Compositions and methods for inhibition of ras

Abstract

Provided herein are compounds, or salts, esters, tautomers, prodrugs, zwitterionic forms, or stereoisomers thereof, as well as pharmaceutical compositions comprising the same. Also provided herein are methods of using the same in modulating (e.g., inhibiting) KRAS (e.g., KRAS having a Q61H, G12D, G12V, G12C, G12S, G12A, G12R, or G13D mutation or wild-type KRAS, including wild-type amplified KRAS) and treating diseases or disorders such as cancers in subjects in need thereof.

Description

COMPOSITIONS AND METHODS FOR INHIBITION OF RAS STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT

[0001] This invention was made with government support under (1) Contract No.: 75N91019D00024 awarded by the National Institutes of Health and (2) Contract No. DE-AC52-07NA27344 awarded by the United States Department of Energy. The government has certain rights in the invention. CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to United States Provisional Application No. 63 / 605,348, filed December 1, 2023, United States Provisional Application No. 63 / 550,896, filed February 7, 2024, and United States Provisional Application No.63 / 658,325, filed June 10, 2024, the entirety of each of which is incorporated herein by reference BACKGROUND

[0003] RAS protein functions as a molecular switch, cycling between inactive (“GDP-bound”) and active (“GTP-bound”) states. RAS signaling occurs through engagement with effector proteins that adapt the signaling cascades regulating tumor cell survival and proliferation. Aberrant activation of RAS by oncogenic mutations results in increased GTP-bound KRAS and constitutive downstream signaling.

[0004] RAS is the most frequently mutated oncogene. Activating mutations in KRAS occur in over 90% of pancreatic tumors. Mutated KRAS is also observed at high frequency in other common tumors, including colorectal cancer (^44%) and non–small cell lung cancer (NSCLC; ^20-30%). Cancer-associated mutations in KRAS cluster in three hotspots (G12, G13, and Q61), with a majority (77%) of mutations causing single amino acid substitutions at G12. The KRAS missense mutation G12D is the most predominant variant in human malignancies (35%), followed by G12V (29%). Besides G12, the hotspots G13 and Q61 show mutation rates of 10% and 6% respectively.

[0005] The development of small molecule KRAS inhibitors has proven to be a challenge. Recent clinical development of covalent KRAS G12C inhibitors indicates potential of targeting the KRAS oncogenic protein directly. Results from clinical trials with the two covalent inhibitors, AMG510 (sotorasib) and MRTX849 (adagrasib), have been promising. These inhibitors demonstrated clinical activity primarily in NSCLC, where the KRAS G12C mutation frequency is highest. Unfortunately, they appeared less effectivein KRAS G12C colorectal cancers. Both compounds only target the inactive (GDP-bound) form of KRAS G12C, and a lack of activity against active (GTP-bound) KRAS G12C may contribute to development of drug resistance. Moreover, these covalent inhibitors are limited to the specific G12C mutant that accounts for approximately 13% of all KRAS-driven cancers, leaving a large population of non-G12C KRAS cancers still undruggable. Therefore, KRAS therapeutics that target additional KRAS alterations or combinations thereof are an unmet clinical need. Pan-KRAS inhibitors hold promise for impact across the majority of KRAS mutant alleles, including the most prevalent G12D and G12V, or KRAS wildtype-amplified cancers.

[0006] KRAS is essential for mouse development, whereas NRAS and HRAS are dispensable. This requirement for KRAS creates toxicity concerns when targeting the wild-type KRAS protein. However, when KRAS is replaced with HRAS, mice are viable, which reduces toxicity concerns and suggests that in contrast to the pan-RAS inhibitors that could pose toxicity issues, KRAS isoform-specific inhibitors should be tolerated. If so, additional advantages of pan-KRAS inhibitors could come from targeting cancers with acquired resistance to KRAS G12C inhibitors. Recent reports provide insights into mechanisms of resistance to the KRAS G12C inhibitors in the clinic, suggesting restoration of RAS / MAPK as a driver of the resistance. Acquisition of a diverse set of mutations in response to KRAS G12C inhibitors in addition to activation of the KRAS wildtype allele through upstream RTK signaling has been shown. It is possible that direct pan-KRAS agents may suppress these events. Accordingly, there remains a need for allele- specific and pan-KRAS inhibitors that could be used to treat KRAS-driven cancers regardless of mutation status. SUMMARY

[0007] The present disclosure provides compounds, as well as compositions and kits comprising the same, and methods of using the same in the treatment of diseases and disorders such as cancers. The present disclosure provides compounds that may be capable of inhibiting one or more mutant forms of KRAS, such as KRAS having a G12D, G12V, G12C, G12S, G12A, G12R, Q61H, or G13D mutation, or wild-type KRAS, including wild-type amplified KRAS. Such compounds may be considered pan-KRAS inhibitors. In some embodiments, the compounds provided herein may be capable of targeting both active GTP-bound protein and inactive GDP-bound protein, which inhibitors may provide therapeutic advantages over compounds capable of targeting only the inactive GDP-bound protein. In some embodiments, compounds provided herein have inhibitory activity against a KRAS protein comprising a glycine to aspartic acid, valine, cysteine, serine, alanine, or arginine mutation at codon 12 (i.e., a G12D, G12V, G12C, G12S, G12A, or G12R mutation); or a glycine to aspartic acid mutation at codon 13 (e.g., a G13D mutation); or aglutamine to histidine mutation at codon 61 (e.g., a Q61H mutation) in both its active and inactive conformations. In some embodiments, compounds provided herein have inhibitory activity against wild- type KRAS, including wild-type amplified KRAS. In some embodiments, compounds provided herein are useful in the treatment of cancers, such as cancers characterized by KRAS proteins having a mutation at codon 12, such as a G12D, G12V, G12C, G12S, G12A, or G12R mutation; or a mutation at codon 13, such as a G13D mutation; or a mutation at codon 61, such as a Q61H mutation, or cancers that may benefit from inhibition of wild-type KRAS, including wild-type amplified KRAS.

[0008] In an aspect, the present disclosure provides compositions comprising compounds represented by Formula X:or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein R1, R2, R3, R4, R5, R6, and R7are as provided herein. In some embodiments, the compound is a compound according to any one of Formulas A, A’, A’-a, B, B-a, BA, BB, BC, BD, BE, BF, BG, BH, BI, BJ, BK, BL, BM, BA1, BB1, BC1, BD1, BE1, BF1, BG1, BH1, BI1, BJ1, BK1, BL1, BM1, II, II’, II’’, II’’-a, II-a, IIR’, IIU’, IIV’, IIZ, IIAA’, IIBB, IICC, IIDD, IIEE, IIFF, IIGG, IIHH, IIJJ, IIR1’, IIU1’, IIV1’, IIZ1, IIAA1’, IIBB1, IICC1, IIDD1, IIEE1, IIFF1, IIGG1, IIHH1, IIJJ1, III, IV, IV-a, IVB, IVC, V’, VA’, VB’, and VC’ provided herein, or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, a compound provided herein, or a salt, ester, tautomer, zwitterionic form, or stereoisomer(s) thereof, can modulate (e.g., inhibit) the activity of a KRAS protein, such as a KRAS protein having a mutation at codon 12, such as a G12D, G12V, G12C, G12S, G12A, or G12R mutation; a KRAS protein having a mutation at codon 13, such as G13D; a KRAS protein having a mutation at codon 61, such as Q61H; or a wild-type KRAS (e.g., a wild-type amplified KRAS). In some embodiments, a compound provided herein, or a salt, ester, tautomer, zwitterionic form, or stereoisomer(s) thereof, is capable of interacting with a KRAS protein comprising a glycine to aspartic acid, valine, cysteine, serine, alanine, or arginine mutation at codon 12 (i.e., a G12D, G12V, G12C, G12S, G12A, or G12R mutation) or a glycine to aspartic acid mutation at codon 13 (e.g., a G13D mutation) or a glutamine to histidine mutation at codon 61 (e.g., a Q61H mutation) in both its active and inactive conformations. In some embodiments, a compound provided herein, or a salt, ester, tautomer, zwitterionic form, or stereoisomer(s) thereof, hasinhibitory activity against wild-type KRAS, including wild-type amplified KRAS. In some embodiments, a compound provided herein, or a salt, ester, tautomer, zwitterionic form, or stereoisomer(s) thereof, is capable of binding a KRAS protein in an active (“GTP-bound”) conformation. In some embodiments, a compound provided herein, or a salt, ester, tautomer, zwitterionic form, or stereoisomer(s) thereof, is capable of binding a KRAS protein in an inactive (“GDP-bound”) conformation. In some embodiments, a compound provided herein, or a salt, ester, tautomer, zwitterionic form, or stereoisomer(s) thereof, is capable of binding a KRAS protein in both its active (“GTP-bound”) and inactive (“GDP-bound”) conformations.

[0009] In another aspect, the present disclosure provides a pharmaceutical composition comprising a compound provided herein (e.g., a compound represented by any one of Formulas A, A’, A’-a, B, B-a, BA, BB, BC, BD, BE, BF, BG, BH, BI, BJ, BK, BL, BM, BA1, BB1, BC1, BD1, BE1, BF1, BG1, BH1, BI1, BJ1, BK1, BL1, BM1, II, II’, II’’, II’’-a, II-a, IIR’, IIU’, IIV’, IIZ, IIAA’, IIBB, IICC, IIDD, IIEE, IIFF, IIGG, IIHH, IIJJ, IIR1’, IIU1’, IIV1’, IIZ1, IIAA1’, IIBB1, IICC1, IIDD1, IIEE1, IIFF1, IIGG1, IIHH1, IIJJ1, III, IV, IV-a, IVB, IVC, V’, VA’, VB’, and VC’, or any other formula set forth herein), or a salt, ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, together with a pharmaceutically acceptable carrier.

[0010] In a further aspect, the present disclosure provides a method of inhibition of KRAS activity in a human or animal subject for the treatment of a disease such as cancer, including pancreatic cancer (e.g., pancreatic ductal adenocarcinoma (PDAC)), colorectal cancer, endometrial endometrioid adenocarcinoma, rectal adenocarcinoma, gastric cancer, esophageal adenocarcinoma, gastroesophageal junction cancer, invasive ductal carcinoma, lung cancer, and neurofibromatosis type 1 (NF1) using, e.g., a compound provided herein (e.g., a compound represented by any one of Formulas A, A’, A’-a, B, B-a, BA, BB, BC, BD, BE, BF, BG, BH, BI, BJ, BK, BL, BM, BA1, BB1, BC1, BD1, BE1, BF1, BG1, BH1, BI1, BJ1, BK1, BL1, BM1, II, II’, II’’, II’’-a, II-a, IIR’, IIU’, IIV’, IIZ, IIAA’, IIBB, IICC, IIDD, IIEE, IIFF, IIGG, IIHH, IIJJ, IIR1’, IIU1’, IIV1’, IIZ1, IIAA1’, IIBB1, IICC1, IIDD1, IIEE1, IIFF1, IIGG1, IIHH1, IIJJ1, III, IV, IV-a, IVB, IVC, V’, VA’, VB’, and VC’, or any other formula set forth herein), or a salt, ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, or a pharmaceutical composition comprising the same.

[0011] In another aspect, the present disclosure provides a use of a compound provided herein (e.g., a compound represented by any one of Formulas A, A’, A’-a, B, B-a, BA, BB, BC, BD, BE, BF, BG, BH, BI, BJ, BK, BL, BM, BA1, BB1, BC1, BD1, BE1, BF1, BG1, BH1, BI1, BJ1, BK1, BL1, BM1, II, II’, II’’, II’’-a, II-a, IIR’, IIU’, IIV’, IIZ, IIAA’, IIBB, IICC, IIDD, IIEE, IIFF, IIGG, IIHH, IIJJ, IIR1’, IIU1’, IIV1’,IIZ1, IIAA1’, IIBB1, IICC1, IIDD1, IIEE1, IIFF1, IIGG1, IIHH1, IIJJ1, III, IV, IV-a, IVB, IVC, V’, VA’, VB’, and VC’, or any other formula set forth herein), or a salt, ester, tautomer, zwitterionic form, or stereoisomer(s) thereof, in the manufacture of a medicament for the treatment of a disease, disorder, or condition (e.g., a cancer) ameliorated, treated, inhibited, or reduced by inhibition of KRAS, including KRAS having a mutation at codon 12 (e.g., a G12D, G12V, G12C, G12S, G12A, or G12R mutation), KRAS having a mutation at codon 13 (e.g., a G13D mutation), KRAS having a mutation at codon 61 (e.g., a Q61H mutation), or a wild-type KRAS, including wild-type amplified KRAS. In some embodiments, the disease, disorder, or condition is pancreatic cancer (e.g., pancreatic ductal adenocarcinoma (PDAC)), colorectal cancer, or lung cancer.

[0012] In a further aspect, the present disclosure provides a compound as provided herein (e.g., a compound represented by any one of Formulas A, A’, A’-a, B, B-a, BA, BB, BC, BD, BE, BF, BG, BH, BI, BJ, BK, BL, BM, BA1, BB1, BC1, BD1, BE1, BF1, BG1, BH1, BI1, BJ1, BK1, BL1, BM1, II, II’, II’’, II’’-a, II-a, IIR’, IIU’, IIV’, IIZ, IIAA’, IIBB, IICC, IIDD, IIEE, IIFF, IIGG, IIHH, IIJJ, IIR1’, IIU1’, IIV1’, IIZ1, IIAA1’, IIBB1, IICC1, IIDD1, IIEE1, IIFF1, IIGG1, IIHH1, IIJJ1, III, IV, IV-a, IVB, IVC, V’, VA’, VB’, and VC’, or any other formula set forth herein), or a salt, ester, tautomer, zwitterionic form, or stereoisomer(s) thereof, for use as a medicament. In some embodiments, the medicament is used in the treatment of a disease, disorder, or condition (e.g., a cancer). In some embodiments, the disease, disorder, or condition is pancreatic cancer (e.g., pancreatic ductal adenocarcinoma (PDAC)), colorectal cancer, or lung cancer. DETAILED DESCRIPTION

[0013] The present disclosure provides compounds (e.g., compounds of Formulas A, A’, A’-a, B, B-a, BA, BB, BC, BD, BE, BF, BG, BH, BI, BJ, BK, BL, BM, BA1, BB1, BC1, BD1, BE1, BF1, BG1, BH1, BI1, BJ1, BK1, BL1, BM1, II, II’, II’’, II’’-a, II-a, IIR’, IIU’, IIV’, IIZ, IIAA’, IIBB, IICC, IIDD, IIEE, IIFF, IIGG, IIHH, IIJJ, IIR1’, IIU1’, IIV1’, IIZ1, IIAA1’, IIBB1, IICC1, IIDD1, IIEE1, IIFF1, IIGG1, IIHH1, IIJJ1, III, IV, IV-a, IVB, IVC, V’, VA’, VB’, and VC’), which compounds may possess useful KRAS inhibitory activity, and may be used in the treatment or prophylaxis of a disease, disorder, or condition in which KRAS plays an active role. In particular, certain compounds provided herein may possess useful inhibitory activity of a KRAS protein having a mutation at codon 12 (e.g., a G12D, G12V, G12C, G12S, G12A, or G12R mutation), a KRAS protein having a mutation at codon 13 (e.g., a G13D mutation), a KRAS protein having a mutation at codon 61 (e.g., a Q61H mutation), or a wild-type KRAS protein, which KRAS protein is in an active (GTP-bound) or inactive (GDP-bound) conformation. Certain compounds providedherein may be capable of inhibiting both active and inactive forms of KRAS. The present disclosure also provides pharmaceutical compositions comprising one or more compounds provided herein together with a pharmaceutically acceptable carrier, as well as methods of making and using the compounds and compositions. The present disclosure also provides methods for inhibiting KRAS, including a KRAS protein having a mutation at codon 12 (e.g., a G12D, G12V, G12C, G12S, G12A, or G12R mutation), a KRAS protein having a mutation at codon 13 (e.g., a G13D mutation), a KRAS protein having a mutation at codon 61 (e.g., a Q61H mutation), or a wild-type KRAS protein, which KRAS is in an active or inactive conformation. In an aspect, the present disclosure provides a method for treating a disorder mediated by KRAS including a KRAS protein having a mutation at codon 12 (e.g., a G12D, G12V, G12C, G12S, G12A, or G12R mutation), a KRAS protein having a mutation at codon 13 (e.g., a G13D mutation), a KRAS protein having a mutation at codon 61 (e.g., a Q61H mutation), or a wild-type KRAS protein in a subject in need of such treatment, which method comprises administering to the subject a therapeutically effective amount of a compound or composition provided herein. Also provided herein is the use of certain compounds provided herein in the manufacture of a medicament for the treatment of a disease, disorder, or condition ameliorated, treated, inhibited, or reduced by inhibition of KRAS, including a KRAS protein having a mutation at codon 12 (e.g., a G12D, G12V, G12C, G12S, G12A, or G12R mutation), a KRAS protein having a mutation at codon 13 (e.g., a G13D mutation), a KRAS protein having a mutation at codon 61 (e.g., a Q61H mutation), or a wild-type KRAS protein. In some embodiments, the disease, disorder, or condition is a cancer (e.g., as described herein).

[0014] When ranges of values are disclosed, and the notation “from n1 … to n2” or “between n1 … and n2” is used, where n1 and n2 are the numbers, then unless otherwise specified, this notation is intended to include the numbers themselves and the range between them. This range may be integral or continuous between and including the end values. By way of example, the range “from 2 to 6 carbons” is intended to include two, three, four, five, and six carbons, since carbons come in integer units. Compare, by way of example, the range “from 1 to 3 µM (micromolar),” which is intended to include 1 µM, 3 µM, and everything in between to any number of significant figures (e.g., 1.255 µM, 2.1 µM, 2.9999 µM, etc.).

[0015] “About,” as used herein, is intended to qualify the numerical values which it modifies, denoting such a value as variable within a margin of error. When no particular margin of error, such as a standard deviation to a mean value given in a chart or table of data, is recited, the term “about” should be understood to mean that range which would encompass the recited value and the range which would be included by rounding up or down to that figure as well, taking into account significant figures.

[0016] “Acyl,” as used herein, alone or in combination, refers to a carbonyl attached to an alkenyl, alkyl, aryl, cycloalkyl, heteroaryl, heterocycle, or any other moiety where the atom attached to the carbonyl is carbon. An “acetyl” group refers to a –C(O)CH3 group. An “alkylcarbonyl” or “alkanoyl” group refers to an alkyl group attached to the parent molecular moiety through a carbonyl group. Examples of such groups include methylcarbonyl and ethylcarbonyl. Examples of acyl groups include formyl, alkanoyl and aroyl.

[0017] “Alkenyl,” as used herein, alone or in combination, refers to a straight-chain or branched-chain hydrocarbon radical having one or more double bonds and containing from 2 to 20 carbon atoms. In certain embodiments, said alkenyl will comprise from 2 to 6 carbon atoms. The term “alkenylene” refers to a carbon-carbon double bond system attached at two or more positions such as ethenylene [(-CH=CH-), (- C::C-)]. Examples of suitable alkenyl radicals include ethenyl, propenyl, 2-methylpropenyl, 1,4-butadienyl and the like. Unless otherwise specified, the term “alkenyl” may include “alkenylene” groups.

[0018] “Alkynyl” refers to either a straight chain or branched-chain hydrocarbon having at least 2 carbon atoms and at least one triple bond and having the number of carbon atoms indicated (i.e.,C2-6means to two to six carbons). Alkynyl can include any number of carbons, such as C2, C2-3, C2-4, C2-5, C,2C-62-7, C2-8, C2-9, C2-10, C3, C3-4, C3-5, C3-6, C4, C4-5, C4-6, C5, C5-6, and C6. Examples of alkynyl groups include, but are not limited to, acetylenyl, propynyl, 1-butynyl, 2-butynyl, butadiynyl, 1-pentynyl, 2-pentynyl, isopentynyl, 1,3-pentadiynyl, 1,4-pentadiynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 1,3-hexadiynyl, 1,4-hexadiynyl, 1,5-hexadiynyl, 2,4-hexadiynyl, and 1,3,5-hexatriynyl.

[0019] “Alkoxy,” as used herein, alone or in combination, refers to an alkyl ether radical, wherein the term alkyl is as described herein. Examples of suitable alkyl ether radicals include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, iso-butoxy, sec-butoxy, tert-butoxy, and the like.

[0020] “Alkyl,” as used herein, alone or in combination, refers to a straight-chain or branched-chain alkyl radical containing from 1 to 20 carbon atoms (e.g., C1-20alkyl). In certain embodiments, said alkyl will comprise from 1 to 10 carbon atoms (e.g., C1-10 alkyl). In further embodiments, said alkyl will comprise from 1 to 8 carbon atoms (e.g., C1-8 alkyl). In further embodiments, said alkyl will comprise from 1 to 6 carbon atoms (e.g., C1-6alkyl). In further embodiments, said alkyl will comprise from 1 to 3 carbon atoms (e.g., C1-3 alkyl). Alkyl groups are unsubstituted or substituted as defined herein. Examples of alkyl radicals include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, iso-amyl, hexyl, octyl, nonyl, and the like. The term “alkylene,” as used herein, alone or in combination, refers to a saturated aliphatic group derived from a straight or branched chain saturated hydrocarbon attached at two or more positions, such as methylene (-CH2-). Unless otherwise specified, the term “alkyl” may include “alkylene” groups.

[0021] “Alkylamino,” as used herein, alone or in combination, refers to an alkyl group attached to the parent molecular moiety through an amino group. Suitable alkylamino groups may be mono- or dialkylated, forming groups such as, for example, N-methylamino, N-ethylamino, N,N-dimethylamino, N,N- ethylmethylamino, and the like.

[0022] “Alkylthio,” as used herein, alone or in combination, refers to an alkyl thioether (R–S–) radical wherein the term alkyl is as described herein and wherein the sulfur may be singly or doubly oxidized. Examples of suitable alkyl thioether radicals include methylthio, ethylthio, n-propylthio, isopropylthio, n- butylthio, iso-butylthio, sec-butylthio, tert-butylthio, methanesulfonyl, ethanesulfinyl, and the like.

[0023] “Amido” and “carbamoyl,” as used herein, alone or in combination, refer to an amino group as described herein attached to the parent molecular moiety through a carbonyl group, or vice versa. The “amido” group as used herein incudes “C-amido” and “N-amido” groups. The term “C-amido” as used herein, alone or in combination, refers to a -C(O)N(RR’) group with R and R’ as defined herein or as defined by the specifically enumerated “R” groups designated. In some embodiments, the “amido” group includes -C(O)NH2, C1-4alkylamido, and di(C1-4alkyl)amido. The term “C1-4alkylamido”, as used herein, refers to -C(O)NH(C1-4alkyl), wherein C1-4alkyl is as defined herein. The term “N-amido” as used herein, alone or in combination, refers to a RC(O)N(R’)- group, with R and R’ as defined herein or as defined by the specifically enumerated “R” groups designated. The term “acylamino” as used herein, alone or in combination, embraces an acyl group attached to the parent moiety through an amino group. An example of an “acylamino” group is acetylamino (CH3C(O)NH-).

[0024] “Amino,” as used herein, alone or in combination, refers to -NRR’, wherein R and R’ are independently selected from hydrogen, alkyl, acyl, heteroalkyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl, any of which may themselves be unsubstituted or substituted. Additionally, R and R’ may combine to form a heterocycloalkyl, which is unsubstituted or substituted. An “amino” group may be a primary amine (e.g., -NH2), secondary or di-substituted amine (e.g., -NHR where R is not hydrogen), or tertiary or tri-substituted amine (e.g., -NRR’ where neither R nor R’ is hydrogen).

[0025] “Aryl,” as used herein, alone or in combination, means a carbocyclic aromatic system containing one, two, or three rings wherein such polycyclic ring systems are fused together. The term “aryl” embraces aromatic groups such as phenyl, naphthyl, anthracenyl, and phenanthryl. An aryl moiety may include, for example, between 5 to 20 carbon atoms, such as between 5 to 12 carbon atoms, such as 5 or 6 carbon atoms.

[0026] “Arylalkenyl” or “aralkenyl,” as used herein, alone or in combination, refers to an aryl group attached to the parent molecular moiety through an alkenyl group.

[0027] “Arylalkoxy” or “aralkoxy,” as used herein, alone or in combination, refers to an aryl group attached to the parent molecular moiety through an alkoxy group.

[0028] “Arylalkyl” or “aralkyl,” as used herein, alone or in combination, refers to an aryl group attached to the parent molecular moiety through an alkyl group.

[0029] “Aryloxy,” as used herein, alone or in combination, refers to an aryl group attached to the parent molecular moiety through an oxy.

[0030] “Carbamate,” as used herein, alone or in combination, refers to an ester of carbamic acid (- NHCOO-) which may be attached to the parent molecular moiety from either the nitrogen or acid end, and which is unsubstituted or substituted as defined herein.

[0031] “O-carbamyl” as used herein, alone or in combination, refers to a -OC(O)NRR’ group, with R and R’ as defined herein.

[0032] “N-carbamyl” as used herein, alone or in combination, refers to a ROC(O)NR’- group, with R and R’ as defined herein.

[0033] “Carbonyl,” as used herein, when alone includes formyl [-C(O)H] and in combination is a -C(O)- group.

[0034] “Carboxyl” or “carboxy,” as used herein, refers to -C(O)OH or the corresponding “carboxylate” anion, such as is in a carboxylic acid salt. An “O-carboxy” group refers to a RC(O)O- group, where R is as defined herein. A “C-carboxy” group refers to a -C(O)OR groups where R is as defined herein.

[0035] “Cyano,” as used herein, alone or in combination, refers to -CN.

[0036] “Cycloalkyl,” or, alternatively, “carbocycle,” as used herein, alone or in combination, refers to a saturated or partially saturated monocyclic, bicyclic, or tricyclic alkyl group wherein each cyclic moiety contains from 3 to 12 carbon atom ring members and which may optionally be a benzo fused ring system which is unsubstituted or substituted as defined herein. A carbocycle may comprise a bridged ring system and / or a spiro ring system (e.g., a system including two rings sharing a single carbon atom). The term “cycloalkenyl” refers to a cycloalkyl group having one or two double bonds. In certain embodiments, said cycloalkyl (or cycloalkenyl) will comprise from 5 to 7 carbon atoms. Examples of such groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, tetrahydronapthyl, indanyl, octahydronaphthyl, 2,3-dihydro-1H-indenyl, adamantyl, and the like. “Bicyclic” and “tricyclic” as used herein are intended to include both fused ring systems, such as decahydronaphthalene and octahydronaphthalene, as well as the multicyclic (multicentered) saturated or partially unsaturated type. The latter type of isomer is exemplified in general by bicyclo[1,1,1]pentane, camphor, adamantane, and bicyclo[3,2,1]octane.

[0037] “Ester,” as used herein, alone or in combination, refers to a carboxy group bridging two moieties linked at carbon atoms.

[0038] “Ether,” as used herein, alone or in combination, refers to an oxy group bridging two moieties linked at carbon atoms.

[0039] “Halo,” or “halogen,” as used herein, alone or in combination, refers to fluorine, chlorine, bromine, or iodine.

[0040] “Haloalkoxy,” as used herein, alone or in combination, refers to a haloalkyl group attached to the parent molecular moiety through an oxygen atom.

[0041] “Haloalkyl,” as used herein, alone or in combination, refers to an alkyl radical having the meaning as described herein wherein one or more hydrogens are replaced with a halogen. Specifically embraced are monohaloalkyl, dihaloalkyl and polyhaloalkyl radicals. A monohaloalkyl radical, for one example, may have an iodo, bromo, chloro, or fluoro atom within the radical. Dihalo and polyhaloalkyl radicals may have two or more of the same halo atoms or a combination of different halo radicals. Examples of haloalkyl radicals include fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl and dichloropropyl. “Haloalkylene” refers to a haloalkyl group attached at two or more positions. Examples include fluoromethylene (-CFH-), difluoromethylene (-CF2- ), chloromethylene (-CHCl-) and the like.

[0042] “Heteroatom,” as used herein, refers to one or more of oxygen, sulfur, nitrogen, phosphorus, boron, or selenium (including, any oxidized form of nitrogen, sulfur, boron, or phosphorus; the quaternized form of any basic nitrogen or; a substitutable nitrogen of a heterocyclic ring, for example N (as in 3,4-dihydro- 2H-pyrrolyl), NH (as in pyrrolidinyl) or NR+ (as in N-substituted pyrrolidinyl)).

[0043] “Heteroalkyl,” as used herein, alone or in combination, refers to a stable straight or branched hydrocarbon chain, fully saturated or containing from 1 to 3 degrees of unsaturation, consisting of the stated number of carbon atoms and from one to three heteroatoms, e.g., selected from N, O, and S, and wherein the N and S atoms may optionally be oxidized and the N heteroatom may optionally be quaternized. The heteroatom(s) may be placed at any interior position of the heteroalkyl group. Up to two heteroatoms may be consecutive, such as, for example, -CH2-NH-OCH3.

[0044] “Heteroaryl,” as used herein, alone or in combination, refers to a 3- to 15-membered aromatic monocyclic ring, or a fused monocyclic, bicyclic, or tricyclic ring system in which at least one of the fused rings is aromatic, which ring or ring system contains at least one heteroatom, e.g., selected from N, O, and S. In certain embodiments, said heteroaryl will comprise from 1 to 4 heteroatoms as ring members. Infurther embodiments, said heteroaryl will comprise from 1 to 2 heteroatoms as ring members. In certain embodiments, said heteroaryl will comprise from 5 to 7 atoms. The term also embraces fused polycyclic groups wherein heterocyclic rings are fused with aryl rings, wherein heteroaryl rings are fused with other heteroaryl rings, wherein heteroaryl rings are fused with heterocycloalkyl rings, or wherein heteroaryl rings are fused with cycloalkyl rings. Examples of heteroaryl groups include pyrrolyl, imidazolyl, pyrazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazolyl, furyl, thienyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, thiadiazolyl, isothiazolyl, indolyl, isoindolyl, indolizinyl, benzimidazolyl, quinolyl, isoquinolyl, quinoxalinyl, quinazolinyl, indazolyl, benzotriazolyl, benzodioxolyl, benzopyranyl, benzoxazolyl, benzoxadiazolyl, benzothiazolyl, benzothiadiazolyl, benzofuryl, benzothienyl, chromonyl, coumarinyl, benzopyranyl, tetrahydroquinolinyl, tetrazolopyridazinyl, tetrahydroisoquinolinyl, thienopyridinyl, furopyridinyl, pyrrolopyridinyl and the like. Exemplary tricyclic heterocyclic groups include carbazolyl, phenanthrolinyl, dibenzofuranyl, acridinyl, phenanthridinyl, xanthenyl and the like.

[0045] “Heterocycloalkyl” and, interchangeably, “heterocycle,” as used herein, alone or in combination, each refer to a saturated, partially unsaturated, or fully unsaturated (but nonaromatic) monocyclic, bicyclic, or tricyclic heterocyclic group containing at least one heteroatom as a ring member, e.g., wherein each said heteroatom may be independently selected from nitrogen, oxygen, and sulfur. In some embodiments, a heterocycle comprises a heteroaryl ring fused to a saturated, partially unsaturated, or fully unsaturated (but nonaromatic) ring that optionally contains a heteroatom. In some embodiments, a heterocycle comprises an aryl ring fused to a saturated, partially unsaturated, or fully unsaturated (but nonaromatic) ring that contains a heteroatom. In some embodiments, a heterocycle comprises a carbocycle ring fused to a saturated, partially unsaturated, or fully unsaturated ring that contains a heteroatom. In some embodiments, a heterocycle comprises a first ring that is saturated, partially unsaturated, or fully unsaturated ring that contains a heteroatom and a second ring that is saturated, partially unsaturated, or fully unsaturated ring that optionally contains a heteroatom. In some embodiments, the first ring and the second ring share a single heteroatom. In certain embodiments, said heterocycloalkyl will comprise from 1 to 4 heteroatoms as ring members. In further embodiments, said heterocycloalkyl will comprise from 1 to 2 heteroatoms as ring members. In certain embodiments, said heterocycloalkyl will comprise from 3 to 8 ring members in each ring. In further embodiments, said heterocycloalkyl will comprise from 3 to 7 ring members in each ring. In yet further embodiments, said heterocycloalkyl will comprise from 5 to 6 ring members in each ring. A heterocycle may comprise a bridged ring system and / or a spiro ring system (e.g., a system including two rings sharing a single atom, such as a single carbon atom). “Heterocycloalkyl” and “heterocycle” are intended to include sulfones, sulfoxides, N-oxides of tertiary nitrogen ring members, and carbocyclic fusedand benzo fused ring systems; additionally, both terms also include systems where a heterocycle ring is fused to an aryl group, as defined herein, or an additional heterocycle group. Examples of heterocycle groups include aziridinyl, azetidinyl, 1,3-benzodioxolyl, dihydroisoindolyl, dihydroisoquinolinyl, dihydrocinnolinyl, dihydrobenzodioxinyl, dihydro[1,3]oxazolo[4,5-b]pyridinyl, dihydroindolyl, dihydropyridinyl, 1,3-dioxanyl, 1,4-dioxanyl, 1,3-dioxolanyl, isoindolinyl, morpholinyl, piperazinyl, pyrrolidinyl, tetrahydropyridinyl, piperidinyl, thiomorpholinyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine, 4,5,6,7-tetrahydro-[1,2,3]triazolo[1,5-a]pyrazine, 4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine, 1- methyl-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine, 5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyrazine, 5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a][1,4]diazepine, 3- oxa-9-azabicyclo[3.3.1]nonane, hexahydro-3,6-epiminofuro[3,2-b]furan, and the like. The heterocycle groups are unsubstituted or substituted unless specifically prohibited.

[0046] “Hydrazinyl” as used herein, alone or in combination, refers to two amino groups joined by a single bond, i.e., -N-N-.

[0047] “Hydroxy,” as used herein, alone or in combination, refers to -OH.

[0048] “Hydroxyalkyl,” as used herein, alone or in combination, refers to a hydroxy group attached to the parent molecular moiety through an alkyl group.

[0049] “Iminohydroxy,” as used herein, alone or in combination, refers to =N(OH) and =N-O-.

[0050] “Lower amino,” as used herein, alone or in combination, refers to -NRR’, wherein R and R’ are independently selected from hydrogen and lower alkyl (e.g., C1-4 alkyl), either of which is unsubstituted or substituted.

[0051] “Mercaptyl” as used herein, alone or in combination, refers to an RS- group, where R is as defined herein.

[0052] “Nitro,” as used herein, alone or in combination, refers to –NO2.

[0053] “Oxy” or “oxa,” as used herein, alone or in combination, refer to –O–.

[0054] “Oxo,” as used herein, alone or in combination, refers to =O.

[0055] “Perhaloalkoxy” refers to an alkoxy group where all of the hydrogen atoms are replaced by halogen atoms.

[0056] “Perhaloalkyl” as used herein, alone or in combination, refers to an alkyl group where all of the hydrogen atoms are replaced by halogen atoms.

[0057] “Ring,” or equivalently, “cycle,” as used herein, in reference to a chemical structure or portion thereof, means a group in which every atom is a member of a common cyclic structure. A ring can be saturated or unsaturated, including aromatic, unless otherwise provided, and may have between 3 and 9members. If the ring is a heterocycle, it may contain between 1 and 4 heteroatoms or heteroatom- comprising groups selected from B, N, O, S, C(O), and S(O)m, wherein m is 0, 1, or 2. Unless specifically prohibited, a ring is unsubstituted or substituted. Two or more rings may be fused together (e.g., they may share a bond and two common atoms). Two or more rings may be linked together in a spiro arrangement such that only a single atom is shared between two rings. Two or more rings may also or alternatively be configured in a bridged arrangement such that three or more atoms are shared between two or more rings.

[0058] “Sulfonate,” “sulfonic acid,” and “sulfonic,” as used herein, alone or in combination, refer to the – SO3H group and its anion as the sulfonic acid is used in salt formation.

[0059] “Sulfanyl,” as used herein, alone or in combination, refers to –S–.

[0060] “Sulfinyl,” as used herein, alone or in combination, refers to –S(O)–.

[0061] “Sulfonyl,” as used herein, alone or in combination, refers to –S(O)2–.

[0062] “N-sulfonamido” refers to a RS(=O)2NR’- group with R and R’ as defined herein.

[0063] “S-sulfonamido” refers to a -S(=O)2NRR’, group, with R and R’ as defined herein.

[0064] “Tautomer”, as used herein, alone or in combination, refers to one of two or more isomers that rapidly interconvert. Generally, this interconversion is sufficiently fast so that an individual tautomer is not isolated in the absence of another tautomer. The ratio of the amount of tautomers can be dependent on solvent composition, ionic strength, and pH, as well as other solution parameters. The ratio of the amount of tautomers can be different in a particular solution and in the microenvironment of a biomolecular binding site in said solution. Examples of tautomers that are well known in the art include keto / enol, enamine / imine, and lactam / lactim tautomers. Examples of tautomers that are well known in the art also include 2- hydroxypyridine / 2(1H)-pyridone and 2-aminopyridine / 2(1H)-iminopyridone tautomers.

[0065] “Thia” and “thio,” as used herein, alone or in combination, refer to a –S– group or an ether wherein the oxygen is replaced with sulfur. The oxidized derivatives of the thio group, namely sulfinyl and sulfonyl, are included in the definition of thia and thio.

[0066] “Thiol,” as used herein, alone or in combination, refers to an –SH group.

[0067] “Thiocarbonyl,” as used herein, when alone includes thioformyl –C(S)H and in combination is a – C(S)– group.

[0068] “N-thiocarbamyl” refers to an ROC(S)NR’– group, with R and R’ as defined herein.

[0069] “O-thiocarbamyl” refers to a –OC(S)NRR’ group, with R and R’ as defined herein.

[0070] “Thiocyanato” refers to a –CNS group.

[0071] Any definition herein may be used in combination with any other definition to describe a composite structural group. By convention, the trailing element of any such definition is that which attaches to theparent moiety. For example, the composite group alkylamido would represent an alkyl group attached to the parent molecule through an amido group, and the term alkoxyalkyl would represent an alkoxy group attached to the parent molecule through an alkyl group.

[0072] As described herein, groups may be substituted or unsubstituted (e.g., “optionally substituted”). Unless otherwise specified, any group may be substituted with one or more substituents, such as one or more substituents provided herein. Examples of substituents that may substitute a group include, but are not limited to, one or more substituents independently selected from the following groups or a particular designated set of groups, alone or in combination: alkyl (e.g., C1-20 alkyl, such as C1-10 alkyl, such as C1-6alkyl, such as C1-3 alkyl), alkenyl (e.g., C2-20 alkenyl, such as C2-10 alkenyl, such asC2-6alkenyl), alkynyl (e.g., C2-20 alkynyl, such as C2-10 alkynyl, such asC2-6alkynyl), alkanoyl (e.g., C1-20 alkanoyl, such as C1-10alkanoyl, such as C1-6alkanoyl), heteroalkyl (e.g., a heteroalkyl moiety including 1-20 carbon atoms and 1-6 heteroatoms, such as a heteroalkyl moiety including 1-6 carbon atoms and 1-3 heteroatoms), haloalkyl (e.g., a halo-substituted C1-20 alkyl, such as a halo-substituted C1-10 alkyl, a halo-substituted C1-6alkyl), haloalkenyl (e.g., a halo-substituted C2-20 alkenyl, such as a halo-substitutedC2-6alkenyl), haloalkynyl (e.g., a halo-substituted C2-20 alkynyl, such as a halo-substitutedC2-6alkynyl), perhaloalkyl (e.g., C1-20perhaloalkyl, such as C1-6perhaloalkyl, such as C1-3perhaloalkyl), perhaloalkoxy (e.g., C1-20perhaloalkoxy, such as C1-6perhaloalkoxy), phenyl, aryl (e.g., C5-20aryl, such as C5-10aryl, such as C5-6aryl), aryloxy (e.g., C5-20 aryloxy, such as C5-10 aryloxy, such as C5-6 aryloxy), alkoxy (e.g., C1-20 alkoxy, such as C1-10 alkoxy, such as C1-6alkoxy), haloalkoxy (e.g., C1-20 haloalkoxy, such as C1-10 haloalkoxy, such as C1-6haloalkoxy), oxo, acyloxy (e.g., an acyloxy group including 1-20 carbon atoms, such as 1-10 carbon atoms, such as 1-6 carbon atoms), carbonyl (e.g., C(O) or C=O), carboxyl (e.g., C(O)O), alkylcarbonyl (e.g., C1-20alkylcarbonyl, such as C1-10alkylcarbonyl, such as C1-6alkylcarbonyl, such as C1-3alkylcarbonyl), carboxyester (e.g., C(O)OR where R is, e.g., alkyl (e.g., C1-20alkyl, such as C1-10alkyl, such as C1-6alkyl, such as C1-3 alkyl), alkenyl (e.g., C2-20 alkenyl, such as C2-10 alkenyl, such as C2-6alkenyl), or alkynyl (e.g., C2-20 alkynyl, such as C2-10 alkynyl, such as C2-6alkynyl), any of which may be substituted by any group provided herein), carboxamido, cyano (e.g., CN), hydrogen, halogen (e.g., iodine, bromine, chlorine, or fluorine), hydroxy, amino (e.g., NR’R” where R’ and R” are independently, e.g., hydrogen, alkyl (e.g., C1-20alkyl, such as C1-10alkyl, such as C1-6alkyl, such as C1-3alkyl), alkenyl (e.g., C2-20alkenyl, such as C2-10 alkenyl, such asC2-6alkenyl), or alkynyl (e.g., C2-20 alkynyl, such as C2-10 alkynyl, such as C2- 6 alkynyl), any of which may be substituted by any group provided herein), alkylamino (e.g., NR’R” where R’ is alkyl (e.g., C1-20 alkyl, such as C1-10 alkyl, such as C1-6alkyl, such as C1-3 alkyl) and R” is, e.g., hydrogen, alkyl (e.g., C1-20 alkyl, such as C1-10 alkyl, such as C1-6alkyl, such as C1-3 alkyl), alkenyl (e.g., C2-20 alkenyl, such as C2-10 alkenyl, such as C2-6 alkenyl), or alkynyl (e.g., C2-20 alkynyl, such as C2-10 alkynyl, such as C2-6 alkynyl), any of which may be substituted by any group provided herein), arylamino (e.g., NR’R” where R’ is aryl (e.g., C5-20 aryl, such as C5-10 aryl, such as C5-6 aryl) and R” is, e.g., hydrogen, alkyl (e.g., C1-20 alkyl, such as C1-10 alkyl, such as C1-6alkyl, such as C1-3 alkyl), alkenyl (e.g., C2-20 alkenyl, such as C2-10alkenyl, such as C2-6alkenyl), or alkynyl (e.g., C2-20alkynyl, such as C2-10alkynyl, such as C2-6alkynyl), any of which may be substituted by any group provided herein), amido (e.g., C(O)NR’R” where R’ and R” are independently, e.g., hydrogen, alkyl (e.g., C1-20 alkyl, such as C1-10 alkyl, such as C1-6alkyl, such as C1-3 alkyl), alkenyl (e.g., C2-20 alkenyl, such as C2-10 alkenyl, such as C2-6 alkenyl), or alkynyl (e.g., C2-20 alkynyl, such as C2-10 alkynyl, such as C2-6 alkynyl), any of which may be substituted by any group provided herein), nitro (e.g., NO2), thiol (e.g., SH), alkylthio (e.g., C1-20 alkyl substituted with a thiol group, such as C1-10alkyl substituted with a thiol group, such as C1-6alkyl substituted with a thiol group, such as C1-3 alkyl substituted with a thiol group), haloalkylthio (e.g., C1-20 haloalkylthio, such as C1-10 haloalkylthio, such as C1-6haloalkylthio, such as C1-3 haloalkylthio), perhaloalkylthio (e.g., C1-20 perhaloalkylthio, such as C1-10 perhaloalkylthio, such as C1-6perhaloalkylthio, such as C1-3 perhaloalkylthio), arylthiol (e.g., C5-20 arylthiol, such as C5-10 arylthiol, such as C5-6 arylthiol), sulfonate (e.g., S(O)2OR where R is, e.g., alkyl (e.g., C1-20alkyl, such as C1-10alkyl, such as C1-6alkyl, such as C1-3alkyl), alkenyl (e.g., C2-20alkenyl, such as C2-10alkenyl, such as C2-6alkenyl), or alkynyl (e.g., C2-20alkynyl, such as C2-10alkynyl, such as C2-6alkynyl), any of which may be substituted by any group provided herein), sulfonic acid (e.g., S(O)2OH), trisubstituted silyl (e.g., SiR’R”R* where R’, R”, and R* are independently selected from, e.g., alkyl (e.g., C1-20 alkyl, such as C1-10 alkyl, such as C1-6alkyl, such as C1-3 alkyl), alkenyl (e.g., C2-20 alkenyl, such as C2-10 alkenyl, such as C2-6 alkenyl), or alkynyl (e.g., C2-20 alkynyl, such as C2-10 alkynyl, such as C2-6 alkynyl), any of which may be substituted by any group provided herein; in some cases, a trisubstituted silyl can be trimethylsilyl), N3, SCH3, C(O)CH3, CO2CH3, CO2H, pyridinyl, thiophene, furanyl, carbamate, and urea. Additional groups may also be contemplated. Where structurally feasible, two substituents may be joined together to form a fused five-, six-, or seven-membered carbocyclic or heterocyclic ring consisting of zero to three heteroatoms (e.g., N, O, S, etc.), for example forming methylenedioxy or ethylenedioxy. An unsubstituted or substituted group may be unsubstituted (e.g., -CH2CH3), fully substituted (e.g., -CF2CF3), monosubstituted (e.g., -CH2CH2F) or substituted at a level anywhere in-between fully substituted and monosubstituted (e.g., -CH2CF3). Where substituents are recited without qualification as to substitution, both substituted and unsubstituted forms are encompassed. Where a substituent is qualified as “substituted,” the substituted form is specifically intended. Additionally, different sets of optionalsubstituents to a particular moiety may be defined as needed; in these cases, the optional substitution will be as defined, often immediately following the phrase, “unsubstituted or substituted with.”

