 3- to 8-membered heterocyclyl, phenyl, or 5- to 6-membered heteroaryl of Ring A is optionally substituted by one or more R4, and the 3- to 8-membered heterocyclyl or 5- to 6-membered heteroaryl of Ring A comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; each R4is independently halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -OR10, -SR10, -SF5, - N(Rx)(Ry), -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, - OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), - C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R4is optionally substituted by one or more R4a, the C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R4is optionally substituted with one or more R4b, and the 3- to 8-membered heterocyclyl of R4comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; R5is H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -C(=O)R12, -S(=O)2R12, -S(=O)2N(R11)(R12), or C3-8cycloalkyl, wherein the C1-6alkyl of R5is optionally substituted with one or more halo, -N(Rx)(Ry), -OR10, -SR10, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, - OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, - C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)2R12, or -S(=O)2N(R11)(R12), and the C3-8cycloalkyl is optionally substituted with one or more R5b; R6is H, halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -OR9, -OR10, -SR10, -SF5, -N(Rx)(Ry), - NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, - OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, - C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, -N(R11)S(=O)2R12, - Attorney Docket No.: 185992002140 S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10- membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R6is optionally substituted by one or more R6a, the C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R6is optionally substituted with one or more R6b, - C(=O)R12, -C(=O)N(R11)(R12), or -C(=O)OR12, and the 3- to 8-membered heterocyclyl of R6comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S, and optionally, two substituents of R6are taken together with the atoms to which they are attached form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with one or more R6b; R7is H, halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -OR9, -OR10, -SR10, -SF5, -N(Rx)(Ry), - NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, - OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, - C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, -N(R11)S(=O)2R12, - S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10- membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R7is optionally substituted by one or more R7a, the 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R7is optionally substituted with one or more R7b, and the 3- to 8-membered heterocyclyl of R7comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S, and optionally, two substituents of R7are taken together with the atoms to which they are attached form a 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10- membered heteroaryl, wherein the 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10- membered heteroaryl is optionally substituted with one or more R7b; and R8is halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -OR9, -OR10, -SR10, -SF5, -N(Rx)(Ry), -NO2, - CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, - OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, - Attorney Docket No.: 185992002140 C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, -N(R11)S(=O)2R12, - S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10- membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R8is optionally substituted by one or more R7a, the 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R8is optionally substituted with one or more R7b, and the 3- to 8-membered heterocyclyl of R8comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S, and optionally, two substituents of R8are taken together with the atoms to which they are attached form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with one or more R7b; each R1a, R3a, R4a, R6a, or R7ais independently halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -NO2, - CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, - OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, - C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, -N(R11)S(=O)2R12, - S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10- membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R1a, R3a, R4a, R6a, or R7ais optionally substituted with one or more R1b, and the 3- to 12-membered heterocyclyl of R1a, R3a, R4a, R6a, or R7acomprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S each R1b, R3b, R4b, R5b, R6b, or R7bis independently halo, C1-6alkyl, -OR9, -N(Rx)(Ry), oxo, - CN, C3-8cycloalkyl, or 3- to 8-membered heterocyclyl, wherein the C1-6alkyl of R1b, R3b, R4b, R5b, R6b, or R7bis optionally substituted by -OR12, - N(Rx)(Ry), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, phenyl, or 5- to 6- membered heteroaryl; and each R12is independently H, C1-6alkyl, C2-6alkenyl, C3-8cycloalkyl, phenyl, 5- to 6-membered heteroaryl, or 3- to 12-membered heterocyclyl, wherein Attorney Docket No.: 185992002140 the C1-6alkyl of R12 is optionally substituted by one or more halo, -OH, -O(C1-6alkyl),-N(Rx)(Ry), C3-8cycloalkyl, phenyl, 5- to 6-membered heteroaryl, or 3- to 12-membered heterocyclyl, and the C3-8cycloalkyl, phenyl, 5- to 6-membered heteroaryl, or 3- to 12-memberedheterocyclyl of R12is optionally substituted with halo, C1-6alkyl, or -N(Rx)(Ry). Enumerated Embodiment 4. The compound of any of Enumerated Embodiments 1-3,or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, orsolvate of any of the foregoing, wherein:R1is H or C1-6alkyl; R2is C1-6alkyl or C3-6cycloalkyl, wherein the C1-6alkyl or C3-6cycloalkyl of R2 is optionally substituted with one or more -OH or-N(Rx)(Ry),or R1 and R2 are taken together with the N to which they are attached to form a 3- to 12-membered heterocyclyl, wherein the 3- to 12-membered heterocyclyl of R1 and R2 is optionally substituted with one ormore R3;Ring A is phenyl or 5- to 6-membered heteroaryl, whereinthe phenyl or 5- to 6-membered heteroaryl of Ring A is optionally substituted by oneor more R4, and the 5- to 6-membered heteroaryl of Ring A comprises 1, 2, or 3 atoms selected fromthe group consisting of N, O, and S;each R4 is independently halo or -OR10;R6 is H, -OR9, -OR10, -N(Rx)(Ry), -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, 5- to 6-membered heteroaryl, or 3- to 8-memberedheterocyclyl, wherein the 3- to 8-membered heterocyclyl is optionally substituted with one or more R6b, -C(=O)R12, -C(=O)N(R11)(R12), or -C(=O)OR12;R7is H; R8is C1-6alkyl, -OR9, -OR10, -N(Rx)(Ry), or -C(=O)R12;each R10 is independently H, C1-6alkyl, or C3-8cycloalkyl, whereinthe C1-6alkyl is optionally substituted with one or more halo, deuterium, or 3- to 8-membered heterocyclyl; and Attorney Docket No.: 185992002140each R12 is independently H, C1-6alkyl, C3-8cycloalkyl, phenyl, 5- to 6-membered heteroaryl,or 3- to 8-membered heterocyclyl, whereinthe C1-6alkyl of R12is optionally substituted by one