Compositions and methods for inhibiting KRAS

Abstract

Provided herein are compounds or salts, esters, tautomers, prodrugs, zwitterionic forms, or stereoisomers thereof, and pharmaceutical compositions comprising the same. Also provided herein are methods of using the above materials to modulate (e.g., inhibit) KRAS (e.g., KRAS having a Q61H, G12D, G12V, G12C, G12S, G12A, G12R, or G13D mutation, or wild-type KRAS) and to treat a disease or condition, such as cancer, in a subject in need thereof.

Description

[0001] STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT

[0002] This invention was made with government support under (1) Contract No. 75N91019D00024 awarded by the National Institutes of Health and (2) Contract No. DE-AC52-07NA27344 awarded by the United States Department of Energy. The government has certain rights in this invention.

[0003] Related applications

[0004] This application claims priority to and the benefit of U.S. Application No. 63 / 395,699, filed on August 5, 2022, U.S. Application No. 63 / 386,285, filed on December 6, 2022, and U.S. Application No. 63 / 496,873, filed on April 18, 2023, the entire contents of each of which are hereby incorporated by reference. Background Art

[0005] RAS proteins act as molecular switches, cycling between inactive ("GDP-bound") and active ("GTP-bound") states. RAS signaling occurs via engagement with effector proteins that regulate signaling cascades that regulate tumor cell survival and proliferation. Aberrant activation of RAS by oncogenic mutations results in increased GTP-bound KRAS and constitutive downstream signaling.

[0006] RAS is the most commonly mutated oncogene. Activating mutations of KRAS occur in more than 90% of pancreatic tumors. Mutated KRAS is also observed at high frequency in other common tumors, including colorectal cancer (about 44%) and non-small cell lung cancer (NSCLC; about 20-30%). Cancer-associated mutations of KRAS are clustered in three hotspots (G12, G13 and Q61), of which the majority (77%) of mutations cause single amino acid substitutions at G12. The KRAS missense mutation G12D is the most common variant in human malignancies (35%), followed by G12V (29%). In addition to G12, hotspots G13 and Q61 show mutation rates of 10% and 6%, respectively.

[0007] The development of small molecule KRAS inhibitors has proven challenging. Recent clinical development of covalent KRAS G12C inhibitors indicates the potential of directly targeting KRAS oncogenic proteins. Clinical trial results of two covalent inhibitors, AMG510 (sotorasib) and MRTX849 (adagrasib), are promising. These inhibitors have been shown to be clinically active primarily in NSCLC, where the frequency of KRAS G12C mutations is the highest. Unfortunately, the inhibitors appear to be less effective in KRAS G12C colorectal cancer. Both compounds target only the inactive (GDP-bound) form of KRASG12C, and the lack of activity against active (GTP-bound) KRAS G12C may contribute to the development of drug resistance. In addition, these covalent inhibitors are limited to specific G12C mutants, which account for approximately 13% of all KRAS-driven cancers, leaving a large number of non-G12CKRAS cancers undruggable. Therefore, there is an unmet clinical need for KRAS therapeutics that target additional KRAS alterations or combinations thereof. Pan-KRAS inhibitors are expected to affect most KRAS mutant alleles (including the most prevalent G12D and G12V) or KRAS wild-type amplified cancers.

[0008] KRAS is essential for mouse development, while NRAS and HRAS are dispensable. This requirement for KRAS raises toxicity concerns when targeting wild-type KRAS protein. However, when KRAS is replaced by HRAS, mice are viable, reducing toxicity concerns and suggesting that KRAS isoform-specific inhibitors should be tolerated, in contrast to pan-RAS inhibitors, which may pose toxicity issues. If so, an additional advantage of pan-KRAS inhibitors may arise from cancers that acquire resistance to KRAS G12C inhibitors. Recent reports have provided insights into the mechanisms of resistance to KRAS G12C inhibitors in the clinic, suggesting that restoration of RAS / MAPK is a driver of resistance. In addition to activation of the KRAS wild-type allele via upstream RTK signaling, a large panel of mutations responsive to KRAS G12C inhibitors has been shown to be acquired. It is possible that direct pan-KRAS agents could inhibit 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 mutational status. Summary of the Invention