[0073] The terms R, R’, R”, R*, etc., appearing by themselves and without a number designation, unless otherwise defined, refer to a moiety selected from hydrogen, alkyl, cycloalkyl, heteroalkyl, aryl, heteroaryl and heterocycloalkyl, any of which is unsubstituted or substituted (e.g., as described herein). Such R and R’ groups should be understood to be unsubstituted or substituted as defined herein. Whether an R group has a number designation or not, every R group, including R, R’ and Rnwhere n=(1, 2, 3, …n), every substituent, and every term should be understood to be independent of every other in terms of selection from a group. Should any variable, substituent, or term (e.g., aryl, heterocycle, R, etc.) occur more than one time in a formula or generic structure, its definition at each occurrence is independent of the definition at every other occurrence. Those of skill in the art will further recognize that certain groups may be attached to a parent molecule or may occupy a position in a chain of elements from either end as written. For example, an unsymmetrical group such as -C(O)N(R)- may be attached to the parent moiety at either the carbon or the nitrogen.

[0074] “Bond” refers to a covalent linkage between two atoms, or two moieties when the atoms joined by the bond are considered to be part of larger substructure. A bond may be single, double, or triple unless otherwise specified. A dashed line between two atoms in a drawing of a molecule indicates that an additional bond may be present or absent at that position.

[0075] Asymmetric centers may exist in the compounds disclosed herein. These centers are designated by the symbols “R” or “S,” depending on the configuration of substituents around the chiral carbon atom. It should be understood that the disclosure encompasses all stereochemical isomeric forms, including diastereomeric, enantiomeric, atropisomeric, and epimeric forms, as well as d-isomers and 1-isomers, and mixtures thereof. Individual stereoisomers of compounds can be prepared synthetically from commercially available starting materials which contain chiral centers or by preparation of mixtures of enantiomeric products followed by separation such as conversion to a mixture of diastereomers followed by separation or recrystallization, chromatographic techniques, direct separation of enantiomers on chiral chromatographic columns, or any other appropriate method known in the art. Starting compounds of particular stereochemistry are either commercially available or can be made and resolved by techniques known in the art. Additionally, the compounds disclosed herein may exist as geometric isomers. The present disclosure includes all cis, trans, syn, anti, entgegen (E), and zusammen (Z) isomers as well as the appropriate mixtures thereof. Additionally, compounds may exist as tautomers; all tautomeric isomers are provided by this disclosure. Additionally, the compounds provided herein may comprise conformationalisomers, which compounds comprise groups that can orient in different conformations in relation to another moiety. Additionally, the compounds disclosed herein can exist in unsolvated as well as solvated forms with pharmaceutically acceptable solvents such as water, ethanol, and the like. In general, the solvated forms are considered equivalent to the unsolvated forms.

[0076] “Combination therapy” means the administration of two or more therapeutic agents to treat a therapeutic condition or disorder described in the present disclosure. Such administration encompasses co- administration of these therapeutic agents in a substantially simultaneous manner, such as in a single dose unit (e.g., capsule) having a fixed ratio of active ingredients or in multiple, separate dose units (e.g., capsules) for each active ingredient. In addition, such administration also encompasses use of each type of therapeutic agent in a sequential manner. In either case, the treatment regimen will provide beneficial effects of the drug combination in treating the conditions or disorders described herein.

[0077] “KRAS inhibitor” is used herein to refer to a compound that exhibits an IC50 with respect to KRAS activity of no more than about 100 μM and more typically not more than about 50 μM, as measured in the assays described generally herein, such as a surface plasmon resonance KRAS-G12D, G12V, G12C, G12S, G12A, G12R, G13D, or Q61H mutation or wild-type KRAS protein binding assay; and / or a KRAS G12D, G12V, G12C, G12S, G12A, G12R, G13D, or Q61H mutation or wild-type KRAS protein-effector protein interaction disruption assay. “IC50” is that concentration of inhibitor which reduces the activity of an enzyme (e.g., KRAS) to half-maximal level. Certain compounds disclosed herein have been discovered to exhibit inhibition against KRAS. In certain embodiments, compounds exhibit an IC50 with respect to KRAS (e.g., a KRAS protein having a mutation at codon 12 (e.g., a G12D, G12V, G12C, G12S, G12A, or G12R mutation), a KRAS protein having a mutation at codon 13 (e.g., a G13D mutation), a KRAS protein having a mutation at codon 61 (e.g., a Q61H mutation), or a wild-type KRAS protein) of no more than about 50 μM; in further embodiments, compounds exhibit an IC50with respect to KRAS (e.g., a KRAS protein having a mutation at codon 12 (e.g., a G12D, G12V, G12C, G12S, G12A, or G12R mutation), a KRAS protein having a mutation at codon 13 (e.g., a G13D mutation), a KRAS protein having a mutation at codon 61 (e.g., a Q61H mutation), or a wild-type KRAS protein) of no more than about 10 μM; in yet further embodiments, compounds exhibit an IC50 with respect to KRAS (e.g., a KRAS protein having a mutation at codon 12 (e.g., a G12D, G12V, G12C, G12S, G12A, or G12R mutation), a KRAS protein having a mutation at codon 13 (e.g., a G13D mutation), a KRAS protein having a mutation at codon 61 (e.g., a Q61H mutation), or a wild-type KRAS protein) of not more than about 1 μM; in yet further embodiments, compounds exhibit an IC50 with respect to KRAS (e.g., a KRAS protein having a mutation at codon 12 (e.g., a G12D, G12V, G12C, G12S, G12A, or G12R mutation), a KRAS protein having a mutation at codon13 (e.g., a G13D mutation), a KRAS protein having a mutation at codon 61 (e.g., a Q61H mutation), or a wild-type KRAS protein) of not more than about 200 nanomolar (nM), as measured in the KRAS assay described herein. In some embodiments, compounds exhibit an IC50 with respect to KRAS (e.g., a KRAS protein having a mutation at codon 12 (e.g., a G12D, G12V, G12C, G12S, G12A, or G12R mutation), a KRAS protein having a mutation at codon 13 (e.g., a G13D mutation), a KRAS protein having a mutation at codon 61 (e.g., a Q61H mutation), or a wild-type KRAS protein) of less than about 50 μM, such as less than about 40 μM, 30 μM, 20 μM, 10 μM, 9 μM, 8 μM, 7 μM, 6 μM, 5 μM, 4 μM, 3 μM, 2 μM, 1 μM, 900 nM, 800 nM, 700 nM, 600 nM, 500 nM, 400 nM, 300 nM, 200 nM, 100 nM, 90 nM, 80 nM, 70 nM, 60 nM, 50 nM, 40 nM, 30 nM, 20 nM, 10 nM, 9 nM, 8 nM, 7 nM, 6 nM, 5 nM, 4 nM, 3 nM, 2 nM, 1 nM, or less. In certain embodiments, compounds exhibit an IC50 with respect to KRAS (e.g., a KRAS protein having a mutation at codon 12 (e.g., a G12D, G12V, G12C, G12S, G12A, or G12R mutation), a KRAS protein having a mutation at codon 13 (e.g., a G13D mutation), a KRAS protein having a mutation at codon 61 (e.g., a Q61H mutation), or a wild-type KRAS protein) of less than about 1 μM, such as less than about 900 nM, 800 nM, 700 nM, 600 nM, 500 nM, 400 nM, 300 nM, 200 nM, 100 nM, 90 nM, 80 nM, 70 nM, 60 nM, 50 nM, 40 nM, 30 nM, 20 nM, 10 nM, 9 nM, 8 nM, 7 nM, 6 nM, 5 nM, 4 nM, 3 nM, 2 nM, 1 nM, or less. In some embodiments, compounds exhibit an IC50with respect to KRAS having a G12D mutation of less than about 50 μM, such as less than about 40 μM, 30 μM, 20 μM, 10 μM, 9 μM, 8 μM, 7 μM, 6 μM, 5 μM, 4 μM, 3 μM, 2 μM, 1 μM, 900 nM, 800 nM, 700 nM, 600 nM, 500 nM, 400 nM, 300 nM, 200 nM, 100 nM, 90 nM, 80 nM, 70 nM, 60 nM, 50 nM, 40 nM, 30 nM, 20 nM, 10 nM, 9 nM, 8 nM, 7 nM, 6 nM, 5 nM, 4 nM, 3 nM, 2 nM, 1 nM, or less. In some embodiments, compounds exhibit an IC50 with respect to KRAS having a G12V mutation of less than about 50 μM, such as less than about 40 μM, 30 μM, 20 μM, 10 μM, 9 μM, 8 μM, 7 μM, 6 μM, 5 μM, 4 μM, 3 μM, 2 μM, 1 μM, 900 nM, 800 nM, 700 nM, 600 nM, 500 nM, 400 nM, 300 nM, 200 nM, 100 nM, 90 nM, 80 nM, 70 nM, 60 nM, 50 nM, 40 nM, 30 nM, 20 nM, 10 nM, 9 nM, 8 nM, 7 nM, 6 nM, 5 nM, 4 nM, 3 nM, 2 nM, 1 nM, or less. In some embodiments, compounds exhibit an IC50 with respect to KRAS having a G12R mutation of less than about 50 μM, such as less than about 40 μM, 30 μM, 20 μM, 10 μM, 9 μM, 8 μM, 7 μM, 6 μM, 5 μM, 4 μM, 3 μM, 2 μM, 1 μM, 900 nM, 800 nM, 700 nM, 600 nM, 500 nM, 400 nM, 300 nM, 200 nM, 100 nM, 90 nM, 80 nM, 70 nM, 60 nM, 50 nM, 40 nM, 30 nM, 20 nM, 10 nM, 9 nM, 8 nM, 7 nM, 6 nM, 5 nM, 4 nM, 3 nM, 2 nM, 1 nM, or less. In some embodiments, compounds exhibit an IC50 with respect to KRAS having a G12A mutation of less than about 50 μM, such as less than about 40 μM, 30 μM, 20 μM, 10 μM, 9 μM, 8 μM, 7 μM, 6 μM, 5 μM, 4 μM, 3 μM, 2 μM, 1 μM, 900 nM, 800 nM, 700 nM, 600 nM, 500 nM, 400 nM, 300 nM, 200 nM, 100 nM, 90 nM, 80 nM, 70 nM, 60 nM, 50 nM, 40 nM, 30 nM, 20 nM, 10 nM, 9 nM, 8 nM, 7 nM, 6 nM, 5 nM, 4nM, 3 nM, 2 nM, 1 nM, or less. In some embodiments, compounds exhibit an IC50 with respect to KRAS having a G12S mutation of less than about 50 μM, such as less than about 40 μM, 30 μM, 20 μM, 10 μM, 9 μM, 8 μM, 7 μM, 6 μM, 5 μM, 4 μM, 3 μM, 2 μM, 1 μM, 900 nM, 800 nM, 700 nM, 600 nM, 500 nM, 400 nM, 300 nM, 200 nM, 100 nM, 90 nM, 80 nM, 70 nM, 60 nM, 50 nM, 40 nM, 30 nM, 20 nM, 10 nM, 9 nM, 8 nM, 7 nM, 6 nM, 5 nM, 4 nM, 3 nM, 2 nM, 1 nM, or less. In some embodiments, compounds exhibit an IC50 with respect to KRAS having a G12C mutation of less than about 50 μM, such as less than about 40 μM, 30 μM, 20 μM, 10 μM, 9 μM, 8 μM, 7 μM, 6 μM, 5 μM, 4 μM, 3 μM, 2 μM, 1 μM, 900 nM, 800 nM, 700 nM, 600 nM, 500 nM, 400 nM, 300 nM, 200 nM, 100 nM, 90 nM, 80 nM, 70 nM, 60 nM, 50 nM, 40 nM, 30 nM, 20 nM, 10 nM, 9 nM, 8 nM, 7 nM, 6 nM, 5 nM, 4 nM, 3 nM, 2 nM, 1 nM, or less. In some embodiments, compounds exhibit an IC50 with respect to KRAS having a G13D mutation of less than about 50 μM, such as less than about 40 μM, 30 μM, 20 μM, 10 μM, 9 μM, 8 μM, 7 μM, 6 μM, 5 μM, 4 μM, 3 μM, 2 μM, 1 μM, 900 nM, 800 nM, 700 nM, 600 nM, 500 nM, 400 nM, 300 nM, 200 nM, 100 nM, 90 nM, 80 nM, 70 nM, 60 nM, 50 nM, 40 nM, 30 nM, 20 nM, 10 nM, 9 nM, 8 nM, 7 nM, 6 nM, 5 nM, 4 nM, 3 nM, 2 nM, 1 nM, or less. In some embodiments, compounds exhibit an IC50 with respect to KRAS having a Q61H mutation of less than about 50 μM, such as less than about 40 μM, 30 μM, 20 μM, 10 μM, 9 μM, 8 μM, 7 μM, 6 μM, 5 μM, 4 μM, 3 μM, 2 μM, 1 μM, 900 nM, 800 nM, 700 nM, 600 nM, 500 nM, 400 nM, 300 nM, 200 nM, 100 nM, 90 nM, 80 nM, 70 nM, 60 nM, 50 nM, 40 nM, 30 nM, 20 nM, 10 nM, 9 nM, 8 nM, 7 nM, 6 nM, 5 nM, 4 nM, 3 nM, 2 nM, 1 nM, or less. In some embodiments, compounds exhibit an IC50 with respect to wild-type KRAS of less than about 50 μM, such as less than about 40 μM, 30 μM, 20 μM, 10 μM, 9 μM, 8 μM, 7 μM, 6 μM, 5 μM, 4 μM, 3 μM, 2 μM, 1 μM, 900 nM, 800 nM, 700 nM, 600 nM, 500 nM, 400 nM, 300 nM, 200 nM, 100 nM, 90 nM, 80 nM, 70 nM, 60 nM, 50 nM, 40 nM, 30 nM, 20 nM, 10 nM, 9 nM, 8 nM, 7 nM, 6 nM, 5 nM, 4 nM, 3 nM, 2 nM, 1 nM, or less.

[0078] In some embodiments, a KRAS inhibitor has inhibitory activity against KRAS having a G12D mutation that exceeds its inhibitory activity against KRAS having another mutation, such as a Q61H, G12C, G12R, G12S, G12A, G12V, or G13D mutation. For example, in some embodiments, a KRAS inhibitor provided herein has at least two-fold, five-fold, ten-fold, twenty-fold, thirty-fold, forty-fold, fifty-fold, one hundred-fold, or higher inhibitory activity against KRAS having a G12D mutation relative to KRAS having another mutation such as a Q61H, G12C, G12R, G12S, G12A, G12V, or G13D mutation.

[0079] In some embodiments, a KRAS inhibitor has inhibitory activity against KRAS having a G12V mutation that exceeds its inhibitory activity against KRAS having another mutation, such as a Q61H, G12C, G12R, G12S, G12A, G12D, or G13D mutation. For example, in some embodiments, a KRAS inhibitor provided herein has at least two-fold, five-fold, ten-fold, twenty-fold, thirty-fold, forty-fold, fifty-fold, onehundred-fold, or higher inhibitory activity against KRAS having a G12V mutation relative to KRAS having another mutation such as a Q61H, G12C, G12R, G12S, G12A, G12D, or G13D mutation.

[0080] In some embodiments, a KRAS inhibitor has inhibitory activity against KRAS having a G12R mutation that exceeds its inhibitory activity against KRAS having another mutation, such as a Q61H, G12C, G12D, G12S, G12A, G12V, or G13D mutation. For example, in some embodiments, a KRAS inhibitor provided herein has at least two-fold, five-fold, ten-fold, twenty-fold, thirty-fold, forty-fold, fifty-fold, one hundred-fold, or higher inhibitory activity against KRAS having a G12R mutation relative to KRAS having another mutation such as a Q61H, G12C, G12D, G12S, G12A, G12V, or G13D mutation.

[0081] In some embodiments, a KRAS inhibitor has inhibitory activity against KRAS having a G12C mutation that exceeds its inhibitory activity against KRAS having another mutation, such as a Q61H, G12R, G12D, G12S, G12A, G12V, or G13D mutation. For example, in some embodiments, a KRAS inhibitor provided herein has at least two-fold, five-fold, ten-fold, twenty-fold, thirty-fold, forty-fold, fifty-fold, one hundred-fold, or higher inhibitory activity against KRAS having a G12C mutation relative to KRAS having another mutation such as a Q61H, G12R, G12D, G12S, G12A, G12V, or G13D mutation.

[0082] In some embodiments, a KRAS inhibitor has inhibitory activity against KRAS having a G12S mutation that exceeds its inhibitory activity against KRAS having another mutation, such as a Q61H, G12C, G12D, G12R, G12A, G12V, or G13D mutation. For example, in some embodiments, a KRAS inhibitor provided herein has at least two-fold, five-fold, ten-fold, twenty-fold, thirty-fold, forty-fold, fifty-fold, one hundred-fold, or higher inhibitory activity against KRAS having a G12S mutation relative to KRAS having another mutation such as a Q61H, G12C, G12D, G12R, G12A, G12V, or G13D mutation.

[0083] In some embodiments, a KRAS inhibitor has inhibitory activity against KRAS having a G12A mutation that exceeds its inhibitory activity against KRAS having another mutation, such as a Q61H, G12C, G12D, G12S, G12R, G12V, or G13D mutation. For example, in some embodiments, a KRAS inhibitor provided herein has at least two-fold, five-fold, ten-fold, twenty-fold, thirty-fold, forty-fold, fifty-fold, one hundred-fold, or higher inhibitory activity against KRAS having a G12A mutation relative to KRAS having another mutation such as a Q61H, G12C, G12D, G12S, G12R, G12V, or G13D mutation.

[0084] In some embodiments, a KRAS inhibitor has inhibitory activity against KRAS having a G13D mutation that exceeds its inhibitory activity against KRAS having another mutation, such as a Q61H, G12C, G12D, G12S, G12R, G12V, or G12A mutation. For example, in some embodiments, a KRAS inhibitor provided herein has at least two-fold, five-fold, ten-fold, twenty-fold, thirty-fold, forty-fold, fifty-fold, one hundred-fold, or higher inhibitory activity against KRAS having a G13D mutation relative to KRAS having another mutation such as a Q61H, G12C, G12D, G12S, G12R, G12V, or G12A mutation.

[0085] In some embodiments, a KRAS inhibitor has inhibitory activity against KRAS having a Q61H mutation that exceeds its inhibitory activity against KRAS having another mutation, such as a G13D, G12C, G12D, G12S, G12R, G12V, or G12A mutation. For example, in some embodiments, a KRAS inhibitor provided herein has at least two-fold, five-fold, ten-fold, twenty-fold, thirty-fold, forty-fold, fifty-fold, one hundred-fold, or higher inhibitory activity against KRAS having a Q61H mutation relative to KRAS having another mutation such as a G13D, G12C, G12D, G12S, G12R, G12V, or G12A mutation.

[0086] In some embodiments, a KRAS inhibitor has inhibitory activity against a wild-type KRAS that exceeds its inhibitory activity against KRAS having a Q61H, G13D, G12C, G12D, G12S, G12R, G12V, or G12A mutation. For example, in some embodiments, a KRAS inhibitor provided herein has at least two- fold, five-fold, ten-fold, twenty-fold, thirty-fold, forty-fold, fifty-fold, one hundred-fold, or higher inhibitory activity against a wild-type KRAS relative to KRAS having a Q61H, G13D, G12C, G12D, G12S, G12R, G12V, or G12A mutation.

[0087] In some embodiments, a KRAS inhibitor provided herein has greater inhibitory activity against KRAS having a Q61H, G13D, G12D, G12S, G12R, G12V, or G12A mutation or a wild-type KRAS than against KRAS having a G12C mutation. In some embodiments, a KRAS inhibitor provided herein has greater inhibitory activity against KRAS having a G12D, G12V, or G12R mutation than against KRAS having a G12C mutation.

[0088] In some embodiments, a KRAS inhibitor provided herein has greater inhibitory activity against KRAS having a G12D mutation than against KRAS having a G12C mutation. In some embodiments, a KRAS inhibitor provided herein has greater inhibitory activity against KRAS having a G12D mutation than against KRAS having a G12R mutation. In some embodiments, a KRAS inhibitor provided herein has greater inhibitory activity against KRAS having a G12D mutation than against a KRAS having a G12S mutation. In some embodiments, a KRAS inhibitor provided herein has greater inhibitory activity against KRAS having a G12D mutation than against KRAS having a G12A mutation. In some embodiments, a KRAS inhibitor provided herein has greater inhibitory activity against KRAS having a G12D mutation than against KRAS having a G12V mutation. In some embodiments, a KRAS inhibitor provided herein has greater inhibitory activity against KRAS having a G12D mutation than against KRAS having a G13D mutation. In some embodiments, a KRAS inhibitor provided herein has greater inhibitory activity against KRAS having a G12D mutation than against KRAS having a Q61H mutation.

[0089] In some embodiments, a KRAS inhibitor provided herein has greater inhibitory activity against KRAS having a G12V mutation than against KRAS having a G12C mutation. In some embodiments, a KRAS inhibitor provided herein has greater inhibitory activity against KRAS having a G12V mutation thanagainst KRAS having a G12R mutation. In some embodiments, a KRAS inhibitor provided herein has greater inhibitory activity against KRAS having a G12V mutation than against a KRAS having a G12S mutation. In some embodiments, a KRAS inhibitor provided herein has greater inhibitory activity against KRAS having a G12V mutation than against KRAS having a G12A mutation. In some embodiments, a KRAS inhibitor provided herein has greater inhibitory activity against KRAS having a G12V mutation than against KRAS having a G12D mutation. In some embodiments, a KRAS inhibitor provided herein has greater inhibitory activity against KRAS having a G12V mutation than against KRAS having a G13D mutation. In some embodiments, a KRAS inhibitor provided herein has greater inhibitory activity against KRAS having a G12V mutation than against KRAS having a Q61H mutation.

[0090] In some embodiments, a KRAS inhibitor provided herein has greater inhibitory activity against KRAS having a G12R mutation than against KRAS having a G12C mutation. In some embodiments, a KRAS inhibitor provided herein has greater inhibitory activity against KRAS having a G12R mutation than against KRAS having a G12D mutation. In some embodiments, a KRAS inhibitor provided herein has greater inhibitory activity against KRAS having a G12R mutation than against a KRAS having a G12S mutation. In some embodiments, a KRAS inhibitor provided herein has greater inhibitory activity against KRAS having a G12R mutation than against KRAS having a G12A mutation. In some embodiments, a KRAS inhibitor provided herein has greater inhibitory activity against KRAS having a G12R mutation than against KRAS having a G12V mutation. In some embodiments, a KRAS inhibitor provided herein has greater inhibitory activity against KRAS having a G12R mutation than against KRAS having a G13D mutation. In some embodiments, a KRAS inhibitor provided herein has greater inhibitory activity against KRAS having a G12R mutation than against KRAS having a Q61H mutation.

[0091] In some embodiments, a KRAS inhibitor provided herein has greater inhibitory activity against active (“GTP-bound”) KRAS having a Q61H, G12D, G12V, G12R, G12A, G12S, G12C, or G13D mutation, or wild-type KRAS, than against an inactive (“GDP-bound”) KRAS having a Q61H, G12D, G12V, G12R, G12A, G12S, G12C, or G13D mutation or wild-type KRAS. In some embodiments, a KRAS inhibitor provided herein has lower inhibitory activity against active (“GTP-bound”) KRAS having a Q61H, G12D, G12V, G12R, G12A, G12S, G12C, or G13D mutation, or wild-type KRAS, than against an inactive (“GDP-bound”) KRAS having a Q61H, G12D, G12V, G12R, G12A, G12S, G12C, or G13D mutation or wild-type KRAS. In some embodiments, a KRAS inhibitor provided herein has inhibitory activity against both active (“GTP-bound”) and inactive (“GDP-bound”) KRAS having a Q61H, G12D, G12V, G12R, G12A, G12S, G12C, or G13D mutation or wild-type KRAS. In some embodiments, a KRAS inhibitor provided herein has similar inhibitory activity against active (“GTP-bound”) and inactive (“GDP-bound”)KRAS having a Q61H, G12D, G12V, G12R, G12A, G12S, G12C, or G13D mutation or wild-type KRAS. In some embodiments, a KRAS inhibitor provided herein has inhibitory activity against a K-RAS4a splice variant. In some embodiments, a KRAS inhibitor provided herein has inhibitory activity against a K- RAS4b splice variant. In some embodiments, a KRAS inhibitor provided herein has inhibitory activity against both K-RAS4a and K-RAS4b splice variants.

[0092] “Therapeutically effective amount” refers to an amount of a compound or of a pharmaceutical composition useful for treating or ameliorating an identified disease, disorder, or condition, or for exhibiting a detectable therapeutic or inhibitory effect. The exact amounts will depend on the purpose of the treatment and will be ascertainable by one skilled in the art using known techniques (see, e.g., Lieberman, Pharmaceutical Dosage Forms (vols. 1-3, 1992); Lloyd, The Art, Science and Technology of Pharmaceutical Compounding (1999); Pickar, Dosage Calculations (1999); and Remington: The Science and Practice of Pharmacy, 20th Edition, 2003, Gennaro, Ed., Lippincott, Williams & Wilkins).

[0093] The term “therapeutically acceptable” refers to those compounds (or salts, prodrugs, tautomers, zwitterionic forms, etc.) which are suitable for use in contact with the tissues of patients without undue toxicity, irritation, and allergic response, are commensurate with a reasonable benefit / risk ratio, and are effective for their intended use.

[0094] “Treat,” “treating,” and “treatment” refer to any indicia of success in the treatment or amelioration of an injury, pathology, disease, disorder, or condition, including any objective or subjective parameter such as abatement; remission; diminishing of symptoms or making the injury, pathology, disease, disorder, or condition more tolerable to the patient; slowing in the rate of degeneration or decline; making the final point of degeneration less debilitating; and / or improving a patient's physical or mental well-being. The treatment or amelioration of symptoms can be based on objective or subjective parameters, including the results of a physical examination, neuropsychiatric exams, and / or a psychiatric evaluation. Treatment may also be preemptive in nature; i.e., it may include prevention of a disease, disorder, or condition, prevention of onset of one or more symptoms of a disease, disorder, or condition, and / or prevention of escalation of a disease, disorder, or condition. Prevention of a disease, disorder, or condition may involve complete protection from disease, and / or prevention of disease progression (e.g., to a later stage of the disease, disorder, or condition). For example, prevention of a disease may not mean complete foreclosure of any effect related to the diseases at any level, but instead may mean prevention of the symptoms of a disease, disorder, or condition to a clinically significant or detectable level.

[0095] “Patient” or “subject” refers to a living organism suffering from or prone to a disease, disorder, or condition that can be treated by administration of a compound or pharmaceutical composition as providedherein. Non-limiting examples include humans, rats, mice, rabbits, hamsters, guinea pigs, cats, dogs, non- human primates (e.g., monkeys), goats, pigs, sheep, cows, deer, horses, and other non-mammalian animals. Examples of mammals that can be treated by administration of a compound or pharmaceutical composition provided herein include, for example, rodents (e.g., rats, mice, squirrels, guinea pigs, hamsters, etc.), lagomorphs (e.g., rabbits, hares, etc.), primates (e.g., monkeys, apes, etc.), bovines (e.g., cattle), odd-toed ungulates (e.g., horses), even-toed ungulates (e.g., bovines such as cattle, ovine such as sheep, caprine such as goats, porcine such as pigs, etc.), and marsupials (e.g., kangaroo, wallaby, wallaroo, sugar glider, etc.). In some embodiments, the patient or subject is human. In some embodiments, the patient or subject is a companion animal such as a cat or dog. In some embodiments, the patient or subject is a farm animal such as a goat, sheep, cow, pig, or horse. In some embodiments, the patient or subject is an exotic animal such as a primate (e.g., monkey), marsupial (e.g., kangaroo, wallaby, wallaroo, sugar glider, etc.), or a non- domesticated or hybrid cat or dog.

[0096] “Composition,” as used herein, is intended to encompass a product comprising the specified ingredients in the specified amounts, as well as any product, which results, directly or indirectly, from combination of the specified ingredients in the specified amounts. By “pharmaceutically acceptable” it is meant the carrier, diluent, or excipient must be compatible with the other ingredients of the formulation and not deleterious to the recipient thereof.

[0097] “Pharmaceutically acceptable excipient” refers to a substance that aids the administration of an active agent to and absorption by a subject. Pharmaceutical excipients useful in the present disclosure include, but are not limited to, binders, fillers, disintegrants, lubricants, coatings, sweeteners, flavors, and colors. One of skill in the art will recognize that other pharmaceutical excipients are useful in the present disclosure.

[0098] The term “prodrug” refers to a compound that is made more active in vivo. Certain compounds disclosed herein may also exist as prodrugs. Prodrugs of the compounds described herein are structurally modified forms of the compound that readily undergo chemical changes under physiological conditions to provide the compound. Additionally, prodrugs can be converted to the compound by chemical or biochemical methods in an ex vivo environment. For example, prodrugs can be slowly converted to a compound when placed in a transdermal patch reservoir with a suitable enzyme or chemical reagent. Prodrugs are often useful because, in some situations, they may be easier to administer than the compound, or parent drug. They may, for instance, be bioavailable by oral administration whereas the parent drug is not. The prodrug may also have improved solubility in pharmaceutical compositions over the parent drug.

[0099] The compounds disclosed herein can exist as therapeutically acceptable salts (also referred to herein as “pharmaceutically acceptable salts”). The present disclosure includes compounds provided herein in the form of salts, including acid addition salts. Suitable salts include those formed with both organic and inorganic acids. Such acid addition salts will normally be pharmaceutically acceptable. However, non- pharmaceutically acceptable salts may be of utility in the preparation and purification of the compound in question. Basic addition salts may also be formed and be pharmaceutically acceptable.

[0100] The terms “therapeutically acceptable salt” and “pharmaceutically acceptable salt” as used herein, represents salts or zwitterionic forms of the compounds disclosed herein which are water or oil-soluble or dispersible and therapeutically acceptable as defined herein. The salts can be prepared during the final isolation and purification of the compounds or separately by reacting the appropriate compound in the form of the free base with a suitable acid. Representative acid addition salts include acetate, adipate, alginate, L- ascorbate, aspartate, benzoate, benzenesulfonate (besylate), bisulfate, butyrate, camphorate, camphorsulfonate, citrate, digluconate, formate, fumarate, gentisate, glutarate, glycerophosphate, glycolate, hemisulfate, heptanoate, hexanoate, hippurate, hydrochloride, hydrobromide, hydroiodide, 2- hydroxyethansulfonate (isethionate), lactate, maleate, malonate, DL-mandelate, mesitylenesulfonate, methanesulfonate, naphthylenesulfonate, nicotinate, 2-naphthalenesulfonate, oxalate, pamoate, pectinate, persulfate, 3-phenylproprionate, phosphonate, picrate, pivalate, propionate, pyroglutamate, succinate, sulfonate, tartrate, L-tartrate, trichloroacetate, trifluoroacetate, phosphate, glutamate, bicarbonate, para- toluenesulfonate (p-tosylate), and undecanoate. Also, basic groups in the compounds disclosed herein can be quaternized with methyl, ethyl, propyl, and butyl chlorides, bromides, and iodides; dimethyl, diethyl, dibutyl, and diamyl sulfates; decyl, lauryl, myristyl, and steryl chlorides, bromides, and iodides; and benzyl and phenethyl bromides. Examples of acids which can be employed to form therapeutically acceptable addition salts include inorganic acids such as hydrochloric, hydrobromic, sulfuric, and phosphoric, and organic acids such as oxalic, maleic, succinic, and citric. Salts can also be formed by coordination of the compounds with an alkali metal or alkaline earth ion. Hence, the present disclosure contemplates sodium, potassium, magnesium, and calcium salts of the compounds disclosed herein, and the like.

[0101] Basic addition salts can be prepared during the final isolation and purification of the compounds by reacting a carboxy group with a suitable base such as the hydroxide, carbonate, or bicarbonate of a metal cation or with ammonia or an organic primary, secondary, or tertiary amine. The cations of therapeutically acceptable salts include lithium, sodium, potassium, calcium, magnesium, and aluminum, as well as nontoxic quaternary amine cations such as ammonium, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, triethylamine, diethylamine, ethylamine, tributylamine,pyridine, N,N-dimethylaniline, N-methylpiperidine, N-methylmorpholine, dicyclohexylamine, procaine, dibenzylamine, N,N-dibenzylphenethylamine, 1-ephenamine, and N,N’-dibenzylethylenediamine. Other representative organic amines useful for the formation of base addition salts include ethylenediamine, ethanolamine, diethanolamine, piperidine, and piperazine.

[0102] A salt of a compound can be made by reacting the appropriate compound in the form of the free base with the appropriate acid.

[0103] “KRAS positive cancer” refers to a cancer characterized by a KRAS mutation, such as a KRAS Q61H, G12C, G12D, G12R, G12A, G12S, G12V, or G13D mutation, and / or by amplified wild-type KRAS activity. In some embodiments, “KRAS positive cancer” refers to a cancer that may benefit from inhibition of KRAS, such as wild-type KRAS or KRAS having a Q61H, G12C, G12D, G12R, G12A, G12S, G12V, or G13D mutation.

[0104] “KRAS G12C-positive cancer” refers to a cancer characterized by a KRAS G12C mutation.

[0105] “KRAS G12D-positive cancer” refers to a cancer characterized by a KRAS G12D mutation.

[0106] “KRAS G12R-positive cancer” refers to a cancer characterized by a KRAS G12R mutation.

[0107] “KRAS G12V-positive cancer” refers to a cancer characterized by a KRAS G12V mutation.

[0108] “KRAS G12A-positive cancer” refers to a cancer characterized by a KRAS G12A mutation.

[0109] “KRAS G12S-positive cancer” refers to a cancer characterized by a KRAS G12S mutation.

[0110] “KRAS G13D-positive cancer” refers to a cancer characterized by a KRAS G13D mutation.

[0111] “KRAS Q61H-positive cancer” refers to a cancer characterized by a KRAS Q61H mutation.

[0112] “Jointly therapeutically effective amount” as used herein means the amount at which the therapeutic agents, when given separately (in a chronologically staggered manner, especially a sequence-specific manner) to a warm-blooded animal, especially to a human to be treated, show an (additive, but preferably synergistic) interaction (joint therapeutic effect). Whether this is the case can be determined inter alia by following the blood levels, showing that both compounds are present in the blood of the human to be treated at least during certain time intervals.

[0113] “Synergistic effect” as used herein refers to an effect of at least two therapeutic agents: a KRAS inhibitor, as defined herein, and an additional agent, which additional agent may be an agent configured to treat a disease, disorder, or condition or a symptom thereof. The effect can be, for example, slowing the symptomatic progression of a proliferative disease, such as cancer, particularly lung cancer, or symptoms thereof. Analogously, a “synergistically effective amount” refers to the amount needed to obtain a synergistic effect.

[0114] “A,” “an,” or “a(n)”, when used in reference to a group of substituents or “substituent group” herein, mean at least one. For example, where a compound is substituted with “an” alkyl or aryl, the compound is unsubstituted or substituted with at least one alkyl and / or at least one aryl, wherein each alkyl and / or aryl is optionally different. In another example, where a compound is substituted with “a” substituent group, the compound is substituted with at least one substituent group, wherein each substituent group is optionally different.

[0115] In some embodiments, a “floating” substituent drawn on a ring indicates that a substituent may exist at any position of the ring. For example, for a ring such assubstituent may exist at any position and may replace a hydrogen atoms of a CH moiety, a hydrogen atom of an NH moiety, and / or one or both hydrogen atoms of a CH2moiety. In some embodiment, a “floating” substituent drawn on one ring of a bicyclic moiety, indicates that a substituent may exist on any ring of the bicyclic moiety (e.g.,ubstituent may exist at any position of any ring of the bicyclic moiety, and may replace one or more hydrogen atoms attached to an atom in one or more of the rings of the bicyclic moiety. For example, for a bicyclic moiety such a, may exist in either ring, and may replace a hydrogen atom of a CH moiety, a hydrogen atom of an NH moiety, and / or one or both hydrogen atoms of a CH2moiety. Compounds

[0116] In an aspect, the present disclosure provides a compound represented by Formula A:or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein:R1is selected from Hmembered heterocycle that is unsubstituted or substituted with one or more R31; Rmis selected from H and -NR2R3; R2is selected from C1-6alkyl; R3is selected from a 4-10 membered heterocycle or -(C1-6alkylenyl)(5-6 membered heteroaryl), wherein any heterocycle or heteroaryl is unsubstituted or substituted with one or more R10; R4is H; R5is selected from C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R6is a bicyclic heteroaryl that is substituted with one or more R15; R7is selected from halogen; R8is selected from a heterocycle and an alkylheterocycle, wherein any heterocycle comprises 4-8 ring atoms and is unsubstituted or is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-6alkyl; each R10is independently selected from deuterium, =O, -C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), - C(O)N(R14)2, -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), halogen, a 5-6 membered heteroaryl, a 3-6 membered carbocycle, a 3-6 membered heterocycle, and C1-6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20; each R12is independently selected from C1-6alkyl, C2-6alkenyl, and H, wherein any C1-6alkyl or C2-6alkenyl is unsubstituted or substituted with one or more R13; each R13is independently halogen; each R14is independently selected from C1-6alkyl, wherein any C1-6alkyl is optionally deuterated; each R15is independently selected from halogen, -N(R12)2, and -CN; each R20is independently selected from =O, -CN, and halogen; R30is selected from -N(R12)2 and a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted or substituted with one or more R28; each R28is independently selected from halogen;each R29is independently selected from halogen and C1-6alkyl; each R31is selected from C1-6alkyl; n is 0-2; and Raand Rbare each independently selected from deuterium, halogen, C1-6alkyl, C2-4alkenyl, and - OR12, wherein an Raand Rboptionally join together to form a 3-6 membered carbocycle or heterocycle, and wherein any C1-6alkyl, C2-6alkenyl, or 3-6 membered carbocycle or heterocycle is unsubstituted or is substituted with one or more R13.

[0117] In some embodiments, the present disclosure provides a compound of Formula A, or a salt (e.g., a pharmaceutically acceptable salt) thereof.

