Compositions and methods for the inhibition of KRAS

Abstract

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

Description

[Technical Field]

[0001] STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT 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 U.S. Department of Energy. The U.S. Government has certain rights in this invention.

[0002] Related Applications This application claims priority to and the benefit of U.S. Patent Application No. 63 / 395,699, filed August 5, 2022, U.S. Patent Application No. 63 / 386,285, filed December 6, 2022, and U.S. Patent Application No. 63 / 496,873, filed April 18, 2023, the entire contents of each of which are incorporated herein by reference. [Background technology]

[0003] RAS proteins function as molecular switches, cycling between inactive ("GDP-bound") and active ("GTP-bound") states. RAS signaling occurs through engagement with effector proteins that orchestrate signaling cascades that regulate tumor cell survival and proliferation. Aberrant activation of RAS by oncogenic mutations leads to 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. Mutant KRAS is also frequently observed in other common tumors, including colorectal cancer (approximately 44%) and non-small cell lung cancer (NSCLC, approximately 20-30%). Cancer-associated mutations in the KRAS cluster at three hotspots (G12, G13, and Q61) account for the majority of mutations (77%), resulting in a single amino acid substitution at G12. The KRAS missense mutation G12D is the most prevalent mutation type in human malignancies (35%), followed by G12V (29%). Besides G12, the hotspots G13 and Q61 exhibit mutation rates of 10% and 6%, respectively.

[0005] Developing small-molecule KRAS inhibitors has proven challenging. Recent clinical development of covalent KRAS G12C inhibitors demonstrates the potential of directly targeting the KRAS oncogenic protein. Clinical trial results with two covalent inhibitors, AMG510 (sotorasib) and MRTX849 (adagrasib), have been promising. These inhibitors primarily demonstrated clinical activity in NSCLC, which harbors the highest KRAS G12C mutation frequency. Unfortunately, they appeared less effective in KRAS G12C colorectal cancer. Both compounds target only the inactive (GDP-bound) form of KRAS G12C, and the lack of activity against active (GTP-bound) KRAS G12C may contribute to the development of drug resistance. Furthermore, these covalent inhibitors are limited to specific G12C mutants, which account for approximately 13% of all KRAS-driven cancers, while a large population of non-G12C KRAS cancers remains intolerable. Therefore, KRAS therapeutics that target additional KRAS alterations or combinations thereof represent an unmet clinical need. Pan-KRAS inhibitors have effects across the majority of KRAS mutant alleles, including the most common G12D and G12V, or KRAS wild-type amplified cancers.

[0006] KRAS is essential for mouse development, whereas NRAS and HRAS are dispensable. This requirement for KRAS raises toxicity concerns when targeting wild-type KRAS protein. However, replacing KRAS with HRAS results in viability, mitigating toxicity concerns and suggesting that KRAS isoform-specific inhibitors should be tolerated, as opposed to pan-RAS inhibitors, which may pose toxicity issues. If so, further benefits of pan-KRAS inhibitors may arise from targeting cancers with acquired resistance to KRAS G12C inhibitors. Recent reports have provided insight into the mechanisms of resistance to KRAS G12C inhibitors in the clinic, suggesting the restoration of RAS / MAPK as a driver of resistance. In addition to activation of the KRAS wild-type allele by upstream RTK signaling, a diverse set of mutations has been shown to be acquired in response to KRAS G12C inhibitors. Direct pan-KRAS agents may suppress these events. Therefore, there remains a need for allele-specific and pan-KRAS inhibitors that can be used to treat KRAS-driven cancers regardless of mutation status. Summary of the Invention

[0007] The present disclosure provides compounds, as well as compositions and kits containing the same, and methods of using the same in the treatment of diseases and disorders, such as cancer. The present disclosure provides compounds capable of inhibiting one or more mutant forms of KRAS, such as KRAS with a G12D, G12V, G12C, G12S, G12A, G12R, Q61H, or G13D mutation, or wild-type KRAS. Such compounds may be considered pan-KRAS inhibitors. In some embodiments, the compounds provided herein can target both active GTP-binding proteins and inactive GDP-binding proteins, and these inhibitors may offer therapeutic advantages over compounds that can only target inactive GDP-binding proteins. In some embodiments, the compounds provided herein have inhibitory activity against KRAS proteins that include an 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, the compounds provided herein have inhibitory activity against wild-type KRAS. In some embodiments, the compounds provided herein are useful for treating cancer, such as cancers characterized by KRAS proteins with codon 12 mutations, such as G12D, G12V, G12C, G12S, G12A, or G12R mutations, codon 13 mutations, such as G13D mutations, or codon 61 mutations, such as Q61H mutations, or cancers that may benefit from inhibition of wild-type KRAS.

[0008] In one aspect, the present disclosure provides a compound of formula X [ka] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein R 1 , R2 , R 3 , R 4 , R 5 , R 6 , and R 7In some embodiments, the compound is one of the compounds of formula I, Ia, IA, IA1, IA2, IB, IB1, IB2, IC, IC1, IC2, ID, ID1, ID2, IE, IE1, IE2, IF, IF1, IF2, II, II', II-a, IIA, IIA1, IIB, IIB1, IIC, IIC1, IID, IID1, IIE, IIE1, IIF, IIF1, IIG, IIG1, IIH, IIH1, IIJ, IIJ1, IIK, IIK1, IIL, IIL1, IIM, IIM1, IIN, IIN1, IIP, IIP1, IIQ, IIQ1, IIR, IIR1, IIS, IIS1, IIT, IIT1, IIU, IIU1, IIV, IIV or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compounds provided herein, or salts, esters, tautomers, zwitterionic forms, 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 wild-type KRAS.In some embodiments, the compounds provided herein, or salts, esters, tautomers, prodrugs, zwitterionic forms, or stereoisomer(s) thereof, can interact with KRAS proteins that contain an 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, the compounds provided herein, or salts, esters, tautomers, zwitterionic forms, or stereoisomer(s) thereof, have inhibitory activity against wild-type KRAS. In some embodiments, the compounds provided herein, or salts, esters, tautomers, zwitterionic forms, or stereoisomer(s) thereof, are capable of binding to KRAS proteins in the active ("GTP-bound") conformation. In some embodiments, the compounds provided herein, or salts, esters, tautomers, zwitterionic forms, or stereoisomer(s) thereof, are capable of binding to KRAS proteins in the inactive ("GDP-bound") conformation. In some embodiments, the compounds provided herein, or salts, esters, tautomers, zwitterionic forms, or stereoisomer(s) thereof, are capable of binding to KRAS proteins in both the active ("GTP-bound") and inactive ("GDP-bound") conformations.

[0009] In another aspect, the disclosure provides a compound provided herein (e.g., a compound represented by Formula I, Ia, IA, IA1, IA2, IB, IB1, IB2, IC, IC1, IC2, ID, ID1, ID2, IE, IE1, IE2, IF, IF1, IF2, II, II', II-a, IIA, IIA1, IIB, IIB1, IIC, IIC1, IID, IID1, IIE, IIE1, IIF, IIF1, IIG, IIG1, IIH, IIH1, IIJ, IIJ1, IIK, IIK1, IIL, IIL1, IIM, IIM1, IIN, IIN1, IIP, IIP1, IIQ, IIQ1, IIR, IIR1, IIS, IIS1, IIT, IIT1, IIU, IIU1, IIV, IIV1, IIW, IIW1, IIX,

[0013] Pharmaceutical compositions are provided comprising a compound represented by one of the formulas: IIX1, IIY, IIY1, IIZ, IIZ1, IIAA, IIAA1, III, III', III-a, IIIA, IIIA1, IIIB, IIIC, IIIC1, IIID, IIIE, IIIF, IIIG, IIIH, IIIJ, IIIK, IIIL, IIIM, IIIN, IIIP, IIIQ, IIIR, IIIS, IIIT, IV, IV-a, IVA, IVB, IVC, V, Va, VA, VB, VC, VI, and VI-a, or any other formula described 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 disclosure provides compounds, e.g., compounds provided herein (e.g., compounds of Formula I, Ia, IA, IA1, IA2, IB, IB1, IB2, IC, IC1, IC2, ID, ID1, ID2, IE, IE1, IE2, IF, IF1, IF2, II, II', II-a, IIA, IIA1, IIB, IIB1, IIC, IIC1, IID, IID1, IIE, IIE1, IIF, IIF1, II G, IIG1, IIH, IIH1, IIJ, IIJ1, IIK, IIK1, IIL, IIL1, IIM, IIM1, IIN, IIN1, IIP, IIP1, IIQ, IIQ1, IIR, IIR1, IIS, IIS1, IIT, IIT1, IIU, IIU1, IIV, IIV1, IIW, IIW1, IIX, IIX1, IIY, IIY1, IIZ, IIZ1, IIAA, IIAA1, III, II Methods are provided for inhibiting KRAS activity in a human or animal subject for the treatment of diseases such as cancer, including pancreatic cancer (e.g., pancreatic ductal adenocarcinoma (PDAC)), colorectal cancer, endometrioid adenocarcinoma, rectal adenocarcinoma, gastric cancer, and lung cancer, using a compound represented by one of the formulas I', III-a, IIIA, IIIA1, IIIB, IIIC, IIIC1, IIID, IIIE, IIIF, IIIG, IIIH, IIIJ, IIIK, IIIL, IIIM, IIIN, IIIP, IIIQ, IIIR, IIIS, IIIT, IV, IV-a, IVA, IVB, IVC, V, Va, VA, VB, VC, VI, and VI-a, or any other formula described herein), or a salt, ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, or a pharmaceutical composition comprising same.

[0011] In another aspect, the disclosure provides a method for the manufacture of a medicament for the treatment of a disease, disorder, or condition that is 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 wild-type KRAS. and the compounds provided herein (e.g., compounds of Formula I, Ia, IA, IA1, IA2, IB, IB1, IB2, IC, IC1, IC2, ID, ID1, ID2, IE, IE1, IE2, IF, IF1, IF2, II, II', II-a, IIA, IIA1, IIB, IIB1, IIC, IIC1, IID, IID1, IIE, IIE1, IIF, IIF1, IIG, IIG1, IIH, IIH1, IIJ, IIJ1, IIK, IIK1, IIL, IIL1, IIM, IIM1, IIN, IIN1, IIP, IIP1, IIQ, IIQ1, IIR, IIR1, IIS, IIS1, IIT, IIT1, IIU, IIU1, IIV, IIV1, I IW, IIW1, IIX, IIX1, IIY, IIY1, IIZ, IIZ1, IIAA, IIAA1, III, III', III-a, IIIA, IIIA1, IIIB, IIIC, IIIC1, IIID, III 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 disclosure provides a compound provided herein (e.g., a compound represented by Formula I, Ia, IA, IA1, IA2, IB, IB1, IB2, IC, IC1, IC2, ID, ID1, ID2, IE, IE1, IE2, IF, IF1, IF2, II, II', II-a, IIA, IIA1, IIB, IIB1, IIC, IIC1, IID, IID1, IIE, IIE1, IIF, IIF1, IIG, IIG1, IIH, IIH1, IIJ, IIJ1, IIK, IIK1, IIL, IIL1, IIM, IIM1, IIN, IIN1, IIP, IIP1, IIQ, IIQ1, IIR, IIR1, IIS, IIS1, IIT, IIT1, IIU, IIU1) for use as a medicament. , IIV, IIV1, IIW, IIW1, IIX, IIX1, IIY, IIY1, IIZ, IIZ1, IIAA, IIAA1, III, III', III-a, IIIA, IIIA1, IIIB, IIIC, IIIC1, IIID, IIIE, IIIF, IIIG, IIIH, IIIJ, IIIK, IIIL, IIIM, IIIN, IIIP, IIIQ, IIIR, IIIS, IIIT, IV, IV-a, IVA, IVB, IVC, V, Va, VA, VB, VC, VI, and VI-a, or any other formula described herein), or a salt, ester, tautomer, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the agent is used to treat a disease, disorder, or condition (e.g., cancer). In some embodiments, the disease, disorder, or condition is pancreatic cancer (eg, pancreatic ductal adenocarcinoma (PDAC)), colorectal cancer, or lung cancer. DETAILED DESCRIPTION OF THE INVENTION

[0013] This disclosure describes the use of compounds of the formula 1, IIF, IIF1, IIG, IIG1, IIH, IIH1, IIJ, IIJ1, IIK, IIK1, IIL, IIL1, IIM, IIM1, IIN, IIN1, IIP, IIP1, IIQ, IIQ1, IIR, IIR1, IIS, IIS1, IIT, IIT1, IIU, IIU1, IIV, IIV1, IIW, and VI-a), which may have useful KRAS inhibitory activity or may be used in the treatment or prevention of diseases, disorders, or conditions in which KRAS plays an active role. Specifically, certain compounds provided herein may have useful inhibitory activity against KRAS proteins having a mutation at codon 12 (e.g., a G12D, G12V, G12C, G12S, G12A, or G12R mutation), KRAS proteins having a mutation at codon 13 (e.g., a G13D mutation), KRAS proteins having a mutation at codon 61 (e.g., a Q61H mutation), or wild-type KRAS proteins in which the KRAS protein is in an active (GTP-bound) or inactive (GDP-bound) conformation. Certain compounds provided herein may be capable of inhibiting both the 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 for preparing and using such compounds and compositions.The present disclosure also provides methods for inhibiting KRAS, including KRAS proteins having a mutation at codon 12 (e.g., a G12D, G12V, G12C, G12S, G12A, or G12R mutation), KRAS proteins having a mutation at codon 13 (e.g., a G13D mutation), KRAS proteins having a mutation at codon 61 (e.g., a Q61H mutation), or wild-type KRAS proteins in which KRAS is in an active or inactive conformation. In one aspect, the present disclosure provides a method for treating a KRAS-mediated disorder, 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 treatment for the KRAS-mediated disorder, the method comprising 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 that is 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 cancer (e.g., as described herein).

[0014] When a range of values is disclosed, where n1 and n2 are numerical values, and the expression "n1... to n2" or "between n1... and n2" is used, the expression is intended to include the numerical values themselves and the range therebetween, unless otherwise specified. The range may be an integer or continuous value between and including the end values. As an example, the range "2 to 6 carbons" is intended to include 2, 3, 4, 5, and 6 carbons, since carbon is an integer unit. As an example, compared to the range "1 to 3 μM (micromolar)," this range is intended to include 1 μM, 3 μM, and all values therebetween, to any significant figure (e.g., 1.255 μM, 2.1 μM, 2.9999 μM, etc.).

[0015] As used herein, "about" is intended to qualify the numerical value it modifies, meaning that such value varies within a margin of error. Unless a specific margin of error, such as the standard deviation for the average value shown in a graph or table of data, is stated, the term "about" should be understood to mean not only a range encompassing the stated value, but also a range encompassed by rounding up or down to that numerical value, taking into account significant digits.

[0016] As used herein, "acyl," alone or in combination, refers to a carbonyl bound to an alkenyl, alkyl, aryl, cycloalkyl, heteroaryl, heterocycle, or any other moiety where the atom bound to the carbonyl is carbon. An "acetyl" group refers to a -C(O)CH group. An "alkylcarbonyl" or "alkanoyl" group refers to an alkyl group bound 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] As used herein, "alkenyl," alone or in combination, refers to a straight- or branched-chain hydrocarbon radical having one or more double bonds and containing 2 to 20 carbon atoms. In certain embodiments, the alkenyl contains 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 groups include ethenyl, propenyl, 2-methylpropenyl, 1,4-butadienyl, and the like. Unless otherwise specified, the term "alkenyl" can include an "alkenylene" group.

[0018] "Alkynyl" refers to a straight or branched chain hydrocarbon having at least two carbon atoms and at least one triple bond, and having the number of carbon atoms indicated (i.e., C 2-6 (means 2 to 6 carbons). Alkynyl is C2, C 2-3 , C 2-4 , C 2-5 , C 2-6 , C 2-7 , C 2-8 , C 2-9 , C 2-10 , C3, C 3-4 , C 3-5 , C 3-6 , C4, C 4-5 , C 4-6 , C5, C 5-6 and C6. Examples of alkynyl groups include, but are not limited to, acetylenyl, propynyl, 1-butynyl, 2-butynyl, 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] As used herein, "alkoxy," alone or in combination, refers to an alkyl ether radical, where the term alkyl is as defined herein. Examples of suitable alkyl ether radicals include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, and the like.

[0020] As used herein, "alkyl," alone or in combination, refers to a straight- or branched-chain alkyl radical containing 1 to 20 carbon atoms (e.g., C 1-20 In certain embodiments, the alkyl refers to a group having 1 to 10 carbon atoms (e.g., C 1-10 In further embodiments, the alkyl may contain 1 to 8 carbon atoms (e.g., C 1-8 In further embodiments, the alkyl may contain 1 to 6 carbon atoms (e.g., C 1-6 In further embodiments, the alkyl may contain 1 to 3 carbon atoms (e.g., C 1-3 The alkyl group may include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isoamyl, hexyl, octyl, nonyl, and the like. As used herein, the term "alkylene," alone or in combination, means a saturated aliphatic group derived from a straight- or branched-chain saturated hydrocarbon bonded at two or more positions, such as methylene (-CH-). Unless otherwise specified, the term "alkyl" may include an "alkylene" group.

[0021] As used herein, "alkylamino," alone or in combination, refers to an alkyl group attached to the parent molecular moiety through an amino group. Suitable alkylamino groups can be mono- or di-alkylated to form, for example, N-methylamino, N-ethylamino, N,N-dimethylamino, N,N-ethylmethylamino, and the like groups.

[0022] As used herein, "alkylthio," alone or in combination, refers to an alkyl thioether (RS-) radical, where the alkyl term is as defined herein and the sulfur may be singly or doubly oxidized. Examples of suitable alkyl thioether radicals include methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio, tert-butylthio, methanesulfonyl, ethanesulfinyl, and the like.

[0023] As used herein, "amido" and "carbamoyl," 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. As used herein, an "amido" group includes "C-amido" and "N-amido" groups. As used herein, the term "C-amido," alone or in combination, refers to a -C(O)N(RR') group, where R and R' are as defined herein or by the specified specifically recited "R" group. In some embodiments, an "amido" group is -C(O)NH, C 1-4 Alkylamides and di(C 1-4 As used herein, "C alkyl" includes amides. 1-4 The term "alkylamide" refers to -C(O)NH(C 1-4 C 1-4 Alkyl is as defined herein. As used herein, the term "N-amido," alone or in combination, refers to the group RC(O)N(R')-, where R and R' are as defined herein or by the specifically recited "R" group specified. As used herein, the term "acylamino," alone or in combination, encompasses an acyl group attached to the parent moiety through an amino group. An example of an "acylamino" group is acetylamino (CHC(O)NH-).

[0024] As used herein, "amino," alone or in combination, refers to -NRR', where 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 an unsubstituted or substituted heterocycloalkyl. An "amino" group can be a primary amine (e.g., -NH), a secondary or disubstituted amine (e.g., -NHR, where R is not hydrogen), or a tertiary or trisubstituted amine (e.g., -NRR', where neither R nor R' is hydrogen).

[0025] As used herein, "aryl," alone or in combination, means a carbocyclic aromatic system containing one, two, or three rings, and such polycyclic ring systems are fused together. The term "aryl" encompasses aromatic groups such as phenyl, naphthyl, anthracenyl, and phenanthryl. The aryl moiety can contain, for example, 5 to 20 carbon atoms, for example, 5 to 12 carbon atoms, for example, 5 or 6 carbon atoms.

[0026] The terms "arylalkenyl" or "aralkenyl," as used herein, alone or in combination, refer to an aryl group attached to the parent molecular moiety through an alkenyl group.

[0027] The terms "arylalkoxy" or "aralkoxy," as used herein, alone or in combination, refer to an aryl group attached to the parent molecular moiety through an alkoxy group.

[0028] The terms "arylalkyl" or "aralkyl," as used herein, alone or in combination, refer to an aryl group attached to the parent molecular moiety through an alkyl group.

[0029] The term "aryloxy," as used herein, alone or in combination, refers to an aryl group attached to the parent molecular moiety through an oxy.

[0030] As used herein, "carbamate," alone or in combination, refers to an ester of carbamic acid (-NHCOO-), which can be attached to the parent molecular moiety through either the nitrogen terminus or the acid terminus, and is unsubstituted or substituted as defined herein.

[0031] As used herein, "O-carbamyl," alone or in combination, refers to an --OC(O)NRR' group, with R and R' as defined herein.

[0032] As used herein, "N-carbamyl," alone or in combination, refers to an ROC(O)NR'- group, with R and R' as defined herein.

[0033] As used herein, "carbonyl" when alone includes formyl [-C(O)H] and in combination is a -C(O)- group.

[0034] As used herein, "carboxyl" or "carboxy" refers to -C(O)OH or the corresponding "carboxylate" anion, e.g., as 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 group, where R is as defined herein.

[0035] As used herein, "cyano," alone or in combination, refers to --CN.

[0036] As used herein, "cycloalkyl" or, alternatively, "carbocycle," alone or in combination, refers to a saturated or partially saturated monocyclic, bicyclic, or tricyclic alkyl group, each cyclic moiety containing 3 to 12 carbon atom ring members, and optionally a benzo-fused ring system that is unsubstituted or substituted as defined herein. Carbocycles can include bridged and / or spirocyclic ring systems (e.g., systems containing two rings that share one carbon atom). The term "cycloalkenyl" refers to a cycloalkyl group having one or two double bonds. In certain embodiments, the cycloalkyl (or cycloalkenyl) group contains 5 to 7 carbon atoms. Examples of such groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, tetrahydronaphthyl, indanyl, octahydronaphthyl, 2,3-dihydro-1H-indenyl, adamantyl, and the like. As used herein, "bicyclic" and "tricyclic" are intended to include both fused ring systems such as decahydronaphthalene and octahydronaphthalene, and polycyclic (multi-center) saturated or partially unsaturated forms. Examples of the latter type of isomer are generally bicyclo[1,1,1]pentane, camphor, adamantane, and bicyclo[3,2,1]octane.

[0037] As used herein, "ester," alone or in combination, refers to a carboxy group bridging two moieties joined at a carbon atom.

[0038] As used herein, "ether," alone or in combination, refers to an oxy group bridging two moieties joined at a carbon atom.

[0039] As used herein, "halo" or "halogen," alone or in combination, refers to fluorine, chlorine, bromine, or iodine.

[0040] The term "haloalkoxy," as used herein, alone or in combination, refers to a haloalkyl group attached to the parent molecular moiety through an oxygen atom.

[0041] As used herein, "haloalkyl," alone or in combination, refers to an alkyl radical having the meaning described herein in which one or more hydrogens are replaced by halogen. Specifically included are monohaloalkyl, dihaloalkyl, and polyhaloalkyl radicals. By way of example, a monohaloalkyl radical can have an iodo, bromo, chloro, or fluoro atom within the radical. Dihalo and polyhaloalkyl radicals can 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] As used herein, "heteroalkyl," alone or in combination, refers to a stable, straight- or branched-chain hydrocarbon chain that is fully saturated or has 1 to 3 degrees of unsaturation, and consists of the specified number of carbon atoms and 1 to 3 heteroatoms selected from N, O, and S, where 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, for example, -CH-NH-OCH.

[0043] As used herein, "heteroaryl," 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, and the ring or ring system contains at least one atom selected from N, O, and S. In certain embodiments, the heteroaryl can contain 1 to 4 heteroatoms as ring members. In further embodiments, the heteroaryl can contain 1 to 2 heteroatoms as ring members. In certain embodiments, the heteroaryl can contain 5 to 7 atoms. The term also encompasses fused polycyclic groups in which a heterocycle is fused to an aryl ring, a heteroaryl ring is fused to another heteroaryl ring, a heteroaryl ring is fused to a heterocycloalkyl ring, or a heteroaryl ring is fused to a cycloalkyl ring. 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.

[0044] As used herein, "heterocycloalkyl" and, interchangeably, "heterocycle," alone or in combination, refer to a saturated, partially unsaturated, or fully unsaturated (but non-aromatic) monocyclic, bicyclic, or tricyclic heterocyclic group containing at least one heteroatom as a ring member, where each heteroatom may be independently selected from nitrogen, oxygen, and sulfur. In some embodiments, a heterocycle comprises a heteroaryl ring optionally fused to a saturated, partially unsaturated, or fully unsaturated (but non-aromatic) ring containing a heteroatom. In some embodiments, a heterocycle comprises an aryl ring fused to a saturated, partially unsaturated, or fully unsaturated (but non-aromatic) ring containing a heteroatom. In some embodiments, a heterocycle comprises a carbocycle fused to a saturated, partially unsaturated, or fully unsaturated ring containing a heteroatom. In some embodiments, a heterocycle includes a first ring that is a saturated, partially unsaturated, or fully unsaturated ring containing a heteroatom, and a second ring that is a saturated, partially unsaturated, or fully unsaturated ring, optionally containing a heteroatom. In some embodiments, the first ring and the second ring share a single heteroatom. In certain embodiments, the heterocycloalkyl can include 1 to 4 heteroatoms as ring members. In further embodiments, the heterocycloalkyl can include 1 to 2 heteroatoms as ring members. In certain embodiments, the heterocycloalkyl can include 3 to 8 ring members in each ring. In further embodiments, the heterocycloalkyl can include 3 to 7 ring members in each ring. In still further embodiments, the heterocycloalkyl can include 5 to 6 ring members in each ring. The heterocycle can include bridged ring systems and / or spiro ring systems (e.g., systems including two rings that share one atom, such as one carbon atom). "Heterocycloalkyl" and "heterocycle" are intended to include sulfone, sulfoxide, N-oxide of tertiary nitrogen ring members, and fused carbocyclic and benzofused ring systems; additionally, both terms also include systems in which a heterocycle is fused to an aryl group or a further heterocyclic group as defined herein.Examples of heterocyclic 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-epimifuro[3,2-b]furan, etc. Heterocyclic groups are unsubstituted or substituted unless specifically prohibited.

[0045] The term "hydrazinyl," as used herein, alone or in combination, refers to two amino groups joined by a single bond, ie, --NN--.

[0046] As used herein, "hydroxy," alone or in combination, refers to --OH.

[0047] The term "hydroxyalkyl," as used herein, alone or in combination, refers to a hydroxy group attached to the parent molecular moiety through an alkyl group.

[0048] As used herein, "iminohydroxy," alone or in combination, refers to ═N(OH) and ═NO—.

[0049] As used herein, "lower amino," alone or in combination, refers to -NRR', where R and R' are independently selected from hydrogen and lower alkyl (e.g., C 1-4 alkyl), any of which is unsubstituted or substituted.

[0050] As used herein, "mercaptyl," alone or in combination, refers to an RS-group, where R is as defined herein.

[0051] As used herein, "nitro," alone or in combination, refers to --NO.sub.2.

[0052] As used herein, "oxy" or "oxa," alone or in combination, refers to --O--.

[0053] As used herein, "oxo," alone or in combination, refers to =O.

[0054] "Perhaloalkoxy" refers to an alkoxy group in which all of the hydrogen atoms are replaced with halogen atoms.

[0055] As used herein, "perhaloalkyl," alone or in combination, refers to an alkyl group in which all of the hydrogen atoms are replaced with halogen atoms.

[0056] As used herein with respect to a chemical structure or portion thereof, "ring" or its equivalent "cycle" means a group in which all atoms are members of a common ring structure. The ring may be saturated or unsaturated (including aromatic) and may have 3 to 9 members, unless otherwise specified. When a ring is heterocyclic, it may contain B, N, O, S, C(O), and S(O). mwherein m is 0, 1, or 2. Unless specifically prohibited, rings may be unsubstituted or substituted. Two or more rings may be fused (e.g., two or more rings may share a bond and two common atoms). Two or more rings may be linked to each other in a spiro configuration, such that only one atom is shared between the two rings. Additionally or alternatively, two or more rings may be configured in a bridged configuration, such that three or more atoms are shared between the two or more rings.

[0057] As used herein, "sulfonate," "sulfonic acid," and "sulfonic" alone or in combination refer to the -SO3H group and its anion when sulfonic acid is used in salt formation.

[0058] As used herein, "sulfanyl," alone or in combination, refers to --S--.

[0059] As used herein, "sulfinyl," alone or in combination, refers to --S(O)--.

[0060] As used herein, "sulfonyl," alone or in combination, refers to -S(O) 2- Refers to...

[0061] "N-sulfonamido" refers to an RS(=O)2NR'- group, with R and R' as defined herein.

[0062] "S-sulfonamido" refers to a -S(=O)2NRR' group, where R and R' are as defined herein.

[0063] As used herein, "tautomer" refers to one of two or more isomers that rapidly interconvert, either alone or in combination. Generally, this interconversion is rapid enough that individual tautomers are not isolated in the absence of other tautomers. The ratio of the amounts of tautomers may depend on solvent composition, ionic strength, pH, and other solution parameters. The ratio of the amounts of tautomers may vary in a particular solution and within the microenvironment of a biomolecule binding site within that solution. Examples of tautomers known in the art include keto / enol, enamine / imine, and lactam / lactim tautomers. Examples of tautomers known in the art also include 2-hydroxypyridine / 2(1H)-pyridone and 2-aminopyridine / 2(1H)-iminopyridone tautomers.

[0064] As used herein, "thia" and "thio," alone or in combination, refer to an -S- group or ether where the oxygen is replaced by sulfur. The oxidized derivatives of the thio group, i.e., sulfinyl and sulfonyl, are included in the definition of thia and thio.

[0065] As used herein, "thiol," alone or in combination, refers to a --SH group.

[0066] As used herein, "thiocarbonyl" when alone includes thioformyl-C(S)H and in combination is a -C(S)- group.

[0067] "N-thiocarbamyl" refers to an ROC(S)NR'- group, with R and R' as defined herein.

[0068] "O-thiocarbamyl" refers to an --OC(S)NRR' group, with R and R' as defined herein.

[0069] "Thiocyanato" refers to the group -CNS.

[0070] Any definition herein can be used in combination with any other definition to describe a composite structural group. By convention, the last element of such a definition is the element that is attached to the parent moiety. For example, the composite group alkylamido represents an alkyl group attached to the parent molecule via an amide group, and the term alkoxyalkyl represents an alkoxy group attached to the parent molecule via an alkyl group.

[0071] As described herein, groups can be substituted or unsubstituted (e.g., "optionally substituted"). Unless otherwise specified, any group can be substituted with one or more substituents, such as one or more of the substituents provided herein. Examples of substituents with which groups may be substituted include, but are not limited to, having one or more substituents independently selected from the following groups or the set of specifically named groups, alone or in combination: alkyl (e.g., C 1-20 Alkyl, e.g., C 1-10 Alkyl, e.g., C 1-6 Alkyl, e.g., C 1-3 alkyl), alkenyl (e.g., C 2-20 Alkenyl, C 2-10 Alkenyl, e.g., C 2-6 alkenyl), alkynyl (e.g., C 2-20 Alkynyl, e.g., C 2-10 Alkynyl, e.g., C 2-6 alkynyl), alkanoyl (e.g., C 1-20 Alkanoyl, e.g., C 1-10 Alkanoyl, e.g., C 1-6 alkanoyl), heteroalkyl (e.g., heteroalkyl moieties containing 1 to 20 carbon atoms and 1 to 6 heteroatoms, e.g., heteroalkyl moieties containing 1 to 6 carbon atoms and 1 to 3 heteroatoms), haloalkyl (e.g., halo-substituted C 1-20 Alkyl, e.g., halo-substituted C 1-10 Alkyl, halo-substituted C 1-6 alkyl), haloalkenyl (e.g., halo-substituted C 2-20 Alkenyl, e.g., halo-substituted C 2-6alkenyl), haloalkynyl (e.g., halo-substituted C 2-20 Alkynyl, e.g., halo-substituted C 2-6 alkynyl), perhaloalkyl (e.g., C 1-20 Perhaloalkyl, e.g., C 1-6 Perhaloalkyl, e.g., C 1-3 perhaloalkyl), perhaloalkoxy (e.g., C 1-20 Perhaloalkoxy, e.g., C 1-6 perhaloalkoxy), phenyl, aryl (e.g., C 5-20 Aryl, e.g., C 5-10 Aryl, e.g., C 5-6 aryl), aryloxy (e.g., C 5-20 Aryloxy, e.g., C 5-10 Aryloxy, e.g., C 5-6 aryloxy), alkoxy (e.g., C 1-20 Alkoxy, e.g., C 1-10 Alkoxy, e.g., C 1-6 alkoxy), haloalkoxy (e.g., C 1-20 Haloalkoxy, e.g., C 1-10 Haloalkoxy, e.g., C 1-6 haloalkoxy), oxo, acyloxy (e.g., acyloxy groups containing 1 to 20 carbon atoms, e.g., 1 to 10 carbon atoms, such as 1 to 6 carbon atoms), carbonyl (e.g., C(O) or C=O), carboxyl (e.g., C(O)O), alkylcarbonyl (e.g., C 1-20 Alkylcarbonyl, e.g., C 1-10 Alkylcarbonyl, e.g., C 1-6 Alkylcarbonyl, e.g., C 1-3 alkylcarbonyl), carboxy esters (e.g., C(O)OR, where R is, for example, alkyl (e.g., C 1-20 Alkyl, e.g., C 1-10 Alkyl, e.g., C 1-6 Alkyl, e.g., C 1-3 alkyl), alkenyl (e.g., C 2-20 Alkenyl, e.g., C 2-10 Alkenyl, e.g., C 2-6alkenyl), or alkynyl (e.g., C 2-20 Alkynyl, e.g., C 2-10 Alkynyl, e.g., C 2-6 alkynyl), 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, for example, hydrogen, alkyl (e.g., C 1-20 Alkyl, e.g., C 1-10 Alkyl, e.g., C 1-6 Alkyl, e.g., C 1-3 alkyl), alkenyl (e.g., C 2-20 Alkenyl, e.g., C 2-10 Alkenyl, C 2-6 alkenyl), or alkynyl (e.g., C 2-20 Alkynyl, e.g., C 2-10 Alkynyl, e.g., C 2-6 alkynyl), any of which may be substituted with any group provided herein), alkylamino (e.g., NR'R", where R' is alkyl (e.g., C 1-20 Alkyl, e.g., C 1-10 Alkyl, e.g., C 1-6 Alkyl, e.g., C 1-3 alkyl), and R" is, for example, hydrogen, alkyl (e.g., C 1-20 Alkyl, e.g., C 1-10 Alkyl, e.g., C 1-6 Alkyl, e.g., C 1-3 alkyl) alkenyl (e.g., C 2-20 Alkenyl, e.g., C 2-10 Alkenyl, e.g., C 2-6 alkenyl), or alkynyl (e.g., C 2-20 Alkynyl, e.g., C 2-20 Alkynyl, e.g., C 2-6 alkynyl), any of which may be substituted with any group provided herein), arylamino (e.g., NR'R", where R' is aryl (e.g., C5-20 Aryl, e.g., C 5-10 Aryl, e.g., C 5-6 aryl), and R" is, for example, hydrogen, alkyl (e.g., C 1-20 Alkyl, e.g., C 1-10 Alkyl, e.g., C 1-6 Alkyl, e.g., C 1-3 alkyl), alkenyl (e.g., C 2-20 Alkenyl, e.g., C 2-10 Alkenyl, e.g., C 2-6 alkenyl), or alkynyl (e.g., C 2-20 Alkynyl, e.g., C 2-10 Alkynyl, e.g., C 2-6 alkynyl), any of which may be substituted with any group provided herein), amide (e.g., C(O)NR'R", where R' and R'' are independently, for example, hydrogen, alkyl (e.g., C 1-20 Alkyl, e.g., C 1-10 Alkyl, e.g., C 1-6 Alkyl, e.g., C 1-3 alkyl), alkenyl (e.g., C 2-20 Alkenyl, e.g., C 1-6 Alkenyl, e.g., C 1-3 alkenyl), or alkynyl (e.g., C 2-20 Alkynyl, e.g., C 2-10 Alkynyl, e.g., C 2-6 alkynyl), any of which may be substituted with any group provided herein), nitro (e.g., NO2), thiol (e.g., SH), alkylthio (e.g., substituted with a thiol group). 1-20 Alkyl, e.g., C substituted with a thiol group 1-10 Alkyl, e.g., C 1-3 C substituted with alkyl or other thiol groups 1-6 alkyl), substituted with a thiol group), haloalkylthio (e.g., C 1-20 Haloalkylthio, e.g., C 1-10 Haloalkylthio, e.g., C 1-6 Haloalkylthio, e.g., C 1-3haloalkylthio), perhaloalkylthio (e.g., C 1-20 Perhaloalkylthio, e.g., C 1-10 Perhaloalkylthio, e.g., C 1-6 Perhaloalkylthio, e.g., C 1-3 perhaloalkylthio), arylthiols (e.g., C 5-20 Aryl thiols, such as C 5-10 Aryl thiols, such as C 5-6 arylthiols), sulfonates (e.g., S(O)OR, where R is, for example, alkyl (e.g., C 1-20 Alkyl, e.g., C 1-10 Alkyl, e.g., C 1-6 Alkyl)C 1-3 alkyl, etc.), alkenyl (e.g., C 2-20 Alkenyl, e.g., C 2-10 Alkenyl, e.g., C 2-6 alkenyl), or alkynyl (e.g., C 2-20 Alkynyl, e.g., C 2-10 Alkynyl, e.g., C 2-6 alkynyl), any of which may be substituted by any group provided herein), sulfonic acid (e.g., S(O)OH), trisubstituted silyl (e.g., SiR'R'R*, where R', R", and R* are independently, for example, alkyl (e.g., C 1-20 Alkyl, e.g., C 1-10 Alkyl, e.g., C 1-6 Alkyl, e.g., C 1-3 Alkyl, ), alkenyl (e.g., C 2-20 Alkenyl, e.g., C 2-10 Alkenyl, e.g., C 2-6 alkynyl), or alkynyl (e.g., C 2-20 Alkynyl, e.g., C 2-10 Alkynyl, e.g., C 2-6 alkynyl), any of which may be substituted with any group provided herein), or alkynyl (e.g., C 2-20 C such as alkynyl 2-10 C such as alkynyl 2-6alkynyl), any of which may be substituted with any group provided herein; in some cases, trisubstituted silyl may be selected from trimethyl), N, SCH, C(O)CH, COCH, COH, pyridinyl, thiophene, furanyl, carbamate, and urea. Additional groups are contemplated. Where structurally possible, two substituents may be joined together to form a fused 5-, 6-, or 7-membered carbocyclic or heterocyclic ring consisting of 0-3 heteroatoms (e.g., N, O, S, etc.), forming, for example, methylenedioxy or ethylenedioxy. Unsubstituted or substituted groups may be unsubstituted (e.g., -CHCH), fully substituted (e.g., -CFCF), monosubstituted (e.g., -CHCHF), or substituted at any level between fully and monosubstituted (e.g., -CHCF). When a substituent is described 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 optional substituents for a particular moiety can be defined as needed, and in such cases, the optional substitutions are as defined, often immediately following the phrase "unsubstituted or substituted."

[0072] R, R', R”, R * Terms such as ", ", ", ", ", ", ", ", ", ", ", ", ", ", ", ", ", ", ", ", ", ", ", ", ", ", nAll R groups, including n=(1, 2, 3, ... n), all substituents, and all terms should be understood as independent of each other with respect to selection from a group. When any variable, substituent, or term (e.g., aryl, heterocycle, R, etc.) occurs more than one time in a formula or generic structure, its definition at each occurrence is independent of its definition at every other occurrence. Those skilled in the art will further recognize that certain groups may be attached to the parent molecule from either end or occupy a given position in the element chain as depicted. For example, an unsymmetrical group such as -C(O)N(R)- can be attached to the parent moiety at either the carbon or the nitrogen.

[0073] A "bond" refers to a covalent bond between two atoms, or between two moieties when the atoms connected by the bond are considered part of a larger substructure. Unless otherwise specified, bonds may be single, double, or triple. A dashed line between two atoms in a molecular diagram indicates that there may or may not be an additional bond at that position.

[0074] 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 is understood that the present disclosure encompasses all stereochemical isomers, including diastereomeric, enantiomeric, atropisomeric, and epimeric forms, as well as d- and 1-isomers, and mixtures thereof. Individual stereoisomers of the compounds can be prepared by synthesis from commercially available starting materials containing chiral centers, or by preparing a mixture of enantiomeric products followed by separation, for example, by conversion to a mixture of diastereomers followed by separation or recrystallization, chromatographic techniques, direct separation of enantiomers on a chiral chromatography column, or other suitable methods known in the art. Starting compounds of particular stereochemistry are commercially available or can be prepared 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 suitable mixtures thereof. Additionally, compounds may exist as tautomers, and all tautomers are provided by the present disclosure. Additionally, compounds provided herein may include conformational isomers, where these compounds contain groups that can orient in different conformations relative to another moiety. Additionally, compounds disclosed herein may exist in unsolvated as well as solvated forms with pharmaceutically acceptable solvents such as water, ethanol, and the like. In general, solvated forms are considered equivalent to unsolvated forms.