or more halo, -OH, -O(C1-6alkyl), -N(Rx)(Ry), C3-8cycloalkyl, phenyl, 5- to 6-membered heteroaryl, or 3- to 12-membered heterocyclyl, and the C3-8cycloalkyl, phenyl, 5- to 6-membered heteroaryl, or 3- to 12-memberedheterocyclyl of R12is optionally substituted with halo, C1-6alkyl, or -N(Rx)(Ry). Enumerated Embodiment 5. The compound of any of Enumerated Embodiments 1-4,wherein the compound is a compound of Formula (II): stereoisomer or tautomer thereof, or apharmaceutically acceptable salt, hydrate, or solvate of any of the foregoing, wherein X1 isCH or N. Enumerated Embodiment 6. The compound of any of Enumerated Embodiments 1-5, wherein the compound is a compound of Formula (II-A): Attorney Docket No.: 185992002140 Enumerated Embodiment 7. The compound of any of Enumerated Embodiments 1-4, wherein the compound is a compound of Formula (III): (III), or a stereoisomer or tautomer thereof, ora pharmaceutically acceptable salt, hydrate, or solvate of any of the foregoing.Enumerated Embodiment 8. The compound of any of Enumerated Embodiments 1-7,or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, orsolvate of any of the foregoing, wherein R1 is H or C1-6alkyl.Enumerated Embodiment 9. The compound of any of Enumerated Embodiments 1-8, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, orsolvate of any of the foregoing, wherein R1 is H.Enumerated Embodiment 10. The compound of any of Enumerated Embodiments 1-9,or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, orsolvate of any of the foregoing, wherein R2 is C1-6alkyl or C3-6cycloalkyl, whereinthe C1-6alkyl or C3-6cycloalkyl of R2is optionally substituted with one or more -OH or -N(Rx)(Ry). Enumerated Embodiment 11. The compound of any of Enumerated Embodiments 1-10, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, orsolvate of any of the foregoing, wherein R2 is -(C1-6alkyl)NH2, -(C1-6alkyl)N(C1-6alkyl)(C1-6alkyl), -(C1-6alkyl)NH(C1-6alkyl-NH2), or -(C3-6cycloalkyl)NH2. Enumerated Embodiment 12. The compound of any of Enumerated Embodiments 1-11, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, orsolvate of any of the foregoing, wherein R2 is selected from the group consisting of Attorney Docket No.: 185992002140 Enumerated Embodiment 13. The compound of any of Enumerated Embodiments 1-7, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, orsolvate of any of the foregoing, wherein:R1 and R2 are taken together with the N to which they are attached to form a 3- to 12-membered heterocyclyl optionally substituted with one or more R3. Enumerated Embodiment 14. The compound of any of Enumerated Embodiments 1-7or 13, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, orsolvate of any of the foregoing, wherein R1 and R2 are taken together with the N to which Attorney Docket No.: 185992002140they are attached to form a 3- to 12-membered heterocyclyl optionally substituted with one ormore R3, wherein the 3- to 12-membered heterocyclyl comprises a 3- to 8-membered monocyclicheterocyclyl, a 5- to 12-membered fused heterocyclyl, or a 6- to 12-memberedspirocyclic heterocyclyl. Enumerated Embodiment 15. The compound of Enumerated Embodiment 13, or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate ofany of the foregoing, wherein R1 and R2 are taken together with the N to which they areattached to form a 4- to 12-membered heterocyclyl optionally substituted with one or moreR3. Enumerated Embodiment 16. The compound of Enumerated Embodiment 15, or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate ofany of the foregoing, wherein R1 and R2 are taken together with the N to which they areattached to form a saturated 3- to 10-membered heterocyclyl optionally substituted with oneor more R3. Enumerated Embodiment 17. The compound of Enumerated Embodiment 16, or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate ofany of the foregoing, wherein R1 and R2 are taken together with the N to which they areattached to form a saturated 4- to 6-membered monocyclic heterocyclyl optionally substitutedwith one or more R3. Enumerated Embodiment 18. The compound Enumerated Embodiment 17, or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate ofany of the foregoing, wherein R1 and R2 are taken together with the N to which they areattached to form an azetidinyl or pyrrolidinyl, wherein the azetidinyl or pyrrolidinyl is optionally substituted with one or more R3. Enumerated Embodiment 19. The compound of any of Enumerated Embodiments 15-18, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, orsolvate of any of the foregoing, wherein R1 and R2 are taken together with the N to whichthey are attached to form a heterocyclyl selected from the group consisting Attorney Docket No.: 185992002140 Attorney Docket No.: 185992002140 Enumerated Embodiment 20. The compound of Enumerated Embodiment 16, or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate ofany of the foregoing, wherein R1 and R2 are taken together with the N to which they areattached to form a saturated 6- to 10-membered fused or bridged heterocyclyl optionallysubstituted with one or more R3. Enumerated Embodiment 21. The compound Enumerated Embodiment 20, or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate ofany of the foregoing, wherein R1 and R2 are taken together with the N to which they areattached to form a group selected from the group consisting of Attorney Docket No.: 185992002140 Enumerated Embodiment 22. The compound of Enumerated Embodiment 16, or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate ofany of the foregoing, wherein R1 and R2 are taken together with the N to which they areattached to form a saturated 7- to 10-membered spirocyclic heterocyclyl optionallysubstituted with one or more R3. Enumerated Embodiment 23. The compound of Enumerated Embodiment 22, or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate ofany of the foregoing, wherein R1 and R2 are taken together with the N to which they areattached to form a group selected from the group consisting of, Attorney Docket No.: 185992002140 Enumerated Embodiment 24. The compound of any of Enumerated Embodiments 1-23, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, orsolvate of any of the foregoing, wherein R6 is H, -OR9, -OR10, -N(Rx)(Ry), -N(R11)C(=O)R12,5- to 6-membered heteroaryl, or 3- to 8-membered heterocyclyl, whereinthe 3- to 8-membered heterocyclyl is optionally substituted with one or more R6b.Enumerated Embodiment 25. The compound of any of Enumerated Embodiments 1-24, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, orsolvate of any of the foregoing, wherein R6 is H, -O(5- to 6-membered heteroaryl), -NH(C1-6alkyl), -NH(C3-6cycloalkyl), -NHC(O)(C1-6alkyl), -NHC(O)(C1-6alkyl)NH2, -N(C1-6alkyl)C(O)(C1-6alkyl)NH2, 5-membered heteroaryl, or 4- to 6-membered N-containingheterocyclyl, wherein the 4- to 6-membered N-containing heterocyclyl is optionally substituted with one ormore R6b, -C(=O)R12, -C(=O)N(R11)(R12), or -C(=O)OR12. Enumerated Embodiment 26. The compound of any of Enumerated Embodiments 1-25, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, orsolvate of any of the foregoing, wherein R6 is selected from the group consisting of , , , Attorney