[0118] In one aspect, the present disclosure provides a compound represented by Formula A’:or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein: R1 is selected from Hmembered heterocyclethat is unsubstituted or substituted with one or more R31; Rmis selected from H and -NR2R3; R2is selected from C1-6alkyl which is optionally deuterated; R3is selected from a C1-6alkyl, 3- to 6-membered cycloalkyl optionally fused to a 5- or 6- membered heterocycle or heteroaryl, 4-10 membered heterocycle or -(C1-6alkylenyl)(5-6 membered heteroaryl), wherein any heterocycle or heteroaryl is unsubstituted or substituted with one or more R10; or R2and R3, together with the atom they attach to, form a 4- to 10-membered heterocycle optionally substituted with one or more R10; R4is H; R5is selected from C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R6is a bicyclic heteroaryl that is substituted with one or more R15; R7is selected from halogen;R8is selected from a heterocycle and an alkylheterocycle, wherein any heterocycle comprises 4-8 ring atoms and is unsubstituted or is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-6alkyl; each R10is independently selected from deuterium, =O, -C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), - C(O)N(R14)2, -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), halogen, a 5-6 membered heteroaryl, a 3-6 membered carbocycle, a 3-6 membered heterocycle, and C1-6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20; each R12is independently selected from C1-6alkyl, C2-6alkenyl, and H, wherein any C1-6alkyl or C2-6alkenyl is unsubstituted or substituted with one or more R13; each R13is independently halogen; each R14is independently selected from C1-6alkyl, wherein any C1-6alkyl is optionally deuterated; each R15is independently selected from halogen, -N(R12)2, and -CN; each R20is independently selected from =O, -CN, -OR12, and halogen; R30is selected from -N(R12)2and a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted or substituted with one or more R28; each R28is independently selected from halogen,-OR12, C1-6alkyl, and C1-6heteroalkyl, wherein two heteroalkyl groups can optionally join together to form a 3-6 membered heterocycle that is unsubstituted or substituted with one or more R13; each R29is independently selected from halogen and C1-6alkyl; each R31is selected from C1-6alkyl; n is 0-2; and Raand Rbare each independently selected from deuterium, halogen, C1-6alkyl, C2-4 alkenyl,, OR12, a 4- to 10-membered heterocycle, and aryl, wherein any 4- to 10- membered heterocycle or aryl is optionally substituted with one or more R28, wherein an Raand Rboptionally join together to form a 3-6 membered carbocycle or heterocycle, and wherein any C1-6alkyl, C2-6alkenyl, or 3-6 membered carbocycle or heterocycle is unsubstituted or is substituted with one or more R13.

[0119] In some embodiments, the present disclosure provides a compound of Formula A, or a salt (e.g., a pharmaceutically acceptable salt) thereof.

[0120] In some embodiments, the present disclosure provides a compound of Formula A’, wherein the compound is of Formula A’-a:or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein R2and R3are as defined for Formula A’ above and described in classes and subclasses herein, both singly and in combination. In some embodiments, the present disclosure provides a compound of Formula A’-a, or a salt (e.g., pharmaceutically acceptable salt) thereof.

[0121] In some embodiments, the present disclosure provides a compound of Formula B:or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein: R1is selected from Hmembered heterocycle that is unsubstituted or substituted with one or more R31; R2is selected from C1-6alkyl; R3is selected from a 4-10 membered heterocycle or -(C1-6alkylenyl)(5-6 membered heteroaryl), wherein any heterocycle or heteroaryl is unsubstituted or substituted with one or more R10; R4is H; R5is selected from C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R6is a bicyclic heteroaryl, wherein the heteroaryl is substituted with one or more R15; R7is selected from halogen;R8is selected from a heterocycle and an alkylheterocycle, wherein any heterocycle comprises 4-8 ring atoms and is unsubstituted or is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-6alkyl; each R10is independently selected from deuterium, =O, -C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), - C(O)N(R14)2, -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), halogen, a 5-6 membered heteroaryl, a 3-6 membered carbocycle, a 3-6 membered heterocycle, and C1-6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20; each R12is independently selected from C1-6alkyl, C2-6alkenyl, and H, wherein any C1-6alkyl or C2-6alkenyl is unsubstituted or substituted with one or more R13; each R13is independently halogen; each R14is independently selected from C1-6alkyl, wherein any C1-6alkyl is optionally deuterated; each R15is independently selected from halogen, -N(R12)2, and -CN; each R20is independently selected from =O, -CN, and halogen; R30is selected from -N(R12)2and a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted or substituted with one or more R28; each R28is independently selected from halogen; each R29is independently selected from halogen and C1-6alkyl; each R31is selected from C1-6alkyl; n is 0-2; and Raand Rbare each independently selected from halogen, C1-6alkyl, C2-4 alkenyl, and -OR12, wherein any C1-6alkyl or C2-4 alkenyl is unsubstituted or is substituted with one or more R13.

[0122] In some embodiments, the present disclosure provides a compound of Formula B, or a salt (e.g., a pharmaceutically acceptable salt) thereof.

[0123] In some embodiments, the present disclosure provides a compound of Formula B, wherein the compound is of Formula B-a:or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein R2and R3are as defined for Formula B above and described in classes and subclasses herein, both singly and in combination. In some embodiments, the present disclosure provides a compound of Formula B-a, or a salt (e.g., pharmaceutically acceptable salt) thereof.

[0124] In some embodiments for a compound according to Formula A or A’, Rmis H.

[0125] In some embodiments for a compound according to Formula A or A’, Rmis -NR2R3.

[0126] In some embodiments for a compound according to Formula A, A’, A’-a, B, or B-a, R3is a 4-10 membered heterocycle that includes 1-2 heteroatoms independently selected from O, S, and N, which heterocycle is unsubstituted or substituted with one or more R10. In some embodiments, R3is a 4-10 membered heterocycle that includes 1-2 heteroatoms independently selected from O, S, and N, which heterocycle is unsubstituted or substituted with one or more R10, provided that (i) when the heterocycle contains a nitrogen atom, the nitrogen atom is substituted with R10or (ii) the heterocycle does not include an -NH- moiety. In some embodiments, R3is a 4-10 membered heterocycle that includes 1-2 heteroatoms independently selected from O, S, and N, which heterocycle is unsubstituted. In some embodiments, R3is a 4-10 membered heterocycle that includes 1-2 heteroatoms independently selected from O, S, and N, which heterocycle is substituted with one or more R10.

[0127] In some embodiments for a compound according to Formula A, A’, A’-a, B, or B-a, R3is a 4-7 membered heterocycle that includes 1-2 heteroatoms independently selected from O, S, and N, which heterocycle is unsubstituted or substituted with one or more R10. In some embodiments, R3is a 4-7 membered heterocycle that includes 1-2 heteroatoms independently selected from O, S, and N, which heterocycle is unsubstituted. In some embodiments, R3is a 4-7 membered heterocycle that includes 1-2 heteroatoms independently selected from O, S, and N, which heterocycle is substituted with one or more R10. In some embodiments, R3is a 4-7 membered heterocycle that includes 1 heteroatom selected from O, S, and N, which heterocycle is unsubstituted or substituted with one or more R10. In some embodiments, R3is a 4-7 membered heterocycle that includes 1 heteroatom selected from O, S, and N, which heterocycle is unsubstituted. In some embodiments, R3is a 4-7 membered heterocycle that includes 1 heteroatomselected from O, S, and N, which heterocycle is substituted with one or more R10. In some embodiments, R3is a 4-7 membered heterocycle that includes 1 heteroatom selected from O, S, and N, which heterocycle is substituted with 1-4 R10. In some embodiments, R3is a 4-7 membered heterocycle that includes 1 heteroatom selected from O, S, and N, which heterocycle is substituted with 1-4 R10, provided that (i) when the heterocycle contains a nitrogen atom, the nitrogen atom is substituted with R10or (ii) the heterocycle does not include an -NH- moiety. In some embodiments, R3is a 4-7 membered heterocycle that includes 1 heteroatom selected from O, S, and N, which heterocycle is substituted with 1-4 R10, provided that when the heterocycle contains a nitrogen atom, the nitrogen atom is substituted with R10. In some embodiments, R3is a pyrrolidine that is substituted with 0-4 R10. In some embodiments, R3is a pyrrolidine that is substituted with 1-4 R10, provided that the nitrogen atom is substituted with R10. In some embodiments, R3is a 4-6 membered heterocycle that is substituted with one or more R10, provided that when the heterocycle contains a nitrogen atom, the nitrogen atom is substituted with R10, and each R10is independently selected from -C(O)(C1-6alkyl), -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), -C(O)O(C1- 6alkyl), -C(O)N(R14)2, a 5-6 membered heteroaryl, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R20, and any 3-6 membered carbocycle is unsubstituted or substituted with one or more R12or R20.

[0128] In some embodiments for a compound according to Formula A, A’, A’-a, B, or B-a, R3is an 8-10 membered heterocycle that includes 1-2 heteroatoms independently selected from O, S, and N, wherein the heterocycle is unsubstituted or substituted with one or more R10. In some embodiments, R3is an 8-10 membered heterocycle that includes 1-2 heteroatoms independently selected from O, S, and N, wherein the heterocycle is unsubstituted or substituted with one or more R10, provided that (i) when the heterocycle contains a nitrogen atom, the nitrogen atom is substituted with R10or (ii) the heterocycle does not include an -NH- moiety. In some embodiments, R3is an 8-10 membered heterocycle that includes 1-2 heteroatoms independently selected from O, S, and N, wherein the heterocycle is substituted with 1-4 R10. In some embodiments, R3is an 8-membered heterocycle that includes 1-2 heteroatoms independently selected from O, S, and N, wherein the heterocycle is substituted with 1-4 R10. In some embodiments, R3is a 9-membered heterocycle that includes 1-2 heteroatoms independently selected from O, S, and N, wherein the heterocycle is substituted with 1-4 R10. In some embodiments, R3is a 10-membered heterocycle that includes 1-2 heteroatoms independently selected from O, S, and N, wherein the heterocycle is substituted with 1-4 R10.

[0129] In some embodiments for a compound according to Formula A, A’, A’-a, B, or B-a, R3is selected from a 4-10 membered heterocycle that is substituted with one or more R10. In some embodiments, at least one R10is selected from =O, C1-6alkyl, a 3-6 membered carbocycle, and halogen. In some embodiments, atleast one R10is =O. In some embodiments, at least one R10is a 3-6 membered carbocycle. In some embodiments, R10is selected from halogen and C1-6alkyl, wherein the C1-6alkyl is unsubstituted or substituted with one or more R20. In some embodiments, at least one R10is C1-6alkyl. In some embodiments, at least one R10is a halogen. In some embodiments, at least one R10is selected from -C(O)(C1-6alkyl), - C(O)O(C1-6alkyl), -C(O)N(R14)2, -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), a 5-6 membered heteroaryl, and a 3-6 membered heterocycle, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, and wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20. In some embodiments, at least one R10is -C(O)(C1-6alkyl). In some embodiments, at least one R10is -C(O)O(C1-6alkyl). In some embodiments, at least one R10is -C(O)N(R14)2. In some embodiments, at least one R10is -C(O)(3-6 membered carbocycle). In some embodiments, at least one R10is -C(O)(3-8 membered heterocycle). In some embodiments, at least one R10is a 5-6 membered heteroaryl. In some embodiments, at least one R10is a 3-6 membered heterocycle.

[0130] In some embodiments for a compound according to Formula A, A’, A’-a, B, or B-a, R3is -(C1-6alkylenyl)(5-6 membered heteroaryl), wherein the heteroaryl is unsubstituted or substituted with one or more R10. In some embodiments, R3is -CH2(5-6 membered heteroaryl), wherein the heteroaryl is unsubstituted or substituted with one or more R10. In some embodiments, the heteroaryl is pyrazole, oxazole, isoxazole, thiazole, isothiazole, or pyridine.

[0131] In some embodiments for a compound according to Formula A, B, or B-a, R3is selected from:, , , , , ,,, , , , , ,, , , , , ,,any of which is optionally further substituted with one or more R10.

[0132] In some embodiments for a compound according to Formula A’ or A’-a, R3is selected from: -CH3,, , , , , ,

[0133] In some embodiments according to Formula A, R3is selected from:one or more R10.

[0134] In some embodiments according to Formula A’, R3is selected from:,optionally further substituted with one or more R10.

[0135] In some embodiments according to Formula B, R3is selected from:,,optionally further substituted with one or more R10.

[0136] In some embodiments for a compound according to Formula A, A’, or B, R3is selected from R

[0137] In some embodiments according to Formula A’ or A’-a, Rmis selected from:,o

[0138] In some embodiments for a compound according to any one of Formulas A, A’, A’-a, B, and B-a, (i) when R3includes a heterocycle or heteroaryl containing a nitrogen atom, the nitrogen atom is substituted with R10or (ii) the heterocycle or heteroaryl does not comprise an –NH- moiety.

[0139] In some embodiments for a compound according to Formula A, A’, A’-a, B, or B-a, the compound is a compound according to Formula BA, BB, BC, BD, BE, BF, BG, BH, BI, BJ, BK, BL, or BM:or a salt (e.g., pharmaceutically acceptable salt) thereof, wherein: R32, if present, is selected from H and C1-5alkyl;each Rdis independently selected from H, deuterium, =O, halogen, and C1-6alkyl, wherein any C1- 6alkyl is unsubstituted or substituted with one or more R20; and Re, if present, is selected from H, -C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), -C(O)N(R14)2, -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), a 5-6 membered heteroaryl, a 3-6 membered carbocycle, a 3-6 membered heterocycle, and C1-6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, and wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20.

[0140] In some embodiments, the compound is a compound according to Formula BA, or a salt (e.g., pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula BB, or a salt (e.g., pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula BC, or a salt (e.g., pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula BD, or a salt (e.g., pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula BE, or a salt (e.g., pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula BF, or a salt (e.g., pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula BG, or a salt (e.g., pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula BH, or a salt (e.g., pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula BI, or a salt (e.g., pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula BJ, or a salt (e.g., pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula BK, or a salt (e.g., pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula BL, or a salt (e.g., pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula BM, or a salt (e.g., pharmaceutically acceptable salt) thereof.

[0141] In some embodiments, for a compound according to any one of Formulas A, A’, B, BA, BB, BC, BD, BE, BF, BG, BH, BI, BJ, BK, BL, or BM, R6is selected from:wherein X is selected from N and C-CN; Y is selected from O, S, and Se; R23is selected from -N(R12)2, C1-6alkyl, and C1-6alkyl-N(R14)2, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; and R24, R25, and R26are independently selected from H, deuterium, halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13. In some embodiments, X is C-CN and Y is S. In some embodiments, X is C-CN and Y is O. In some embodiments, X is C-CN and Y is Se. In some embodiments, X is N and Y is S. In some embodiments, X is N and Y is O. In some embodiments, X is N and Y is Se. In some embodiments, X is C-CN, Y is S, and R23is -N(R12)2. In some embodiments, X is C- CN, Y is S, and R23is -NH2. In some embodiments, R24is halogen (e.g., fluoro). In some embodiments, R26is deuterium.

[0142] In some embodiments, for a compound according to any one of Formulas A, A’, B, BA, BB, BC, BD, BE, BF, BG, BH, BI, BJ, BK, BL, or BM, R6is selected from:any of which is substituted with one or more R15.

[0143] In some embodiments, for a compound according to any one of Formulas A, A’, B, BA, BB, BC, BD, BE, BF, BG, BH, BI, BJ, BK, BL, or BM, R6is selected from:, , , ,

[0144] In some embodiments, for a compound according to Formula A’ , R6is selected from:

[0145] In some embodiments, for a compound according to any one of Formulas A, A’, B, BA, BB, BC, BD, BE, BF, BG, BH, BI, BJ, BK, BL, or BM, R6is selected from:.

[0146] In some embodiments, for a compound according to any one of Formulas A, A’, B, BA, BB, BC, BD, BE, BF, BG, BH, BI, BJ, BK, BL, or BM, R6is selected from:, which is substitutedwith one or more R15. In some embodiments, R6is selected from:, , . In some embodiments, R6is

[0147] In some embodiments, the compound is a compound according to Formula BA1, BB1, BC1, BD1, BE1, BF1, BG1, BH1, BI1, BJ1, BK1, BL1, or BM1:or a salt (e.g., pharmaceutically acceptable salt) thereof, wherein: R32, if present, is selected from H and C1-5alkyl; each Rdis independently selected from H, deuterium, =O, halogen, and C1-6alkyl, wherein any C1- 6alkyl is unsubstituted or substituted with one or more R20; Re, if present, is selected from -C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), -C(O)N(R14)2, -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), a 5-6 membered heteroaryl, a 3-6 membered carbocycle, a 3-6 membered heterocycle, and C1-6alkyl, wherein any C1- 6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, and wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20; X is C-CN; Y is S; R23is selected from -N(R12)2; and R24, R25, and R26are independently selected from H and halogen.

[0148] In some embodiments, the compound is a compound according to Formula BA1, or a salt (e.g., pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula BB1, or a salt (e.g., pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula BC1, or a salt (e.g., pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula BD, or a salt (e.g., pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula BE11, or a salt (e.g., pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula BF1, or a salt (e.g., pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula BG1, or a salt (e.g., pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula BH1, or a salt (e.g., pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula BI1, or a salt (e.g., pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula BJ1, or a salt (e.g., pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula BK1, or a salt (e.g., pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula BL1, or a salt (e.g., pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula BM1, or a salt (e.g., pharmaceutically acceptable salt) thereof.

[0149] In some embodiments for a compound according to any one of Formulas BA, BB, BC, BD, BE, BF, BG, BH, BI, BJ, BK, BL, BM, BA1, BB1, BC1, BD1, BE1, BF1, BG1, BH1, BI1, BJ1, BK1, BL1, or BM1, one or more of R24, R25, and R26is a halogen (e.g., F).

[0150] In some embodiments for a compound according to any one of Formulas BA, BB, BC, BD, BE, BF, BG, BH, BI, BJ, BK, BL, BM, BA1, BB1, BC1, BD1, BE1, BF1, BG1, BH1, BI1, BJ1, BK1, BL1, or BM1, Reis -C(O)(3-6 membered carbocycle). In some embodiments, Reis selected from -C(O)(C1-6alkyl), -C(O)N(R14)2, -C(O)(3-6 membered carbocycle), and -C(O)O(C1-6alkyl), a 5-6 membered heteroaryl, a 3-6 membered carbocycle, a 3-6 membered heterocycle, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R20, and any 3-6 membered carbocycle is unsubstituted or substituted with one or more R12or R20.

[0151] In some embodiments for a compound according to any one of Formulas BA, BB, BC, BD, BE, BF, BG, BH, BI, BJ, BK, BL, BM, BA1, BB1, BC1, BD1, BE1, BF1, BG1, BH1, BI1, BJ1, BK1, BL1, or BM1, each Rdis H.

[0152] In some embodiments for a compound according to any one of Formulas A, A’, A’-a, B, B-a, BA, BB, BC, BD, BE, BF, BG, BH, BI, BJ, BK, BL, BM, BA1, BB1, BC1, BD1, BE1, BF1, BG1, BH1, BI1, BJ1, BK1, BL1, or BM1, R2is H. In some embodiments, R2is selected from C1-2alkyl. In some embodiments, R2is methyl. In some embodiments, R2is ethyl.

[0153] In some embodiments, for a compound according to any one of Formulas A, A’, B, BA, BB, BC, BD, BE, BF, BG, BH, BI, BJ, BK, BL, BM, BA1, BB1, BC1, BD1, BE1, BF1, BG1, BH1, BI1, BJ1, BK1, BL1, or BM1, R1is selected from -OR8. In some embodiments, R8is a heterocycle or an alkylheterocycle, wherein any heterocycle contains 4-8 ring atoms and is substituted with one or more Raor Rb. In some embodiments, R8is a heterocycle that is unsubstituted or substituted with one or more Raor Rb. In some embodiments, R8is an alkylheterocycle that is unsubstituted or substituted with one or more Raor Rb. In some embodiments, R8is –CH2(heterocycle), where the heterocycle is unsubstituted or substituted with one or more Raor Rb. In some embodiments, a heterocycle or a heterocycle of an alkylheterocycle is a 4-6 membered monocyclic heterocycle having 1-2 heteroatoms independently selected from N, O, and S. In some embodiments, a heterocycle or a heterocycle of an alkylheterocycle is an 8-membered bicyclic heterocycle having 1-2 heteroatoms independently selected from N, O, and S. In some embodiments, a heterocycle or a heterocycle of an alkylheterocycle is substituted with one or more Raor Rb, wherein the one or more Raor Rbis a halogen (e.g., F). In some embodiments, a heterocycle or a heterocycle of an alkylheterocycle is substituted with one or more Raor Rb, wherein the one or more Raor Rbis a C1-6alkyl (e.g., methyl). In some embodiments, a heterocycle or a heterocycle of an alkylheterocycle is substituted with one or more Raor Rb, wherein the one or more Raor Rbis a -OR12(e.g., -OCH3). In some embodiments, a heterocycle or a heterocycle of an alkylheterocycle is substituted with one or more Raor Rb, wherein the one or more Raor Rbis a 3-6 membered carbocycle (e.g., a cyclopropane). In some embodiments, a heterocycle or a heterocycle of an alkylheterocycle is substituted with one or more Raor Rb, wherein the one or more Raor Rbis deuterium.

[0154] In some embodiments, for a compound according to any one of Formulas A, A’, B, BA, BB, BC, BD, BE, BF, BG, BH, BI, BJ, BK, BL, BM, BA1, BB1, BC1, BD1, BE1, BF1, BG1, BH1, BI1, BJ1, BK1, BL1, or BM1, R1is selected from:,wherein Ra1, Ra2, Rb1, and Rb2are each independently selected from deuterium, halogen, -OR12, and H, wherein Ra1and Rb1can optionally join together to form a exocyclic double bond that is unsubstituted or is substituted by halogen. In some embodiments, Ra1and Rb1are each independently selected from halogen, C1-6alkyl, -OR12, and H, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13. In some embodiments, Ra1is a halogen. In some embodiments, Ra1is F. In some embodiments, Ra1is C1-6alkyl that is unsubstituted or is substituted with one or more R13. In some embodiments, Ra1is methyl. In some embodiments, Ra1is -OC1-6alkyl. In some embodiments, Ra1is H. In some embodiments, Rb1is H. In some embodiments, Rb1is a halogen. In some embodiments, Rb1is F. In some embodiments, Rb1is C1- 6alkyl that is unsubstituted or is substituted with one or more R13. In some embodiments, Rb1is methyl. In some embodiments, each of Ra1and Rb1is F. In some embodiments, each of Ra1and Rb1is methyl. In some embodiments, each of Ra1and Rb1is H. In some embodiments, R1is selected from:, wherein Raand Rbare each independently selected from halogen, -OR12, C2-4 alkenyl, and H, wherein any C2-4 alkenyl is unsubstituted or is substituted by halogen. In some embodiments, Rais a halogen. In some embodiments, Rais F. In some embodiments, Rais C2-4alkenyl that is unsubstituted or is substituted with halogen. In some embodiments, Rais -OC1-6alkyl. In some embodiments, Rbis H. In some embodiments, Rbis a halogen. In some embodiments, Rbis F. In some embodiments, Rbis C2-4alkenyl that is unsubstituted or is substituted with halogen. In some embodiments, Rbis methyl. In some embodiments, R1is selected from:

[0155] In some embodiments, for a compound according to any one of Formulas A, A’, B, BA, BB, BC, BD, BE, BF, BG, BH, BI, BJ, BK, BL, BM, BA1, BB1, BC1, BD1, BE1, BF1, BG1, BH1, BI1, BJ1, BK1, BL1, or BM1, R1is selected from:wherein Ra1, Ra2, Rb1, Rb2, Ra3, and Rb3are each independently selected from deuterium, halogen, -OR12, a 4- to 10-membered heterocycle, and a 4- to 10-membered aryl, wherein any 4- to 10-membered heterocycle or 4- to 10-membered aryl is optionally substituted with one or more R28, and H, wherein Ra1and Rb1can optionally join together to form a exocyclic double bond that is unsubstituted or is substituted by halogen. In some embodiments, Ra1and Rb1are each independently selected from halogen, C1-6alkyl, -OR12, and H, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13. In some embodiments, Ra1is a halogen. In some embodiments, Ra1is F. In some embodiments, Ra1is C1-6alkyl that is unsubstituted or is substituted with one or more R13. In some embodiments, Ra1is methyl. In some embodiments, Ra1is - OC1-6alkyl. In some embodiments, Ra1is H. In some embodiments, Rb1is H. In some embodiments, Rb1is a halogen. In some embodiments, Rb1is F. In some embodiments, Rb1is C1-6alkyl that is unsubstituted or is substituted with one or more R13. In some embodiments, Rb1is methyl. In some embodiments, each of Ra1and Rb1is F. In some embodiments, each of Ra1and Rb1is methyl. In some embodiments, each of Ra1and Rb1is H. In some embodiments, R1is selected from:wherein Raand Rbare each independently selected from halogen, -OR12, C2-4 alkenyl, and H, wherein any C2-4 alkenyl is unsubstituted or is substituted by halogen. In some embodiments, Rais a halogen. In some embodiments, Rais F. In some embodiments, Rais C2-4alkenyl that is unsubstituted or is substituted with halogen. In some embodiments, Rais -OC1-6alkyl. In some embodiments, Rbis H. In some embodiments, Rbis a halogen. In some embodiments, Rbis F. In some embodiments, Rbis C2-4alkenyl that is unsubstituted or is substituted with halogen. In some embodiments, Rbis methyl.

[0156] In some embodiments, R1is selected from:

[0157] In some embodiments, for a compound according to any one of Formulas A, A’, B, BA, BB, BC, BD, BE, BF, BG, BH, BI, BJ, BK, BL, BM, BA1, BB1, BC1, BD1, BE1, BF1, BG1, BH1, BI1, BJ1, BK1, BL1, or BM1, R1is selected from:, wherein each Raand Rbis independently selected from halogen, -OR12, C2-4 alkenyl, and H; and each Rcis independently selected from H and C1-6alkyl, wherein any C2-4alkenyl is unsubstituted or is substituted by halogen. In some embodiments, each Rcis independently selected from C1-6alkyl that is unsubstituted. In some embodiments, each Rcis independently selected from C1-6alkyl that is substituted with halogen. In some embodiments, each Rcis independently selected from C1-2 alkyl that is unsubstituted. In some embodiments, the Rcthat is not linked to a nitrogen atom is H. In some embodiments, each Raand Rbis H. In some embodiments, one Raor Rbis selected from halogen, -OR12, and C2-4 alkenyl, wherein any C2-4 alkenyl is unsubstituted or is substituted by halogen, and the other Raand Rbgroups are H. In some embodiments, one Raor Rbis halogen (e.g., F). In some embodiments, one Raor Rbis -OR12(e.g., -OCH3). In some embodiments, one Raor Rbis C1-6alkyl (e.g., methyl). In some embodiments, one Rais selected from C2-4 alkenyl that is unsubstituted or is substituted by halogen and the other Raand Rbgroups are H, provided that the Rbconnected to the same atom as the Rathat is substituted or unsubstituted C2-4alkenyl is absent. In some embodiments, one Rais selected from C2-4 alkenyl that is unsubstituted and the other Raand Rbgroups are H, provided that the Rbconnected to the same atom as the Rathat is C2-4alkenyl is absent.In some embodiments, one Rais selected from C2-4 alkenyl that is substituted by halogen and the other Raand Rbgroups are H, provided that the Rbconnected to the same atom as the Rathat is substituted C2-4 alkenyl is absent. In some embodiments, R1is selected from:.

[0158] In some embodiments according to Formula A’, R1is selected from:,

[0159] In some embodiments, for a compound according to any one of Formulas A, A’, B, BA, BB, BC, BD, BE, BF, BG, BH, BI, BJ, BK, BL, BM, BA1, BB1, BC1, BD1, BE1, BF1, BG1, BH1, BI1, BJ1, BK1, BL1, or BM1, R1is In some embodiments, n is 0. In someembodiments, n is 1. In some embodiments, n is 2. In some embodiments, each R29is independently halogen. In some embodiments, each R29is independently C1-6alkyl. In some embodiments, R30is -N(R12)2. In some embodiments, R30is a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted or substituted with one or more R28. In some embodiments, R1is selected from, , , and

[0160] In some embodiments according to Formula A’, R1is selected from ,

[0161] In some embodiments according to Formula A, R1is selected from:

[0162] In some embodiments according to Formula A’, R1is selected from:

[0163] In some embodiments according to Formula B, R1is selected from:

[0164] In some embodiments, for a compound according to any one of Formulas A, A’, A’-a, B, BA, BB, BC, BD, BE, BF, BG, BH, BI, BJ, BK, BL, BM, BA1, BB1, BC1, BD1, BE1, BF1, BG1, BH1, BI1, BJ1, BK1, BL1, or BM1, R5is selected from C1-6alkyl that is unsubstituted. In some embodiments, R5is selected from C1-6alkyl that is substituted with one or more R13. In some embodiments, R5is selected from C1-6alkyl that is substituted with one or more F. In some embodiments, R5is -CF3.

[0165] In some embodiments, for a compound according to any one of Formulas A, A’, A’-a, B, BA, BB, BC, BD, BE, BF, BG, BH, BI, BJ, BK, BL, BM, BA1, BB1, BC1, BD1, BE1, BF1, BG1, BH1, BI1, BJ1, BK1, BL1, or BM1, R7is Cl. In some embodiments, R7is F.

[0166] In another aspect, the present disclosure provides a compound represented by Formula II:or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein: Z is N or C-R5; R1is selected from H, , , heterocycle comprising one or more N atoms, wherein the heterocycle is unsubstituted or substituted with one or more R31; R2is selected from H, C1-6alkyl, and a 3-6 membered carbocycle, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13and is optionally deuterated;R3is selected from 3- to 12-membered cycloalkyl optionally fused to a 5- or 6-membered aryl, heterocycle, or heteroaryl, a 4-10 membered heterocycle, or -(C1-6alkylenyl)(5-6 membered heteroaryl), wherein any cycloalkyl, aryl, heterocycle, or heteroaryl is unsubstituted or substituted with one or more R10; R4is H; R5is selected from halogen, -CN, 5- to 6-membered heteroaryl, -OC1-6alkyl, C1-6alkyl, and H, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R6is a phenyl or a bicyclic heteroaryl, wherein the phenyl or bicyclic heteroaryl is substituted with one or more R15; R7is selected from halogen or H; R8is selected from a heterocycle and an alkylheterocycle, wherein any heterocycle comprises 4-9 ring atoms and is unsubstituted or is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-6alkyl; each R10is independently selected from deuterium, -OR12, =O, =S, -CN, -N=S(=O)Me2, -C(O)(C1- 6alkylene)CN, -C(O)(C1-6alkylene)OH, -C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), - C(O)N(R14)2, -C(O)OR14, -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), -C(O)(5-6 membered heteroaryl), -C(O)O(3-6 membered carbocycle), - C(O)O(3-6 membered heterocycle), -C(O)O(5-6 membered heteroaryl),-C(O)O(C1- 6alkylene)(3-6 membered heterocycle), -S(O)2(C1-6alkyl), -C(S)(C1-6alkyl), -C(S)O(C1- 6alkyl), -C(S)N(C1-6alkyl)2, -C(=N-OR12)(C1-6 alkyl), -C(O)N(R12)OR12,^ halogen, a 5-6membered heteroaryl, a 3-6 membered carbocycle, a 3-6 membered heterocycle, and C1- 6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20, and wherein two R10s optionally join together to form, together with the atom(s) to which they are attached, a 3-6 membered carbocycle or heterocycle; each R12is independently selected from C1-6alkyl, C2-6 alkenyl, and H, wherein any C1-6alkyl or C2- 6 alkenyl is unsubstituted or substituted with one or more R13; each R13is independently selected from -OR14, -CN, -N(R14)2, and halogen; each R14is independently selected from a 3-6 membered carbocycle, a 3-6 membered heterocycle, C1-6alkyl, -OR12, C2-6 alkenyl, and H, wherein any C1-6alkyl is optionally deuterated;each R15is independently selected from deuterium, halogen, -N(R12)2, -CN, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; each R20is independently selected from -OH, -OC1-6alkyl, -OC1-6haloalkyl, =O, -CN, -NH2, -NHC1- 6alkyl, -C(O)(C1-6alkyl), -C(O)OR12, -C(O)N(R12)2, -S(O)2R12, a 3-6 membered carbocycle, phenyl, and halogen; each R28is independently selected from C1-6alkyl, -OR12, C1-6heteroalkyl, wherein two heteroalkyl groups can optionally join together to form a 3-6 membered heterocycle that is unsubstituted or substituted with one or more R13and halogen; each R29is independently selected from halogen and C1-6alkyl; R30is N(R12)2 or a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted or substituted with one or more R28; each R31is selected from C1-6alkyl; n is 0-2; and Raand Rbare each independently selected from deuterium, halogen, C1-6alkyl, alCk2e-6nyl,,-C1-6heteroalkyl, a 3-6 membered carbocycle, -OR12, and H, wherein an Raand Rboptionally join together to form a 3-6 membered carbocycle or heterocycle, and wherein any C1-6alkyl, C2-6alkenyl, or 3-6 membered carbocycle or heterocycle is unsubstituted or is substituted with one or more R13.

[0167] In some embodiments, the present disclosure provides a compound of Formula II, or a salt (e.g., a pharmaceutically acceptable salt) thereof.

[0168] In some embodiments, R3is selected from 3- to 12-membered cycloalkyl optionally fused to a 5- or 6-membered aryl, heterocycle, or heteroaryl, a 5-10 membered heterocycle, or -(C1-6alkylenyl)(5-6 membered heteroaryl), wherein any cycloalkyl, aryl, heterocycle, or heteroaryl is unsubstituted or substituted with one or more R10.

[0169] In some embodiments, the present disclosure provides a compound represented by Formula II, or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein: R1is selected from -OR8; R2is selected from H, C1-6alkyl, and a 3-6 membered carbocycle, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13and is optionally deuterated;R3is selected from 3- to 12-membered cycloalkyl that is unsubstituted or substituted with one or more R10; R4is H; R5is selected from halogen, -CN, 5- to 6-membered heteroaryl, -OC1-6alkyl, C1-6alkyl, and H, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R6is a phenyl or a bicyclic heteroaryl, wherein the phenyl or bicyclic heteroaryl is substituted with one or more R15; R7is selected from halogen or H; R8is selected from a heterocycle and an alkylheterocycle, wherein any heterocycle comprises 4-9 ring atoms and is unsubstituted or is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-6alkyl; each R10is independently selected from deuterium, -OR12, =O, =S, -CN, -N=S(=O)Me2, -C(O)(C1- 6alkylene)CN, -C(O)(C1-6alkylene)OH, -C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), - C(O)N(R14)2, -C(O)OR14, -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), -C(O)(5-6 membered heteroaryl), -C(O)O(3-6 membered carbocycle), - C(O)O(3-6 membered heterocycle), -C(O)O(5-6 membered heteroaryl),-C(O)O(C1-6alkylene)(3-6 membered heterocycle), -S(O)2(C1-6alkyl), -C(S)(C1-6alkyl), -C(S)O(C1-6alkyl), -C(S)N(C1-6alkyl)2, -C(=N-OR12)(C1-6 alkyl), -C(O)N(R12)OR12,^ halogen, a 5-6membered heteroaryl, a 3-6 membered carbocycle, a 3-6 membered heterocycle, and C1- 6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20, and wherein two R10s optionally join together to form, together with the atom(s) to which they are attached, a 3-6 membered carbocycle or heterocycle; each R12is independently selected from C1-6alkyl, C2-6 alkenyl, and H, wherein any C1-6alkyl or C2- 6 alkenyl is unsubstituted or substituted with one or more R13; each R13is independently selected from -OR14, -CN, -N(R14)2, and halogen; each R14is independently selected from a 3-6 membered carbocycle, a 3-6 membered heterocycle, C1-6alkyl, -OR12, C2-6 alkenyl, and H, wherein any C1-6alkyl is optionally deuterated; each R15is independently selected from deuterium, halogen, -N(R12)2, -CN, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13;each R20is independently selected from -OH, -OC1-6alkyl, -OC1-6haloalkyl, =O, -CN, -NH2, -NHC1- 6alkyl, -C(O)(C1-6alkyl), -C(O)OR12, -C(O)N(R12)2, -S(O)2R12, a 3-6 membered carbocycle, phenyl, and halogen; each R28is independently selected from C1-6alkyl, -OR12, C1-6heteroalkyl, wherein two heteroalkyl groups can optionally join together to form a 3-6 membered heterocycle that is unsubstituted or substituted with one or more R13and halogen; each R29is independently selected from halogen and C1-6alkyl; R30is N(R12)2 or a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted or substituted with one or more R28; each R31is selected from C1-6alkyl; n is 0-2; and Raand Rbare each independently selected from deuterium, halogen, C1-6alkyl,C2-6alkenyl,,-C1-6heteroalkyl, a 3-6 membered carbocycle, -OR12, and H, wherein an Raand Rboptionally join together to form a 3-6 membered carbocycle or heterocycle, and wherein any C1-6alkyl,C2-6alkenyl, or 3-6 membered carbocycle or heterocycle is unsubstituted or is substituted with one or more R13.

[0170] In some embodiments, the present disclosure provides a compound represented by Formula II, or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein: R1is selected from -OR8; R2is selected from H, C1-6alkyl, and a 3-6 membered carbocycle, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13and is optionally deuterated; R3is selected from 3- to 12-membered cycloalkyl that is unsubstituted or substituted with one or more R10; R4is H; R5is selected from C1-6alkyl that is unsubstituted or substituted with one or more R13; R6is a bicyclic heteroaryl, wherein the phenyl or bicyclic heteroaryl is substituted with one or more R15; R7is selected from halogen;R8is selected from a heterocycle and an alkylheterocycle, wherein any heterocycle comprises 4-9 ring atoms and is unsubstituted or is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-6alkyl; Each R10is independently selected from deuterium, -OR12, =O, =S, -CN, -N=S(=O)Me2, -C(O)(C1- 6alkylene)CN, -C(O)(C1-6alkylene)OH, -C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), - C(O)N(R14)2, -C(O)OR14, -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), -C(O)(5-6 membered heteroaryl), -C(O)O(3-6 membered carbocycle), - C(O)O(3-6 membered heterocycle), -C(O)O(5-6 membered heteroaryl),-C(O)O(C1- 6alkylene)(3-6 membered heterocycle), -S(O)2(C1-6alkyl), -C(S)(C1-6alkyl), -C(S)O(C1- 6alkyl), -C(S)N(C1-6alkyl)2, -C(=N-OR12)(C1-6 alkyl), -C(O)N(R12)OR12,^ halogen, a 5-6membered heteroaryl, a 3-6 membered carbocycle, a 3-6 membered heterocycle, and C1-6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20, and wherein two R10s optionally join together to form, together with the atom(s) to which they are attached, a 3-6 membered carbocycle or heterocycle; each R12is independently selected from C1-6alkyl, C2-6alkenyl, and H, wherein any C1-6alkyl or C2-6 alkenyl is unsubstituted or substituted with one or more R13; each R13is independently selected from -OR14, -CN, -N(R14)2, and halogen; each R14is independently selected from a 3-6 membered carbocycle, a 3-6 membered heterocycle, C1-6alkyl, -OR12, C2-6 alkenyl, and H, wherein any C1-6alkyl is optionally deuterated; each R15is independently selected from deuterium, halogen, -N(R12)2, -CN, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; each R20is independently selected from -OH, -OC1-6alkyl, -OC1-6haloalkyl, =O, -CN, -NH2, -NHC1- 6alkyl, -C(O)(C1-6alkyl), -C(O)OR12, -C(O)N(R12)2, -S(O)2R12, a 3-6 membered carbocycle, phenyl, and halogen; each R28is independently selected from C1-6alkyl, -OR12, C1-6heteroalkyl, wherein two heteroalkyl groups can optionally join together to form a 3-6 membered heterocycle that is unsubstituted or substituted with one or more R13and halogen; each R29is independently selected from halogen and C1-6alkyl; R30is N(R12)2 or a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted or substituted with one or more R28;each R31is selected from C1-6alkyl; n is 0-2; and Raand Rbare each independently selected from deuterium, halogen, C1-6alkyl, C2-6alkenyl,,-C1-6heteroalkyl, a 3-6 membered carbocycle, -OR12, and H, wherein an Raand Rboptionally join together to form a 3-6 membered carbocycle or heterocycle, and wherein any C1-6alkyl, C2-6 alkenyl, or 3-6 membered carbocycle or heterocycle is unsubstituted or is substituted with one or more R13.

[0171] In some embodiments, the present disclosure provides a compound represented by Formula II, or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein: R1is selected from -OR8; R2is selected from H, C1-6alkyl, and a 3-6 membered carbocycle, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13and is optionally deuterated; R3is selected from 3- to 12-membered cycloalkyl fused to a 5- or 6-membered aryl, heterocycle, or heteroaryl, a 4-10 membered heterocycle, or -(C1-6alkylenyl)(5-6 membered heteroaryl), wherein any cycloalkyl, aryl, heterocycle, or heteroaryl is unsubstituted or substituted with one or more R10; R4is H; R5is selected from halogen, -CN, 5- to 6-membered heteroaryl, -OC1-6alkyl, C1-6alkyl, and H, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R6is a phenyl or a bicyclic heteroaryl, wherein the phenyl or bicyclic heteroaryl is substituted with one or more R15; R7is selected from halogen or H; R8is selected from a heterocycle and an alkylheterocycle, wherein any heterocycle comprises 4-9 ring atoms and is unsubstituted or is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-6alkyl; each R10is independently selected from deuterium, -OR12, =O, =S, -CN, -N=S(=O)Me2, -C(O)(C1-6alkylene)CN, -C(O)(C1-6alkylene)OH, -C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), - C(O)N(R14)2, -C(O)OR14, -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), -C(O)(5-6 membered heteroaryl), -C(O)O(3-6 membered carbocycle), - C(O)O(3-6 membered heterocycle), -C(O)O(5-6 membered heteroaryl),-C(O)O(C1-6alkylene)(3-6 membered heterocycle), -S(O)2(C1-6alkyl), -C(S)(C1-6alkyl), -C(S)O(C1- 6alkyl), -C(S)N(C1-6alkyl)2, -C(=N-OR12)(C1-6 alkyl), -C(O)N(R12)OR12,^ halogen, a 5-6membered heteroaryl, a 3-6 membered carbocycle, a 3-6 membered heterocycle, and C1- 6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20, and wherein two R10s optionally join together to form, together with the atom(s) to which they are attached, a 3-6 membered carbocycle or heterocycle; each R12is independently selected from C1-6alkyl,C2-6alkenyl, and H, wherein any C1-6alkyl or C2- 6 alkenyl is unsubstituted or substituted with one or more R13; each R13is independently selected from -OR14, -CN, -N(R14)2, and halogen; each R14is independently selected from a 3-6 membered carbocycle, a 3-6 membered heterocycle, C1-6alkyl, -OR12, C2-6alkenyl, and H, wherein any C1-6alkyl is optionally deuterated; each R15is independently selected from deuterium, halogen, -N(R12)2, -CN, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; each R20is independently selected from -OH, -OC1-6alkyl, -OC1-6haloalkyl, =O, -CN, -NH2, -NHC1-6alkyl, -C(O)(C1-6alkyl), -C(O)OR12, -C(O)N(R12)2, -S(O)2R12, a 3-6 membered carbocycle, phenyl, and halogen; each R28is independently selected from C1-6alkyl, -OR12, C1-6heteroalkyl, wherein two heteroalkyl groups can optionally join together to form a 3-6 membered heterocycle that is unsubstituted or substituted with one or more R13and halogen; each R29is independently selected from halogen and C1-6alkyl; R30is N(R12)2or a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted or substituted with one or more R28; each R31is selected from C1-6alkyl; n is 0-2; and Raand Rbare each independently selected from deuterium, halogen, C1-6alkyl, C2-6alkenyl,,-C1-6heteroalkyl, a 3-6 membered carbocycle, -OR12, and H, wherein an Raand Rboptionally join together to form a 3-6 membered carbocycle or heterocycle, and wherein any C1-6alkyl,C2-6alkenyl, or 3-6 membered carbocycle or heterocycle is unsubstituted or is substituted with one or more R13.