[0075] "Combination therapy" refers to the administration of two or more therapeutic agents to treat a therapeutic condition or disorder described in this disclosure. Such administration includes co-administration of these therapeutic agents substantially simultaneously, e.g., as a single dosage unit (e.g., capsule) having a fixed ratio of active ingredients, or as multiple separate dosage units (e.g., capsules) for each active ingredient. In addition, such administration also includes the sequential use of each type of therapeutic agent. In either case, the treatment regimen provides the beneficial effect of the drug combination in treating the condition or disorder described herein.

[0076] A "KRAS inhibitor" has an IC for KRAS activity of about 100 μM or less, more typically about 50 μM or less, as measured in assays generally described herein, such as a surface plasmon resonance KRAS-G12D, G12V, G12C, G12S, G12A, G12R, G13D, or Q61H mutant or wild-type KRAS protein binding assay; and / or a KRAS G12D, G12V, G12C, G12S, G12A, G12R, G13D, or Q61H mutant or wild-type KRAS protein-effector protein interaction disruption assay. 50 "IC" is used herein to refer to a compound exhibiting 50 " is the concentration of an inhibitor that reduces the activity of an enzyme (e.g., KRAS) to half of its maximum level. Certain compounds disclosed herein have been discovered to exhibit inhibitory activity against KRAS. In certain embodiments, the compound exhibits an inhibitory effect of about 50 μM or less 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). IC50; in a further embodiment, the compound exhibits an activity of about 10 μM or less 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). IC 50; in yet another embodiment, the compound exhibits an activity of about 1 μM or less relative to KRAS (e.g., a KRAS protein having a mutation at codon 12 (e.g., a G12D, G12V, G12C, G12S, G12A, 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). IC in still further embodiments, the compound exhibits an IC of about 200 nanomolar (nM) or less 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), as measured in a KRAS assay described herein. 50In some embodiments, the compound has an activity of less than about 50 μM, e.g., about 40 μM, 30 μM, or less against 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). IC of less than 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 50 In certain embodiments, the compound inhibits 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. an IC50 of less than about 1 μM, e.g., 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 50In some embodiments, the compound exhibits an IC of less than about 50 μM against KRAS harboring a G12D mutation, e.g., 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. 50 In some embodiments, the compound exhibits an IC of less than about 50 μM, e.g., 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, against KRAS harboring a G12V mutation. 50 In some embodiments, the compound exhibits an IC of less than about 50 μM against KRAS harboring a G12R mutation, e.g., 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. 50In some embodiments, the compound exhibits an IC of less than about 50 μM, e.g., 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, against KRAS harboring a G12A mutation. 50 In some embodiments, the compound exhibits an IC of less than about 50 μM, e.g., 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, against KRAS harboring a G12S mutation. 50 In some embodiments, the compound exhibits an IC of less than about 50 μM, e.g., 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, against KRAS harboring a G12C mutation. 50In some embodiments, the compound exhibits an IC of less than about 50 μM against KRAS harboring a G13D mutation, e.g., 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. 50 In some embodiments, the compound exhibits an IC of less than about 50 μM, e.g., 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, against KRAS harboring a Q61H mutation. 50 In some embodiments, the compound exhibits an IC of less than about 50 μM against wild-type KRAS, e.g., 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. 50 Shows.

[0077] In some embodiments, the KRAS inhibitor has inhibitory activity against a KRAS having a G12D mutation that exceeds its inhibitory activity against a KRAS having another mutation, such as a Q61H, G12C, G12R, G12S, G12A, G12V, or G13D mutation. For example, in some embodiments, the KRAS inhibitors provided herein have at least 2-fold, 5-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 100-fold, or more inhibitory activity against a KRAS having a G12D mutation compared to a KRAS having another mutation, such as a Q61H, G12C, G12R, G12S, G12A, G12V, or G13D mutation.

[0078] In some embodiments, the KRAS inhibitor has inhibitory activity against a KRAS having a G12V mutation that exceeds its inhibitory activity against a KRAS having another mutation, such as a Q61H, G12C, G12R, G12S, G12A, G12D, or G13D mutation. For example, in some embodiments, the KRAS inhibitors provided herein have at least 2-fold, 5-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 100-fold, or more inhibitory activity against a KRAS having a G12V mutation compared to a KRAS having another mutation, such as a Q61H, G12C, G12R, G12S, G12A, G12D, or G13D mutation.

[0079] In some embodiments, the KRAS inhibitor has inhibitory activity against a KRAS having a G12R mutation that exceeds its inhibitory activity against a KRAS having another mutation, such as a Q61H, G12C, G12D, G12S, G12A, G12V, or G13D mutation. For example, in some embodiments, the KRAS inhibitors provided herein have at least 2-fold, 5-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 100-fold, or more inhibitory activity against a KRAS having a G12R mutation compared to a KRAS having another mutation, such as a Q61H, G12C, G12D, G12S, G12A, G12V, or G13D mutation.

[0080] In some embodiments, the KRAS inhibitor has inhibitory activity against a KRAS having a G12C mutation that exceeds its inhibitory activity against a KRAS having another mutation, such as a Q61H, G12R, G12D, G12S, G12A, G12V, or G13D mutation. For example, in some embodiments, the KRAS inhibitors provided herein have at least 2-fold, 5-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 100-fold, or more inhibitory activity against a KRAS having a G12C mutation compared to a KRAS having another mutation, such as a Q61H, G12R, G12D, G12S, G12A, G12V, or G13D mutation.

[0081] In some embodiments, the KRAS inhibitor has inhibitory activity against a KRAS having a G12S mutation that exceeds its inhibitory activity against a KRAS having another mutation, such as a Q61H, G12C, G12D, G12R, G12A, G12V, or G13D mutation. For example, in some embodiments, the KRAS inhibitors provided herein have at least 2-fold, 5-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 100-fold, or more inhibitory activity against a KRAS having a G12S mutation compared to a KRAS having another mutation, such as a Q61H, G12C, G12D, G12R, G12A, G12V, or G13D mutation.

[0082] In some embodiments, the KRAS inhibitor has inhibitory activity against a KRAS with a G12A mutation that exceeds its inhibitory activity against a KRAS with another mutation, such as a Q61H, G12C, G12D, G12S, G12R, G12V, or G13D mutation. For example, in some embodiments, the KRAS inhibitors provided herein have at least 2-fold, 5-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 100-fold, or more inhibitory activity against a KRAS with a G12A mutation compared to a KRAS with another mutation, such as a Q61H, G12C, G12D, G12S, G12R, G12V, or G13D mutation.

[0083] In some embodiments, the KRAS inhibitor has inhibitory activity against a KRAS with a G13D mutation that exceeds its inhibitory activity against a KRAS with another mutation, such as a Q61H, G12C, G12D, G12S, G12R, G12V, or G12A mutation. For example, in some embodiments, the KRAS inhibitors provided herein have at least 2-fold, 5-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 100-fold, or more inhibitory activity against a KRAS with a G13D mutation compared to a KRAS with another mutation, such as a Q61H, G12C, G12D, G12S, G12R, G12V, or G12A mutation.

[0084] In some embodiments, the KRAS inhibitor has inhibitory activity against a KRAS having a Q61H mutation that exceeds its inhibitory activity against a KRAS having another mutation, such as a G13D, G12C, G12D, G12S, G12R, G12V, or G12A mutation. For example, in some embodiments, the KRAS inhibitors provided herein have at least 2-fold, 5-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 100-fold, or more inhibitory activity against a KRAS having a Q61H mutation compared to a KRAS having another mutation, such as a G13D, G12C, G12D, G12S, G12R, G12V, or G12A mutation.

[0085] In some embodiments, the KRAS inhibitor has inhibitory activity against wild-type KRAS that exceeds the inhibitory activity against KRAS having a Q61H, G13D, G12C, G12D, G12S, G12R, G12V, or G12A mutation. For example, in some embodiments, the KRAS inhibitors provided herein have at least 2-fold, 5-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 100-fold, or more inhibitory activity against wild-type KRAS compared to KRAS having a Q61H, G13D, G12C, G12D, G12S, G12R, G12V, or G12A mutation.

[0086] In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS with a Q61H, G13D, G12D, G12S, G12R, G12V, or G12A mutation, or wild-type KRAS, than against KRAS with a G12C mutation. In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS with a G12D, G12V, or G12R mutation than against KRAS with a G12C mutation.

[0087] In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS having a G12D mutation than against KRAS having a G12C mutation. In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS having a G12D mutation than against KRAS having a G12R mutation. In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS having a G12D mutation than against KRAS having a G12S mutation. In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS having a G12D mutation than against KRAS having a G12A mutation. In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS having a G12D mutation than against KRAS having a G12V mutation. In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS having a G12D mutation than against KRAS having a G13D mutation. In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS with a G12D mutation than against KRAS with a Q61H mutation.

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

[0089] In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS having a G12R mutation than against KRAS having a G12C mutation. In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS having a G12R mutation than against KRAS having a G12D mutation. In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS having a G12R mutation than against KRAS having a G12S mutation. In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS having a G12R mutation than against KRAS having a G12A mutation. In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS having a G12R mutation than against KRAS having a G12V mutation. In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS having a G12R mutation than against KRAS having a G13D mutation. In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS with a G12R mutation than against KRAS with a Q61H mutation.

[0090] In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against active ("GTP-bound") KRAS or wild-type KRAS having a Q61H, G12D, G12V, G12R, G12A, G12S, G12C, or G13D mutation than against inactive ("GDP-bound") KRAS or wild-type KRAS having a Q61H, G12D, G12V, G12R, G12A, G12S, G12C, or G13D mutation. In some embodiments, the KRAS inhibitors provided herein have lower inhibitory activity against active ("GTP-bound") KRAS or wild-type KRAS with a Q61H, G12D, G12V, G12R, G12A, G12S, G12C, or G13D mutation than against inactive ("GDP-bound") KRAS or wild-type KRAS with a Q61H, G12D, G12V, G12R, G12A, G12S, G12C, or G13D mutation. In some embodiments, the KRAS inhibitors provided herein have inhibitory activity against both active ("GTP-bound") and inactive ("GDP-bound") KRAS or wild-type KRAS with a Q61H, G12D, G12V, G12R, G12A, G12S, G12C, or G13D mutation. In some embodiments, the KRAS inhibitors provided herein have similar inhibitory activity against active ("GTP-bound") and inactive ("GDP-bound") KRAS with a Q61H, G12D, G12V, G12R, G12A, G12S, G12C, or G13D mutation or wild-type KRAS. In some embodiments, the KRAS inhibitors provided herein have inhibitory activity against the K-RAS4a splice variant. In some embodiments, the KRAS inhibitors provided herein have inhibitory activity against the K-RAS4b splice variant. In some embodiments, the KRAS inhibitors provided herein have inhibitory activity against both the K-RAS4a and K-RAS4b splice variants.

[0091] A "therapeutically effective amount" refers to the amount of a compound or pharmaceutical composition useful for treating or ameliorating a specified disease, disorder, or condition, or for exhibiting a detectable therapeutic or inhibitory effect. The exact amount will depend on the purpose of the treatment and can be ascertained 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).

[0092] The term "therapeutically acceptable" refers to a compound (or salt, prodrug, tautomer, zwitterionic form, etc.) that is suitable for use in contact with the tissues of a patient without excessive toxicity, irritation, and allergic response, commensurate with a reasonable benefit / risk ratio, and is effective for its intended use.

[0093] "Treate," "treating," and "treatment" refer to any indicator of success in treating or ameliorating an injury, pathology, disease, disorder, or condition, including any objective or subjective parameter, such as remission, remission, relief of symptoms, or making the injury, pathology, disease, disorder, or condition more tolerable to the patient, slowing the rate of degeneration or decline, reducing the ultimate point of degeneration, and / or improving the 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 examination, and / or psychiatric evaluation. Treatment may be preemptive in nature, i.e., can include prevention of the disease, disorder, or condition, prevention of the onset of one or more symptoms of the disease, disorder, or condition, and / or prevention of the worsening of the disease, disorder, or condition. Prevention of a disease, disorder, or condition can include complete protection from the disease and / or prevention of the progression of the disease (e.g., to a later stage of the disease, disorder, or condition). For example, preventing a disease may mean preventing the symptoms of a disease, disorder, or condition to a clinically significant or detectable level, rather than completely eliminating all effects associated with the disease at all levels.

[0094] "Patient" or "subject" refers to a living organism suffering from or likely to suffer from a disease, disorder, or condition treatable by administration of a compound or pharmaceutical composition provided herein. 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 administering 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.), bovine species (e.g., cattle), ungulates (e.g., horses), ungulates (e.g., bovine species such as cattle, ovine species such as sheep, caprine species such as goats, porcine species such as pigs, etc.), and marsupials (e.g., kangaroos, wallabies, wallaroos, sugar gliders, etc.). In some embodiments, the patient or subject is a 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 livestock animal such as a goat, sheep, cow, pig, or horse. In some embodiments, the patient or subject is a primate (e.g., monkey), marsupial (e.g., kangaroo, wallaby, wallaroo, sugar glider, etc.), or exotic animal such as a non-domesticated or hybrid cat or dog.

[0095] As used herein, "composition" is intended to encompass a product containing the specified ingredients in the specified amounts, as well as any product resulting directly or indirectly from combining the specified ingredients in the specified amounts. "Pharmaceutically acceptable" means the carrier, diluent, or excipient must be compatible with the other ingredients of the formulation and not deleterious to the recipient thereof.

[0096] A "pharmaceutically acceptable excipient" refers to a substance that aids in the administration of and absorption by a subject of an active agent. Pharmaceutical excipients useful in the present disclosure include, but are not limited to, binders, fillers, disintegrants, lubricants, coatings, sweeteners, flavorings, and coloring agents. Those skilled in the art will recognize that other pharmaceutical excipients are also useful in the present disclosure.

[0097] The term "prodrug" refers to a compound that is 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 compounds that readily undergo chemical changes under physiological conditions to yield the compounds. Additionally, prodrugs can be converted to the compounds by chemical or biochemical methods in an ex vivo environment. For example, prodrugs can be slowly converted to the compounds 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. For example, prodrugs may be bioavailable by oral administration even when the parent drug is not. Prodrugs may also have improved solubility in pharmaceutical compositions compared to the parent drug.

[0098] 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 salts formed with both organic and inorganic acids. Such acid addition salts are generally pharmaceutically acceptable. However, non-pharmaceutically acceptable salts may be useful in the preparation and purification of the compound in question. Base addition salts are also formed and are pharmaceutically acceptable.

[0099] As used herein, the terms "therapeutically acceptable salt" and "pharmaceutically acceptable salt" refer to water- or oil-soluble or dispersible, therapeutically acceptable salts or zwitterionic forms of the compounds disclosed herein, as defined herein. Salts can be prepared during the final isolation and purification of the compounds, or separately by reacting the free base form of the appropriate compound 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-hydroxyethanesulfonate (isethionate), lactate, maleate, malonate, and the like. Acid salts include, but are not limited to, acetic acid salts, DL-mandelate, mesitylenesulfonate, methanesulfonate, naphthylenesulfonate, nicotinate, 2-naphthalenesulfonate, oxalate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphonate, picrate, pivalate, propionate, pyroglutamate, succinate, sulfonate, tartrate, L-tartrate, trichloroacetate, trifluoroacetate, phosphate, glutamate, bicarbonate, p-toluenesulfonate (p-tosylate), and undecanoate. In addition, the basic groups of the compounds disclosed herein can be quaternized with methyl chloride, bromide, and iodide, ethyl chloride, bromide, and iodide, propyl chloride, bromide, and iodide, and butyl chloride, bromide, and iodide; dimethyl sulfate, diethyl sulfate, dibutyl sulfate, and diamyl sulfate; decyl chloride, bromide, and iodide, lauryl chloride, bromide, and iodide, myristyl chloride, bromide, and iodide, and steryl chloride, bromide, and iodide; and benzyl bromide and phenethyl bromide. Examples of acids that can be used to form therapeutically acceptable addition salts include inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, and phosphoric acid, and organic acids such as oxalic acid, maleic acid, succinic acid, and citric acid.Salts can also be formed by coordination of the compounds with alkali metal or alkaline earth ions. Thus, the present disclosure contemplates sodium, potassium, magnesium, and calcium salts of the compounds disclosed herein, and the like.

[0100] Base addition salts can be prepared during the final isolation and purification of the compound by reacting the carboxyl group with a suitable base, such as a hydroxide, carbonate, or bicarbonate of a metal cation, or with ammonia or an organic primary, secondary, or tertiary amine. Therapeutically acceptable salt cations include lithium, sodium, potassium, calcium, magnesium, and aluminum, as well as non-toxic quaternary amine catylamine 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.

[0101] Salts of compounds can be prepared by reacting the appropriate compound in the form of a free base with a suitable acid.

[0102] "KRAS-positive cancer" refers to cancers characterized by KRAS mutations, such as KRAS Q61H, G12C, G12D, G12R, G12A, G12S, G12V, or G13D mutations, and / or amplified wild-type KRAS activity. In some embodiments, "KRAS-positive cancer" refers to cancers that can benefit from inhibition of KRAS, e.g., wild-type KRAS or KRAS with Q61H, G12C, G12D, G12R, G12A, G12S, G12V, or G13D mutations.

[0103] "KRAS G12C-positive cancer" refers to cancer characterized by the KRAS G12C mutation.

[0104] "KRAS G12D-positive cancer" refers to cancer characterized by the KRAS G12D mutation.

[0105] "KRAS G12R-positive cancer" refers to cancer characterized by the KRAS G12R mutation.

[0106] "KRAS G12V-positive cancer" refers to cancer characterized by the KRAS G12V mutation.

[0107] "KRAS G12A-positive cancer" refers to cancer characterized by the KRAS G12A mutation.

[0108] "KRAS G12S-positive cancer" refers to cancer characterized by the KRAS G12S mutation.

[0109] "KRAS G13D-positive cancer" refers to cancer characterized by the KRAS G13D mutation.

[0110] "KRAS Q61H-positive cancer" refers to cancer characterized by the KRAS Q61H mutation.

[0111] As used herein, a "combined therapeutically effective amount" refers to amounts of therapeutic agents that, when administered separately (chronologically staggered, especially sequentially) to a warm-blooded animal, especially a human being, exhibit an (additive, but preferably synergistic) interaction (combined therapeutic effect). Whether this is the case can be determined, inter alia, by following blood levels indicating that both compounds are present in the blood of the human being for at least a certain time interval.

[0112] As used herein, "synergistic effect" refers to the effect of at least two therapeutic agents, a KRAS inhibitor as defined herein, and an additional agent, which may be an agent configured to treat a disease, disorder, or condition, or a symptom thereof. The effect may be, for example, slowing the progression of a symptom of a proliferative disease, such as cancer, particularly lung cancer, or a symptom thereof. Similarly, a "synergistically effective amount" refers to the amount necessary to achieve a synergistic effect.

[0113] "A," "an," or "a(n)," when used herein with respect to a group of substituents or "substituents," means at least one. For example, when 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, where each alkyl and / or aryl is optionally different. In another example, when a compound is substituted with "a" substituents, the compound is substituted with at least one substituent, where each substituent is optionally different.

[0114] compound In one aspect, the present disclosure provides a compound of formula I: [ka] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein: R 1 But, -OR 8 and [ka] is selected from R 2 However, H and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 3 is unsubstituted or contains one or more R 10is selected from a 3- to 11-membered carbocyclic ring substituted with R 4 is H, R 5 H, halogen, -CN, -OR 12 , 3- to 6-membered heterocycle, 5- to 6-membered heteroaryl, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 6 But there is one or more R 15 is a bicyclic heteroaryl substituted with R 7 is selected from halogen, —CN, and H; R 8 is selected from heterocycle and alkylheterocycle, and any heterocycle contains 4 to 8 members and is unsubstituted or contains one or more R a or R b and the alkyl portion of any alkyl heterocycle is substituted with C 1-6 alkyl, Each R 10 but independently, -OR 12 , -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene)OH, -C(O)(C 1-6 alkyl), -C(O)N(R 14 )2, -S(O)2(C 1-6 alkyl), halogen, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 is replaced by Each R 12 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H, and any C 1-6 Alkyl or C 2-6 Alkenyl is unsubstituted or has one or more R 13 is replaced by Each R 13 but independently, -OR 14 , -CN, -N(R14 )2, and halogen; Each R 14 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H; Each R 15 are independently deuterium, halogen, -N(R 12 )2, -CN, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by Each R 20 Independently, -OH, -OC 1-6 Alkyl, -CN, -NH2, -NHC 1-6 alkyl, and halogen; R 27 is a 3- to 6-membered heterocycle containing one or more heteroatoms selected from N, O, and S, and the heterocycle is unsubstituted or contains one or more R 28 is replaced by Each R 28 But independently, C 1-6 selected from alkyl and halogen; R a and R b are each independently deuterium, halogen, C 1-6 Alkyl, 3-6 membered carbocyclic ring, -OR 12 and H; a and R b are optionally linked together to form a 3- to 6-membered carbocyclic or heterocyclic ring, and any C 1-6 The alkyl or 3- to 6-membered carbocyclic or heterocyclic ring is unsubstituted or contains one or more R 13 The compound or a salt thereof, wherein the compound is substituted with

[0115] In some embodiments, the disclosure provides a compound of Formula I or a salt thereof (eg, a pharmaceutically acceptable salt).

[0116] In some embodiments, the disclosure provides a compound of formula I, wherein: R 1But, -OR 8 and [ka] is selected from R 2 However, H and C 1-6 alkyl, R 3 is unsubstituted or contains one or more R 10 is selected from a 3- to 11-membered carbocyclic ring substituted with R 4 is H, R 5 H, halogen, -CN, -OR 12 , 5-6 membered heteroaryl, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 6 But there is one or more R 15 is a bicyclic heteroaryl substituted with R 7 is selected from halogen, —CN, and H; R 8 is an alkylheterocycle, and any heterocycle contains 4 to 8 members and is unsubstituted or contains one or more R a Or R b and the alkyl portion of any alkyl heterocycle is substituted with C 1-6 alkyl, Each R 10 but independently, -OR 12 , -C(O)N(R 14 )2, halogens, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 is replaced by Each R 12 But independently, C 1-6 alkyl and H, and any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by Each R13 are independently selected from halogen; Each R 14 But independently, C 1-6 alkyl, Each R 15 are independently halogen, -N(R 12 )2, and -CN; Each R 20 Independently, -OH, -OC 1-6 alkyl, and -CN; R 27 is a 3- to 6-membered heterocycle containing one or more heteroatoms selected from N, O, and S, and the heterocycle is unsubstituted or contains one or more R 28 is replaced by Each R 28 are independently selected from halogen; R a and R b are each independently a halogen, C 1-6 Alkyl, -OR 12 , and H, and any C 1-6 The alkyl is unsubstituted.

[0117] In some embodiments, the disclosure provides compounds of Formula I, wherein the compound has Formula Ia: [ka] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein R 2 and R 3 is as defined for Formula I above and is described herein in classes and subclasses, alone and in combination. In some embodiments, the present disclosure provides compounds of Formula Ia, or salts (e.g., pharmaceutically acceptable salts) thereof:

[0118] In some embodiments of the compounds according to Formula I or Ia, R 3 is selected from unsubstituted 3- to 11-membered carbocyclic rings.3 is one or more R 10 In some embodiments, R 3 is selected from unsubstituted 3- to 8-membered carbocyclic rings. 3 is one or more R 10 In some embodiments, R 3 is unsubstituted or contains one or more R 10 In some embodiments, R 3 is an unsubstituted 3- to 6-membered carbocyclic ring. In some embodiments, R 3 is one or more R 10 In some embodiments, R 3 is 1 to 4 R 10 In some embodiments, R 3 is 0 to 4 R 10 In some embodiments, R 3 is 1 to 4 R 10 In some embodiments, R 3 is one or more R 10 and one or more R 10 At least one of the R 20 C replaced by 1-6 In some embodiments, R 3 is 0 to 4 R 10 In some embodiments, R 3 is 1 to 4 R 10 In some embodiments, R 3 is 0 to 4 R 10 In some embodiments, R 3 is 1 to 4 R 10 In some embodiments, R 3 is 0 to 4 R 10In some embodiments, R 3 is 1 to 4 R 10 In some embodiments, R 3 is one or more R 10 and a 3- to 6-membered carbocyclic ring (e.g., cyclopropane, cyclobutane, cyclopentane, or cyclohexane) substituted with at least one R 10 -OR 12 and C substituted with -OH 1-6 In some embodiments, R 3 is one or more R 10 and a 3- to 6-membered carbocyclic ring (e.g., cyclopropane, cyclobutane, cyclopentane, or cyclohexane) substituted with at least one R 10 -OR 12 In some embodiments, R 3 is one or more R 10 and a 3- to 6-membered carbocyclic ring (e.g., cyclopropane, cyclobutane, cyclopentane, or cyclohexane) substituted with at least one R 10 is substituted with -OH 1-6 In some embodiments, R 3 is one or more R 10 and a 3- to 6-membered carbocyclic ring (e.g., cyclopropane, cyclobutane, cyclopentane, or cyclohexane) substituted with at least one R 10 is -C(O)N(R 14 )2. In some embodiments, R 3 is one or more R 10 and at least one R 10 is -C(O)N(R 14 )2. In some embodiments, R 3 is one or more R 10 and a 3- to 6-membered carbocyclic ring (e.g., cyclopropane, cyclobutane, cyclopentane, or cyclohexane) substituted with at least one R 10 is the unsubstituted C 1-6 It is alkyl.

[0119] In some embodiments of the compounds according to Formula I or Ia, R 3 is unsubstituted or contains one or more R 10 In some embodiments, R 3 is unsubstituted or contains one or more R 10 and the spiro ring comprises a four-membered ring (e.g., cyclobutane). 3 is unsubstituted or contains one or more R 10 and the spiro ring comprises a 5-membered ring (e.g., cyclopentane). 3 is unsubstituted or contains one or more R 10 and the spiro ring comprises a six-membered ring (e.g., cyclohexane). 3 is unsubstituted or contains one or more R 10 and spiro rings include four-membered rings (e.g., cyclobutane) and five-membered rings (e.g., cyclopentane). 3 is unsubstituted or contains one or more R 10 In some embodiments, R is a spiro ring substituted with R, and R is a 5-membered ring (e.g., cyclopentane) and R is a 6-membered ring (e.g., cyclopentane). 3 is unsubstituted or contains one or more R 10 and spiro rings include six-membered rings (e.g., cyclohexane) and five-membered rings (e.g., cyclopentane). 3 is unsubstituted or contains one or more R 10 In some embodiments, R is a spiro ring substituted with R, and R is a 6-membered ring (e.g., cyclohexane). 3 is unsubstituted or contains one or more R 10 and one or more R 10 At least one of the is -OR 12In some embodiments, R 3 is unsubstituted or contains one or more R 10 spiro rings include four-membered rings (e.g., cyclobutane) and five-membered rings (e.g., cyclopentane), and are substituted with one or more R 10 At least one of the is -OR 12 is.

[0120] In some embodiments of the compounds according to Formula I or Ia, R 3 is unsubstituted or contains one or more R 10 In some embodiments, R 3 is unsubstituted or contains one or more R 10 and the bridged carbocycle comprises a four-membered ring (e.g., cyclobutane). 3 is unsubstituted or contains one or more R 10 and the bridged carbocycle comprises a 5-membered ring (e.g., cyclopentane). 3 is unsubstituted or contains one or more R 10 wherein the bridged carbocycle comprises a 6-membered ring (e.g., cyclohexane). 3 is unsubstituted or contains one or more R 10 and one or more R 10 is unsubstituted or contains one or more R 20 C replaced by 1-6 It is alkyl.

[0121] In some embodiments of the compounds according to Formula I or Ia, R 10 -C(O)N(R 14 )2, then at least one R 14 is not H. In some embodiments, R 10 -C(O)N(R 14 )2, then each R 14 is C 1-6 alkyl (for example, methyl or ethyl).

[0122] In some embodiments of the compounds according to Formula I or Ia, R 3 teeth, [ka] is selected from Any of them has one or more R 10 The compound according to any one of embodiments C103 to C129, substituted with:

[0123] In some embodiments, the compound has formula IA, IB, IC, ID, IE, or IF: [ka] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein R 1 But, -OR 8 and [ka] is selected from R 2 However, H and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 4 is H, if present, R 5 H, halogen, -CN, -OR 12 , 3- to 6-membered heterocycle, 5- to 6-membered heteroaryl, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 6 But there is one or more R 15 is a bicyclic heteroaryl substituted with R 7is selected from halogen, —CN, and H; R 8 is selected from heterocycle and alkylheterocycle, and any heterocycle contains 4 to 8 members and is unsubstituted or contains one or more R a or R b and the alkyl portion of any alkyl heterocycle is substituted with C 1-6 alkyl, Each R 12 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H, and any C 1-6 Alkyl or C 2-6 Alkenyl is unsubstituted or has one or more R 13 is replaced by Each R 13 but independently, -OR 14 , -CN, -N(R 14 )2, and halogen; Each R 14 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H; Each R 15 are independently deuterium, halogen, -N(R 12 )2, -CN, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by Each R 20 Independently, -OH, -OC 1-6 Alkyl, -CN, -NH2, -NHC 1-6 alkyl, and halogen; R 27 is a 3- to 6-membered heterocycle containing one or more heteroatoms selected from N, O, and S, and the heterocycle is unsubstituted or contains one or more R 28 is replaced by Each R 28 But independently, C 1-6 selected from alkyl and halogen; R a and R bare each independently deuterium, halogen, C 1-6 Alkyl, -OR 12 and H; a and R b are optionally linked together to form a 3- to 6-membered carbocyclic or heterocyclic ring, and any C 1-6 The alkyl or 3- to 6-membered carbocyclic or heterocyclic ring is unsubstituted or contains one or more R 13 is replaced by Each R d But independently, H, -OR 12 , -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene)OH, -C(O)(C 1-6 alkyl), -C(O)N(R 14 )2, -S(O)2(C 1-6 alkyl), halogen, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 is replaced by

[0124] In some embodiments, the compound is a compound according to Formula IA, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IB, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IC, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula ID, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IE, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to formula IF, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof.

[0125] In some embodiments, the compound is a compound according to formula IA or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to formula IB or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to formula IC or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to formula ID or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to formula IE or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to formula IF or a salt (e.g., a pharmaceutically acceptable salt) thereof.

[0126] In some embodiments, for a compound according to any one of Formulas I, IA, IB, IC, ID, IE, and IF, R 6 teeth, [ka] wherein X is selected from N and C-CN, Y is selected from O and S, and R 23 But -N(R 12 )2, C 1-6 Alkyl, and C 1-6 Alkyl-N(R 14 )2 and any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 24 , R 25 , and R 26 are independently H, deuterium, halogens, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 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 and Y is S and R 23 is -N(R 12 In some embodiments, X is C-CN, Y is S, and R 23 is -NH. In some embodiments, R 24 is halogen (e.g., fluoro). In some embodiments, R 26 is deuterium.

[0127] In some embodiments, for a compound according to any one of Formulas I, IA, IB, IC, ID, IE, and IF, R 6 teeth, [ka] is selected from Any of them has one or more R 15 is replaced by

[0128] In some embodiments, for a compound according to any one of Formulas I, IA, IB, IC, ID, IE, and IF, R 6 teeth, [ka] is selected from.

[0129] In some embodiments, for a compound according to any one of Formulas I, IA, IB, IC, ID, IE, and IF, R 6 teeth, [ka] is selected from.

[0130] In some embodiments, for a compound according to any one of Formulas I, IA, IB, IC, ID, IE, and IF, R 6 teeth, [ka] is.

[0131] In some embodiments, the compounds have formula IA1, IB1, IC1, ID1, IE1, and IF1: [ka] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein R 1 But, -OR 8 and [ka] is selected from R 2 However, H and C1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 4 is H, if present, R 5 H, halogen, -CN, -OR 12 , 3- to 6-membered heterocycle, 5- to 6-membered heteroaryl, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 7 is selected from halogen, —CN, and H; R 8 is selected from heterocycle and alkylheterocycle, and any heterocycle contains 4 to 8 members and is unsubstituted or contains one or more R a or R b and the alkyl portion of any alkyl heterocycle is substituted with C 1-6 alkyl, Each R 12 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H, and any C 1-6 Alkyl or C 2-6 Alkenyl is unsubstituted or has one or more R 13 is replaced by Each R 13 but independently, -OR 14 , -CN, -N(R 14 )2, and halogen; Each R 14 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H; Each R 20 Independently, -OH, -OC 1-6 Alkyl, -CN, -NH2, -NHC 1-6 alkyl, and halogen; R 27is a 3- to 6-membered heterocycle containing one or more heteroatoms selected from N, O, and S, and the heterocycle is unsubstituted or contains one or more R 28 is replaced by Each R 28 But independently, C 1-6 selected from alkyl and halogen; R a and R b are each independently deuterium, halogen, C 1-6 Alkyl, -OR 12 , and H, and Ra and R b are optionally linked together to form a 3- to 6-membered carbocyclic or heterocyclic ring, and any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by Each R d But independently, H, -OR 12 , -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene)OH, -C(O)(C 1-6 alkyl), -C(O)N(R 14 )2, -S(O)2(C 1-6 alkyl), halogen, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 is replaced by X is selected from N and C-CN; Y is selected from O and S; R 23 But -N(R 12 )2, C 1-6 Alkyl, and C 1-6 Alkyl-N(R 14 )2 and any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 24 , R 25 , and R 26 are independently H, deuterium, halogens, and C 1-6 alkyl, any C 1-6The alkyl may be unsubstituted or may contain one or more R 13 is replaced by

[0132] In some embodiments, the compound is a compound according to Formula IA1, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IB1, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IC1, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula ID1, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to formula IE1, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to formula IF1, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof.

[0133] In some embodiments, the compound is a compound according to Formula IA1 or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IB1 or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IC1 or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula ID1 or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IE1 or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IF1 or a salt (e.g., a pharmaceutically acceptable salt) thereof.

[0134] In some embodiments, for the compound according to any one of formulas IA1, IB1, IC1, ID1, IE1, and IF1, 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 and Y is S and R 23 is -N(R 12 In some embodiments, X is C-CN, Y is S, and R 23 In some embodiments, X is C—CN, Y is S, and R 23 is -N(R 12 )2 and R 24 is halogen (e.g., F). In some embodiments, X is C—CN, Y is S, and R 23 is -N(R 12 )2 and R 24 , R 25 , and R 26 One or more of R is halogen (e.g., F). In some embodiments, R 26 is deuterium.

[0135] In some embodiments, for a compound according to any one of Formulas I, IA, IA1, IB, IB1, IC, IC1, ID, ID1, IE, IE1, IF, and IF1, R 1 -OR 8 Selected from R 8 is selected from heterocycle and alkylheterocycle, any heterocycle containing 4 to 8 members and is unsubstituted or contains one or more R a or R b and the alkyl portion of any alkyl heterocycle is C 1-6 In some embodiments, R 8 is a heterocycle or alkylheterocycle, any heterocycle containing 4 to 8 members and containing one or more R a or R b In some embodiments, R 8 is unsubstituted or contains one or more R a or R b In some embodiments, R 8 is unsubstituted or contains one or more R a or R b In some embodiments, R 8 is —CH2 (heterocycle), the heterocycle is unsubstituted or contains one or more R a or R b In some embodiments, the heterocycle of the heterocycle or alkylheterocycle is a 4-6 membered monocyclic heterocycle having 1-2 heteroatoms independently selected from N, O, and S. In some embodiments, the heterocycle of the heterocycle or alkylheterocycle is an 8 membered bicyclic heterocycle having 1-2 heteroatoms independently selected from N, O, and S. In some embodiments, the heterocycle of the heterocycle or alkylheterocycle is substituted with one or more R a or R b and one or more R a or R b is halogen (e.g., F). In some embodiments, the heterocycle or heterocycle of an alkylheterocycle is selected from the group consisting of one or more R a or R band one or more R a or R b is C 1-6 In some embodiments, the heterocycle or heterocycle of the alkylheterocycle is selected from one or more R a or R b and one or more R a or R b -OR 12 (e.g., —OCH). In some embodiments, the heterocycle or heterocycle of the alkylheterocycle is selected from one or more R a or R b and one or more R a or R b is a 3-6 membered carbocyclic ring (e.g., cyclopropane). In some embodiments, the heterocycle or heterocycle of an alkylheterocycle ... a or R b and one or more R a or R b is deuterium.

[0136] In some embodiments, for a compound according to any one of the compounds of formula I, IA, IA1, IB, IB1, IC, IC1, ID, ID1, IE, IE1, IF, or IF1, R 1 teeth, [ka] In the formula, R a and R b are each independently a halogen, C 1-6 Alkyl, -OR 12 , and H, and any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 In some embodiments, R a is halogen. In some embodiments, R a is F. In some embodiments, R a is unsubstituted or contains one or more R 13 C replaced by 1-6 In some embodiments, Ra is methyl. In some embodiments, R a -OC 1-6 In some embodiments, R a is H. In some embodiments, R b is H. In some embodiments, R b is halogen. In some embodiments, R b is F. In some embodiments, R b is unsubstituted or contains one or more R 13 C replaced by 1-6 In some embodiments, R b is methyl. In some embodiments, R a and R b Each of R is F. In some embodiments, R a and R b Each of R is methyl. 1 teeth, [ka] is selected from.

[0137] In some embodiments, for a compound according to any one of the compounds of formula I, IA, IA1, IB, IB1, IC, IC1, ID, ID1, IE, IE1, IF, or IF1, R 1 teeth, [ka] is selected from.

[0138] In some embodiments, for a compound according to any one of the compounds of formula I, IA, IA1, IB, IB1, IC, IC1, ID, ID1, IE, IE1, IF, or IF1, R 1 teeth, [ka] is selected from. In some embodiments, Ra is unsubstituted or contains one or more R 13 C replaced by 1-6 In some embodiments, R a is methyl. In some embodiments, R 1 teeth, [ka] is selected from.

[0139] In some embodiments, for a compound according to any one of the compounds of formula I, IA, IA1, IB, IB1, IC, IC1, ID, ID1, IE, IE1, IF, or IF1, R 1 teeth, [ka] is selected from In the formula, each R a and R b are independently halogen, C 1-6 Alkyl, -OR 12 and H; c But C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R a and R b or R c are optionally linked together to form a 3- to 6-membered carbocyclic or heterocyclic ring. a and R b are independently halogen, C 1-6 Alkyl, -OR 12 and H; c is C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 and R bonded to the same carbon atom a and R b are linked together to form a 3- to 6-membered carbocyclic ring. In some embodiments, each R aand R b are independently halogen, C 1-6アルキル , -OR 12 and H; a and R c are linked together to form a 3- to 6-membered heterocycle. In some embodiments, each R a and R b are independently halogen, C 1-6 Alkyl, -OR 12 and H; c is C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 In some embodiments, one R a or R b is a halogen, C 1-6 Alkyl, and -OR 12 Selected from other R a and R b The group is H. In some embodiments, one R a or R b is halogen (e.g., F). In some embodiments, two R a group, two R b group, or R a and R b is halogen (e.g., F). In some embodiments, one R a or R b -OR 12 (e.g., —OCH or —CHF). In some embodiments, one R a or R b is C 1-6 In some embodiments, two R a group, two R b group, or R a and R b is C 1-6 In some embodiments, R c is selected from -CH, -CHCHF, -CHCHF, and -CHCHCN. aand R b are linked together to form a 3- to 6-membered carbocyclic ring, such as cyclopropane. In some embodiments, R a and R b are linked together to form a 3- to 6-membered carbocyclic ring, such as cyclopropane. In some embodiments, R a and R c are linked together to form a 3- to 6-membered heterocycle. In some embodiments, R 1 teeth, [ka] is selected from.

[0140] In some embodiments, for a compound according to any one of the compounds of formula I, IA, IA1, IB, IB1, IC, IC1, ID, ID1, IE, IE1, IF, or IF1, R 1 teeth, [ka] is selected from

[0141] In some embodiments, for a compound according to any one of the compounds of formula I, IA, IA1, IB, IB1, IC, IC1, ID, ID1, IE, IE1, IF, or IF1, R 1 teeth, [ka] is selected from.