Docket No.: 185992002140 . Enumerated Embodiment 27. The compound of any of Enumerated Embodiments 1-26, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, orsolvate of any of the foregoing, wherein R8 is C1-6alkyl, -(C1-6alkyl)OH, -C1-6alkyl-O(C1-6alkyl), -(C1-6alkyl)(4- to 7-membered heterocyclyl), -O(C1-6alkyl), -O(C1-6alkyl)(4- to 7-membered heterocyclyl), -N(C1-6alkyl)(C1-6alkyl), or -C(O)(4- to 7-membered heterocyclyl),wherein each 4- to 7-membered heterocyclyl is optionally substituted by C1-6alkyl.Enumerated Embodiment 28. The compound of any of Enumerated Embodiments 1-27, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, orsolvate of any of the foregoing, wherein R8 is selected from the group consisting of -CH3, - Enumerated Embodiment 29. The compound of any of Enumerated Embodiments 1-4,or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, orsolvate of any of the foregoing, wherein:L is a bond or -O(C1-6alkyl)-; andR3 is H, -N(Rx)(Ry), or 4- to 12-membered heterocyclyl optionally substituted withone or more R3a. Attorney Docket No.: 185992002140 Enumerated Embodiment 30. The compound of any of Enumerated Embodiments 1-4,or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, orsolvate of any of the foregoing, wherein:R1 and R2 are taken together with the N to which they are attached to form a 4- to 12-membered heterocyclyl optionally substituted with one or more R3; L is a bond; and R6 is 4- to 12-membered heterocyclyl optionally substituted with one or more R6b, -C(=O)R12, -C(=O)N(R11)(R12), or -C(=O)OR12. Enumerated Embodiment 31. The compound of Enumerated Embodiment 30, or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate ofany of the foregoing, wherein:R6is piperazinyl optionally substituted with one or more R6b, -C(=O)R12, - C(=O)N(R11)(R12), or -C(=O)OR12. Enumerated Embodiment 32. The compound of any of Enumerated Embodiments 1-4,or 29, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, orsolvate of any of the foregoing, wherein:L is -O(C1-6alkyl)-; and R6is H or -N(Rx)(Ry). Enumerated Embodiment 33. The compound of any of Enumerated Embodiments 1-4,or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, orsolvate of any of the foregoing, or 31, wherein:Ring A is phenyl; and R6is C1-6alkyl. Enumerated Embodiment 34. The compound of Enumerated Embodiment 1, or astereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate ofany of the foregoing, wherein the compound is selected from Table 1. Enumerated Embodiment 35. A pharmaceutical composition comprising a compoundof any of Enumerated Embodiments 1-34, or a stereoisomer or tautomer thereof, or apharmaceutically acceptable salt, hydrate, or solvate of any of the foregoing, and one or morepharmaceutically acceptable excipients or carriers. Enumerated Embodiment 36. A method for treating a disease or condition mediatedby TDP-43, comprising administering to a subject in need thereof a compound of any of Attorney Docket No.: 185992002140 Enumerated Embodiments 1-34, or a stereoisomer or tautomer thereof, or a pharmaceuticallyacceptable salt, hydrate, or solvate of any of the foregoing, or the pharmaceutical compositionof Enumerated Embodiment 35.Enumerated Embodiment 37. The method of Enumerated Embodiment 36, wherein atherapeutically effective amount of the compound is administered. Enumerated Embodiment 38. The method of Enumerated Embodiment 36 or 37,wherein said disease or condition mediated by TDP-43 is a neurological disease or condition. Enumerated Embodiment 39. The method of Enumerated Embodiment 38, whereinthe neurological disease is selected from the group consisting of Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, traumatic brain injury (TBI), chronic traumatic encephalopathy (CTE), frontotemporal dementia (FTD), inclusion body myositis, Perry syndrome, corticobasaldegeneration, spinocerebellar ataxia type 3, and amyotrophic lateral sclerosis (ALS). Enumerated Embodiment 40. The method of Enumerated Embodiment 38 or 39,wherein the neurological disease or condition is traumatic brain injury (TBI). Enumerated Embodiment 41. The method of Enumerated Embodiment 38 or 39,wherein the neurological disease or condition is frontotemporal dementia (FTD). Enumerated Embodiment 42. The method of Enumerated Embodiment 38 or 39,wherein the neurological disease or condition is amyotrophic lateral sclerosis (ALS). Enumerated Embodiment 43. The method of any of Enumerated Embodiments 38, 39,or 42, wherein the neurological disease or condition is sporadic amyotrophic lateral sclerosis or C9ORF72 amyotrophic lateral sclerosis. Enumerated Embodiment 44. The method of any of Enumerated Embodiments 36-43,wherein the subject is a human. Enumerated Embodiment 45. A method of modulating TDP-43, comprisingcontacting a cell with an effective amount of a compound of any of Enumerated Embodiments 1-34, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptablesalt, hydrate, or solvate of any of the foregoing, or the pharmaceutical composition ofEnumerated Embodiment 35, wherein Attorney Docket No.: 185992002140 modulating TDP-43 comprises modulating TDP-43 incorporation into condensates,modulating TDP-43 binding to RNA in condensates, modulating TDP-43 aggregation, or modulating TDP-43 protein-protein interactions. Enumerated Embodiment 46. A method of modulating TDP-43 driven geneexpression levels, comprising contacting a cell with an effective amount of a compound of any of Enumerated Embodiments 1-34, or a stereoisomer or tautomer thereof, or apharmaceutically acceptable salt, hydrate, or solvate of any of the foregoing, or thepharmaceutical composition of Enumerated Embodiment 35.Enumerated Embodiment 47. The method of Enumerated Embodiment 46, whereinthe gene expression levels are for STMN2.Enumerated Embodiment 48. The method of Enumerated Embodiment 46, whereinthe gene expression levels are for POLDIP3.Enumerated Embodiment 49. The compound of any of Enumerated Embodiments 1-34, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, orsolvate thereof, or the pharmaceutical composition of Enumerated Embodiment 35 for use inthe treatment of a TDP-43 mediated disease or disorder. Enumerated Embodiment 50. Use of a compound of any of Enumerated Embodiments1-34, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, orsolvate thereof in the manufacture of a medicament for the treatment of a disease or disordermediated by TDP-43. Enumerated Embodiment 51. A kit, comprising (i) a compound of any one ofEnumerated Embodiments 1-34, or a stereoisomer or tautomer thereof, or a pharmaceuticallyacceptable salt, hydrate, or solvate of any of the foregoing, or the pharmaceutical compositionof Enumerated Embodiment 35 and (ii) instructions for use in treating a TDP-43 mediateddisease or condition in a subject in need thereof.EXAMPLES The reagents and starting materials are commercially available and / or, using well- known techniques, can be readily synthesized by one of ordinary skill in the art. Unless otherwise noted, all commercially starting materials were used without further purification. Specifically, the following abbreviations may be used in the examples and throughout the specification. Attorney Docket No.: 185992002140 Table 2. Attorney Docket No.: 185992002140 SCX general protocol. The hydrochloride salt product was neutralized by StrongCation Exchange Resin. The resin was first washed with two volumes of deionized water. The compound to neutralized was absorbed to the resin by washing the resin with a solution of the compound in methanol. The resin was then washed with deionized water until the pH of the solution is neutral. A solution of ammonium hydroxide and methanol was used tocleave compound from the resin. Solvents were then concentrated and lyophilized to get thedesired product. Prep-HPLC. Experiments were carried out at room temperature and detection wasdone by UV at 220 and 254 nm. The different methods used are described as follows. 