[0172] In some embodiments, the present disclosure provides a compound represented by Formula II, or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein: R1is selected from -OR8; R2is selected from H, C1-6alkyl, and a 3-6 membered carbocycle, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13and is optionally deuterated; R3is selected from 3- to 12-membered cycloalkyl fused to a 5- or 6-membered aryl, heterocycle, or heteroaryl, a 4-10 membered heterocycle, or -(C1-6alkylenyl)(5-6 membered heteroaryl), wherein any cycloalkyl, aryl, heterocycle, or heteroaryl is unsubstituted or substituted with one or more R10; R4is H; R5is selected from C1-6alkyl that is unsubstituted or substituted with one or more R13; R6is a bicyclic heteroaryl, wherein the phenyl or bicyclic heteroaryl is substituted with one or more R15; R7is selected from halogen; R8is selected from a heterocycle and an alkylheterocycle, wherein any heterocycle comprises 4-9 ring atoms and is unsubstituted or is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-6alkyl; each R10is independently selected from deuterium, -OR12, =O, =S, -CN, -N=S(=O)Me2, -C(O)(C1- 6alkylene)CN, -C(O)(C1-6alkylene)OH, -C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), - C(O)N(R14)2, -C(O)OR14, -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), -C(O)(5-6 membered heteroaryl), -C(O)O(3-6 membered carbocycle), - C(O)O(3-6 membered heterocycle), -C(O)O(5-6 membered heteroaryl),-C(O)O(C1-6alkylene)(3-6 membered heterocycle), -S(O)2(C1-6alkyl), -C(S)(C1-6alkyl), -C(S)O(C1- 6alkyl), -C(S)N(C1-6alkyl)2, -C(=N-OR12)(C1-6 alkyl), -C(O)N(R12)OR12,^ halogen, a 5-6membered heteroaryl, a 3-6 membered carbocycle, a 3-6 membered heterocycle, and C1- 6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20, and wherein two R10s optionally join together to form, together with the atom(s) to which they are attached, a 3-6 membered carbocycle or heterocycle;each R12is independently selected from C1-6alkyl, C2-6 alkenyl, and H, wherein any C1-6alkyl or C2- 6 alkenyl is unsubstituted or substituted with one or more R13; each R13is independently selected from -OR14, -CN, -N(R14)2, and halogen; each R14is independently selected from a 3-6 membered carbocycle, a 3-6 membered heterocycle, C1-6alkyl, -OR12, C2-6alkenyl, and H, wherein any C1-6alkyl is optionally deuterated; each R15is independently selected from deuterium, halogen, -N(R12)2, -CN, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; each R20is independently selected from -OH, -OC1-6alkyl, -OC1-6haloalkyl, =O, -CN, -NH2, -NHC1- 6alkyl, -C(O)(C1-6alkyl), -C(O)OR12, -C(O)N(R12)2, -S(O)2R12, a 3-6 membered carbocycle, phenyl, and halogen; each R28is independently selected from C1-6alkyl, -OR12, C1-6heteroalkyl, wherein two heteroalkyl groups can optionally join together to form a 3-6 membered heterocycle that is unsubstituted or substituted with one or more R13and halogen; each R29is independently selected from halogen and C1-6alkyl; R30is N(R12)2 or a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted or substituted with one or more R28; each R31is selected from C1-6alkyl; n is 0-2; and Raand Rbare each independently selected from deuterium, halogen, C1-6alkyl, C2-6alkenyl,,-C1-6heteroalkyl, a 3-6 membered carbocycle, -OR12, and H, wherein an Raand Rboptionally join together to form a 3-6 membered carbocycle or heterocycle, and wherein any C1-6alkyl, C2-6 alkenyl, or 3-6 membered carbocycle or heterocycle is unsubstituted or is substituted with one or more R13.

[0173] In another aspect, the present disclosure provides a compound represented by Formula II’:or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein:R1is selected from Heterocycle comprising one or more N atoms, wherein the heterocycle is unsubstituted or substituted with one or more R31; R2is selected from H, C1-6alkyl, and a 3-6 membered carbocycle, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13; R3is selected from a 4-10 membered heterocycle that is unsubstituted or substituted with one or more R10; R4is H; R5is selected from halogen and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R6is a bicyclic heteroaryl that is substituted with one or more R15; R7is selected from halogen; R8is selected from a heterocycle and an alkylheterocycle, wherein any heterocycle comprises 4-8 ring atoms and is unsubstituted or is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-6alkyl; each R10is independently selected from deuterium, -OR12, =O, -C(O)(C1-6alkylene)CN, -C(O)(C1- 6alkylene)OH, -C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), -C(O)N(R14)2, -C(O)OR14, -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), -C(O)(5-6 membered heteroaryl), -C(O)O(3-6 membered carbocycle), -C(O)O(3-6 membered heterocycle), - C(O)O(C1-6alkylene)(3-6 membered heterocycle), -S(O)2(C1-6alkyl), halogen, a 5-6 membered heteroaryl, a 3-6 membered carbocycle, a 3-6 membered heterocycle, and C1-6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20, and wherein two R10s optionally join together to form, together with the atom(s) to which they are attached, a 3-6 membered carbocycle or heterocycle; each R12is independently selected from C1-6alkyl, C2-6alkenyl, and H, wherein any C1-6alkyl or C2-6 alkenyl is unsubstituted or substituted with one or more R13; each R13is independently selected from -OR14, -CN, -N(R14)2, and halogen;each R14is independently selected from a 3-6 membered carbocycle, a 3-6 membered heterocycle, C1-6alkyl, C2-6 alkenyl, and H, wherein any C1-6alkyl is optionally deuterated; each R15is independently selected from deuterium, halogen, -N(R12)2, -CN, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; each R20is independently selected from -OH, -OC1-6alkyl, -OC1-6haloalkyl, =O, -CN, -NH2, -NHC1-6alkyl, -C(O)(C1-6alkyl), a 3-6 membered carbocycle, phenyl, and halogen; R30is N(R12)2 or a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted or substituted with one or more R28; each R28is independently selected from C1-6alkyl and halogen; each R29is independently selected from halogen and C1-6alkyl; each R31is selected from C1-6alkyl; n is 0-2; and Raand Rbare each independently selected from deuterium, halogen, C1-6alkyl, C2-6 alkenyl, a 3-6 membered carbocycle, -OR12, and H, wherein an Raand Rboptionally join together to form a 3-6 membered carbocycle or heterocycle, and wherein any C1-6alkyl, C2-6 alkenyl, or 3-6 membered carbocycle or heterocycle is unsubstituted or is substituted with one or more R13.

[0174] In some embodiments, the present disclosure provides a compound of Formula II’, or a salt (e.g., a pharmaceutically acceptable salt) thereof.

[0175] In some embodiments, for a compound of Formula II’, R3is selected from a 4-10 membered heterocycle that is unsubstituted or substituted with one or more R10, provided that (i) when the heterocycle contains a nitrogen atom, the nitrogen atom is substituted with R10, or (ii) the heterocycle does not comprise an –NH- moiety.

[0176] In some embodiments, the present disclosure provides a compound represented by Formula II’, or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein: R1is selected from -OR8; R2is selected from C1-6alkyl that is unsubstituted or is substituted with one or more R13; R3is selected from a 4-10 membered heterocycle that is unsubstituted or substituted with one or more R10; R4is H; R5is selected from C1-6alkyl that is unsubstituted or substituted with one or more R13;R6is a bicyclic heteroaryl that is substituted with one or more R15; R7is selected from halogen; R8is an alkylheterocycle, wherein the heterocycle comprises 4-8 ring atoms and is unsubstituted or is substituted with one or more Raor Rb, and wherein an alkyl moiety of the alkylheterocycle is selected from C1-6alkyl; each R10is independently selected from deuterium, -OR12, =O, -C(O)(C1-6alkylene)CN, -C(O)(C1- 6alkylene)OH, -C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), -C(O)N(R14)2, -C(O)OR14, -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), -C(O)(5-6 membered heteroaryl), -C(O)O(3-6 membered carbocycle), -C(O)O(3-6 membered heterocycle), - C(O)O(C1-6alkylene)(3-6 membered heterocycle), -S(O)2(C1-6alkyl), halogen, a 5-6 membered heteroaryl, a 3-6 membered carbocycle, a 3-6 membered heterocycle, and C1-6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20, and wherein two R10s optionally join together to form, together with the atom(s) to which they are attached, a 3-6 membered carbocycle or heterocycle; each R12is independently selected from C1-6alkyl, C2-6alkenyl, and H, wherein any C1-6alkyl or C2-6 alkenyl is unsubstituted or substituted with one or more R13; each R13is independently selected from -OR14, -CN, -N(R14)2, and halogen; each R14is independently selected from a 3-6 membered carbocycle, a 3-6 membered heterocycle, C1-6alkyl, C2-6 alkenyl, and H, wherein any C1-6alkyl is optionally deuterated; each R15is independently selected from deuterium, halogen, -N(R12)2, -CN, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; each R20is independently selected from -OH, -OC1-6alkyl, -OC1-6haloalkyl, =O, -CN, -NH2, -NHC1- 6alkyl, -C(O)(C1-6alkyl), a 3-6 membered carbocycle, phenyl, and halogen; and Raand Rbare each independently selected from deuterium, halogen, C1-6alkyl, C2-6 alkenyl, a 3-6 membered carbocycle, -OR12, and H, wherein an Raand Rboptionally join together to form a 3-6 membered carbocycle or heterocycle, and wherein any C1-6alkyl, C2-6alkenyl, or 3-6 membered carbocycle or heterocycle is unsubstituted or is substituted with one or more R13.

[0177] In some embodiments, the present disclosure provides a compound represented by Formula II’, or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein: R1is selected from -OR8; R2is selected from C1-2alkyl that is unsubstituted or is substituted with one or more R13; R3is selected from a 4-10 membered heterocycle that is unsubstituted or substituted with one or more R10; R4is H; R5is selected from C1-2alkyl that is substituted with one or more R13; R6is a bicyclic heteroaryl that is substituted with one or more R15; R7is selected from halogen; R8is an alkylheterocycle, wherein the heterocycle comprises 4-8 ring atoms and is unsubstituted or is substituted with one or more Raor Rb, and wherein an alkyl moiety of the alkylheterocycle is selected from C1-6alkyl; each R10is independently selected from deuterium, =O, -C(O)(C1-6alkylene)CN, -C(O)(C1- 6alkylene)OH, -C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), -C(O)N(R14)2, -C(O)OR14, -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), -C(O)(5-6 membered heteroaryl), -C(O)O(3-6 membered carbocycle), -C(O)O(3-6 membered heterocycle), - C(O)O(C1-6alkylene)(3-6 membered heterocycle), a 5-6 membered heteroaryl, a 3-6 membered carbocycle, a 3-6 membered heterocycle, and C1-6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20, and wherein two R10s optionally join together to form, together with the atom(s) to which they are attached, a 3-6 membered carbocycle or heterocycle; each R12is independently selected from C1-6alkyl, C2-6 alkenyl, and H, wherein any C1-6alkyl or C2- 6 alkenyl is unsubstituted or substituted with one or more R13; each R13is independently selected from -OR14, -CN, -N(R14)2, and halogen; each R14is independently selected from a 3-6 membered carbocycle, a 3-6 membered heterocycle, C1-6alkyl, C2-6 alkenyl, and H, wherein any C1-6alkyl is optionally deuterated; each R15is independently selected from deuterium, halogen, -N(R12)2, -CN, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13;each R20is independently selected from -OH, -OC1-6alkyl, -OC1-6haloalkyl, =O, -CN, -NH2, -NHC1- 6alkyl, -C(O)(C1-6alkyl), a 3-6 membered carbocycle, phenyl, and halogen; and Raand Rbare each independently selected from deuterium, halogen, C1-6alkyl, C2-6 alkenyl, a 3-6 membered carbocycle, -OR12, and H, wherein an Raand Rboptionally join together to form a 3-6 membered carbocycle or heterocycle, and wherein any C1-6alkyl, C2-6alkenyl, or 3-6 membered carbocycle or heterocycle is unsubstituted or is substituted with one or more R13.

[0178] In some embodiments, the present disclosure provides a compound represented by Formula II’, or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein: R1is selected from, wherein Ra1, Ra2, Rb1, and Rb2are each independently selected from deuterium, halogen, C1-6alkyl, C2-6alkenyl, -OR12, and H, wherein Ra2and Rb2can optionally join together to form a 3-6 membered carbocycle, and wherein any C1-6alkyl, C2-6alkenyl, or 3-6 membered carbocycle is unsubstituted or is substituted with one or more R13; R2is selected from C1-2alkyl that is unsubstituted or is substituted with one or more R13; R3is selected from a 4-10 membered heterocycle that is unsubstituted or substituted with one or more R10; R4is H; R5is selected from C1-2alkyl that is substituted with one or more R13; R6is a bicyclic heteroaryl that is substituted with one or more R15; R7is selected from halogen; each R10is independently selected from deuterium, =O, -C(O)(C1-6alkylene)CN, -C(O)(C1-6alkylene)OH, -C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), -C(O)N(R14)2, -C(O)OR14, -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), -C(O)(5-6 membered heteroaryl), -C(O)O(3-6 membered carbocycle), -C(O)O(3-6 membered heterocycle), - C(O)O(C1-6alkylene)(3-6 membered heterocycle), a 5-6 membered heteroaryl, a 3-6 membered carbocycle, a 3-6 membered heterocycle, and C1-6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, whereinany 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20, and wherein two R10s optionally join together to form, together with the atom(s) to which they are attached, a 3-6 membered carbocycle or heterocycle; each R12is independently selected from C1-6alkyl, C2-6alkenyl, and H, wherein any C1-6alkyl or C2-6 alkenyl is unsubstituted or substituted with one or more R13; each R13is independently selected from -OR14, -CN, -N(R14)2, and halogen; each R14is independently selected from a 3-6 membered carbocycle, a 3-6 membered heterocycle, C1-6alkyl, C2-6 alkenyl, and H, wherein any C1-6alkyl is optionally deuterated; each R15is independently selected from deuterium, halogen, -N(R12)2, -CN, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; and each R20is independently selected from -OH, -OC1-6alkyl, -OC1-6haloalkyl, =O, -CN, -NH2, -NHC1- 6alkyl, -C(O)(C1-6alkyl), a 3-6 membered carbocycle, phenyl, and halogen.

[0179] In some embodiments, the present disclosure provides a compound represented by Formula II’, or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein: R1is selected from, wherein Ra1, Ra2, Rb1, and Rb2are each independently selected from deuterium, halogen, C1-6alkyl, C2-6alkenyl, -OR12, and H, wherein Ra2and Rb2can optionally join together to form a 3-6 membered carbocycle, and wherein any C1-6alkyl, C2-6alkenyl, or 3-6 membered carbocycle is unsubstituted or is substituted with one or more R13; R2is selected from C1-2alkyl that is unsubstituted or is substituted with one or more R13; R3is selected from a 4-10 membered heterocycle that is unsubstituted or substituted with one or more R10; R4is H; R5is selected from C1-2alkyl that is substituted with one or more R13;R6is selected from:wherein X is selected from N and C-CN; Y is selected from O, S, and Se; R23is selected from -N(R12)2, C1-6alkyl, and C1-6alkyl-N(R14)2, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; and R24, R25, and R26are independently selected from H, deuterium, halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R7is selected from halogen; each R10is independently selected from deuterium, =O, -C(O)(C1-6alkylene)CN, -C(O)(C1-6alkylene)OH, -C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), -C(O)N(R14)2, -C(O)OR14, -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), -C(O)(5-6 membered heteroaryl), -C(O)O(3-6 membered carbocycle), -C(O)O(3-6 membered heterocycle), - C(O)O(C1-6alkylene)(3-6 membered heterocycle), a 5-6 membered heteroaryl, a 3-6 membered carbocycle, a 3-6 membered heterocycle, and C1-6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20, and wherein two R10s optionally join together to form, together with the atom(s) to which they are attached, a 3-6 membered carbocycle or heterocycle; each R12is independently selected from C1-6alkyl, C2-6 alkenyl, and H, wherein any C1-6alkyl or C2- 6 alkenyl is unsubstituted or substituted with one or more R13; each R13is independently selected from -OR14, -CN, -N(R14)2, and halogen; each R14is independently selected from a 3-6 membered carbocycle, a 3-6 membered heterocycle, C1-6alkyl, C2-6 alkenyl, and H, wherein any C1-6alkyl is optionally deuterated; and each R20is independently selected from -OH, -OC1-6alkyl, -OC1-6haloalkyl, =O, -CN, -NH2, -NHC1-6alkyl, -C(O)(C1-6alkyl), a 3-6 membered carbocycle, phenyl, and halogen.

[0180] In some embodiments, the present disclosure provides a compound represented by Formula II’, or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein:R1is selected from, wherein Ra1, Ra2, Rb1, and Rb2are each independently selected from deuterium, halogen, C1-6alkyl, C2-6alkenyl, -OR12, and H, wherein Ra2and Rb2can optionally join together to form a 3-6 membered carbocycle, and wherein any C1-6alkyl, C2-6alkenyl, or 3-6 membered carbocycle is unsubstituted or is substituted with one or more R13; R2is selected from C1-2alkyl that is unsubstituted or is substituted with one or more R13; R3is a 4-6 membered heterocycle that includes one or more heteroatoms selected from O, S, and N, wherein the heterocycle is unsubstituted or is substituted with one or more R10; R4is H; R5is selected from C1-2alkyl that is substituted with one or more R13; R6is selected from:, wherein X is selected from N and C-CN; Y is selected from O, S, and Se; R23is selected from -N(R12)2, C1-6alkyl, and C1-6alkyl-N(R14)2, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; and R24, R25, and R26are independently selected from H, deuterium, halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R7is selected from halogen; each R10is independently selected from deuterium, =O, -C(O)(C1-6alkylene)CN, -C(O)(C1- 6alkylene)OH, -C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), -C(O)N(R14)2, -C(O)OR14, -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), -C(O)(5-6 membered heteroaryl), -C(O)O(3-6 membered carbocycle), -C(O)O(3-6 membered heterocycle), - C(O)O(C1-6alkylene)(3-6 membered heterocycle), a 5-6 membered heteroaryl, a 3-6 membered carbocycle, a 3-6 membered heterocycle, and C1-6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20, and wherein twoR10s optionally join together to form, together with the atom(s) to which they are attached, a 3-6 membered carbocycle or heterocycle; each R12is independently selected from C1-6alkyl, C2-6 alkenyl, and H, wherein any C1-6alkyl or C2- 6 alkenyl is unsubstituted or substituted with one or more R13; each R13is independently selected from -OR14, -CN, -N(R14)2, and halogen; each R14is independently selected from a 3-6 membered carbocycle, a 3-6 membered heterocycle, C1-6alkyl, C2-6 alkenyl, and H, wherein any C1-6alkyl is optionally deuterated; and each R20is independently selected from -OH, -OC1-6alkyl, -OC1-6haloalkyl, =O, -CN, -NH2, -NHC1- 6alkyl, -C(O)(C1-6alkyl), a 3-6 membered carbocycle, phenyl, and halogen.

[0181] In some embodiments, the present disclosure provides a compound represented by Formula II’, or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein: R1is selected from, wherein Ra1, Ra2, Rb1, and Rb2are each independently selected from deuterium, halogen, C1-6alkyl, C2-6alkenyl, -OR12, and H, wherein Ra2and Rb2can optionally join together to form a 3-6 membered carbocycle, and wherein any C1-6alkyl, C2-6alkenyl, or 3-6 membered carbocycle is unsubstituted or is substituted with one or more R13; R2is selected from C1-2alkyl that is unsubstituted or is substituted with one or more R13; R3is a 7-10 membered heterocycle comprising a fused ring system that includes one or more heteroatoms selected from O, S, and N, wherein the heterocycle is unsubstituted or is substituted with one or more R10; R4is H; R5is selected from C1-2alkyl that is substituted with one or more R13; R6is selected from:, wherein X is selected from N and C-CN; Y is selected from O, S, and Se; R23is selected from -N(R12)2, C1-6alkyl, and C1-6alkyl-N(R14)2, wherein anyC1-6alkyl is unsubstituted or substituted with one or more R13; and R24, R25, and R26are independently selected from H, deuterium, halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R7is selected from halogen; each R10is independently selected from deuterium, =O, -C(O)(C1-6alkylene)CN, -C(O)(C1-6alkylene)OH, -C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), -C(O)N(R14)2, -C(O)OR14, -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), -C(O)(5-6 membered heteroaryl), -C(O)O(3-6 membered carbocycle), -C(O)O(3-6 membered heterocycle), - C(O)O(C1-6alkylene)(3-6 membered heterocycle), a 5-6 membered heteroaryl, a 3-6 membered carbocycle, a 3-6 membered heterocycle, and C1-6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20, and wherein two R10s optionally join together to form, together with the atom(s) to which they are attached, a 3-6 membered carbocycle or heterocycle; each R12is independently selected from C1-6alkyl, C2-6alkenyl, and H, wherein any C1-6alkyl or C2-6alkenyl is unsubstituted or substituted with one or more R13; each R13is independently selected from -OR14, -CN, -N(R14)2, and halogen; each R14is independently selected from a 3-6 membered carbocycle, a 3-6 membered heterocycle, C1-6alkyl, C2-6 alkenyl, and H, wherein any C1-6alkyl is optionally deuterated; and each R20is independently selected from -OH, -OC1-6alkyl, -OC1-6haloalkyl, =O, -CN, -NH2, -NHC1- 6alkyl, -C(O)(C1-6alkyl), a 3-6 membered carbocycle, phenyl, and halogen.

[0182] In another aspect, the present disclosure provides a compound represented by Formula II’’:or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein:R1is selected from Heterocycle comprising one or more N atoms, wherein the heterocycle is unsubstituted or substituted with one or more R31; R2is selected from H, C1-6alkyl, and a 3-6 membered carbocycle, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13; R3is selected from a 4-10 membered heterocycle that is unsubstituted or substituted with one or more R10; R4is H; R5is selected from halogen, -CN, 5- to 6-membered heteroaryl, -OC1-6alkyl, C1-6alkyl, and H, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R6is a bicyclic heteroaryl that is substituted with one or more R15; R7is selected from halogen or H; R8is selected from a heterocycle and an alkylheterocycle, wherein any heterocycle comprises 4-8 ring atoms and is unsubstituted or is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-6alkyl; each R10is independently selected from deuterium, -OR12, =O, =S, -C(O)(C1-6alkylene)CN, - C(O)(C1-6alkylene)OH, -C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), -C(O)N(R14)2, -C(O)OR14, - C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), -C(O)(5-6 membered heteroaryl), -C(O)O(3-6 membered carbocycle), -C(O)O(3-6 membered heterocycle), - C(O)O(C1-6alkylene)(3-6 membered heterocycle), -S(O)2(C1-6alkyl), -C(S)(C1-6alkyl), - C(S)O(C1-6alkyl), -C(S)N(C1-6alkyl)2, -C(=N-OR12)(C1-6alkyl), -C(O)N(R12)OR12,^ halogen, a 5-6 membered heteroaryl, a 3-6 membered carbocycle, a 3-6 membered heterocycle, and C1-6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20, and wherein two R10s optionally join together to form, together with the atom(s) to which they are attached, a 3-6 membered carbocycle or heterocycle; each R12is independently selected from C1-6alkyl, C2-6alkenyl, and H, wherein any C1-6alkyl or C2-6 alkenyl is unsubstituted or substituted with one or more R13;each R13is independently selected from -OR14, -CN, -N(R14)2, and halogen; each R14is independently selected from a 3-6 membered carbocycle, a 3-6 membered heterocycle, C1-6alkyl, -OC1-6alkyl, C2-6 alkenyl, and H, wherein any C1-6alkyl is optionally deuterated; each R15is independently selected from deuterium, halogen, -N(R12)2, -CN, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; each R20is independently selected from -OH, -OC1-6alkyl, -OC1-6haloalkyl, =O, -CN, -NH2, -NHC1- 6alkyl, -C(O)(C1-6alkyl), -C(O)OR12, -C(O)N(R12)2, a 3-6 membered carbocycle, phenyl, and halogen; R30is N(R12)2 or a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted or substituted with one or more R28; each R28is independently selected from C1-6alkyl and halogen; each R29is independently selected from halogen and C1-6alkyl; each R31is selected from C1-6alkyl; n is 0-2; and Raand Rbare each independently selected from deuterium, halogen, C1-6alkyl, C2-6 alkenyl, a 3-6 membered carbocycle, -OR12, and H, wherein an Raand Rboptionally join together to form a 3-6 membered carbocycle or heterocycle, and wherein any C1-6alkyl, C2-6alkenyl, or 3-6 membered carbocycle or heterocycle is unsubstituted or is substituted with one or more R13.

[0183] In some embodiments, the present disclosure provides a compound of Formula II’, wherein the compound is of Formula II-a:or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein R2and R3are as defined for Formula II’ above and described in classes and subclasses herein, both singly and in combination. In some embodiments, R2and R3are as defined for Formula II’ above and described in classes and subclasses herein, both singly and in combination. In someembodiments, the present disclosure provides a compound of Formula II-a, or a salt (e.g., pharmaceutically acceptable salt) thereof.

[0184] In some embodiments, the present disclosure provides a compound of Formula II’’, wherein the compound is of Formula II’’-a:or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein R2and R3are as defined for Formula II’’ above and described in classes and subclasses herein, both singly and in combination. In some embodiments, R2and R3are as defined for Formula II’’ above and described in classes and subclasses herein, both singly and in combination. In some embodiments, the present disclosure provides a compound of Formula II’’-a, or a salt (e.g., pharmaceutically acceptable salt) thereof.

[0185] In some embodiments, for a compound according to Formula II, Z is N. In some embodiments, for a compound according to Formula II, Z is C-R5.

[0186] In some embodiments, for a compound according to Formula II, II’, II’’, II’’-a, II-a, or III, R3is a 4-6 membered heterocycle that includes one or more heteroatoms selected from O, S, and N, wherein the heterocycle is unsubstituted or is substituted with one or more R10. In some embodiments, R3is a 4-6 membered heterocycle that includes one or more heteroatoms selected from O, S, and N, wherein the heterocycle is unsubstituted or is substituted with one or more R10, provided that when the heterocycle contains a nitrogen atom, the nitrogen atom is substituted with R10. In some embodiments, R3is a 4-6 membered heterocycle that includes one heteroatom selected from O, S, and N, wherein the heterocycle is unsubstituted or is substituted with one or more R10, provided that when the heterocycle contains a nitrogen atom, the nitrogen atom is substituted with R10. In some embodiments, R3is a 4-6 membered heterocycle that includes 1 heteroatom selected from O, S, and N, wherein the heterocycle is substituted with 1-4 R10, provided that when the heterocycle contains a nitrogen atom, the nitrogen atom is substituted with R10. In some embodiments, R3is a 4-6 membered heterocycle that includes a nitrogen atom, wherein the heterocycle is substituted with 1-4 R10, provided that the nitrogen atom is substituted with R10. In some embodiments, R3is a 4-6 membered heterocycle that includes an oxygen atom, wherein the heterocycle issubstituted with 1-4 R10. In some embodiments, R3is a pyrrolidine that is substituted with 0-4 R10, provided that the nitrogen atom of the heterocycle is substituted with R10. In some embodiments, R3is a pyrrolidine that is substituted with 1-4 R10, provided that the nitrogen atom of the heterocycle is substituted with R10. In some embodiments, R3is an oxetane that is substituted with 0-4 R10. In some embodiments, R3is an oxetane that is substituted with 1-4 R10. In some embodiments, R3is a tetrahydrofuran that is substituted with 0-4 R10. In some embodiments, R3is a tetrahydrofuran that is substituted with 1-4 R10. In some embodiments, R3is a 4-6 membered heterocycle that is substituted with one or more R10, wherein at least one R10is an unsubstituted C1-6alkyl, provided that when the heterocycle contains a nitrogen atom, the nitrogen atom is substituted with R10. In some embodiments, R3is selected from a 4-6 membered heterocycle that is substituted with one or more R10, provided that when the heterocycle contains a nitrogen atom, the nitrogen atom is substituted with an R10that is selected from -C(O)(C1-6alkylene)CN, -C(O)(C1-6alkylene)OH, -C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), -C(O)N(R14)2, -C(O)OR14, -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), -C(O)(5-6 membered heteroaryl), -C(O)O(3-6 membered carbocycle), -C(O)O(3-6 membered heterocycle), -C(O)O(C1-6alkylene)(3-6 membered heterocycle), a 5-6 membered heteroaryl, a 3-6 membered carbocycle, a 3-6 membered heterocycle, and C1-6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20, and wherein two R10s optionally join together to form, together with the atom(s) to which they are attached, a 3-6 membered carbocycle or heterocycle. In some embodiments, R3is selected from a 4-6 membered heterocycle that is substituted with one or more R10, provided that when the heterocycle contains a nitrogen atom, the nitrogen atom is substituted with an R10that is selected from -C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), -C(O)N(R14)2, -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), -C(O)(5-6 membered heteroaryl), -C(O)O(3-6 membered carbocycle), -C(O)O(3-6 membered heterocycle), -C(O)O(C1-6alkylene)(3-6 membered heterocycle), a 5-6 membered heteroaryl, a 3-6 membered carbocycle, and a 3-6 membered heterocycle, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20, and wherein two R10s optionally join together to form, together with the atom(s) to which they are attached, a 3-6 membered carbocycle or heterocycle. In some embodiments, R3is selected from a 4-6 membered heterocycle that is substituted with one or more R10, provided that when the heterocycle contains a nitrogen atom, the nitrogen atom is substituted with an R10that is a 5-6 membered heteroaryl that is unsubstituted or substituted with one or more R12or R20.

[0187] In some embodiments, for a compound according to Formula II, II’, II’’, II’’-a, II-a, or III, two R10s join together to form, together with the atom(s) to which they are attached, a 3-6 membered carbocycle or heterocycle. In some embodiments, two R10s connected to adjacent atoms join together to form, together with the atoms to which they are attached, a 3-6 membered carbocycle or heterocycle. In some embodiments, two R10s connected to adjacent atoms join together to form, together with the atoms to which they are attached, a 5-6 membered heterocycle, such as a pyrrolidine or oxazolidine. In some embodiments, the 3-6 membered carbocycle or heterocycle formed by the joining of two R10s is substituted with one or more R10. In some embodiments, the 5-6 membered heterocycle formed by the joining of two R10s is substituted with one or more R10. In some embodiments, the 5-6 membered heterocycle (e.g., pyrrolidine or oxazolidine) formed by the joining of two R10s is substituted with =O. In some embodiments, each R10is independently selected from -OR12, =O, -C(O)(C1-6alkylene)CN, -C(O)(C1-6alkylene)OH, -C(O)(C1-6alkyl), -C(O)(3-6 membered carbocycle), -C(O)N(R14)2, -S(O)2(C1-6alkyl), halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R20, and wherein two R10s optionally join together to form, together with the atom(s) to which they are attached, a 3-6 membered carbocycle or heterocycle. In some embodiments, each R10is independently selected from -OR12, =O, -C(O)(C1-6alkylene)CN, -C(O)(C1-6alkylene)OH, -C(O)(C1-6alkyl), -C(O)(3-6 membered carbocycle), -C(O)N(R14)2, -S(O)2(C1-6alkyl), halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R20. In some embodiments, each R10is independently selected from -OR12, -C(O)(C1-6alkylene)CN, -C(O)(C1-6alkylene)OH, -C(O)(C1-6alkyl), halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R20. In some embodiments, each R10is independently selected from -C(O)(C1- 6alkyl), -C(O)(3-6 membered carbocycle), -C(O)O(C1-6alkyl), halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R20, and any 3-6 membered carbocycle is unsubstituted or substituted with one or more R12or R20. In some embodiments, each R10is independently selected from deuterium, -C(O)N(R14)2, -C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), -C(O)(3-6 membered carbocycle), -C(O)(3- 8 membered heterocycle), a 3-6 membered heterocycle, a 5-6 membered heteroaryl, halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R20, and wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20.

[0188] In some embodiments, for a compound according to Formula II’, II-a, or III, R3is selected from:^, , , , ,, , , , , ,, , , , , , ,with one or more R10.

[0189] In some embodiments, for a compound according to Formula II’, II’’, II’’-a, II-a, or III, R3issel^,, , , , , , ,,, , , , , ,, , any of which is optionally further substituted with one or more R10.

[0190] In some embodiments, for a compound according to Formula II, II’, II’’, II’’-a, II-a, or III, R3is^,,, , , , , ,, , , , , , ,substituted with one or more R10.

[0191] In some embodiments, for a compound according to Formula II’, II-a, or III, R3is selected from:any of which isoptionally further substituted with one or more R10.

[0192] In some embodiments according to Formula II or Formula III, R3is selected from:,any of which isoptionally further substituted with one or more R10.

[0193] In some embodiments according to Formula II’, R3is selected from:optionally further substituted with one or more R10.

[0194] In some embodiments according to Formula II’’, R3is selected from:,,,, , , , ,,,or more R10.

[0195] In some embodiments for a compound according to Formula II, II’, or II’’, R3is selected from, either of which is optionally further substituted with one or more R10.

[0196] In some embodiments, for a compound according to Formula II, II’, II’’, II’’-a, or II-a, R3is a 7- 10 membered heterocycle that includes one or more heteroatoms selected from O, S, and N, wherein theheterocycle is unsubstituted or is substituted with one or more R10. In some embodiments, R3is a 7-10 membered heterocycle that includes one or more heteroatoms selected from O, S, and N, wherein the heterocycle is unsubstituted or is substituted with one or more R10, provided that (i) when the heterocycle contains a nitrogen atom, the nitrogen atom is substituted with R10or (ii) the heterocycle does not comprise an –NH- moiety. In some embodiments, R3is a 7-10 membered heterocycle that includes one or more heteroatoms selected from O, S, and N, wherein the heterocycle is unsubstituted or is substituted with one or more R10, provided that (i) when the heterocycle contains a nitrogen atom, the nitrogen atom is substituted with R10or (ii) when the heterocycle contains a single ring, the heterocycle does not comprise an –NH- moiety. In some embodiments, R3is a 7-10 membered bridged heterocycle that includes one or more heteroatoms selected from O, S, and N, wherein the bridged heterocycle is unsubstituted or is substituted with one or more R10. In some embodiments, R3is a 7-10 membered bridged heterocycle that includes one or more heteroatoms selected from O, S, and N, wherein the bridged heterocycle is unsubstituted or is substituted with one or more R10, provided that (i) when the bridged heterocycle contains a nitrogen atom, the nitrogen atom is substituted with R10or (ii) the bridged heterocycle does not comprise an –NH- moiety. In some embodiments, R3is a bridged pyrrolidine that is unsubstituted or is substituted with one or more R10. In some embodiments, R3is a bridged pyrrolidine that is unsubstituted or is substituted with one or more R10, provided that the bridged pyrrolidine does not comprise an NH moiety. In some embodiments, R3is a bridged pyrrolidine that is substituted with one or more R10, provided that the bridged pyrrolidine does not comprise an NH moiety. In some embodiments, R3is a 7-10 membered heterocycle comprising a fused ring system that includes one or more heteroatoms selected from O, S, and N, wherein the heterocycle is unsubstituted or is substituted with one or more R10. In some embodiments, R3is a 7-10 membered heterocycle comprising a fused ring system that includes one or more heteroatoms selected from O, S, and N, wherein the heterocycle is unsubstituted or is substituted with one or more R10, provided that (i) when the heterocycle contains a nitrogen atom, the nitrogen atom is substituted with R10or (ii) the heterocycle does not comprise an –NH- moiety. In some embodiments, R3is a 7-10 membered heterocycle comprising a fused ring system comprising two rings, wherein the heterocycle includes one or more heteroatoms selected from O, S, and N, and the heterocycle is unsubstituted or is substituted with one or more R10. In some embodiments, R3is a 7-10 membered heterocycle comprising a fused ring system comprising two rings, wherein the heterocycle includes one or more heteroatoms selected from O, S, and N, and the heterocycle is unsubstituted or is substituted with one or more R10, provided that (i) when the heterocycle contains a nitrogen atom, the nitrogen atom is substituted with R10or (ii) the heterocycle does not comprise an –NH- moiety. In some embodiments, R3comprises a fused ring system comprising two rings, whereinat least one ring is a 5-membered heterocycle that is unsubstituted or is substituted with one or more R10. In some embodiments, R3comprises a fused ring system comprising two rings, wherein at least one ring is a pyrrolidine that is unsubstituted or is substituted with one or more R10. In some embodiments, R3comprises a fused ring system comprising two rings, wherein each ring is a 5-membered heterocycle that is unsubstituted or is substituted with one or more R10. In some embodiments, R3comprises a fused ring system comprising two rings, wherein one ring is a 5-membered heterocycle that is unsubstituted or is substituted with one or more R10and the second ring is a 6-membered heterocycle that is unsubstituted or is substituted with one or more R10. In some embodiments, R3comprises a fused ring system comprising two rings, wherein one ring is a pyrrolidine that is unsubstituted or is substituted with one or more R10and the second ring is a piperidine, oxazinane, oxazolidine, imidazolidine, or pyrrolidine that is unsubstituted or is substituted with one or more R10. In some embodiments, the fused ring system is substituted with at least one R10, wherein the at least one R10is selected from =and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R20.

[0197] In some embodiments, for a compound according to Formula II’ or II-a, when R10is -C(O)N(R14)2, then at least one R14is not H. In some embodiments, when R10is -C(O)N(R14)2, then each R14is C1-6alkyl (e.g., methyl or ethyl).

[0198] In some embodiments, for a compound according to Formula II’or II-a, R3is selected from:, , , , ,, , , , , , , ,, any of which is optionally further substituted with one or more R10.

[0199] In some embodiments, for a compound according to Formula II, II’, II’’, II’’-a, or II-a, R3is selected, any of which is optionally further substituted with one or more R10.

[0200] In some embodiments, for a compound according to Formula II, II’, II’’, II’’-a, or II-a, R3is selected, , , , ,any of which is optionally further substituted with one or more R10.

[0201] In some embodiments, for a compound according to Formula II, II’, II’’, II’’-a, or II-a, R3isselected from: , , , , ,, any of which is optionally further substituted with one or more R10.

[0202] In some embodiments, the compound is a compound according to Formula IIR’, IIU’, IIV’, or IIZ:or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein: R1is selected from Heterocycle comprising one or more N atoms, wherein the heterocycle is unsubstituted or substituted with one or more R31; R2is selected from H, C1-6alkyl, and a 3-6 membered carbocycle, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13; R4is H; R5is selected from halogen and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R6is a bicyclic heteroaryl that is substituted with one or more R15;R7is selected from halogen; R8is selected from a heterocycle and an alkylheterocycle, wherein any heterocycle comprises 4-8 ring atoms and is unsubstituted or is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-6alkyl; each R12is independently selected from C1-6alkyl, C2-6alkenyl, and H, wherein any C1-6alkyl or C2-6alkenyl is unsubstituted or substituted with one or more R13; each R13is independently selected from -OR14, -CN, -N(R14)2, and halogen; each R14is independently selected from a 3-6 membered carbocycle, a 3-6 membered heterocycle, C1-6alkyl, C2-6alkenyl, and H, wherein any C1-6alkyl is optionally deuterated; each R15is independently selected from deuterium, halogen, -N(R12)2, -CN, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; each R20is independently selected from -OH, -OC1-6alkyl, -OC1-6haloalkyl, =O, -CN, -NH2, - NHC1-6alkyl, -C(O)(C1-6alkyl), a 3-6 membered carbocycle, phenyl, and halogen; each R28is independently selected from C1-6alkyl and halogen; each R29is independently selected from halogen and C1-6alkyl; R30is N(R12)2or a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted or substituted with one or more R28; each R31is selected from C1-6alkyl; n is 0-2; Raand Rbare each independently selected from deuterium, halogen, C1-6alkyl, C2-6 alkenyl, a 3-6 membered carbocycle, -OR12, and H, wherein an Raand Rboptionally join together to form a 3-6 membered carbocycle or heterocycle, and wherein any C1-6alkyl, C2-6 alkenyl, or 3-6 membered carbocycle or heterocycle is unsubstituted or is substituted with one or more R13; each Rdis independently selected from H, deuterium, -OR12, =O, -C(O)(C1-6alkylene)CN, - C(O)(C1-6alkylene)OH, -C(O)(C1-6alkyl), -C(O)N(R14)2, -C(O)(3-6 membered carbocycle), -S(O)2(C1-6alkyl), halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R20, and wherein any 3-6 membered carbocycle is unsubstituted or substituted with one or more R12or R20; and Reis selected from -C(O)(C1-6alkyl)CN, -C(O)(C1-6alkyl)OH, -C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), -C(O)N(R14)2, -C(O)OR14, -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), -C(O)(5-6 membered heteraryl), -C(O)O(3-6 membered carbocycle), - C(O)O(3-6 membered heterocycle), -C(O)O(C1-6alkylene)(3-6 membered heterocycle), -S(O)2(C1-6alkyl), a 5-6 membered heteroaryl, a 3-6 membered carbocycle, and C1-6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, and wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20.

[0203] In some embodiments, the present disclosure provides a compound of Formula IIR’, or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the present disclosure provides a compound of Formula IIU’, or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the present disclosure provides a compound of Formula IIV’, or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the present disclosure provides a compound of Formula IIZ, or a salt (e.g., a pharmaceutically acceptable salt) thereof.

[0204] In some embodiments, for a compound according to any one of Formulas IIR’, IIU’, IIV’, or IIZ, each Rdis H. In some embodiments, at least one Rdis selected from deuterium, -OR12, =O, -C(O)(C1- 6alkylene)CN, -C(O)(C1-6alkylene)OH, -C(O)(C1-6alkyl), -C(O)N(R14)2, -C(O)(3-6 membered carbocycle), -S(O)2(C1-6alkyl), halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R20, and wherein any 3-6 membered carbocycle is unsubstituted or substituted with one or more R12or R20. In some embodiments, at least one Rdis selected from -OR12, =O, -C(O)(C1-6alkylene)CN, -C(O)(C1-6alkylene)OH, -C(O)(C1-6alkyl), -C(O)N(R14)2, -C(O)(3-6 membered carbocycle), -S(O)2(C1-6alkyl), halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R20, and wherein any 3-6 membered carbocycle is unsubstituted or substituted with one or more R12or R20. In some embodiments, at least one Rdis selected from C1-6alkyl that is unsubstituted or substituted with one or more R20, and wherein any 3-6 membered carbocycle is unsubstituted or substituted with one or more R12or R20.