[0142] In some embodiments, the compound has formula IA2, IB2, IC2, ID2, IE2, or IF2: [ka] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein R 2 However, H and C1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 4 is H, if present, R 5 H, halogen, -CN, -OR 12 , 3- to 6-membered heterocycle, 5- to 6-membered heteroaryl, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 7 is selected from halogen, —CN, and H; Each R 12 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H, and any C 1-6 Alkyl or C 2-6 Alkenyl is unsubstituted or has one or more R 13 is replaced by Each R 13 but independently, -OR 14 , -CN, -N(R 14 )2, and halogen; Each R 14 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H; Each R 20 Independently, -OH, -OC 1-6 Alkyl, -CN, -NH2, -NHC 1-6 alkyl, and halogen; R a and R b are each independently a halogen, C 1-6 Alkyl, -OR 12 , and H, and any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by Each R d But independently, H, -OR 12 , -C(O)(C1-6 alkylene)CN, -C(O)(C 1-6 alkylene)OH, -C(O)(C 1-6 alkyl), -C(O)N(R 14 )2, -S(O)2(C 1-6 alkyl), halogen, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 is replaced by X is selected from N and C-CN; Y is selected from O and S; R 23 But -N(R 12 )2, C 1-6 Alkyl, and C 1-6 Alkyl-N(R 14 )2 and any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 24 , R 25 , and R 26 are independently H, deuterium, halogens, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by

[0143] In some embodiments, the compound is a compound according to Formula IA2, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IB2, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IC2, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula ID2, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to formula IE2, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to formula IF2, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof.

[0144] In some embodiments, the compound is a compound according to formula IA2 or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to formula IB2 or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to formula IC2 or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to formula ID2 or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to formula IE2 or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to formula IF2 or a salt (e.g., a pharmaceutically acceptable salt) thereof.

[0145] In some embodiments, for the compound according to any one of formulas IA2, IB2, IC2, ID2, IE2, and IF2, 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 and Y is S and R 23 is -N(R 12 In some embodiments, X is C-CN, Y is S, and R 23 In some embodiments, X is C—CN, Y is S, and R 23 is -N(R 12 )2 and R 24 is halogen (e.g., F). In some embodiments, X is C—CN, Y is S, and R 23 is -N(R 12 )2 and R 24 , R 25 , and R 26 One or more of R is halogen (e.g., F). In some embodiments, R 26 is deuterium.

[0146] In some embodiments, for a compound according to any one of formulas IA2, IB2, IC2, ID2, IE2, and IF2, R a is halogen. In some embodiments, R a is F. In some embodiments, R a is unsubstituted or contains one or more R 13 C replaced by 1-6 In some embodiments, R a is methyl. In some embodiments, R a -OC 1-6 In some embodiments, R a is H. In some embodiments, R b is H. In some embodiments, R bis halogen. In some embodiments, R b is F. In some embodiments, R b is unsubstituted or contains one or more R 13 C replaced by 1-6 In some embodiments, R b is methyl. In some embodiments, R a and R b Each of R is F. In some embodiments, R a and R b Each of is methyl.

[0147] In some embodiments, for a compound according to any one of IA, IA1, IA2, IB, IB1, IB2, IC, IC1, IC2, ID, ID1, ID2, IE, IE1, IE2, IF, IF1, and IF2, at least one R d -OR 12 , -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene)OH, -C(O)(C 1-6 alkyl), -C(O)N(R 14 )2, -S(O)2(C 1-6 alkyl), halogen, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, at least one R d -OR 12 , -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene)OH, -C(O)(C 1-6 alkyl), -C(O)N(R 14 )2, -S(O)2(C 1-6 alkyl), halogen, and unsubstituted or one or more R 20 C replaced by 1-6 In some embodiments, at least one R d -OR 12 , -C(O)(C1-6 alkylene)CN, -C(O)(C 1-6 alkylene)OH, -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), halogen, and unsubstituted or one or more R 20 C replaced by 1-6 In some embodiments, at least one R d -OR 12 and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, at least one R d is —OH. In some embodiments, at least one R d is halogen (e.g., F). In some embodiments, at least one R d is -C(O)N(R 14 )2. In some embodiments, at least one R d is -C(O)N(R 14 )2, and each R 14 independently, C 1-6 In some embodiments, at least one R d is —C(O)N(CH). In some embodiments, R d -C(O)N(R 14 )2, then at least one R 14 is not H. In some embodiments, R d -C(O)N(R 14 )2, then each R 14 is C 1-6 In some embodiments, each R d is H.

[0148] In some embodiments, for a compound according to any one of Formulas I, Ia, IA, IA1, IA2, IB, IB1, IB2, IC, IC1, IC2, ID, ID1, ID2, IE, IE1, IE2, IF, IF1, and IF2, R 2 is H. In some embodiments, R 2 is unsubstituted or contains one or more R 13 C replaced by 1-6 In some embodiments, R 2 is a non-substituted C 1-6 In some embodiments, R 2 is one or more R 13 C replaced by 1-6 In some embodiments, R 2 is unsubstituted or contains one or more R 13 C replaced by 1-2 In some embodiments, R 2 is a non-substituted C 1-2 In some embodiments, R 2 is one or more R 13 C replaced by 1-2 In some embodiments, R 2 is methyl. In some embodiments, R 2 is methyl.

[0149] In some embodiments, for a compound according to any one of Formulas I, IA, IA1, IA2, IB, IB1, IB2, IC, IC1, IC2, ID, ID1, ID2, IE, IE1, IE2, IF, IF1, and IF2, R 5 is H. In some embodiments, R 5 is halogen (e.g., F or Cl). In some embodiments, R 5 is Cl. In some embodiments, R 5 is F. In some embodiments, R 5 is -CN. In some embodiments, R 5 -OR 12 and R 12is C 1-6 alkyl and H. In some embodiments, R 5 is —OCH. In some embodiments, R 5 is -OCF3. In some embodiments, R 5 is unsubstituted or contains one or more R 13 C replaced by 1-6 In some embodiments, R 5 is unsubstituted or contains one or more R 13 C replaced by 1-2 In some embodiments, R 5 is unsubstituted, such as methyl or ethyl 1-6 In some embodiments, R 5 is C substituted with one or more halogens or -CN 1-6 In some embodiments, R 5 is a C substituted with one or more halogens, such as one or more fluorines 1-6 In some embodiments, R 5 is -CF3. In some embodiments, R 5 is -CHF. In some embodiments, R 5 is selected from -CFH, -CF, -CHCN, and -CHCH. In some embodiments, R 5 is selected from —CH, —CHCH, —CFH, —CF, —CFCH, and —CHCN. In some embodiments, R 5 is one or more R 13 C replaced by 1-6 alkyl, and each R 13 are independently -OR 14 , -CN, and -N(R 14 In some embodiments, R 5 is —CHCN. In some embodiments, R 5 is a 3- to 6-membered heterocycle. In some embodiments, R 5 is a 5- to 6-membered heteroaryl such as furan.

[0150] In some embodiments, for a compound according to any one of Formulas I, IA, IA1, IA2, IB, IB1, IB2, IC, IC1, IC2, ID, ID1, ID2, IE, IE1, IE2, IF, IF1, and IF2, R 7 is H. In some embodiments, R 7 is halogen (e.g., F or Cl). In some embodiments, R 7 is Cl. In some embodiments, R 7 is F. In some embodiments, R 7 is -CN.

[0151] In another aspect, the present disclosure provides a compound of formula II': [ka] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein: R 1 But, -OR 8 and [ka] is selected from R 2 But H, C 1-6 alkyl, and 3- to 6-membered carbocyclic rings, 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 3 is unsubstituted or contains one or more R 10 is selected from a 4- to 9-membered heterocycle substituted with R 4 is H, R 5 H, halogen, -CN, -OR 12 , 3- to 6-membered heterocycle, 5- to 6-membered heteroaryl, and C 1-6 alkyl, any C 1-6The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 6 is a monocyclic or bicyclic heteroaryl, and the heteroaryl is selected from one or more R 15 is replaced by R 7 is selected from halogens, R 8 is selected from heterocycle and alkylheterocycle, and any heterocycle contains 4 to 8 members and is unsubstituted or contains one or more R a or R b and the alkyl portion of any alkyl heterocycle is substituted with C 1-6 alkyl, Each R 10 independently, deuterium, -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene)OH, -C(O)(C 1-6 alkyl), -C(O)O(C 1-6 alkylene), -C(O)(3- to 6-membered carbocyclic), -C(O)(3- to 8-membered heterocyclic), -C(O)(5- to 6-membered heteroaryl), -C(O)O(3- to 6-membered carbocyclic), -C(O)O(3- to 6-membered heterocyclic), -C(O)O(C 1-6 alkylene)(3- to 6-membered heterocycle), -C(O)N(R 14 )2, -C(O)OR 14 , -S(O)2(C 1-6 alkyl), halogen, 5- to 6-membered heteroaryl, 3- to 6-membered carbocyclic ring, 3- to 6-membered heterocyclic ring and C 1-6 alkyl, any C 1-6 The alkyl is optionally deuterated, unsubstituted, or has one or more R 20 and any 3- to 6-membered carbocyclic, 5- to 6-membered heteroaryl, or 3- to 6- or 3- to 8-membered heterocyclic ring is unsubstituted or substituted with one or more R 12 Or R 20 and two R 10 optionally joined together with the atom(s) to which they are attached to form a 3- to 6-membered carbocyclic or heterocyclic ring; Each R12 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H, and any C 1-6 Alkyl or C 2-6 Alkenyl is unsubstituted or has one or more R 13 is replaced by Each R 13 but independently, -OR 14 , -CN, -N(R 14 )2, and halogen; Each R 14 are independently a 3- to 6-membered carbocyclic ring, a 3- to 6-membered heterocyclic ring, C 1-6 Alkyl, C 2-6 alkenyl, and H, and any C 1-6 the alkyl is optionally deuterated; Each R 15 are independently deuterium, halogen, -N(R 12 )2, -CN, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by Each R 20 Independently, -OH, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, =O, -CN, -NH2, -NHC 1-6 Alkyl, -C(O)(C 1-6 alkyl), a 3- to 6-membered carbocyclic ring, phenyl, and halogen; R 27 is a 3- to 6-membered heterocycle containing one or more heteroatoms selected from N, O, and S, and the heterocycle is unsubstituted or contains one or more R 28 is replaced by Each R 28 But independently, C 1-6 selected from alkyl and halogen; R a and R b are each independently deuterium, halogen, C 1-6 Alkyl, 3-6 membered carbocyclic ring, -OR 12 and H; aand R b are optionally linked together to form a 3- to 6-membered carbocyclic or heterocyclic ring, and any C 1-6 The alkyl or 3- to 6-membered carbocyclic or heterocyclic ring is unsubstituted or contains one or more R 13 The compound or a salt thereof, wherein the compound is substituted with

[0152] In some embodiments, the disclosure provides a compound of formula II' or a salt thereof (eg, a pharmaceutically acceptable salt):

[0153] In another aspect, the present disclosure provides a compound of formula II: [ka] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein: R 1 But, -OR 8 and [ka] is selected from R 2 But H, C 1-6 alkyl, and 3- to 6-membered carbocyclic rings, 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 3 is unsubstituted or contains one or more R 10 and (i) when the heterocycle contains a nitrogen atom, the nitrogen atom is selected from the group consisting of a 4- to 9-membered heterocycle substituted with R 10 or (ii) the heterocycle does not contain an —NH— moiety; R 4 is H, R 5 H, halogen, -CN, -OR 12 , 3- to 6-membered heterocycle, 5- to 6-membered heteroaryl, and C 1-6 alkyl, any C 1-6The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 6 is a monocyclic or bicyclic heteroaryl, and the heteroaryl is selected from one or more R 15 is replaced by R 7 is selected from halogens, R 8 is selected from heterocycle and alkylheterocycle, and any heterocycle contains 4 to 8 members and is unsubstituted or contains one or more R a or R b and the alkyl portion of any alkyl heterocycle is substituted with C 1-6 alkyl, Each R 10 independently, deuterium, -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene)OH, -C(O)(C 1-6 alkyl), -C(O)O(C 1-6 alkylene), -C(O)(3- to 6-membered carbocyclic), -C(O)(3- to 8-membered heterocyclic), -C(O)(5- to 6-membered heteroaryl), -C(O)O(3- to 6-membered carbocyclic), -C(O)O(3- to 6-membered heterocyclic), -C(O)O(C 1-6 alkylene)(3- to 6-membered heterocycle), -C(O)N(R 14 )2, -C(O)OR 14 , -S(O)2(C 1-6 alkyl), halogen, 5-6 membered heteroaryl, 3-6 membered carbocyclic ring, and C 1-6 alkyl, any C 1-6 The alkyl is optionally deuterated, unsubstituted, or has one or more R 20 and any 3- to 6-membered carbocyclic, 5- to 6-membered heteroaryl, or 3- to 6- or 3- to 8-membered heterocyclic ring is unsubstituted or substituted with one or more R 12 Or R 20 and two R 10 optionally joined together with the atom(s) to which they are attached to form a 3- to 6-membered carbocyclic or heterocyclic ring; Each R 12But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H, and any C 1-6 Alkyl or C 2-6 Alkenyl is unsubstituted or has one or more R 13 is replaced by Each R 13 but independently, -OR 14 , -CN, -N(R 14 )2, and halogen; Each R 14 are independently a 3- to 6-membered carbocyclic ring, a 3- to 6-membered heterocyclic ring, C 1-6 Alkyl, C 2-6 alkenyl, and H, and any C 1-6 the alkyl is optionally deuterated; Each R 15 are independently deuterium, halogen, -N(R 12 )2, -CN, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by Each R 20 Independently, -OH, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, =O, -CN, -NH2, -NHC 1-6 Alkyl, -C(O)(C 1-6 alkyl), a 3- to 6-membered carbocyclic ring, phenyl, and halogen; R 27 is a 3- to 6-membered heterocycle containing one or more heteroatoms selected from N, O, and S, and the heterocycle is unsubstituted or contains one or more R 28 is replaced by Each R 28 But independently, C 1-6 selected from alkyl and halogen; R a and R b are each independently deuterium, halogen, C 1-6 Alkyl, -OR 12 , a 3- to 6-membered carbocyclic ring, and H; a and Rb are optionally linked together to form a 3- to 6-membered carbocyclic or heterocyclic ring, and any C 1-6 The alkyl or 3- to 6-membered carbocyclic or heterocyclic ring is unsubstituted or contains one or more R 13 is replaced by

[0154] In some embodiments, the disclosure provides a compound of Formula II or a salt thereof (eg, a pharmaceutically acceptable salt):

[0155] In some embodiments, the present disclosure provides a compound of formula II, wherein: R 1 But, -OR 8 and R 2 But C 1-6 alkyl and 3- to 6-membered carbocyclic rings, 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 3 is unsubstituted or contains one or more R 10 and (i) when the heterocycle contains a nitrogen atom, the nitrogen atom is selected from the group consisting of a 4- to 9-membered heterocycle substituted with R 10 or (ii) the heterocycle does not contain an —NH— moiety; R 4 is H, R 5 But halogen and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 6 is a bicyclic heteroaryl, and the heteroaryl is selected from one or more R 15 is replaced by R 7 is a halogen, R 8 is an alkylheterocycle, and any heterocycle contains 4 to 8 members and is unsubstituted or contains one or more R a Or R band the alkyl portion of any alkyl heterocycle is substituted with C 1-6 alkyl, Each R 10 independently, deuterium, -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene)OH, -C(O)(C 1-6 alkyl), -C(O)O(C 1-6 alkyl), -C(O)(3- to 6-membered carbocyclic), -C(O)(3- to 8-membered heterocyclic), -C(O)(5- to 6-membered heteroaryl), -C(O)O(3- to 6-membered carbocyclic), -C(O)O(3- to 6-membered heterocyclic), -C(O)O(C 1-6 alkylene)(3- to 6-membered heterocycle), -C(O)N(R 14 )2, -S(O)2(C 1-6 alkyl), halogen, 5-6 membered heteroaryl, 3-6 membered carbocyclic ring, and C 1-6 alkyl, any C 1-6 The alkyl is optionally deuterated, unsubstituted, or has one or more R 20 and any 3- to 6-membered carbocyclic, 5- to 6-membered heteroaryl, or 3- to 6- or 3- to 8-membered heterocyclic ring is unsubstituted or substituted with one or more R 12 Or R 20 is replaced by Each R 12 But independently, C 1-6 alkyl and H, and any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by Each R 13 are independently selected from halogen; Each R 14 are independently a 3- to 6-membered carbocyclic ring, a 3- to 6-membered heterocyclic ring, C 1-6 alkyl, and H; Each R 15 are independently halogen, -N(R 12 )2, and -CN; Each R 20 Independently, -OH, -OC 1-6 Alkyl, -OC1-6 Haloalkyl, -CN, -C(O)(C 1-6 alkyl), a 3- to 6-membered carbocyclic ring, phenyl, and halogen; R a and R b are each independently deuterium, halogen, C 1-6 Alkyl, -OR 12 and H; a and R b are optionally linked together to form a 3- to 6-membered carbocyclic ring.

[0156] In some embodiments, the disclosure provides a compound of formula II' or II, wherein the compound has formula II-a: [ka] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein R 2 and R 3 is as defined for formula II above and is described herein in classes and subclasses, both alone and in combination. In some embodiments, R 2 and R 3 is as defined above in formula II' and is described herein in classes and subclasses, both alone and in combination. In some embodiments, the disclosure provides a compound of formula II-a, or a salt (e.g., a pharmaceutically acceptable salt) thereof:

[0157] In some embodiments, for a compound according to any one of Formulas II, II', and II-a, R 3 is a 4-6 membered heterocycle containing one or more heteroatoms selected from O, S, and N, the heterocycle being unsubstituted or containing one or more R 10 In some embodiments, R 3 is a 4-6 membered heterocycle containing one or more heteroatoms selected from O, S, and N, the heterocycle being unsubstituted or containing one or more R 10with the proviso that if the heterocycle contains a nitrogen atom, the nitrogen atom is substituted with R 10 In some embodiments, R 3 is a 4-6 membered heterocycle containing one or more heteroatoms selected from O and S, the heterocycle being unsubstituted or containing one or more R 10 In some embodiments, R 3 is a 4-6 membered heterocycle containing one heteroatom selected from O, S, and N, the heterocycle being unsubstituted or containing one or more R 10 with the proviso that if the heterocycle contains a nitrogen atom, the nitrogen atom is substituted with R 10 In some embodiments, R 3 is a 4- to 6-membered heterocycle containing one heteroatom selected from O, S, and N, and the heterocycle is 10 provided that if the heterocycle contains a nitrogen atom, the nitrogen atom is substituted with R 10 In some embodiments, R 3 is a 4- to 6-membered heterocyclic ring containing a nitrogen atom, and the heterocyclic ring is 10 with the proviso that the nitrogen atom is substituted with R 10 In some embodiments, R 3 is a 4- to 6-membered heterocyclic ring containing a sulfur atom, and the heterocyclic ring is 10 In some embodiments, R 3 is a 4- to 6-membered heterocyclic ring containing an oxygen atom, and the heterocyclic ring is 10 In some embodiments, R 3 is 0 to 4 R 10 and wherein the nitrogen atom of the heterocycle is substituted with R 10 In some embodiments, R 3 is 1 to 4 R 10 and wherein the nitrogen atom of the heterocycle is substituted with R 10 In some embodiments, R 3 is 0 to 4 R 10 In some embodiments, R is an oxetane or thietane substituted with 3is 1 to 4 R 10 In some embodiments, R is an oxetane or thietane substituted with 3 is 0 to 4 R 10 In some embodiments, R is tetrahydrofuran or tetrahydrothiophene substituted with 3 is 1 to 4 R 10 In some embodiments, R is tetrahydrofuran or tetrahydrothiophene substituted with 3 is one or more R 10 and at least one R 10 -OR 12 and C substituted with -OH 1-6 alkyl, provided that if the heterocycle contains a nitrogen atom, the nitrogen atom is selected from R 10 In some embodiments, R 3 is one or more R 10 and at least one R 10 is the unsubstituted C 1-6 alkyl, provided that if the heterocycle contains a nitrogen atom, the nitrogen atom is not R 10 In some embodiments, R 3 is one or more R 10 provided that if the heterocycle contains a nitrogen atom, the nitrogen atom is selected from the group consisting of 4- to 6-membered heterocycles substituted with R 10 Each R is replaced by 10 are independently -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene)OH, -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), halogen, and unsubstituted or one or more R 20 C replaced by 1-6 In some embodiments, R 3 is one or more R 10 provided that if the heterocycle contains a nitrogen atom, the nitrogen atom is selected from the group consisting of 4- to 6-membered heterocycles substituted with R 10 Each R is replaced by10 are independently -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene)OH, -C(O)(C 1-6 alkyl), -C(O)O(C 1-6 alkyl), -C(O)(3- to 6-membered carbocyclic), -C(O)(3- to 7-membered heterocyclic), -C(O)(5- to 6-membered heteroaryl), -C(O)O(3- to 6-membered heterocyclic), -C(C 1-6 alkylene) (3- to 6-membered heterocycle), -C(O)OR 14 , -S(O)2(C 1-6 alkyl), halogen, a 3- to 6-membered carbocyclic ring, and unsubstituted or one or more R 20 C replaced by 1-6 alkyl, and any 3- to 6-membered carbocyclic, 5- to 6-membered heteroaryl, or 3- to 6-membered heterocyclic ring is unsubstituted or contains one or more R 12 Or R 20 In some embodiments, R 3 is one or more R 10 provided that if the heterocycle contains a nitrogen atom, the nitrogen atom is selected from the group consisting of 4- to 6-membered heterocycles substituted with R 10 Each R is replaced by 10 are independently -C(O)(C 1-6 alkyl), -C(O)(3- to 6-membered carbocyclic ring), -C(O)O(C 1-6 alkyl), halogen, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 and any 3- to 6-membered carbocyclic ring is unsubstituted or substituted with one or more R 12 Or R 20 In some embodiments, R 3 is one or more R 10 provided that if the heterocycle contains a nitrogen atom, the nitrogen atom is selected from the group consisting of 4- to 6-membered heterocycles substituted with R 10 and at least one R 10 is -C(O)(C 1-6 alkyl) and -C(O)O(C1-6 In some embodiments, two R 10 are linked together to form a 3- to 6-membered carbocyclic or heterocyclic ring together with the atom(s) to which they are attached. In some embodiments, two R attached to adjacent atoms 10 are joined together with the atoms to which they are attached to form a 3- to 6-membered carbocyclic or heterocyclic ring. In some embodiments, two R attached to adjacent atoms 10 are joined together with the atoms to which they are attached to form a 5- to 6-membered heterocycle, such as pyrrolidine or oxazolidine. In some embodiments, two R 10 The 3- to 6-membered carbocyclic or heterocyclic ring formed by the bonding of 10 In some embodiments, two R 10 The 5- to 6-membered heterocyclic ring formed by the bonding of 10 In some embodiments, each R 10 are independently -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene)OH, -C(O)(C 1-6 alkyl), -C(O)(3- to 6-membered carbocyclic ring), -C(O)N(R 14 )2, -S(O)2(C 1-6 alkyl), halogen, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 and two R 10 are optionally joined together with the atom(s) to which they are attached to form a 3- to 6-membered carbocyclic or heterocyclic ring. 10 are independently -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene)OH, -C(O)(C 1-6 alkyl), -C(O)(3- to 6-membered carbocyclic ring), -C(O)N(R 14 )2, -S(O)2(C 1-6alkyl), halogen, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, each R 10 are independently -OR 12 , -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene)OH, -C(O)(C 1-6 alkyl), halogen, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, each R 10 are independently -C(O)(C 1-6 alkyl), -C(O)(3- to 6-membered carbocyclic ring), -C(O)O(C 1-6 alkyl), halogen, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 and any 3- to 6-membered carbocyclic ring is unsubstituted or substituted with one or more R 12 or R 20 is replaced by

[0158] In some embodiments, for a compound according to any one of Formulas II, II', and II-a, R 3 is a 7-9 membered heterocycle containing one or more heteroatoms selected from O, S, and N, the heterocycle being unsubstituted or containing one or more R 10 In some embodiments, R 3 is a 7-9 membered heterocycle containing one or more heteroatoms selected from O, S, and N, the heterocycle being unsubstituted or containing one or more R 10 with the proviso that (i) if the heterocycle contains a nitrogen atom, the nitrogen atom is substituted with R 10 or (ii) the heterocycle does not contain an —NH— moiety. In some embodiments, R 3is a 7-9 membered heterocycle containing one or more heteroatoms selected from O, S, and N, the heterocycle being unsubstituted or containing one or more R 10 with the proviso that (i) if the heterocycle contains a nitrogen atom, the nitrogen atom is substituted with R 10 or (ii) if the heterocycle contains a single ring, the heterocycle does not contain an —NH— moiety. 3 is a 7- to 9-membered bridged heterocycle containing one or more heteroatoms selected from O, S, and N, and the bridged heterocycle is unsubstituted or contains one or more R 10 In some embodiments, R 3 is a 7- to 9-membered bridged heterocycle containing one or more heteroatoms selected from O, S, and N, and the bridged heterocycle is unsubstituted or contains one or more R 10 with the proviso that (i) if the bridged heterocycle contains a nitrogen atom, the nitrogen atom is substituted with R 10 or (ii) the bridged heterocycle does not contain an —NH— moiety. In some embodiments, R 3 is unsubstituted or contains one or more R 10 In some embodiments, R 3 is unsubstituted or contains one or more R 10 wherein the bridged pyrrolidine does not contain an NH moiety. 3 is one or more R 10 wherein the bridged pyrrolidine does not contain an NH moiety. 3 is a 7-9 membered heterocycle including a fused ring system containing one or more heteroatoms selected from O, S, and N, the heterocycle being unsubstituted or containing one or more R 10 In some embodiments, R 3 is a 7-9 membered heterocycle including a fused ring system containing one or more heteroatoms selected from O, S, and N, the heterocycle being unsubstituted or containing one or more R 10 with the proviso that (i) if the heterocycle contains a nitrogen atom, the nitrogen atom is substituted with R10 or (ii) the heterocycle does not contain an —NH— moiety. In some embodiments, R 3 is a 7-9 membered heterocycle, including a fused ring system containing two rings, wherein the heterocycle contains one or more heteroatoms selected from O, S, and N, and the heterocycle is unsubstituted or contains one or more R 10 In some embodiments, R 3 is a 7-9 membered heterocycle, including a fused ring system containing two rings, wherein the heterocycle contains one or more heteroatoms selected from O, S, and N, and the heterocycle is unsubstituted or contains one or more R 10 with the proviso that (i) if the heterocycle contains a nitrogen atom, the nitrogen atom is substituted with R 10 or (ii) the heterocycle does not contain an —NH— moiety. In some embodiments, R 3 includes fused ring systems containing two rings, where at least one ring is unsubstituted or contains one or more R 10 In some embodiments, R 3 includes fused ring systems containing two rings, where at least one ring is unsubstituted or contains one or more R 10 In some embodiments, R 3 includes fused ring systems containing two rings, each ring being unsubstituted or containing one or more R 10 In some embodiments, R 3 includes fused ring systems containing two rings, one ring being unsubstituted or containing one or more R 10 and the second ring is unsubstituted or substituted with one or more R 10 In some embodiments, R 3 includes fused ring systems containing two rings, one ring being unsubstituted or containing one or more R 10 and the second ring is unsubstituted or substituted with one or more R 10In some embodiments, the fused ring system is a piperidine, oxazinane, oxazolidine, imidazolidine, or pyrrolidine substituted with at least one R 10 and at least one R 10 =O and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 is replaced by

[0159] In some embodiments, R 10 -C(O)N(R 14 )2, then at least one R 14 is not H. In some embodiments, R 10 -C(O)N(R 14 )2, then each R 14 is C 1-6 alkyl (for example, methyl or ethyl).

[0160] In some embodiments, for compounds according to Formula II' or II-a, R 3 teeth, [ka] Any of them has one or more R 10 The compound according to any one of embodiments C103 to C129, substituted with:

[0161] In some embodiments, for a compound according to any one of Formulas II', II, and II-a, R 3 teeth, [ka] [ka] [ka] [ka] [ka] [ka] [ka] is selected from Any of them has one or more R 10 The compound according to any one of embodiments C103 to C129, substituted with:

[0162] In some embodiments, for compounds according to Formula II' or II, R 3 teeth, [ka] is selected from Any of them has one or more R 10 The compound according to any one of embodiments C103 to C129, substituted with:

[0163] In some embodiments, the compound has formula IIa, IIB, IIC, IID, IIe, IIF, IIG, IIh, IIJ, IIK, IIL, IIM, IIN, IIP, IIQ, IIR, IIS, IIT, IIU, IIV, IIW, IIX, IIY, or IIZ: [ka] [ka] [ka] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein R 1 But, -OR 8 and [ka] is selected from R 2 But H, C 1-6 alkyl, and 3- to 6-membered carbocyclic rings, 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 4 is H, if present, R 5 H, halogen, -CN, -OR 12 , 3- to 6-membered heterocycle, 5- to 6-membered heteroaryl, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 6 is a monocyclic or bicyclic heteroaryl, and the heteroaryl is selected from one or more R 15 is replaced by R 7 is selected from halogens, R 8 is selected from heterocycle and alkylheterocycle, and any heterocycle contains 4 to 8 members and is unsubstituted or contains one or more R a or R b and the alkyl portion of any alkyl heterocycle is substituted with C 1-6 alkyl, Each R 12 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H, and any C 1-6 Alkyl or C 2-6 Alkenyl is unsubstituted or has one or more R 13 is replaced by Each R 13 but independently, -OR 14 , -CN, -N(R 14 )2, and halogen; Each R 14 are independently a 3- to 6-membered carbocyclic ring, a 3- to 6-membered heterocyclic ring, C 1-6 Alkyl, C 2-6 alkenyl, and H, and any C 1-6the alkyl is optionally deuterated; Each R 15 are independently deuterium, halogen, -N(R 12 )2, -CN, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by Each R 20 Independently, -OH, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, =O, -CN, -NH2, -NHC 1-6 Alkyl, -C(O)(C 1-6 alkyl), a 3- to 6-membered carbocyclic ring, phenyl, and halogen; R 27 is a 3- to 6-membered heterocycle containing one or more heteroatoms selected from N, O, and S, and the heterocycle is unsubstituted or contains one or more R 28 is replaced by Each R 28 But independently, C 1-6 selected from alkyl and halogen; R a and R b are each independently deuterium, halogen, C 1-6 Alkyl, -OR 12 , a 3- to 6-membered carbocyclic ring, and H; a and R b are optionally linked together to form a 3- to 6-membered carbocyclic or heterocyclic ring, and any C 1-6 The alkyl or 3- to 6-membered carbocyclic or heterocyclic ring is unsubstituted or contains one or more R 13 is replaced by Each R d are independently H, deuterium, -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene)OH, -C(O)(C 1-6 alkyl), -C(O)(3- to 6-membered carbocyclic ring), -S(O)2(C 1-6 alkyl), halogen, and C 1-6 alkyl, any C1-6 The alkyl may be unsubstituted or may contain one or more R 20 and any 3- to 6-membered carbocyclic ring is unsubstituted or substituted with one or more R 12 or R 20 is replaced by R e If present, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene)OH, -C(O)(C 1-6 alkyl), -C(O)O(C 1-6 alkyl), -C(O)OR 14 , -C(O)(3- to 6-membered carbocyclic ring), -C(O)(3- to 8-membered heterocyclic ring), -C(O)(5- to 6-membered heteroaryl), -C(O)O(3- to 6-membered carbocyclic ring), -C(O)O(3- to 6-membered heterocyclic ring), -C(O)O(C 1-6 alkylene)(3- to 6-membered heterocycle), -C(O)N(R 14 )2, -S(O)2(C 1-6 alkyl), 5-6 membered heteroaryl, 3-6 membered carbocyclic ring, and C 1-6 alkyl, any C 1-6 The alkyl is optionally deuterated, unsubstituted, or has one or more R 20 and any 3- to 6-membered carbocyclic, 5- to 6-membered heteroaryl, or 3- to 6- or 3- to 8-membered heterocyclic ring is unsubstituted or substituted with one or more R 12 Or R 20 is replaced by Each R f is optionally absent, and when present, is =O, -NH2, -NHC 1-6 Alkyl, and -N(C 1-6 alkyl)2.

[0164] In some embodiments, the compound is a compound according to Formula IIA, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIB, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIC, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IID, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIE, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIF, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIG, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIH, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIJ, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIK, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof.In some embodiments, the compound is a compound according to Formula IIL, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIM, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIN, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIP, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIQ, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIR, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIS, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIT, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIU, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIV, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof.In some embodiments, the compound is a compound according to Formula IIW, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIX, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIY, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIZ, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof.

[0165] In some embodiments, the compound is a compound according to Formula IIA or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIB or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIC or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IID or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIE or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIF or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIG or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIH or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIJ or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIK or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIL or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIM or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIN or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIP or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIQ or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIR or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIS or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIT or a salt (e.g., a pharmaceutically acceptable salt) thereof.In some embodiments, the compound is a compound according to Formula IIU or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIV or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIW or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIX or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIY or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIZ or a salt (e.g., a pharmaceutically acceptable salt) thereof.

[0166] In some embodiments, the compound has formula IIAA: [ka] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein R 1 But, -OR 8 and [ka] is selected from R 2 But H, C 1-6 alkyl, and 3- to 6-membered carbocyclic rings, 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 4 is H, R 5 H, halogen, -CN, -OR 12 , 3- to 6-membered heterocycle, 5- to 6-membered heteroaryl, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 6is a monocyclic or bicyclic heteroaryl, and the heteroaryl is selected from one or more R 15 is replaced by R 7 is selected from halogens, R 8 is selected from heterocycle and alkylheterocycle, and any heterocycle contains 4 to 8 members and is unsubstituted or contains one or more R a or R b and the alkyl portion of any alkyl heterocycle is substituted with C 1-6 alkyl, Each R 12 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H, and any C 1-6 Alkyl or C 2-6 Alkenyl is unsubstituted or has one or more R 13 is replaced by Each R 13 but independently, -OR 14 , -CN, -N(R 14 )2, and halogen; Each R 14 are independently a 3- to 6-membered carbocyclic ring, a 3- to 6-membered heterocyclic ring, C 1-6 Alkyl, C 2-6 alkenyl, and H, and any C 1-6 the alkyl is optionally deuterated; Each R 15 are independently deuterium, halogen, -N(R 12 )2, -CN, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by Each R 20 Independently, -OH, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, =O, -CN, -NH2, -NHC 1-6 Alkyl, -C(O)(C 1-6 alkyl), a 3- to 6-membered carbocyclic ring, phenyl, and halogen; R 27is a 3- to 6-membered heterocycle containing one or more heteroatoms selected from N, O, and S, and the heterocycle is unsubstituted or contains one or more R 28 is replaced by Each R 28 But independently, C 1-6 selected from alkyl and halogen; R a and R b are each independently deuterium, halogen, C 1-6 Alkyl, -OR 12 , a 3- to 6-membered carbocyclic ring, and H; a and R b are optionally linked together to form a 3- to 6-membered carbocyclic or heterocyclic ring, and any C 1-6 The alkyl or 3- to 6-membered carbocyclic or heterocyclic ring is unsubstituted or contains one or more R 13 is replaced by Each R d are independently H, deuterium, -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene)OH, -C(O)(C 1-6 alkyl), -C(O)(3- to 6-membered carbocyclic ring), -S(O)2(C 1-6 alkyl), halogen, 3- to 6-membered carbocyclic ring, 3- to 6-membered heterocyclic ring, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 and any 3-6 membered carbocyclic or 3-6 membered heterocyclic ring is unsubstituted or substituted with one or more R 12 Or R 20 is replaced by (i)R q1 , R q2 , and R p2 are each independently R d Selected from R e and R p1 together with the atoms to which they are attached are unsubstituted or contain one or more R d or forming a 5- to 6-membered heterocyclic ring substituted with (ii)R p1 , Rp2 , and R q2 are each independently R d Selected from R e and R q1 together with the atoms to which they are attached are unsubstituted or contain one or more R d Forms a 5- to 6-membered heterocyclic ring substituted with

[0167] In some embodiments, the compound is a compound according to Formula IIAA or a salt thereof (eg, a pharmaceutically acceptable salt).

[0168] In some embodiments, for a compound according to any one of Formulas II, II', II-a, IIA, IIB, IIC, IID, IIE, IIF, IIG, IIH, IIJ, IIK, IIL, IIM, IIN, IIP, IIQ, IIR, IIS, IIT, IIU, IIV, IIW, IIX, IIY, IIZ, and IIAA, R 6 is one or more R 15 In some embodiments, R is a monocyclic heteroaryl substituted with 6 is one or more R 15 In some embodiments, at least one R 15 is C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 In some embodiments, at least one R 15 is -N(R 12 )2. In some embodiments, R 6 teeth, [ka] any of which may optionally be selected from one or more R 15 In some embodiments, R 6 teeth, [ka] is.

[0169] In some embodiments, for a compound according to any one of Formulas II, II', II-a, IIA, IIB, IIC, IID, IIE, IIF, IIG, IIH, IIJ, IIK, IIL, IIM, IIN, IIP, IIQ, IIR, IIS, IIT, IIU, IIV, IIW, IIX, IIY, IIZ, and IIAA, R 6 is one or more R 15 In some embodiments, R is a bicyclic heteroaryl substituted with 6 teeth, [ka] wherein X is selected from N and C-CN, Y is selected from O and S, and R 23 But -N(R 12 )2, C 1-6 Alkyl, and C 1-6 Alkyl-N(R 14 )2 and any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 24 , R 25 , and R 26 are independently H, deuterium, halogens, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 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 and Y is S and R 23 is -N(R 12 In some embodiments, X is C-CN, Y is S, and R 23 is -NH. In some embodiments, R 24 is halogen (e.g., fluoro). In some embodiments, R 26 is deuterium.

[0170] In some embodiments, for a compound according to any one of Formulas II, II', II-a, IIA, IIB, IIC, IID, IIE, IIF, IIG, IIH, IIJ, IIK, IIL, IIM, IIN, IIP, IIQ, IIR, IIS, IIT, IIU, IIV, IIW, IIX, IIY, IIZ, and IIAA, R 6 teeth, [ka] is selected from Any of them has one or more R 15 is replaced by

[0171] In some embodiments, for a compound according to any one of Formulas II, II', II-a, IIA, IIB, IIC, IID, IIE, IIF, IIG, IIH, IIJ, IIK, IIL, IIM, IIN, IIP, IIQ, IIR, IIS, IIT, IIU, IIV, IIW, IIX, IIY, IIZ, and IIAA, R 6 teeth, [ka] is selected from.

[0172] In some embodiments, for a compound according to any one of Formulas II, II', II-a, IIA, IIB, IIC, IID, IIE, IIF, IIG, IIH, IIJ, IIK, IIL, IIM, IIN, IIP, IIQ, IIR, IIS, IIT, IIU, IIV, IIW, IIX, IIY, IIZ, and IIAA, R 6 teeth, [ka] is selected from.

[0173] In some embodiments, for a compound according to any one of Formulas II, II', II-a, IIA, IIB, IIC, IID, IIE, IIF, IIG, IIH, IIJ, IIK, IIL, IIM, IIN, IIP, IIQ, IIR, IIS, IIT, IIU, IIV, IIW, IIX, IIY, IIZ, and IIAA, R 6 teeth, [ka] is.