1: ACSWH-GX-N; YMC triart C18 column 150 x 25 mm x 5 mm; mobile phase: water (HCl)-ACN 2: ACSWH-GX-N; Phenomenex Luna C18 column 150 x 25 mm x 10 mm; mobile phase: water (FA)-ACN 3: ACSWH-GX-N; Phenomenex Luna C18 column 150 x 25 mm x 10 mm; mobile phase: water (TFA)-ACN 4: ACSWH-GX-N; Unisil 3-100 C18 ultra column 150 x 50 mm x 3 mm; mobile phase: water (0.23% FA)-ACN 5: Agilent Infinity II 1260 / 1290, Agilent Infinity Lab Poroshell 1204; HPH-C18 column 21.2 x 150 mm; mobile phase: water (0.1% FA)-ACN (0.1% FA) 6 (basic system): Agilent Infinity II 1260 / 1290, Agilent Infinity Lab Poroshell 1204; HPH-C18 column 21.2 x 150 mm; mobile phase: water-ACN (0.1 % NH3) 7: ACSWH-GX-N; Waters Xbridge 150 x 25 mm x 5 mm; mobile phase: water (ammonia hydroxide v / v)-ACN Attorney Docket No.: 185992002140 8: ACSWH-GX-O; Phenomenex luna C18150 x 25 mm x 10mm; mobile phase: water (HCl)-ACN Flash chromatography. 1: Puri Flash XS520Plus, Interchim, PF-30SIHP-JP-F00xx, 30 μm 2: ISCO®, SepaFlash® Silica Flash columnNMR and LCMS. The analytical characterization of synthesized compounds wasdone by NMR and LCMS.1H NMR spectra were recorded on a Bruker AVANCE III 400, Bruker AVANCE NEO 400, Bruker AVANCE III HD 400 or on a Jeol ECZ 400 spectrometer at 400 MHz Data are reported as follows: chemical shift in ppm, deuterated solvent (CDCl3 for deuterated chloroform, DMSO-d6 for deuterated dimethylsulfoxide and methanol-d4for deuterated methanol), multiplicity (s = singulet, d = doublet, t = triplet, q = quartet, m = multiplet or overlap of non-equivalent resonances, integration, br = broad singulet, dd = doublet of doublet, dt = doublet of triplet, td = triplet of doublet, dq = doubletof quintuplet). Coupling constants J were measured in Hertz.LCMS spectra were recorded according to the following conditions. SHIMADZU LCMS-2020 using LabSolution software Version 5.89 and 5.93; HALO C18 column 3.0 x 30 mm x 5.0 um or Kinetex EVO C18 column 2.1 x 30 mm x 5 um; mobile phase: water (0.04% TFA)-ACN (0.02% TFA), at 50 °C on a 1 to 2 minutes gradient (flow rate 1.5 to 2.0 mL / min) with UV detection at 220 and 254 nm; ESI formass spectra. Agilent 1260 Infinity II, Agilent Poroshell 120 EC C18 or HPH C18 column 2.7 μm 2.1 x 50 mm; mobile phase: water (0.1% FA)-ACN on a two-minute gradient (flow rate 0.6 mL / min) or mobile phase: water (0.1% FA)-ACN on a five-minute gradient (flow rate 0.6 mL / min) or water (0.1% NH3)-ACN (flow rate 0.7 mL / min) with UV detection at 220 and 254 nm; ESI for mass spectra.Synthesis of non-commercially available boronic ester derivative reagentsbor.1: 1-(3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenoxy) propyl) pyrrolidine To a solution of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenol 4.1 (0.50 g,2.3 mmol, 1.0 equiv) and 1-(3-chloropropyl)pyrrolidine (0.30 g, 2.0 mmol, 0.90 equiv) in Attorney Docket No.: 185992002140 DMF (5.0 mL) was added KI (0.10 g, 0.60 mmol, 0.27 equiv) and Cs2CO3(2.2 g, 6.8 mmol,3.0 equiv) at 25 °C. The mixture was stirred at 65 °C for 16 hours. The reaction mixture wasconcentrated under reduced pressure to give a residue. The residue obtained was purified byprep-HPLC 3 (gradient: 25%-55% over 10 min) to give 1-[3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenoxy] propyl] pyrrolidine bor.1 (0.12 g, 0.36 mmol, 16% yield) as awhite solid. MS m / z (ESI) [M+H]+= 332.2.bor.2: tert-butyl methyl(2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenoxy) ethyl)carbamate To a solution of 4-(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) phenol 5.1 (0.50g, 2.3 mmol, 1.0 equiv) and tert-butyl N-(2-chloroethyl) -N-methyl-carbamate (0.40 g, 2.0mmol, 0.90 equiv) in DMF (5.0 mL) were added Cs2CO3 (1.5 g, 4.5 mmol, 2.0 equiv) and KI(75 mg, 0.45 mmol, 0.2 equiv) at 25 °C. The mixture was stirred at 60 °C for 12 hours. Themixture was diluted with water (10 mL) and then extracted with ethyl acetate (10 mL, three times). The combined organic layers were washed with brine (10 mL, three times), dried over Na2SO3, filtered, and concentrated under reduced pressure to give a residue. The residueobtained was purified by prep-HPLC 3 (gradient: 55%-85% over 10 min) to give tert-butyl N-methyl-N- [2- [4-(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) phenoxy] ethyl] carbamatebor.2 (0.15 g, 0.36 mmol, 16% yield, 90% purity) as a white solid.bor.3: tert-butyl methyl(2-((5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridin-2-yl)oxy) ethyl) carbamate Step1: To a mixture of tert-butyl N-(2-hydroxyethyl)-N-methylcarbamate 6.1 (1.0 g,5.7 mmol, 1.0 equiv) and 5-bromopyridin-2-ol (1.0 g, 5.8 mmol, 1.0 equiv) in THF (10 mL)were added PPh3 (1.8 g, 6.9 mmol, 1.2 equiv) and diisopropyl azodiformate (1.4 g, 6.9 mmol,1.2 equiv) at 25 °C. After stirring at 20 °C for 16 h, the reaction mixture was filtered and thefiltrate was concentrated in vacuo to give a crude product. The crude product was purified by Attorney Docket No.: 185992002140 column chromatography (SiO2, PE / EtOAc 10:1 to 3:1) to give tert-butyl N-[2-[(5-bromo-2-pyridyl) oxy] ethyl]-N-methylcarbamate 6.2 (1.5 g, 4.5 mmol, 79% yield, 99% purity) ascolorless oil. MS m / z (ESI) [M+H]+= 333.3. Step 2: To a mixture of tert-butyl N-[2-[(5-bromo-2-pyridyl)oxy]ethyl]-N-methyl-carbamate 6.2 (1.0 g, 3.0 mmol, 1.0 equiv) and 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3, 2-dioxaborolane (0.81 g, 3.2 mmol, 1.1 equiv) in dioxane (15 mL) were added KOAc (0.59 g, 6.0 mmol, 2.0 equiv) and Pd(dppf)Cl2 (0.25 g, 0.30 mmol,0.10 equiv) at 25 °C. After stirring at 80 °C for 3 h, the reaction mixture was filtered. Thefiltrate was concentrated in vacuo to give a crude product. The crude product was purified bycolumn chromatography (SiO2, PE / EtOAc 10:1 to 1:1) to give tert-butyl N-methyl-N- [2- [[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan- 2-yl)-2-pyridyl] oxy] ethyl] carbamate bor.3 (1.1 g,2.5 mmol, 82% yield, 85% purity) as yellow oil. MS m / z (ESI) [M-80] + = 297.2 .bor.4: tert-butyl N-[1-methyl-2-oxo-2-[4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl] piperazin-1-yl] ethyl] carbamate To a solution of 1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine7.1 (2.0 g, 6.9 mmol, 1.0 equiv) in DMF (5.0 mL) was added HATU (4.0 g, 10 mmol, 1.5equiv), 2-(tert-butoxycarbonylamino)propanoic acid (1.6 g, 8.3 mmol, 1.2 equiv) and DIEA (2.7 g, 20.8 mmol, 3.6 mL, 3.0 equiv) at 25 °C. The mixture was stirred at 25 °C for 16 hours. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was diluted with water (30 mL) and extracted with ethyl acetate (40 mL, three times). The combined organic layers were washed with brine (30 mL), dried over anhydrous Na2SO3, filtered, and concentrated under reduced pressure to give a residue. The crude product was triturated with MeOH (30 mL) at 25 °C for 20 min to give tert-butyl N-[1-methyl-2-oxo-2-[4- [4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazin-1-yl]ethyl]carbamate bor.4 (1.7 g, 3.5 mmol, 51% yield, 95% purity) was obtained as a white solid. MS m / z (ESI)[M+H]+ = 460.3. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 7.52 (d, J = 8.6 Hz, 2H), 6.99 (r d,J = 7.8 Hz, 1H), 6.92 (d, J = 8.7 Hz, 2H), 4.47 (quin, J = 7.2 Hz, 1H), 3.68 - 3.54 (m, 4H),3.26 - 3.16 (m, 4H), 1.37 (s, 9H), 1.26 (s, 12H), 1.15 (d, J = 6.8 Hz, 3H). Attorney Docket No.: 185992002140 bor.5: trimethyl- tetramethyl-1,3,2-dioxaborolan-2-yl) phenoxy] imidazol- 1-yl] methoxy] ethyl] silane Step 1: To a solution of 4-iodo-1H-imidazole 8.1 (10 g, 52 mmol, 1.0 equiv) in DMF(0.10 L) was added NaH (2.5 g, 62 mmol, 60% purity, 1.2 equiv) at 0 °C, the mixture was stirred at 0 °C for 0.5 h, then SEM-Cl (9.5 g, 57 mmol, 10 mL, 1.1 equiv) was added. Themixture was stirred at 25 °C for 2 hours. The reaction mixture was quenched by saturatedammonium chloride aqueous solution (0.20 L) at 0 °C, and then extracted with ethyl acetate (0.10 L, three times). The combined organic layers were washed with saturated brine (0.30 L), dried over anhydrous Na2SO3, filtered, and concentrated under reduced pressure to give aresidue. The residue obtained was purified by Flash chromatography (ISCO®; 80 gSepaFlash® Silica Flash Column, Eluent of 0~50% EtOAc / PE, gradient: 50 mL / min) to give2-[(4-iodoimidazol-1-yl) methoxy] ethyl-trimethyl-silane 8.2 (13 g, 30 mmol, 58% yield,74% purity) as colourless oil. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.01 (s, 1H), 7.77 (d,J = 0.9 Hz, 1H), 7.48 (d, J = 1.0 Hz, 1H), 7.05 (s, 1H), 5.29 (d, J = 11.3 Hz, 4H), 3.50 - 3.45(m, 4H), 0.86 - 0.82 (m, 4H), -0.04 (s, 18H).Step 2: A mixture of 2-[(4-iodoimidazol-1-yl)methoxy]ethyl-trimethyl-silane 8.2 (5.0g, 15 mmol, 1.0 equiv) , 4-bromophenol (4.0 g, 23 mmol, 1.5 equiv), bis[(Z)-1-methyl-3-oxo- but-1-enoxy]copper (0.81 g, 3.1 mmol, 0.20 equiv), Cs2CO3(15 g, 46 mmol, 3.0 equiv) in dioxane (50 mL) was degassed and purged with N2 three times, and then the mixture wasstirred at 120 °C for 16 hours under N2 atmosphere. The mixture was diluted with water (0.10L) and extracted with ethyl acetate (0.10 L, three times). The organic phase was washed with brine (0.20 L), dried over anhydrous Na2SO3, filtered and the filtrate was concentrated. The residue obtained was purified by Flash chromatography (ISCO®; 80 g SepaFlash® Silica Attorney Docket No.: 185992002140 Flash Column, Eluent of 0~100% EtOAc / PE, gradient: 50 mL / min) and prep-HPLC 7 (gradient: 62%-82% over 8 min) to give 2-[[4-(4-bromophenoxy)imidazol-1-yl]methoxy]ethyl-trimethyl-silane 8.3 (0.16 g, 0.42 mmol, 2.7% yield, 97% purity) as pinkoil. MS m / z (ESI) [M+H]+= 369.0. Step 3: A mixture of 2-[[4-(4-bromophenoxy)imidazol-1-yl]methoxy]ethyl-trimethyl-silane 8.3 (0.16 g, 0.43 mmol, 1.0 equiv), 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane (0.17 g, 0.65 mmol, 1.5 equiv), KOAc (0.13 g, 1.3 mmol, 3.0 equiv), Pd(dppf)Cl2(32 mg, 43 μmol, 0.10 equiv) in dioxane (2.0 mL) was degassed and purged with N2 three times, and then the mixture was stirred at 100 °C for 16 hours under N2 atmosphere. The mixture was diluted with water (10 mL) and extracted with ethyl acetate (10 mL, three times). The organic phase was washed with brine (20 mL), dried over anhydrous Na2SO3, filtered and the filtrate was concentrated. The residue obtained was purified by prep-TLC (SiO2, PE / EtOAc = 3:1) to give trimethyl-[2-[[4-[4-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl) phenoxy] imidazol-1-yl] methoxy] ethyl] silane bor.5 (0.12 g, 0.20 mmol, 47% yield, 70% purity) as colourless oil. MS m / z (ESI) [M+H]+= 417.2. Synthesis of amine intermediates Amine 1: cis- [3,4-c] pyridin-6-one To a solution of Pd / C (20 mg, 10% purity) in EtOAc (5.0 mL) / THF (5.0 mL) was added benzyl 6-oxo-3,3a,4,5,7,7a-hexahydro-1H-pyrrolo[3,4-c] pyridine-2-carboxylate (0.10 g, 0.36 mmol, 1.0 equiv) under N2 atmosphere at 25 °C. The suspension was degassed and purged with H2 three times. After stirring under H2 (50 Psi) at 25 °C for 16 h, the reactionmixture was filtered and concentrated under reduced pressure to give Amine 1 (0.12 mg,crude) as a yellow solid. Attorney Docket No.: 185992002140 Amine 2: cis-tert-butyl 7,7-difluoro-2,3,3a,4,6,7a-hexahydro-1H-pyrrolo[3,4-c] pyridine-5- carboxylate Step 1: To a solution of tert-butyl 3-hydroxy-3,6-dihydro-2H-pyridine-1-carboxylate10.1 (3.0 g, 15 mmol, 1.0 equiv) in DCM (30 mL) was added (1,1-diacetoxy-3-oxo-1,2-benziodoxol-1-yl) acetate (13 g, 30 mmol, 9.3 mL, 2.0 equiv) at 25 °C. The mixture wasstirred at 25 °C for 2 hours. The mixture was filtered, and the filtrate was concentrated. Theresidue obtained was purified by Flash chromatography (ISCO®; 25 g SepaFlash® Silica Flash Column, Eluent of 0~50% EtOAc / PE, gradient: 40 mL / min) to give tert-butyl 3-oxo-2,6-dihydropyridine-1-carboxylate 10.2 (2.0 g, 10 mmol, 67% yield, 99% purity) ascolourless oil. MS (ESI) m / z [M+H-56]+= 142.1. Step 2: A mixture of 10.2 (0.50 g, 2.5 mmol, 1.0 equiv) and N-(methoxymethyl)-1-phenyl-N-(trimethylsilyl methyl) methanamine (1.2 g, 5.1 mmol, 2.0 equiv) in CH3CN (5.0 mL) was degassed and purged with N2 three times, and then the mixture was stirred at 25 °Cfor 2 hours under N2 atmosphere. The reaction mixture was purified by prep-HPLC 7(gradient: 39%-69% over 10 min) to give 10.3 (0.47 g, 1.4 mmol, 54% yield, 96% purity) asyellow oil. MS (ESI) m / z [M+H]+= 331.1. Step 3: To a solution of 10.3 (0.32 g, 0.97 mmol, 1.0 equiv) in DCM (5.0 mL) wasadded DAST (0.47 g, 2.9 mmol, 0.38 mL, 3.0 equiv) at - 78 °C. The mixture was stirred at 20°C for 2 hours. The mixture was diluted with water (10 mL) and extracted with ethyl acetate(20 mL, three times). The organic phase was washed with brine (50 mL), dried over anhydrous Na2SO3, filtered and the filtrate was concentrated. The residue obtained was purified by flash silica gel chromatography (ISCO®; 4 g SepaFlash® Silica Flash Column, Attorney Docket No.: 185992002140Eluent of 0~100% EtOAc / PE, gradient: 20 mL / min) to give 10.4 (0.10 g, 0.28 mmol, 29%yield, 100% purity) as yellow oil. MS (ESI) m / z [M+H]+= 353.1. Step 4: To a solution of Pd / C (10 mg, 9.4 μmol, 10% purity) and Pd(OH)2 (10 mg, 36μmol, 20% purity) in MeOH (5.0 mL) was added 10.4 (0.10 g, 0.28 mmol, 1.0 equiv) underN2. The suspension was degassed under vacuum and purged with H2three times. The mixturewas stirred under H2 (50 psi) at 50 °C for 16 hours. The reaction mixture was diluted withMeOH (10 mL), the mixture was filtered through a pad of celite, and the filtrate wasconcentrated to give Amine 2 (50 mg, crude) as yellow oil. The crude was used next stepwithout purification. Amine 3: cis-tert-butyl 4-oxo-2,3,3a,6,7,7a-hexahydro-1H-pyrrolo[3,4-c] pyridine-5- Step 1: To a