[0205] In some embodiments, for a compound according to any one of Formulas IIR’, IIU’, IIV’, or IIZ, Reis selected from -C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), -C(O)N(R14)2, -C(O)OR14, -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), -C(O)(5-6 membered heteraryl), -C(O)O(3-6 membered carbocycle), -C(O)O(3-6 membered heterocycle), -C(O)O(C1-6alkylene)(3-6 membered heterocycle), - S(O)2(C1-6alkyl), a 5-6 membered heteroaryl, a 3-6 membered carbocycle, and C1-6alkyl, wherein any C1- 6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, and wherein any 3- 6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20. In some embodiments, Reis selected from -C(O)(C1-6alkyl), - C(O)O(C1-6alkyl), -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), -C(O)(5-6 membered heteraryl), -C(O)O(3-6 membered carbocycle), -C(O)O(3-6 membered heterocycle), - C(O)O(C1-6alkylene)(3-6 membered heterocycle), -S(O)2(C1-6alkyl), a 5-6 membered heteroaryl, a 3-6membered carbocycle, and C1-6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, and wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20. In some embodiments, Reis a 5-6 membered heteroaryl that is unsubstituted or substituted with one or more R12or R20.

[0206] In some embodiments, the compound is a compound according to Formula IIAA’:or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein: R1is selected from Heterocycle comprising one or more N atoms, wherein the heterocycle is unsubstituted or substituted with one or more R31; R2is selected from H, C1-6alkyl, and a 3-6 membered carbocycle, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13; R4is H; R5is selected from halogen and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R6is a bicyclic heteroaryl that is substituted with one or more R15; R7is selected from halogen; R8is selected from a heterocycle and an alkylheterocycle, wherein any heterocycle comprises 4-8 ring atoms and is unsubstituted or is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-6alkyl; each R12is independently selected from C1-6alkyl, C2-6 alkenyl, and H, wherein any C1-6alkyl or C2-6alkenyl is unsubstituted or substituted with one or more R13; each R13is independently selected from -OR14, -CN, -N(R14)2, and halogen;each R14is independently selected from a 3-6 membered carbocycle, a 3-6 membered heterocycle, C1-6alkyl, C2-6alkenyl, and H, wherein any C1-6alkyl is optionally deuterated; each R15is independently selected from deuterium, halogen, -N(R12)2, -CN, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; each R20is independently selected from -OH, -OC1-6alkyl, -OC1-6haloalkyl, =O, -CN, -NH2, - NHC1-6alkyl, -C(O)(C1-6alkyl), a 3-6 membered carbocycle, phenyl, and halogen; each R28is independently selected from C1-6alkyl and halogen; each R29is independently selected from halogen and C1-6alkyl; R30is N(R12)2or a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted or substituted with one or more R28; each R31is selected from C1-6alkyl; n is 0-2; Raand Rbare each independently selected from deuterium, halogen, C1-6alkyl, C2-6alkenyl, a 3-6 membered carbocycle, -OR12, and H, wherein an Raand Rboptionally join together to form a 3-6 membered carbocycle or heterocycle, and wherein any C1-6alkyl, C2-6alkenyl, or 3-6 membered carbocycle or heterocycle is unsubstituted or is substituted with one or more R13; each Rdis independently selected from deuterium, H, -OR12, =O, -C(O)(C1-6alkylene)CN, - C(O)(C1-6alkylene)OH, -C(O)(C1-6alkyl), -C(O)(3-6 membered carbocycle), -S(O)2(C1-6alkyl), halogen, a 3-6 membered carbocycle, a 3-6 membered heterocycle, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R20, wherein any 3- 6 membered carbocycle or 3-6 membered heterocycle, is unsubstituted or substituted with one or more R12or R20; and (i) Rq1, Rq2, and Rp2are each independently selected from Rd, and Reand Rp1, together with the atoms to which they are attached, form a 5-6 membered heterocycle that is unsubstituted or is substituted with one or more Rd; or (ii) Rp1, Rp2, and Rq2are each independently selected from Rd, and Reand Rq1, together with the atoms to which they are attached, form a 5-6 membered heterocycle that is unsubstituted or is substituted with one or more Rd.

[0207] In some embodiments, the compound is a compound according to Formula IIAA’, or a salt (e.g., pharmaceutically acceptable salt) thereof.

[0208] In some embodiments, for a compound according to Formula IIAA’, Rq1, Rq2, and Rp2are each independently selected from Rd, and Reand Rp1, together with the atoms to which they are attached, form a 5-6 membered heterocycle that is unsubstituted or is substituted with one or more Rd. In some embodiments, Rp1, Rp2, and Rq2are each independently selected from Rd, and Reand Rq1, together with the atoms to which they are attached, form a 5-6 membered heterocycle that is unsubstituted or is substituted with one or more Rd.

[0209] In some embodiments, the compound is a compound according to Formula IIBB, IICC, IIDD, IIEE, IIFF, IIGG, IIHH, or IIJJ:or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein: R1is selected from Heterocycle comprising one or more N atoms, wherein the heterocycle is unsubstituted or substituted with one or more R31; R2is selected from H, C1-6alkyl, and a 3-6 membered carbocycle, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13; R4is H; R5is selected from halogen and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13;R6is a bicyclic heteroaryl that is substituted with one or more R15; R7is selected from halogen; R8is selected from a heterocycle and an alkylheterocycle, wherein any heterocycle comprises 4-8 ring atoms and is unsubstituted or is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-6alkyl; each R12is independently selected from C1-6alkyl, C2-6alkenyl, and H, wherein any C1-6alkyl or C2-6alkenyl is unsubstituted or substituted with one or more R13; each R13is independently selected from -OR14, -CN, -N(R14)2, and halogen; each R14is independently selected from a 3-6 membered carbocycle, a 3-6 membered heterocycle, C1-6alkyl, C2-6alkenyl, and H, wherein any C1-6alkyl is optionally deuterated; each R15is independently selected from deuterium, halogen, -N(R12)2, -CN, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; each R20is independently selected from -OH, -OC1-6alkyl, -OC1-6haloalkyl, =O, -CN, -NH2, - NHC1-6alkyl, -C(O)(C1-6alkyl), a 3-6 membered carbocycle, phenyl, and halogen; each R28is independently selected from C1-6alkyl and halogen; each R29is independently selected from halogen and C1-6alkyl; R30is N(R12)2or a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted or substituted with one or more R28; each R31is selected from C1-6alkyl; n is 0-2; Raand Rbare each independently selected from deuterium, halogen, C1-6alkyl, C2-6 alkenyl, a 3-6 membered carbocycle, -OR12, and H, wherein an Raand Rboptionally join together to form a 3-6 membered carbocycle or heterocycle, and wherein any C1-6alkyl, C2-6 alkenyl, or 3-6 membered carbocycle or heterocycle is unsubstituted or is substituted with one or more R13; each Rdis independently selected from H, deuterium, -OR12, =O, -C(O)(C1-6alkylene)CN, - C(O)(C1-6alkylene)OH, -C(O)(C1-6alkyl), -C(O)N(R14)2, -C(O)(3-6 membered carbocycle), -S(O)2(C1-6alkyl), halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R20, and wherein any 3-6 membered carbocycle is unsubstituted or substituted with one or more R12or R20; and Re, if present, is selected from -C(O)(C1-6alkyl)CN, -C(O)(C1-6alkyl)OH, -C(O)(C1-6alkyl), - C(O)O(C1-6alkyl), -C(O)N(R14)2, -C(O)OR14, -C(O)(3-6 membered carbocycle), -C(O)(3- 8 membered heterocycle), -C(O)(5-6 membered heteraryl), -C(O)O(3-6 memberedcarbocycle), -C(O)O(3-6 membered heterocycle), -C(O)O(C1-6alkylene)(3-6 membered heterocycle), -S(O)2(C1-6alkyl), a 5-6 membered heteroaryl, a 3-6 membered carbocycle, and C1-6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, and wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20.

[0210] In some embodiments, the present disclosure provides a compound of Formula IIBB, or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the present disclosure provides a compound of Formula IICC, or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the present disclosure provides a compound of Formula IIDD, or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the present disclosure provides a compound of Formula IIEE, or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the present disclosure provides a compound of Formula IIFF, or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the present disclosure provides a compound of Formula IIGG, or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the present disclosure provides a compound of Formula IIHH, or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the present disclosure provides a compound of Formula IIJJ, or a salt (e.g., a pharmaceutically acceptable salt) thereof.

[0211] In some embodiments, for a compound according to any one of Formulas II, II’, II’’, IIR’, IIU’, IIV’, IIZ, IIAA’, IIBB, IICC, IIDD, IIEE, IIFF, IIGG, IIHH, and IIJJ, R6is a bicyclic heteroaryl that is substituted with one or more R15. In some embodiments, R6is selected from:, wherein X is selected from N and C-CN; Y is selected from O, S, and Se; R23is selected from -N(R12)2, C1-6alkyl, and C1-6alkyl-N(R14)2, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; and R24, R25, and R26are independently selected from H, deuterium, halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13. In some embodiments, X is C-CN and Y is S. In some embodiments, X is C-CN and Y is O. In some embodiments, X is C-CN and Y is Se. In some embodiments, X is N and Y is S. In some embodiments, X is N and Y is O. In some embodiments, X is N and Y is Se. In some embodiments, X is C-CN, Y is S, and R23is -N(R12)2. In some embodiments, X is C-CN, Y is Se, and R23is -N(R12)2. In some embodiments, X is C-CN, Y is S, and R23is -NH2. In some embodiments, X is C-CN, Y is Se, and R23is -NH2. In some embodiments, R24is a halogen (e.g., fluoro). In some embodiments, R26is deuterium.

[0212] In some embodiments, for a compound according to any one of Formulas II, II’, II’’, III, IIR’, IIU’, IIV’, IIZ, IIAA’, IIBB, IICC, IIDD, IIEE, IIFF, IIGG, IIHH, and IIJJ, R6is selected from:any of which is substituted with one or more R15.

[0213] In some embodiments, for a compound according to any one of Formulas II, II’, II’’, III, IIR’, IIU’, IIV’, IIZ, IIAA’, IIBB, IICC, IIDD, IIEE, IIFF, IIGG, IIHH, and IIJJ, R6is selected from:, , , ,

[0214] In some embodiments, for a compound according to any one of Formulas II, II’, II’’, III, IIR’, IIU’, IIV’, IIZ, IIAA’, IIBB, IICC, IIDD, IIEE, IIFF, IIGG, IIHH, and IIJJ, R6is selected from:.

[0215] In some embodiments, for a compound according to Formula II’’ or III, R6is selected from:,compound according to Formula II or III, R6is selected from:,

[0216] In some embodiments, for a compound according to any one of Formulas II, II’, II’’, III, IIR’, IIU’, IIV’, IIZ, IIAA’, IIBB, IICC, IIDD, IIEE, IIFF, IIGG, IIHH, and IIJJ, R6is selected from:which is substituted with one or more R15. In some embodiments, R6is selected from:,.

[0217] In some embodiments, for a compound according to Formula II, R6is a phenyl optionally substituted with one or more R15. In some embodiments, R6is a phenyl optionally substituted with two or more R15. In some embodiments, R6is selected from:

[0218] In some embodiments, the compound is a compound according to Formula IIR1’, IIU1’, IIV1’, or IIZ1:or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein: R1is selected from Heterocycle comprising one or more N atoms, wherein the heterocycle is unsubstituted or substituted with one or more R31; R2is selected from H, C1-6alkyl, and a 3-6 membered carbocycle, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13; R4is H; R5is selected from halogen and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R7is selected from halogen; R8is selected from a heterocycle and an alkylheterocycle, wherein any heterocycle comprises 4-8 ring atoms and is unsubstituted or is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-6alkyl; each R12is independently selected from C1-6alkyl, C2-6 alkenyl, and H, wherein any C1-6alkyl or C2-6alkenyl is unsubstituted or substituted with one or more R13; each R13is independently selected from -OR14, -CN, -N(R14)2, and halogen;each R14is independently selected from a 3-6 membered carbocycle, a 3-6 membered heterocycle, C1-6alkyl, C2-6alkenyl, and H, wherein any C1-6alkyl is optionally deuterated; each R20is independently selected from -OH, -OC1-6alkyl, -OC1-6haloalkyl, =O, -CN, -NH2, - NHC1-6alkyl, -C(O)(C1-6alkyl), a 3-6 membered carbocycle, phenyl, and halogen; each R28is independently selected from C1-6alkyl and halogen; each R29is independently selected from halogen and C1-6alkyl; R30is N(R12)2or a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted or substituted with one or more R28; each R31is selected from C1-6alkyl; n is 0-2; Raand Rbare each independently selected from deuterium, halogen, C1-6alkyl, C2-6alkenyl, a 3-6 membered carbocycle, -OR12, and H, wherein an Raand Rboptionally join together to form a 3-6 membered carbocycle or heterocycle, and wherein any C1-6alkyl, C2-6alkenyl, or 3-6 membered carbocycle or heterocycle is unsubstituted or is substituted with one or more R13; each Rdis independently selected from H, deuterium, -OR12, =O, -C(O)(C1-6alkylene)CN, - C(O)(C1-6alkylene)OH, -C(O)(C1-6alkyl), -C(O)N(R14)2, -C(O)(3-6 membered carbocycle), -S(O)2(C1-6alkyl), halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R20, and wherein any 3-6 membered carbocycle is unsubstituted or substituted with one or more R12or R20; Reis selected from -C(O)(C1-6alkylene)CN, -C(O)(C1-6alkylene)OH, -C(O)(C1-6alkyl), -C(O)O(C1- 6alkyl), -C(O)N(R14)2, -C(O)OR14, -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), -C(O)(5-6 membered heteraryl), -C(O)O(3-6 membered carbocycle), -C(O)O(3-6 membered heterocycle), -C(O)O(C1-6alkylene)(3-6 membered heterocycle), -S(O)2(C1-6alkyl), a 5-6 membered heteroaryl, a 3-6 membered carbocycle, and C1-6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, and wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20; X is selected from N and C-CN; Y is selected from O and S; R23is selected from -N(R12)2, C1-6alkyl, and C1-6alkyl-N(R14)2, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; andR24, R25, and R26are independently selected from H, deuterium, halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13.

[0219] In some embodiments, the compound is a compound according to Formula IIR1’, or a salt (e.g., pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIU1’, or a salt (e.g., pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIV1’, or a salt (e.g., pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIZ1’, or a salt (e.g., pharmaceutically acceptable salt) thereof.

[0220] In some embodiments, the compound is a compound according to Formula IIAA1’:or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein: R1is selected from Heterocycle comprising one or more N atoms, wherein the heterocycle is unsubstituted or substituted with one or more R31; R2is selected from H, C1-6alkyl, and a 3-6 membered carbocycle, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13; R4is H; R5is selected from halogen and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R7is selected from halogen; R8is selected from a heterocycle and an alkylheterocycle, wherein any heterocycle comprises 4-8 ring atoms and is unsubstituted or is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-6alkyl;each R12is independently selected from C1-6alkyl, C2-6 alkenyl, and H, wherein any C1-6alkyl or C2-6alkenyl is unsubstituted or substituted with one or more R13; each R13is independently selected from -OR14, -CN, -N(R14)2, and halogen; each R14is independently selected from a 3-6 membered carbocycle, a 3-6 membered heterocycle, C1-6alkyl, C2-6alkenyl, and H, wherein any C1-6alkyl is optionally deuterated; each R20is independently selected from -OH, -OC1-6alkyl, -OC1-6haloalkyl, =O, -CN, -NH2, - NHC1-6alkyl, -C(O)(C1-6alkyl), a 3-6 membered carbocycle, phenyl, and halogen; each R28is independently selected from C1-6alkyl and halogen; each R29is independently selected from halogen and C1-6alkyl; R30is N(R12)2or a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted or substituted with one or more R28; each R31is selected from C1-6alkyl; n is 0-2; Raand Rbare each independently selected from deuterium, halogen, C1-6alkyl, C2-6alkenyl, a 3-6 membered carbocycle, -OR12, and H, wherein an Raand Rboptionally join together to form a 3-6 membered carbocycle or heterocycle, and wherein any C1-6alkyl, C2-6alkenyl, or 3-6 membered carbocycle or heterocycle is unsubstituted or is substituted with one or more R13; each Rdis independently selected from H, deuterium, -OR12, =O, -C(O)(C1-6alkylene)CN, - C(O)(C1-6alkylene)OH, -C(O)(C1-6alkyl), -C(O)(3-6 membered carbocycle), - C(O)N(R14)2, -S(O)2(C1-6alkyl), a 3-6 membered carbocycle, a 3-6 membered heterocycle, halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R20, and wherein any 3-6 membered carbocycle or 3-6 membered heterocycle is unsubstituted or substituted with one or more R12or R20; X is selected from N and C-CN; Y is selected from O and S; R23is selected from -N(R12)2, C1-6alkyl, and C1-6alkyl-N(R14)2, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R24, R25, and R26are independently selected from H, deuterium, halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; and (i) Rq1, Rq2, and Rp2are each independently selected from Rd, and Reand Rp1, together with the atoms to which they are attached, form a 5-6 membered heterocycle that is unsubstituted or is substituted with one or more Rd; or(ii) Rp1, Rp2, and Rq2are each independently selected from Rd, and Reand Rq1, together with the atoms to which they are attached, form a 5-6 membered heterocycle that is unsubstituted or is substituted with one or more Rd.

[0221] In some embodiments, the compound is a compound according to Formula IIAA1’, or a salt (e.g., pharmaceutically acceptable salt) thereof.

[0222] In some embodiments, the compound is a compound according to Formula IIBB1, IICC1, IIDD1, IIEE1, IIFF1, IIGG1, IIHH1, or IIJJ1:or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein: R1is selected from Heterocycle comprising one or more N atoms, wherein the heterocycle is unsubstituted or substituted with one or more R31; R2is selected from H, C1-6alkyl, and a 3-6 membered carbocycle, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13; R4is H; R5is selected from halogen and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R7is selected from halogen; R8is selected from a heterocycle and an alkylheterocycle, wherein any heterocycle comprises 4-8 ring atoms and is unsubstituted or is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-6alkyl;each R12is independently selected from C1-6alkyl, C2-6 alkenyl, and H, wherein any C1-6alkyl or C2-6alkenyl is unsubstituted or substituted with one or more R13; each R13is independently selected from -OR14, -CN, -N(R14)2, and halogen; each R14is independently selected from a 3-6 membered carbocycle, a 3-6 membered heterocycle, C1-6alkyl, C2-6alkenyl, and H, wherein any C1-6alkyl is optionally deuterated; each R20is independently selected from -OH, -OC1-6alkyl, -OC1-6haloalkyl, =O, -CN, -NH2, - NHC1-6alkyl, -C(O)(C1-6alkyl), a 3-6 membered carbocycle, phenyl, and halogen; each R28is independently selected from C1-6alkyl and halogen; each R29is independently selected from halogen and C1-6alkyl; R30is N(R12)2or a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted or substituted with one or more R28; each R31is selected from C1-6alkyl; n is 0-2; Raand Rbare each independently selected from deuterium, halogen, C1-6alkyl, C2-6alkenyl, a 3-6 membered carbocycle, -OR12, and H, wherein an Raand Rboptionally join together to form a 3-6 membered carbocycle or heterocycle, and wherein any C1-6alkyl, C2-6alkenyl, or 3-6 membered carbocycle or heterocycle is unsubstituted or is substituted with one or more R13; each Rdis independently selected from H, deuterium, -OR12, =O, -C(O)(C1-6alkylene)CN, - C(O)(C1-6alkylene)OH, -C(O)(C1-6alkyl), -C(O)N(R14)2, -C(O)(3-6 membered carbocycle), -S(O)2(C1-6alkyl), halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R20, and wherein any 3-6 membered carbocycle is unsubstituted or substituted with one or more R12or R20; Re, if present, is selected from -C(O)(C1-6alkyl)CN, -C(O)(C1-6alkyl)OH, -C(O)(C1-6alkyl), - C(O)O(C1-6alkyl), -C(O)N(R14)2, -C(O)OR14, -C(O)(3-6 membered carbocycle), -C(O)(3- 8 membered heterocycle), -C(O)(5-6 membered heteraryl), -C(O)O(3-6 membered carbocycle), -C(O)O(3-6 membered heterocycle), -C(O)O(C1-6alkylene)(3-6 membered heterocycle), -S(O)2(C1-6alkyl), a 5-6 membered heteroaryl, a 3-6 membered carbocycle, and C1-6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, and wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20;X is selected from N and C-CN; Y is selected from O and S; R23is selected from -N(R12)2, C1-6alkyl, and C1-6alkyl-N(R14)2, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; and R24, R25, and R26are independently selected from H, deuterium, halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13.

[0223] In some embodiments, the compound is a compound according to Formula IIBB1, or a salt (e.g., pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IICC1, or a salt (e.g., pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIDD1, or a salt (e.g., pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIEE1, or a salt (e.g., pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIFF1, or a salt (e.g., pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIGG1, or a salt (e.g., pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIHH1, or a salt (e.g., pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIJJ1, or a salt (e.g., pharmaceutically acceptable salt) thereof.

[0224] In some embodiments, for a compound according to any one of Formulas IIBB, IICC, IIDD, IIEE, IIFF, IIGG, IIHH, IIJJ, IIBB1, IICC1, IIDD1, IIEE1, IIFF1, IIGG1, IIHH1, or IIJJ1, each Rdis H. In some embodiments, at least one Rdis selected from deuterium, -OR12, =O, -C(O)(C1-6alkylene)CN, -C(O)(C1- 6alkylene)OH, -C(O)(C1-6alkyl), -C(O)N(R14)2, -C(O)(3-6 membered carbocycle), -S(O)2(C1-6alkyl), halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R20, and wherein any 3-6 membered carbocycle is unsubstituted or substituted with one or more R12or R20. In some embodiments, at least one Rdis selected from -OR12, =O, -C(O)(C1-6alkylene)CN, -C(O)(C1-6alkylene)OH, -C(O)(C1-6alkyl), -C(O)N(R14)2, -C(O)(3-6 membered carbocycle), -S(O)2(C1-6alkyl), halogen, and C1- 6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R20, and wherein any 3-6 membered carbocycle is unsubstituted or substituted with one or more R12or R20. In some embodiments, at least one Rdis selected from C1-6alkyl that is unsubstituted or substituted with one or more R20, and wherein any 3-6 membered carbocycle is unsubstituted or substituted with one or more R12or R20.

[0225] In some embodiments, for a compound according to any one of Formulas IIBB, IIGG, IIBB1, or IIGG1, Reis selected from -C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), -C(O)N(R14)2, -C(O)OR14, -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), -C(O)(5-6 membered heteraryl), -C(O)O(3-6membered carbocycle), -C(O)O(3-6 membered heterocycle), -C(O)O(C1-6alkylene)(3-6 membered heterocycle), -S(O)2(C1-6alkyl), a 5-6 membered heteroaryl, a 3-6 membered carbocycle, and C1-6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, and wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20. In some embodiments, Reis selected from - C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), -C(O)(5-6 membered heteraryl), -C(O)O(3-6 membered carbocycle), -C(O)O(3-6 membered heterocycle), -C(O)O(C1-6alkylene)(3-6 membered heterocycle), -S(O)2(C1-6alkyl), a 5-6 membered heteroaryl, a 3-6 membered carbocycle, and C1-6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, and wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20. In some embodiments, Reis a 5-6 membered heteroaryl that is unsubstituted or substituted with one or more R12or R20. In some embodiments, Reis C1-6alkyl that is unsubstituted or substituted with one or more R20. In some embodiments, Reis -C(O)(3-6 membered carbocycle). In some embodiments, Reis selected from - C(O)(C1-6alkyl), -C(O)(3-6 membered carbocycle), and -C(O)O(C1-6alkyl), wherein any C1-6alkyl is unsubstituted or substituted with one or more R20, and any 3-6 membered carbocycle is unsubstituted or substituted with one or more R12or R20.

[0226] In some embodiments, for a compound according to any one of Formulas IIR1’, IIU1’, IIV1’, IIZ1, IIAA1, IIBB1, IICC1, IIDD1, IIEE1, IIFF1, IIGG1, IIHH1, or IIJJ1, X is C-CN. In some embodiments, Y is S. In some embodiments, R23is -N(R12)2. In some embodiments, one or more of R24, R25, and R26is a halogen (e.g., F).

[0227] In some embodiments, for a compound according to any one of Formulas II, II’, II’’, II’’-a, II-a, IIR’, IIU’, IIV’, IIZ, IIAA’, IIBB, IICC, IIDD, IIEE, IIFF, IIGG, IIHH, IIJJ, IIR1’, IIU1’, IIV1’, IIZ1’, IIAA1, IIBB1, IICC1, IIDD1, IIEE1, IIFF1, IIGG1, IIHH1, or IIJJ1, R2is H. In some embodiments, R2is selected from C1-6alkyl that is unsubstituted or is substituted with one or more R13. In some embodiments, R2is selected from C1-6alkyl that is unsubstituted. In some embodiments, R2is selected from C1-2alkyl that is unsubstituted or is substituted with one or more R13. In some embodiments, R2is selected from C1-2alkyl that is unsubstituted. In some embodiments, R2is methyl. In some embodiments, R2is ethyl.

[0228] In some embodiments, for a compound according to any one of Formulas II, II’, II’’, IIR’, IIU’, IIV’, IIZ, IIAA’, IIBB, IICC, IIDD, IIEE, IIFF, IIGG, IIHH, IIJJ, IIR1’, IIU1’, IIV1’, IIZ1’, IIAA1, IIBB1, IICC1, IIDD1, IIEE1, IIFF1, IIGG1, IIHH1, or IIJJ1, R1is selected from -OR8. In some embodiments, R8is a heterocycle or an alkylheterocycle, wherein any heterocycle contains 4-8 ring atoms and is substitutedwith one or more Raor Rb. In some embodiments, R8is a heterocycle that is unsubstituted or substituted with one or more Raor Rb. In some embodiments, R8is an alkylheterocycle that is unsubstituted or substituted with one or more Raor Rb. In some embodiments, R8is –CH2(heterocycle), where the heterocycle is unsubstituted or substituted with one or more Raor Rb. In some embodiments, a heterocycle or a heterocycle of an alkylheterocycle is a 4-6 membered monocyclic heterocycle having 1-2 heteroatoms independently selected from N, O, and S. In some embodiments, a heterocycle or a heterocycle of an alkylheterocycle is an 8-membered bicyclic heterocycle having 1-2 heteroatoms independently selected from N, O, and S. In some embodiments, a heterocycle or a heterocycle of an alkylheterocycle is substituted with one or more Raor Rb, wherein the one or more Raor Rbis a halogen (e.g., F). In some embodiments, a heterocycle or a heterocycle of an alkylheterocycle is substituted with one or more Raor Rb, wherein the one or more Raor Rbis a C1-6alkyl (e.g., methyl). In some embodiments, a heterocycle or a heterocycle of an alkylheterocycle is substituted with one or more Raor Rb, wherein the one or more Raor Rbis a -OR12(e.g., -OCH3). In some embodiments, a heterocycle or a heterocycle of an alkylheterocycle is substituted with one or more Raor Rb, wherein the one or more Raor Rbis a 3-6 membered carbocycle (e.g., a cyclopropane). In some embodiments, a heterocycle or a heterocycle of an alkylheterocycle is substituted with one or more Raor Rb, wherein the one or more Raor Rbis deuterium.

[0229] In some embodiments according to Formula IIAA’, R3is selected from:optionally further substituted with one or more R10.

[0230] In some embodiments according to Formula IIAA1’, R3is selected from:any of which is optionally further substituted with one or more R10.

[0231] In some embodiments, for a compound according to any one of Formulas II, II’, II’’, III, IIR’, IIU’, IIV’, IIZ, IIAA’, IIBB, IICC, IIDD, IIEE, IIFF, IIGG, IIHH, IIJJ, IIR1’, IIU1’, IIV1’, IIZ1’, IIAA1, IIBB1, IICC1, IIDD1, IIEE1, IIFF1, IIGG1, IIHH1, or IIJJ1, R1is selected from:, wherein Ra1, Ra2, Rb1, and Rb2are each independently selected from deuterium, halogen, C1-6alkyl, C2-6alkenyl, -OR12, and H, wherein Ra2and Rb2can optionally join together to form a 3-6 membered carbocycle, and wherein any C1-6alkyl, C2-6alkenyl, or 3-6 membered carbocycle is unsubstituted or is substituted with one or more R13. In some embodiments, Ra1and Rb1can optionally join together to form an exocyclic double bond that is unsubstituted or is substituted by halogen. In some embodiments, Ra1and Rb1are each independently selected from halogen, C1-6alkyl, -OR12, and H, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13. In some embodiments, Ra1is a halogen. In some embodiments, Ra1is F. In some embodiments, Ra1is C1-6alkyl that is unsubstituted or is substituted with one or more R13. In some embodiments, Ra1is methyl. In some embodiments, Ra1is -OC1-6alkyl. In some embodiments, Ra1is H. Insome embodiments, Rb1is H. In some embodiments, Rb1is a halogen. In some embodiments, Rb1is F. In some embodiments, Rb1is C1-6alkyl that is unsubstituted or is substituted with one or more R13. In some embodiments, Rb1is methyl. In some embodiments, each of Ra1and Rb1is F. In some embodiments, each of Ra1and Rb1is methyl. In some embodiments, each of Ra1and Rb1is H. In some embodiments, each of Ra2and Rb2is H. In some embodiments, one of Ra1and Rb1is deuterium. In some embodiments, each of Ra1and Rb1is deuterium. In some embodiments, Ra2and Rb2join together to form a 3-6 membered carbocycle, such as cyclopropyl. In some embodiments, R1is selected from:

[0232] In some embodiments, for a compound according to any one of Formulas II, II’, II’’, III, IIR’, IIU’, IIV’, IIZ, IIAA’, IIBB, IICC, IIDD, IIEE, IIFF, IIGG, IIHH, IIJJ, IIR1’, IIU1’, IIV1’, IIZ1’, IIAA1, IIBB1, IICC1, IIDD1, IIEE1, IIFF1, IIGG1, IIHH1, or IIJJ1, R1is selected from:, wherein Ra1, Ra2, Rb1, Rb2, Ra3, and Rb3are each independently selected from deuterium, halogen, C1-6alkyl, C2-6alkenyl,, eteroalkyl, -OR12, and H, wherein Ra2and Rb2can optionally join together toform a 3-6 membered carbocycle, and wherein any C1-6alkyl, C2-6alkenyl, or 3-6 membered carbocycle is unsubstituted or is substituted with one or more R13. In some embodiments, Ra1and Rb1can optionally join together to form an exocyclic double bond that is unsubstituted or is substituted by halogen. In some embodiments, Ra1and Rb1are each independently selected from halogen, C1-6alkyl, -OR12, and H, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13. In some embodiments, Ra1is a halogen. In some embodiments, Ra1is F. In some embodiments, Ra1is C1-6alkyl that is unsubstituted or is substituted with one or more R13. In some embodiments, Ra1is methyl. In some embodiments, Ra1is -OC1-6alkyl. In some embodiments, Ra1is H. In some embodiments, Rb1is H. In some embodiments, Rb1is a halogen. In some embodiments, Rb1is F. In some embodiments, Rb1is C1-6alkyl that is unsubstituted or is substituted with one or more R13. In some embodiments, Rb1is methyl. In some embodiments, each of Ra1and Rb1is F. In some embodiments, each of Ra1and Rb1is methyl. In some embodiments, each of Ra1and Rb1is H. In some embodiments, each of Ra2and Rb2is H. In some embodiments, one of Ra1and Rb1is deuterium. In some embodiments, each of Ra1and Rb1is deuterium. In some embodiments, Ra2and Rb2join together to form a 3-6 membered carbocycle, such as cyclopropyl. In some embodiments, R1is selected from:

[0233] In some embodiments, for a compound according to any one of Formulas II, II’, II’’, III, IIR’, IIU’, IIV’, IIZ, IIAA’, IIBB, IICC, IIDD, IIEE, IIFF, IIGG, IIHH, IIJJ, IIR1’, IIU1’, IIV1’, IIZ1’, IIAA1, IIBB1, IICC1, IIDD1, IIEE1, IIFF1, IIGG1, IIHH1, or IIJJ1, R1is selected from:^^wherein each Raand Rbis independently selected from halogen, C1-6alkyl, C2-6alkenyl, -OR12, and H; and each Rcis independently selected from C1-6alkyl and H, wherein an Raand Rbor Rcoptionally join together to form a 3-6 membered carbocycle or heterocycle, and wherein any C1-6alkyl, C2-6alkenyl, or 3-6 membered carbocycle or heterocycle is unsubstituted or is substituted with one or more R13. In some embodiments, each Rais H. In some embodiments, each Rbis H. In some embodiments, each Raand Rbis H. In some embodiments, at least one Raor Rbis selected from halogen, C1-6alkyl, C2-6alkenyl, and -OR12. In some embodiments, one Raor Rbis selected from halogen, C1-6alkyl, C2-6alkenyl, and -OR12, and the other Ras and Rbs are H. In some embodiments, one Rais C2-6alkenyl that is unsubstituted or substituted with one or more R13, and the Rbthat is connected to the same atom is absent. In some embodiments, one Rais C2alkenyl that is unsubstituted or substituted with one or more R13, and the Rbthat is connected to the same atom is absent. In some embodiments, one Rais C2-6alkenyl that is unsubstituted, and the Rbthat is connected to the same atom is absent. In some embodiments, one Rais C2alkenyl that is substituted with one or more R13, and the Rbthat is connected to the same atom is absent. In some embodiments, the Rclinked to the nitrogen atom is selected from C1-6alkyl. In some embodiments, the Rclinked to the nitrogen atom is selected from methyl. In some embodiments, the Rcthat is not linked to the nitrogen atom is H. In some embodiments, the Rcthat is not linked to the nitrogen atom is selected from C1-6alkyl. In some embodiments, the Rcthat is not linked to the nitrogen atom is methyl. In some embodiments, R1is selected fr ,, , , , , ,

[0234] In some embodiments, R1is selected from:

[0235] In some embodiments, for a compound according to any one of Formulas II, II’, II’’, III, IIR’, IIU’, IIV’, IIZ, IIAA’, IIBB, IICC, IIDD, IIEE, IIFF, IIGG, IIHH, IIJJ, IIR1’, IIU1’, IIV1’, IIZ1’, IIAA1, IIBB1, IICC1, IIDD1, IIEE1, IIFF1, IIGG1, IIHH1, or IIJJ1, R1is selected from, wherein: R30is N(R14)2or a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted or substituted with one or more R28; each R28is independently selected from C1-6alkyl and halogen; and each R29is independently selected from halogen and C1-6alkyl; and n is 0-2. In some embodiments, n is 0. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, at least one R29is halogen. In some embodiments, each R29is independently selected from halogen. In some embodiments, at least one R29is independently selected from C1-6alkyl. In some embodiments, each R29is independently selected from C1-6alkyl. In some embodiments, R30is N(R14)2. In some embodiments, R30is N(CH3)2. In some embodiments, R30is a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted or substituted with one or more R28. In some embodiments, R30is a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted. In some embodiments, R30is a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is substituted with one or more R28. In some embodiments, R1is selected from:, ,

[0236] In some embodiments, for a compound according to any one of Formulas II, II’, II’’, III, IIR’, IIU’, IIV’, IIZ, IIAA’, IIBB, IICC, IIDD, IIEE, IIFF, IIGG, IIHH, IIJJ, IIR1’, IIU1’, IIV1’, IIZ1’, IIAA1, IIBB1, IICC1, IIDD1, IIEE1, IIFF1, IIGG1, IIHH1, or IIJJ1, R1is selected from, wherein: R30is N(R14)2or a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted or substituted with one or more R28; R28is independently selected from C1-6alkyl, -OR12, C1-6heteroalkyl, wherein two heteroalkyl groups can optionally join together to form a 3-6 membered heterocycle that is unsubstituted or substituted with one or more R13and halogen; and eachR29is independently selected from halogen and C1-6alkyl; and n is 0-2. In some embodiments, n is 0. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, at least one R29is halogen. In some embodiments, each R29is independently selected from halogen. In some embodiments, at least one R29is independently selected from C1-6alkyl. In some embodiments, each R29is independently selected from C1-6alkyl. In some embodiments, R30is N(R14)2. In some embodiments, R30is N(CH3)2. In some embodiments, R30is a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted or substituted with one or more R28. In some embodiments, R30is a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted. In some embodiments, R30is a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is substituted with one or more R28. In some embodiments, R1 is selected from:

[0237] In some embodiments according to Formula II or III, R1is selected from:, , and .

[0238] In some embodiments according to Formula II’ or III, R1is selected from:

[0239] In some embodiments according to Formula II’’ or III, R1is selected from:, , , , and .

[0240] In some embodiments according to Formula IIAA’ or III, R1is selected from:a

[0241] In some embodiments according to Formula IIAA1’ or III, R1is selected from:

[0242] In some embodiments, for a compound according to any one of Formulas II, II’, II’’, III, IIR’, IIU’, IIV’, IIZ, IIAA’, IIBB, IICC, IIDD, IIEE, IIFF, IIGG, IIHH, IIJJ, IIR1’, IIU1’, IIV1’, IIZ1’, IIAA1, IIBB1, IICC1, IIDD1, IIEE1, IIFF1, IIGG1, IIHH1, or IIJJ1, R1is a heterocycle comprising one or more N atoms, wherein the heterocycle is unsubstituted or substituted with one or more R31, wherein each R31is selected from C1-6alkyl. In some embodiments, R1is an unsubstituted heterocycle comprising one or more N atoms. In some embodiments, R1is a heterocycle comprising one or more N atoms, wherein the heterocycle is substituted with one or more R31, wherein each R31is selected from C1-6alkyl. In some embodiments, R1is a 6-10 membered heterocycle comprising one or more N atoms, wherein the heterocycle is unsubstituted or substituted with one or more R31, wherein each R31is selected from C1-6alkyl. In some embodiments, R1is a monocyclic heterocycle containing one or more N atoms, wherein the heterocycle is unsubstituted or substituted with one or more R31. In some embodiments, R1is a piperazine that is unsubstituted or substituted with one or more R31. In some embodiments, R1is a piperazine that is substituted with one or more R31. In some embodiments, R1is a bicyclic heterocycle containing one or more N atoms, wherein the heterocycle is unsubstituted or substituted with one or more R31. In some embodiments, R1is a 10- membered bicyclic heterocycle containing one or more N atoms, wherein the heterocycle is unsubstituted or substituted with one or more R31. In some embodiments, R1is a 10-membered bicyclic heterocyclecontaining two N atoms, wherein the heterocycle is unsubstituted or substituted with one or more R31. In some embodiments, R1is selected from:

[0243] In some embodiments, for a compound according to any one of Formulas II, II’, II’’, III, IIR’, IIU’, IIV’, IIZ, IIAA’, IIBB, IICC, IIDD, IIEE, IIFF, IIGG, IIHH, IIJJ, IIR1’, IIU1’, IIV1’, IIZ1’, IIAA1, IIBB1, IICC1, IIDD1, IIEE1, IIFF1, IIGG1, IIHH1, or IIJJ1, R1is H.

[0244] In some embodiments, for a compound according to any one of Formulas II, II’, II’’, III, IIR’, IIU’, IIV’, IIZ, IIAA’, IIBB, IICC, IIDD, IIEE, IIFF, IIGG, IIHH, IIJJ, IIR1’, IIU1’, IIV1’, IIZ1’, IIAA1, IIBB1, IICC1, IIDD1, IIEE1, IIFF1, IIGG1, IIHH1, or IIJJ1, R5is a halogen (e.g., F or Cl). In some embodiments, R5is Cl. In some embodiments, R5is F. In some embodiments, R5is selected from C1-6alkyl that is unsubstituted or substituted with one or more R13. In some embodiments, R5is selected from C1-6alkyl that is unsubstituted. In some embodiments, R5is selected from C1-6alkyl that is substituted with one or more R13. In some embodiments, R5is selected from -CF2H, -CF3, -CH2CN, and -CH2CH3. In some embodiments, R5is -CF3. In some embodiments, R5is -OC1-6alkyl that is unsubstituted or substituted with one or more R13. In some embodiments, R5is -OC1-6alkyl that is substituted with one or more R13. In some embodiments, R5is -OCH3 or -OCF3. In some embodiments, R5is -CN. In some embodiments, R5is H. In some embodiments, R5is 5- to 6-membered heteroaryl. In some such embodiments, R5is furanyl.

[0245] In some embodiments, for a compound according to any one of Formulas II, II’, II’’, III, IIR’, IIU’, IIV’, IIZ, IIAA’, IIBB, IICC, IIDD, IIEE, IIFF, IIGG, IIHH, IIJJ, IIR1’, IIU1’, IIV1’, IIZ1’, IIAA1, IIBB1, IICC1, IIDD1, IIEE1, IIFF1, IIGG1, IIHH1, or IIJJ1, R7is F. In some embodiments, R7is Cl.

[0246] In some embodiments, for a compound according to any one of Formulas II, II’, II’’, III, II’’-a, II- a, IIR’, IIU’, IIV’, IIZ, IIAA’, IIBB, IICC, IIDD, IIEE, IIFF, IIGG, IIHH, IIJJ, IIR1’, IIU1’, IIV1’, IIZ1’, IIAA1, IIBB1, IICC1, IIDD1, IIEE1, IIFF1, IIGG1, IIHH1, or IIJJ1, the compound is not a compound included in Table 1, or a salt, ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. Table 1.