[0174] In some embodiments, the compound has formula IIA1, IIB1, IIC1, IID1, IIE1, IIF1, IIG1, IIH1, IIJ1, IIK1, IIL1, IIM1, IIN1, IIP1, IIQ1, IIR1, IIS1, IIT1, IIU1, IIV1, IIW1, IIX1, IIY1, or IIZ1: [ka] [ka] [ka] [ka] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein R 1 But, -OR 8 and [ka] is selected from R 2 But H, C 1-6 alkyl, and 3- to 6-membered carbocyclic rings, 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 4is H, if present, R 5 H, halogen, -CN, -OR 12 , 3- to 6-membered heterocycle, 5- to 6-membered heteroaryl, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 7 is selected from halogens, R 8 is selected from heterocycle and alkylheterocycle, and any heterocycle contains 4 to 8 members and is unsubstituted or contains one or more R a or R b and the alkyl portion of any alkyl heterocycle is substituted with C 1-6 alkyl, Each R 12 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H, and any C 1-6 Alkyl or C 2-6 Alkenyl is unsubstituted or has one or more R 13 is replaced by Each R 13 but independently, -OR 14 , -CN, -N(R 14 )2, and halogen; Each R 14 are independently a 3- to 6-membered carbocyclic ring, a 3- to 6-membered heterocyclic ring, C 1-6 Alkyl, C 2-6 alkenyl, and H, and any C 1-6 the alkyl is optionally deuterated; Each R 20 Independently, -OH, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, =O, -CN, -NH2, -NHC 1-6 Alkyl, -C(O)(C 1-6 alkyl), a 3- to 6-membered carbocyclic ring, phenyl, and halogen; R 27is a 3- to 6-membered heterocycle containing one or more heteroatoms selected from N, O, and S, and the heterocycle is unsubstituted or contains one or more R 28 is replaced by Each R 28 But independently, C 1-6 selected from alkyl and halogen; R a and R b are each independently deuterium, halogen, C 1-6 Alkyl, -OR 12 , a 3- to 6-membered carbocyclic ring, and H; a and R b are optionally linked together to form a 3- to 6-membered carbocyclic or heterocyclic ring, and any C 1-6 The alkyl or 3- to 6-membered carbocyclic or heterocyclic ring is unsubstituted or contains one or more R 13 is replaced by Each R d are independently H, deuterium, -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene)OH, -C(O)(C 1-6 alkyl), -C(O)(3- to 6-membered carbocyclic ring), -C(O)N(R 14 )2, -S(O)2(C 1-6 alkyl), halogen, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 and any 3- to 6-membered carbocyclic ring is unsubstituted or substituted with one or more R 12 or R 20 is replaced by R e If present, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene)OH, -C(O)(C 1-6 alkyl), -C(O)O(C 1-6 alkyl), -C(O)OR 14 , -C(O)(3-6 membered carbocycle), -C(O)N(R 14)2, -C(O)(3- to 8-membered heterocycle), -C(O)(5- to 6-membered heteroaryl), -C(O)O(3- to 6-membered carbocycle), -C(O)O(3- to 6-membered heterocycle), -C(O)O(C 1-6 alkylene) (3- to 6-membered heterocycle), -S(O2(C 1-6 alkyl), 5-6 membered heteroaryl, 3-6 membered carbocyclic ring, and C 1-6 alkyl, any C 1-6 The alkyl is optionally deuterated, unsubstituted, or has one or more R 20 and any 3- to 6-membered carbocyclic, 5- to 6-membered heteroaryl, or 3- to 6- or 3- to 8-membered heterocyclic ring is unsubstituted or substituted with one or more R 12 Or R 20 is replaced by Each R f is optionally absent, and when present, is =O, -NH2, -NHC 1-6 Alkyl, and -N(C 1-6 alkyl)2; X is selected from N and C-CN; Y is selected from O and S; R 23 But -N(R 12 )2, C 1-6 Alkyl, and C 1-6 Alkyl-N(R 14 )2 and any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 24 , R 25 , and R 26 are independently H, deuterium, halogens, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by

[0175] In some embodiments, the compound is a compound according to Formula IIA1, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIB1, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIC1, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IID1, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIE1, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIF1, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIG1, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIH1, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIJ1, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIK1, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof.In some embodiments, the compound is a compound according to Formula IIH1, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIH1, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIH1, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIH1, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIQ1, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIR1, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIS1, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIIT1, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIU1, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIV1, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof.In some embodiments, the compound is a compound according to Formula IIW1, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIX1, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIY1, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIZ1, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof.

[0176] In some embodiments, the compound is a compound according to Formula IIA1 or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIB1 or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIC1 or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IID1 or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIE1 or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIF1 or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIG1 or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIH1 or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIJ1 or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIK1 or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIL1 or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIM1 or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIN1 or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIP1 or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIQ1 or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIR1 or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIS1 or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIT1 or a salt (e.g., a pharmaceutically acceptable salt) thereof.In some embodiments, the compound is a compound according to Formula IIU1 or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIV1 or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIW1 or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIX1 or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIY1 or a salt (e.g., a pharmaceutically acceptable salt) thereof. In some embodiments, the compound is a compound according to Formula IIZ1 or a salt (e.g., a pharmaceutically acceptable salt) thereof.

[0177] In some embodiments, the compound has the formula IIAA1: [ka] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein R 1 But, -OR 8 and [ka] is selected from R 2 But H, C 1-6 alkyl, and 3- to 6-membered carbocyclic rings, 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 4 is H, R 5 H, halogen, -CN, -OR 12 , 3- to 6-membered heterocycle, 5- to 6-membered heteroaryl, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 7is selected from halogens, R 8 is selected from heterocycle and alkylheterocycle, and any heterocycle contains 4 to 8 members and is unsubstituted or contains one or more R a or R b and the alkyl portion of any alkyl heterocycle is substituted with C 1-6 alkyl, Each R 12 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H, and any C 1-6 Alkyl or C 2-6 Alkenyl is unsubstituted or has one or more R 13 is replaced by Each R 13 but independently, -OR 14 , -CN, -N(R 14 )2, and halogen; Each R 14 are independently a 3- to 6-membered carbocyclic ring, a 3- to 6-membered heterocyclic ring, C 1-6 Alkyl, C 2-6 alkenyl, and H, and any C 1-6 the alkyl is optionally deuterated; Each R 20 Independently, -OH, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, =O, -CN, -NH2, -NHC 1-6 Alkyl, -C(O)(C 1-6 alkyl), a 3- to 6-membered carbocyclic ring, phenyl, and halogen; R 27 is a 3- to 6-membered heterocycle containing one or more heteroatoms selected from N, O, and S, and the heterocycle is unsubstituted or contains one or more R 28 is replaced by Each R 28 But independently, C 1-6 selected from alkyl and halogen; R a and R b are each independently deuterium, halogen, C 1-6 Alkyl, -OR12 , a 3- to 6-membered carbocyclic ring, and H; a and R b are optionally linked together to form a 3- to 6-membered carbocyclic or heterocyclic ring, and any C 1-6 The alkyl or 3- to 6-membered carbocyclic or heterocyclic ring is unsubstituted or contains one or more R 13 is replaced by Each R d are independently H, deuterium, -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene)OH, -C(O)(C 1-6 alkyl), -C(O)(3- to 6-membered carbocyclic ring), -C(O)N(R 14 )2, -S(O)2(C 1-6 alkyl), 3- to 6-membered carbocyclic ring, 3- to 6-membered heterocyclic ring, halogen, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 and any 3- to 6-membered carbocyclic or 3- to 6-membered heterocyclic ring is unsubstituted or substituted with one or more R 12 Or R 20 is replaced by X is selected from N and C-CN; Y is selected from O and S; R 23 But -N(R 12 )2, C 1-6 Alkyl, and C 1-6 Alkyl-N(R 14 )2 and any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 24 , R 25 , and R 26 are independently H, deuterium, halogens, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by (i)R q1 , R q2, and R p2 are each independently R d Selected from R e and R p1 together with the atoms to which they are attached are unsubstituted or contain one or more R d or forming a 5- to 6-membered heterocyclic ring substituted with (ii)R p1 , R p2 , and R q2 are each independently R d Selected from R e and R q1 together with the atoms to which they are attached are unsubstituted or contain one or more R d Forms a 5- to 6-membered heterocyclic ring substituted with

[0178] In some embodiments, the compound is a compound according to Formula IIAA1 or a salt thereof (eg, a pharmaceutically acceptable salt).

[0179] In some embodiments, for a compound according to formula IIAA or IIAA1, R q1 , R q2 , and R p2 are each independently R d Selected from R e and R p1 together with the atoms to which they are attached, are unsubstituted or contain one or more R d In some embodiments, R e and R p1 together with the atoms to which they are attached, are unsubstituted or contain one or more R d In some embodiments, R e and R p1 together with the atoms to which they are attached, are unsubstituted or contain one or more R d In some embodiments, R e and R p1 together with the atoms to which they are attached form an unsubstituted 5- to 6-membered heterocyclic ring. e and Rp1 consists of one or more R d and forming a 5- to 6-membered heterocyclic ring substituted with at least one R d is not H. In some embodiments, R e and R p1 together with the atoms to which they are attached, are unsubstituted or contain one or more R d In some embodiments, R e and R p1 together with the atoms to which they are attached, are unsubstituted or contain one or more R d In some embodiments, R p2 is H.

[0180] In some embodiments, for a compound according to formula IIAA or IIAA1, R p1 , R p2 , and R q2 are each independently R d Selected from R e and R q1 together with the atoms to which they are attached, are unsubstituted or contain one or more R d In some embodiments, R e and R q1 together with the atoms to which they are attached, are unsubstituted or contain one or more R d In some embodiments, R e and R q1 together with the atoms to which they are attached, are unsubstituted or contain one or more R d In some embodiments, R e and R q1 together with the atoms to which they are attached form an unsubstituted 5- to 6-membered heterocyclic ring. e and R q1consists of one or more R d and forming a 5- to 6-membered heterocyclic ring substituted with at least one R d is not H. In some embodiments, R e and R q1 together with the atoms to which they are attached, are unsubstituted or contain one or more R d In some embodiments, R e and R p1 together with the atoms to which they are attached, are unsubstituted or contain one or more R d In some embodiments, R q2 is H.

[0181] In some embodiments, for a compound according to any one of formulas IIA1, IIB1, IIC1, IID1, IIE1, IIF1, IIG1, IIH1, IIJ1, IIK1, IIL1, IIM1, IIN1, IIP1, IIQ1, IIR1, IIS1, IIT1, IIU1, IIV1, IIW1, IIX1, IIY1, IIZ1, and IIAA1, 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 and Y is S and R 23 is -N(R 12 In some embodiments, X is C-CN, Y is S, and R 23 In some embodiments, X is C—CN, Y is S, and R 23 is -N(R 12 )2 and R 24 is halogen (e.g., F). In some embodiments, X is C—CN, Y is S, and R 23 is -N(R 12)2 and R 24 , R 25 , and R 26 One or more of R is halogen (e.g., F). In some embodiments, R 26 is deuterium.

[0182] In some embodiments, for a compound according to any one of Formulas IIC, IIC1, IIE, IIE1, IIL, IIL1, IIM, IIM1, IIQ, IIQ1, IIS, IIS1, IIY, IIY1, IIZ, and IIZ1, each R f is ═O. In some embodiments, each R f is optionally absent, and when present, is ═O. In some embodiments, each R f does not exist.

[0183] In some embodiments, for a compound of any one of formulas IIA, IIA1, IIB, IIB1, IIC, IIC1, IID, IID1, IIE, IIE1, IIF, IIF1, IIG, IIG1, IIH, IIH1, IIJ, IIJ1, IIK, IIK1, IIL, IIL1, IIM, IIM1, IIN, IIN1, IIP, IIP1, IIQ, IIQ1, IIR, IIR1, IIS, IIS1, IIT, IIT1, IIU, IIU1, IIU1, IIV, IIV1, IIW, IIW1, IIX, IIX1, IIY, IIY1, IIZ, IIZ1, IIAA, and IIAA1, each R d is H. In some embodiments, at least one R d -OR 12 and C substituted with -OH 1-6 In some embodiments, each R d are independently H, -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene)OH, -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), halogen, and unsubstituted or one or more R 20 C replaced by 1-6R is selected from alkyl. d If =O, then the other R atoms on the same carbon atom should be removed so that the carbon has the appropriate valence. d It is understood that there is no

[0184] In some embodiments, for a compound according to any one of formulas IIA, IIA1, IID, IID1, IIG, IIG1, IIH, IIH1, IIN, IIN1, IIR, IIR1, IIU, IIU1, IIV, and IIV1, R e is -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene)OH, -C(O)(C 1-6 alkyl), -C(O)(3- to 6-membered carbocyclic ring), -C(O)N(R 14 )2, -C(O)OR 14 , -S(O)2(C 1-6 alkyl), and C 1-6 alkyl, any C 1-6 Alkyl is unsubstituted or has one or more R 20 and any 3- to 6-membered carbocyclic ring is unsubstituted or substituted with one or more R 12 Or R 20 In some embodiments, R e is -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene)OH, -C(O)( 1-6 alkyl), -C(O)O(C 1-6 alkyl), -C(O)OR 14 , —C(O)(3- to 6-membered carbocyclic), —C(O)(3- to 7-membered heterocyclic), —C(O)(5- to 6-membered heteroaryl), —C(O)O(3- to 6-membered heterocyclic), and —C(O)O(C 1-6 alkylene) (3- to 6-membered heterocycle), and any C 1-6 Alkyl is unsubstituted or has one or more R 20 and any 3- to 6-membered carbocyclic, 5- to 6-membered heteroaryl, or 3- to 6-membered heterocyclic ring is unsubstituted or substituted with one or more R 12 Or R 20In some embodiments, R e is -C(O)(3- to 6-membered carbocyclic), -C(O)(3- to 7-membered heterocyclic), -C(O)(5- to 6-membered heteroaryl), -C(O)O(3- to 6-membered heterocyclic) and -C(O)O(C 1-6 alkylene) (3- to 6-membered heterocycle), any C 1-6 Alkyl is unsubstituted or has one or more R 20 and any 3- to 6-membered carbocyclic, 5- to 6-membered heteroaryl, or 3- to 6-membered heterocyclic ring is unsubstituted or substituted with one or more R 12 Or R 20 In some embodiments, R e is -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene)OH, -C(O)(C 1-6 alkyl), -C(O)N(R 14 )2, -C(O)OR 14 , and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, R e is -C(O)(C 1-6 alkyl), -C(O)(3- to 6-membered carbocyclic ring), and -C(O)O(C 1-6 alkyl), and any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 and any 3- to 6-membered carbocyclic ring is unsubstituted or substituted with one or more R 12 Or R 20 In some embodiments, R e is unsubstituted or contains one or more R 20 C replaced by 1-6 In some embodiments, R e is one or more R 20 C replaced by 1-6 In some embodiments, R e is one or more R 20 C replaced by 1-6 alkyl, and each R20 are independently -OH, -OC 1-6 In some embodiments, R e is -C(O)(C 1-6 alkyl), and any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, R e is -C(O)(C 1-6 alkyl), and any C 1-6 The alkyl is unsubstituted. In some embodiments, R e is -C(O)(C 1-6 alkyl), and any C 1-6 Alkyl is one or more R 20 and one or more R 20 independently, -OC 1-6 In some embodiments, each R e is -C(O)(C 1-6 alkylene)CN, and any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, each R e is -C(O)(C 1-6 alkylene)OH, and any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, R e is -C(O)N(R 14 In some embodiments, R e is -C(O)N(R 14 )2, and each R 14 are independently a 3- to 6-membered carbocyclic ring, a 3- to 6-membered heterocyclic ring, C 1-6 alkyl, and H. In some embodiments, R e is -C(O)N(R 14 )2, and each R 14 independently, C 1-6 alkyl and H. In some embodiments, Re -C(O)N(R 14 )2, then at least one R 14 is not H. In some embodiments, R e -C(O)N(R 14 )2, then each R 14 is C 1-6 alkyl (e.g., methyl or ethyl). In some embodiments, R e is -C(O)OR 14 In some embodiments, R e is -C(O)OR 14 Selected from R 14 is a 3- to 6-membered carbocyclic ring, a 3- to 6-membered heterocyclic ring, C 1-6 Alkyl, and C 2-6 alkenyl, any C 1-6 The alkyl is optionally deuterated. In some embodiments, R e is -C(O)OR 14 Selected from R 14 is selected from a 3- to 6-membered carbocyclic ring and a 3- to 6-membered heterocyclic ring. e is -S(O)2(C 1-6 alkyl), and C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, R e is selected from -C(O)(3- to 6-membered carbocyclic ring), which is unsubstituted or contains one or more R 12 Or R 20 In some embodiments, R e is an unsubstituted —C(O) (3- to 6-membered carbocyclic ring). In some embodiments, R e is selected from -C(O)(3- to 6-membered carbocyclic ring), and the 3- to 6-membered carbocyclic ring is selected from one or more R 12 or R 20 In some embodiments, R e is selected from -C(O)(3- to 6-membered carbocycle), wherein the 3- to 6-membered carbocycle is cyclopropane or cyclobutane, and the 3- to 6-membered carbocycle is unsubstituted or contains one or more R 12Or R 20 In some embodiments, R e is —C(O)(cyclopropane). In some embodiments, R e is selected from —C(O)(cyclopropane), wherein the cyclopropane is selected from one or more R 12 or R 20 (e.g., one or more fluoro). In some embodiments, R e is selected from —C(O)(3- to 8-membered heterocycle), wherein the 3- to 8-membered heterocycle is unsubstituted or contains one or more R 12 Or R 20 In some embodiments, R e is selected from —C(O)(3- to 8-membered heterocycle), wherein the 3- to 8-membered heterocycle is unsubstituted. e is selected from -C(O)(3- to 8-membered heterocycle), and the 3- to 8-membered heterocycle is selected from one or more R 12 or R 20 In some embodiments, R e is selected from —C(O)(3- to 7-membered heterocycle), wherein the 3- to 7-membered heterocycle is unsubstituted or contains one or more R 12 Or R 20 In some embodiments, R e is selected from -C(O)(3- to 7-membered heterocycle), wherein the 3- to 7-membered heterocycle is unsubstituted. e is selected from -C(O)(3- to 7-membered heterocycle), and the 3- to 7-membered heterocycle is selected from one or more R 12 or R 20 In some embodiments, R e is selected from —C(O)(3- to 7-membered heterocycle), wherein the 3- to 7-membered heterocycle is oxetane, azetidine, pyrrolidine, azabicyclo[3.1.0]hexane, morpholine, bridged morpholine, tetrahydropyran, piperidine, piperazine, or 2-oxa-6-azaspiro[3.3]heptane, and the 3- to 7-membered heterocycle is unsubstituted or substituted with one or more R 12 Or R 20 In some embodiments, R eis selected from —C(O)(3- to 7-membered heterocycle), wherein the 3- to 7-membered heterocycle is oxetane, azetidine, pyrrolidine, morpholine, tetrahydropyran, piperidine, or piperazine, and the 3- to 7-membered heterocycle is unsubstituted or contains one or more R 12 Or R 20 In some embodiments, R e is selected from —C(O)(3- to 7-membered heterocycle), wherein the 3- to 7-membered heterocycle is morpholine or a bridged morpholine, and the morpholine or bridged morpholine is unsubstituted or is substituted with one or more R 12 Or R 20 In some embodiments, R e is selected from -C(O)(3- to 7-membered heterocycle), and the 3- to 7-membered heterocycle is [ka] wherein the bridged morpholine is unsubstituted or has one or more R 12 Or R 20 In some embodiments, R e is selected from -C(O)(3- to 7-membered heterocycle), and the 3- to 7-membered heterocycle is selected from one or more R 12 or R 20 Each R is replaced by 12 independently, C 1-6 alkyl, and each R 20 independently, -OC 1-6 Alkyl, -C(O)(C 1-6 alkyl), and halogen. In some embodiments, R e is selected from —C(O)(5- to 6-membered heteroaryl), wherein the 5- to 6-membered heteroaryl is unsubstituted or has one or more R 12 Or R 20 In some embodiments, R e is selected from -C(O)(5-6 membered heteroaryl), wherein the 5-6 membered heteroaryl is unsubstituted. e is selected from —C(O)(5- to 6-membered heteroaryl), wherein the 5- to 6-membered heteroaryl is selected from one or more R12 or R 20 In some embodiments, R e is selected from —C(O)(5- to 6-membered heteroaryl), wherein 5- to 6-membered heteroaryl is thiophene, pyrazole, oxazole, isoxazole, thiazole, isothiazole, triazole, oxadiazole, thiadiazole, pyridine, or pyrimidine, any of which is unsubstituted or substituted by one or more R 12 Or R 20 In some embodiments, R e is selected from —C(O)(5- to 6-membered heteroaryl), wherein the 5- to 6-membered heteroaryl is oxazole or isoxazole, and the oxazole or isoxazole is unsubstituted or contains one or more R 12 Or R 20 In some embodiments, R e is selected from -C(O)O (3- to 6-membered carbocyclic ring), which is unsubstituted or contains one or more R 12 Or R 20 In some embodiments, R e is selected from -C(O)(3- to 6-membered carbocycle), wherein the 3- to 6-membered carbocycle is unsubstituted. e is selected from -C(O)O (3- to 6-membered carbocyclic ring), and the 3- to 6-membered carbocyclic ring is selected from one or more R 12 or R 20 In some embodiments, R e is selected from —C(O)O(3- to 6-membered carbocyclic ring), wherein the 3- to 6-membered carbocyclic ring is cyclopropane or cyclobutane, and the 3- to 6-membered carbocyclic ring is unsubstituted or contains one or more R 12 Or R 20 In some embodiments, R e is selected from —C(O)O(3- to 6-membered heterocycle), wherein the 3- to 6-membered heterocycle is unsubstituted or contains one or more R 12 Or R 20 In some embodiments, R eis selected from -C(O)O(3- to 6-membered heterocycle), wherein the 3- to 6-membered heterocycle is unsubstituted. e is selected from —C(O)O(3- to 6-membered heterocycle), and the 3- to 6-membered heterocycle is selected from one or more R 12 or R 20 In some embodiments, R e is selected from —C(O)O(3- to 6-membered heterocycle), wherein the 3- to 6-membered heterocycle is oxetane, tetrahydrofuran, tetrahydropyran, or pyrrolidine, and the 3- to 6-membered heterocycle is unsubstituted or is substituted with one or more R 12 Or R 20 In some embodiments, R e is -C(O)O(C 1-6 alkylene)(3- to 6-membered heterocycle), wherein the 3- to 6-membered heterocycle is unsubstituted or is substituted with one or more R 12 Or R 20 In some embodiments, R e is -C(O)O(C 1-6 In some embodiments, R e is -C(O)O(C 1-6 alkylene)(3- to 6-membered heterocycle), and the 3- to 6-membered heterocycle is selected from one or more R 12 or R 20 In some embodiments, R e is a 3- to 6-membered carbocyclic ring, which is unsubstituted or has one or more R 12 Or R 20 In some embodiments, R e is a 3- to 6-membered carbocyclic ring, and the 3- to 6-membered carbocyclic ring is unsubstituted. e is a 3- to 6-membered carbocyclic ring, and the 3- to 6-membered carbocyclic ring is 12 or R 20 In some embodiments, R e is a 5- to 6-membered heteroaryl, which is unsubstituted or has one or more R 12 Or R 20In some embodiments, R e is a 5- to 6-membered heteroaryl, and the 5- to 6-membered heteroaryl is unsubstituted. In some embodiments, R e is a 5- to 6-membered heteroaryl, and the 3- to 6-membered carbocyclic ring is 12 or R 20 is replaced by

[0185] In some embodiments, for a compound according to any one of Formulas IID, IID1, IIR, and IIR1: [ka] or [ka] teeth, [ka] TIFF2025525938000064.tif223164 [ka] [ka] [ka] [ka] [ka] The structure is selected from:

[0186] In some embodiments, for a compound of any one of Formulas II, II', II-a, IIA, IIA1, IIB, IIB1, IIC, IIC1, IID, IID1, IIE, IIE1, IIF, IIF1, IIG, IIG1, IIH, IIH1, IIJ, IIJ1, IIK, IIK1, IIL, IIL1, IIM, IIM1, IIN, IIN1, IIP, IIP1, IIQ, IIQ1, IIR, IIR1, IIS, IIS1, IIT, IIT1, IIU, IIU1, IIV, IIV1, IIW, IIW1, IIX, IIX1, IIY, IIY1, IIZ, IIZ1, IIAA, and IIAA1, R 2 is H. In some embodiments, R 2 is unsubstituted or contains one or more R 13 C replaced by 1-6 In some embodiments, R 2 is unsubstituted C 1-6 In some embodiments, R 2 is one or more R 13 C replaced by 1-6 In some embodiments, R 2 is unsubstituted or contains one or more R 13 C replaced by 1-2 In some embodiments, R 2 is unsubstituted C 1-2 In some embodiments, R 2 is one or more R 13 C replaced by 1-2 In some embodiments, R 2 is methyl. In some embodiments, R 2 is methyl.

[0187] In some embodiments, for a compound of any one of formulas II, II', IIA, IIA1, IIB, IIB1, IIC, IIC1, IID, IID1, IIE, IIE1, IIF, IIF1, IIG, IIG1, IIH, IIH1, IIJ, IIJ1, IIK, IIK1, IIL, IIL1, IIM, IIM1, IIN, IIN1, IIP, IIP1, IIQ, IIQ1, IIR, IIR1, IIS, IIS1, IIT, IIT1, IIU, IIU1, IIV, IIV1, IIW, IIW1, IIX, IIX1, IIY, IIY1, IIZ, IIZ1, IIAA, and IIAA1, R 1 -OR 8 Selected from R 8 is selected from heterocycle and alkylheterocycle, any heterocycle containing 4 to 8 members and is unsubstituted or contains one or more R a Or R b and the alkyl portion of any alkyl heterocycle is C 1-6 In some embodiments, R 8 is a heterocycle or alkylheterocycle, any heterocycle containing 4 to 8 members and containing one or more R a or R b In some embodiments, R 8 is unsubstituted or contains one or more R a or R b In some embodiments, R 8 is unsubstituted or contains one or more R a or R b In some embodiments, R 8 is —CH2 (heterocycle), the heterocycle is unsubstituted or contains one or more R a or R bIn some embodiments, the heterocycle of the heterocycle or alkylheterocycle is a 4-6 membered monocyclic heterocycle having 1-2 heteroatoms independently selected from N, O, and S. In some embodiments, the heterocycle of the heterocycle or alkylheterocycle is an 8 membered bicyclic heterocycle having 1-2 heteroatoms independently selected from N, O, and S. In some embodiments, the heterocycle of the heterocycle or alkylheterocycle is substituted with one or more R a or R b and one or more R a or R b is halogen (e.g., F). In some embodiments, the heterocycle or heterocycle of an alkylheterocycle is selected from the group consisting of one or more R a or R b and one or more R a or R b is C 1-6 In some embodiments, the heterocycle or heterocycle of the alkylheterocycle is selected from one or more R a or R b and one or more R a or R b -OR 12 (e.g., —OCH). In some embodiments, the heterocycle or heterocycle of the alkylheterocycle is selected from one or more R a or R b and one or more R a or R b is a 3-6 membered carbocyclic ring (e.g., cyclopropane). In some embodiments, the heterocycle or heterocycle of an alkylheterocycle ... a or R b and one or more R a or R b is deuterium.

[0188] In some embodiments, for a compound according to any one of Formulas II, II', IIA, IIA1, IIB, IIB1, IIC, IIC1, IID, IID1, IIE, IIE1, IIF, IIF1, IIG, IIG1, IIH, IIH1, IIJ, IIJ1, IIK, IIK1, IIL, IIL1, IIM, IIM1, IIN, IIN1, IIP, IIP1, IIQ, IIQ1, IIR, IIR1, IIS, IIS1, IIT, IIT1, IIU, IIU1, IIV, IIV1, IIW, IIW1, IIX, IIX1, IIY, IIY1, IIZ, IIZ1, IIAA, and IIAA1, R 1 teeth, [ka] is selected from In the formula, R a1 , R a2 , R b1 , and R b2 are each independently deuterium, halogen, C 1-6 Alkyl, -OR 12 and H; a1 and R b1 and / or R a2 and R b2 can be optionally linked together to form a 3- to 6-membered carbocyclic ring, any C 1-6 The alkyl or 3- to 6-membered carbocyclic ring is unsubstituted or contains one or more R 13 In some embodiments, R a1 and / or R a2 is halogen. In some embodiments, R a1 and / or R a2 is F. In some embodiments, R a1 and / or R a2 is unsubstituted or contains one or more R 13 C replaced by 1-6 In some embodiments, R a1 and / or R a2 is methyl. In some embodiments, R a1 and / or R a2 -OC 1-6In some embodiments, R a1 and / or R a2 is H. In some embodiments, R b1 and / or R b2 is H. In some embodiments, R b1 and / or R b2 is halogen. In some embodiments, R b1 and / or R b2 is F. In some embodiments, R b1 and / or R b2 is unsubstituted or contains one or more R 13 C replaced by 1-6 In some embodiments, R b1 and / or R b2 is methyl. In some embodiments, R a1 and R b1 Each of R is F. In some embodiments, R a2 and / or R b2 is D. In some embodiments, R a2 and R b2 are linked together to form a 3- to 6-membered carbocyclic ring (e.g., cyclopropane), which carbocyclic ring may optionally contain one or more R 13 In some embodiments, R a1 and R b1 are linked together to form a 3- to 6-membered carbocyclic ring (e.g., cyclopropane). In some embodiments, R 1 teeth, [ka] is selected from.

[0189] In some embodiments, for a compound of any one of formulas II, II', IIA, IIA1, IIB, IIB1, IIC, IIC1, IID, IID1, IIE, IIE1, IIF, IIF1, IIG, IIG1, IIH, IIH1, IIJ, IIJ1, IIK, IIK1, IIL, IIL1, IIM, IIM1, IIN, IIN1, IIP, IIP1, IIQ, IIQ1, IIR, IIR1, IIS, IIS1, IIT, IIT1, IIU, IIU1, IIV, IIV1, IIW, IIW1, IIX, IIX1, IIY, IIY1, IIZ, IIZ1, IIAA, and IIAA1, R 1 teeth, [ka] is selected from In the formula, R a and R b are each independently a halogen, C 1-6 Alkyl, -OR 12 , and H, and any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 In some embodiments, R a is halogen. In some embodiments, R a is F. In some embodiments, R a is unsubstituted or contains one or more R 13 C replaced by 1-6 In some embodiments, R a is methyl. In some embodiments, R a -OC 1-6 In some embodiments, R a is H. In some embodiments, R b is H. In some embodiments, R b is halogen. In some embodiments, R b is F. In some embodiments, R b is unsubstituted or contains one or more R 13 C replaced by 1-6 In some embodiments, Rb is methyl. In some embodiments, R a and R b Each of R is F. In some embodiments, R a and R b Each of R is methyl. 1 teeth, [ka] is selected from.

[0190] In some embodiments, for a compound of any one of formulas II, II', IIA, IIA1, IIB, IIB1, IIC, IIC1, IID, IID1, IIE, IIE1, IIF, IIF1, IIG, IIG1, IIH, IIH1, IIJ, IIJ1, IIK, IIK1, IIL, IIL1, IIM, IIM1, IIN, IIN1, IIP, IIP1, IIQ, IIQ1, IIR, IIR1, IIS, IIS1, IIT, IIT1, IIU, IIU1, IIV, IIV1, IIW, IIW1, IIX, IIX1, IIY, IIY1, IIZ, IIZ1, IIAA, and IIAA1, R 1 teeth, [ka] is selected from.

[0191] In some embodiments, for a compound of any one of formulas II, II', IIA, IIA1, IIB, IIB1, IIC, IIC1, IID, IID1, IIE, IIE1, IIF, IIF1, IIG, IIG1, IIH, IIH1, IIJ, IIJ1, IIK, IIK1, IIL, IIL1, IIM, IIM1, IIN, IIN1, IIP, IIP1, IIQ, IIQ1, IIR, IIR1, IIS, IIS1, IIT, IIT1, IIU, IIU1, IIV, IIV1, IIW, IIW1, IIX, IIX1, IIY, IIY1, IIZ, IIZ1, IIAA, and IIAA1, R 1 teeth, [ka] is selected from. In some embodiments, R a is unsubstituted or contains one or more R 13 C replaced by 1-6 In some embodiments, R a is methyl. In some embodiments, R 1 teeth, [ka] is selected from

[0192] In some embodiments, for a compound of any one of formulas II, II', IIA, IIA1, IIB, IIB1, IIC, IIC1, IID, IID1, IIE, IIE1, IIF, IIF1, IIG, IIG1, IIH, IIH1, IIJ, IIJ1, IIK, IIK1, IIL, IIL1, IIM, IIM1, IIN, IIN1, IIP, IIP1, IIQ, IIQ1, IIR, IIR1, IIS, IIS1, IIT, IIT1, IIU, IIU1, IIV, IIV1, IIW, IIW1, IIX, IIX1, IIY, IIY1, IIZ, IIZ1, IIAA, and IIAA1, R 1 teeth, [ka] is selected from In the formula, each R a and R b are independently halogen, C 1-6 Alkyl, -OR 12 and H; c But C 1-6 alkyl, and R a and R b or R c are optionally linked together to form a 3- to 6-membered carbocyclic or heterocyclic ring, and any C 1-6 The alkyl or 3- to 6-membered carbocyclic or heterocyclic ring is unsubstituted or contains one or more R 13 In some embodiments, each R a and R bare independently halogen, C 1-6 Alkyl, -OR 12 and H; c is C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 and R bonded to the same carbon atom a and R b are linked together to form a 3- to 6-membered carbocyclic ring. In some embodiments, each R a and R b are independently halogen, C 1-6アルキル , -OR 12 and H; a and R c are linked together to form a 3- to 6-membered heterocycle. In some embodiments, each R a and R b are independently halogen, C 1-6 Alkyl, -OR 12 and H; c is C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 In some embodiments, one R a or R b is a halogen, C 1-6 Alkyl, and -OR 12 Selected from other R a and R b The group is H. In some embodiments, one R a or R b is halogen (e.g., F). In some embodiments, two R a group, two R b group, or R a and R b is halogen (e.g., F). In some embodiments, one R a or R b -OR 12 (e.g., —OCH or —CHF). In some embodiments, one R a or Rb is C 1-6 In some embodiments, two R a group, two R b group, or R a and R b is C 1-6 In some embodiments, R c is selected from -CH, -CHCHF, -CHCHF, and -CHCHCN. a and R b are linked together to form a 3- to 6-membered carbocyclic ring, such as cyclopropane. In some embodiments, R a and R b are linked together to form a 3- to 6-membered carbocyclic ring, such as cyclopropane. In some embodiments, R a and R c are linked together to form a 3- to 6-membered heterocycle. In some embodiments, R 1 teeth, [ka] is selected from.

[0193] In some embodiments, for a compound of any one of formulas II, II', IIA, IIA1, IIB, IIB1, IIC, IIC1, IID, IID1, IIE, IIE1, IIF, IIF1, IIG, IIG1, IIH, IIH1, IIJ, IIJ1, IIK, IIK1, IIL, IIL1, IIM, IIM1, IIN, IIN1, IIP, IIP1, IIQ, IIQ1, IIR, IIR1, IIS, IIS1, IIT, IIT1, IIU, IIU1, IIV, IIV1, IIW, IIW1, IIX, IIX1, IIY, IIY1, IIZ, IIZ1, IIAA, and IIAA1, R 1 teeth, [ka] is selected from

[0194] In some embodiments, for a compound of any one of formulas II, II', IIA, IIA1, IIB, IIB1, IIC, IIC1, IID, IID1, IIE, IIE1, IIF, IIF1, IIG, IIG1, IIH, IIH1, IIJ, IIJ1, IIK, IIK1, IIL, IIL1, IIM, IIM1, IIN, IIN1, IIP, IIP1, IIQ, IIQ1, IIR, IIR1, IIS, IIS1, IIT, IIT1, IIU, IIU1, IIV, IIV1, IIW, IIW1, IIX, IIX1, IIY, IIY1, IIZ, IIZ1, IIAA, and IIAA1, R 1 teeth, [ka] is selected from.

[0195] In some embodiments, for a compound of any one of formulas II, II', IIA, IIA1, IIB, IIB1, IIC, IIC1, IID, IID1, IIE, IIE1, IIF, IIF1, IIG, IIG1, IIH, IIH1, IIJ, IIJ1, IIK, IIK1, IIL, IIL1, IIM, IIM1, IIN, IIN1, IIP, IIP1, IIQ, IIQ1, IIR, IIR1, IIS, IIS1, IIT, IIT1, IIU, IIU1, IIV, IIV1, IIW, IIW1, IIX, IIX1, IIY, IIY1, IIZ, IIZ1, IIAA, and IIAA1, R 5 is H. In some embodiments, R 5 includes a halogen (e.g., F or Cl). In some embodiments, R 5 is Cl. In some embodiments, R 5 is F. In some embodiments, R 5 is -CN. In some embodiments, R 5 -OR 12 and R 12 is C 1-6 alkyl and H. In some embodiments, R 5 is —OCH. In some embodiments, R 5is -OCF3. In some embodiments, R 5 is unsubstituted or contains one or more R 13 C replaced by 1-6 In some embodiments, R 5 is unsubstituted or contains one or more R 13 C replaced by 1-2 In some embodiments, R 5 is unsubstituted, such as methyl or ethyl 1-6 In some embodiments, R 5 is C substituted with one or more halogens or -CN 1-6 In some embodiments, R 5 is a C substituted with one or more halogens, such as one or more fluorines 1-6 In some embodiments, R 5 is -CF3. In some embodiments, R 5 is -CHF. In some embodiments, R 5 is selected from -CFH, -CF, -CHCN, and -CHCH. In some embodiments, R 5 is selected from —CH, —CHCH, —CFH, —CF, —CFCH, and —CHCN. In some embodiments, R 5 is one or more R 13 C replaced by 1-6 alkyl, and each R 13 are independently -OR 14 , -CN, and -N(R 14 In some embodiments, R 5 is —CHCN. In some embodiments, R 5 is a 3- to 6-membered heterocycle. In some embodiments, R 5 is a 5- to 6-membered heteroaryl such as furan.

[0196] In some embodiments, for a compound of any one of formulas II, II', IIA, IIA1, IIB, IIB1, IIC, IIC1, IID, IID1, IIE, IIE1, IIF, IIF1, IIG, IIG1, IIH, IIH1, IIJ, IIJ1, IIK, IIK1, IIL, IIL1, IIM, IIM1, IIN, IIN1, IIP, IIP1, IIQ, IIQ1, IIR, IIR1, IIS, IIS1, IIT, IIT1, IIU, IIU1, IIV, IIV1, IIW, IIW1, IIX, IIX1, IIY, IIY1, IIZ, IIZ1, IIAA, and IIAA1, R 7 is Cl. In some embodiments, R 7 is F.