solution of tert-butyl 6-oxo-2,3-dihydropyridine-1-carboxylate 11.1 (0.85g, 4.3 mmol, 1.0 equiv) in MeCN (10 mL) was added N-(methoxymethyl)-1-phenyl-N- (trimethylsilylmethyl) methanamine (1.7 g, 7.2 mmol, 1.7 equiv), then the resulting mixturewas stirred at 25 °C for 12 hours. The reaction mixture was filtered and evaporated underreduced pressure to give the crude product. The crude product was purified by prep-HPLC 2(gradient: 13%-43% over 15 min) to give 11.2 (0.56 g, 1.7 mmol, 39% yield) as a white solid.1H NMR (400 MHz, CDCl3) δ (ppm): 7.38 - 7.35 (m, 5H), 4.19 - 4.04 (m, 1H), 3.91 - 3.81(m, 2H), 3.45 (d, J = 2.4, 11.2, 13.4 Hz, 1H), 3.35 (s, 2H), 3.18 (d, J = 3.5 Hz, 2H), 3.15 -2.77 (m, 2H), 2.37 - 2.27 (m, 1H), 2.09 (d, J = 2.3, 4.9, 7.0, 14.0 Hz, 1H), 1.54 (s, 9H).Step 2: To a solution of 11.2 (0.15 g, 0.45 mmol, 1.0 equiv) in MeOH (5.0 mL) wasadded Pd / C (15 mg, 14 μmol, 10% purity, 0.03 equiv), Pd(OH)2 (15 mg, 21 μmol, 20% purity, 0.05 equiv), The suspension was degassed and purged with H2three times. Themixture was stirred under H2 (50 Psi) at 40 °C for 3 hours. The reaction mixture was filteredand evaporated under reduced pressure to give the Amine 3 (0.11 g, crude) as the yellowsolid. 1H NMR (400 MHz, CDCl3) δ (ppm): 3.24 - 3.12 (m, 4H), 3.05 - 2.88 (m, 2H), 2.58 (d,J = 6.1, 11.2 Hz, 1H), 2.52 - 2.41 (m, 1H), 2.05 - 1.90 (m, 1H), 1.85 (d, J = 4.1, 13.5 Hz, 1H),1.46 (s, 9H). Attorney Docket No.: 185992002140 Amine 4: cis-5-methyloctahydro-4H-pyrrolo[3,4-c]pyridin-4-one Step 1: To a solution of 12.1 (13.6 g, 56.60 mmol, 1 eq) in DCM (150 mL) wasadded CbzCl (9.80 g, 57.44 mmol, 8.2 mL, 1.01 eq) and TEA (14.54 g, 143.69 mmol, 20 mL, 2.54 eq). The reaction solution was stirred at 25 °C for 1 hour. The mixture was diluted with water (60 ml), and then extracted with EtOAc (50 mL, twice). The combined organic phase was washed with brine (50 mL, three times), dried over Na2SO4, filtrated and evaporated. The residue was purified by flash silica gel chromatography (ISCO®; 330 g SepaFlash® SilicaFlash Column, Eluent of 0~3% Ethyl acetate / Petroleum ether gradient @ 100 mL / min) togive 12.2 (6 g, 14.74 mmol, 26.05% yield, 92% purity) as a colorless oil. MS m / z (ESI)[M+Na]+= 397.1. Step 2: 12.2 (5 g, 13.35 mmol, 1 eq) was added to HCl / dioxane (2 M, 100 mL). Thereaction solution was stirred at 25°C for 1 hour. The reaction solution was concentrated undervacuum to give 12.3 (4 g, crude) as a yellow oil which was used for next step without furtherpurification. Step 3: To a solution of 12.3 (3.5 g, 12.76 mmol, 1 eq) in DMF (40 mL) wasadded NaH (1.5 g, 37.50 mmol, 60% purity, 2.94 eq) at 0 °C under N2. The reaction solution was stirred at 25 °C for 1 hour. MeI (2.28 g, 16.06 mmol, 1 mL, 1.26 eq) was added to the solution at 0°C and stirred at 25 °C for another 1 hour. The mixture was quenched by H2O (100 mL), then the aqueous phase was extracted with EtOAc (100 mL, three times). The combined organic layers were dried over Na2SO4, filtrated and evaporated. The residue was purified by flash silica gel chromatography (ISCO®; 330 g SepaFlash® Silica Flash Column,Eluent of 0~70% THF / Petroleum ether gradient @ 100 mL / min) to give 12.4 (2.6 g, 8.66mmol, 67.85% yield, 96% purity) as a colorless oil. MS m / z (ESI) [M+H]+= 289.1. Step 4: To a solution of 12.4 (2.5 g, 8.67 mmol, 1 eq) in MeOH (200 mL) wasadded Pd / C (300 mg, 10% purity) and Pd(OH)2 (300 mg, 20% purity) under N2. The reaction solution was degassed and purged under H2 for three times. The reaction solution was stirred at 40 °C for 3 hours. The reaction solution was filtered and the filtrate was concentratedunder vacuum to give Amine 4 (1.5 g, crude) as a colorless oil which was used for next stepwithout further purification. Attorney Docket No.: 185992002140 Amine 5: cis-5-methyloctahydro-1H-pyrrolo[3,4-c]pyridine To a solution of tert-butyl cis-octahydro-5H-pyrrolo[3,4-c]pyridine-5-carboxylate (1.5 g, 5.71 mmol, 1 eq, HCl salt) in THF (30 mL) was added dropwise LiAlH4 (2.5 M, 7 mL, 3 eq) at 0 °C over 1 min. After addition, the mixture was stirred at 50 °C for 16 hours under N2atmosphere. The reaction mixture was added Na2SO4(2 g) and water (0.5 mL) at 20 °C, and then diluted with EtOAc (20 mL) filtered and concentrated under reduced pressure to giveAmine 5 (800 mg, crude) as yellow oil. 1H NMR (400 MHz, CDCl3) d (ppm): 3.06 - 2.52 (m,8H), 2.24 - 2.22 (m, 3H), 1.81 - 1.60 (m, 4H).Synthesis of dichlorothienopyridines intermediatesA.1a (R8 = -CH3, R7 = -H): 5,7-dichloro-2-methylthieno [3,2-b] pyridine Step1: To a solution of methyl 3-amino-5-methyl-thiophene-2-carboxylate 13.1 (12 g,70 mmol, 1.0 equiv) and diethyl propanedioate (34 g, 0.21 mol, 32 mL, 3.0 equiv) in EtOH(0.15 L) was added EtONa (14 g, 0.21 mol, 3.0 equiv) at 25 °C. The mixture was stirred at 90°C for 16 hours. The mixture was adjusted to pH = 7 with HCl (2M) and filtered. The filtercake was triturated with petroleum ether (0.10 L) at 25 °C for 15 min. The title compoundethyl 5, 7-dihydroxy-2-methyl-thieno [3, 2-b] pyridine-6-carboxylate 13.2 (17 g, 67.12 mmol,95.77% yield) as a brown solid was collected by filtration. The crude was used next step without purification. MS (ESI) m / z. [M+H]+= 254.0. Step 2: 13.2 (34 g, 0.13 mol, 1.0 equiv) was added in concentrated solution of HCl12N (0.20 L) at 25 °C and then the mixture was stirred at 100 °C for 16 hours. The mixturewas concentrated to give crude 2-methylthieno [3, 2-b] pyridine-5, 7-diol 13.3 (20 g, 0.11mol, 82% yield) as black, brown solid which was used in the next step without purification. MS (ESI) m / z. [M+H]+= 182.0. Step 3: A solution of 13.3 (20 g, 110.37 mmol, 1 eq) and POCl3 (0.20 L) was stirredat 100°C for 16 hours. The reaction mixture was concentrated under reduced pressure to Attorney Docket No.: 185992002140remove POCl3 and the residue was quenched with water (0.20 L) at 25 °C. The pH wasadjusted to 7~8 with NaHCO3. The mixture was diluted with water (0.20 L) and extractedwith EtOAc (0.20 L, three times). The combined organic layers were washed with brine (0.60L), dried over anhydrous Na2SO3, filtered and the filtrate was concentrated. The residue obtained was purified by column chromatography (SiO2, PE / EtOAc = 5:1 to 1:1) to give 5, 7-dichloro-2-methyl-thieno [3, 2-b] pyridine A.1a (14 g, 62 mmol, 56% yield, 96% purity) as awhite solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 7.68 (s, 1H), 7.35 (d, J = 1.2 Hz, 1H),2.65 (s, 3H). MS (ESI) m / z. [M+H]+ = 217.9.A.1b (R8 = -OCH3, R7 = -H): 5,7-dichloro-2-methoxythieno[3,2-b] pyridine Step1: To a solution of 14.1 (1.6 g, 7.8 mmol, 1.0 equiv) and 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane (2.1 g, 8.2 mmol, 1.0equiv) in THF (15 mL) was added (1Z,5Z)-cycloocta-1,5-diene;2,4-dimethyl-BLAHbicyclo[1.1.0]butane (5.3 g, 8.0 mmol, 1.0 equiv) and 3,4,7,8-tetramethyl-1,10-phenanthroline (1.9 g, 8.1 mmol, 1.0 equiv) .The mixture was stirred at 80 °C for 12 hours.The reaction mixture was filtered and concentrated under reduced pressure to give residue.The crude product 14.2 (3.6 g, crude) was directly used into the next step without furtherpurification as brown gum. Step 2: To a solution of 14.2 (3.6 g, 11 mmol, 1.0 equi...