[0247] In another aspect, the present disclosure provides a compound represented by Formula III:or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein: Z is N or C-R5; R1is selected from Heterocycle comprising one or more N atoms, wherein the heterocycle is unsubstituted or substituted with one or more R31; R2is selected from H, C1-6alkyl, and a 3-6 membered carbocycle, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13and is optionally deuterated; R3is selected from 3- to 12-membered cycloalkyl optionally fused to a 5- or 6-membered aryl, heterocycle, or heteroaryl, a 4-10 membered heterocycle, or -(C1-6alkylenyl)(5-6 membered heteroaryl), wherein any cycloalkyl, aryl, heterocycle, or heteroaryl is unsubstituted or substituted with one or more R10;or wherein R2and R3optionally come together to form a 7-9 membered heterocyle, which is optionally substituted with one or more R10; R4is H, -OR12,or -N(R14)2; R5is selected from halogen, -CN, 5- to 6-membered heteroaryl, -OC1-6alkyl, C1-6alkyl, and H, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R6is a phenyl, naphthyl, or bicyclic heteroaryl, wherein the phenyl, naphthyl, or bicyclic heteroaryl is substituted with one or more R15; R7is selected from halogen or H; R8is selected from a heterocycle and an alkylheterocycle, wherein any heterocycle comprises 4-9 ring atoms and is unsubstituted or is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-6alkyl, and C1-6alkyl is optionally deuterated (e.g. -CH2- or -CD2-); each R10is independently selected from deuterium, -OR12, =O, =S, -CN, -N=S(=O)Me2, -C(O)(C1- 6alkylene)CN, -C(O)(C1-6alkylene)OH, -C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), - C(O)N(R14)2, -C(O)OR14, -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), -C(O)(5-6 membered heteroaryl), -C(O)O(3-6 membered carbocycle), - C(O)O(3-6 membered heterocycle), -C(O)O(5-6 membered heteroaryl),-C(O)O(C1-6alkylene)(3-6 membered heterocycle), -S(O)2(C1-6alkyl), -C(S)(C1-6alkyl), -C(S)O(C1- 6alkyl), -C(S)N(C1-6alkyl)2, -C(=N-OR12)(C1-6alkyl), -C(O)N(R12)OR12,^halogen, phenyl, a 5-6 membered heteroaryl, a 3-6 membered carbocycle, a 3-6 membered heterocycle, C2-6 alkenyl, and C1-6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20, and wherein two R10s optionally join together to form, together with the atom(s) to which they are attached, a 3-6 membered carbocycle or heterocycle; each R12is independently selected from C1-6alkyl, C2-6 alkenyl, and H, wherein any C1-6alkyl or C2- 6 alkenyl is unsubstituted or substituted with one or more R13; each R13is independently selected from -OR14, -OC(O)R14, -CN, -N(R14)2, and halogen; each R14is independently selected from a 3-6 membered carbocycle, a 3-8 membered heterocycle, C1-6alkyl, -OR12, C2-6 alkenyl, and H, wherein any C1-6alkyl is optionally deuterated; each R15is independently selected from deuterium, -OH, halogen, -N(R12)2, -CN, C2-6 alkynyl, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13;each R20is independently selected from -OH, -OC1-6alkyl, -OC1-6haloalkyl, =O, -CN, -NH2, -NHC1- 6alkyl, -C(O)(C1-6alkyl), -C(O)OR12, -C(O)N(R12)2, -S(O)2R12, a 3-6 membered carbocycle, phenyl, and halogen; each R28is independently selected from C1-6alkyl, -OR12, C1-6heteroalkyl, wherein two heteroalkyl groups can optionally join together to form a 3-6 membered heterocycle that is unsubstituted or substituted with one or more R13and halogen; each R29is independently selected from halogen and C1-6alkyl; R30is N(R12)2 or a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted or substituted with one or more R28; each R31is selected from C1-6alkyl; n is 0-2; and Raand Rbare each independently selected from deuterium, halogen, C1-6alkyl, C2-6 alkenyl,,, -C1-6heteroalkyl, a 3-6 membered carbocycle, -OR12, and H, wherein an Raand Rboptionally join together to form a 3-6 membered carbocycle or heterocycle, and wherein any C1-6alkyl, C2-6 alkenyl, or 3-6 membered carbocycle or heterocycle is unsubstituted or is substituted with one or more R13.

[0248] In some embodiments, the present disclosure provides a compound of Formula III, or a salt (e.g., a pharmaceutically acceptable salt) thereof.

[0249] As described herein, for a compound according to Formula II or III, Z is N or C-R5.

[0250] In some embodiments of Formula II or III, Z is N.

[0251] In some embodiments of Formula II or III, Z is C-R5. In some embodiments,of Formula II or III, Z is C-R5, wherein R5is halogen. In some embodiments of Formula II or III, Z is C-R5, wherein R5is Cl. In some embodiments of Formula II or III, Z is C-R5, wherein R5is F. In some embodiments of Formula II or III, Z is C-R5, wherein R5is C1-6alkyl, wherein C1-6alkyl unsubstituted or substituted with one or more R13. In some embodiments of Formula II or III, Z is C-R5, wherein R5is C1-2alkyl, wherein C1-2 alkyl is unsubstituted or substituted with one or more R13. In some embodiments,of Formula II or III, Z is C-R5, wherein R5is CH3. In some embodiments of Formula II or III, Z is C-R5, wherein R5is CF3. In some embodiments of Formula II or III, Z is C-R5, wherein R5is H. In some embodiments of Formula II or III, Z is C-R5, wherein R5is CN.

[0252] In some embodiments of Formula II or III, Z is N or C-R5, wherein R5is selected from halogen, C1-2alkyl, H, and CN, wherein C1-2 alkyl is unsubstituted or substituted with one or more R13.

[0253] In some embodiments of Formula II or III, Z is N or C-R5, wherein R5is selected from Cl, F, CH3, CF3, H, and CN.

[0254] As described herein, for a compound of Formula II or III, R1is selected from H, -OR8,, and a heterocycle comprising one or more N atoms, wherein the heterocycle is unsubstituted or substituted with one or more R31.

[0255] In some embodiments of Formula II or III, R1is H.

[0256] In some embodiments of Formula II or III, R1is -OR8. In some embodiments of Formula II or III, R1is -O(alkylheterocycle), wherein any heterocycle comprises 4-9 ring atoms and is unsubstituted or is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-6alkyl, and C1-6alkyl is optionally deuterated (e.g. -CH2- or -CD2-). In some embodiments of Formula II or III, R1is -O(alkylheterocycle), wherein any heterocycle comprises 4-9 ring atoms and is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-6alkyl, and C1-6alkyl is optionally deuterated (e.g. -CH2- or -CD2-). In some embodiments of Formula II or III, R1is - O(alkylheterocycle), wherein any heterocycle comprises 4-9 ring atoms and is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-2 alkyl, and C1-2 alkyl is optionally deuterated (e.g. -CH2- or -CD2-). In some embodiments of Formula II or III, R1is - O(alkylheterocycle), wherein any heterocycle comprises 4-9 ring atoms and is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-2alkyl. In some embodiments of Formula II or III, R1is -O(alkylheterocycle), wherein any heterocycle comprises 4-9 ring atoms and is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-2 alkyl, and C1-2 alkyl is deuterated (e.g. -CD2-).

[0257] In some embodiments of Formula II or III, R1is selected from:

[0258] In some embodiments of Formula II or III, R1is selected from:

[0259] In some embodiments of Formula II or III, R1is

[0260] In some embodiments of Formula II or III, R1is a heterocycle comprising one or more N atoms, wherein the heterocycle is unsubstituted or substituted with one or more R31.

[0261] As described herein, for a compound of Formula II or III, R2is selected from H, C1-6alkyl, and a 3- 6 membered carbocycle, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13and is optionally deuterated. In some embodiments, R5is selected from halogen. In some embodiments, R5is Cl. In some embodiments, R5is selected from C1-6alkyl that is unsubstituted or substituted with one or more R13. In some embodiments, R5is selected from C1-6alkyl that is substituted with one or more halogen. In some embodiments, R5is CF2H or CF3. In some embodiments, R5is CF3.

[0262] In some embodiments of Formula II or III, R2is H.

[0263] In some embodiments of Formula II or III, R2is C1-6alkyl, which is unsubstituted or is substituted with one or more R13and is optionally deuterated. In some embodiments of Formula II or III, R2is C1-2alkyl, which is unsubstituted or is substituted with one or more R13and is optionally deuterated. In someembodiments of Formula II or III, R2is C1-6alkyl. In some embodiments of Formula II or III, R2is C1- 6alkyl and is deuterated. In some embodiments of Formula II or III, R2is C1-2alkyl. In some embodiments of Formula II or III, R2is C1-2alkyl and is deuterated. In some embodiments of Formula II or III, R2is methyl. In some embodiments of Formula II or III, R2is ethyl. In some embodiments of Formula II or III, R2is propyl. In some embodiments of Formula II or III, R2is deuterated ethyl.

[0264] In some embodiments of Formula II or III, R2is a 3-6 membered carbocycle.

[0265] In some embodiments of Formula II or III, R2is selected from C1-6alkyl, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13and is optionally deuterated. In some embodiments, for a compound according to Formula II or III, R2is ethyl (e.g., -CH2CH3).

[0266] In some embodimentsof Formula II or III, R2is selected from methyl ethyl, propyl, and deuterated ethyl.

[0267] As described herein, for a compound of Formula II or III, R3is selected from 3- to 12-membered cycloalkyl optionally fused to a 5- or 6-membered aryl, heterocycle, or heteroaryl, a 4-10 membered heterocycle, or -(C1-6alkylenyl)(5-6 membered heteroaryl), wherein any cycloalkyl, aryl, heterocycle, or heteroaryl is unsubstituted or substituted with one or more R10.

[0268] In some embodiments of Formula II or III, R3is 3- to 12-membered cycloalkyl optionally fused to a 5- or 6-membered aryl, heterocycle, or heteroaryl, wherein any cycloalkyl, aryl, heterocycle, or heteroaryl is unsubstituted or substituted with one or more R10. In some embodiments of Formula II or III, R3is 3- to 6-membered cycloalkyl optionally fused to a 5- or 6-membered aryl, heterocycle, or heteroaryl, wherein any cycloalkyl, aryl, heterocycle, or heteroaryl is unsubstituted or substituted with one or more R10. In some embodimentsof Formula II or III, R3is 3- to 12-membered cycloalkyl optionally fused to a 5- or 6- membered aryl, which is unsubstituted or substituted with one or more R10. In some embodimentsof Formula II or III, R3is 3- to 12-membered cycloalkyl optionally fused to a 5- or 6-membered heterocycle, which is unsubstituted or substituted with one or more R10. In some embodiments of Formula II or III, R3is 3- to 12-membered cycloalkyl optionally fused to a 5- or 6-membered heteroaryl, which is unsubstituted or substituted with one or more R10. In some embodiments, R2is ethyl.

[0269] In some embodiments of Formula II or III, R3is a 4-10 membered heterocycle, which is unsubstituted or substituted with one or more R10.

[0270] In some embodiments of Formula II or III, R3is -(C1-6alkylenyl)(5-6 membered heteroaryl), wherein a heteroaryl is unsubstituted or substituted with one or more R10.

[0271] In some embodiments of Formula II or III, R3is selected from:

[0272] In some embodiments of Formula II or III, R3is selected from:

[0273] In some embodiments, for a compound according to Formula II.

[0274] In some embodiments, Relected from halogen, -OR12, and-CN. R10is selected from F, -CN, and -OCH3.

[0275] In some embodiments, for a compound according to Formula IIs.

[0276] In some embodiments, Rselected fromhalogen, -OR12, -CN, and C1-6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20. In some embodiments, R10is selected from -CH3, -CF2H, -CH2F, -F, - OCH3, and -CN.

[0277] In some embodiments, for a compound according to Formula II or III,Insome embodiments,some embodiments, R

[0278] As described herein, for a compound of Formula II or III, R2and R3can optionally come together to form a 7-9 membered heterocycle, which is optionally substituted with one or more R10

[0279] In some embodimentsof Formula II or III, R2and R3optionally come together to form a 7-9 membered heterocycle, which is optionally substituted with -C(O)(C1-6alkyl). In some embodimentsof Formula II or III, R2and R3optionally come together to form.

[0280] As described herein, for a compound of Formula II or III, R4is H, -OR12,or -N(R14)2.

[0281] In some embodiments of Formula II or III, R4is H.

[0282] In some embodiments of Formula II or III, R4is -OR12. In some embodiments of Formula II or III, R4is -O(C1-6alkyl). In some embodiments, for a compound according to Formula II or III, R4is -O(C1-2 alkyl). In some embodiments of Formula II or III, R4is -OCH3.

[0283] In some embodiments of Formula II or III, R4is -N(R14)2. In some embodiments of Formula II or III, R4is -N(C1-6alkyl)2. In some embodiments of Formula II or III, R4is -N(C1-2alkyl)2. In some embodiments of Formula II or III, R4is -N(CH3)2.

[0284] In some embodimentsof Formula II or III, R4is H, -OCH3, or -N(CH3)2.

[0285] As described herein, for a compound of Formula II or III, R5is selected from halogen, -CN, 5- to 6-membered heteroaryl, -OC1-6alkyl, C1-6alkyl, and H, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13.

[0286] In some embodimentsof Formula II or III, R5is halogen. In some embodimentsof Formula II or III, R5is fluoro. In some embodimentsof Formula II or III, R5is chloro.

[0287] In some embodimentsof Formula II or III, R5is -CN.

[0288] In some embodimentsof Formula II or III, R5is 5- to 6-membered heteroaryl.

[0289] In some embodimentsof Formula II or III, R5is -OC1-6alkyl.

[0290] In some embodimentsof Formula II or III, R5is C1-6alkyl, which is unsubstituted or substituted with one or more R13. In some embodimentsof Formula II or III, R5is C1-2alkyl, which is unsubstituted or substituted with one or more R13. In some embodimentsof Formula II or III, R5is -CH3. In some embodimentsof Formula II or III, R5is -CF3.

[0291] In some embodimentsof Formula II or III, R5is H.

[0292] In some embodimentsof Formula II or III, R5is selected from halogen, -CN, C1-2 alkyl, and H, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13.

[0293] In some embodimentsof Formula II or III, R5is selected from fluoro, chloro, -CN, -CH3, -CF3, and H.

[0294] As described herein, for a compound of Formula II or III, R6is a phenyl, naphthyl, or bicyclic heteroaryl, wherein the phenyl, naphthyl, or bicyclic heteroaryl is substituted with one or more R15. In some embodimentsof Formula II or III, R6is a phenyl or a bicyclic heteroaryl, wherein the phenyl or bicyclic heteroaryl is substituted with one or more R15.

[0295] In some embodimentsof Formula II or III, R6is a phenyl, wherein the phenyl is substituted with one or more R15.

[0296] In some embodimentsof Formula II or III, R6is a naphthyl, wherein the naphthyl is substituted with one or more R15.

[0297] In some embodimentsof Formula II or III, R6is a bicyclic heteroaryl, wherein the bicyclic heteroaryl is substituted with one or more R15.

[0298] In some embodimentsof Formula II or III, R6is selected from:

[0299] In some embodimentsof Formula II or III, R6is selected from:

[0300] As described herein, for a compound of Formula II or III, R7is selected from halogen or H.

[0301] In some embodiments of Formula II or III, R7is H.

[0302] In some embodiments of Formula II or III, R7is halogen. In some embodiments of Formula II or III, R7is fluoro.

[0303] In some embodiments of Formula II or III, R7is H or fluoro.

[0304] As described herein, for a compound of Formula II or III, R8is selected from a heterocycle and an alkylheterocycle, wherein any heterocycle comprises 4-9 ring atoms and is unsubstituted or is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-6alkyl, and C1-6alkyl is optionally deuterated (e.g. -CH2- or -CD2-). In some embodiments of Formula II or III, R8is selected from a heterocycle and an alkylheterocycle, wherein any heterocycle comprises 4-9 ring atoms and is unsubstituted or is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-6alkyl.

[0305] In some embodiments of Formula II or III, R8is a heterocycle, wherein any heterocycle comprises 4-9 ring atoms and is substituted with one or more Raor Rb.

[0306] In some embodiments of Formula II or III, R8is an alkylheterocycle, wherein any heterocycle comprises 4-9 ring atoms and is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-6alkyl, and C1-6alkyl is optionally deuterated (e.g. -CH2- or -CD2-). In some embodiments of Formula II or III, R8is an alkylheterocycle wherein any heterocycle comprises 4-9 ring atoms and is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-2 alkyl, and C1-2 alkyl is optionally deuterated (e.g. -CH2- or -CD2-). In some embodiments of Formula II or III, R8is an alkylheterocycle wherein any heterocycle comprises 4-9 ring atoms and is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-2alkyl. In some embodiments of Formula II or III, R8is an alkylheterocycle wherein any heterocycle comprises 4-9 ring atoms and is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-2 alkyl, and C1-2 alkyl is deuterated (e.g. -CD2-).

[0307] As described herein, for a compound of Formula II or III, each R10is independently selected from deuterium, -OR12, =O, =S, -CN, -N=S(=O)Me2, -C(O)(C1-6alkylene)CN, -C(O)(C1-6alkylene)OH, - C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), -C(O)N(R14)2, -C(O)OR14, -C(O)(3-6 membered carbocycle), -C(O)(3- 8 membered heterocycle), -C(O)(5-6 membered heteroaryl), -C(O)O(3-6 membered carbocycle), - C(O)O(3-6 membered heterocycle), -C(O)O(5-6 membered heteroaryl),-C(O)O(C1-6alkylene)(3-6 membered heterocycle), -S(O)2(C1-6alkyl), -C(S)(C1-6alkyl), -C(S)O(C1-6alkyl), -C(S)N(C1-6alkyl)2, -C(=N-OR12)(C1-6alkyl), -C(O)N(R12)OR12, halogen, phenyl, a 5-6 membered heteroaryl, a 3-6 membered carbocycle, a 3-6 membered heterocycle, C2-6 alkenyl, and C1-6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20, and wherein two R10s optionally join together to form, together with the atom(s) to which they are attached, a 3-6 membered carbocycle or heterocycle. In some embodiments of Formula II or III, each R10is independently selected from deuterium, -OR12, =O, =S, -CN, -N=S(=O)Me2, -C(O)(C1- 6alkylene)CN, -C(O)(C1-6alkylene)OH, -C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), -C(O)N(R14)2, -C(O)OR14, - C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), -C(O)(5-6 membered heteroaryl), - C(O)O(3-6 membered carbocycle), -C(O)O(3-6 membered heterocycle), -C(O)O(5-6 membered heteroaryl),-C(O)O(C1-6alkylene)(3-6 membered heterocycle), -S(O)2(C1-6alkyl), -C(S)(C1-6alkyl), - C(S)O(C1-6alkyl), -C(S)N(C1-6alkyl)2, -C(=N-OR12)(C1-6alkyl), -C(O)N(R12)OR12, halogen, a 5-6 membered heteroaryl, a 3-6 membered carbocycle, a 3-6 membered heterocycle, and C1-6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20, and wherein two R10s optionally join together to form, together with the atom(s) to which they are attached, a 3-6 membered carbocycle or heterocycle.

[0308] In some embodiments of Formula II or III, each R10is independently -OR12. In some embodiments of Formula II or III, each R10is independently -O(C1-6alkyl). In some embodiments of Formula II or III, each R10is independently -O(C1-2 alkyl). In some embodiments of Formula II or III, each R10is independently -OCH3.

[0309] In some embodiments of Formula II or III, each R10is independently =O.

[0310] In some embodiments of Formula II or III, each R10is independently =S.

[0311] In some embodiments of Formula II or III, each R10is independently -CN.

[0312] In some embodiments of Formula II or III, each R10is independently -C(O)O(C1-6alkyl), wherein C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20. In some embodiments, for a compound according to Formula II or III, each R10is independently -C(O)O(C1-2alkyl), wherein C1-2alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20. In some embodiments of Formula II or III, each R10is independently -C(O)OCH3. In some embodiments of Formula II or III, each R10is independently -C(O)O(CD3).

[0313] In some embodiments of Formula II or III, each R10is independently halogen. In some embodiments of Formula II or III, each R10is independently fluoro. In some embodiments of Formula II or III, each R10is independently chloro.

[0314] In some embodiments of Formula II or III, each R10is independently phenyl.

[0315] In some embodiments of Formula II or III, each R10is independently a 5-6 membered heteroaryl. In some embodiments of Formula II or III, each R10is independently.

[0316] In some embodiments of Formula II or III, each R10is independently a 3-6 membered carbocycle. In some embodiments of Formula II or III, each R10is independently cyclopropyl or cyclobutyl.

[0317] In some embodiments of Formula II or III, each R10is independently C2-6 alkenyl. In some embodiments of Formula II or III, each R10is independently C2alkenyl.

[0318] In some embodiments of Formula II or III, each R10is independently C1-6alkyl, which is optionally deuterated and is unsubstituted or substituted with one or more R20. In some embodiments of Formula II or III, each R10is independently C1-2alkyl, which is optionally deuterated and is unsubstituted or substituted with one or more R20. In some embodiments of Formula II or III, each R10is independently C1-2alkyl, which is substituted with one or more R20. In some embodiments of Formula II or III, each R10is independently methyl. In some embodiments of Formula II or III, each R10is independently ethyl. In some embodiments of Formula II or III, each R10is independently -CH2OH. In some embodiments of Formula II or III, each R10is independently -CH2OCH3. In some embodiments of Formula II or III, each R10is independently - CHF2. In some embodiments of Formula II or III, each R10is independently -CH2F.

[0319] In some embodiments of Formula II or III, two R10s optionally join together to form, together with the atom(s) to which they are attached, a 3-6 membered carbocycle. In some embodiments of Formula II or III, two R10s join together to form, together with the atom to which they are attached, a cyclopropyl ring.

[0320] In some embodiments of Formula II or III, each R10is independently selected from -OR12, =O, =S, -CN, -C(O)O(C1-6alkyl), halogen, phenyl, a 5-6 membered heteroaryl, a 3-6 membered carbocycle, C2-6alkenyl, and C1-6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, and wherein two R10s optionally join together to form, together with the atom(s) to which they are attached, a 3-6 membered carbocycle or heterocycle. In some embodiments of Formula II or III, each R10is independently selected from -OR12, =O, =S, -CN, -C(O)O(C1-6alkyl), halogen, a 5-6 membered heteroaryl, a 3-6 membered carbocycle, and C1-6alkyl, wherein any C1-6alkyl is optionallydeuterated and is unsubstituted or substituted with one or more R20, and wherein two R10s optionally join together to form, together with the atom(s) to which they are attached, a 3-6 membered carbocycle or heterocycle.

[0321] In some embodiments of Formula II or III, each R10is independently selected from -OCH3, =O, =S, -CN, -C(O)OCH3, -C(O)OCD3, fluoro, chloro, phenyl,, , , cyclopropyl, cyclobutyl, C2 alkenyl, methyl, ethyl, -CH2OH, -CH2OCH3, -CHF2, -CH2F, wherein two R10s optionally join together to form, together with the atom(s) to which they are attached, a cyclopropyl ring. In some embodiments, for a compound according to Formula II or III, each R10is independently selected from -OCH3, =O, =S, -CN, -C(O)OCH3, -C(O)OCD3, fluoro, chloro,cyclopropyl, cyclobutyl, methyl, ethyl, -CH2OH, -CH2OCH3, -CHF2, -CH2F, wherein two R10s optionally join together to form, together with the atom(s) to which they are attached, a cyclopropyl ring.

[0322] As described herein, for a compound of Formula II or III, each R12is independently selected from C1-6alkyl, C2-6alkenyl, and H, wherein any C1-6alkyl or C2-6alkenyl is unsubstituted or substituted with one or more R13.

[0323] In some embodiments of Formula II or III, each R12is independently C1-6alkyl, which is unsubstituted or substituted with one or more R13. In some embodiments of Formula II or III, each R12is independently C1-2alkyl, which is unsubstituted or substituted with one or more R13. In some embodiments of Formula II or III, each R12is independently methyl.

[0324] In some embodiments of Formula II or III, each R12is independently C2-6alkenyl, which is unsubstituted or substituted with one or more R13.

[0325] In some embodiments of Formula II or III, each R12is independently H.

[0326] In some embodiments of Formula II or III, each R12is independently selected from C1-6alkyl and H.

[0327] In some embodiments of Formula II or III, each R12is independently selected from methyl and H.

[0328] As described herein, for a compound of Formula II or III, each R13is independently selected from -OR14, -OC(O)R14, -CN, -N(R14)2, and halogen. In some embodiments, of Formula II or III, each R13is independently selected from -OR14, -CN, -N(R14)2, and halogen.

[0329] In some embodiments of Formula II or III, each R13is independently selected from -OR14.

[0330] In some embodiments of Formula II or III, each R13is independently selected from -OC(O)R14. In some embodiments of Formula II or III, each R13is independently -OC(O)(3-8 membered heterocycle).

[0331] In some embodiments of Formula II or III, each R13is independently selected from -CN.

[0332] In some embodiments of Formula II or III, each R13is independently selected from -N(R14)2.

[0333] In some embodiments of Formula II or III, each R13is independently selected from halogen. In some embodiments of Formula II or III, each R13is fluoro.

[0334] In some embodiments of Formula II or III, each R13is independently selected from -OC(O)R14and halogen. In some embodiments of Formula II or III, each R13is independently selected from –OC(O)(3-8 membered heterocycle) and fluoro.

[0335] In some embodiments of Formula II or III, each R13is independently selected from -OC(O)R14, - CN, and halogen. In some embodiments of Formula II or III, each R13is independently selected from – OC(O)(3-8 membered heterocycle), CN, and fluoro.

[0336] As described herein, each R14is independently selected from a 3-6 membered carbocycle, a 3-8 membered heterocycle, C1-6alkyl, -OR12, C2-6alkenyl, and H, wherein any C1-6alkyl is optionally deuterated. In some embodiments of Formula II or III, each R14is independently selected from a 3-6 membered carbocycle, a 3-6 membered heterocycle, C1-6alkyl, -OR12, C2-6alkenyl, and H, wherein any C1-6alkyl is optionally deuterated.

[0337] In some embodiments of Formula II or III, each R14is a 3-6 membered carbocycle.

[0338] In some embodiments of Formula II or III, each R14is a 3-8 membered heterocycle. In some embodiments of Formula II or III, each R14is^. In some embodiments ofFormula II or III, each R14is. some embodiments of Formula II or III, each R14is a 3-6 membered heterocycle.

[0339] In some embodiments of Formula II or III, each R14is C1-6alkyl, which is optionally deuterated. In some embodiments of Formula II or III, each R14is C1-2alkyl, which is optionally deuterated. In some embodiments of Formula II or III, each R14is C1-2 alkyl. In some embodiments of Formula II or III, each R14is methyl.

[0340] In some embodiments of Formula II or III, each R14is -OR12.

[0341] In some embodiments of Formula II or III, each R14is C2-6alkenyl.

[0342] In some embodiments of Formula II or III, each R14is H.

[0343] In some embodiments of Formula II or III, each R14is independently selected from a 3-8 membered heterocycle and C1-2 alkyl. In some embodiments of Formula II or III, each R14is independently selected from a 3-8 membered heterocycle, H, and C1-2 alkyl. In some embodiments of Formula II or III, each R14is independently selected from a 3-6 membered heterocycle and C1-2 alkyl. In some embodiments of Formula II or III, each R14is independently selected from a 3-6 membered heterocycle, H, and C1-2alkyl.

[0344] In some embodiments, for a compound according to Formula II or III, each R14is independentlyselected from^, , methyl, and H. In some embodiments of Formula II or III, each R14is ^ independently selected from^, H, and methyl. In some embodiments of Formula II or III, each R14is independently selected from^methyl. In some embodiments of Formula II or III, each R14is independently selected from^and methyl.

[0345] As described herein, for a compound of Formula II or III, each R15is independently selected from deuterium, -OH, halogen, -N(R12)2, -CN, C2a-6lkynyl, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13. In some embodiments of Formula II or III, each R15is independently selected from deuterium, halogen, -N(R12)2, -CN, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13.

[0346] In some embodiments of Formula II or III, each R15is independently deuterium.

[0347] In some embodiments of Formula II or III, each R15is independently -OH.

[0348] In some embodiments of Formula II or III, each R15is independently halogen. In some embodiments of Formula II or III, each R15is independently fluoro. In some embodiments of Formula II or III, each R15is independently chloro.

[0349] In some embodiments of Formula II or III, each R15is independently -N(R12)2. In some embodiments of Formula II or III, each R15is independently -NH2.

[0350] In some embodiments of Formula II or III, each R15is independently -CN.

[0351] In some embodiments of Formula II or III, each R15is independently C2-6 alkynyl. In some embodiments of Formula II or III, each R15is independently C2 alkynyl.

[0352] In some embodiments of Formula II or III, each R15is independently C1-6alkyl, which is unsubstituted or substituted with one or more R13. In some embodiments of Formula II or III, each R15is independently C1-2alkyl, which is unsubstituted or substituted with one or more R13. In some embodiments of Formula II or III, each R15is independently methyl. In some embodiments of Formula II or III, each R15is independently -CF3.

[0353] In some embodiments of Formula II or III, each R15is independently selected from -OH, halogen, -N(R12)2, -CN, C2-6 alkynyl, and C1-2alkyl, wherein any C1-2alkyl is unsubstituted or substituted with one or more R13. In some embodiments ofFormula II or III, each R15is independently selected from halogen, - N(R12)2, -CN, and C1-2alkyl, wherein any C1-2alkyl is unsubstituted or substituted with one or more R13.

[0354] In some embodiments of Formula II or III, each R15is independently selected from -OH, fluoro, chloro, -NH2, -CN, C2 alkynyl, methyl, and -CF3. In some embodiments of Formula II or III, each R15is independently selected from fluoro, chloro, -NH2, -CN, methyl, and -CF3.

[0355] As described herein, for a compound of Formula II or III, each R20is independently selected from -OH, -OC1-6alkyl, -OC1-6haloalkyl, =O, -CN, -NH2, -NHC1-6alkyl, -C(O)(C1-6alkyl), -C(O)OR12, - C(O)N(R12)2, -S(O)2R12, a 3-6 membered carbocycle, phenyl, and halogen.

[0356] In some embodiments of Formula II or III, each R20is independently halogen. In some embodiments of Formula II or III, each R20is independently fluoro.

[0357] In some embodiments of Formula II or III, each R20is independently -OH.

[0358] In some embodiments of Formula II or III, each R20is independently -OC1-6alkyl. In some embodiments of Formula II or III, each R20is independently -OC1-2alkyl. In some embodiments of Formula II or III, each R20is independently -OCH3.

[0359] In some embodiments of Formula II or III, each R20is independently selected from -OH, -OCH3, and fluoro.

[0360] In some embodiments of Formula II or III, each R20is independently selected from -OH, -OC1- 6alkyl, and halogen.

[0361] As described herein, for a compound of Formula II or III, each R31is selected from C1-6alkyl. In some embodiments of Formula II or III, each R31is selected from C1-2 alkyl.

[0362] As described herein, for a compound of Formula II or III, n is 0-2. In some embodiments n is 0-1. In some embodiments n is 1-2. In some embodiments n is 0 or 2.

[0363] In some embodiments n is 0.

[0364] In some embodiments n is 1.

[0365] In some embodiments n is 2.

[0366] As described herein, for a compound of Formula II or III, Raand Rbare each independently selected from deuterium, halogen, C1-6alkyl,C2-6alkenyl,heteroalkyl, a 3-6 membered carbocycle, -OR12, and H, wherein an Raand Rboptionally join together to form a 3-6 membered carbocycle or heterocycle, and wherein any C1-6alkyl,C2-6alkenyl, or 3-6 membered carbocycle or heterocycle is unsubstituted or is substituted with one or more R13. In some embodiments, of Formula II or III, Raand Rbare each independently selected from deuterium, halogen, C1-6alkyl, C2-6alkenyl,, -C1-6heteroalkyl, a 3-6 membered carbocycle, -OR12, and H, wherein an Raand Rboptionally join together to form a 3-6 membered carbocycle or heterocycle, and wherein any C1-6alkyl, C2-6alkenyl, or 3-6 membered carbocycle or heterocycle is unsubstituted or is substituted with one or more R13.

[0367] In some embodiments of Formula II or III, Raand Rbare each independently deuterium.

[0368] In some embodiments of Formula II or III, Raand Rbare each independently halogen. In some embodiments of Formula II or III, Raand Rbare each independently fluoro.

[0369] In some embodiments of Formula II or III, Raand Rbare each independently C1-6alkyl, which is unsubstituted or is substituted with one or more R13. In some embodiments of Formula II or III, Raand Rbare each independently C1-2 alkyl, which is unsubstituted or is substituted with one or more R13. In some embodiments, of Formula II or III, Raand Rbare each independently C1-2alkyl, which is substituted with - OC(O)R14. In some embodiments of Formula II or III, Raand Rbare each independently C1-2 alkyl, which is substituted with -OC(O)(3-8 membered heterocycle). In some embodiments of Formula II or III, Raand Rbare each independently -CF2H. In some embodiments of Formula II or III, Raand Rbare each independently methyl.

[0370] In some embodiments of Formula II or III, Raand Rbare each independentlyC2-6alkenyl, which is unsubstituted or is substituted with one or more R13.

[0371] In some embodiments of Formula II or III, Raand Rbare each independently

[0372] In some embodiments of Formula II or III, Raand Rbare each independently.

[0373] In some embodiments, of Formula II or III, Raand Rbare each independently-C1-6heteroalkyl.

[0374] In some embodiments of Formula II or III, Raand Rbare each independently a 3-6 membered carbocycle.

[0375] In some embodiments of Formula II or III, Raand Rbare each independently -OR12. In some embodiments of Formula II or III, Raand Rbare each independently -OH. In some embodiments, of Formula II or III, Raand Rbare each independently -OCH3.

[0376] In some embodiments of Formula II or III, Raand Rbare each independently H.

[0377] In some embodiments of Formula II or III, Raand Rboptionally join together to form a 3-6 membered carbocycle or heterocycle which is unsubstituted or is substituted with one or more R13. In some embodiments of Formula II or III, Raand Rboptionally join together to form a 3-6 membered carbocycle. In some embodiments of Formula II or III, Raand Rboptionally join together to form a cyclopropyl ring.

[0378] In some embodiments of Formula II or III, Raand Rbare each independently selected from halogen, C1-2 alkyl,, , and -OR12, wherein an Raand Rboptionally join together to form a 3-6 membered carbocycle, and wherein any C1-2alkyl is unsubstituted or is substituted with one or more R13. In some embodiments of Formula II or III, Raand Rbare each independently selected from halogen, C1-2 alkyl,, and -OR12, wherein an Raand Rboptionally join together to form a 3-6 membered carbocycle, and wherein any C1-2alkyl is unsubstituted or is substituted with one or more R13.

[0379] In some embodiments of Formula II or III, Raand Rbare each independently selected from fluoro, -OC(O)(3-8 membered heterocycle), -CF2H, methyl,, , OH, and-OCH3, wherein an Raand Rboptionally join together to form a cyclopropyl ring. In some embodiments of Formula II or III, Raand Rbare each independently selected from fluoro, -CF2H, methyl,a-OH, and-OCH3, wherein an R and Rboptionally join together to form a cyclopropyl ring.

[0380] In some embodiments, for a compound according to Formula III, or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof: Z is C-R5; R1 is selected fromR2is selected from C1-6alkyl; R3is selected from:^R4is H; R5is selected from halogen and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13;R6is selected from:R7is selected from halogen.

[0381] In some embodiments, for a compound according to Formula III, or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof: Z is C-R5; R1is selected from: ^ ^^R2is selected from C1-6alkyl;R3is selected from: ^R5is selected from halogen and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R6is selected from:R7is selected from halogen.

[0382] In some embodiments, for a compound according to Formula III, or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof: Z is C-R5; RR2is selected from CH3- and CH3CH2-;R4is H; R5is selected from halogen and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R6is selected from:R7is selected from halogen.

[0383] In some embodiments, for a compound according to Formula III, or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof: Z is C-R5; R1 is selected fromR2is selected from CH3- and CH3CH2-;R3 is selected fromR4is H; R5is selected from halogen and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R6is selected from:R7is selected from halogen. In some embodiments, R1is selected from: ^^^

[0384] In another aspect, the present disclosure provides a compound represented by Formula IV:or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein: R1is selected from -OR2is selected from H, C1-6alkyl, and a 3-6 membered carbocycle, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13; R3is selected from C1-6alkyl that is substituted with one or more R10; R4is H; R5is selected from halogen and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R6is a bicyclic heteroaryl substituted with one or more R15; R7is selected from halogen; R8is selected from a heterocycle and an alkylheterocycle, wherein any heterocycle comprises 4-8 ring atoms and is unsubstituted or is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-6alkyl; each R10is independently selected from a 3-6 membered heterocycle, a 5-6 membered heteroaryl, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R20,and any 3-6 membered heterocycle or 5-6 membered heteroaryl is unsubstituted or substituted with one or more =O, R12, or R13; each R12is independently selected from C1-6alkyl, C2-6alkenyl, and H, wherein any C1-6alkyl or C2-6alkenyl is unsubstituted or substituted with one or more R13; each R13is independently selected from -OR14, -CN, -N(R14)2, and halogen; each R14is independently selected from C1-6alkyl, C2-6alkenyl, and H; each R15is independently selected from deuterium, halogen, -N(R12)2, -CN, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; each R20is independently selected from -OH, -OC1-6alkyl, -CN, -NH2, -NHC1-6alkyl, and halogen; R27is a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted or substituted with one or more R28; each R28is independently selected from C1-6alkyl and halogen; and Raand Rbare each independently selected from halogen, C1-6alkyl, -OR12, and H, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13, and wherein an Raand Rboptionally join together to form a 3-6 membered carbocycle or heterocycle.

[0385] In some embodiments, the present disclosure provides a compound of Formula IV or a salt (e.g., a pharmaceutically acceptable salt) thereof.

[0386] In some embodiments, the present disclosure provides a compound of Formula IV, wherein: R1is selected from -OR8; R2is selected from C1-6alkyl that is unsubstituted or is substituted with one or more R13; R3is selected from C1-6alkyl that is substituted with one or more R10; R4is H; R5is selected from C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R6is a bicyclic heteroaryl substituted with one or more R15; R7is selected from halogen; R8is selected from an alkylheterocycle, wherein any heterocycle comprises 4-8 ring atoms and is unsubstituted or is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-6alkyl; each R10is independently selected from a 3-6 membered heterocycle and a 5-6 membered heteroaryl, wherein any 3-6 membered heterocycle or 5-6 membered heteroaryl is unsubstituted or substituted with one or more =O, R12, or R13; each R12is independently selected from C1-6alkyl and H, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13;each R13is independently selected from -OR14, -CN, -N(R14)2, and halogen; each R14is independently selected from C1-6alkyl and H; each R15is independently selected from halogen, -N(R12)2, and -CN; and Raand Rbare each independently selected from halogen, C1-6alkyl, -OR12, and H, wherein an Raand Rboptionally join together to form a 3-6 membered carbocycle or heterocycle.

[0387] In some embodiments, the present disclosure provides a compound of Formula IV-a:or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein R2and R3are as defined for Formula IV above and described in classes and subclasses herein, both singly and in combination. In some embodiments, the present disclosure provides a compound of Formula IV-a, or a salt (e.g., pharmaceutically acceptable salt) thereof.

[0388] In some embodiments, for a compound according to Formula IV, R6is selected from:, wherein X is selected from N and C-CN; Y is selected from O and S; R23is selected from -N(R12)2, C1-6alkyl, and C1-6alkyl-N(R14)2, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; and R24, R25, and R26are independently selected from H, deuterium, halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13. In some embodiments, X is C-CN and Y is S. In some embodiments, X is C-CN and Y is O. In some embodiments, X is N and Y is S. In some embodiments, X is N and Y is O. In some embodiments, X is C-CN, Y is S, and R23is -N(R12)2. In some embodiments, X is C-CN, Y is S, and R23is -NH2. In some embodiments, R24is halogen (e.g., fluoro). In some embodiments, R26is deuterium.

[0389] In some embodiments, for a compound according to Formula IV, R6is selected from:any of which is substituted with one or more R15.

[0390] In some embodiments, for a compound according to Formula IV, R6is selected from:, , , , and .

[0391] In some embodiments, for a compound according to Formula IV, R6is selected from:

[0392] In some embodiments, for a compound according to Formula IV, R6is selected from:In some embodiments, R6is selected from: e,

[0393] In some embodiments, the compound is a compound according to Formula IVB:or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein: R1 is selected from -OR2is selected from H, C1-6alkyl, and a 3-6 membered carbocycle, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13; R3is selected from C1-6alkyl that is substituted with one or more R10; R5is selected from halogen and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R7is selected from halogen; R8is selected from a heterocycle and an alkylheterocycle, wherein any heterocycle comprises 4-8 members and is unsubstituted or is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-6alkyl; each R10is independently selected from a 3-6 membered heterocycle, a 5-6 membered heteroaryl, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R20, and any 3-6 membered heterocycle or 5-6 membered heteroaryl is unsubstituted or substituted with one or more =O, R12, or R13; each R12is independently selected from C1-6alkyl, C2-6alkenyl, and H, wherein any C1-6alkyl or C2-6alkenyl is unsubstituted or substituted with one or more R13; each R13is independently selected from -OR14, -CN, -N(R14)2, and halogen; each R14is independently selected from C1-6alkyl, C2-6alkenyl, and H; each R20is independently selected from -OH, -OC1-6alkyl, -CN, -NH2, -NHC1-6alkyl, and halogen; R27is a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted or substituted with one or more R28; each R28is independently selected from C1-6alkyl and halogen; and Raand Rbare each independently selected from halogen, C1-6alkyl, -OR12, and H, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13, and wherein an Raand Rboptionally join together to form a 3-6 membered carbocycle or heterocycle. X is selected from N and C-CN; Y is selected from O and S; R23is selected from -N(R12)2, C1-6alkyl, and C1-6alkyl-N(R14)2, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; and R24, R25, and R26are independently selected from H, deuterium, halogen, -OR12, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13.

[0394] In some embodiments, the present disclosure provides a compound of Formula IVB or a salt (e.g., a pharmaceutically acceptable salt) thereof.

[0395] In some embodiments, for a compound of Formula IV or IVB, R1is selected from -OR8, wherein R8is selected from a heterocycle and an alkylheterocycle, wherein any heterocycle comprises 4-8 ringatoms and is unsubstituted or is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-6alkyl. In some embodiments, R8is a heterocycle or an alkylheterocycle, wherein any heterocycle contains 4-8 ring atoms and is substituted with one or more Raor Rb. In some embodiments, R8is a heterocycle that is unsubstituted or substituted with one or more Raor Rb. In some embodiments, R8is an alkylheterocycle that is unsubstituted or substituted with one or more Raor Rb. In some embodiments, R8is -CH2(heterocycle), where the heterocycle is unsubstituted or substituted with one or more Raor Rb. In some embodiments, a heterocycle or a heterocycle of an alkylheterocycle is a 4-6 membered monocyclic heterocycle having 1-2 heteroatoms independently selected from N, O, and S. In some embodiments, a heterocycle or a heterocycle of an alkylheterocycle is an 8- membered bicyclic heterocycle having 1-2 heteroatoms independently selected from N, O, and S. In some embodiments, a heterocycle or a heterocycle of an alkylheterocycle is substituted with one or more Raor Rb, wherein the one or more Raor Rbis a halogen (e.g., F). In some embodiments, a heterocycle or a heterocycle of an alkylheterocycle is substituted with one or more Raor Rb, wherein the one or more Raor Rbis a C1-6alkyl (e.g., methyl). In some embodiments, a heterocycle or a heterocycle of an alkylheterocycle is substituted with one or more Raor Rb, wherein the one or more Raor Rbis a -OR12(e.g., -OCH3).