[0197] In some embodiments, for a compound of any one of Formulas II, II', II-a, IIA, IIA1, IIB, IIB1, IIC, IIC1, IID, IID1, IIE, IIE1, IIF, IIF1, IIG, IIG1, IIH, IIH1, IIJ, IIJ1, IIK, IIK1, IIL, IIL1, IIM, IIM1, IIN, IIN1, IIP, IIP1, IIQ, IIQ1, IIR, IIR1, IIS, IIS1, IIT, IIT1, IIU, IIU1, IIV, IIV1, IIW, IIW1, IIX, IIX1, IIY, IIY1, IIZ, IIZ1, IIAA, and IIAA1, the compound is not a compound included in Table 1, or a salt, ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. [Table 1-1] [Table 1-2] [Table 1-3]

[0198] In another aspect, the present disclosure provides a compound of formula III': [ka] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein: R 1 But, -OR 8 and [ka] is selected from R 2 and R 3 together with the nitrogen atom to which they are attached are unsubstituted or contain one or more R 11 forming a 4- to 10-membered heterocyclic ring substituted with R 4 is H, R 5 But halogen and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 6 is a monocyclic or bicyclic heteroaryl, and the heteroaryl is selected from one or more R 15 is replaced by R 7 is selected from halogens, R 8 is selected from heterocycle and alkylheterocycle, and any heterocycle contains 4 to 8 members and is unsubstituted or contains one or more R a or R b and the alkyl portion of any alkyl heterocycle is substituted with C 1-6 alkyl, Each R 11 independently, deuterium, -OR 12 , =O, =N(R 14 ), -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -C(O)O(C 1-6 alkyl), -C(O)N(R 14)2, -C(O)(3- to 6-membered carbocyclic or heterocyclic ring), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogen, -CN, 3- to 6-membered carbocyclic or heterocyclic ring, 5- to 6-membered heteroaryl, and C 1-6 alkyl, any C 1-6 The alkyl, carbocycle, heterocycle, or heteroaryl is unsubstituted or contains one or more R 20 is replaced by Each R 12 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H, and any C 1-6 Alkyl or C 2-6 Alkenyl is unsubstituted or has one or more R 13 is replaced by Each R 13 but independently, -OR 14 , -CN, -N(R 14 )2, and halogen; Each R 14 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H; Each R 15 are independently deuterium, halogen, -N(R 12 )2, -CN, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by Each R 20 Independently, -OH, -OC 1-6 Alkyl, -CN, -NH2, -NHC 1-6 alkyl, and halogen; R 27 is a 3- to 6-membered heterocycle containing one or more heteroatoms selected from N, O, and S, and the heterocycle is unsubstituted or contains one or more R 28 is replaced by Each R 28 But independently, C 1-6 selected from alkyl and halogen; R a and R b are each independently deuterium, halogen, C 1-6 Alkyl, 3-6 membered carbocyclic ring, -OR 12 and H; a and R b are optionally linked together to form a 3- to 6-membered carbocyclic or heterocyclic ring, and any C 1-6 The alkyl or 3- to 6-membered carbocyclic or heterocyclic ring is unsubstituted or contains one or more R 13 The compound or a salt thereof, wherein the compound is substituted with

[0199] In some embodiments, the disclosure provides a compound of formula III' or a salt thereof (eg, a pharmaceutically acceptable salt):

[0200] In another aspect, the present disclosure provides a compound of formula III: [ka] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein: R 1 But, -OR 8 and [ka] is selected from R 2 and R 3 together with the nitrogen atom to which they are attached are unsubstituted or contain one or more R 11 with the proviso that (i) if the heterocycle contains an additional nitrogen atom, then the additional nitrogen atom is substituted with R 11 or (ii) the heterocycle does not contain an —NH— moiety; R 4 is H, R5 But halogen and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 6 is a monocyclic or bicyclic heteroaryl, and the heteroaryl is selected from one or more R 15 is replaced by R 7 is selected from halogens, R 8 is selected from heterocycle and alkylheterocycle, and any heterocycle contains 4 to 8 members and is unsubstituted or contains one or more R a or R b and the alkyl portion of any alkyl heterocycle is substituted with C 1-6 alkyl, Each R 11 independently, deuterium, -OR 12 , =O, =N(R 14 ), -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -C(O)O(C 1-6 alkyl), -C(O)N(R 14 )2, -C(O)(3- to 6-membered carbocyclic or heterocyclic ring), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogen, -CN, 3- to 6-membered carbocyclic or heterocyclic ring, 5- to 6-membered heteroaryl, and C 1-6 alkyl, any C 1-6 The alkyl, carbocycle, heterocycle, or heteroaryl is unsubstituted or contains one or more R 20 is replaced by Each R 12 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H, and any C1-6 Alkyl or C 2-6 Alkenyl is unsubstituted or has one or more R 13 is replaced by Each R 13 but independently, -OR 14 , -CN, -N(R 14 )2, and halogen; Each R 14 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H; Each R 15 are independently deuterium, halogen, -N(R 12 )2, -CN, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by Each R 20 Independently, -OH, -OC 1-6 Alkyl, -CN, -NH2, -NHC 1-6 alkyl, and halogen; R 27 is a 3- to 6-membered heterocycle containing one or more heteroatoms selected from N, O, and S, and the heterocycle is unsubstituted or contains one or more R 28 is replaced by Each R 28 But independently, C 1-6 selected from alkyl and halogen; R a and R b are each independently deuterium, halogen, C 1-6 Alkyl, 3-6 membered carbocyclic ring, -OR 12 and H; a and R b are optionally linked together to form a 3- to 6-membered carbocyclic or heterocyclic ring, and any C 1-6 The alkyl or 3- to 6-membered carbocyclic or heterocyclic ring is unsubstituted or contains one or more R 13 The compound or a salt thereof, wherein the compound is substituted with

[0201] In some embodiments, the disclosure provides a compound of Formula III or a salt thereof (eg, a pharmaceutically acceptable salt):

[0202] In some embodiments, the present disclosure provides a compound of formula III, wherein: R 1 But, -OR 8 is selected from R 2 and R 3 together with the nitrogen atom to which they are attached are unsubstituted or contain one or more R 11 with the proviso that (i) if the heterocycle contains an additional nitrogen atom, then the additional nitrogen atom is substituted with R 11 or (ii) the heterocycle does not contain an —NH— moiety; R 4 is H, R 5 But C 1-6 alkyl and any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 6 is a monocyclic or bicyclic heteroaryl, and the heteroaryl is selected from one or more R 15 is replaced by R 7 is selected from halogens, R 8 is an alkylheterocycle, and any heterocycle contains 4 to 8 members and is unsubstituted or contains one or more R a Or R b and the alkyl portion of any alkyl heterocycle is substituted with C 1-6 alkyl, Each R 11 independently, deuterium, -OR 12 , =O, =N(R 14 ), -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -C(O)O(C 1-6 alkyl), -C(O)N(R14 )2, -C(O)(3- to 6-membered carbocyclic or heterocyclic ring), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogen, -CN, 3- to 6-membered carbocyclic or heterocyclic ring, 5- to 6-membered heteroaryl, and C 1-6 alkyl, any C 1-6 The alkyl, carbocycle, heterocycle, or heteroaryl is unsubstituted or contains one or more R 20 is replaced by Each R 12 But independently, C 1-6 alkyl and H, and any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by Each R 13 are independently selected from halogen; Each R 14 But independently, C 1-6 alkyl and H; Each R 15 are independently deuterium, halogen, -N(R 12 )2, -CN, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by Each R 20 Independently, -OH, -OC 1-6 selected from alkyl, —CN, and halogen; R a and R b are each independently deuterium, halogen, C 1-6 alkyl, and H; R a and R b are optionally linked together to form a 3- to 6-membered carbocyclic ring, and any C 1-6 The alkyl or 3- to 6-membered carbocyclic ring is unsubstituted or contains one or more R 13 is replaced by

[0203] In some embodiments, the disclosure provides a compound of formula III' or III, wherein the compound has formula III-a: [ka] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) of the formula: 2 and R 3 is as defined for formula III above and is described alone and in combination in classes and subclasses herein. 2 and R 3 is as defined above in formula III' and is described herein in classes and subclasses, both alone and in combination. In some embodiments, the present disclosure provides a compound of formula III-a, or a salt (e.g., a pharmaceutically acceptable salt) thereof:

[0204] In some embodiments, for compounds according to formula III, III', or III-a, R 2 and R 3 together with the nitrogen atom to which they are attached are unsubstituted or contain one or more R 11 In some embodiments, R 2 and R 3 together with the nitrogen atom to which they are attached are unsubstituted or contain one or more R 11 with the proviso that (i) if the heterocycle contains an additional nitrogen atom, the additional nitrogen atom is not substituted with R 11 or (ii) the heterocycle does not contain an —NH— moiety. 2 and R 3 together with the nitrogen atom to which they are attached are unsubstituted or contain one or more R 11 with the proviso that (i) if the heterocycle contains an additional nitrogen atom, the additional nitrogen atom is not substituted with R 11or (ii) if the heterocycle contains a single ring, the heterocycle does not contain an -NH- moiety. 2 and R 3 together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycle containing a single ring, the heterocycle being unsubstituted or containing one or more R 11 With the proviso that the heterocycle does not contain an -NH- moiety. 2 and R 3 together with the nitrogen atom to which they are attached are unsubstituted or contain one or more R 11 In some embodiments, R 2 and R 3 together with the nitrogen atom to which they are attached are unsubstituted or contain one or more R 11 with the proviso that (i) if the heterocycle contains an additional nitrogen atom, the additional nitrogen atom is not substituted with R 11 or (ii) the heterocycle does not contain an —NH— moiety. 2 and R 3 together with the nitrogen atom to which they are attached are unsubstituted or contain one or more R 11 with the proviso that (i) if the heterocycle contains an additional nitrogen atom, the additional nitrogen atom is not substituted with R 11 or (ii) if the heterocycle contains a single ring, the heterocycle does not contain an -NH- moiety. 2 and R 3 together with the nitrogen atom to which they are attached form an unsubstituted 4-6 membered heterocycle, with the proviso that the 4-6 membered heterocycle does not contain an -NH- moiety. 2 and R 3 together with the nitrogen atom to which they are attached form an unsubstituted 7-membered heterocycle, with the proviso that the 7-membered heterocycle does not contain an -NH- moiety. 2 and R 3 together with the nitrogen atoms to which they are attached, may contain one or more R 11with the proviso that (i) if the heterocycle contains an additional nitrogen atom, the additional nitrogen atom is not substituted with R 11 or (ii) the heterocycle does not contain an —NH— moiety. 2 and R 3 together with the nitrogen atom to which they are attached form a 4- to 6-membered heterocycle containing one or two heteroatoms selected from O, S, and N, the heterocycle being unsubstituted or containing one or more R 11 with the proviso that (i) if the heterocycle contains an additional nitrogen atom, the additional nitrogen atom is substituted with R 11 or (ii) the heterocycle does not contain an —NH— moiety. 2 and R 3 together with the nitrogen atom to which they are attached form a 4- to 6-membered heterocyclic ring containing 1 or 2 heteroatoms selected from O, S, and N, and the heterocyclic ring is 11 with the proviso that (i) if the heterocycle contains an additional nitrogen atom, the additional nitrogen atom is substituted with R 11 or (ii) the heterocycle does not contain an —NH— moiety. In some embodiments, R 2 and R 3 together with the nitrogen atom to which they are attached, 0 to 4 R 11 In some embodiments, R 2 and R 3 together with the nitrogen atom to which they are attached, 0 to 4 R 11 In some embodiments, R 2 and R 3 together with the nitrogen atom to which they are attached, 0 to 4 R 11 In some embodiments, R 2 and R 3 together with the nitrogen atom to which they are attached, 0 to 4 R 11 wherein the additional nitrogen atom of the piperazine is substituted with R 11 In some embodiments, R 2 and R3 together with the nitrogen atom to which they are attached, 0 to 4 R 11 In some embodiments, R 2 and R 3 together with the nitrogen atom to which they are attached, form one R 11 and (i) if the heterocycle contains an additional nitrogen atom, the additional nitrogen atom is substituted with R 11 or (ii) the heterocycle does not contain an —NH— moiety and is substituted with at least one R 11 -OR 12 and C substituted with -OH 1-6 In some embodiments, R 2 and R 3 together with the nitrogen atom to which they are attached, form one R 11 and (i) if the heterocycle contains an additional nitrogen atom, the additional nitrogen atom is substituted with R 11 or (ii) the heterocycle does not contain an —NH— moiety and is substituted with at least one R 11 is the unsubstituted C 1-6 In some embodiments, R 2 and R 3 together with the nitrogen atom to which they are attached form a seven-membered ring containing 1 to 3 heteroatoms selected from O, S, and N, the heterocycle being unsubstituted or containing one or more R 11 In some embodiments, R 2 and R 3 together with the nitrogen atom to which they are attached form a 7-membered heterocycle containing 1 to 3 heteroatoms selected from O, S, and N, the heterocycle being unsubstituted or containing one or more R 11 with the proviso that (i) if the heterocycle contains an additional nitrogen atom, the additional nitrogen atom is substituted with R 11 or (ii) the heterocycle does not contain an —NH— moiety. 2 and R 3together with the nitrogen atom to which they are attached form a 7-membered heterocycle containing 1 to 3 heteroatoms selected from O, S, and N, and the heterocycle is 11 In some embodiments, R 2 and R 3 together with the nitrogen atom to which they are attached form a 7-membered heterocycle containing 1 to 3 heteroatoms selected from O, S, and N, and the heterocycle is 11 with the proviso that (i) if the heterocycle contains an additional nitrogen atom, the additional nitrogen atom is substituted with R 11 or (ii) the heterocycle does not contain an —NH— moiety. In some embodiments, R 2 and R 3 together with the nitrogen atom to which they are attached form a 7-membered heterocycle containing the nitrogen atom. 2 and R 3 together with the nitrogen atom to which they are attached form a 7-membered heterocycle containing a nitrogen atom and an oxygen atom. 2 and R 3 together with the nitrogen atom to which they are attached form a 7-membered heterocycle comprising a nitrogen atom and a sulfur atom, the sulfur atom being optionally substituted with two oxo moieties. 2 and R 3 together with the nitrogen atom to which they are attached form a 7-membered heterocycle containing two nitrogen atoms. 2 and R 3 together with the nitrogen atom to which they are attached form a seven-membered heterocycle containing one additional nitrogen atom, provided that the additional nitrogen atom is not R 11 is replaced by

[0205] In some embodiments, for compounds according to formula III, III', or III-a, R 2 and R 3 together with the nitrogen atom to which they are attached are unsubstituted or contain one or more R 11 In some embodiments, for compounds according to formula III, III', or III-a, R 2and R 3 together with the nitrogen atom to which they are attached are unsubstituted or contain one or more R 11 with the proviso that (i) if the heterocycle contains an additional nitrogen atom, the additional nitrogen atom is substituted with R 11 or (ii) the heterocycle does not contain an —NH— moiety. 2 and R 3 together with the nitrogen atom to which they are attached form a 7- to 9-membered bridged heterocycle containing one or two heteroatoms selected from O, S, and N, the bridged heterocycle being unsubstituted or containing one or more R 11 with the proviso that (i) if the heterocycle contains an additional nitrogen atom, the additional nitrogen atom is substituted with R 11 or (ii) the heterocycle does not contain an —NH— moiety. 2 and R 3 together with the nitrogen atom to which they are attached form a 7- to 9-membered bridged heterocycle containing 1 or 2 heteroatoms selected from O, S, and N, and the bridged heterocycle is 11 with the proviso that (i) if the heterocycle contains an additional nitrogen atom, the additional nitrogen atom is substituted with R 11 or (ii) the heterocycle does not contain an —NH— moiety. In some embodiments, R 2 and R 3 together with the nitrogen atom to which they are attached, 0 to 4 R 11 In some embodiments, R 2 and R 3 together with the nitrogen atom to which they are attached, 0 to 4 R 11 and forming a bridged piperazine substituted with R 11 or (ii) the bridged piperazine does not contain an —NH— moiety. In some embodiments, R 2 and R 3 together with the nitrogen atom to which they are attached, 0 to 4 R 11 In some embodiments, R2 and R 3 together with the nitrogen atoms to which they are attached, may contain one or more R 11 with the proviso that (i) if the heterocycle contains an additional nitrogen atom, the additional nitrogen atom is not substituted with R 11 or (ii) the heterocycle does not contain an —NH— moiety and is substituted with at least one R 11 -OR 12 and C substituted with -OH 1-6 In some embodiments, R 2 and R 3 together with the nitrogen atoms to which they are attached, may contain one or more R 11 with the proviso that (i) if the heterocycle contains an additional nitrogen atom, the additional nitrogen atom is not substituted with R 11 or (ii) the heterocycle does not contain an —NH— moiety and is substituted with at least one R 11 is the unsubstituted C 1-6 It is alkyl.

[0206] In some embodiments, for compounds according to formula III, III', or III-a, R 2 and R 3 together with the nitrogen atom to which they are attached are unsubstituted or contain one or more R 11 In some embodiments, for compounds according to formula III, III', or III-a, R 2 and R 3 together with the nitrogen atom to which they are attached are unsubstituted or contain one or more R 11 with the proviso that (i) if the spiro ring contains an additional nitrogen atom, the additional nitrogen atom is not substituted with R 11 or (ii) the spiro ring does not contain an -NH- moiety. 2 and R 3 together with the nitrogen atom to which they are attached form an unsubstituted spiro ring, with the proviso that the spiro ring does not contain an -NH- moiety. 2 and R 3consists of one or more R 11 with the proviso that (i) if the spiro ring contains an additional nitrogen atom, the additional nitrogen atom is not substituted with R 11 or (ii) the spiro ring does not contain an -NH- moiety. 2 and R 3 together with the nitrogen atom to which they are attached form a spiro ring, including four- and three-membered rings. 2 and R 3 together with the nitrogen atom to which they are attached form a spiro ring containing two four-membered rings. 2 and R 3 together with the nitrogen atom to which they are attached form a spiro ring, including four- and five-membered rings. 2 and R 3 together with the nitrogen atom to which they are attached form a spiro ring, including four- and six-membered rings. 2 and R 3 together with the nitrogen atom to which they are attached form a spiro ring, including six- and five-membered rings. 2 and R 3 together with the nitrogen atom to which they are attached form a spiro ring containing two five-membered rings.

[0207] In some embodiments, for compounds of formula III, III', or III-a, R 2 and R 3 together with the nitrogen atom to which they are attached form a fused ring system containing at least two rings, the fused ring system being unsubstituted or containing one or more R 11 In some embodiments, R 2 and R 3 together with the nitrogen atom to which they are attached form a fused ring system containing at least two rings, the fused ring system being unsubstituted or containing one or more R 11 with the proviso that the fused ring system does not contain an -NH- moiety. 2 and R3 together with the nitrogen atom to which they are attached form a fused ring system containing at least two rings, at least one of the rings being selected from azetidine, pyrrolidine, piperidine, piperazine, triazole (e.g., 1,2,3-triazole or 1,2,4-triazole), pyrazole, pyrrole, imidazole, isoxazole, thiazole, oxazolidine, morpholine, tetrahydrofuran, azepane, and diazepane, and the fused ring system is unsubstituted or is substituted with one or more R 11 In some embodiments, R 2 and R 3 together with the nitrogen atom to which they are attached form a fused ring system comprising at least two rings, at least one of the rings being selected from azetidine, pyrrolidine, piperidine, piperazine, triazole (e.g., 1,2,3-triazole or 1,2,4-triazole), pyrazole, pyrrole, imidazole, isoxazole, thiazole, oxazolidine, morpholine, pyridine, tetrahydrofuran, azepane, and diazepane, and the fused ring system is unsubstituted or is substituted with one or more R 11 In some embodiments, R 2 and R 3 together with the nitrogen atom to which they are attached form a fused ring system containing two five-membered rings. 2 and R 3 together with the nitrogen atom to which they are attached form a fused ring system, including 5- and 6-membered rings. 2 and R 3 together with the nitrogen atom to which they are attached form a fused ring system including a 5-membered ring and a 4-membered ring. 2 and R 3 together with the nitrogen atom to which they are attached form a fused ring system including a 6-membered ring and a 3-membered ring. 2 and R 3 together with the nitrogen atom to which they are attached form a fused ring system including a 7-membered ring and a 5-membered ring. 2 and R 3together with the nitrogen atom to which they are attached form a fused ring system containing at least two rings, and the fused ring system is unsubstituted. 2 and R 3 together with the nitrogen atom to which they are attached form a fused ring system containing at least two rings, the fused ring system being unsubstituted, with the proviso that the fused ring system does not contain an -NH- moiety. 2 and R 3 together with the nitrogen atom to which they are attached form a fused ring system containing at least two rings, and the fused ring system is formed by one or more R 11 In some embodiments, R 2 and R 3 together with the nitrogen atom to which they are attached form a fused ring system containing at least two rings, and the fused ring system is formed by one or more R 11 with the proviso that (i) if the fused ring system contains an additional nitrogen atom, then the additional nitrogen atom is substituted with R 11 or (ii) the fused ring system does not contain an —NH— moiety. In some embodiments, R 2 and R 3 together with the nitrogen atom to which they are attached form a fused ring system containing at least two rings, and the fused ring system is 11 In some embodiments, R 2 and R 3 together with the nitrogen atom to which they are attached form a fused ring system containing at least two rings, and the fused ring system is 11 with the proviso that (i) if the fused ring system contains an additional nitrogen atom, then the additional nitrogen atom is substituted with R 11 or (ii) the fused ring system does not contain an -NH- moiety.

[0208] In some embodiments, for compounds according to formula III, III', or III-a, R 2 and R 3 together with the nitrogen atom to which they are attached are unsubstituted or contain one or more R 11 and each R 11 are independently deuterium, -OR12 , =O, =N(R 14 ), -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -C(O)N(R 14 )2, -C(O)(3- to 6-membered carbocyclic or heterocyclic ring), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogen, —CN, a 3- to 6-membered carbocyclic or heterocyclic ring, and C alkyl; 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, each R 11 are independently deuterium, -OR 12 , =O, =N(R 14 ), -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -C(O)N(R 14 )2, -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, each R 11 are independently -OR 12 , -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -C(O)N(R 14)2, -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, each R 11 are independently deuterium, -OR 12 , -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -C(O)N(R 14 )2, halogens, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, at least one R 11 is —C(O)(3- to 6-membered carbocyclic or heterocyclic ring), and any carbocyclic or heterocyclic ring is unsubstituted or contains one or more R 20 In some embodiments, at least one R 11 is —C(O) (a 3- to 6-membered carbocyclic ring), the carbocyclic ring being unsubstituted or containing one or more R 20 In some embodiments, at least one R 11 is —C(O) (a 3- to 6-membered carbocyclic ring), and the heterocycle is unsubstituted or contains one or more R 20 In some embodiments, at least one R 11 is -C(O)N(R 14 )2. In some embodiments, at least one R 11 is ═O. In some embodiments, R 11 -C(O)N(R 14 )2, then at least one R 14 is not H. In some embodiments, R11 -C(O)N(R 14 )2, then each R 14 is C 1-6 alkyl (for example, methyl or ethyl).

[0209] In some embodiments, for compounds according to formula III, III', or III-a, R 2 and R 3 together with the nitrogen atom to which they are attached are unsubstituted or contain one or more R 11 and forming a 4- to 10-membered heterocyclic ring substituted with R 11 and one or more R 11 are independently -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogen, and unsubstituted or one or more R 20 C replaced by 1-6 In some embodiments, R 2 and R 3 together with the nitrogen atom to which they are attached are unsubstituted or contain one or more R 11 and (i) if the heterocycle contains an additional nitrogen atom, the additional nitrogen atom is substituted with R 11 or (ii) the heterocycle does not contain an —NH— moiety and is substituted with one or more R 11 are independently deuterium, -OR 12 , =O, =N(R 14 ), -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14, -C(O)(C 1-6 alkyl), -C(O)(3- to 6-membered carbocyclic or heterocyclic ring), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogen, —CN, 3- to 6-membered carbocyclic or heterocyclic rings, and unsubstituted or one or more R 20 C replaced by 1-6 In some embodiments, R 2 and R 3 together with the nitrogen atom to which they are attached are unsubstituted or contain one or more R 11 and (i) if the heterocycle contains an additional nitrogen atom, the additional nitrogen atom is substituted with R 11 or (ii) the heterocycle does not contain an —NH— moiety and is substituted with one or more R 11 are independently deuterium, -OR 12 , =O, =N(R 14 ), -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -C(O)O(C 1-6 alkyl), -C(O)(3- to 6-membered carbocyclic or heterocyclic ring), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogen, —CN, 3- to 6-membered carbocyclic or heterocyclic rings, 5- to 6-membered heterocyclic rings, and unsubstituted or one or more R 20 C replaced by 1-6 alkyl.

[0210] In some embodiments, for compounds according to formula III, III', or III-a, R 2 and R3 together with the nitrogen atoms to which they are attached, [ka] [ka] [ka] [ka] [ka] forming a structure selected from Any of them has one or more R 11 The compound according to any one of embodiments C103 to C129, substituted with:

[0211] In some embodiments, the compound has formula IIIA [ka] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein R 1 But, -OR 8 and [ka] is selected from R 5 But halogen and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 6 is a monocyclic or bicyclic heteroaryl, and the heteroaryl is selected from one or more R 15 is replaced by R 7 is selected from halogens, R8 is selected from heterocycle and alkylheterocycle, and any heterocycle contains 4 to 8 members and is unsubstituted or contains one or more R a or R b and the alkyl portion of any alkyl heterocycle is substituted with C 1-6 alkyl, Each R 12 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H, and any C 1-6 Alkyl or C 2-6 Alkenyl is unsubstituted or has one or more R 13 is replaced by Each R 13 but independently, -OR 14 , -CN, -N(R 14 )2, and halogen; Each R 14 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H; Each R 15 are independently deuterium, halogen, -N(R 12 )2, -CN, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by Each R 20 Independently, -OH, -OC 1-6 Alkyl, -CN, -NH2, -NHC 1-6 alkyl, and halogen; R 27 is a 3- to 6-membered heterocycle containing one or more heteroatoms selected from N, O, and S, and the heterocycle is unsubstituted or contains one or more R 28 is replaced by Each R 28 But independently, C 1-6 selected from alkyl and halogen; R a and R b are each independently deuterium, halogen, C 1-6Alkyl, 3-6 membered carbocyclic ring, -OR 12 and H; a and R b are optionally linked together to form a 3- to 6-membered carbocyclic or heterocyclic ring, and any C 1-6 The alkyl or 3- to 6-membered carbocyclic or heterocyclic ring is unsubstituted or contains one or more R 13 is replaced by Each R e are independently hydrogen, deuterium, -OR 12 , =O, =N(R 14 ), -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -C(O)N(R 14 )2, -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 is replaced by R f and R g are each independently hydrogen, deuterium, -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 alkyl, any C 1-6 The alkyl is unsubstituted or has one or more R 20is replaced by, or R f and R g are linked together and are unsubstituted or -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 Forms a 3- to 6-membered carbocyclic or heterocyclic ring substituted with one or more substituents selected from alkyl, and any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 is replaced by

[0212] In some embodiments, the disclosure provides a compound of formula IIIA or a salt thereof (eg, a pharmaceutically acceptable salt):

[0213] In some embodiments, for a compound according to Formula IIIA, each R e , R f , and R g are independently hydrogen, -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20In some embodiments, each R e , R f , and R g are independently hydrogen, -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogen, and unsubstituted or one or more R 20 C replaced by 1-6 R is selected from alkyl. e , R f , or R g When =O, other R groups on the same carbon atom should be added so that the carbon has the appropriate valence. e , R f , or R g It is understood that R is not present. In some embodiments, each R e is independently hydrogen. In some embodiments, each R e , R f , and R g are independently hydrogen.

[0214] In some embodiments, for compounds according to Formula IIIA, R f and R g are linked together and are unsubstituted or -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR14 , halogens, and C 1-6 Forms a 3- to 6-membered carbocyclic or heterocyclic ring substituted with one or more substituents selected from alkyl, and any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, R f and R g are linked together to form an unsubstituted 3- to 6-membered carbocyclic or heterocyclic ring. In some embodiments, R f and R g are concatenated together, -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 Forms a 3- to 6-membered carbocyclic or heterocyclic ring substituted with one or more substituents selected from alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, R f and R g are linked together and are unsubstituted or -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6Forms a 3- to 6-membered carbocyclic ring substituted with one or more substituents selected from alkyl, and any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, R f and R g are linked together and are unsubstituted or -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 alkyl, forming a cyclopropane substituted with one or more substituents selected from any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, R f and R g are linked together and are unsubstituted or -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 alkyl, forming a cyclobutane substituted with one or more substituents selected from any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, R f and R gare linked together and are unsubstituted or -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 alkyl, and any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, R f and R g are linked together and are unsubstituted or -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 alkyl, forming an oxetane substituted with one or more substituents selected from any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 is replaced by

[0215] In some embodiments, for compounds according to Formula IIIA: [ka] teeth [ka] The structure is selected from:

[0216] In some embodiments, the compound has formula IIIA1: [ka] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein R 1 But, -OR 8 and [ka] is selected from R 5 But halogen and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 6 is a monocyclic or bicyclic heteroaryl, and the heteroaryl is selected from one or more R 15 is replaced by R 7 is selected from halogens, R 8 is selected from heterocycle and alkylheterocycle, and any heterocycle contains 4 to 8 members and is unsubstituted or contains one or more R a or R b and the alkyl portion of any alkyl heterocycle is substituted with C 1-6 alkyl, Each R 12 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H, and any C 1-6 Alkyl or C 2-6 Alkenyl is unsubstituted or has one or more R 13 is replaced by Each R 13 but independently, -OR 14 , -CN, -N(R 14)2, and halogen; Each R 14 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H; Each R 15 are independently deuterium, halogen, -N(R 12 )2, -CN, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by Each R 20 Independently, -OH, -OC 1-6 Alkyl, -CN, -NH2, -NHC 1-6 alkyl, and halogen; R 27 is a 3- to 6-membered heterocycle containing one or more heteroatoms selected from N, O, and S, and the heterocycle is unsubstituted or contains one or more R 28 is replaced by Each R 28 But independently, C 1-6 selected from alkyl and halogen; R a and R b are each independently deuterium, halogen, C 1-6 Alkyl, 3-6 membered carbocyclic ring, -OR 12 and H; a and R b are optionally linked together to form a 3- to 6-membered carbocyclic or heterocyclic ring, and any C 1-6 The alkyl or 3- to 6-membered carbocyclic or heterocyclic ring is unsubstituted or contains one or more R 13 is replaced by Each R e are independently hydrogen, deuterium, -OR 12 , =O, =N(R 14 ), -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -C(O)(3- to 6-membered carbocyclic ring), -C(O)N(R14 )2, -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 is replaced by R f and R g are linked together and are unsubstituted, or -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -C(O)O(C 1-6 alkyl), -C(O)N(R 14 )2, -C(O)(3- to 6-membered carbocyclic or heterocyclic ring), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 Forms a 3- to 6-membered carbocyclic or heterocyclic ring substituted with one or more substituents selected from alkyl, and any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 is replaced by

[0217] In some embodiments, the disclosure provides a compound of formula IIIA1 or a salt thereof (eg, a pharmaceutically acceptable salt):

[0218] In some embodiments, for a compound according to Formula IIIA1, each R e are independently hydrogen, -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, for compounds according to formula IIIA1, each R e are independently hydrogen, -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogen, and unsubstituted or one or more R 20 C replaced by 1-6 R is selected from alkyl. e But R f or R g If it is bonded to a carbon that is also bonded to R e is =O or =N(R 14 ) but R e is =O or =N(R 14 ), other R on the same carbon atom should be added so that the carbon has the appropriate valence. e It is understood that R is not present. In some embodiments, each R e are independently hydrogen.

[0219] In some embodiments, for compounds according to formula IIIA1, R f and R gare linked together to form an unsubstituted 3- to 6-membered carbocyclic or heterocyclic ring. In some embodiments, R f and R g are concatenated together, -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -C(O)O(C 1-6 alkyl), -C(O)N(R 14 )2, -C(O)(3- to 6-membered carbocyclic or heterocyclic ring), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 Forms a 3- to 6-membered carbocyclic or heterocyclic ring substituted with one or more substituents selected from alkyl, any C 1-6 The alkyl, carbocycle, or heterocycle may be unsubstituted or may contain one or more R 20 In some embodiments, R f and R g are concatenated together, -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -C(O)(3- to 6-membered carbocyclic or heterocyclic ring), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 Forms a 3- to 6-membered carbocyclic or heterocyclic ring substituted with one or more substituents selected from alkyl, any C 1-6 The alkyl, carbocycle, or heterocycle may be unsubstituted or may contain one or more R 20In some embodiments, R f and R g are concatenated together, -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -C(O)(3- to 6-membered carbocyclic or heterocyclic ring), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogen, and unsubstituted or one or more R 20 C replaced by 1-6 alkyl, and any carbocyclic or heterocyclic ring may be unsubstituted or may contain one or more R 20 In some embodiments, R f and R g are concatenated together, -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -C(O)(3- to 6-membered carbocyclic or heterocyclic ring), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 forming a pyrrolidine substituted with one or more substituents selected from alkyl, any C 1-6 The alkyl, carbocycle, or heterocycle may be unsubstituted or may contain one or more R 20 In some embodiments, R f and R g are concatenated together, -OR 12 , =O, -C(O)(C1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -C(O)O(C 1-6 alkyl), -C(O)N(R 14 )2, -C(O)(3- to 6-membered carbocyclic or heterocyclic ring), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 forming a pyrrolidine substituted with one or more substituents selected from alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, R f and R g The ring formed by joining together is -C(O)N(R 14 )2, at least one R 14 is C 1-6 It is alkyl.

[0220] In some embodiments, for compounds according to formula IIIA1: [ka] The structure is selected from:

[0221] In some embodiments, the compound has formula IIIB: [ka] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein R 1 But, -OR 8 and [ka] is selected from R 5 But halogen and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 6 is a monocyclic or bicyclic heteroaryl, and the heteroaryl is selected from one or more R 15 is replaced by R 7 is selected from halogens, R 8 is selected from heterocycle and alkylheterocycle, and any heterocycle contains 4 to 8 members and is unsubstituted or contains one or more R a or R b and the alkyl portion of any alkyl heterocycle is substituted with C 1-6 alkyl, Each R 12 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H, and any C 1-6 Alkyl or C 2-6 Alkenyl is unsubstituted or has one or more R 13 is replaced by Each R 13 but independently, -OR 14 , -CN, -N(R 14 )2, and halogen; Each R 14 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H; Each R 15 are independently deuterium, halogen, -N(R 12 )2, -CN, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by Each R 20 Independently, -OH, -OC 1-6 Alkyl, -CN, -NH2, -NHC1-6 alkyl, and halogen; R 27 is a 3- to 6-membered heterocycle containing one or more heteroatoms selected from N, O, and S, and the heterocycle is unsubstituted or contains one or more R 28 is replaced by Each R 28 But independently, C 1-6 selected from alkyl and halogen; R a and R b are each independently deuterium, halogen, C 1-6 Alkyl, 3-6 membered carbocyclic ring, -OR 12 and H; a and R b are optionally linked together to form a 3- to 6-membered carbocyclic or heterocyclic ring, and any C 1-6 The alkyl or 3- to 6-membered carbocyclic or heterocyclic ring is unsubstituted or contains one or more R 13 is replaced by Each R e are independently hydrogen, deuterium, -OR 12 , =O, =N(R 14 ), -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -C(O)N(R 14 )2, -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 is replaced by

[0222] In some embodiments, the disclosure provides a compound of formula IIIB or a salt thereof (eg, a pharmaceutically acceptable salt):

[0223] In some embodiments, for a compound according to Formula IIIB, each R e is hydrogen. In some embodiments, at least one R e -OR 12 In some embodiments, each R e are independently hydrogen, -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogen, and unsubstituted or one or more R 20 C replaced by 1-6 R is selected from alkyl. e If =O, then the other R atoms on the same carbon atom should be removed so that the carbon has the appropriate valence. e It is understood that there is no

[0224] In some embodiments, the compound has formula IIIC: [ka] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein R 1 But, -OR 8 and [ka] is selected from R 5 But halogen and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 6 is a monocyclic or bicyclic heteroaryl, and the heteroaryl is selected from one or more R 15 is replaced by R 7 is selected from halogens, R 8 is selected from heterocycle and alkylheterocycle, and any heterocycle contains 4 to 8 members and is unsubstituted or contains one or more R a or R b and the alkyl portion of any alkyl heterocycle is substituted with C 1-6 alkyl, Each R 12 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H, and any C 1-6 Alkyl or C 2-6 Alkenyl is unsubstituted or has one or more R 13 is replaced by Each R 13 but independently, -OR 14 , -CN, -N(R 14 )2, and halogen; Each R 14 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H; Each R 15 are independently deuterium, halogen, -N(R 12 )2, -CN, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by Each R 20 Independently, -OH, -OC 1-6 Alkyl, -CN, -NH2, -NHC 1-6 alkyl, and halogen; R 27 is a 3- to 6-membered heterocycle containing one or more heteroatoms selected from N, O, and S, and the heterocycle is unsubstituted or contains one or more R 28 is replaced by Each R 28 But independently, C 1-6 selected from alkyl and halogen; R a and R b are each independently deuterium, halogen, C 1-6 Alkyl, 3-6 membered carbocyclic ring, -OR 12 and H; a and R b are optionally linked together to form a 3- to 6-membered carbocyclic or heterocyclic ring, and any C 1-6 The alkyl or 3- to 6-membered carbocyclic or heterocyclic ring is unsubstituted or contains one or more R 13 is replaced by Each R e are independently hydrogen, deuterium, -OR 12 , =O, =N(R 14 ), -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -C(O)N(R 14 )2, -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogen, 5-6 membered heteroaryl, and C 1-6 alkyl, any C 1-6 The alkyl or heteroaryl may be unsubstituted or may contain one or more R 20 is replaced by

[0225] In some embodiments, the disclosure provides a compound of formula IIIC or a salt thereof (eg, a pharmaceutically acceptable salt):

[0226] In some embodiments, for compounds according to Formula IIIC: [ka] The structure is selected from:

[0227] In some embodiments, the compound has formula IIIC1: [ka] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein R 1 But, -OR 8 and [ka] is selected from R 5 But halogen and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 6 is a monocyclic or bicyclic heteroaryl, and the heteroaryl is selected from one or more R 15 is replaced by R 7 is selected from halogens, R 8 is selected from heterocycle and alkylheterocycle, and any heterocycle contains 4 to 8 members and is unsubstituted or contains one or more R a or R b and the alkyl portion of any alkyl heterocycle is substituted with C 1-6 alkyl, Each R 12 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H, and any C 1-6 Alkyl or C 2-6 Alkenyl is unsubstituted or has one or more R 13 is replaced by Each R 13 but independently, -OR 14 , -CN, -N(R 14 )2, and halogen; Each R14 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H; Each R 15 are independently deuterium, halogen, -N(R 12 )2, -CN, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by Each R 20 Independently, -OH, -OC 1-6 Alkyl, -CN, -NH2, -NHC 1-6 alkyl, and halogen; R 27 is a 3- to 6-membered heterocycle containing one or more heteroatoms selected from N, O, and S, and the heterocycle is unsubstituted or contains one or more R 28 is replaced by Each R 28 But independently, C 1-6 selected from alkyl and halogen; R a and R b are each independently deuterium, halogen, C 1-6 Alkyl, 3-6 membered carbocyclic ring, -OR 12 and H; a and R b are optionally linked together to form a 3- to 6-membered carbocyclic or heterocyclic ring, and any C 1-6 The alkyl or 3- to 6-membered carbocyclic or heterocyclic ring is unsubstituted or contains one or more R 13 is replaced by Each R e are independently hydrogen, deuterium, -OR 12 , =O, =N(R 14 ), -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -C(O)N(R 14 )2, -S(O)2(C 1-6 alkyl), -N(R 14)C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 is replaced by R f , R g , and R h are each independently hydrogen, deuterium, -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 and optionally, (i)R f and R g are linked together and are unsubstituted or -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 alkyl, forming a 3- to 6-membered carbocyclic or heterocyclic ring or a 5- to 6-membered heteroaryl, substituted with one or more substituents selected from any C1-6 The alkyl is unsubstituted or has one or more R 20 is replaced by, or (ii)R g and R h are linked together and are unsubstituted or -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 alkyl, forming a 3- to 6-membered carbocyclic or heterocyclic ring or a 5- to 6-membered heteroaryl, substituted with one or more substituents selected from any C 1-6 The alkyl is unsubstituted or has one or more R 20 is replaced by

[0228] In some embodiments, the disclosure provides a compound of formula IIIC1 or a salt thereof (eg, a pharmaceutically acceptable salt):

[0229] In some embodiments, for a compound according to Formula IIIC or IIIC1, each R e is hydrogen. In some embodiments, at least one R e -OR 12 , halogen, and unsubstituted or one or more R 20 C replaced by 1-6 Alkyl (e.g., C substituted with -OH) 1-6 In some embodiments, each R e are independently hydrogen, -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogen, and unsubstituted or one or more R 20 C replaced by 1-6 R is selected from alkyl. e If =O, then the other R atoms on the same carbon atom should be removed so that the carbon has the appropriate valence. e , R f , R g , or R h It is understood that there is no

[0230] In some embodiments, for a compound according to Formula IIIC1, (i) R f and R g , or (ii) R g and R h are linked together and are unsubstituted or -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 Forms a 3- to 6-membered carbocyclic or heterocyclic ring substituted with one or more substituents selected from alkyl, and any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, R f and R g are linked together and are unsubstituted or -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 Forms a 3- to 6-membered carbocyclic or heterocyclic ring substituted with one or more substituents selected from alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, R g and R h are linked together and are unsubstituted or -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 Forms a 3- to 6-membered carbocyclic or heterocyclic ring substituted with one or more substituents selected from alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, (i) R f and R g or (ii) R g and R h are linked together to form an unsubstituted 3- to 6-membered carbocyclic or heterocyclic ring. In some embodiments, (i) R f and R g , or (ii) R g and R h are concatenated together, -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 Forms a 3- to 6-membered carbocyclic or heterocyclic ring substituted with one or more substituents selected from alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, (i) R f and R g , or (ii) R g and R h are linked together and are unsubstituted or -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 alkyl, and any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, (i) R f and R g or (ii) R g and R h are linked together and are unsubstituted or -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 alkyl, and any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, (i) R f and R g , or (ii) R g and R h are linked together and are unsubstituted or -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 forming a pyrrolidine substituted with one or more substituents selected from alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, for compounds according to Formula IIIC1, (i) R f and R g , or (ii) R g and R h are linked together and are unsubstituted or -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14)C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 alkyl, forming a 5- to 6-membered heteroaryl substituted with one or more substituents selected from any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, R f and R g are linked together and are unsubstituted or -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 alkyl, forming a 5- to 6-membered heteroaryl substituted with one or more substituents selected from any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, R g and R h are linked together and are unsubstituted or -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 c) alkylene OR 14 , halogens, and C 1-6alkyl, forming a 5- to 6-membered heteroaryl substituted with one or more substituents selected from any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, (i) R f and R g or (ii) R g and R h are linked together to form an unsubstituted 5-6 membered heteroaryl (e.g., pyridine). In some embodiments, (i) R f and R g , or (ii) R g and R h are linked together and are unsubstituted or -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 alkyl, forming a 5- to 6-membered heteroaryl substituted with one or more substituents selected from any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, (i) R f and R g or (ii) R g and R h The ring formed when R are joined together does not contain an -NH- moiety. e , R f , R g , or R h It will be understood that when is =0, then any other substituents on the same carbon atom otherwise present are absent so that the carbon has the appropriate valence.