Claims

Attorney Docket No.: 185992002140 CLAIMS What is claimed is:

1. A compound of Formula (I)or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R1is H or C1-6alkyl; R2is C1-6alkyl or C3-6cycloalkyl, wherein the C1-6alkyl or C3-6cycloalkyl of R2is optionally substituted with one or more -OH or -N(Rx)(Ry), or R1and R2are taken together with the N to which they are attached to form a 3- to 12- membered heterocyclyl, wherein 3- to 12-membered heterocyclyl of R1and R2is optionally substituted with one or more R3; each R3is independently halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, oxo, -OR10, -SR10, -SF5, - N(Rx)(Ry), -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, - OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), - C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, - S(=NR13)N(R11)R12, -S(=NR13)OR13, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R3is optionally substituted with one or more R3a; the C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with one or more R3b; and optionally, two substituents of R3are taken together with the atoms to which they are attached form a C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl,Attorney Docket No.: 185992002140 wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10- membered aryl, or 5- to 10-membered heteroaryl is optionally substituted one or more R3b; Ring A is phenyl or 5- to 6-membered heteroaryl, wherein the phenyl or 5- to 6-membered heteroaryl of Ring A is optionally substituted by one or more R4, and the 5- to 6-membered heteroaryl of Ring A comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; each R4is independently halo, C1-6alkyl, or -OR10; L is a bond, C1-6alkyl, -O-(C1-6alkyl)-, -S-(C1-6alkyl)-, or -N(R5)(C1-6alkyl)-, wherein the C1-6alkyl, -O-(C1-6alkyl)-, -S-(C1-6alkyl)-, or -N(R5)(C1-6alkyl)- is optionally substituted by one or more RL; each RLis independently halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -NO2, -CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, -OC(=O)N(R11)R12, - OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, C3-8cycloalkyl, 3- to 8- membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, or two RLare taken together along with the atoms to which they are attached to form a C3-8cycloalkyl or 3- to 8-membered heterocyclyl; R5is H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, -C(=O)R12, -S(=O)2R12, -S(=O)2N(R11)(R12), or C3-8cycloalkyl, wherein the C1-6alkyl of R5is optionally substituted with one or more halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, - OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), - C(=O)OR12, -C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, - N(R11)S(=O)2R12, -S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, - S(=NR13)N(R11)R12, -S(=NR13)OR13, -S(=O)2R12, or -S(=O)2N(R11)(R12), and the C3-8cycloalkyl is optionally substituted with one or more R5b; R6is H, -OR9, -OR10, -N(Rx)(Ry), -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, - N(R11)C(=O)OR12, -OC(=O)R12, -OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, - C(=O)N(R11)(R12), -C(=O)OR12, 5- to 6-membered heteroaryl, or 3- to 8-membered heterocyclyl, wherein the 3- to 8-membered heterocyclyl is optionally substituted with one or more R6b, - C(=O)R12, -C(=O)N(R11)(R12), or -C(=O)OR12;Attorney Docket No.: 185992002140 R7is H; R8is halo, C1-6alkyl, C1-6haloalkyl, -OR9, -OR10, -N(Rx)(Ry), -N(R11)C(=O)R12, - N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, -OC(=O)N(R11)R12, - OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, 3- to 8-membered heterocyclyl, wherein the 3- to 8-membered heterocyclyl of R8is optionally substituted with one or more R7b, and the 3- to 8-membered heterocyclyl of R8comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; each R1a, R3a, R4a, R6a, or R7ais independently halo, -N(Rx)(Ry), -OR10, -SR10, -SF5, -NO2, - CN, -N(R11)C(=O)R12, -N(R11)C(=O)N(R11)R12, -N(R11)C(=O)OR12, -OC(=O)R12, - OC(=O)N(R11)R12, -OC(=O)OR12, -C(=O)R12, -C(=O)N(R11)(R12), -C(=O)OR12, - C(=NR13)R12, -C(=NOR12)R12, -C(=NR13)N(R11)R12, -C(=NR13)OR12, -N(R11)S(=O)2R12, - S(=O)R12, -S(=O)N(R11)R12, -S(=O)OR12, -S(=NR13)R12, -S(=NR13)N(R13)R12, - S(=NR13)OR12, -S(=O)2R12, -S(=O)2N(R11)(R12), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C3-8cycloalkyl, 3- to 12-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R1a, R3a, R4a, R6a, or R7ais optionally substituted with one or more R1b, and the 3- to 12-membered heterocyclyl of R1a, R3a, R4a, R6a, or R7acomprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S; each R1b, R3b, R4b, R5b, R6b, or R7bis independently halo, C1-6alkyl, -OR9, -N(Rx)(Ry), oxo, - CN, C3-8cycloalkyl, or 3- to 8-membered heterocyclyl, wherein the C1-6alkyl of R1b, R3b, R4b, R5b, R6b, or R7bis optionally substituted by -OR12, - N(Rx)(Ry), C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl; each R9is independently H, C1-6alkyl, C2-6alkenyl, C3-8cycloalkyl, 3- to 8-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C1-6alkyl of R9is optionally substituted with 6- to 10-membered aryl, or 5- to 10- membered heteroaryl wherein the 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, or -N(Rx)(Ry), andAttorney Docket No.: 185992002140 the 6- to 10-membered aryl, or 5- to 10-membered heteroaryl of R9is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, -N(Rx)(Ry), or 3- to 12- membered heterocyclyl; each R10is independently H, C1-6alkyl, or C3-8cycloalkyl, wherein the C1-6alkyl is optionally substituted with one or more halo, deuterium, 3- to 8-membered heterocyclyl, phenyl, or 5- to 6-membered heteroaryl, wherein the C3-8cycloalkyl, phenyl, or 5- to 6-membered heteroaryl is optionally substituted with halo, C1-3alkyl, C1-3alkoxy, or -N(Rx)(Ry); each R11is independently H, C1-6alkyl, or C3-8cycloalkyl; each R12is independently H, C1-6alkyl, C3-8cycloalkyl, phenyl, 5- to 6-membered heteroaryl, or 3- to 8-membered heterocyclyl, wherein the C1-6alkyl of R12is optionally substituted by one or more halo, -OH, -O(C1-6alkyl), -N(Rx)(Ry), C3-8cycloalkyl, phenyl, 5- to 6-membered heteroaryl, or 3- to 12- membered heterocyclyl, and the C3-8cycloalkyl, phenyl, 5- to 6-membered heteroaryl, or 3- to 12-membered heterocyclyl of R12is optionally substituted with halo, C1-6alkyl, or -N(Rx)(Ry); each R13is independently H or C1-6alkyl; and each Rxand Ryis independently H, C1-6alkyl, C3-8cycloalkyl, -C(=O)(C1-6alkyl), or - C(=O)O(C1-6alkyl), wherein the C1-6alkyl of Rxor Ryis optionally substituted with 6- to 10-membered aryl, 5- to 10-membered heteroaryl, or -NH2, NH(C1-6alkyl), or -N(C1-6alkyl)(C1-6alkyl), and the C1-6alkyl of -C(=O)(C1-6alkyl) or -C(=O)O(C1-6alkyl) is optionally substituted with -O(C=O)C1-8alkyl); wherein(i) when R1 and R2 are taken together with the N to which they are attached to form , -(Ring A)-L-R6are not taken together to form a pyrazolyl substituted by Br; and(ii) when -(Ring A)-L-R6 are taken together to form, R1 is H, and R2 is -CH3, R8is not -CH3.

2. The compound of claim 1, wherein Ring A is phenyl or 6-membered heteroaryl, whereinAttorney Docket No.: 185992002140 the phenyl or 6-membered heteroaryl is optionally substituted by one or more R4, and the 5- to 6-membered heteroaryl of Ring A comprises 1, 2, or 3 atoms selected from the group consisting of N, O, and S.

3. The compound of claim 1 or 2, wherein the compound is a compound of Formula (II)stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein X1is CH or N.

4. The compound of any of claims 1-3, wherein the compound is a compound of Formula (II-A)stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

5. The compound of claim 1 or 2, wherein the compound is a compound of Formula (III)stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.Attorney Docket No.: 185992002140 6. The compound of any of claims 1-5, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R1is H or C1-6alkyl.