[0396] In some embodiments, for a compound of Formula IV or IVB, R1is selected from:wherein Raand Rbare each independently selected from halogen, C1-6alkyl, -OR12, and H, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13. In some embodiments, Rais a halogen. In some embodiments, Rais F. In some embodiments, Rais C1-6alkyl that is unsubstituted or is substituted with one or more R13. In some embodiments, Rais methyl. In some embodiments, Rais -OC1-6alkyl. In some embodiments, Rais H. In some embodiments, Rbis H. In some embodiments, Rbis a halogen. In some embodiments, Rbis F. In some embodiments, Rbis C1-6alkyl that is unsubstituted or is substituted with one or more R13. In some embodiments, Rbis methyl. In some embodiments, each of Raand Rbis F. In some embodiments, each of Raand Rbis methyl. In some embodiments, R1is selected from:, , , ,

[0397] In some embodiments, for a compound of Formula IV or IVB, R1is selected from:

[0398] In some embodiments, for a compound of Formula IV or IVB, R1is selected from: ^wherein each Raand Rbis independently selected from halogen, C1-6alkyl, -OR12, and H; and Rcis selected from C1-6alkyl, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13, and wherein an Raand Rbor Rcoptionally join together to form a 3-6 membered carbocycle or heterocycle. In some embodiments, each Raand Rbis independently selected from halogen, C1-6alkyl, -OR12, and H; and Rcis selected from C1-6alkyl, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13, and wherein an Raand Rbattached to the same carbon atom join together to form a 3-6 membered carbocycle. In some embodiments, each Raand Rbis independently selected from halogen, C1-6alkyl, -OR12, and H; and wherein an Raand Rcjoin together to form a 3-6 membered heterocycle. In some embodiments, each Raand Rbis independently selected from halogen, C1-6alkyl, -OR12, and H; and Rcis selected from C1-6alkyl, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13. In some embodiments, one Raor Rbis selected from halogen, C1-6alkyl, and -OR12, and the other Raand Rbgroups are H. In some embodiments, one Raor Rbis halogen (e.g., F). In some embodiments, two Ragroups, two Rbgroups, or an Raand an Rbare halogen (e.g., F). In some embodiments, one Raor Rbis -OR12(e.g., -OCH3or – OCHF2). In some embodiments, one Raor Rbis C1-6alkyl (e.g., methyl). In some embodiments, two Ragroups, two Rbgroups, or an Raand an Rbare C1-6alkyl (e.g., methyl). In some embodiments, Rcis selected from –CH3, -CH2CH2F, -CH2CHF2, and –CH2CH2CN. In some embodiments, an Raand Rbjoin together to form a 3-6 membered carbocycle, such as a cyclopropane. In some embodiments, an Raand Rbattached to the same carbon atom join together to form a 3-6 membered carbocycle, such as a cyclopropane. In some embodiments, an Raand Rcjoin together to form a 3-6 membered heterocycle. In some embodiments, R1is selected from:, , , , , and .

[0399] In some embodiments, for a compound of Formula IV or IVB, R1is selected from:, , , and .

[0400] In some embodiments, for a compound of Formula IV or IVB, R1is selected from:and .

[0401] In some embodiments, the compound is a compound according to Formula IVC,or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein: R2is selected from H, C1-6alkyl, and a 3-6 membered carbocycle, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13; R3is selected from C1-6alkyl that is substituted with one or more R10;R5is selected from halogen and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R7is selected from halogen; each R10is independently selected from a 3-6 membered heterocycle, a 5-6 membered heteroaryl, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R20, and any 3-6 heterocycle or 5-6 membered heteroaryl is unsubstituted or substituted with one or more =O, R12, or R13; each R12is independently selected from C1-6alkyl, C2-6alkenyl, and H, wherein any C1-6alkyl or C2-6alkenyl is unsubstituted or substituted with one or more R13; each R13is independently selected from -OR14, -CN, -N(R14)2, and halogen; each R14is independently selected from C1-6alkyl, C2-6alkenyl, and H; each R20is independently selected from -OH, -OC1-6alkyl, -CN, -NH2, -NHC1-6alkyl, and halogen; Raand Rbare each independently selected from halogen, C1-6alkyl, -OR12, and H, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13; X is selected from N and C-CN; Y is selected from O and S; R23is selected from -N(R12)2, C1-6alkyl, and C1-6alkyl-N(R14)2, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; and R24, R25, and R26are independently selected from H, deuterium, halogen, -OR12, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13.

[0402] In some embodiments, the present disclosure provides a compound of Formula IVC or a salt (e.g., a pharmaceutically acceptable salt) thereof.

[0403] In some embodiments, for a compound according to Formula IVC, Rais a halogen. In some embodiments, Rais F. In some embodiments, Rais C1-6alkyl that is unsubstituted or is substituted with one or more R13. In some embodiments, Rais methyl. In some embodiments, Rais -OC1-6alkyl. In some embodiments, Rais H. In some embodiments, Rbis H. In some embodiments, Rbis a halogen. In some embodiments, Rbis F. In some embodiments, Rbis C1-6alkyl that is unsubstituted or is substituted with one or more R13. In some embodiments, Rbis methyl. In some embodiments, each of Raand Rbis F. In some embodiments, each of Raand Rbis methyl.

[0404] In some embodiments, for a compound according to Formula IVB or IVC, X is C-CN and Y is S. In some embodiments, X is C-CN and Y is O. In some embodiments, X is N and Y is S. In some embodiments, X is N and Y is O. In some embodiments, R23is selected from -N(R12)2. In some embodiments, R23is selected from C1-6alkyl that is unsubstituted or substituted with one or more R13. In some embodiments, R23is selected from C1-6alkyl-N(R14)2, wherein any C1-6alkyl is unsubstituted orsubstituted with one or more R13. In some embodiments, X is C-CN, Y is S, and R23is -N(R12)2. In some embodiments, X is C-CN, Y is S, and R23is -NH2. In some embodiments, at least one of R24, R25, and R26are independently selected from deuterium, halogen, -OR12, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13. In some embodiments, at least one of R24, R25, and R26are independently selected from halogen. In some embodiments, X is C-CN, Y is S, R23is selected from - N(R12)2, and at least one of R24, R25, and R26are independently selected from halogen. In some embodiments, X is C-CN, Y is S, R23is -N(R12)2, and R24is a halogen (e.g., F). In some embodiments, X is C-CN, Y is S, R23is -N(R12)2, and one or more of R24, R25, and R26is a halogen (e.g., F). In some embodiments, R26is deuterium.

[0405] In some embodiments, for a compound according to any one of Formulas IV, IV-a, IVB, or IVC, R2is H. In some embodiments, R2is selected from C1-6alkyl that is unsubstituted or is substituted with one or more R13. In some embodiments, R2is selected from C1-6alkyl that is unsubstituted. In some embodiments, R2is selected from C1-6alkyl that is substituted with one or more R13. In some embodiments, R2is selected from C1-2alkyl that is unsubstituted or is substituted with one or more R13. In some embodiments, R2is selected from C1-2alkyl that is unsubstituted. In some embodiments, R2is selected from C1-2alkyl that is substituted with one or more R13. In some embodiments, R2is methyl. In some embodiments, R2is ethyl. In some embodiments, R2is a 3-6 membered carbocycle (e.g., a cyclopropane).

[0406] In some embodiments, for a compound according to any one of Formula IV, IV-a, IVB, and IVC, R3is selected from C1-3alkyl that is substituted with one or more R10. In some embodiments, R3is selected from C1-3alkyl that is substituted with one or more R10, wherein each R10is independently selected from a 3-6 membered heterocycle, a 5-6 membered heteroaryl, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R20, and any 5-6 membered heteroaryl or 3-6 membered heterocycle is unsubstituted or substituted with one or more R13. In some embodiments, R3is C1-3alkyl that is substituted with a 3-6 membered heterocycle that is unsubstituted or substituted with one or more =O, R12, or R13. In some embodiments, R3is C1-3alkyl that is substituted with a 5-6 membered heteroaryl that is unsubstituted or substituted with one or more =O, R12, or R13. In some embodiments, R3is C2-3alkyl that is substituted with a 5-6 membered heteroaryl that is unsubstituted or substituted with one or more R13. In some embodiments, R3is C1-3alkyl that is substituted with an oxazole, isoxazole, thiazole, isothiazole, pyrazole, pyridine, pyrazine, pyridazine, or pyrimidine that is unsubstituted or substituted with one or more =O, R12, or R13. In some embodiments, R3is C2-3alkyl that is substituted with a pyridine that is unsubstituted or substituted with one or more R13. In some embodiments, R3is C2-3alkyl that is substituted with a pyridine that is substituted with one or more R13.

[0407] In some embodiments, for a compound according to any one of Formula IV, IV-a, IVB, and IVC,toptionally further substituted with one or more R10.

[0408] In some embodiments, for a compound according to any one of Formula IV, IVB, and IVC, R5is a halogen (e.g., F or Cl). In some embodiments, R5is Cl. In some embodiments, R5is F. In some embodiments, R5is selected from C1-6alkyl that is unsubstituted or substituted with one or more R13. In some embodiments, R5is selected from C1-2alkyl that is unsubstituted or substituted with one or more R13. In some embodiments, R5is selected from C1-6alkyl that is unsubstituted, such as methyl or ethyl. In some embodiments, R5is selected from C1-6alkyl that is substituted with one or more halogens or -CN. In some embodiments, R5is C1-6alkyl that is substituted with one or more halogens, such as one or more fluorines. In some embodiments, R5is -CF3. In some embodiments, R5is -CHF2. In some embodiments, R5is selected from -CF2H, -CF3, -CH2CN, and -CH2CH3. In some embodiments, R5is selected from –CH3, -CH2CH3, - CF2H, -CF3, -CF2CH3, and -CH2CN. In some embodiments, R5is C1-6alkyl that is substituted with one ormore R13, wherein each R13is independently selected from –OR14, -CN, and -N(R14)2. In some embodiments, R5is -CH2CN.

[0409] In some embodiments, for a compound according to any one of Formulas IV, IVB, and IVC, R7is Cl. In some embodiments, R7is F.

[0410] In some embodiments, for a compound of any one of Formulas IV, IV-a, IVB, and IVC, the compound is not a compound included in Table 2, or a salt, ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. Table 2.

[0411] In another aspect, the present disclosure provides a compound represented by Formula V’:or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein:R1is selected from -Oheterocycle comprising one or more N atoms, wherein the heterocycle is unsubstituted or substituted with one or more R31; Rmis selected from hydrogen and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R4is H; R5is selected from halogen and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R6is a bicyclic heteroaryl that is substituted with one or more R15; R7is selected from halogen; R8is selected from a heterocycle and an alkylheterocycle, wherein any heterocycle comprises 4-8 ring atoms and is unsubstituted or is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-6alkyl; each R12is independently selected from C1-6alkyl, C2-6alkenyl, and H, wherein any C1-6alkyl or C2-6alkenyl is unsubstituted or substituted with one or more R13; each R13is independently selected from -OR14, -CN, -N(R14)2, and halogen; each R14is independently selected from C1-6alkyl, C2-6alkenyl, and H; each R15is independently selected from deuterium, halogen, -N(R12)2, -CN, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; each R28is independently selected from C1-6alkyl and halogen; each R29is independently selected from halogen and C1-6alkyl; R30is N(R14)2or a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted or substituted with one or more R28; n is 0-2; each R31is selected from C1-6alkyl; and Raand Rbare each independently selected from deuterium, halogen, C1-6alkyl, C2-6 alkenyl, a 3-6 membered carbocycle, -OR12, and H, wherein an Raand Rboptionally join together to form a 3-6 membered carbocycle or heterocycle, and wherein any C1-6alkyl, C2-6alkenyl, or 3-6 membered carbocycle or heterocycle is unsubstituted or is substituted with one or more R13.

[0412] In some embodiments, the present disclosure provides a compound of Formula V’ or a salt (e.g., a pharmaceutically acceptable salt) thereof.

[0413] In some embodiments, the present disclosure provides a compound of Formula V’, wherein:R1is selected from -OR8; Rmis H; R4is H; R5is C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R6is a bicyclic heteroaryl, wherein the heteroaryl is substituted with one or more R15; R7is selected from halogen; R8is an alkylheterocycle, wherein the heterocycle comprises 4-8 ring atoms and is unsubstituted or is substituted with one or more Raor Rb, and wherein an alkyl moiety of the alkylheterocycle is selected from C1-6alkyl; each R12is independently selected from C1-6alkyl, C2-6alkenyl, and H, wherein any C1-6alkyl or C2-6alkenyl is unsubstituted or substituted with one or more R13; each R13is independently selected from -OR14, -CN, -N(R14)2, and halogen; each R14is independently selected from C1-6alkyl, C2-6alkenyl, and H; each R15is independently selected from halogen, -N(R12)2, and -CN; and Raand Rbare each independently selected from deuterium, halogen, C1-6alkyl, C2-6alkenyl, a 3-6 membered carbocycle, -OR12, and H, wherein an Raand Rboptionally join together to form a 3-6 membered carbocycle or heterocycle, and wherein any C1-6alkyl, C2-6alkenyl, or 3-6 membered carbocycle or heterocycle is unsubstituted or is substituted with one or more R13.

[0414] In some embodiments, for a compound according to Formula V’, Rmis hydrogen. In some embodiments, Rmis C1-6alkyl that is unsubstituted or substituted with one or more R13. In some embodiments, Rmis C1-6alkyl that is unsubstituted. In some embodiments, Rmis methyl that is unsubstituted. In some embodiments, Rmis C1-6alkyl that is substituted with one or more R13.

[0415] In some embodiments, the compound is a compound according to Formula VA’:or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein:R1is selected from -Oheterocycle comprising one or more N atoms, wherein the heterocycle is unsubstituted or substituted with one or more R31; R4is H; R5is selected from halogen and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R6is a bicyclic heteroaryl that is substituted with one or more R15; R7is selected from halogen; R8is selected from a heterocycle and an alkylheterocycle, wherein any heterocycle comprises 4-8 ring atoms and is unsubstituted or is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-6alkyl; each R12is independently selected from C1-6alkyl, C2-6alkenyl, and H, wherein any C1-6alkyl or C2-6alkenyl is unsubstituted or substituted with one or more R13; each R13is independently selected from -OR14, -CN, -N(R14)2, and halogen; each R14is independently selected from C1-6alkyl, C2-6alkenyl, and H; each R15is independently selected from deuterium, halogen, -N(R12)2, -CN, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; each R28is independently selected from C1-6alkyl and halogen; each R29is independently selected from halogen and C1-6alkyl; R30is N(R14)2or a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted or substituted with one or more R28; n is 0-2; each R31is selected from C1-6alkyl; and Raand Rbare each independently selected from deuterium, halogen, C1-6alkyl, C2-6alkenyl, a 3-6 membered carbocycle, -OR12, and H, wherein an Raand Rboptionally join together to form a 3-6 membered carbocycle or heterocycle, and wherein any C1-6alkyl, C2-6 alkenyl, or 3-6 membered carbocycle or heterocycle is unsubstituted or is substituted with one or more R13.

[0416] In some embodiments, the present disclosure provides a compound of Formula VA’ or a salt (e.g., a pharmaceutically acceptable salt) thereof.

[0417] In some embodiments, the compound is a compound according to Formula VB’:or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein: R1is selected from -eterocycle comprising one or more N atoms, wherein the heterocycle is unsubstituted or substituted with one or more R31; Rmis selected from C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R4is H; R5is selected from halogen and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R6is a bicyclic heteroaryl that is substituted with one or more R15; R7is selected from halogen; R8is selected from a heterocycle and an alkylheterocycle, wherein any heterocycle comprises 4-8 ring atoms and is unsubstituted or is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-6alkyl; each R12is independently selected from C1-6alkyl, C2-6 alkenyl, and H, wherein any C1-6alkyl or C2-6alkenyl is unsubstituted or substituted with one or more R13; each R13is independently selected from -OR14, -CN, -N(R14)2, and halogen; each R14is independently selected from C1-6alkyl, C2-6alkenyl, and H; each R15is independently selected from deuterium, halogen, -N(R12)2, -CN, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; each R28is independently selected from C1-6alkyl and halogen; each R29is independently selected from halogen and C1-6alkyl; R30is N(R14)2or a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted or substituted with one or more R28; n is 0-2; each R31is selected from C1-6alkyl; andRaand Rbare each independently selected from deuterium, halogen, C1-6alkyl, C2-6 alkenyl, a 3-6 membered carbocycle, -OR12, and H, wherein an Raand Rboptionally join together to form a 3-6 membered carbocycle or heterocycle, and wherein any C1-6alkyl, C2-6alkenyl, or 3-6 membered carbocycle or heterocycle is unsubstituted or is substituted with one or more R13.

[0418] In some embodiments, the present disclosure provides a compound of Formula VB’ or a salt (e.g., a pharmaceutically acceptable salt) thereof.

[0419] In some embodiments, for a compound according to any one of Formulas V’, VA’, and VB’, R6is selected from:, wherein X is selected from N and C-CN; Y is selected from O and S; R23is selected from -N(R12)2, C1-6alkyl, and C1-6alkyl-N(R14)2, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; and R24, R25, and R26are independently selected from H, deuterium, halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13. In some embodiments, X is C-CN and Y is S. In some embodiments, X is C-CN and Y is O. In some embodiments, X is N and Y is S. In some embodiments, X is N and Y is O. In some embodiments, X is C-CN, Y is S, and R23is -N(R12)2. In some embodiments, X is C-CN, Y is S, and R23is -NH2. In some embodiments, R24is halogen (e.g., fluoro). In some embodiments, R26is deuterium.

[0420] In some embodiments, for a compound according to any one of Formulas V’, VA’, and VB’, R6is selected from:, , , , , any of which is substituted with one or more R15.

[0421] In some embodiments, for a compound according to any one of Formulas V’, VA’, and VB’, R6is selected from:, , , , and .

[0422] In some embodiments, for a compound according to any one of Formulas V’, VA’, and VB’, R6is selected from:.

[0423] In some embodiments, for a compound according to any one of Formulas V’, VA’, and VB’, R6is selected from:which is substituted with one or more R15. In some embodiments, R6is s .

[0424] In some embodiments, the compound is a compound according to Formula VC’:or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein: R1is selected from -O, , heterocycle comprising one or more N atoms, wherein the heterocycle is unsubstituted or substituted with one or more R31; Rmis selected from hydrogen and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R4is H; R5is selected from halogen and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or su...

Claims

Claims 1. A compound represented by Formula A’:or a salt (e.g., pharmaceutically acceptable salt) thereof, wherein: R1is selected from Hmembered heterocycle that is unsubstituted or substituted with one or more R31; Rmis selected from H and -NR2R3; R2is selected from C1-6alkyl which is optionally deuterated; R3is selected from a C1-6alkyl, 3- to 6-membered cycloalkyl optionally fused to a 5- or 6- membered heterocycle or heteroaryl, 4-10 membered heterocycle or -(C1-6alkylenyl)(5-6 membered heteroaryl), wherein any heterocycle or heteroaryl is unsubstituted or substituted with one or more R10, or R2and R3, together with the atom they attach to, form a 4- to 10-membered heterocycle optionally substituted with one or more R10; R4is H; R5is selected from C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R6is a bicyclic heteroaryl that is substituted with one or more R15; R7is selected from halogen; R8is selected from a heterocycle and an alkylheterocycle, wherein any heterocycle comprises 4-8 ring atoms and is unsubstituted or is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-6alkyl; each R10is independently selected from deuterium, =O, -C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), - C(O)N(R14)2, -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), halogen, a 5-6 membered heteroaryl, a 3-6 membered carbocycle, a 3-6 membered heterocycle, and C1-6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, wherein any 3-6 membered carbocycle,5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20; each R12is independently selected from C1-6alkyl, C2-6alkenyl, and H, wherein any C1-6alkyl or C2-6alkenyl is unsubstituted or substituted with one or more R13; each R13is independently halogen; each R14is independently selected from C1-6alkyl, wherein any C1-6alkyl is optionally deuterated; each R15is independently selected from halogen, -N(R12)2, and -CN; each R20is independently selected from =O, -CN, -CN, -OR12,^and halogen; each R28is independently selected from halogen,-OR12, C1-6alkyl, and C1-6heteroalkyl, wherein two heteroalkyl groups can optionally join together to form a 3-6 membered heterocycle that is unsubstituted or substituted with one or more R13; each R29is independently selected from halogen and C1-6alkyl; R30is selected from -N(R12)2and a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted or substituted with one or more R28; each R31is selected from C1-6alkyl; n is 0-2; and Raand Rbare each independently selected from deuterium, halogen, C1-6alkyl, C2-4alkenyl,, -OR12, a 4- to 10-membered heterocycle, and a 4- to 10-membered aryl, wherein any 4- to 10-membered heterocycle or 4- to 10-membered aryl is optionally substituted with one or more R28, wherein an Raand Rboptionally join together to form a 3-6 membered carbocycle or heterocycle, and wherein any C1-6alkyl, C2-6alkenyl, or 3-6 membered carbocycle or heterocycle is unsubstituted or is substituted with one or more R13.

2. The compound of claim 1, wherein the compound is a compound represented by Formula B:or a salt (e.g., pharmaceutically acceptable salt) thereof, wherein:R1is selected from Hmembered heterocycle that is unsubstituted or substituted with one or more R31; R2is selected from C1-6alkyl; R3is selected from a 4-10 membered heterocycle or -(C1-6alkylenyl)(5-6 membered heteroaryl), wherein any heterocycle or heteroaryl is unsubstituted or substituted with one or more R10; R4is H; R5is selected from C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R6is a bicyclic heteroaryl, wherein the heteroaryl is substituted with one or more R15; R7is selected from halogen; R8is selected from a heterocycle and an alkylheterocycle, wherein any heterocycle comprises 4-8 ring atoms and is unsubstituted or is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-6alkyl; each R10is independently selected from deuterium, =O, -C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), - C(O)N(R14)2, -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), halogen, a 5-6 membered heteroaryl, a 3-6 membered carbocycle, a 3-6 membered heterocycle, and C1-6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20; each R12is independently selected from C1-6alkyl, C2-6alkenyl, and H, wherein any C1-6alkyl or C2-6alkenyl is unsubstituted or substituted with one or more R13; each R13is independently halogen; each R14is independently selected from C1-6alkyl, wherein any C1-6alkyl is optionally deuterated; each R15is independently selected from halogen, -N(R12)2, and -CN; each R20is independently selected from =O, -CN, and halogen; each R28is independently selected from halogen; each R29is independently selected from halogen and C1-6alkyl; R30is selected from -N(R12)2 and a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted or substituted with one or more R28;each R31is selected from C1-6alkyl; n is 0-2; and Raand Rbare each independently selected from halogen, C1-6alkyl, C2-4alkenyl, and -OR12, wherein any C1-6alkyl or C2-4alkenyl is unsubstituted or is substituted with one or more R13.

3. The compound of claim 2, wherein the compound is of Formula B-a:alt (e.g., pharmaceutically acceptable salt) thereof.

4. The compound of any one of claims 1-3, wherein R3is a 4-10 membered heterocycle that includes 1-2 heteroatoms independently selected from O, S, and N.

5. The compound of claim 4, wherein R3is a 4-7 membered heterocycle that includes 1 heteroatom selected from O, S, and N, wherein the heterocycle is substituted with 1-4 R10.

6. The compound of claim 4, wherein R3is a 4-7 membered heterocycle that includes 1 heteroatom selected from O, S, and N, wherein the heterocycle is substituted with 1-4 R10, provided that when the heterocycle contains a nitrogen atom, the nitrogen atom is substituted with R10.

7. The compound of any one of claims 1-6, wherein R3is a pyrrolidine that is substituted with 0-4 R10.

8. The compound of any one of claims 1-6, wherein R3is a pyrrolidine that is substituted with 0-4 R10, provided that the nitrogen atom is substituted with R10.

9. The compound of any one of claims 1-6, wherein R3is a 4-6 membered heterocycle that is substituted with one or more R10, provided that when the heterocycle contains a nitrogen atom, the nitrogen atom is substituted with R10, and each R10is independently selected from -C(O)(C1- 6alkyl), -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), -C(O)O(C1-6alkyl), -C(O)N(R14)2, a 5-6 membered heteroaryl, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R20, and any 3-6 membered carbocycle is unsubstituted or substituted with one or more R12or R20.

10. The compound of any one of claims 1-4, wherein R3is an 8-10 membered heterocycle that includes 1-2 heteroatoms independently selected from O, S, and N.

11. The compound of claim 10, wherein R3is an 8-10 membered heterocycle that includes 1-2 heteroatoms independently selected from O, S, and N, wherein the heterocycle is substituted with 1-4 R10.

12. The compound of claim 10 or 11, wherein R3is an 8-membered heterocycle that includes 1-2 heteroatoms independently selected from O, S, and N, wherein the heterocycle is substituted with 1-4 R10.

13. The compound of claim 10 or 11, wherein R3is a 9-membered heterocycle that includes 1-2 heteroatoms independently selected from O, S, and N, wherein the heterocycle is substituted with 1-4 R10.

14. The compound of claim 10 or 11, wherein R3is a 10-membered heterocycle that includes 1-2 heteroatoms independently selected from O, S, and N, wherein the heterocycle is substituted with 1-4 R10.

15. The compound of any one of claims 12-14, wherein R10is selected from =O, C1-6alkyl, a 3-6 membered carbocycle, and halogen.

16. The compound of any one of claims 1-3, wherein R3is -(C1-6alkylenyl)(5-6 membered heteroaryl), wherein the heteroaryl is unsubstituted or substituted with one or more R10.

17. The compound of claim 16, wherein R3is -CH2(5-6 membered heteroaryl), wherein the heteroaryl is unsubstituted or substituted with one or more R10.

18. The compound of claim 17, wherein R10is selected from halogen and C1-6alkyl, wherein the C1- 6alkyl is unsubstituted or substituted with one or more R20.

19. The compound of any one of claims 1-18, wherein R3is selected from: -CH3,,, , , , , ,a20. The compound of any one of claims 1-19, wherein the compound is a compound according to Formula BA, BB, BC, BD, BE, BF, BG, BH, BI, BJ, BK, BL, or BM:or a salt (e.g., pharmaceutically acceptable salt) thereof, wherein: R32, if present, is selected from H and C1-5alkyl; each Rdis independently selected from H, deuterium, =O, halogen, and C1-6alkyl, wherein any C1- 6alkyl is unsubstituted or substituted with one or more R20; and Re, if present, is selected from H, -C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), -C(O)N(R14)2, -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), a 5-6 membered heteroaryl, a 3-6 membered carbocycle, a 3-6 membered heterocycle, and C1-6alkyl, wherein any C1- 6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, and wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20.

21. The compound of claim 20, wherein the compound is a compound according to Formula BA, or a salt (e.g., pharmaceutically acceptable salt) thereof.

22. The compound of claim 20, wherein the compound is a compound according to Formula BB, or a salt (e.g., pharmaceutically acceptable salt) thereof.

23. The compound of claim 20, wherein the compound is a compound according to Formula BC, or a salt (e.g., pharmaceutically acceptable salt) thereof.

24. The compound of claim 20, wherein the compound is a compound according to Formula BD, or a salt (e.g., pharmaceutically acceptable salt) thereof.

25. The compound of claim 20, wherein the compound is a compound according to Formula BE, or a salt (e.g., pharmaceutically acceptable salt) thereof.

26. The compound of claim 20, wherein the compound is a compound according to Formula BF, or a salt (e.g., pharmaceutically acceptable salt) thereof.

27. The compound of claim 20, wherein the compound is a compound according to Formula BG, or a salt (e.g., pharmaceutically acceptable salt) thereof.

28. The compound of claim 20, wherein the compound is a compound according to Formula BH, or a salt (e.g., pharmaceutically acceptable salt) thereof.

29. The compound of claim 20, wherein the compound is a compound according to Formula BI, or a salt (e.g., pharmaceutically acceptable salt) thereof.

30. The compound of claim 20, wherein the compound is a compound according to Formula BJ, or a salt (e.g., pharmaceutically acceptable salt) thereof.

31. The compound of claim 20, wherein the compound is a compound according to Formula BK, or a salt (e.g., pharmaceutically acceptable salt) thereof.

32. The compound of claim 20, wherein the compound is a compound according to Formula BL, or a salt (e.g., pharmaceutically acceptable salt) thereof.

33. The compound of claim 20, wherein the compound is a compound according to Formula BM, or a salt (e.g., pharmaceutically acceptable salt) thereof.

34. The compound of any one of claims 1-33, wherein (i) when R3includes a heterocycle or heteroaryl containing a nitrogen atom, the nitrogen atom is substituted with R10or (ii) the heterocycle or heteroaryl does not comprise an –NH- moiety.

35. The compound of any one of claims 1, 2, or 4-34, wherein R6 is selected from:,wherein:X is selected from N and C-CN; Y is selected from O and S; R23is selected from -N(R12)2, C1-6alkyl, and C1-6alkyl-N(R14)2, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; and R24, R25, and R26are independently selected from H, deuterium, halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13.^^^ 36. The compound of claim 35, wherein R6is selected from:one or more R15.

37. The compound of claim 36, wherein R6is selected from:

38. The compound of any one of claims 1, 2, or 4-37, wherein the compound is a compound according to Formula BA1, BB1, BC1, BD1, BE1, BF1, BG1, BH1, BI1, BJ1, BK1, BL1, or BM1:or a salt (e.g., pharmaceutically acceptable salt) thereof, wherein: R32, if present, is selected from H and C1-5alkyl; each Rdis independently selected from H, deuterium, =O, halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R20; Re, if present, is selected from -C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), -C(O)N(R14)2, -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), a 5-6 membered heteroaryl, a 3-6 membered carbocycle, a 3-6 membered heterocycle, and C1-6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, and wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20; X is C-CN; Y is S; R23is selected from -N(R12)2; and R24, R25, and R26are independently selected from H and halogen.

39. The compound of any one of claims 35-38, wherein one or more of R24, R25, and R26is a halogen (e.g., F).

40. The compound of any one of claims 20-39, wherein Reis -C(O)(3-6 membered carbocycle).

41. The compound of any one of claims 20-39, wherein Reis selected from -C(O)(C1-6alkyl), - C(O)N(R14)2, -C(O)(3-6 membered carbocycle), and -C(O)O(C1-6alkyl), a 5-6 membered heteroaryl, a 3-6 membered carbocycle, a 3-6 membered heterocycle, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R20, and any 3-6 membered carbocycle is unsubstituted or substituted with one or more R12or R20.

42. The compound of any one of claims 20-41, wherein each Rdis H.

43. The compound of any one of claims 1-42, wherein R2is H.

44. The compound of any one of claims 1-42, wherein R2is selected from C1-2alkyl.

45. The compound of any one of claims 1, 2, or 4-44, wherein R1is selected from -OR8.

46. The compound of claim 45, wherein R1is selected from:, wherein Ra1, Ra2, Rb1, Rb2, Ra3, and Rb3are each independently selected from deuterium, halogen, - OR12, a 4- to 10-membered heterocycle, and a 4- to 10-membered aryl, wherein any 4- to 10- membered heterocycle or 4- to 10-membered aryl is optionally substituted with one or more R28, and H, wherein Ra1and Rb1can optionally join together to form a exocyclic double bond that is unsubstituted or is substituted by halogen.

47. The compound of claim 46, wherein R1 is selected from:wherein Raand Rbare each independently selected from halogen, -OR12, C2-4alkenyl, and H, wherein any C2-4alkenyl is unsubstituted or is substituted by halogen.

48. The compound of claim 47, wherein R1is selected from:, , 49. The compound of claim 45, wherein R1is: wherein each Raand Rbis independently selected from halogen, -OR12, C2-4alkenyl, and H; and each Rcis independently selected from H and C1-6alkyl, wherein any C2-4alkenyl is unsubstituted or is substituted by halogen.

50. The compound of claim 49, wherein R1is selected from:.

51. The compound of any one of claims 1, 2, or 4-44, wherein R.

52. The compound of claim 51, wherein R1is selected from, , , 53. The compound of any one of claims 1, 2, or 4-52, wherein R5is -CF3.

54. A compound represented by Formula II:or a salt (e.g., pharmaceutically acceptable salt) thereof, wherein: Z is N or C-R5; R1is selected from Hheterocycle comprising one or more N atoms, wherein the heterocycle is unsubstituted or substituted with one or more R31; R2is selected from H, C1-6alkyl, and a 3-6 membered carbocycle, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13and is optionally deuterated; R3is selected from 3- to 12-membered cycloalkyl optionally fused to a 5- or 6-membered aryl, heterocycle, or heteroaryl, a 4-10 membered heterocycle, or -(C1-6alkylenyl)(5-6 membered heteroaryl), wherein any cycloalkyl, aryl, heterocycle, or heteroaryl is unsubstituted or substituted with one or more R10; R4is H; R5is selected from halogen, -CN, 5- to 6-membered heteroaryl, -OC1-6alkyl, C1-6alkyl, and H, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R6is a phenyl or a bicyclic heteroaryl, wherein the phenyl or bicyclic heteroaryl is substituted with one or more R15; R7is selected from halogen or H; R8is selected from a heterocycle and an alkylheterocycle, wherein any heterocycle comprises 4-9 ring atoms and is unsubstituted or is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-6alkyl; each R10is independently selected from deuterium, -OR12, =O, =S, -CN, -N=S(=O)Me2, -C(O)(C1-6alkylene)CN, -C(O)(C1-6alkylene)OH, -C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), - C(O)N(R14)2, -C(O)OR14, -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), -C(O)(5-6 membered heteroaryl), -C(O)O(3-6 membered carbocycle), - C(O)O(3-6 membered heterocycle), -C(O)O(5-6 membered heteroaryl),-C(O)O(C1-6alkylene)(3-6 membered heterocycle), -S(O)2(C1-6alkyl), -C(S)(C1-6alkyl), -C(S)O(C1-6alkyl), -C(S)N(C1-6alkyl)2, -C(=N-OR12)(C1-6 alkyl), -C(O)N(R12)OR12,^ halogen, a 5-6membered heteroaryl, a 3-6 membered carbocycle, a 3-6 membered heterocycle, and C1- 6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20, and wherein two R10s optionally join together to form, together with the atom(s) to which they are attached, a 3-6 membered carbocycle or heterocycle; each R12is independently selected from C1-6alkyl, C2-6 alkenyl, and H, wherein any C1-6alkyl or C2- 6 alkenyl is unsubstituted or substituted with one or more R13; each R13is independently selected from -OR14, -CN, -N(R14)2, and halogen; each R14is independently selected from a 3-6 membered carbocycle, a 3-6 membered heterocycle, C1-6alkyl, -OR12, C2-6 alkenyl, and H, wherein any C1-6alkyl is optionally deuterated; each R15is independently selected from deuterium, halogen, -N(R12)2, -CN, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; each R20is independently selected from -OH, -OC1-6alkyl, -OC1-6haloalkyl, =O, -CN, -NH2, -NHC1- 6alkyl, -C(O)(C1-6alkyl), -C(O)OR12, -C(O)N(R12)2, -S(O)2R12, a 3-6 membered carbocycle, phenyl, and halogen; each R28is independently selected from C1-6alkyl, -OR12, C1-6heteroalkyl, wherein two heteroalkyl groups can optionally join together to form a 3-6 membered heterocycle that is unsubstituted or substituted with one or more R13and halogen; each R29is independently selected from halogen and C1-6alkyl; R30is N(R12)2or a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted or substituted with one or more R28; each R31is selected from C1-6alkyl; n is 0-2; and Raand Rbare each independently selected from deuterium, halogen, C1-6alkyl, C2-6 alkenyl,,-C1-6heteroalkyl, a 3-6 membered carbocycle, -OR12, and H, wherein an Raand Rboptionally join together to form a 3-6 membered carbocycle or heterocycle, and wherein any C1-6alkyl, C2-6 alkenyl, or 3-6 membered carbocycle or heterocycle is unsubstituted or is substituted with one or more R13.

55. The compound of claim 54, wherein R3is selected from a 4-10 membered heterocycle that is unsubstituted or substituted with one or more R10, provided that (i) when the heterocycle contains a nitrogen atom, the nitrogen atom is substituted with R10, or (ii) the heterocycle does not comprise an –NH- moiety.

56. The compound of claim 54 or 55, wherein the compound is of Formula II-a:or a salt (e.g., pharmaceutically acceptable salt) thereof.

57. The compound of any one of claims 54-56, wherein R3is a 4-6 membered heterocycle that includes 1 heteroatom selected from O, S, and N.

58. The compound of claim 57, wherein R3is a 4-6 membered heterocycle that includes 1 heteroatom selected from O, S, and N, wherein the heterocycle is substituted with 1-4 R10, provided that when the heterocycle contains a nitrogen atom, the nitrogen atom is substituted with R10.

59. The compound of any one of claims 54-58, wherein R3is a pyrrolidine that is substituted with 1-4 R10, provided that the nitrogen atom is substituted with R10.

60. The compound of claim 59, wherein each R10is independently selected from deuterium, - C(O)N(R14)2, -C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), a 3-6 membered heterocycle, a 5-6 membered heteroaryl, halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R20, and wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20.

61. The compound of any one of claims 54-60, wherein R3 is selected from:, ,,,, , , , ,,, , , , , ,, , , , , , , and any of which is optionally further substituted with one or more R10.

362. The compound of claim 61, wherein R is selected from: , ,with one or more R10.

63. The compound of any one of claims 54-56, wherein R3is a 7-10 membered heterocycle that includes one or more heteroatoms selected from O, S, and N, wherein the heterocycle is unsubstituted or is substituted with one or more R10.

64. The compound of claim 63, wherein R3is a 7-10 membered heterocycle that includes one or more heteroatoms selected from O, S, and N, wherein the heterocycle is unsubstituted or is substituted with one or more R10, provided that (i) when the heterocycle contains a nitrogen atom, the nitrogen atom is substituted with R10or (ii) the heterocycle does not comprise an –NH- moiety.

65. The compound of claim 63 or 64, wherein R3is a 7-10 membered heterocycle comprising a fused ring system that includes one or more heteroatoms selected from O, S, and N, wherein the heterocycle is unsubstituted or is substituted with one or more R10.

66. The compound of any one of claims 54-56 and 63-65, wherein R3is selected from:,, , , , , ,,, , , , , , and any of which is optionally further substituted with one or more R10.

67. The compound of claim 66, wherein R3is selected from:, , ,,, , , ,, , , , ,,any of which is optionally further substituted with one or more R10.

68. The compound of any one of claims 54, 55, and 57-67, wherein the compound is a compound according to Formula IIR’, IIU’, IIV’, or IIZ:or a salt (e.g., pharmaceutically acceptable salt) thereof, wherein: each Rdis independently selected from H, deuterium, -OR12, =O, -C(O)(C1-6alkylene)CN, - C(O)(C1-6alkylene)OH, -C(O)(C1-6alkyl), -C(O)N(R14)2, -C(O)(3-6 membered carbocycle), -S(O)2(C1-6alkyl), halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R20, and wherein any 3-6 membered carbocycle is unsubstituted or substituted with one or more R12or R20; and Reis selected from -C(O)(C1-6alkyl)CN, -C(O)(C1-6alkyl)OH, -C(O)(C1-6alkyl), -C(O)O(C1- 6alkyl), -C(O)N(R14)2, -C(O)OR14, -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), -C(O)(5-6 membered heteraryl), -C(O)O(3-6 membered carbocycle), -C(O)O(3-6 membered heterocycle), -C(O)O(C1-6alkylene)(3-6 membered heterocycle), -S(O)2(C1-6alkyl), a 5-6 membered heteroaryl, a 3-6 membered carbocycle, and C1-6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, and wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20.

69. The compound of any one of claims 54, 55, and 57-67, wherein the compound is a compound according to Formula IIAA’:or a salt (e.g., pharmaceutically acceptable salt) thereof, wherein: each Rdis independently selected from deuterium, H, -OR12, =O, -C(O)(C1-6alkylene)CN, - C(O)(C1-6alkylene)OH, -C(O)(C1-6alkyl), -C(O)(3-6 membered carbocycle), -S(O)2(C1-6alkyl), halogen, a 3-6 membered carbocycle, a 3-6 membered heterocycle, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R20, wherein any 3-6 membered carbocycle or 3-6 membered heterocycle, is unsubstituted or substituted with one or more R12or R20; and (i) Rq1, Rq2, and Rp2are each independently selected from Rd, and Reand Rp1, together with the atoms to which they are attached, form a 5-6 membered heterocycle that is unsubstituted or is substituted with one or more Rd; or (ii) Rp1, Rp2, and Rq2are each independently selected from Rd, and Reand Rq1, together with the atoms to which they are attached, form a 5-6 membered heterocycle that is unsubstituted or is substituted with one or more Rd.

70. The compound of any one of claims 54, 55 and 69, wherein the compound is a compound according to Formula IIBB, IICC, IIDD, IIEE, IIFF, IIGG, IIHH, or IIJJ:or a salt (e.g., pharmaceutically acceptable salt) thereof, wherein: each Rdis independently selected from H, deuterium, -OR12, =O, -C(O)(C1-6alkylene)CN, - C(O)(C1-6alkylene)OH, -C(O)(C1-6alkyl), -C(O)N(R14)2, -C(O)(3-6 membered carbocycle), -S(O)2(C1-6alkyl), halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R20, and wherein any 3-6 membered carbocycle is unsubstituted or substituted with one or more R12or R20; and Re, if present, is selected from -C(O)(C1-6alkyl)CN, -C(O)(C1-6alkyl)OH, -C(O)(C1-6alkyl), - C(O)O(C1-6alkyl), -C(O)N(R14)2, -C(O)OR14, -C(O)(3-6 membered carbocycle), -C(O)(3- 8 membered heterocycle), -C(O)(5-6 membered heteraryl), -C(O)O(3-6 membered carbocycle), -C(O)O(3-6 membered heterocycle), -C(O)O(C1-6alkylene)(3-6 membered heterocycle), -S(O)2(C1-6alkyl), a 5-6 membered heteroaryl, a 3-6 membered carbocycle, and C1-6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted orsubstituted with one or more R20, and wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20.