[0231] In some embodiments, for compounds according to Formula IIIC1: [ka] teeth, [ka] The structure is selected from:

[0232] In some embodiments, the compound has formula IIID: [ka] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein R 1 But, -OR 8 and [ka] is selected from R 5 But halogen and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 6 is a monocyclic or bicyclic heteroaryl, and the heteroaryl is selected from one or more R 15 is replaced by R 7 is selected from halogens, R 8 is selected from heterocycle and alkylheterocycle, and any heterocycle contains 4 to 8 members and is unsubstituted or contains one or more R a or R b and the alkyl portion of any alkyl heterocycle is substituted with C 1-6 alkyl, Each R 11 independently, deuterium, -OR 12 , =O, =N(R 14 ), -C(O)(C1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -C(O)O(C 1-6 alkyl), -C(O)N(R 14 )2, -C(O)(3- to 6-membered carbocyclic or heterocyclic ring), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogen, -CN, 3- to 6-membered carbocyclic or heterocyclic ring, 5- to 6-membered heteroaryl, and C 1-6 alkyl, any C 1-6 The alkyl, carbocycle, heterocycle, or heteroaryl is unsubstituted or contains one or more R 20 is replaced by Each R 12 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H, and any C 1-6 Alkyl or C 2-6 Alkenyl is unsubstituted or has one or more R 13 is replaced by Each R 13 but independently, -OR 14 , -CN, -N(R 14 )2, and halogen; Each R 14 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H; Each R 15 are independently deuterium, halogen, -N(R 12 )2, -CN, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by Each R 20 Independently, -OH, -OC 1-6 Alkyl, -CN, -NH2, -NHC1-6 alkyl, and halogen; R 27 is a 3- to 6-membered heterocycle containing one or more heteroatoms selected from N, O, and S, and the heterocycle is unsubstituted or contains one or more R 28 is replaced by Each R 28 But independently, C 1-6 selected from alkyl and halogen; R a and R b are each independently deuterium, halogen, C 1-6 Alkyl, 3-6 membered carbocyclic ring, -OR 12 and H; a and R b are optionally linked together to form a 3- to 6-membered carbocyclic or heterocyclic ring, and any C 1-6 The alkyl or 3- to 6-membered carbocyclic or heterocyclic ring is unsubstituted or contains one or more R 13 is replaced by Q is CR h R j , N.R. g , O, S, and SO2; Each R e and R f But independently, R 11 and hydrogen; (i)R e and R f can optionally be linked together to form a 4- to 6-membered ring; (ii) the first R connected to the adjacent atom f and the second R f can optionally be linked together to form a 3- to 5-membered ring; (iii) the first R connected to the adjacent atom e and the second R e can optionally be linked together to form a 3- to 5-membered ring; or (iv) the first R connected to the same atom f and the second R f can optionally be linked together to form a 3- to 5-membered ring; One or more Re and / or one or more R f Any ring formed by is unsubstituted or contains one or more R 11 is replaced by R g exists, then R 11 and R h and R j , if present, independently, R 11 and hydrogen, or optionally linked together, unsubstituted, or -OR 12 , =O, =N(R 14 ), -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -C(O)N(R 14 )2, -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 Forms a 3- to 4-membered carbocyclic or heterocyclic ring substituted with one or more substituents selected from alkyl, and any C 1-6 The alkyl is unsubstituted or has one or more R 20 or substituted with R h and R e Or R h and R f are optionally linked together and are unsubstituted or are one or more R 11 Forms a 3- to 6-membered ring substituted with

[0233] In some embodiments, the disclosure provides a compound of formula IIID or a salt thereof (eg, a pharmaceutically acceptable salt):

[0234] In some embodiments, for compounds according to formula IIID, Q is NR g In some embodiments, Rg is -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, R g is -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), and unsubstituted or one or more R 20 C replaced by 1-6 alkyl.

[0235] In some embodiments, for compounds according to formula IIID, Q is O, S, or SO. In some embodiments, Q is O. In some embodiments, Q is S. In some embodiments, Q is SO.

[0236] In some embodiments, in the compound according to formula IIID, Q is CR h R j In some embodiments, Q is CR h R j and R e and R f are linked together to form a 4- to 6-membered ring. In some embodiments, Q is CR h R j and R e and R f When R are linked together to form a 4- to 6-membered ring, h and R j do not join together to form a 3- or 4-membered carbocyclic or heterocyclic ring. In some embodiments, Q is CR h R j and Rh and R j are linked together to form a 3- to 4-membered carbocyclic or heterocyclic ring. h R j and R h and R j When R are linked together to form a 3- or 4-membered carbocyclic or heterocyclic ring, e and R f do not join together to form a 4- to 6-membered ring. In some embodiments, Q is CR h R j and R h and R j When R are linked together to form a 3- or 4-membered carbocyclic or heterocyclic ring, one or more R e s and / or one or more R f In some embodiments, Q is CR h R j and R h and R j In some embodiments, Q is CR h R j and R h is hydrogen and R j is deuterium, -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, Q is substituted with CR h R j and R h is hydrogen and R j -OR12 , -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O))2(C 1-6 alkyl), -N(R 14 C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, Q is substituted with CR h R j and R h is hydrogen and R j -OR 12 , -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogen, and unsubstituted or one or more R 20 C replaced by 1-6 In some embodiments, Q is selected from CR alkyl. h R j and R j is hydrogen and R h and R e or R h and R f are optionally linked together and are unsubstituted or are one or more R 11 It forms a 3- to 6-membered ring (for example, pyridine) substituted with

[0237] In some embodiments, for compounds according to formula IIID, Rh and R j are independently 11 and hydrogen. In some embodiments, each R 11 are independently -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogen, and unsubstituted or one or more R 20 C replaced by 1-6 In some embodiments, R h and R j At least one of the R 20 Replaced with -OR 12 or C 1-6 Alkyl (e.g., C, unsubstituted or substituted with —OH or —CN) 1-6 In some embodiments, R h and R j is hydrogen. h or R j If =O, then the other R atoms on the same carbon atom should be removed so that the carbon has the appropriate valence. h or R j It is understood that there is no

[0238] In some embodiments, for compounds according to formula IIID, R h and R j are linked together and are unsubstituted or -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogen, and unsubstituted or one or more R 20 C replaced by 1-6 In some embodiments, R h and R j At least one of the R 20 Replaced with -OR 12 or C 1-6 Alkyl (e.g., C, unsubstituted or substituted with —OH or —CN) 1-6 In some embodiments, R h and R j Both of R are hydrogen. h or R j If =O, then the other R atoms on the same carbon atom should be removed so that the carbon has the appropriate valence. h or R j It is understood that there is no

[0239] In some embodiments, for a compound according to formula IIID, each R e and R f are independently 11 and hydrogen. In some embodiments, each R 11 are independently deuterium, -OR 12 , =O, =N(R 14 ), -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -C(O)N(R 14 )2, -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C1-6 alkylene) OR 14 , halogen, and unsubstituted or one or more R 20 C replaced by 1-6 In some embodiments, R e and R f At least one of the R 20 Replaced with -OR 12 or C 1-6 Alkyl (e.g., C, unsubstituted or substituted with —OH or —CN) 1-6 In some embodiments, each R e and R f are independently hydrogen and R 11 Each R 11 are independently -OR 12 , halogen, 5- to 6-membered heteroaryl, and unsubstituted or one or more R 20 C replaced by 1-6 In some embodiments, each R e is hydrogen. In some embodiments, each R f is hydrogen. In some embodiments, each R e and R f is hydrogen. e or R f If =O, then the other R atoms on the same carbon atom should be removed so that the carbon has the appropriate valence. e or R f It is understood that there is no

[0240] In some embodiments, the compound has formula IIIE: [ka] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein R 1 But, -OR 8 and [ka] is selected from R 5 But halogen and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 6 is a monocyclic or bicyclic heteroaryl, and the heteroaryl is selected from one or more R 15 is replaced by R 7 is selected from halogens, R 8 is selected from heterocycle and alkylheterocycle, and any heterocycle contains 4 to 8 members and is unsubstituted or contains one or more R a or R b and the alkyl portion of any alkyl heterocycle is substituted with C 1-6 alkyl, Each R 11 independently, deuterium, -OR 12 , =O, =N(R 14 ), -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -C(O)N(R 14 )2, -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogen, 5-6 membered heteroaryl, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 is replaced by Each R 12 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H, and any C 1-6 Alkyl or C 2-6Alkenyl is unsubstituted or has one or more R 13 is replaced by Each R 13 but independently, -OR 14 , -CN, -N(R 14 )2, and halogen; Each R 14 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H; Each R 15 are independently deuterium, halogen, -N(R 12 )2, -CN, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by Each R 20 Independently, -OH, -OC 1-6 Alkyl, -CN, -NH2, -NHC 1-6 alkyl, and halogen; R 27 is a 3- to 6-membered heterocycle containing one or more heteroatoms selected from N, O, and S, and the heterocycle is unsubstituted or contains one or more R 28 is replaced by Each R 28 But independently, C 1-6 selected from alkyl and halogen; R a and R b are each independently deuterium, halogen, C 1-6 Alkyl, 3-6 membered carbocyclic ring, -OR 12 and H; a and R b are optionally linked together to form a 3- to 6-membered carbocyclic or heterocyclic ring, and any C 1-6 The alkyl or 3- to 6-membered carbocyclic or heterocyclic ring is unsubstituted or contains one or more R 13 is replaced by Each R e and R f But independently, R 11 and hydrogen; (i)Re and R f can optionally be linked together to form a 4- to 6-membered ring; (ii) the first R connected to the adjacent atom f and the second R f can optionally be linked together to form a 3- to 5-membered ring; (iii) the first R connected to the adjacent atom e and the second R e can optionally be linked together to form a 3- to 5-membered ring; or (iv) the first R connected to the same atom f and the second R f can optionally be linked together to form a 3- to 5-membered ring; One or more R e and / or one or more R f Any ring formed by is unsubstituted or contains one or more R 11 is replaced by R h and R j But independently, R 11 and hydrogen, or optionally linked together, unsubstituted, or -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 Forms a 3- to 4-membered carbocyclic or heterocyclic ring substituted with one or more substituents selected from alkyl, and any C 1-6 The alkyl is unsubstituted or has one or more R 20 or substituted with R h and R e Or R h and R fare optionally linked together and are unsubstituted or are one or more R 11 Forms a 3- to 6-membered ring substituted with

[0241] In some embodiments, the disclosure provides a compound of formula IIIE or a salt thereof (eg, a pharmaceutically acceptable salt):

[0242] In some embodiments, for compounds according to formula IIIE, R h and R j are independently 11 and hydrogen. In some embodiments, each R 11 are independently -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogen, and unsubstituted or one or more R 20 C replaced by 1-6 In some embodiments, R h and R j At least one of the R 20 Replaced with -OR 12 or C 1-6 Alkyl (e.g., C, unsubstituted or substituted with —OH or —CN) 1-6 In some embodiments, R h is hydrogen and R j is R 11 In some embodiments, R h and R j is hydrogen. h or R jIf =O, then the other R atoms on the same carbon atom should be removed so that the carbon has the appropriate valence. h or R j It is understood that R is absent. In some embodiments, h and R j are independently 11 and hydrogen; (i) R e and R f are linked together to form a 4- to 6-membered ring, or (ii) a first R linked to adjacent atoms f and the second R f can be optionally linked together to form a 3- to 5-membered ring, or (iii) a first R e and the second R e can optionally be linked together to form a 3- to 5-membered ring, or (iv) a first R f and the second R f can optionally be linked together to form a 3- to 5-membered ring, and one or more R e and / or one or more R f Any ring formed by may be unsubstituted or may contain one or more R 11 is replaced by

[0243] In some embodiments, for compounds according to formula IIIE, R h and R j are linked together and are unsubstituted or -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R)C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 Forms a 3- to 4-membered carbocyclic or heterocyclic ring substituted with one or more substituents selected from alkyl, and any C 1-6The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, for compounds according to formula IIIE, R h and R j are linked together and are unsubstituted or -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogen, and unsubstituted or one or more R 20 C replaced by 1-6 In some embodiments, R h and R j When R are linked together to form a 3- or 4-membered carbocyclic or heterocyclic ring, e and R f The combination of R does not join together to form a 4- to 6-membered ring. h and R j When R are linked together to form a 3- or 4-membered carbocyclic or heterocyclic ring, one or more R e s and / or one or more R f In some embodiments, R h and R j are linked together to form an unsubstituted 3- to 4-membered carbocyclic or heterocyclic ring. In some embodiments, R h and R j are concatenated together, -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 Forms a 3- to 4-membered carbocyclic or heterocyclic ring substituted with one or more substituents selected from alkyl, and any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, R h and R j are linked together and are unsubstituted or -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 Forms a 3- to 4-membered carbocyclic ring substituted with one or more substituents selected from alkyl, and any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, R h and R j are linked together and are unsubstituted or -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6alkyl, forming a cyclopropane substituted with one or more substituents selected from any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, R h and R j are linked together and are unsubstituted or -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 alkyl, forming a cyclobutane substituted with one or more substituents selected from any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, R h and R j are linked together and are unsubstituted or -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 Form a 3- to 4-membered heterocyclic ring substituted with one or more substituents selected from alkyl, and any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 In some embodiments, R j is hydrogen and R h and Re or R h and R f are optionally linked together and are unsubstituted or are one or more R 11 It forms a 3- to 6-membered ring (for example, pyridine) substituted with

[0244] In some embodiments, for a compound according to formula IIIE, each R e and R f are independently 11 and hydrogen. In some embodiments, each R 11 are independently deuterium, -OR 12 , =O, =N(R 14 ), -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -C(O)N(R 14 )2, -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogen, and unsubstituted or one or more R 20 C replaced by 1-6 In some embodiments, R e and R f At least one of the R 20 Replaced with -OR 12 or C 1-6 Alkyl (e.g., C, unsubstituted or substituted with —OH or —CN) 1-6 In some embodiments, each R e and R f are independently hydrogen and R 11 Each R 11 are independently -OR 12 , halogen, 5- to 6-membered heteroaryl, and unsubstituted or one or more R 20 C replaced by1-6 In some embodiments, each R e and R f is hydrogen. e or R f If =O, then the other R atoms on the same carbon atom should be removed so that the carbon has the appropriate valence. e or R f It is understood that there is no

[0245] In some embodiments, for compounds according to formula IIIE: [ka] teeth, [ka] The structure is selected from:

[0246] In some embodiments, the compound has formula IIIF, IIIG, or IIIH: [ka] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein R 1 But, -OR 8 and [ka] is selected from R 5 But halogen and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 6 is a monocyclic or bicyclic heteroaryl, and the heteroaryl is selected from one or more R 15 is replaced by R 7 is selected from halogens, R 8 is selected from heterocycle and alkylheterocycle, and any heterocycle contains 4 to 8 members and is unsubstituted or contains one or more R a or R b and the alkyl portion of any alkyl heterocycle is substituted with C 1-6 alkyl, Each R 11 independently, deuterium, -OR 12 , =O, =N(R 14 ), -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -C(O)N(R 14 )2, -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogens, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 20 is replaced by Each R 12 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H, and any C 1-6 Alkyl or C 2-6 Alkenyl is unsubstituted or has one or more R 13 is replaced by Each R 13 but independently, -OR 14 , -CN, -N(R 14 )2, and halogen; Each R 14 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H; Each R 15 are independently deuterium, halogen, -N(R 12 )2, -CN, and C 1-6alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by Each R 20 Independently, -OH, -OC 1-6 Alkyl, -CN, -NH2, -NHC 1-6 alkyl, and halogen; R 27 is a 3- to 6-membered heterocycle containing one or more heteroatoms selected from N, O, and S, and the heterocycle is unsubstituted or contains one or more R 28 is replaced by Each R 28 But independently, C 1-6 selected from alkyl and halogen; R a and R b are each independently deuterium, halogen, C 1-6 Alkyl, 3-6 membered carbocyclic ring, -OR 12 and H; a and R b are optionally linked together to form a 3- to 6-membered carbocyclic or heterocyclic ring, and any C 1-6 The alkyl or 3- to 6-membered carbocyclic or heterocyclic ring is unsubstituted or contains one or more R 13 is replaced by Each R e and R f But independently, R 11 and hydrogen; (i)R e and R f can optionally be linked together to form a 4- to 6-membered ring; (ii) the first R connected to the adjacent atom f and the second R f can optionally be linked together to form a 3- to 5-membered ring; (iii) the first R connected to the adjacent atom e and the second R e can optionally be linked together to form a 3- to 5-membered ring; or (iv) the first R connected to the same atom fand the second R f can optionally be linked together to form a 3- to 5-membered ring; One or more R e and / or one or more R f Any ring formed by is unsubstituted or contains one or more R 11 is replaced by

[0247] In some embodiments, the compound is a compound according to Formula IIIF, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIIG, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof. In some embodiments, the compound is a compound according to Formula IIIH, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof.

[0248] In some embodiments, the disclosure provides a compound of formula IIIF or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the disclosure provides a compound of formula IIIG or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the disclosure provides a compound of formula IIIH or a salt thereof (e.g., a pharmaceutically acceptable salt).

[0249] In some embodiments, for compounds according to formula IIIF, IIIG, or IIIH, each R e and R f are independently 11 and hydrogen. In some embodiments, each R 11 are independently deuterium, -OR 12 , =O, =N(R 14 ), -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6alkyl), -C(O)N(R 14 )2, -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogen, and unsubstituted or one or more R 20 C replaced by 1-6 In some embodiments, R e and R f At least one of the R 20 Replaced with -OR 12 or C 1-6 Alkyl (e.g., C, unsubstituted or substituted with —OH or —CN) 1-6 In some embodiments, each R e is hydrogen. In some embodiments, each R f is hydrogen. In some embodiments, each R e and R f is hydrogen. e or R f If =O, then the other R atoms on the same carbon atom should be removed so that the carbon has the appropriate valence. e or R f It is understood that there is no

[0250] In some embodiments, for compounds according to formula IIIF, IIIG, or IIIH: [ka] teeth, [ka] The structure is selected from:

[0251] In some embodiments, the compound has formula IIIJ: [ka] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein R 1 But, -OR 8 and [ka] is selected from R 5 But halogen and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 6 is a monocyclic or bicyclic heteroaryl, and the heteroaryl is selected from one or more R 15 is replaced by R 7 is selected from halogens, R 8 is selected from heterocycle and alkylheterocycle, and any heterocycle contains 4 to 8 members and is unsubstituted or contains one or more R a or R b and the alkyl portion of any alkyl heterocycle is substituted with C 1-6 alkyl, Each R 11 independently, deuterium, -OR 12 , =O, =N(R 14 ), -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -C(O)N(R 14 )2, -C(O)(3- to 6-membered carbocyclic or heterocyclic ring), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogen, -CN, 3- to 6-membered carbocyclic or heterocyclic ring, and C 1-6alkyl, any C 1-6 The alkyl, carbocycle, or heterocycle may be unsubstituted or may contain one or more R 20 is replaced by Each R 12 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H, and any C 1-6 Alkyl or C 2-6 Alkenyl is unsubstituted or has one or more R 13 is replaced by Each R 13 but independently, -OR 14 , -CN, -N(R 14 )2, and halogen; Each R 14 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H; Each R 15 are independently deuterium, halogen, -N(R 12 )2, -CN, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by Each R 20 Independently, -OH, -OC 1-6 Alkyl, -CN, -NH2, -NHC 1-6 alkyl, and halogen; R 27 is a 3- to 6-membered heterocycle containing one or more heteroatoms selected from N, O, and S, and the heterocycle is unsubstituted or contains one or more R 28 is replaced by Each R 28 But independently, C 1-6 selected from alkyl and halogen; R a and R b are each independently deuterium, halogen, C 1-6 Alkyl, 3-6 membered carbocyclic ring, -OR 12 and H; a and R bare optionally linked together to form a 3- to 6-membered carbocyclic or heterocyclic ring, and any C 1-6 The alkyl or 3- to 6-membered carbocyclic or heterocyclic ring is unsubstituted or contains one or more R 13 is replaced by Each R e and R f But independently, R 11 and hydrogen; (i)R e and R f can optionally be linked together to form a 4- to 6-membered ring; (ii) the first R connected to the adjacent atom f and the second R f can optionally be linked together to form a 3- to 5-membered ring; (iii) the first R connected to the adjacent atom e and the second R e can optionally be linked together to form a 3- to 5-membered ring; or (iv) the first R connected to the same atom f and the second R f can optionally be linked together to form a 3- to 5-membered ring; One or more R e and / or one or more R f Any ring formed by is unsubstituted or contains one or more R 11 is replaced by R g But R 11 or R g and R e , or R g and R f are optionally linked together and are unsubstituted or are one or more R 11 Forms a 3- to 6-membered ring substituted with

[0252] In some embodiments, the disclosure provides a compound of formula IIIJ or a salt thereof (eg, a pharmaceutically acceptable salt):

[0253] In some embodiments, for a compound according to formula IIIJ, each Re and R f are independently 11 and hydrogen. In some embodiments, each R 11 are independently deuterium, -OR 12 , =O, =N(R 14 ), -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -C(O)N(R 14 )2, -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogen, and unsubstituted or one or more R 20 C replaced by 1-6 In some embodiments, each R 11 are independently deuterium, -OR 12 , =O, =N(R 14 ), -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogen, and unsubstituted or one or more R 20 C replaced by 1-6 In some embodiments, R e and R f At least one of the R 20 Replaced with -OR 12 or C 1-6 Alkyl (e.g., C, unsubstituted or substituted with —OH or —CN) 1-6In some embodiments, each R e is hydrogen. In some embodiments, each R f is hydrogen. In some embodiments, each R e and R f is hydrogen. e or R f If =O, then the other R atoms on the same carbon atom should be removed so that the carbon has the appropriate valence. e or R f It is understood that R is absent. In some embodiments, e and R f are linked together to form a 4- to 6-membered ring.

[0254] In some embodiments, for compounds according to formula IIIJ: [ka] teeth [ka] The structure is selected from:

[0255] In some embodiments, for a compound according to any one of formulas IIID, IIIE, IIIF, IIIG, IIIH, and IIIJ, R e and R f are linked together to form a 4- to 6-membered ring. In some embodiments, the 4- to 6-membered ring is an unsubstituted 4- to 6-membered carbocyclic or heterocyclic ring. In some embodiments, the 4- to 6-membered ring is an unsubstituted 4- to 6-membered carbocyclic ring. In some embodiments, the 4- to 6-membered ring is an unsubstituted 4- to 6-membered heterocyclic ring. In some embodiments, the 4- to 6-membered ring is linked together to form a 4- to 6-membered ... 11 In some embodiments, R e and R f When R are linked together to form a 4- to 6-membered ring, e s and R f No additional rings are formed by any combination of s.

[0256] In some embodiments, for a compound according to any one of formulas IIID, IIIE, IIIF, IIIG, IIIH, and IIIJ, the first R connected to an adjacent atom f and the second R f are linked together to form a 3- to 5-membered ring. In some embodiments, the 3- to 5-membered ring is an unsubstituted 3- to 5-membered carbocyclic or heterocyclic ring. In some embodiments, the 3- to 5-membered ring is an unsubstituted 3- to 5-membered carbocyclic ring. In some embodiments, the 3- to 5-membered ring is an unsubstituted 3- to 5-membered heterocyclic ring. In some embodiments, the 3- to 5-membered ring is a ring containing one or more R 11 In some embodiments, the first R attached to adjacent atoms is a 3- to 5-membered carbocyclic or heterocyclic ring substituted with f and the second R f When R are linked together to form a 3- to 5-membered ring, e s and R f No additional rings are formed by any combination of s.

[0257] In some embodiments, for a compound according to any one of formulas IIID, IIIE, IIIF, IIIG, IIIH, and IIIJ, the first R connected to an adjacent atom e and the second R e are linked together to form a 3- to 5-membered ring. In some embodiments, the 3- to 5-membered ring is an unsubstituted 3- to 5-membered carbocyclic or heterocyclic ring. In some embodiments, the 3- to 5-membered ring is an unsubstituted 3- to 5-membered carbocyclic ring. In some embodiments, the 3- to 5-membered ring is an unsubstituted 3- to 5-membered heterocyclic ring. In some embodiments, the 3- to 5-membered ring is a ring containing one or more R 11 In some embodiments, the first R attached to adjacent atoms is a 3- to 5-membered carbocyclic or heterocyclic ring substituted with e and the second R e When R are linked together to form a 3- to 5-membered ring, e s and R f No additional rings are formed by any combination of s.

[0258] In some embodiments, for a compound according to any one of formulas IIID, IIIE, IIIF, IIIG, IIIH, and IIIJ, two first R f and the second R f are linked together to form a 3- to 5-membered ring. In some embodiments, the 3- to 5-membered ring is an unsubstituted 3- to 5-membered carbocyclic or heterocyclic ring. In some embodiments, the 3- to 5-membered ring is an unsubstituted 3- to 5-membered carbocyclic ring. In some embodiments, the 3- to 5-membered ring is an unsubstituted 3- to 5-membered heterocyclic ring. In some embodiments, the 3- to 5-membered ring is a ring containing one or more R 11 In some embodiments, the first R attached to the same atom is a 3- to 5-membered carbocyclic or heterocyclic ring substituted with f and the second f When R are linked together to form a 3- to 5-membered ring, e s and R f No additional rings are formed by any combination of s.

[0259] In some embodiments, for compounds according to formula IIIJ, R g -OR 12 , =O, -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -C(O)N(R 14 )2, -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogen, and unsubstituted or one or more R 20 C replaced by 1-6 In some embodiments, R g is -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -C(O)N(R14 )2, -S(O)2(C 1-6 alkyl), and unsubstituted or one or more R 20 C replaced by 1-6 In some embodiments, R g is -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -S(O)2(C 1-6 alkyl), and unsubstituted or one or more R 20 C replaced by 1-6 In some embodiments, R g and R e or R g and R f are optionally linked together and are unsubstituted or are one or more R 11 Forms a 3- to 6-membered ring substituted with

[0260] In some embodiments, the compound has formula IIIK, IIIL, IIIM, IIIN, IIIP, IIIQ, or IIIR: [ka] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer(s) thereof, wherein R 1 But, -OR 8 and [ka] is selected from R 5 But halogen and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by R 6is a monocyclic or bicyclic heteroaryl, and the heteroaryl is selected from one or more R 15 is replaced by R 7 is selected from halogens, R 8 is selected from heterocycle and alkylheterocycle, and any heterocycle contains 4 to 8 members and is unsubstituted or contains one or more R a or R b and the alkyl portion of any alkyl heterocycle is substituted with C 1-6 alkyl, Each R 11 independently, deuterium, -OR 12 , =O, =N(R 14 ), -C(O)(C 1-6 alkylene)CN, -C(O)(C 1-6 alkylene) OR 14 , -C(O)(C 1-6 alkyl), -C(O)N(R 14 )2, -C(O)(3- to 6-membered carbocyclic or heterocyclic ring), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkylene) OR 14 , halogen, -CN, 3- to 6-membered carbocyclic or heterocyclic ring, and C 1-6 alkyl, any C 1-6 The alkyl, carbocycle, or heterocycle may be unsubstituted or may contain one or more R 20 is replaced by Each R 12 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H, and any C 1-6 Alkyl or C 2-6 Alkenyl is unsubstituted or has one or more R 13 is replaced by Each R 13 but independently, -OR 14 , -CN, -N(R 14 )2, and halogen; Each R14 But independently, C 1-6 Alkyl, C 2-6 alkenyl, and H; Each R 15 are independently deuterium, halogen, -N(R 12 )2, -CN, and C 1-6 alkyl, any C 1-6 The alkyl may be unsubstituted or may contain one or more R 13 is replaced by Each R 20 Independently, -OH, -OC 1-6 Alkyl, -CN, -NH2, -NHC 1-6 alkyl, and halogen; R 27 is a 3- to 6-membered heterocycle containing one or more heteroatoms selected from N, O, and S, and the heterocycle is unsubstituted or contains one or more R 28 is replaced by Each R 28 But independently, C 1-6 selected from alkyl and halogen; R a and R b are each independently deuterium, halogen, C 1-6 Alkyl, 3-6 membered carbocyclic ring, -OR 12 and H; a and R b are optionally linked together to form a 3- to 6-membered carbocyclic or heterocyclic ring, and any C 1-6 The alkyl or 3- to 6-membered carbocyclic or heterocyclic ring is unsubstituted or contains one or more R 13 is replaced by Q is CR h R j , N.R. g , O, S, and SO2; ...

Claims

1. Formula II': 【Chemical 1】 or a salt thereof (e.g., a pharmaceutically acceptable salt), wherein R １ But, -OR ８ and 【Chemistry 2】 is selected from R ２ But H, C １－６ alkyl, and 3- to 6-membered carbocyclic rings, １－６ The alkyl is unsubstituted or has one or more R １３ is replaced by R ３ is unsubstituted or is substituted with one or more R １０ and selected from 4-9 membered heterocycles substituted with R ４ is H, R ５ is H, halogen, -CN, -OR １２ , 3- to 6-membered heterocycle, 5- to 6-membered heteroaryl, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R １３ is replaced by R ６ is a monocyclic or bicyclic heteroaryl, and the heteroaryl is selected from one or more R １５ is replaced by R ７ is selected from halogens, R ８ is selected from heterocycle and alkylheterocycle, any heterocycle containing 4 to 8 members and is unsubstituted or contains one or more R ａ or R ｂ and the alkyl portion of any alkyl heterocycle is substituted with C １－６ alkyl, Each R １０ are independently deuterium, -OR １２ , =O, -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene)OH, —C(O)(C １－６ alkyl), —C(O)O(C １－６ alkyl), —C(O)N(R １４ ) ２ , -C(O)OR １４ , —C(O)(3- to 6-membered carbocyclic ring), —C(O)(3- to 8-membered heterocyclic ring), —C(O)(5- to 6-membered heteroaryl), —C(O)O(3- to 6-membered carbocyclic ring), —C(O)O(3- to 6-membered heterocyclic ring), —C(O)O(C １－６ alkylene) (3- to 6-membered heterocycle), —S(O) ２ (C １－６ alkyl), halogen, 5- to 6-membered heteroaryl, 3- to 6-membered carbocyclic ring, 3- to 6-membered heterocyclic ring, and C １－６ alkyl, any C １－６ The alkyl is optionally deuterated, unsubstituted, or has one or more R ２０ and any 3- to 6-membered carbocycle, 5- to 6-membered heteroaryl, or 3- to 6- or 3- to 8-membered heterocycle is unsubstituted or substituted with one or more R １２ Or R ２０ and two R １０ optionally joined together with the atom(s) to which they are attached to form a 3- to 6-membered carbocyclic or heterocyclic ring; Each R １２ But independently, C １－６ Alkyl, C ２－６ alkenyl, and H, and any C １－６ Alkyl or C ２－６ Alkenyl is unsubstituted or has one or more R １３ is replaced by Each R １３ But independently, -OR １４ , -CN, -N(R １４ ) ２ and halogen; Each R １４ are independently a 3- to 6-membered carbocyclic ring, a 3- to 6-membered heterocyclic ring, C １－６ Alkyl, C ２－６ alkenyl, and H, and any C １－６ the alkyl is optionally deuterated; Each R １５ are independently deuterium, halogen, -N(R １２ ) ２ , -CN, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R １３ is replaced by Each R ２０ are independently —OH, —OC １－６ Alkyl, —OC １－６ Haloalkyl, ═O, —CN, —NH ２ , -NHC １－６ Alkyl, —C(O)(C １－６ alkyl), a 3- to 6-membered carbocycle, phenyl, and halogen; R ２７ is a 3- to 6-membered heterocycle containing one or more heteroatoms selected from N, O, and S, and the heterocycle is unsubstituted or contains one or more R ２８ is replaced by Each R ２８ But independently, C １－６ selected from alkyl and halogen; R ａ and R ｂ are each independently deuterium, halogen, C １－６ alkyl, 3- to 6-membered carbocyclic ring, —OR １２ and H; R ａ and R ｂ are optionally linked together to form a 3- to 6-membered carbocyclic or heterocyclic ring, and any C １－６ The alkyl or 3- to 6-membered carbocyclic or heterocyclic ring is unsubstituted or contains one or more R １３ The compound or a salt thereof, wherein the compound is substituted with

2. Formula II: 【Chemistry 3】 or a salt thereof (e.g., a pharmaceutically acceptable salt), wherein R １ But, -OR ８ and 【Chemistry 4】 is selected from R ２ But H, C １－６ alkyl, and 3- to 6-membered carbocyclic rings, １－６ The alkyl is unsubstituted or has one or more R １３ is replaced by R ３ is unsubstituted or is substituted with one or more R １０ with the proviso that (i) if said heterocycle contains a nitrogen atom, then said nitrogen atom is selected from a 4- to 9-membered heterocycle substituted with R １０ or (ii) said heterocycle does not contain an —NH— moiety; R ４ is H, R ５ is H, halogen, -CN, -OR １２ , 3- to 6-membered heterocycle, 5- to 6-membered heteroaryl, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R １３ is replaced by R ６ is a monocyclic or bicyclic heteroaryl, said heteroaryl being selected from one or more R １５ is replaced by R ７ is selected from halogens, R ８ is selected from heterocycle and alkylheterocycle, any heterocycle containing 4 to 8 members and is unsubstituted or contains one or more R ａ or R ｂ and the alkyl portion of any alkyl heterocycle is substituted with C １－６ alkyl, Each R １０ are independently deuterium, -OR １２ , =O, -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene)OH, —C(O)(C １－６ alkyl), —C(O)O(C １－６ alkyl), —C(O)N(R １４ ) ２ , -C(O)OR １４ , —C(O)(3- to 6-membered carbocyclic ring), —C(O)(3- to 8-membered heterocyclic ring), —C(O)(5- to 6-membered heteroaryl), —C(O)O(3- to 6-membered carbocyclic ring), —C(O)O(3- to 6-membered heterocyclic ring), —C(O)O(C １－６ alkylene) (3- to 6-membered heterocycle), —S(O) ２ (C １－６ alkyl), halogen, 5- to 6-membered heteroaryl, 3- to 6-membered carbocyclic ring, and C １－６ alkyl, any C １－６ The alkyl is optionally deuterated, unsubstituted, or has one or more R ２０ and any 3- to 6-membered carbocycle, 5- to 6-membered heteroaryl, or 3- to 6- or 3- to 8-membered heterocycle is unsubstituted or substituted with one or more R １２ Or R ２０ and two R １０ optionally joined together with the atom(s) to which they are attached to form a 3- to 6-membered carbocyclic or heterocyclic ring; Each R １２ But independently, C １－６ Alkyl, C ２－６ alkenyl, and H, and any C １－６ Alkyl or C ２－６ Alkenyl is unsubstituted or has one or more R １３ is replaced by Each R １３ But independently, -OR １４ , -CN, -N(R １４ ) ２ and halogen; Each R １４ are independently a 3- to 6-membered carbocyclic ring, a 3- to 6-membered heterocyclic ring, C １－６ Alkyl, C ２－６ alkenyl, and H, and any C １－６ the alkyl is optionally deuterated; Each R １５ are independently deuterium, halogen, -N(R １２ ) ２ , -CN, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R １３ is replaced by Each R ２０ are independently —OH, —OC １－６ Alkyl, —OC １－６ Haloalkyl, ═O, —CN, —NH ２ , -NHC １－６ Alkyl, —C(O)(C １－６ alkyl), a 3- to 6-membered carbocycle, phenyl, and halogen; R ２７ is a 3- to 6-membered heterocycle containing one or more heteroatoms selected from N, O, and S, and the heterocycle is unsubstituted or contains one or more R ２８ is replaced by Each R ２８ But independently, C １－６ selected from alkyl and halogen; R ａ and R ｂ are each independently deuterium, halogen, C １－６ alkyl, 3- to 6-membered carbocyclic ring, —OR １２ and H; R ａ and R ｂ are optionally linked together to form a 3- to 6-membered carbocyclic or heterocyclic ring, and any C １－６ The alkyl or 3- to 6-membered carbocyclic or heterocyclic ring is unsubstituted or contains one or more R １３ The compound or a salt thereof, wherein the compound is substituted with

3. The compound has the formula II-a: 【Chemistry 5】 or a salt thereof (e.g., a pharmaceutically acceptable salt) thereof.

4. R ３ The compound according to any one of claims 1 to 3, wherein is a 4- to 6-membered heterocycle containing one heteroatom selected from O, S, and N.

5. R ３ is a 4- to 6-membered heterocycle containing one heteroatom selected from O, S, and N, and the heterocycle is １０ with the proviso that if the heterocycle contains a nitrogen atom, the nitrogen atom is substituted with R １０ 5. The compound of claim 4 , substituted with:

6. R ３ But 0 to 4 R １０ and wherein the nitrogen atom is substituted with R １０ The compound of any one of claims 1 to 5, substituted with

7. R ３ But 0 to 4 R １０ 6. The compound according to claim 1, which is an oxetane or thietane substituted with

8. R ３ But 0 to 4 R １０ The compound according to any one of claims 1 to 5, which is tetrahydrofuran or tetrahydrothiopene substituted with

9. R ３ But there are one or more R １０ and wherein when said heterocycle contains a nitrogen atom, said nitrogen atom is substituted with R １０ and each R １０ are independently —C(O)(C １－６ alkyl), —C(O)(3- to 6-membered carbocyclic ring), —C(O)O(C １－６ alkyl), halogen, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R ２０ and any 3- to 6-membered carbocyclic ring is unsubstituted or substituted with one or more R １２ Or R ２０ The compound of any one of claims 1 to 5, substituted with

10. R ３ But there are one or more R １０ and at least one R １０ But, -OR １２ and C substituted with —OH １－６ The compound according to any one of claims 1 to 5, wherein the aryl group is selected from alkyl.

11. R ３ But there are one or more R １０ and at least one R １０ is unsubstituted C １－６ The compound of any one of claims 1 to 10, which is alkyl.

12. R ３ but, 【Chemistry 6】 【Chemistry 7】 【Chemistry 8】 【Chemistry 9】 【Chemistry 10】 【Chemistry 11】 【Chemistry 12】 any of which may optionally be selected from one or more R １０ The compound of any one of claims 1 to 11, further substituted with:

13. R ３ is a 7-9 membered heterocycle containing one or more heteroatoms selected from O, S, and N, and said heterocycle is unsubstituted or contains one or more R １０ The compound of any one of claims 1 to 3, substituted with

14. R ３ is a 7-9 membered heterocycle containing one or more heteroatoms selected from O, S, and N, and said heterocycle is unsubstituted or contains one or more R １０ with the proviso that (i) if the heterocycle contains a nitrogen atom, then the nitrogen atom is substituted with R １０ or (ii) the heterocycle does not contain an -NH- moiety.