7. The compound of any of claims 1-6, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R1is H.

8. The compound of any of claims 1-7, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R2is C1-6alkyl or C3- 6cycloalkyl, wherein the C1-6alkyl or C3-6cycloalkyl of R2is optionally substituted with one or more -OH or -N(Rx)(Ry).

9. The compound of any of claims 1-8, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R2is -(C1-6alkyl)NH2, -(C1-6alkyl)N(C1-6alkyl)(C1-6alkyl), -(C1-6alkyl)NH(C1-6alkyl-NH2), or -(C3-6cycloalkyl)NH2.

10. The compound of any of claims 1-9, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R2is selected from theAttorney Docket No.: 185992002140 11. The compound of any of claims 1-5, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R1and R2are taken together with the N to which they are attached to form a 3- to 12- membered heterocyclyl optionally substituted with one or more R3.

12. The compound of any of claims 1-5 or 11, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R1and R2are taken together with the N to which they are attached to form a 3- to 12-membered heterocyclyl optionally substituted with one or more R3, wherein the 3- to 12-membered heterocyclyl comprises a 3- to 8-membered monocyclic heterocyclyl, a 5- to 12-membered fused heterocyclyl, or a 6- to 12-membered spirocyclic heterocyclyl.

13. The compound of claim 12, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R1and R2are taken together with the N to which they are attached to form a 4- to 12-membered heterocyclyl optionally substituted with one or more R3.

14. The compound of claim 13, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R1and R2are taken together with the N to which they are attached to form a saturated 3- to 10-membered heterocyclyl optionally substituted with one or more R3.

15. The compound of claim 14, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R1and R2are taken together with the N to which they are attached to form a saturated 4- to 6-membered monocyclic heterocyclyl optionally substituted with one or more R3.

16. The compound claim 15, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R1and R2are taken together with the N to which they are attached to form an azetidinyl or pyrrolidinyl, wherein the azetidinyl or pyrrolidinyl is optionally substituted with one or more R3.

17. The compound of any of claims 13-16, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R1and R2are taken together with the N to which they are attached to form a heterocyclyl selected from the groupAttorney Docket No.: 185992002140Attorney Docket No.: 185992002140 18. The compound of claim 13, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R1and R2are taken together with the N to which they are attached to form a saturated 6- to 10-membered fused or bridged heterocyclyl optionally substituted with one or more R3.

19. The compound claim 18, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R1and R2are taken together with the N to which they are attached to form a group selected from the group consisting of ,20. The compound of claim 14, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R1and R2are taken together with the N to which they are attached to form a saturated 7- to 10-membered spirocyclic heterocyclyl optionally substituted with one or more R3.

21. The compound of claim 20, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R1and R2are taken together with the N to which they are attached to form a group selected from the group consisting ofAttorney Docket No.: 18599200214022. The compound of any of claims 1-21, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R6is H, -OR9, -OR10, - N(Rx)(Ry), -N(R11)C(=O)R12, 5- to 6-membered heteroaryl, or 3- to 8-membered heterocyclyl, wherein the 3- to 8-membered heterocyclyl is optionally substituted with one or more R6b.

23. The compound of any of claims 1-22, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R6is H, -O(5- to 6- membered heteroaryl), -NH(C1-6alkyl), -NH(C3-6cycloalkyl), -NHC(O)(C1-6alkyl), - NHC(O)(C1-6alkyl)NH2, -N(C1-6alkyl)C(O)(C1-6alkyl)NH2, 5-membered heteroaryl, or 4- to 6-membered N-containing heterocyclyl, wherein the 4- to 6-membered N-containing heterocyclyl is optionally substituted with one or more R6b, -C(=O)R12, -C(=O)N(R11)(R12), or -C(=O)OR12.

24. The compound of any of claims 1-23, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R6is selected from the group consisting ofAttorney Docket No.: 185992002140.

25. The compound of any of claims 1-24, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R8is C1-6alkyl, -(C1-6alkyl)OH, -C1-6alkyl-O(C1-6alkyl), -(C1-6alkyl)(4- to 7-membered heterocyclyl), -O(C1-6alkyl), -O(C1-6alkyl)(4- to 7-membered heterocyclyl), -N(C1-6alkyl)(C1-6alkyl), or -C(O)(4- to 7-membered heterocyclyl), wherein each 4- to 7-membered heterocyclyl is optionally substituted by C1-6alkyl.

26. The compound of any of claims 1-25, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R8is selected from the27. The compound of claim 1 or 2, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein L is a bond or -O(C1-6alkyl)-; and R3is H, -N(Rx)(Ry), or 4- to 12-membered heterocyclyl optionally substituted with one or more R3a.

28. The compound of claim 1 or 2, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R1and R2are taken together with the N to which they are attached to form a 4- to 12- membered heterocyclyl optionally substituted with one or more R3; L is a bond; andAttorney Docket No.: 185992002140 R6is 4- to 12-membered heterocyclyl optionally substituted with one or more R6b, - C(=O)R12, -C(=O)N(R11)(R12), or -C(=O)OR12.

29. The compound of claim 28, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R6is piperazinyl optionally substituted with one or more R6b, -C(=O)R12, - C(=O)N(R11)(R12), or -C(=O)OR12.

30. The compound of any of claims 1, 2, or 27, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein L is -O(C1-6alkyl)-; and R6is H or -N(Rx)(Ry).

31. The compound of claim 1 or 2, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or 31, wherein Ring A is phenyl; and R6is C1-6alkyl.

32. The compound of claim 1 or 2, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the compound is selected from Table 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

33. The compound of claim 1 or 2, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the compound is selected from compounds 1 to 65 of Table 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

34. A pharmaceutical composition comprising a compound of any of claims 1-33, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and one or more pharmaceutically acceptable excipients or carriers.

35. A method for treating a disease or condition mediated by TDP-43, comprising administering to an individual in need thereof a compound of any of claims 1-33, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or the pharmaceutical composition of claim 34.

36. The method of claim 35, wherein said disease or condition mediated by TDP-43 is a neurological disease or condition.Attorney Docket No.: 185992002140 37. The method of claim 36, wherein the neurological disease is selected from the group consisting of Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, traumatic brain injury (TBI), chronic traumatic encephalopathy (CTE), frontotemporal dementia (FTD), inclusion body myositis, Perry syndrome, corticobasal degeneration, spinocerebellar ataxia type 3, and amyotrophic lateral sclerosis (ALS).

38. The method of claim 36 or 37, wherein the neurological disease or condition is traumatic brain injury (TBI).

39. The method of claim 36 or 37, wherein the neurological disease or condition is frontotemporal dementia (FTD).

40. The method of claim 36 or 37, wherein the neurological disease or condition is amyotrophic lateral sclerosis (ALS).

41. The method of any of claims 36, 37, or 40, wherein the neurological disease or condition is sporadic amyotrophic lateral sclerosis or C9ORF72 amyotrophic lateral sclerosis.

42. The method of any of claims 35-41, wherein the individual is a human.

43. A method of modulating TDP-43, comprising contacting a cell with an effective amount of a compound of any of claims 1-33, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or the pharmaceutical composition of claim 34, wherein modulating TDP-43 comprises modulating TDP-43 incorporation into condensates, modulating TDP-43 binding to RNA in condensates, modulating TDP-43 aggregation, or modulating TDP-43 protein-protein interactions.

44. A method of modulating TDP-43 driven gene expression levels, comprising contacting a cell with an effective amount of a compound of any of claims 1-33, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or the pharmaceutical composition of claim 34.

45. The method of claim 44, wherein the gene expression levels are for STMN2.

46. The method of claim 44, wherein the gene expression levels are for POLDIP3.

47. The compound of any of claims 1-33, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 34 for use in the treatment of a TDP-43 mediated disease or disorder.Attorney Docket No.: 185992002140 48. Use of a compound of any of claims 1-33, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the treatment of a disease or disorder mediated by TDP-43.

49. A kit, comprising (i) a compound of any one of claims 1-33, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or the pharmaceutical composition of claim 34 and (ii) instructions for use in treating a TDP-43 mediated disease or condition in an individual in need thereof.

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