71. The compound of any one of claims 54, 55, and 57-70, wherein R6is selected from:X is selected from N and C-CN; Y is selected from O, S, and Se; R23is selected from -N(R12)2, C1-6alkyl, and C1-6alkyl-N(R14)2, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; and R24, R25, and R26are independently selected from H, deuterium, halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13.^^^ 72. The compound of claim 71, wherein R6is selected from:, ,673. The compound of claim 71 or 72, wherein R is selected from: , ,74. The compound of any one of claims 71-73, wherein R6is selected from:,75. The compound of any one of claims 54, 55, and 57-70, wherein the compound is a compound according to Formula IIR1’, IIU1’, IIV1’, or IIZ1:or a salt (e.g., pharmaceutically acceptable salt) thereof, wherein: each Rdis independently selected from H, deuterium, -OR12, =O, -C(O)(C1-6alkylene)CN, - C(O)(C1-6alkylene)OH, -C(O)(C1-6alkyl), -C(O)N(R14)2, -C(O)(3-6 membered carbocycle), -S(O)2(C1-6alkyl), halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R20, and wherein any 3-6 membered carbocycle is unsubstituted or substituted with one or more R12or R20; Reis selected from -C(O)(C1-6alkylene)CN, -C(O)(C1-6alkylene)OH, -C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), -C(O)N(R14)2, -C(O)OR14, -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), -C(O)(5-6 membered heteraryl), -C(O)O(3-6 membered carbocycle), -C(O)O(3-6 membered heterocycle), -C(O)O(C1-6alkylene)(3-6 membered heterocycle), -S(O)2(C1-6alkyl), a 5-6 membered heteroaryl, a 3-6 membered carbocycle, and C1-6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, and wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20; X is selected from N and C-CN; Y is selected from O and S; R23is selected from -N(R12)2, C1-6alkyl, and C1-6alkyl-N(R14)2, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; andR24, R25, and R26are independently selected from H, deuterium, halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13.

76. The compound of any one of claims 54, 55, and 57-70, wherein the compound is a compound according to Formula IIAA1’:or a salt (e.g., a pharmaceutically acceptable salt) thereof, wherein: each Rdis independently selected from H, deuterium, -OR12, =O, -C(O)(C1-6alkylene)CN, - C(O)(C1-6alkylene)OH, -C(O)(C1-6alkyl), -C(O)(3-6 membered carbocycle), - C(O)N(R14)2, -S(O)2(C1-6alkyl), a 3-6 membered carbocycle, a 3-6 membered heterocycle, halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R20, and wherein any 3-6 membered carbocycle or 3-6 membered heterocycle is unsubstituted or substituted with one or more R12or R20; X is selected from N and C-CN; Y is selected from O and S; R23is selected from -N(R12)2, C1-6alkyl, and C1-6alkyl-N(R14)2, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R24, R25, and R26are independently selected from H, deuterium, halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; and (i) Rq1, Rq2, and Rp2are each independently selected from Rd, and Reand Rp1, together with the atoms to which they are attached, form a 5-6 membered heterocycle that is unsubstituted or is substituted with one or more Rd; or (ii) Rp1, Rp2, and Rq2are each independently selected from Rd, and Reand Rq1, together with the atoms to which they are attached, form a 5-6 membered heterocycle that is unsubstituted or is substituted with one or more Rd.

77. The compound of claim 76, wherein the compound is a compound according to Formula IIBB1, IICC1, IIDD1, IIEE1, IIFF1, IIGG1, IIHH1, or IIJJ1:or a salt (e.g., pharmaceutically acceptable salt) thereof, wherein: each Rdis independently selected from H, deuterium, -OR12, =O, -C(O)(C1-6alkylene)CN, - C(O)(C1-6alkylene)OH, -C(O)(C1-6alkyl), -C(O)N(R14)2, -C(O)(3-6 membered carbocycle), -S(O)2(C1-6alkyl), halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R20, and wherein any 3-6 membered carbocycle is unsubstituted or substituted with one or more R12or R20; Re, if present, is selected from -C(O)(C1-6alkyl)CN, -C(O)(C1-6alkyl)OH, -C(O)(C1-6alkyl), - C(O)O(C1-6alkyl), -C(O)N(R14)2, -C(O)OR14, -C(O)(3-6 membered carbocycle), -C(O)(3- 8 membered heterocycle), -C(O)(5-6 membered heteraryl), -C(O)O(3-6 membered carbocycle), -C(O)O(3-6 membered heterocycle), -C(O)O(C1-6alkylene)(3-6 membered heterocycle), -S(O)2(C1-6alkyl), a 5-6 membered heteroaryl, a 3-6 membered carbocycle, and C1-6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, and wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20; X is selected from N and C-CN; Y is selected from O and S; R23is selected from -N(R12)2, C1-6alkyl, and C1-6alkyl-N(R14)2, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; and R24, R25, and R26are independently selected from H, deuterium, halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13.

78. The compound of any one of claims 75-77, wherein X is C-CN, Y is S, and R23is -N(R12)2.

79. The compound of any one of claims 75-78, wherein one or more of R24, R25, and R26is a halogen (e.g., F).

80. The compound of any one of claims 68-79, wherein Reis C1-6alkyl that is unsubstituted or substituted with one or more R20.

81. The compound of any one of claims 68-79, wherein Reis -C(O)(3-6 membered carbocycle).

82. The compound of any one of claims 68-79, wherein Reis selected from -C(O)(C1-6alkyl), - C(O)(3-6 membered carbocycle), and -C(O)O(C1-6alkyl), wherein any C1-6alkyl is unsubstituted or substituted with one or more R20, and any 3-6 membered carbocycle is unsubstituted or substituted with one or more R12or R20.

83. The compound of any one of claims 68-82, wherein each Rdis H.

84. The compound of any one of claims 54-83, wherein R2is H.

85. The compound of any one of claims 54-84, wherein R2is selected from C1-6alkyl that is unsubstituted or is substituted with one or more R13and is optionally deuterated.

86. The compound of claim 85, wherein R2is selected from C1-2alkyl and is optionally deuterated.

87. The compound of any one of claims 54, 55, and 57-86, wherein R1is selected from -OR8.

88. The compound of claim 87, wherein R1is selected from:, ,, Ra1, Ra2, Rb1, Rb2, Ra3, and Rb3are each independently selected from deuterium, halogen, C1-6alkyl, C2-6alkenyl,12 a2C1-6heteroalkyl, -OR , and H, wherein R and Rb2or Ra3and Rb3can optionally join together to form a 3-6 membered carbocycle, and wherein any C1-6alkyl, C2-6alkenyl, or 3-6 membered carbocycle is unsubstituted or is substituted with one or more R13.

89. The compound of claim 88, wherein R1is selected from:^^ ^^90. The compound of claim 87, wherein R1is selected from:wherein each Raand Rbis independently selected from halogen, C1-6alkyl, C2-6alkenyl, -OR12, and H; and each Rcis independently selected from C1-6alkyl and H, wherein an Raand Rbor Rcoptionally join together to form a 3-6 membered carbocycle or heterocycle, and wherein any C1-6alkyl, C2-6alkenyl, or 3-6 membered carbocycle or heterocycle is unsubstituted or is substituted with one or more R13.

91. The compound of claim 90, wherein R1is selected from:, ,92. The compound of any one of claims 54, 55, and 57-86, wherein R1is selected from, wherein: each R28is independently selected from C1-6alkyl and halogen; and each R29is independently selected from halogen and C1-6alkyl; R30is N(R14)2or a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted or substituted with one or more R28; and n is 0-2.

93. The compound of claim 92, wherein R30is N(R14)2.

94. The compound of claim 92 or 93, wherein at least one R29is a halogen such as F.

95. The compound of any one of claims 92-94, wherein R1is selected from:

96. The compound of any one of claims 54-86, wherein R1is a heterocycle comprising one or more N atoms, wherein the heterocycle is unsubstituted or substituted with one or more R31, wherein each R31is selected from C1-6alkyl.

97. The compound of claim 96, wherein R1is a 6-10 membered heterocycle comprising one or more N atoms, wherein the heterocycle is unsubstituted or substituted with one or more R31, wherein each R31is selected from C1-6alkyl.

98. The compound of claim 96 or 97, wherein R1is selected from:57-86, wherein R1is H.

100. The compound of any one of claims 54, 55, and 57-99, wherein R5is a halogen (e.g., F or Cl).

101. The compound of any one of claims 54, 55, and 57-99, wherein R5is selected from C1-6alkyl that is unsubstituted or substituted with one or more R13.

102. The compound of claim 101, wherein R5is selected from - CH3, -CF2H, -CF3, -CH2CN, and - CH2CH3.

103. The compound of claim 102, wherein R5is -CF3.

104. The compound of any one of claims 54-103, wherein the compound is not a compound included in Table 1.

105. A compound represented by Formula IV:or a salt (e.g., pharmaceutically acceptable salt) thereof, wherein:R1 is selected from -OR2is selected from H, C1-6alkyl, and a 3-6 membered carbocycle, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13; R3is selected from C1-6alkyl that is substituted with one or more R10; R4is H; R5is selected from halogen and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R6is a bicyclic heteroaryl substituted with one or more R15; R7is selected from halogen; R8is selected from a heterocycle and an alkylheterocycle, wherein any heterocycle comprises 4-8 ring atoms and is unsubstituted or is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-6alkyl; each R10is independently selected from a 3-6 membered heterocycle, a 5-6 membered heteroaryl, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R20, and any 3-6 membered heterocycle or 5-6 membered heteroaryl is unsubstituted or substituted with one or more =O, R12, or R13; each R12is independently selected from C1-6alkyl, C2-6 alkenyl, and H, wherein any C1-6alkyl or C2-6 alkenyl is unsubstituted or substituted with one or more R13; each R13is independently selected from -OR14, -CN, -N(R14)2, and halogen; each R14is independently selected from C1-6alkyl, C2-6 alkenyl, and H; each R15is independently selected from deuterium, halogen, -N(R12)2, -CN, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; each R20is independently selected from -OH, -OC1-6alkyl, -CN, -NH2, -NHC1-6alkyl, and halogen; R27is a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted or substituted with one or more R28; each R28is independently selected from C1-6alkyl and halogen; andRaand Rbare each independently selected from halogen, C1-6alkyl, -OR12, and H, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13, and wherein an Raand Rboptionally join together to form a 3-6 membered carbocycle or heterocycle.

106. The compound of claim 105, wherein the compound is of Formula IV-a:or a salt (e.g., pharmaceutically acceptable salt) thereof.

107. The compound of claim 105, wherein R6 is selected from:X is selected from N and C-CN; Y is selected from O and S; R23is selected from -N(R12)2, C1-6alkyl, and C1-6alkyl-N(R14)2, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; and R24, R25, and R26are independently selected from H, deuterium, halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13.^^^108. The compound of claim 105 or claim 107, wherein R6is selected from:any of which is substituted with one or more R15.

109. The compound of any one of claims 105, and 107-108, wherein R6is selected from:.

110. The compound of any one of claims 105, and 107-109, wherein R6is selected from:

111. The compound of claim 105, wherein the compound is a compound according to Formula IVB:( ), or a salt (e.g., pharmaceutically acceptable salt) thereof, wherein: X is selected from N and C-CN; Y is selected from O and S; R23is selected from -N(R12)2, C1-6alkyl, and C1-6alkyl-N(R14)2, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; and R24, R25, and R26are independently selected from H, deuterium, halogen, -OR12, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13.

112. The compound of any one of claims 105, and 107-111, wherein R1is selected from -OR8.

113. The compound of claim 112, wherein R1is selected from:, wherein Raand Rbare each independently selected from halogen, C1-6alkyl, -OR12, and H, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13.

114. The compound of claim 113, wherein R1is selected from:, , , , 115. The compound of claim 112, wherein R1is selected from:^^wherein each Raand Rbis independently selected from halogen, C1-6alkyl, -OR12, and H; and Rcis selected from C1-6alkyl, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13, and wherein an Raand Rbor Rcoptionally join together to form a 3-6 membered carbocycle or heterocycle.

116. The compound of claim 115, wherein R1is selected from:, ,, , , , and .

117. The compound of any one of claims 105, and 107-111, wherein R1is selected from.

118. The compound of claim 105, wherein the compound is a compound according to Formula IVC:or a salt (e.g., pharmaceutically acceptable salt) thereof, wherein: Raand Rbare each independently selected from halogen, C1-6alkyl, -OR12, and H, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13; X is selected from N and C-CN; Y is selected from O and S; R23is selected from -N(R12)2, C1-6alkyl, and C1-6alkyl-N(R14)2, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; and R24, R25, and R26are independently selected from H, deuterium, halogen, -OR12, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13.

119. The compound of claim 118, wherein Rais a halogen (e.g., F).

120. The compound of claim 118 or 119, wherein Rbis H.

121. The compound of any one of claims 111-120, wherein X is C-CN, Y is S, and R23is selected from -N(R12)2.

122. The compound of any one of claims 111-121, wherein at least one of R24, R25, and R26is a halogen (e.g., F).

123. The compound of any one of claims 105-122, wherein R3is selected from C1-3alkyl that is substituted with one or more R10.

124. The compound of claim 123, wherein each R10is independently selected from 3-6 membered heterocycle and a 5-6 membered heteroaryl, wherein any 3-6 membered heterocycle or 5-6 membered heteroaryl is unsubstituted or substituted with one or more =O, R12, or R13.

125. The compound of claim 124, wherein each R10is independently selected from thiazole, oxazole, isoxazole, isothiazole, pyrazole, and pyridine, any of which is unsubstituted or substituted with one or more R12, or R13.

126. The compound of any one of claims 105-125, wherein R2is H.

127. The compound of any one of claims 105-125, wherein R2is selected from C1-6alkyl that is unsubstituted or is substituted with one or more R13.

128. The compound of claim 127, wherein R2is selected from C1-2alkyl that is unsubstituted.

129. The compound of any one of claims 105-125, wherein R2is a 3-6 membered carbocycle.

130. The compound of any one of claims 105-122, wherein the moiety is selected from:a, any of which is optionally further substituted with one or more R10.

131. The compound of any one of claims 105, and 107-130, wherein R5is a halogen (e.g., F or Cl).

132. The compound of any one of claims 105, and 107-130, wherein R5is selected from C1-6alkyl that is unsubstituted or substituted with one or more R13.

133. The compound of claim 132, wherein R5is selected from -CF2H, -CF3, -CH2CN, and -CH2CH3.

134. The compound of claim 133, wherein R5is –CF3.

135. The compound of any one of claims 105, and 107-134, wherein R7is F.

136. A compound represented by Formula V’:or a salt (e.g., pharmaceutically acceptable salt) thereof, wherein: R1is selected from -Oheterocycle comprising one or more N atoms, wherein the heterocycle is unsubstituted or substituted with one or more R31; Rmis selected from hydrogen and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R4is H; R5is selected from halogen and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R6is a bicyclic heteroaryl that is substituted with one or more R15; R7is selected from halogen; R8is selected from a heterocycle and an alkylheterocycle, wherein any heterocycle comprises 4-8 ring atoms and is unsubstituted or is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-6alkyl; each R12is independently selected from C1-6alkyl, C2-6 alkenyl, and H, wherein any C1-6alkyl or C2-6 alkenyl is unsubstituted or substituted with one or more R13; each R13is independently selected from -OR14, -CN, -N(R14)2, and halogen; each R14is independently selected from C1-6alkyl, C2-6alkenyl, and H; each R15is independently selected from deuterium, halogen, -N(R12)2, -CN, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; each R28is independently selected from C1-6alkyl and halogen; each R29is independently selected from halogen and C1-6alkyl; R30is N(R14)2or a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted or substituted with one or more R28; n is 0-2; each R31is selected from C1-6alkyl; and Raand Rbare each independently selected from deuterium, halogen, C1-6alkyl, C2-6alkenyl, a 3-6 membered carbocycle, -OR12, and H, wherein an Raand Rboptionally join together toform a 3-6 membered carbocycle or heterocycle, and wherein any C1-6alkyl, C2-6 alkenyl, or 3-6 membered carbocycle or heterocycle is unsubstituted or is substituted with one or more R13.

137. The compound of claim 136, wherein Rmis hydrogen.

138. The compound of claim 136, wherein Rmis C1-6alkyl that is unsubstituted or substituted with one or more R13.

139. The compound of claim 138, wherein Rmis methyl that is unsubstituted.

140. The compound of any one of claims 136-139, wherein Rwherein: X is selected from N and C-CN; Y is selected from O and S; R23is selected from -N(R12)2, C1-6alkyl, and C1-6alkyl-N(R14)2, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; and R24, R25, and R26are independently selected from H, deuterium, halogen, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13.

141. The compound of any one of claims 136-140, wherein R6is selected from:any of which is substituted with one or more R15.

142. The compound of any one of claims 136-141, wherein R6is selected fr143. The compound of any one of claims 136-142, wherein R6is selected from:,144. The compound of any one of claims 136-140, wherein the compound is a compound of Formula VC’:or a salt (e.g., pharmaceutically acceptable salt) thereof, wherein: X is selected from N and C-CN; Y is selected from O and S; R23is selected from -N(R12)2, C1-6alkyl, and C1-6alkyl-N(R14)2, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; and R24, R25, and R26are independently selected from H, deuterium, halogen, -OR12, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13.

145. The compound of any one of claims 140-144, wherein X is C-CN, Y is S, R23is -N(R12)2, and one or more of R24, R25, and R26is a halogen (e.g., F).

146. The compound of any one of claims 136-145, wherein R1is selected from -OR8.

147. The compound of claim 146, wherein R1 is selected from, wherein:Ra1, Ra2, Rb1, and Rbare each independently selected from deuterium, halogen, C1-6alkyl, C2- 6alkenyl, -OR12, and H or are absent, wherein Ra2and Rb2can optionally join together to form a 3-6 membered carbocycle, and wherein any C1-6alkyl, C2-6alkenyl, or 3-6 membered carbocycle is unsubstituted or is substituted with one or more R13.

148. The compound of claim 147, wherein R1is selected from:, , , , ,, 149. The compound of claim 146, wherein R1is selected from: ^^, , , , wherein each Raand Rbis independently selected from halogen, C1-6alkyl, C2-6alkenyl, -OR12, and H; and each Rcis independently selected from H and C1-6alkyl, wherein an Raand Rbor Rcoptionally join together to form a 3-6 membered carbocycle or heterocycle, and wherein any C1-6alkyl, C2-6alkenyl, or 3-6 membered carbocycle or heterocycle is unsubstituted or is substituted with one or more R13.

150. The compound of claim 149, wherein R1is selected from:.

151. The compound of any one of claims 136-145, wherein R1is selected from, wherein: each R28is independently selected from C1-6alkyl and halogen; each R29is independently selected from halogen and C1-6alkyl; R30is N(R14)2 or a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted or substituted with one or more R28; and n is 0-2.

152. The compound of claim 151, wherein R30is N(R14)2.

153. The compound of claim 151 or 152, wherein at least one R29is a halogen such as F.

154. The compound of any one of claims 151-153, wherein R1is selected from:, ,155. The compound of any one of claims 136-145, wherein R1is a heterocycle comprising one or more N atoms, wherein the heterocycle is unsubstituted or substituted with one or more R31, wherein each R31is selected from C1-6alkyl.

156. The compound of claim 155, wherein R1is a 6-10 membered heterocycle comprising one or more N atoms, wherein the heterocycle is unsubstituted or substituted with one or more R31, wherein each R31is selected from C1-6alkyl.

157. The compound of claim 156, wherein R1is selected from:

158. The compound of any one of claims 136-157, wherein R5is a halogen (e.g., F or Cl).

159. The compound of any one of claims 136-157, wherein R5is selected from C1-6alkyl that is unsubstituted or substituted with one or more R13.

160. The compound of claim 159, wherein R5is selected from C1-6alkyl that is substituted with one or more halogens or -CN.

161. The compound of claim 160, wherein R5is selected from -CF2H, -CF3, -CH2CN, and -CH2CH3.

162. The compound of claim 161, wherein R5is –CF3.

163. The compound of any one of claims 136-162, wherein R7is F.

164. A compound represented by Formula III:or a salt (e.g., pharmaceutically acceptable salt) thereof, wherein: Z is N or C-R5; R1is selected from H, , , heterocycle comprising one or more N atoms, wherein the heterocycle is unsubstituted or substituted with one or more R31; R2is selected from H, C1-6alkyl, and a 3-6 membered carbocycle, wherein any C1-6alkyl is unsubstituted or is substituted with one or more R13and is optionally deuterated;R3is selected from 3- to 12-membered cycloalkyl optionally fused to a 5- or 6-membered aryl, heterocycle, or heteroaryl, a 4-10 membered heterocycle, or -(C1-6alkylenyl)(5-6 membered heteroaryl), wherein any cycloalkyl, aryl, heterocycle, or heteroaryl is unsubstituted or substituted with one or more R10; R4is H, -OR12,or -N(R14)2; R5is selected from halogen, -CN, 5- to 6-membered heteroaryl, -OC1-6alkyl, C1-6alkyl, and H, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; R6is a phenyl, naphthyl, or bicyclic heteroaryl, wherein the phenyl, naphthyl, or bicyclic heteroaryl is substituted with one or more R15; R7is selected from halogen or H; R8is selected from a heterocycle and an alkylheterocycle, wherein any heterocycle comprises 4-9 members and is unsubstituted or is substituted with one or more Raor Rb, and wherein an alkyl moiety of any alkylheterocycle is selected from C1-6alkyl, and C1-6alkyl is optionally deuterated (e.g. -CH2- or -CD2-); each R10is independently selected from deuterium, -OR12, =O, =S, -CN, -NSOMe2, -C(O)(C1- 6alkylene)CN, -C(O)(C1-6alkylene)OH, -C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), - C(O)N(R14)2, -C(O)OR14, -C(O)(3-6 membered carbocycle), -C(O)(3-8 membered heterocycle), -C(O)(5-6 membered heteroaryl), -C(O)O(3-6 membered carbocycle), - C(O)O(3-6 membered heterocycle), -C(O)O(5-6 membered heteroaryl),-C(O)O(C1- 6alkylene)(3-6 membered heterocycle), -S(O)2(C1-6alkyl), -C(S)(C1-6alkyl), -C(S)O(C1- 6alkyl), -C(S)N(C1-6alkyl)2, -C(=N-OR12)(C1-6alkyl), -C(O)N(R12)OR12,^halogen, phenyl, a 5-6 membered heteroaryl, a 3-6 membered carbocycle, a 3-6 membered heterocycle, C2-6alkenyl, and C1-6alkyl, wherein any C1-6alkyl is optionally deuterated and is unsubstituted or substituted with one or more R20, wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20, and wherein two R10s optionally join together to form, together with the atom(s) to which they are attached, a 3-6 membered carbocycle or heterocycle; each R12is independently selected from C1-6alkyl, C2-6alkenyl, and H, wherein any C1-6alkyl or C2-6 alkenyl is unsubstituted or substituted with one or more R13; each R13is independently selected from -OR14, -OC(O)R14, -CN, -N(R14)2, and halogen; each R14is independently selected from a 3-6 membered carbocycle, a 3-8 membered heterocycle, C1-6alkyl, -OR12, C2-6 alkenyl, and H, wherein any C1-6alkyl is optionally deuterated;each R15is independently selected from deuterium, -OH, halogen, -N(R12)2, -CN, C2-6 alkynyl, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; each R20is independently selected from -OH, -OC1-6alkyl, -OC1-6haloalkyl, =O, -CN, -NH2, -NHC1- 6alkyl, -C(O)(C1-6alkyl), -C(O)OR12, -C(O)N(R12)2, -S(O)2R12, a 3-6 membered carbocycle, phenyl, and halogen; each R28is independently selected from C1-6alkyl, -OR12, C1-6heteroalkyl, wherein two heteroalkyl groups can optionally join together to form a 3-6 membered heterocycle that is unsubstituted or substituted with one or more R13and halogen; each R29is independently selected from halogen and C1-6alkyl; R30is N(R12)2 or a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted or substituted with one or more R28; each R31is selected from C1-6alkyl; n is 0-2; and Raand Rbare each independently selected from deuterium, halogen, C1-6alkyl, C2-6 alkenyl,, , -C1-6heteroalkyl, a 3-6 membered carbocycle, -OR12, and H, wherein an Raand Rboptionally join together to form a 3-6 membered carbocycle or heterocycle, and wherein any C1-6alkyl, C2-6 alkenyl, or 3-6 membered carbocycle or heterocycle is unsubstituted or is substituted with one or more R13.

165. The compound of claim 164, wherein R3is selected from a 4-10 membered heterocycle that is unsubstituted or substituted with one or more R10, provided that (i) when the heterocycle contains a nitrogen atom, the nitrogen atom is substituted with R10, or (ii) the heterocycle does not comprise an –NH- moiety.

166. The compound of any one of claims 164-165, wherein R3is a 4-6 membered heterocycle that includes 1 heteroatom selected from O, S, and N.

167. The compound of claim 166, wherein R3is a 4-6 membered heterocycle that includes 1 heteroatom selected from O, S, and N, wherein the heterocycle is substituted with 1-4 R10, provided that when the heterocycle contains a nitrogen atom, the nitrogen atom is substituted with R10.

168. The compound of any one of claims 164-167, wherein R3is a pyrrolidine that is substituted with 1-4 R10, provided that the nitrogen atom is substituted with R10.

169. The compound of claim 168, wherein each R10is independently selected from deuterium, - C(O)N(R14)2, -C(O)(C1-6alkyl), -C(O)O(C1-6alkyl), -C(O)(3-6 membered carbocycle), -C(O)(3-8membered heterocycle), a 3-6 membered heterocycle, C2-6 alkenyl, a 5-6 membered heteroaryl, halogen, phenyl, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R20, and wherein any 3-6 membered carbocycle, 5-6 membered heteroaryl, or 3-6 or 3-8 membered heterocycle is unsubstituted or substituted with one or more R12or R20.

170. The compound of any one of claims 164-169, wherein R3is selected from:,, , , , ,, , , , , ,,, , , , , ,, , , , , , ny of which is optionally further substituted with one ormore R0.

171. The compound of claim 170, wherein R3is selected from:, ,w172. The compound of any one of claims 164-165, wherein R3is a 7-10 membered heterocycle that includes one or more heteroatoms selected from O, S, and N, wherein the heterocycle is unsubstituted or is substituted with one or more R10.

173. The compound of claim 172, wherein R3is a 7-10 membered heterocycle that includes one or more heteroatoms selected from O, S, and N, wherein the heterocycle is unsubstituted or is substituted with one or more R10, provided that (i) when the heterocycle contains a nitrogen atom, the nitrogen atom is substituted with R10or (ii) the heterocycle does not comprise an –NH- moiety.

174. The compound of claim 172, wherein R3is a 7-10 membered heterocycle comprising a fused ring system that includes one or more heteroatoms selected from O, S, and N, wherein the heterocycle is unsubstituted or is substituted with one or more R10.

175. The compound of any one of claims 164-165 and 172-174, wherein R3is selected from:, , , , , ,, , , , , and any of which is optionally further substituted with one or10more R .

176. The compound of claim 175, wherein R3is selected from:, ,,, , , , ,, , , , , any of which is optionally further substituted with one or more R10.

177. The compound of any one of claims 164-176, wherein R6 is selected from:,X is selected from N and C-CN; Y is selected from O, S, and Se; R23is selected from -N(R12)2, C1-6alkyl, and C1-6alkyl-N(R14)2, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13; and R24, R25, and R26are independently selected from H, deuterium, -OH, halogen, C2-6alkynyl, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13.^^^ 178. The compound of claim 177, wherein R6is selected from:any of which is substituted with one or more R15.

179. The compound of claim 177 or 178, wherein R6is selected from:,.

180. The compound of any one of claims 177-179, wherein R6is selected from: ,181. The compound of any one of claims 177-180, wherein Reis C1-6alkyl that is unsubstituted or substituted with one or more R20.

182. The compound of any one of claims 177-180, wherein Reis -C(O)(3-6 membered carbocycle).

183. The compound of any one of claims 177-180, wherein Reis selected from -C(O)(C1-6alkyl), - C(O)(3-6 membered carbocycle), and -C(O)O(C1-6alkyl), wherein any C1-6alkyl is unsubstituted or substituted with one or more R20, and any 3-6 membered carbocycle is unsubstituted or substituted with one or more R12or R20.

184. The compound of any one of claims 177-183, wherein each Rdis H.

185. The compound of any one of claims 164-184, wherein R2is H.

186. The compound of any one of claims 164-185, wherein R2is selected from C1-6alkyl that is unsubstituted or is substituted with one or more R13and is optionally deuterated.

187. The compound of claim 186, wherein R2is selected from C1-2alkyl and is optionally deuterated.

188. The compound of any one of claims 164-187, wherein R1is selected from -OR8.

189. The compound of claim 188, wherein R1is selected from:, Ra1, Ra2, Rb1, Rb2, Ra3, and Rb3areeach independently selected from deuterium, halogen, C1-6alkyl, C2-6alkenyl,heteroalkyl, -OR12, and H, wherein Ra2and Rb2or Ra3and Rb3can optionally join together to form a 3-6 membered carbocycle, and wherein any C1-6alkyl, C2-6alkenyl, or 3-6 membered carbocycle is unsubstituted or is substituted with one or more R13.

190. The compound of claim 189, wherein R1is selected from:

191. The compound of claim 188, wherein R1is selected from:, wherein each Raand Rbis independently selected from halogen, C1-6alkyl, C2-6alkenyl,, - OR12, and H; and each Rcis independently selected from C1-6alkyl and H, wherein an Raand Rbor Rcoptionally join together to form a 3-6 membered carbocycle or heterocycle, and wherein any C1-6alkyl, C2-6alkenyl, or 3-6 membered carbocycle or heterocycle is unsubstituted or is substituted with one or more R13. 1192. The compound of claim 191, wherein R is selected from: , ,193. The compound of any one of claims 164-187, wherein R1is selected fromeach R28is independently selected from C1-6alkyl and halogen; and each R29is independently selected from halogen and C1-6alkyl; R30is N(R14)2 or a 3-6 membered heterocycle including one or more heteroatoms selected from N, O, and S, wherein the heterocycle is unsubstituted or substituted with one or more R28; and n is 0-2.

194. The compound of claim 193, wherein R30is N(R14)2.

195. The compound of claim 193 or 194, wherein at least one R29is a halogen such as F.

196. The compound of any one of claims 193-195, wherein R1is selected from:

197. The compound of any one of claims 164-187, wherein R1is a heterocycle comprising one or more N atoms, wherein the heterocycle is unsubstituted or substituted with one or more R31, wherein each R31is selected from C1-6alkyl.

198. The compound of claim 197, wherein R1is a 6-10 membered heterocycle comprising one or more N atoms, wherein the heterocycle is unsubstituted or substituted with one or more R31, wherein each R31is selected from C1-6alkyl.

199. The compound of claim 197 or 198, wherein R1is selected from:

200. The compound of any one of claims 164-187, wherein R1is H.

201. The compound of any one of claims 164-200, wherein R5is a halogen (e.g., F or Cl).

202. The compound of any one of claims 164-200, wherein R5is selected from C1-6alkyl that is unsubstituted or substituted with one or more R13.

203. The compound of claim 202, wherein R5is selected from - CH3, -CF2H, -CF3, -CH2CN, and - CH2CH3.

204. The compound of claim 203, wherein R5is -CF3.

205. The compound of any one of claims 164-204, wherein the compound is a compound included in Table 1.^ 206. A compound shown in Table 3, Table 3a, Table 3b, or Table 3b, or a salt (e.g., pharmaceutically acceptable salt) thereof.

207. A pharmaceutical composition comprising a compound of any one of claims 1-206, or a salt (e.g., pharmaceutically acceptable salt) thereof, and a pharmaceutically acceptable excipient.

208. A compound of any one of claims 1-206, or a salt (e.g., pharmaceutically acceptable salt) thereof, for use as a medicament.

209. The compound of claim 208, wherein the medicament is useful in the prevention or treatment of a disease, disorder, or condition ameliorated by the inhibition of KRAS having a Q61H, G13D,G12D, G12V, G12C, G12S, G12A, or G12R mutation, or wild-type KRAS, including wild-type amplified KRAS.

210. The compound of claim 209, wherein the medicament is useful in the prevention or treatment of a disease, disorder, or condition ameliorated by the inhibition of wild-type KRAS, including wild- type amplified KRAS.

211. The compound of claim 209, wherein the medicament is useful in the prevention or treatment of a disease, disorder, or condition ameliorated by the inhibition of KRAS having a G12D, G12R, or G12V mutation.

212. The compound of any one of claims 208-211, wherein the medicament is useful in the prevention or treatment of a cancer.

213. The compound of claim 212, wherein the cancer is selected from the group consisting of pancreatic cancer, colorectal cancer, and lung cancer.

214. A compound of any one of claims 1-205, or a salt (e.g., pharmaceutically acceptable salt) thereof, for use in the treatment of a disease, disorder, or condition.

215. The compound of claim 214, wherein the disease, disorder, or condition is a cancer.

216. The compound of claim 215, wherein the cancer is selected from the group consisting of pancreatic cancer, colorectal cancer, and lung cancer.

217. The compound of any one of claims 214-216, wherein the compound is used in the treatment of a disease, disorder, or condition in a subject in need thereof.

218. A compound of any one of claims 1-205, or a salt (e.g., pharmaceutically acceptable salt) thereof, for use in the manufacture of a medicament.

219. The compound of claim 218, wherein the medicament is useful in the prevention or treatment of a disease, disorder, or condition ameliorated by the inhibition of KRAS having a Q61H, G13D, G12D, G12V, G12C, G12S, G12A, or G12R mutation, or wild-type KRAS, including wild-type amplified KRAS.

220. The compound of claim 219, wherein the medicament is useful in the prevention or treatment of a disease, disorder, or condition ameliorated by the inhibition of wild-type KRAS, including wild- type amplified KRAS.

221. The compound of claim 219 or 220, wherein the medicament is useful in the prevention or treatment of a disease, disorder, or condition ameliorated by the inhibition of KRAS having a G12D, G12R, or G12V mutation.

222. The compound of any one of claims 218-221, wherein the medicament is useful in the treatment of a cancer.

223. The compound of claim 222, wherein the cancer is selected from the group consisting of pancreatic cancer, colorectal cancer, and lung cancer.

224. A method, comprising administering a therapeutically effective amount of a compound of any one of claims 1-205, or a salt (e.g., pharmaceutically acceptable salt) thereof, to a subject in need thereof.

225. The method of claim 224, wherein the subject has a disease, disorder, or condition ameliorated by the inhibition of KRAS having a Q61H, G13D, G12D, G12V, G12C, G12S, G12A, or G12R mutation, or wild-type KRAS, including wild-type amplified KRAS.

226. The method of claim 225, wherein the disease, disorder, or condition is ameliorated by the inhibition of wild-type KRAS, including wild-type amplified KRAS.

227. The method of claim 225 or 226, wherein the disease, disorder, or condition is ameliorated by the inhibition of KRAS having a G12D, G12R, or G12V mutation.

228. The method of any one of claims 224-227, wherein the subject has a cancer.

229. The method of claim 228, wherein the subject was previously diagnosed with the cancer.

230. The method of claim 228 or 229, wherein the subject has previously undergone a treatment regimen for the cancer.

231. The method of any one of claims 228-230, wherein the subject has previously entered remission from the cancer.

232. The method of any one of claims 228-231, wherein the cancer is selected from the group consisting of pancreatic cancer, colorectal cancer, and lung cancer.

233. The method of any one of claims 224-232, wherein the compound, or the salt thereof, is administered in combination with an additional therapeutic agent.

234. The use of a compound of any one of claims 1-205, or a salt (e.g., pharmaceutically acceptable salt) thereof, for the manufacture of a medicament for the treatment of a cancer.

235. The use of claim 234, wherein the cancer is selected from the group consisting of pancreatic cancer, colorectal cancer, and lung cancer.

236. A method, comprising contacting a KRAS protein with a compound of any one of claims 1-205, or a salt (e.g., pharmaceutically acceptable salt) thereof.

237. The method of claim 236, wherein contacting the KRAS protein with the compound modulates KRAS.

238. The method of claim 236 or 237, wherein the KRAS protein has a Q61H, G13D, G12D, G12V, G12C, G12S, G12A, or G12R mutation.

239. The method of claim 236 or 237, wherein the KRAS protein is a wild-type KRAS protein, including wild-type amplified KRAS.

240. The method of any one of claims 236-239, wherein the KRAS protein is in an active (GTP- bound) state.

241. The method of any one of claims 236-239, wherein the KRAS protein is in an inactive (GDP- bound) state.

242. The method of any one of claims 236-241, wherein the KRAS protein is located within a cell.

243. The method of claim 242, wherein the cell is located within a subject.

244. The method of claim 243, wherein the subject is a human.

245. The method of claim 243 or 244, wherein the subject has a cancer.

246. The method of claim 245, wherein the cancer is selected from the group consisting of pancreatic cancer, colorectal cancer, and lung cancer.

247. A method of inhibiting the function of a wild-type KRAS protein, including wild-type amplified KRAS, or a KRAS protein having a Q61H, G13D, G12D, G12V, G12C, G12S, G12A, or G12R mutation, comprising contacting the KRAS protein with a compound of any one of claims 1-205, or a salt (e.g., pharmaceutically acceptable salt) thereof.

248. The method of claim 247, wherein the KRAS protein is a wild-type KRAS protein, including wild-type amplified KRAS.

249. The method of claim 247, wherein the KRAS protein has a Q61H, G13D, G12D, G12V, G12C, G12S, G12A, or G12R mutation.

250. The method of claim 247, wherein the KRAS protein has a G12D, G12V, or G12R mutation.

251. The method of any one of claims 247-250, wherein the KRAS protein is in an active (GTP- bound) state.

252. The method of any one of claims 247-250, wherein the KRAS protein is in an inactive (GDP- bound) state.

253. The method of any one of claims 247-252, wherein the KRAS protein is located within a cell.

254. The method of claim 253, wherein the cell is located within a subject.

255. The method of claim 254, wherein the subject is a human.

256. The method of claim 254 or 255, wherein the subject has a cancer.

257. The method of claim 256, wherein the cancer is selected from the group consisting of pancreatic cancer, colorectal cancer, esophageal adenocarcinoma, gastroesophageal junction cancer, invasive ductal carcinoma, and lung cancer.

258. A compound capable of inhibiting a wild-type KRAS protein, including wild-type amplified KRAS, or a KRAS protein having a Q61H, G13D, G12D, G12V, G12C, G12S, G12A, or G12R mutation in both its active (GTP-bound) and inactive (GDP-bound) state.

259. The compound of claim 258, wherein the compound: (i) has IC50 ^0.1 µM, 0.1 µM< IC50 ^1 µM, 1 µM< IC50 ^10 µM, or 10 µM< IC50 in the assay of Biological Example 1 (e.g., a protein:protein interaction (PPI) Homogenous Time Resolved Fluorescence (HTRF) analysis of 50 nM Avi-KRAS G12D (amino acids2-169) GTP / RAF1 RBD-3xFLAG (51-131), 50 nM Avi-KRAS G12C (amino acids 2- 169) GTP / RAF1 RBD-3xFLAG (51-131), 50 nM Avi-KRAS G12V (amino acids 2-169) GTP / RAF1 RBD-3xFLAG (51-131), 50 nM Avi-KRAS WT (amino acids 2-169) GTP / RAF1 RBD-3xFLAG (51-131), and / or 75 nM 3xFLAG-RAF1 RBD (51-131)-Avi; and / or (ii) has IC50^0.1 µM, or IC50>0.1 µM in the assay of Biological Example 2 or 4 (e.g., cell- based pERK HTRF assay in GP2d (G12D) cell); and / or (iii) has IC50^0.1 µM, 0.1 µM< IC50^1 µM, or IC50>1 µM in the assay of Biological Example 3 (cell-based pERK HTRF assay in GP2d (G12D) cell); and / or (iv) has IC50^0.1 µM, 0.1 µM< IC50^1 µM, or IC50>1 µM in the assay of Biological Example 4 (cell-based pERK HTRF assay in AsPC-1, SW1900, HPAC, Capan-2, RKN, H358, HCT116, KP-2, H1573, A549, MKN1, and HT1080); and / or (v) has IC50^0.1 µM, 0.1 µM< IC50^1 µM, or IC50>1 µM in the assay of Biological Example 5 (3D Cell viability assay in AsPC-1, SW1900, HPAC, Capan-2, RKN, H358, HCT116, KP-2, H1573, A549, MKN1, and HT1080).

260. The compound of claim 259, wherein the compound: (i) has IC50 ^0.1 µM, 0.1 µM< IC50 ^1 µM, or 1 µM< IC50 ^10 µM in the assay of Biological Example 1 (e.g., a protein:protein interaction (PPI) Homogenous Time Resolved Fluorescence (HTRF) analysis of 50 nM Avi-KRAS G12D (amino acids 2-169) GTP / RAF1 RBD-3xFLAG (51-131), 50 nM Avi-KRAS G12C (amino acids 2-169) GTP / RAF1 RBD-3xFLAG (51-131), 50 nM Avi-KRAS G12V (amino acids 2-169) GTP / RAF1 RBD-3xFLAG (51-131), 50 nM Avi-KRAS WT (amino acids 2-169) GTP / RAF1 RBD-3xFLAG (51-131), and / or 75 nM 3xFLAG-RAF1 RBD (51-131)-Avi; and / or (ii) has IC50 ^0.1 µM in the assay of Biological Example 2 or 4 (e.g., cell-based pERK HTRF assay in GP2d (G12D) cell); and / or (iii) has IC50 ^0.1 µM or 0.1 µM< IC50 ^1 µM in the assay of Biological Example 3 (cell- based pERK HTRF assay in GP2d (G12D) cell); and / or (iv) has IC50 ^0.1 µM or 0.1 µM< IC50 ^1 µM in the assay of Biological Example 4 (cell- based pERK HTRF assay in AsPC-1, SW1900, HPAC, Capan-2, RKN, H358, HCT116, KP-2, H1573, A549, MKN1, and HT1080); and / or (v) has IC50 ^0.1 µM or 0.1 µM< IC50 ^1 µM in the assay of Biological Example 5 (3D Cell viability assay in AsPC-1, SW1900, HPAC, Capan-2, RKN, H358, HCT116, KP-2, H1573, A549, MKN1, and HT1080).

261. The compound of any one of claims 258-260, wherein the compound is capable of irreversibly binding the KRAS protein.

262. The compound of any one of claims 258-260, wherein the compound is capable of reversibly binding the KRAS protein.

263. The compound of any one of claims 258-262, wherein the compound is a compound according to any one of claims 1-205.