15. R ３ is a 7- to 9-membered bridged heterocycle containing one or more heteroatoms selected from O, S, and N, and the bridged heterocycle is unsubstituted or is substituted with one or more R １０ 15. The compound of claim 13 or 14, substituted with:

16. R ３ is a 7-9 membered heterocycle including a fused ring system containing one or more heteroatoms selected from O, S, and N, said heterocycle being unsubstituted or containing one or more R １０ 15. The compound of claim 13 or 14, substituted with:

17. R ３ but, 【Chemistry 13】 any of which may optionally be selected from one or more R １０ 17. The compound of any one of claims 1, 2, 3, or 13-16, further substituted with:

18. 10. The compound of claim 1, wherein the compound has formula IIA, IIB, IIC, IID, IIE, IIF, IIG, IIH, IIJ, IIK, IIL, IIM, IIN, IIP, IIQ, IIR, IIS, IIT, IIU, IIV, IIW, IIX, IIY, or IIZ: 【Chemistry 14】 【Chemistry 15】 【Chemistry 16】 or a salt (e.g., a pharmaceutically acceptable salt) thereof, wherein Each R ｄ are independently H, deuterium, -OR １２ , =O, -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene)OH, —C(O)(C １－６ alkyl), —C(O)N(R １４ ) ２ , -C(O) (3-6 membered carbocycle), -S(O) ２ (C １－６ alkyl), halogen, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R ２０ and any 3- to 6-membered carbocyclic ring is unsubstituted or substituted with one or more R １２ or R ２０ is replaced by R ｅ When present, -C(O)(C １－６ alkyl)CN, -C(O)(C １－６ alkyl)OH, —C(O)(C １－６ alkyl), —C(O)O(C １－６ alkyl), —C(O)N(R １４ ) ２ , -C(O)OR １４ , —C(O)(3- to 6-membered carbocyclic ring), —C(O)(3- to 8-membered heterocyclic ring), —C(O)(5- to 6-membered heteroaryl), —C(O)O(3- to 6-membered carbocyclic ring), —C(O)O(3- to 6-membered heterocyclic ring), —C(O)O(C １－６ alkylene) (3- to 6-membered heterocycle), —S(O) ２ (C １－６ alkyl), 5- to 6-membered heteroaryl, 3- to 6-membered carbocyclic ring, and C １－６ alkyl, any C １－６ The alkyl is optionally deuterated, unsubstituted, or has one or more R ２０ and any 3- to 6-membered carbocycle, 5- to 6-membered heteroaryl, or 3- to 6- or 3- to 8-membered heterocycle is unsubstituted or substituted with one or more R １２ Or R ２０ is replaced by Each R ｆ is optionally absent, and when present, is ═O, —NH ２ , -NHC １－６ Alkyl, and —N(C １－６ alkyl) ２ The compound according to any one of claims 1 to 17, selected from:

19. The compound has the formula IIAA: 【Chemistry 17】 or a salt (e.g., a pharmaceutically acceptable salt) thereof, wherein Each R ｄ are independently deuterium, H, -OR １２ , =O, -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene)OH, —C(O)(C １－６ alkyl), —C(O) (3- to 6-membered carbocyclic ring), —S(O) ２ (C １－６ alkyl), halogen, 3- to 6-membered carbocyclic ring, 3- to 6-membered heterocyclic ring, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R ２０ and any 3-6 membered carbocyclic or 3-6 membered heterocyclic ring is unsubstituted or substituted with one or more R １２ Or R ２０ is replaced by (i) R ｑ１ , R ｑ２ , and R ｐ２ are each independently R ｄ and R ｅ and R ｐ１ together with the atoms to which they are attached are unsubstituted or contain one or more R ｄ or forming a 5- to 6-membered heterocyclic ring substituted with (ii) R ｐ１ , R ｐ２ , and R ｑ２ are each independently R ｄ and R ｅ and R ｑ１ together with the atoms to which they are attached are unsubstituted or contain one or more R ｄ The compound according to any one of claims 1 to 17, selected from:

20. R ６ But there are one or more R １５ The compound of any one of claims 1 to 19, which is a monocyclic heteroaryl substituted with

21. R ６ But there are one or more R １５ 21. The compound of claim 20, which is a pyridine substituted with

22. R ６ But the structure 【Chemistry 18】 22. The compound of claim 21 having the formula:

23. R ６ But there are one or more R １５ 20. The compound of any one of claims 1 to 19, which is a bicyclic heteroaryl substituted with:

24. R ６ but, 【Chemistry 19】 is selected from X is selected from N and C—CN; Y is selected from O and S; R ２３ But -N(R １２ ) ２ , C １－６ Alkyl, and C １－６ Alkyl-N(R １４ ) ２ and any C １－６ The alkyl is unsubstituted or has one or more R １３ is replaced by R ２４ , R ２５ , and R ２６ are independently H, deuterium, halogen, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R １３ 24. The compound of claim 23 substituted with:

25. R ６ but, 【Chemistry 20】 any of which is selected from one or more R １５ 25. The compound of claim 23 or 24, substituted with:

26. R ６ but, 【Chemical 21】 The compound according to any one of claims 23 to 25, selected from:

27. R ６ but, 【Chemical 22】 The compound according to any one of claims 23 to 26, selected from:

28. 10. The compound of claim 1, wherein the compound has the formula IIA1, IIB1, IIC1, IID1, IIE1, IIF1, IIG1, IIH1, IIJ1, IIK1, IIL1, IIM1, IIN1, IIP1, IIQ1, IIR1, IIS1, IIT1, IIU1, IIV1, IIW1, IIX1, IIY1, or IIZ1: 【Chemical 23】 【Chemistry 24】 【Chemistry 25】 or a salt (e.g., a pharmaceutically acceptable salt) thereof, wherein Each R ｄ are independently H, deuterium, -OR １２ , =O, -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene)OH, —C(O)(C １－６ alkyl), —C(O)N(R １４ ) ２ , -C(O) (3-6 membered carbocycle), -S(O) ２ (C １－６ alkyl), halogen, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R ２０ and any 3- to 6-membered carbocyclic ring is unsubstituted or substituted with one or more R １２ or R ２０ is replaced by R ｅ When present, -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene)OH, —C(O)(C １－６ alkyl), —C(O)O(C １－６ alkyl), —C(O)N(R １４ ) ２ , -C(O)OR １４ , —C(O)(3- to 6-membered carbocyclic ring), —C(O)(3- to 8-membered heterocyclic ring), —C(O)(5- to 6-membered heteroaryl), —C(O)O(3- to 6-membered carbocyclic ring), —C(O)O(3- to 6-membered heterocyclic ring), —C(O)O(C １－６ alkylene) (3- to 6-membered heterocycle), —S(O) ２ (C １－６ alkyl), 5- to 6-membered heteroaryl, 3- to 6-membered carbocyclic ring, and C １－６ alkyl, any C １－６ The alkyl is optionally deuterated, unsubstituted, or has one or more R ２０ and any 3- to 6-membered carbocycle, 5- to 6-membered heteroaryl, or 3- to 6- or 3- to 8-membered heterocycle is unsubstituted or substituted with one or more R １２ Or R ２０ is replaced by Each R ｆ is optionally absent, and when present, is ═O, —NH ２ , -NHC １－６ Alkyl, and —N(C １－６ alkyl) ２ is selected from X is selected from N and C—CN; Y is selected from O and S; R ２３ But -N(R １２ ) ２ , C １－６ Alkyl, and C １－６ Alkyl-N(R １４ ) ２ and any C １－６ The alkyl is unsubstituted or has one or more R １３ is replaced by R ２４ , R ２５ , and R ２６ are independently H, deuterium, halogen, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R １３ The compound according to any one of claims 23 to 26, selected from:

29. The compound has the formula IIAA1: 【Chemical 26】 or a salt (e.g., a pharmaceutically acceptable salt) thereof, wherein: Each R ｄ are independently H, deuterium, -OR １２ , =O, -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene)OH, —C(O)(C １－６ alkyl), —C(O)(3- to 6-membered carbocyclic ring), —C(O)N(R １４ ) ２ , -S(O) ２ (C １－６ alkyl), 3- to 6-membered carbocyclic ring, 3- to 6-membered heterocyclic ring, halogen, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R ２０ and any 3- to 6-membered carbocyclic or 3- to 6-membered heterocyclic ring is unsubstituted or substituted with one or more R １２ Or R ２０ is replaced by X is selected from N and C—CN; Y is selected from O and S; R ２３ But -N(R １２ ) ２ , C １－６ Alkyl, and C １－６ Alkyl-N(R １４ ) ２ and any C １－６ The alkyl is unsubstituted or has one or more R １３ is replaced by R ２４ , R ２５ , and R ２６ are independently H, deuterium, halogen, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R １３ is replaced by (i) R ｑ１ , R ｑ２ , and R ｐ２ are each independently R ｄ and R ｅ and R ｐ１ together with the atoms to which they are attached are unsubstituted or contain one or more R ｄ or forming a 5- to 6-membered heterocyclic ring substituted with (ii) R ｐ１ , R ｐ２ , and R ｑ２ are each independently R ｄ and R ｅ and R ｑ１ together with the atoms to which they are attached are unsubstituted or contain one or more R ｄ The compound according to any one of claims 1 to 27, which forms a 5- to 6-membered heterocyclic ring substituted with

30. X is C—CN, Y is S, and R ２３ But -N(R １２ ) ２ 30. The compound of claim 28 or 29, wherein:

31. R ２４ , R ２５ , and R ２６ The compound of any one of claims 28 to 30, wherein one or more of is halogen (e.g. F).

32. Each R ｆ 29. The compound of claim 18 or 28, wherein is =O.

33. Each R ｆ The compound of claim 18 or 28, wherein is absent.

34. R ｅ is unsubstituted or is substituted with one or more R ２０ C substituted with １－６ 30. The compound of claim 18 or 28, which is alkyl.

35. R ｅ The compound according to claim 18 or 28, wherein is -C(O) (3- to 6-membered carbocyclic ring).

36. R ｅ But -C(O)(C １－６ alkyl), —C(O)(3- to 6-membered carbocyclic ring), and —C(O)O(C １－６ alkyl), and any C １－６ The alkyl is unsubstituted or has one or more R ２０ and any 3- to 6-membered carbocyclic ring is unsubstituted or substituted with one or more R １２ Or R ２０ 29. The compound of claim 18 or 28, substituted with:

37. Each R ｄ The compound of any one of claims 18 to 36, wherein is H.

38. At least one R ｄ But, -OR １２ and C substituted with —OH １－６ 37. The compound of any one of claims 18 to 36, wherein the alkyl is selected from the group consisting of aryl, arylsulfonyl ...

39. R ２ The compound of any one of claims 1 to 38, wherein is H.

40. R ２ is unsubstituted or is substituted with one or more R １３ C substituted with １－６ 39. The compound of any one of claims 1 to 38, wherein the aryl group is selected from alkyl.

41. R ２ But C １－２ 41. The compound of claim 40, wherein the alkyl is selected from alkyl.

42. R ２ The compound of any one of claims 1 to 38, wherein is selected from a 3- to 6-membered carbocycle.

43. R １ But, -OR ８ 43. The compound according to any one of claims 1 to 42, selected from:

44. R １ But the following compound: 【Chemical 27】 wherein R ａ１ , R ａ２ , R ｂ１ , and R ｂ２ are each independently deuterium, halogen, C １－６ Alkyl, -OR １２ and H; R ａ２ and R ｂ２ can optionally be linked together to form a 3- to 6-membered carbocyclic ring, and any C １－６ The alkyl or 3- to 6-membered carbocyclic ring is unsubstituted or has one or more R １３ 44. The compound of claim 43, substituted with:

45. R １ but, 【Chemical formula 28】 45. The compound of claim 44, selected from:

46. R １ but, 【Chemical Formula 29】 wherein R ａ and R ｂ are each independently a halogen, C １－６ Alkyl, -OR １２ , and H, and any C １－６ Alkyl is unsubstituted or has one or more R １３ 44. The compound of claim 43, substituted with:

47. R １ but, 【Chemistry 30】 47. The compound of claim 46, selected from:

48. R １ but, 【Chemical 31】 is selected from In the formula, each R ａ and R ｂ are independently halogen, C １－６ Alkyl, -OR １２ and H; R ｃ But C １－６ alkyl, and R ａ and R ｂ or R ｃ are optionally linked together to form a 3- to 6-membered carbocyclic or heterocyclic ring, and any C １－６ The alkyl or 3- to 6-membered carbocyclic or heterocyclic ring is unsubstituted or contains one or more R １３ 44. The compound of claim 43, substituted with:

49. R １ but, 【Chemical 32】 49. The compound of claim 48, selected from:

50. R １ but, 【Chemical 33】 43. The compound according to any one of claims 1 to 42, selected from:

51. R ５ The compound of any one of claims 1 to 50, wherein is H.

52. R ５ 51. The compound of any one of claims 1 to 50, wherein is halogen (for example F or Cl).

53. R ５ is unsubstituted or is substituted with one or more R １３ C substituted with １－６ 51. The compound of any one of claims 1 to 50, wherein the compound is selected from alkyl.

54. R ５ is substituted with one or more halogens or —CN １－６ 54. The compound of claim 53, wherein the alkyl is selected from:

55. R ５ But, -CF ２ H, -CF ３ , -CH ２ CN, and -CH ２ CH ３ 55. The compound of claim 54, selected from:

56. R ５ But, -CF ３ 56. The compound of claim 55, wherein:

57. 57. The compound of any one of claims 1 to 56, wherein the compound is not a compound included in Table 1.

58. Formula III': 【Chemical 34】 or a salt thereof (e.g., a pharmaceutically acceptable salt), wherein R １ But, -OR ８ and 【Chemical 35】 is selected from R ２ and R ３ together with the nitrogen atom to which they are attached are unsubstituted or contain one or more R １１ forming a 4- to 10-membered heterocyclic ring substituted with R ４ is H, R ５ is halogen and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R １３ is replaced by R ６ is a monocyclic or bicyclic heteroaryl, and the heteroaryl is selected from one or more R １５ is replaced by R ７ is selected from halogens, R ８ is selected from heterocycle and alkylheterocycle, any heterocycle containing 4 to 8 members and is unsubstituted or contains one or more R ａ or R ｂ and the alkyl portion of any alkyl heterocycle is substituted with C １－６ alkyl, Each R １１ are independently deuterium, -OR １２ , =O, =N(R １４ ), —C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), —C(O)O(C １－６ alkyl), —C(O)N(R １４ ) ２ , —C(O) (3- to 6-membered carbocyclic or heterocyclic ring), —S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkylene) OR １４ , halogen, —CN, 3- to 6-membered carbocyclic or heterocyclic ring, 5- to 6-membered heteroaryl, and C １－６ alkyl, any C １－６ The alkyl, carbocycle, heterocycle, or heteroaryl is unsubstituted or has one or more R ２０ is replaced by Each R １２ But independently, C １－６ Alkyl, C ２－６ alkenyl, and H, and any C １－６ Alkyl or C ２－６ Alkenyl is unsubstituted or has one or more R １３ is replaced by Each R １３ But independently, -OR １４ , -CN, -N(R １４ ) ２ and halogen; Each R １４ But independently, C １－６ Alkyl, C ２－６ alkenyl, and H; Each R １５ are independently deuterium, halogen, -N(R １２ ) ２ , -CN, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R １３ is replaced by Each R ２０ are independently —OH, —OC １－６ Alkyl, -CN, -NH ２ , -NHC １－６ alkyl, and halogen; R ２７ is a 3- to 6-membered heterocycle containing one or more heteroatoms selected from N, O, and S, and the heterocycle is unsubstituted or contains one or more R ２８ is replaced by Each R ２８ But independently, C １－６ selected from alkyl and halogen; R ａ and R ｂ are each independently deuterium, halogen, C １－６ alkyl, 3- to 6-membered carbocyclic ring, —OR １２ and H; R ａ and R ｂ are optionally linked together to form a 3- to 6-membered carbocyclic or heterocyclic ring, and any C １－６ The alkyl or 3- to 6-membered carbocyclic or heterocyclic ring is unsubstituted or contains one or more R １３ The compound or a salt thereof, wherein the compound is substituted with

59. Formula III: 【Chemical 36】 or a salt thereof (e.g., a pharmaceutically acceptable salt), wherein R １ But, -OR ８ and 【Chemical 37】 is selected from R ２ and R ３ together with the nitrogen atom to which they are attached are unsubstituted or contain one or more R １１ and R １１ is replaced by R ４ is H, R ５ is halogen and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R １３ is replaced by R ６ is a monocyclic or bicyclic heteroaryl, and the heteroaryl is selected from one or more R １５ is replaced by R ７ is selected from halogens, R ８ is selected from heterocycle and alkylheterocycle, any heterocycle containing 4 to 8 members and is unsubstituted or contains one or more R ａ or R ｂ and the alkyl portion of any alkyl heterocycle is substituted with C １－６ alkyl, Each R １１ are independently deuterium, -OR １２ , =O, =N(R １４ ), —C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), —C(O)O(C １－６ alkyl), —C(O)N(R １４ ) ２ , —C(O) (3- to 6-membered carbocyclic or heterocyclic ring), —S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkylene) OR １４ , halogen, —CN, 3- to 6-membered carbocyclic or heterocyclic ring, 5- to 6-membered heteroaryl, and C １－６ alkyl, any C １－６ The alkyl, carbocycle, heterocycle, or heteroaryl is unsubstituted or has one or more R ２０ is replaced by Each R １２ But independently, C １－６ Alkyl, C ２－６ alkenyl, and H, and any C １－６ Alkyl or C ２－６ Alkenyl is unsubstituted or has one or more R １３ is replaced by Each R １３ But independently, -OR １４ , -CN, -N(R １４ ) ２ and halogen; Each R １４ But independently, C １－６ Alkyl, C ２－６ alkenyl, and H; Each R １５ are independently deuterium, halogen, -N(R １２ ) ２ , -CN, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R １３ is replaced by Each R ２０ are independently —OH, —OC １－６ Alkyl, -CN, -NH ２ , -NHC １－６ alkyl, and halogen; R ２７ is a 3- to 6-membered heterocycle containing one or more heteroatoms selected from N, O, and S, and the heterocycle is unsubstituted or contains one or more R ２８ is replaced by Each R ２８ But independently, C １－６ selected from alkyl and halogen; R ａ and R ｂ are each independently deuterium, halogen, C １－６ alkyl, 3- to 6-membered carbocyclic ring, —OR １２ and H; R ａ and R ｂ are optionally linked together to form a 3- to 6-membered carbocyclic or heterocyclic ring, and any C １－６ The alkyl or 3- to 6-membered carbocyclic or heterocyclic ring is unsubstituted or contains one or more R １３ The compound or a salt thereof, wherein the compound is substituted with

60. The compound has the formula III-a: 【Chemical 38】 or a salt thereof (e.g., a pharmaceutically acceptable salt).

61. R ２ and R ３ together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycle.

62. R ２ and R ３ together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycle containing one or two heteroatoms selected from O, S, and N.

63. R ２ and R ３ together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycle containing one or two heteroatoms selected from O, S, and N, and said heterocycle is １１ 63. The compound of claim 62, substituted with:

64. R ２ and R ３ together with the nitrogen atom to which they are attached, 0 to 4 R １１ 64. The compound of any one of claims 58 to 63, wherein the compound forms a pyrrolidine substituted with

65. R ２ and R ３ together with the nitrogen atom to which they are attached, 0 to 4 R １１ 64. The compound of any one of claims 58 to 63, which forms an azetidine substituted with

66. R ２ and R ３ together with the nitrogen atom to which they are attached, 0 to 4 R １１ 64. The compound of any one of claims 58 to 63, which forms a piperidine substituted with

67. R ２ and R ３ together with the nitrogen atom to which they are attached, 0 to 4 R １１ 64. The compound of any one of claims 58 to 63, which forms a piperazine substituted with

68. R ２ and R ３ together with the nitrogen atom to which they are attached, 0 to 4 R １１ 64. A compound according to any one of claims 58 to 63, which forms a morpholine or thiomorpholine substituted with

69. R ２ and R ３ together with the nitrogen atom to which they are attached form a 7-membered heterocycle containing 1 to 3 heteroatoms selected from O, S, and N.

70. R ２ and R ３ together with the nitrogen atom to which they are attached, one or more R １１ and forming a 4- to 7-membered heterocyclic ring substituted with at least one R １１ But, -OR １２ and C substituted with —OH １－６ 70. The compound of any one of claims 58 to 69, wherein the group is selected from alkyl.

71. R ２ and R ３ together with the nitrogen atom to which they are attached, one or more R １１ and forming a 4- to 7-membered heterocyclic ring substituted with at least one R １１ is unsubstituted C １－６ The compound of any one of claims 58 to 70, which is alkyl.

72. R ２ and R ３ together with the nitrogen atom to which they are attached form an unsubstituted 4- to 7-membered heterocycle.

73. R ２ and R ３ together with the nitrogen atom to which they are attached form a bridged heterocycle.

74. R ２ and R ３ together with the nitrogen atom to which they are attached form a 7-9 membered bridged heterocycle containing one or two heteroatoms selected from O, S, and N.

75. R ２ and R ３ together with the nitrogen atom to which they are attached form a 7- to 9-membered bridged heterocycle containing one or two heteroatoms selected from O, S, and N, and the bridged heterocycle is １１ 75. The compound of claim 74, substituted with:

76. R ２ and R ３ together with the nitrogen atom to which they are attached, 0 to 4 R １１ 76. The compound of any one of claims 73 to 75, which forms a bridged piperidine substituted with

77. R ２ and R ３ together with the nitrogen atom to which they are attached, 0 to 4 R １１ 76. The compound of any one of claims 73 to 75, which forms a piperazine substituted with

78. R ２ and R ３ together with the nitrogen atom to which they are attached, 0 to 4 R １１ 76. A compound according to any one of claims 73 to 75, which forms a bridged morpholine or thiomorpholine substituted with

79. R ２ and R ３ together with the nitrogen atom to which they are attached, one or more R １１ and forming a bridged heterocycle substituted with at least one R １１ But, -OR １２ and C substituted with —OH １－６ 79. The compound of any one of claims 73 to 78, wherein the compound is selected from alkyl.

80. R ２ and R ３ together with the nitrogen atom to which they are attached, one or more R １１ and forming a bridged heterocycle substituted with at least one R １１ is unsubstituted C １－６ 80. The compound of any one of claims 73 to 79, which is alkyl.

81. R ２ and R ３ together with the nitrogen atom to which they are attached form an unsubstituted bridged heterocycle.

82. R ２ and R ３ together with the nitrogen atom to which they are attached form a spiro ring.

83. R ２ and R ３ together with the nitrogen atom to which they are attached form a fused ring system comprising at least two rings.

84. R2 and R ３ together with the nitrogen atom to which they are attached, one or more R １１ and one or more of R １１ are independently deuterium, -OR １２ , =O, =N(R １４ ), —C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), —C(O)N(R １４ ) ２ , -S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkylene) OR １４ , halogen, and unsubstituted or one or more R ２０ C substituted with １－６ 84. The compound of any one of claims 58 to 71, 73 to 80, 82, and 83, wherein the alkyl is selected from the group consisting of:

85. R ２ and R ３ together with the nitrogen atom to which they are attached, one or more R １１ and one or more of R １１ But independently, -OR １２ , -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), —C(O)N(R １４ ) ２ , -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkylene) OR １４ , halogen, and unsubstituted or one or more R ２０ C substituted with １－６ 85. The compound of claim 84, wherein the alkyl is selected from:

86. R ２ and R ３ together with the nitrogen atoms to which they are attached. 【Chemical Formula 39】 【Chemistry 40】 【Chemistry 41】 【Chemistry 42】 【Chemistry 43】 and forming a structure selected from any of the following: １１ 86. The compound of any one of claims 58 to 85, further substituted with:

87. The compound has the formula IIIA: 【Chemical 44】 or a salt (e.g., a pharmaceutically acceptable salt) thereof, wherein Each R ｅ are independently deuterium, hydrogen, -OR １２ , =O, =N(R １４ ), —C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), —C(O)N(R １４ ) ２ , -S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkylene) OR １４ , halogens, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R ２０ is replaced by R ｆ and R ｇ are each independently hydrogen, deuterium, or —OR １２ , =O, -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), -S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkylene) OR １４ , halogens, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R ２０ is replaced by, or R ｆ and R ｇ are linked together and are unsubstituted or -OR １２ , =O, -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), -S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkylene) OR １４ , halogens, and C １－６ alkyl, forming a 3- to 6-membered carbocyclic or heterocyclic ring substituted with one or more substituents selected from any C １－６ The alkyl is unsubstituted or has one or more R ２０ 87. The compound of any one of claims 58 to 86, substituted with:

88. Each R ｅ , R ｆ , and R ｇ are independently hydrogen, -OR １２ , =O, -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), -S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkylene) OR １４ , halogens, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R ２０ 88. The compound of claim 87, substituted with:

89. Each R ｅ , R ｆ , and R ｇ are independently hydrogen, -OR １２ , -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), halogen, and unsubstituted or one or more R ２０ C substituted with １－６ 88. The compound of claim 87, wherein said alkyl is selected from:

90. Each R ｅ The compound of any one of claims 87 to 89, wherein is hydrogen.

91. R ｆ and R ｇ are linked together and are unsubstituted or -OR １２ , =O, -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), -S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkylene) OR １４ , halogens, and C １－６ alkyl, forming a 3- to 6-membered carbocyclic or heterocyclic ring substituted with one or more substituents selected from any C １－６ The alkyl is unsubstituted or has one or more R ２０ 91. The compound of any one of claims 87 to 90, substituted with:

92. R ｆ and R ｇ are linked together to form an unsubstituted 3- to 6-membered carbocyclic or heterocyclic ring.

93. R ｆ and R ｇ are linked together to form -OR １２ , =O, -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), -S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkylene) OR １４ , halogens, and C １－６ alkyl, forming a 3- to 6-membered carbocyclic or heterocyclic ring substituted with one or more substituents selected from any C １－６ The alkyl is unsubstituted or has one or more R ２０ 92. The compound of claim 91 , substituted with:

94. R ｆ and R ｇ are linked together and are unsubstituted or -OR １２ , =O, -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), -S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl) OR １４ , halogens, and C １－６ alkyl, forming a 3- to 6-membered carbocyclic ring substituted with one or more substituents selected from any C １－６ The alkyl is unsubstituted or has one or more R ２０ 92. The compound of claim 91 , substituted with:

95. R ｆ and R ｇ are linked together and are unsubstituted or -OR １２ , =O, -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), -S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkylene) OR １４ , halogens, and C １－６ alkyl, forming a cyclopropane substituted with one or more substituents selected from any C １－６ The alkyl is unsubstituted or has one or more R ２０ 95. The compound of claim 94, substituted with:

96. R ｆ and R ｇ are linked together and are unsubstituted or -OR １２ , =O, -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), -S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkylene) OR １４ , halogens, and C １－６ alkyl, and any C １－６ The alkyl may be unsubstituted or may have one or more R ２０ 92. The compound of claim 91 , substituted with:

97. R ｆ and R ｇ are linked together and are unsubstituted or -OR １２ , =O, -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), -S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkylene) OR １４ , halogens, and C １－６ alkyl, forming an oxetane substituted with one or more substituents selected from any C １－６ The alkyl is unsubstituted or has one or more R ２０ 97. The compound of claim 96, substituted with:

98. The compound has the formula IIIB: 【Chemistry 45】 or a salt (e.g., a pharmaceutically acceptable salt) thereof, wherein Each R ｅ are independently hydrogen, deuterium, -OR １２ , =O, =N(R １４ ), —C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), —C(O)N(R １４ ) ２ , -S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkylene) OR １４ , halogens, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R ２０ 87. The compound according to any one of claims 58 to 86, or a salt thereof, substituted with:

99. Each R ｅ 99. The compound of claim 98, wherein is hydrogen.

100. The compound has the formula IIIC: 【Chemistry 46】 or a salt (e.g., a pharmaceutically acceptable salt) thereof, wherein Each R ｅ are independently hydrogen, deuterium, -OR １２ , =O, =N(R １４ ), —C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), —C(O)N(R １４ ) ２ , -S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkylene) OR １４ , halogen, 5- to 6-membered heteroaryl, and C １－６ alkyl, any C １－６ The alkyl or heteroaryl may be unsubstituted or may be substituted with one or more R ２０ 87. The compound of any one of claims 58 to 86, substituted with:

101. Each R ｅ is hydrogen.

102. The compound has the formula IIIC1: 【Chemistry 47】 or a salt (e.g., a pharmaceutically acceptable salt) thereof, wherein Each R ｅ are independently hydrogen, deuterium, -OR １２ , =O, =N(R １４ ), —C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), —C(O)N(R １４ ) ２ , -S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkylene) OR １４ , halogens, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R ２０ is replaced by R ｆ , R ｇ , and R ｈ are each independently hydrogen, deuterium, or —OR １２ , =O, -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), -S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkylene) OR １４ , halogens, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R ２０ and optionally, (i) R ｆ and R ｇ are linked together and are unsubstituted or -OR １２ , =O, -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), -S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkylene) OR １４ , halogens, and C １－６ alkyl, forming a 3- to 6-membered carbocyclic or heterocyclic ring or a 5- to 6-membered heteroaryl, substituted with one or more substituents selected from any C １－６ The alkyl is unsubstituted or has one or more R ２０ is replaced by, or (ii) R ｇ and R ｈ are linked together and are unsubstituted or -OR １２ , =O, -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), -S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkylene) OR １４ , halogens, and C １－６ alkyl, forming a 3- to 6-membered carbocyclic or heterocyclic ring or a 5- to 6-membered heteroaryl, substituted with one or more substituents selected from any C １－６ The alkyl is unsubstituted or has one or more R ２０ 87. The compound of any one of claims 58 to 86, substituted with:

103. Each R ｅ 103. The compound of claim 102, wherein is hydrogen.

104. R ｆ and R ｇ are linked together and are unsubstituted or -OR １２ , =O, -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), -S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkylene) OR １４ , halogens, and C １－６ alkyl, forming a 3- to 6-membered carbocyclic or heterocyclic ring substituted with one or more substituents selected from any C １－６ The alkyl is unsubstituted or has one or more R ２０ 104. The compound of claim 102 or 103, substituted with:

105. R ｆ and R ｇ are linked together and are unsubstituted or -OR １２ , =O, -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), -S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl) OR １４ , halogens, and C １－６ alkyl, forming a 3- to 6-membered carbocyclic ring substituted with one or more substituents selected from any C １－６ The alkyl is unsubstituted or has one or more R ２０ 105. The compound of claim 104, substituted with:

106. R ｆ and R ｇ are linked together and are unsubstituted or -OR １２ , =O, -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), -S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkylene) OR １４ , halogens, and C １－６ alkyl, and any C １－６ The alkyl may be unsubstituted or may have one or more R ２０ 105. The compound of claim 104, substituted with:

107. R ｇ and R ｈ are linked together and are unsubstituted or -OR １２ , =O, -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), -S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkylene) OR １４ , halogens, and C １－６ alkyl, forming a 3- to 6-membered carbocyclic or heterocyclic ring substituted with one or more substituents selected from any C １－６ The alkyl is unsubstituted or has one or more R ２０ 104. The compound of claim 102 or 103, substituted with:

108. R ｇ and R ｈ are linked together and are unsubstituted or -OR １２ , =O, -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), -S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkylene) OR １４ , halogens, and C １－６ alkyl, forming a 3- to 6-membered carbocyclic ring substituted with one or more substituents selected from any C １－６ The alkyl is unsubstituted or has one or more R ２０ 108. The compound of claim 107, substituted with:

109. R ｇ and R ｈ are linked together and are unsubstituted or -OR １２ , =O, -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), -S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkylene) OR １４ , halogens, and C １－６ alkyl, and any C １－６ The alkyl is unsubstituted or has one or more R ２０ 108. The compound of claim 107, substituted with:

110. The compound has the formula IIID: 【Chemistry 48】 or a salt (e.g., a pharmaceutically acceptable salt) thereof, wherein Q is CR ｈ R ｊ , N.R. ｇ , O, S, and SO ２ is selected from Each R ｅ and R ｆ But independently, R １１ and hydrogen; (i) R ｅ and R ｆ can optionally be linked together to form a 4- to 6-membered ring; (ii) a first R connected to an adjacent atom ｆ and the second R ｆ can optionally be linked together to form a 3- to 5-membered ring; (iii) a first R connected to an adjacent atom ｅ and the second R ｅ can optionally be linked together to form a 3- to 5-membered ring; or (iv) the first R attached to the same atom ｆ and the second R ｆ can optionally be linked together to form a 3- to 5-membered ring; One or more R ｅ and / or one or more R ｆ Any ring formed by is unsubstituted or contains one or more R １１ is replaced by R ｇ exists, then R １１ and R ｈ and R ｊ is, if present, independently R １１ and hydrogen, or optionally linked together, are unsubstituted or are selected from -OR １２ , =O, =N(R １４ ), —C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), —C(O)N(R １４ ) ２ , -S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkylene) OR １４ , halogens, and C １－６ forming a 3- to 4-membered carbocyclic or heterocyclic ring substituted with one or more substituents selected from alkyl, any C １－６ The alkyl is unsubstituted or has one or more R ２０ or substituted with R ｈ and R ｅ Or R ｈ and R ｆ are optionally linked together and are unsubstituted or are one or more R １１ The compound according to any one of claims 58 to 86, which forms a 3- to 6-membered ring substituted with

111. Q is NR ｇ and R ｇ But -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), -S(O) ２ (C １－６ alkyl), and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R ２０ 111. The compound of claim 110, substituted with:

112. 111. The compound of claim 110, wherein Q is O.

113. The compound has the formula IIIE: 【Chemistry 49】 or a salt thereof (e.g., a pharmaceutically acceptable salt).

114. R ｅ and R ｆ are linked together to form a 4- to 6-membered ring.

115. R ｈ and R ｊ But independently, R １１ and hydrogen.

116. R ｈ and / or R ｊ is deuterium, -OR １２ , =O, -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), -S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkylene) OR １４ , halogens, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R ２０ 116. The compound of any one of claims 113 to 115, substituted with

117. R ｈ and R ｊ The compound of any one of claims 113 to 115, wherein each is hydrogen.

118. R ｈ and R ｊ are linked together to form a 3- to 4-membered carbocyclic or heterocyclic ring.

119. R ｈ and R ｊ are linked together to form an unsubstituted 3- to 4-membered carbocyclic or heterocyclic ring.

120. R ｈ and R ｊ are connected together, -OR １２ , =O, -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), -S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkylene) OR １４ , halogen, and unsubstituted or one or more R ２０ C substituted with １－６ 119. The compound of claim 118, which forms a 3-4 membered carbocyclic or heterocyclic ring substituted with one or more substituents selected from alkyl.

121. One or more R ｅ and / or one or more R ｆ 121. The compound of any one of claims 118 to 120, wherein combinations of s are not linked together to form a ring.

122. R ｅ and R ｆ The compound according to any one of claims 118 to 121, wherein is hydrogen.

123. The compound has the formula IIIF, IIIG, or IIIH: 【Chemistry 50】 or a salt thereof (e.g., a pharmaceutically acceptable salt).

124. Each R ｅ and R ｆ But independently, R １１ and hydrogen.

125. R ｅ and R ｆ are linked together to form a 4- to 6-membered ring.

126. The compound has the formula IIIJ: 【Chemistry 51】 or a salt thereof (e.g., a pharmaceutically acceptable salt).

127. Each R ｅ and R ｆ But independently, R １１ and hydrogen.

128. R ｅ and R ｆ are linked together to form a 4- to 6-membered ring.

129. The compound has the formula IIIK, IIIL, IIIM, IIIN, IIIP, IIIQ, or IIIR: 【Chemistry 52】 or a salt (e.g., a pharmaceutically acceptable salt) according to the formula: Each R ｅ and R ｆ But independently, R １１ and hydrogen; R ｇ exists, then R １１ and R ｈ and R ｊ are present, each independently R １１ and hydrogen.

130. Q is CR ｈ R ｊ , N.R. ｇ 130. The compound of claim 129, wherein the compound is selected from:

131. Q is CR ｈ R ｊ 131. The compound of claim 130, wherein:

132. R ｈ and R ｊ are present, each independently R １１ and hydrogen, and each R １１ are independently deuterium, -OR １２ , =O, =N(R １４ ), —C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), —C(O)N(R １４ ) ２ , —C(O) (3- to 6-membered carbocyclic or heterocyclic ring), —S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkylene) OR １４ , halogen, —CN, 3- to 6-membered carbocyclic or heterocyclic ring, and C １－６ alkyl, any C １－６ The alkyl, carbocycle, or heterocycle is unsubstituted or is substituted with one or more R ２０ 132. The compound of claim 131 substituted with:

133. R ｈ and / or R ｊ each independently, if present, represents -OR １２ , =O, =N(R １４ ), —C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), —C(O)N(R １４ ) ２ , -S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkylene) OR １４ , halogens, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R ２０ 133. The compound of claim 132, substituted with:

134. R ｈ and R ｊ 132. The compound of claim 131, wherein each is hydrogen.

135. Q is NR ｇ 131. The compound of claim 130, wherein:

136. R ｇ But -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), —C(O)N(R １４ ) ２ , and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R ２０ 136. The compound of claim 135, substituted with:

137. 131. The compound of claim 130, wherein Q is O.

138. Q is S or SO ２ 130. The compound of claim 129, wherein:

139. Each R ｅ and R ｆ But independently, R １１ and hydrogen, and each R １１ are independently deuterium, -OR １２ , =O, =N(R １４ ), —C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), —C(O)N(R １４ ) ２ , —C(O) (3- to 6-membered carbocyclic or heterocyclic ring), —S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkylene) OR １４ , halogen, —CN, 3- to 6-membered carbocyclic or heterocyclic ring, and C １－６ alkyl, any C １－６ The alkyl, carbocycle, or heterocycle is unsubstituted or is substituted with one or more R ２０ 139. The compound of any one of claims 129 to 138, substituted with:

140. Each R ｅ and / or R ｆ are independently deuterium, -OR １２ , =O, =N(R １４ ), —C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), —C(O)N(R １４ ) ２ , -S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkylene) OR １４ , halogen, and unsubstituted or one or more R ２０ C substituted with １－６ 140. The compound of claim 139, wherein the alkyl is selected from alkyl.

141. Each R ｅ and R ｆ is hydrogen.

142. The compound has the formula IIIS: 【Chemistry 53】 or a salt (e.g., a pharmaceutically acceptable salt) according to the formula: Q １ But NR ｇ１ , O., S.R. ｈ ２ , and C.R. ｉ R ｊ is selected from Q ２ But NR ｇ２ , O., S.R. ｈ ２ , and C.R. ｉ R ｊ is selected from R ｇ１ and R ｇ２ is, if present, independently hydrogen, —C(O)(C １－６ alkyl), and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R ２０ is replaced by Each R ｈ is absent or, if present, independently represents ═O, ═N(R １４ ), and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R ２０ is replaced by Each R ｉ and R ｊ are, if present, independently hydrogen, deuterium, -OR １２ , =O, =N(R １４ ), —C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), —C(O)N(R １４ ) ２ , -S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkylene) OR １４ , halogens, and C １－６ alkyl, and any CC １－６ The alkyl is unsubstituted or has one or more R ２０ is replaced by Each R ｅ１ , R ｅ２ , R ｅ３ , and R ｅ４ are independently hydrogen, deuterium, -OR １２ , =O, =N(R １４ ), —C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), —C(O)N(R １４ ) ２ , -S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkylene) OR １４ , halogens, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R ２０ is replaced by During the ceremony, (i) R ｅ２ and R ｅ３ are optionally linked together to form a 5- or 6-membered ring; or (ii) Q ２ NR ｇ２ , R ｇ２ and R ｅ３ together with the atoms to which they are attached, optionally joined together, may be unsubstituted or may be one or more R １１ and each R forms a 5-membered heterocycle or heteroaryl substituted with １１ are independently deuterium, -OR １２ , =O, =N(R １４ ), —C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), —C(O)N(R １４ ) ２ , -S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkylene) OR １４ , halogens, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R ２０ 87. The compound of any one of claims 58 to 86, substituted with:

143. Q １ and Q ２ However, each ｉ R ｊ 143. The compound of claim 142, wherein:

144. At least one R ｅ１ , R ｅ２ , R ｅ３ , or R ｅ４ But, -OR １２ , =O, =N(R １４ ), —C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), —C(O)N(R １４ ) ２ , -S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkylene) OR １４ , halogens, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R ２０ 144. The compound of claim 143, substituted with:

145. Each R ｅ１ , R ｅ２ , R ｅ３ , and R ｅ４ is hydrogen.

146. R ｅ２ and R ｅ３ are linked together to form a 5- to 6-membered ring.

147. Q １ But, CR ｉ R ｊ and Q ２ But NR ｇ２ 143. The compound of claim 142, wherein:

148. R ｇ２ and R ｅ３ are joined together with the atoms to which they are attached and are unsubstituted or are one or more R １１ 148. The compound of claim 147, wherein the compound forms a 5-membered heterocycle or heteroaryl substituted with:

149. R ｇ２ is hydrogen, -C(O)(C １－６ alkyl), and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R ２０ 148. The compound of claim 147, substituted with:

150. Q ２ But, CR ｉ R ｊ and Q １ But NR ｇ１ 143. The compound of claim 142, wherein:

151. R ｇ１ is hydrogen, -C(O)(C １－６ alkyl), and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R ２０ 151. The compound of claim 150, substituted with:

152. Each R ｅ１ , R ｅ２ , R ｅ３ , and R ｅ４ 152. The compound of claim 150 or 151, wherein is hydrogen.

153. (i) Q １ But, CR ｉ R ｊ and Q ２ is O, or (ii) Q ２ But, CR ｉ R ｊ and Q １ is O.

154. Each R ｅ１ , R ｅ２ , R ｅ３ , and R ｅ４ is hydrogen.

155. R ｅ２ and R ｅ３ are linked together to form a 5- to 6-membered ring.

156. (i) Q １ But, CR ｉ R ｊ and Q ２ But, SR ｈ ２ or (ii) Q ２ But, CR ｉ R ｊ and Q １ But, SR ｈ ２ 143. The compound of claim 142, wherein:

157. Each R ｅ１ , R ｅ２ , R ｅ３ , and R ｅ４ is hydrogen.

158. R ｅ２ and R ｅ３ are linked together to form a 5- to 6-membered ring.

159. Each R ｈ The compound of any one of claims 156 to 158, wherein is =O.

160. Each R ｉ and R ｊ The compound of any one of claims 142 to 159, wherein is hydrogen.

161. (i) NR ｇ１ and Q ２ But, SR ｈ ２ or (ii) NR ｇ２ and Q １ But, SR ｈ ２ 143. The compound of claim 142, wherein:

162. Each R ｅ１ , R ｅ２ , R ｅ３ , and R ｅ４ 162. The compound of claim 161, wherein is hydrogen.

163. R ｅ２ and R ｅ３ are linked together to form a 5- to 6-membered ring.

164. Each R ｈ The compound according to any one of claims 161 to 163, wherein is =O.

165. The compound has the formula IIIT: 【Chemical 54】 or a salt (e.g., a pharmaceutically acceptable salt) according to the formula: The dashed line is Q １ , Q ２ , Q ３ , and Q ４ represents a single or double bond so that the ring containing Q １ , Q ２ , Q ３ , and Q ４ is independently selected from C, N, O, and S; Q １ , Q ２ , Q ３ , and Q ４ is N; Each R ｅ and R ｆ But independently, R １１ and hydrogen; Each R ｇ is not present or independently R １１ and hydrogen.

166. Q １ The compound of claim 165, wherein is C.

167. Q ２ is C and Q ３ is N and Q ４ The compound of claim 166, wherein is N.

168. Q １ is N.

169. Q ２ is N and Q ３ and Q ４ The compound of claim 168, wherein is C.

170. Q ２ and Q ３ is N and Q ４ The compound of claim 168, wherein is C.

171. Q ３ and Q ４ is N and Q ２ The compound of claim 168, wherein is C.

172. Q ２ and Q ４ is N and Q ３ The compound of claim 168, wherein is C.

173. The following formula: 【Chemistry 55】 But the following: 【Chemical 56】 166. The compound of claim 165, having a structure selected from:

174. Each R ｇ is hydrogen or absent.

175. R ６ But there are one or more R １５ 175. The compound of any one of claims 58 to 174, which is a bicyclic heteroaryl substituted with

176. R ６ but, 【Chemical 57】 is selected from: X is selected from N and C—CN; Y is selected from O and S; R ２３ But -N(R １２ ) ２ , C １－６ Alkyl, and C １－６ Alkyl-N(R １４ ) ２ and any C １－６ The alkyl is unsubstituted or has one or more R １３ is replaced by R ２４ , R ２５ , and R ２６ are independently H, deuterium, halogen, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R １３ 176. The compound of claim 175, substituted with:

177. R ６ but, 【Chemistry 58】 is selected from Any of them has one or more R １５ 177. The compound of claim 175 or 176, substituted with:

178. R ６ but, 【Chemical 59】 178. The compound according to any one of claims 175 to 177, selected from:

179. R ６ but, 【Chemistry 60】 179. The compound according to any one of claims 175 to 178, selected from:

180. R ６ But there are one or more R １５ 175. The compound of any one of claims 58 to 174, which is a monocyclic heteroaryl substituted with

181. R ６ But there are one or more R １５ 181. The compound of claim 180, which is a pyridine substituted with:

182. R ６ But the structure 【Hua 61】 182. The compound of claim 181, having the formula:

183. R １ But, -OR ８ The compound according to any one of claims 58 to 182, selected from:

184. R １ but, 【Hua 62】 R ａ１ , R ａ２ , R ｂ１ , and R ｂ２ are each independently deuterium, halogen, C １－６ Alkyl, -OR １２ and H; R ａ２ and R ｂ２ can optionally be linked together to form a 3- to 6-membered carbocyclic ring, and any C １－６ The alkyl or 3- to 6-membered carbocyclic ring is unsubstituted or has one or more R １３ 184. The compound of claim 183, substituted with:

185. R １ but, 【Chemistry 63】 185. The compound of claim 184, selected from:

186. R １ but, 【Hua 64】 In the formula, R ａ and R ｂ are each independently a halogen, C １－６ Alkyl, -OR １２ , and H, and any C １－６ Alkyl is unsubstituted or has one or more R １３ 184. The compound of claim 183, substituted with:

187. R １ but, 【Chemistry 65】 187. The compound of claim 186, selected from:

188. R １ but, 【Hua 66】 is selected from In the formula, each R ａ and R ｂ are independently halogen, C １－６ Alkyl, -OR １２ and H; R ｃ But C １－６ alkyl, and R ａ and R ｂ or R ｃ are optionally linked together to form a 3- to 6-membered carbocyclic or heterocyclic ring, and any C １－６ The alkyl or 3- to 6-membered carbocyclic or heterocyclic ring is unsubstituted or contains one or more R １３ 184. The compound of claim 183, substituted with:

189. R １ but, 【Hua 67】 189. The compound of claim 188, selected from:

190. R １ but, 【Chemistry 68】 The compound according to any one of claims 58 to 182, selected from:

191. Each R １１ But independently, -OR １２ , =O, -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene) OR １４ , -C(O)(C １－６ alkyl), -S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkylene) OR １４ , halogen, and unsubstituted or one or more R ２０ C substituted with １－６ 191. The compound of any one of claims 58 to 190, wherein the compound is selected from alkyl.

192. R ５ 192. The compound of any one of claims 58 to 191, wherein is halogen (for example F or Cl).

193. R ５ is unsubstituted or is substituted with one or more R １３ C substituted with １－６ 192. The compound of any one of claims 58 to 191, wherein the compound is selected from alkyl.

194. R ５ is substituted with one or more halogens or —CN １－６ 194. The compound of claim 193, wherein said alkyl is selected from:

195. R ５ But, -CF ２ H, -CF ３ , -CH ２ CN, and -CH ２ CH ３ 195. The compound of claim 194, selected from:

196. R ５ But, -CF ３ 196. The compound of claim 195,

197. 200. The compound of any one of claims 58 to 196, wherein the compound is not a compound included in Table 2.

198. Compounds of Formula I: 【Chemical Formula 69】 or a salt thereof (e.g., a pharmaceutically acceptable salt), wherein: R １ But, -OR ８ and 【Chemistry 70】 is selected from R ２ However, H and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R １３ is replaced by R ３ is unsubstituted or is substituted with one or more R １０ and selected from 3- to 11-membered carbocyclic rings substituted with R ４ is H, R ５ is H, halogen, -CN, -OR １２ , 3- to 6-membered heterocycle, 5- to 6-membered heteroaryl, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R １３ is replaced by R ６ But there are one or more R １５ is a bicyclic heteroaryl substituted with R ７ is selected from halogen, —CN, and H; R ８ is selected from heterocycle and alkylheterocycle, any heterocycle containing 4 to 8 members and is unsubstituted or contains one or more R ａ or R ｂ and the alkyl portion of any alkyl heterocycle is substituted with C １－６ alkyl, Each R １０ But independently, -OR １２ , -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene)OH, —C(O)(C １－６ alkyl), —C(O)N(R １４ ) ２ , -S(O) ２ (C １－６ alkyl), halogen, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R ２０ is replaced by Each R １２ But independently, C １－６ Alkyl, C ２－６ alkenyl, and H, and any C １－６ Alkyl or C ２－６ Alkenyl is unsubstituted or has one or more R １３ is replaced by Each R １３ But independently, -OR １４ , -CN, -N(R １４ ) ２ and halogen; Each R １４ But independently, C １－６ Alkyl, C ２－６ alkenyl, and H; Each R １５ are independently deuterium, halogen, -N(R １２ ) ２ , -CN, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R １３ is replaced by Each R ２０ are independently —OH, —OC １－６ Alkyl, —CN, —NH ２ , -NHC １－６ alkyl, and halogen; R ２７ is a 3- to 6-membered heterocycle containing one or more heteroatoms selected from N, O, and S, and the heterocycle is unsubstituted or contains one or more R ２８ is replaced by Each R ２８ But independently, C １－６ selected from alkyl and halogen; R ａ and R ｂ are each independently deuterium, halogen, C １－６ alkyl, 3- to 6-membered carbocyclic ring, —OR １２ and H; R ａ and R ｂ are optionally linked together to form a 3- to 6-membered carbocyclic or heterocyclic ring, and any C １－６ The alkyl or 3- to 6-membered carbocyclic or heterocyclic ring is unsubstituted or contains one or more R １３ The compound or a salt thereof, wherein the compound is substituted with

199. The compound has the formula Ia: 【Chemical 71】 or a salt thereof (e.g., a pharmaceutically acceptable salt).

200. R ３ is unsubstituted or is substituted with one or more R １０ 200. The compound of claim 198 or 199, which is a 3- to 6-membered heterocycle substituted with

201. R ３ But 1 to 4 R １０ The compound of claim 200, wherein the ring is a 3- to 6-membered carbocyclic ring substituted with

202. R ３ But 0 to 4 R １０ 201. The compound of claim 200, which is a cyclopropane substituted with:

203. R ３ But 0 to 4 R １０ 201. The compound of claim 200, which is a cyclobutane substituted with:

204. R ３ But 0 to 4 R １０ 201. The compound of claim 200, which is a cyclopentane substituted with:

205. R ３ But 0 to 4 R １０ 201. The compound of claim 200, which is a cyclohexane substituted with:

206. R ３ is unsubstituted or is substituted with one or more R １０ 201. The compound of any one of claims 198 to 200, which is a spiro ring substituted with

207. R ３ is unsubstituted or is substituted with one or more R １０ 201. The compound of any one of claims 198 to 200, which is a bridged carbocycle substituted with

208. R ３ But there are one or more R １０ and at least one R １０ But, -OR １２ and C substituted with —OH １－６ 208. The compound of any one of claims 198 to 207, wherein the compound is selected from alkyl.

209. R ３ But there are one or more R １０ and at least one R １０ is unsubstituted C １－６ The compound of any one of claims 198 to 208, which is alkyl.

210. The compound has formula IA, IB, IC, ID, IE, or IF: 【Chemical Formula 72】 or a salt (e.g., a pharmaceutically acceptable salt) thereof, wherein Each R ｄ are independently H, -OR １２ , -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene)OH, —C(O)(C １－６ alkyl), —C(O)N(R １４ ) ２ , -S(O) ２ (C １－６ alkyl), halogen, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R ２０ 210. The compound of any one of claims 198 to 209, substituted with:

211. At least one R ｄ But, -OR １２ , -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene)OH, —C(O)(C １－６ alkyl), —C(O)N(R １４ ) ２ , -S(O) ２ (C １－６ alkyl), halogen, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R ２０ 211. The compound of claim 210, substituted with:

212. At least one R ｄ But OR １２ and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R ２０ 212. The compound of claim 211, substituted with:

213. R ６ but, 【Chemical Formula 73】 is selected from: X is selected from N and C—CN; Y is selected from O and S; R ２３ But -N(R １２ ) ２ , C １－６ Alkyl, and C １－６ Alkyl-N(R １４ ) ２ and any C １－６ The alkyl is unsubstituted or has one or more R １３ is replaced by R ２４ , R ２５ , and R ２６ are independently H, deuterium, halogen, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R １３ 213. The compound of any one of claims 198 to 212, substituted with:

214. R ６ but, 【Chemical 74】 is selected from Any of them has one or more R １５ 214. The compound of any one of claims 198 to 213, substituted with:

215. R ６ but, 【Chemistry 75】 The compound according to any one of claims 198 to 214, selected from:

216. R ６ but, 【Chemical Formula 76】 The compound according to any one of claims 198 to 215, selected from:

217. The compound has the formula IA1, IB1, IC1, ID1, IE1, or IF1: 【Chemical Formula 77】 or a salt (e.g., a pharmaceutically acceptable salt) thereof, wherein Each R ｄ are independently H, -OR １２ , -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene)OH, —C(O)(C １－６ alkyl), —C(O)N(R １４ ) ２ , -S(O) ２ (C １－６ alkyl), halogen, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R ２０ is replaced by X is selected from N and C—CN; Y is selected from O and S; R ２３ But -N(R １２ ) ２ , C １－６ Alkyl, and C １－６ Alkyl-N(R １４ ) ２ and any C １－６ The alkyl is unsubstituted or has one or more R １３ is replaced by R ２４ , R ２５ , and R ２６ are independently H, deuterium, halogen, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R １３ 217. The compound of any one of claims 198 to 216, substituted with:

218. X is C—CN, Y is S, and R ２３ But -N(R １２ ) ２ The compound of claim 217, wherein:

219. R ２４ , R ２５ , and R ２６ 219. The compound of claim 217 or 218, wherein one or more of is halogen (e.g., F).

220. R １ But, -OR ８ 220. The compound according to any one of claims 198 to 219, selected from:

221. R １ but, 【Chemical 78】 In the formula, R ａ and R ｂ are each independently a halogen, C １－６ Alkyl, -OR １２ , and H, and any C １－６ Alkyl is unsubstituted or has one or more R １３ 221. The compound of claim 220, substituted with:

222. R １ but, 【Chemical 79】 222. The compound of claim 221, selected from:

223. R １ but, 【Chemistry 80】 is selected from In the formula, each R ａ and R ｂ are independently halogen, C １－６ Alkyl, -OR １２ and H; R ｃ But C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R １３ is substituted with R ａ and R ｂ or R ｃ are optionally linked together to form a 3- to 6-membered carbocyclic or heterocyclic ring.

224. R １ but, 【Chemistry 81】 224. The compound of claim 223, selected from:

225. R １ but, 【Chemistry 82】 220. The compound according to any one of claims 198 to 219, selected from:

226. The compound has formula IA2, IB2, IC2, ID2, IE2, or IF2: 【Chemistry 83】 or a salt (e.g., a pharmaceutically acceptable salt) thereof, wherein R ａ and R ｂ each independently represents a halogen, C １－６ Alkyl, -OR １２ , and H, and any C １－６ The alkyl is unsubstituted or has one or more R １３ is replaced by Each R ｄ are independently H, -OR １２ , -C(O)(C １－６ alkylene)CN, -C(O)(C １－６ alkylene)OH, —C(O)(C １－６ alkyl), —C(O)N(R １４ ) ２ , -S(O) ２ (C １－６ alkyl), halogen, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R ２０ is replaced by X is selected from N and C—CN; Y is selected from O and S; R ２３ But -N(R １２ ) ２ , C １－６ Alkyl, and C １－６ Alkyl-N(R １４ ) ２ and any C １－６ The alkyl is unsubstituted or has one or more R １３ is replaced by R ２４ , R ２５ , and R ２６ are independently H, deuterium, halogen, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R １３ 224. The compound of claim 223, selected from:

227. R ａ The compound of claim 226, wherein is halogen (e.g., F).

228. R ｂ The compound of claim 226 or 227, wherein is H.

229. X is C—CN, Y is S, and R ２３ But -N(R １２ ) ２ The compound according to any one of claims 226 to 228,

230. R ２４ , R ２５ , and R ２６ 230. The compound of any one of claims 226 to 229, wherein one or more of: is halogen (e.g., F).

231. R ２ The compound of any one of claims 198 to 230, wherein

232. R ２ is unsubstituted or is substituted with one or more R １３ C substituted with １－６ 231. The compound of any one of claims 198 to 230, wherein the compound is selected from alkyl.

233. R ２ But C １－２ 233. The compound of claim 232, wherein said alkyl is selected from:

234. R ５ The compound of any one of claims 198 to 223, wherein is H.

235. R ５ is halogen (e.g., F or Cl).

236. R ５ is unsubstituted or is substituted with one or more R １３ C substituted with １－６ 224. The compound of any one of claims 198 to 223, wherein the compound is selected from alkyl.

237. R ５ is substituted with one or more halogens or —CN １－６ 237. The compound of claim 236, wherein said alkyl is selected from:

238. R ５ But, -CF ２ H, -CF ３ , -CH ２ CN, and -CH ２ CH ３ 238. The compound of claim 237, selected from:

239. R ５ But, -CF ３ The compound of claim 238, wherein:

240. R ７ The compound of any one of claims 198 to 239, wherein is H.

241. R ７ 240. The compound of any one of claims 198-239, wherein is halogen (e.g., F or Cl).

242. R ７ The compound of any one of claims 198 to 239, wherein is -CN.

243. Formula IV: 【Chemistry 84】 or a salt thereof (e.g., a pharmaceutically acceptable salt), wherein R １ But, -OR ８ and 【Chemistry 85】 is selected from R ２ But H, C １－６ alkyl, and 3- to 6-membered carbocyclic rings, １－６ The alkyl is unsubstituted or has one or more R １３ is replaced by R ３ is unsubstituted or is substituted with one or more R １０ C substituted with １－６ alkyl, R ４ is H, R ５ is H, halogen, -CN, -OR １２ , 3- to 6-membered heterocycle, 5- to 6-membered heteroaryl, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R １３ is replaced by R ６ But there are one or more R １５ is a bicyclic heteroaryl substituted with R ７ is selected from halogen, —CN, and H; R ８ is selected from heterocycle and alkylheterocycle, any heterocycle containing 4 to 8 members and is unsubstituted or contains one or more R ａ or R ｂ and the alkyl portion of any alkyl heterocycle is substituted with C １－６ alkyl, Each R １０ But independently, -OR １４ , =O, -CN, -N(R １４ ) ２ , 3- to 6-membered carbocyclic ring, 3- to 6-membered heterocyclic ring, 5- to 6-membered heteroaryl, phenyl, —S(O) ２ (C １－６ alkyl), -N(R １４ )C(O)(C １－６ alkyl), C １－６ alkyl, and halogen; １－６ The alkyl is unsubstituted or has one or more R ２０ and any 3- to 6-membered carbocyclic ring is unsubstituted or substituted with one or more R １２ and any 3- to 6-membered heterocycle or 5- to 6-membered heteroaryl is unsubstituted or substituted with one or more of =O, R １２ , or R １３ is replaced by Each R １２ But independently, C １－６ Alkyl, C ２－６ alkenyl, and H, and any C １－６ Alkyl or C ２－６ Alkenyl is unsubstituted or has one or more R １３ is replaced by Each R １３ But independently, -OR １４ , -CN, -N(R １４ ) ２ and halogen; Each R １４ But independently, C １－６ Alkyl, C ２－６ alkenyl, and H; Each R １５ are independently deuterium, halogen, -N(R １２ ) ２ , -CN, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R １３ is replaced by Each R ２０ are independently —OH, —OC １－６ Alkyl, —CN, —NH ２ , -NHC １－６ alkyl, and halogen; R ２７ is a 3- to 6-membered heterocycle containing one or more heteroatoms selected from N, O, and S, and the heterocycle is unsubstituted or contains one or more R ２８ is replaced by Each R ２８ But independently, C １－６ selected from alkyl and halogen; R ａ and R ｂ each independently represents a halogen, C １－６ Alkyl, -OR １２ , and H, and any C １－６ The alkyl is unsubstituted or has one or more R １３ is substituted with R ａ and R ｂ are optionally linked together to form a 3- to 6-membered carbocyclic or heterocyclic ring, or a salt thereof.

244. The compound has formula IV-a: 【Chemistry 86】 or a salt (e.g., a pharmaceutically acceptable salt) thereof.

245. The compound has formula IVA: 【Hua 87】 or a salt (e.g., a pharmaceutically acceptable salt) thereof, wherein Each R ｉ and R ｈ independently H and R １０ 245. The compound of claim 243 or 244, selected from:

246. Each R ｉ and R ｈ independently H and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R ２０ 246. The compound of claim 245, substituted with:

247. R １４ The compound of claim 245 or 246, wherein is H.

248. R ６ but, 【Hua 88】 is selected from: X is selected from N and C—CN; Y is selected from O and S; R ２３ But -N(R １２ ) ２ , C １－６ Alkyl, and C １－６ Alkyl-N(R １４ ) ２ and any C １－６ The alkyl is unsubstituted or has one or more R １３ is replaced by R ２４ , R ２５ , and R ２６ are independently H, deuterium, halogen, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R １３ 248. The compound of any one of claims 243 to 247, substituted with:

249. R ６ but, 【Chemistry 89】 is selected from Any of them has one or more R １５ 249. The compound of any one of claims 243 to 248, substituted with:

250. R ６ but, 【Chemistry 90】 250. The compound according to any one of claims 243 to 249, selected from:

251. R ６ but, 【Chemistry 91】 251. The compound according to any one of claims 243 to 250, selected from:

252. The compound has formula IVB: 【Chemistry 92】 or a salt (e.g., a pharmaceutically acceptable salt) thereof, wherein X is selected from N and C—CN; Y is selected from O and S; R ２３ But -N(R １２ ) ２ , C １－６ Alkyl, and C １－６ Alkyl-N(R １４ ) ２ and any C １－６ The alkyl is unsubstituted or has one or more R １３ is replaced by R ２４ , R ２５ , and R ２６ are independently H, deuterium, halogen, -OR １２ , and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R １３ 244. The compound of claim 243, substituted with:

253. R １ But, -OR ８ 253. The compound according to any one of claims 243 to 252, selected from:

254. R １ but, 【Chemistry 93】 In the formula, R ａ and R ｂ are each independently a halogen, C １－６ Alkyl, -OR １２ , and H, and any C １－６ Alkyl is unsubstituted or has one or more R １３ 254. The compound of claim 253, substituted with:

255. R １ but, 【Chemistry 94】 255. The compound of claim 254, selected from:

256. R １ but, 【Chemistry 95】 is selected from In the formula, each R ａ and R ｂ are independently halogen, C １－６ Alkyl, -OR １２ and H; R ｃ But C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R １３ is substituted with R ａ and R ｂ or R ｃ are optionally linked together to form a 3- to 6-membered carbocyclic or heterocyclic ring.

257. R １ but, 【Chemistry 96】 257. The compound of claim 256, selected from:

258. R １ but, 【Chemistry 97】 253. The compound according to any one of claims 243 to 252, selected from:

259. The compound is according to formula IVC: 【Chemistry 98】 or a salt (e.g., a pharmaceutically acceptable salt) thereof, wherein R ａ and R ｂ each independently represents a halogen, C １－６ Alkyl, -OR １２ , and H, and any C １－６ The alkyl is unsubstituted or has one or more R １３ is replaced by X is selected from N and C—CN; Y is selected from O and S; R ２３ But -N(R １２ ) ２ , C １－６ Alkyl, and C １－６ Alkyl-N(R １４ ) ２ and any C １－６ The alkyl is unsubstituted or has one or more R １３ is replaced by R ２４ , R ２５ , and R ２６ are independently H, deuterium, halogen, -OR １２ , and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R １３ 259. The compound of any one of claims 243 to 258, substituted with:

260. R ａ The compound of claim 259, wherein is halogen (e.g., F).

261. R ｂ The compound of claim 259 or 260, wherein is H.

262. X is C—CN, Y is S, and R ２３ But -N(R １２ ) ２ 262. The compound of any one of claims 252 to 261, selected from:

263. R ２４ , R ２５ , and R ２６ The compound of any one of claims 252 to 262, wherein at least one of is halogen (e.g., F).

264. R ３ is unsubstituted or is substituted with one or more R １０ C substituted with １－３ The compound of any one of claims 243, 244, and 252-263, wherein the alkyl is selected from the group consisting of:

265. Each R １０ But independently, -OR １４ , =O, -CN, -NH(R １６ ), -N(R １６ ) ２ , 3-6 membered carbon ring, C １－６ alkyl, and halogen; １－６ The alkyl is unsubstituted or has one or more R ２０ and any 3- to 6-membered carbocyclic ring is unsubstituted or substituted with one or more R １２ and each R １６ But independently, C １－６ Alkyl and C ２－６ The compound of claim 264, selected from alkenyl.

266. Each R １０ But independently, -OR １４ , -CN,C １－６ alkyl, and halogen; １－６ The alkyl is unsubstituted or has one or more R ２０ 266. The compound of claim 265, substituted with:

267. Each R １０ is independently selected from halogen.

268. R ３ But C １－３ 265. The compound of claim 264, wherein said alkyl is selected from:

269. The part 【Hua99】 but, 【Chemistry 100】 【Chemistry 101】 any of which may optionally be selected from one or more R １０ 264. The compound of any one of claims 243, 244, and 252-263, further substituted with:

270. R ２ The compound of any one of claims 243 to 269, wherein is H.

271. R ２ is unsubstituted or is substituted with one or more R １３ C substituted with １－６ 270. The compound of any one of claims 243 to 269, wherein the compound is selected from alkyl.

272. R ２ But C １－２ 272. The compound of claim 271, wherein said alkyl is selected from:

273. R ２ is a 3- to 6-membered carbocyclic ring.

274. R ５ The compound according to any one of claims 243 to 273, wherein is H.

275. R ５ is halogen (e.g., F or Cl).

276. R ５ is unsubstituted or is substituted with one or more R １３ C substituted with １－６ 274. The compound of any one of claims 243 to 273, wherein the compound is selected from alkyl.

277. R ５ is substituted with one or more halogens or —CN １－６ 277. The compound of claim 276, wherein said alkyl is selected from:

278. R ５ But, -CF ２ H, -CF ３ , -CH ２ CN, and -CH ２ CH ３ 278. The compound of claim 277, selected from:

279. R ５ But, -CF ３ The compound of claim 278, wherein:

280. R ７ The compound of any one of claims 243 to 279, wherein is H.

281. R ７ 279. The compound of any one of claims 243 to 279, wherein is halogen (e.g., F or Cl).

282. R ７ The compound of any one of claims 243 to 279, wherein is -CN.

283. 283. The compound of any one of claims 243-282, wherein the compound is not a compound included in Table 3.

284. Formula V: 【Chemistry 102】 or a salt thereof (e.g., a pharmaceutically acceptable salt), wherein R １ But, -OR ８ and 【Chemistry 103】 is selected from R ｍ is hydrogen and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R １３ is replaced by R ４ is H, R ５ is halogen and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R １３ is replaced by R ６ is a monocyclic or bicyclic heteroaryl, and the heteroaryl is selected from one or more R １５ is replaced by R ７ is selected from halogens, R ８ is selected from heterocycle and alkylheterocycle, any heterocycle containing 4 to 8 members and is unsubstituted or contains one or more R ａ or R ｂ and the alkyl portion of any alkyl heterocycle is substituted with C １－６ alkyl, Each R １２ But independently, C １－６ Alkyl, C ２－６ alkenyl, and H, and any C １－６ Alkyl or C ２－６ Alkenyl is unsubstituted or has one or more R １３ is replaced by Each R １３ But independently, -OR １４ , -CN, -N(R １４ ) ２ and halogen; Each R １４ But independently, C １－６ Alkyl, C ２－６ alkenyl, and H; Each R １５ are independently deuterium, halogen, -N(R １２ ) ２ , -CN, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R １３ is replaced by R ２７ is a 3- to 6-membered heterocycle containing one or more heteroatoms selected from N, O, and S, and the heterocycle is unsubstituted or contains one or more R ２８ is replaced by Each R ２８ But independently, C １－６ selected from alkyl and halogen; R ａ and R ｂ are each independently deuterium, halogen, C １－６ alkyl, 3- to 6-membered carbocyclic ring, —OR １２ and H; R ａ and R ｂ are optionally linked together to form a 3- to 6-membered carbocyclic or heterocyclic ring, and any C １－６ The alkyl or 3- to 6-membered carbocyclic or heterocyclic ring is unsubstituted or contains one or more R １３ The compound or a salt thereof, wherein the compound is substituted with

285. Formula VI: 【Chemistry 104】 or a salt thereof (e.g., a pharmaceutically acceptable salt), wherein R １ But, -OR ８ and 【Chemistry 105】 is selected from R ２ But H, C １－６ alkyl, and 3- to 6-membered carbocyclic rings, １－６ The alkyl is unsubstituted or has one or more R １３ is replaced by R ４ is H, R ５ is H, halogen, -CN, -OR １２ , 3- to 6-membered heterocycle, 5- to 6-membered heteroaryl, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R １３ is replaced by R ６ is a monocyclic or bicyclic heteroaryl, and the heteroaryl is selected from one or more R １５ is replaced by R ７ is selected from H and halogen; R ８ is selected from heterocycle and alkylheterocycle, any heterocycle containing 4 to 8 members and is unsubstituted or contains one or more R ａ or R ｂ and the alkyl portion of any alkyl heterocycle is substituted with C １－６ alkyl, Each R １２ But independently, C １－６ Alkyl, C ２－６ alkenyl, and H, and any C １－６ Alkyl or C ２－６ Alkenyl is unsubstituted or has one or more R １３ is replaced by Each R １３ But independently, -OR １４ , -CN, -N(R １４ ) ２ and halogen; Each R １４ are independently a 3- to 6-membered carbocyclic ring, a 3- to 6-membered heterocyclic ring, C １－６ Alkyl, C ２－６ alkenyl, and H, and any C １－６ the alkyl is optionally deuterated; Each R １５ are independently deuterium, halogen, -N(R １２ ) ２ , -CN, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R １３ is replaced by Each R ２０ are independently —OH, —OC １－６ Alkyl, ═O, —CN, —NH ２ , -NHC １－６ Alkyl, —C(O)(C １－６ alkyl), a 3- to 6-membered carbocycle, a 5- to 6-membered aryl, and halogen; R ２７ is a 3- to 6-membered heterocycle containing one or more heteroatoms selected from N, O, and S, and the heterocycle is unsubstituted or contains one or more R ２８ is replaced by Each R ２８ But independently, C １－６ selected from alkyl and halogen; R ａ and R ｂ are each independently deuterium, halogen, C １－６ Alkyl, -OR １２ , a 3- to 6-membered carbocyclic ring, and H; R ａ and R ｂ are optionally linked together to form a 3- to 6-membered carbocyclic or heterocyclic ring, and any C １－６ The alkyl or 3- to 6-membered carbocyclic or heterocyclic ring is unsubstituted or contains one or more R １３ is replaced by Each R ｄ are independently H, halogen, and C １－６ alkyl, any C １－６ The alkyl is unsubstituted or has one or more R ２０ is replaced by R ｅ but, 【Chemistry 106】 is selected from R ｆ is H, halogen, and C １－６ alkyl, R ｇ and R ｈ independently H and C １－６ alkyl, R ｊ But C １－６ alkyl, However, R ｅ but, 【Chemistry 107】 The compound, or a salt thereof, which is not

286. 286. The compound of claim 285, wherein the compound is not a compound included in Table 4.

287. A compound shown in Table 5, or a salt thereof (e.g., a pharmaceutically acceptable salt).

288. A compound shown in Table 6, or a salt thereof (e.g., a pharmaceutically acceptable salt).

289. A compound shown in Table 7, or a salt thereof (e.g., a pharmaceutically acceptable salt).

290. A compound shown in Table 8, or a salt thereof (e.g., a pharmaceutically acceptable salt).

291. A compound shown in Table 9, or a salt thereof (e.g., a pharmaceutically acceptable salt).

292. A compound shown in Table 10, or a salt thereof (e.g., a pharmaceutically acceptable salt).

293. 300. A pharmaceutical composition comprising a compound according to any one of claims 1 to 292, or a salt thereof (eg, a pharmaceutically acceptable salt), and a pharmaceutically acceptable excipient.

294. 293. A compound according to any one of claims 1 to 292, or a salt thereof (eg a pharmaceutically acceptable salt), for use as a medicament.

295. The compound of claim 294, wherein the agent is useful in the prevention or treatment of a disease, disorder, or condition ameliorated by inhibition of KRAS having a Q61H, G13D, G12D, G12V, G12C, G12S, G12A, or G12R mutation, or wild-type KRAS.

296. 296. The compound of claim 295, wherein said agent is useful in the prevention or treatment of a disease, disorder, or condition ameliorated by the inhibition of wild-type KRAS.

297. 296. The compound of claim 295, wherein the agent is useful in the prevention or treatment of a disease, disorder, or condition ameliorated by inhibition of KRAS having a G12D, G12R, or G12V mutation.

298. 297. The compound of any one of claims 294 to 296, wherein the medicament is useful in the prevention or treatment of cancer.

299. 299. The compound of claim 298, wherein the cancer is selected from the group consisting of pancreatic cancer, colorectal cancer, and lung cancer.

300. 293. A compound according to any one of claims 1 to 292, or a salt thereof (eg a pharmaceutically acceptable salt), for use in the treatment of a disease, disorder, or condition.

301. 301. The compound of claim 300, wherein the disease, disorder, or condition is cancer.

302. 302. The compound of claim 301, wherein the cancer is selected from the group consisting of pancreatic cancer, colorectal cancer, and lung cancer.

303. 303. The compound of any one of claims 300-302, wherein said compound is used in the treatment of a disease, disorder, or condition in a subject in need thereof.

304. 293. A compound according to any one of claims 1 to 292, or a salt thereof (eg a pharmaceutically acceptable salt), for use in the manufacture of a medicament.

305. The compound of claim 304, wherein the agent is useful in the prevention or treatment of a disease, disorder, or condition ameliorated by inhibition of KRAS having a Q61H, G13D, G12D, G12V, G12C, G12S, G12A, or G12R mutation, or wild-type KRAS.

306. 306. The compound of claim 305, wherein said agent is useful in the prevention or treatment of a disease, disorder, or condition ameliorated by the inhibition of wild-type KRAS.

307. 306. The compound of claim 305, wherein the agent is useful in the prevention or treatment of a disease, disorder, or condition ameliorated by inhibition of KRAS having a G12D, G12R, or G12V mutation.

308. 308. The compound of any one of claims 304 to 307, wherein the agent is useful in the treatment of cancer.

309. 309. The compound of claim 308, wherein the cancer is selected from the group consisting of pancreatic cancer, colorectal cancer, and lung cancer.

310. 30. A method comprising administering a therapeutically effective amount of a compound of any one of claims 1 to 292, or a salt thereof (e.g., a pharmaceutically acceptable salt) to a subject in need thereof.

311. 311. The method of claim 310, wherein the subject has a disease, disorder, or condition that is ameliorated by inhibition of KRAS having a Q61H, G13D, G12D, G12V, G12C, G12S, G12A, or G12R mutation, or wild-type KRAS.

312. 312. The method of claim 311, wherein the disease, disorder, or condition is ameliorated by inhibition of wild-type KRAS.

313. 312. The method of claim 311, wherein the subject has a disease, disorder, or condition that is ameliorated by inhibition of KRAS having a G12D, G12R, or G12V mutation.

314. 314. The method of any one of claims 310 to 313, wherein the subject has cancer.

315. 315. The method of claim 314, wherein the subject has previously been diagnosed with said cancer.

316. The method of claim 314, wherein the subject has previously undergone a therapeutic regimen for the cancer.

317. 317. The method of claim 315 or 316, wherein the subject was previously in remission from the cancer.

318. 318. The method of any one of claims 314 to 317, wherein the cancer is selected from the group consisting of pancreatic cancer, colorectal cancer, and lung cancer.

319. 319. The method of any one of claims 310 to 318, wherein the compound or salt thereof is administered in combination with an additional therapeutic agent.

320. 30. Use of a compound according to any one of claims 1 to 292, or a salt thereof (eg, a pharmaceutically acceptable salt), for the manufacture of a medicament for the treatment of cancer.

321. 321. The use of claim 320, wherein the cancer is selected from the group consisting of pancreatic cancer, colorectal cancer, and lung cancer.

322. 300. A method comprising contacting a KRAS protein with a compound of any one of claims 1 to 292, or a salt thereof (eg, a pharmaceutically acceptable salt).

323. 323. The method of claim 322, wherein contacting the KRAS protein with the compound modulates KRAS.

324. 324. The method of claim 322 or 323, wherein the KRAS protein has a Q61H, G13D, G12D, G12V, G12C, G12S, G12A, or G12R mutation.

325. 324. The method of claim 322 or 323, wherein the KRAS protein is a wild-type KRAS protein.

326. The method of any one of claims 322 to 325, wherein the KRAS protein is in an active (GTP-bound) state.

327. The method of any one of claims 322 to 325, wherein the KRAS protein is in an inactive (GDP-bound) state.

328. The method of any one of claims 322 to 327, wherein the KRAS protein is located intracellularly.

329. The method of claim 328, wherein the cell is present in a subject.

330. 330. The method of claim 329, wherein the subject is a human.

331. 331. The method of claim 329 or 330, wherein the subject has cancer.

332. 332. The method of claim 331, wherein the cancer is selected from the group consisting of pancreatic cancer, colorectal cancer, and lung cancer.

333. 293. A method of inhibiting the function of wild-type 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 to 292, or a salt thereof (e.g., a pharmaceutically acceptable salt).

334. 334. The method of claim 333, wherein the KRAS protein is a wild-type KRAS protein.

335. 334. The method of claim 333, wherein the KRAS protein has a Q61H, G13D, G12D, G12V, G12C, G12S, G12A, or G12R mutation.

336. 336. The method of claim 335, wherein the KRAS protein has a G12D, G12V, or G12R mutation.

337. The method of any one of claims 333 to 336, wherein the KRAS protein is in an active (GTP-bound) state.

338. The method of any one of claims 333 to 336, wherein the KRAS protein is in an inactive (GDP-bound) state.

339. The method of any one of claims 333 to 338, wherein the KRAS protein is located intracellularly.

340. The method of claim 339, wherein the cell is present in a subject.

341. 341. The method of claim 340, wherein the subject is a human.

342. 342. The method of claim 340 or 341, wherein the subject has cancer.

343. 343. The method of claim 342, wherein the cancer is selected from the group consisting of pancreatic cancer, colorectal cancer, and lung cancer.

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

345. The compound is (i) IC in the assay of Biological Example 1 ５０ ≦0.1μM, 0.1μM<IC ５０ ≦1 μM, 1 μM ≦ IC ５０ ≦10 μM, or 10 μM<IC ５０ (e.g., 50 nM Avi-KRAS G12D (amino acids 1-169) GppNHp / RAF1 RBD-3xFLAG(52-151), 50 nM Avi-KRAS G12R (amino acids 1-169) GppNHp / RAF1 RBD-3xFLAG(52-151), 50 nM Avi-KRAS G12V (amino acids 1-169) GppNHp / RAF1 RBD-3xFLAG(52-151), 50 nM Avi-KRAS WT (amino acids 1-169) GppNHp / RAF1 RBD-3xFLAG(52-151), and / or 75 nM Avi-RAF1 Homogenous time-resolved fluorescence (HTRF) analysis of protein:protein interactions (PPI) of RBD-3xFLAG; (ii) IC in the assay of Biological Example 2 or 4 (e.g., a cell-based pERK HTRF assay in GP2d (G12D) or SW620 (G12V) cells) ５０ ≦0.1μM, 0.1μM<IC ５０ ≤ 1 μM, or IC ５０ >1 μM, and / or (iii) The assay of Biological Example 3 (e.g., 50 nM Avi-KRAS G12D(2-169)GTP / RAF1 RBD-3xFLAG(51-131); 50 nM Avi-KRAS G12C(2-169)GTP / RAF1 RBD-3xFLAG(51-131); 50 nM Avi-KRAS G12V(2-169)GTP / RAF1 RBD-3xFLAG(51-131); 50 nM Avi-KRAS WT(2-169)GTP / RAF1 RBD-3xFLAG(51-131); and / or 75 nM 3xFLAG-RAF1 Homogeneous time-resolved fluorescence (HTRF) analysis of protein:protein interactions (PPI) of RBD(51-131)-Avi ５０ ≦0.1μM, 0.1μM<IC ５０ ≦1μM, 1μM<IC ５０ ≦10 μM, or 10 μM<IC ５０ and (iv) IC in an assay of Biological Example 5 (e.g., a cell-based pERK HTRF assay in AsPC-1, SW1900, HPAC, Capan-2, RKN, H358, HCT116, KP-2, H1573, A549, MKN1, or HT1080 cells). ５０ ≦0.1μM, 0.1μM<IC ５０ ≤ 1 μM, or IC ５０ >1 μM, and / or (v) IC in an assay of Biological Example 6 (e.g., a 3D cell viability assay in AsPC-1, SW1900, HPAC, Capan-2, RKN, H358, HCT116, KP-2, H1573, A549, MKN1, or HT1080 cells). ５０ ≦0.1μM, 0.1μM<IC ５０ ≤ 1 μM, or IC ５０ The compound of claim 344, having a .gtoreq.1 .mu.M.

346. The compound is (i) In the assay of Biological Example 1, IC ５０ ≦0.1 μM or 0.1 μM<IC ５０ ≦1 μM (e.g., 50 nM Avi-KRAS G12D (amino acids 1-169) GppNHp / RAF1 RBD-3×FLAG(52-151); 50 nM Avi-KRAS G12R (amino acids 1-169) GppNHp / RAF1 RBD-3×FLAG(52-151); 50 nM Avi-KRAS G12V (amino acids 1-169) GppNHp / RAF1 RBD-3×FLAG(52-151); 50 nM Avi-KRAS WT (amino acids 1-169) GppNHp / RAF1 RBD-3×FLAG(52-151); and / or 75 nM Protein:protein interaction (PPI) homogeneous time-resolved fluorescence (HTRF) analysis of Avi-RAF1 RBD-3xFLAG; and / or (ii) IC in the assays of Biological Examples 2 or 4 (e.g., cell-based pERK HTRF assays in GP2d(G12D) and SW620(G12V) cells). ５０ ≦0.1 μM or 0.1 μM<IC ５０ and / or (iii) The assay of Biological Example 3 (e.g., 50 nM Avi-KRAS G12D(2-169)GTP / RAF1 RBD-3xFLAG(51-131); 50 nM Avi-KRAS G12C(2-169)GTP / RAF1 RBD-3xFLAG(51-131); 50 nM Avi-KRAS G12V(2-169)GTP / RAF1 RBD-3xFLAG(51-131); 50 nM Avi-KRAS WT(2-169)GTP / RAF1 RBD-3xFLAG(51-131); and / or 75 nM 3xFLAG-RAF1 Homogeneous time-resolved fluorescence (HTRF) analysis of protein:protein interactions (PPI) of RBD(51-131)-Avi ５０ ≦0.1 μM or 0.1 μM<IC ５０ and / or (iv) IC in an assay of Biological Example 5 (e.g., a cell-based pERK HTRF assay in AsPC-1, SW1900, HPAC, Capan-2, RKN, H358, HCT116, KP-2, H1573, A549, MKN1, or HT1080 cells). ５０ ≦0.1 μM or 0.1 μM<IC ５０ and / or (v) IC in an assay of Biological Example 6 (e.g., a 3D cell viability assay in AsPC-1, SW1900, HPAC, Capan-2, RKN, H358, HCT116, KP-2, H1573, A549, MKN1, or HT1080 cells). ５０ ≦0.1 μM or 0.1 μM<IC ５０ The compound of claim 345, having a concentration of ≦1 μM.

347. The compound of any one of claims 344 to 346, wherein the compound is capable of irreversibly binding to the KRAS protein.

348. The compound of any one of claims 344 to 346, wherein the compound is capable of reversibly binding to the KRAS protein.

349. The compound according to any one of claims 344 to 348, wherein the compound is a compound according to any one of claims 1 to 292.

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