[0009] The present disclosure provides compounds and compositions and kits comprising the same, and methods of using the above substances to treat diseases and conditions such as cancer. The present disclosure provides compounds that may be able to inhibit one or more mutant forms of KRAS, such as KRAS with G12D, G12V, G12C, G12S, G12A, G12R, Q61H or G13D mutations, or wild-type KRAS. Such compounds can be considered pan-KRAS inhibitors. In some embodiments, the compounds provided herein may be able to target both active GTP-binding proteins and inactive GDP-binding proteins, which inhibitors may provide 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 in active and inactive conformations comprising a glycine to aspartic acid, valine, cysteine, serine, alanine, or arginine mutation at codon 12 (i.e., a G12D, G12V, G12C, G12S, G12A, or G12R mutation); or a glycine to aspartic acid mutation at codon 13 (e.g., a G13D mutation); or a glutamine to histidine mutation at codon 61 (e.g., a Q61H mutation). In some embodiments, the compounds provided herein have inhibitory activity against wild-type KRAS. In some embodiments, the compounds provided herein can be used to treat cancer, e.g., a cancer characterized by a KRAS protein having a mutation at codon 12, e.g., a G12D, G12V, G12C, G12S, G12A, or G12R mutation; or a mutation at codon 13, e.g., a G13D mutation; or a mutation at codon 61, e.g., a Q61H mutation, or a cancer that would benefit from inhibition of wild-type KRAS.

[0010] In one aspect, the present disclosure provides a composition comprising a compound represented by Formula X:

[0011]

[0012] or a salt (eg, a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof, wherein R 1 、R 2 、R 3 、R 4 、R 5 、R 6 and R 7As provided herein. In some embodiments, the compound is provided herein according to 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, II In some embodiments, the present invention comprises a compound of any one of: IIV, IIV, IIW, IIIX, IIX, IIY, IIY, IIZ, IIZ, IIAA, IIAA, III, III', III-a, IIIA, IIIA1, IIIB, IIIC, IIIC1, IIID, IIIE, IIIF, IIIG, IIIH, IIIJ, IIIK, IIIL, IIIM, IIIN, IIIP, IIIQ, IIIR, IIS, IIIT, IV, IV-a, IVA, IVB, IVC, V, Va, VA, VB, VC, VI, and VI-a, or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof. In some embodiments, the compounds provided herein, or salts, esters, tautomers, zwitterionic forms, or stereoisomers thereof, can modulate (e.g., inhibit) the activity of a KRAS protein, such as 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., G13D; a KRAS protein having a mutation at codon 61, e.g., Q61H; or wild-type KRAS. In some embodiments, the compounds provided herein, or salts, esters, tautomers, zwitterionic forms, or stereoisomers thereof, are capable of interacting with KRAS proteins in active and inactive conformations comprising a glycine to aspartic acid, valine, cysteine, serine, alanine, or arginine mutation at codon 12 (i.e., a G12D, G12V, G12C, G12S, G12A, or G12R mutation), or a glycine to aspartic acid mutation at codon 13 (e.g., a G13D mutation), or a glutamine to histidine mutation at codon 61 (e.g., a Q61H mutation). In some embodiments, the compounds provided herein, or salts, esters, tautomers, zwitterionic forms, or stereoisomers thereof, have inhibitory activity against wild-type KRAS.In some embodiments, the compounds provided herein, or their salts, esters, tautomers, zwitterionic forms, or stereoisomers, are capable of binding to KRAS proteins in an active ("GTP-bound") conformation. In some embodiments, the compounds provided herein, or their salts, esters, tautomers, zwitterionic forms, or stereoisomers, are capable of binding to KRAS proteins in an inactive ("GDP-bound") conformation. In some embodiments, the compounds provided herein, or their salts, esters, tautomers, zwitterionic forms, or stereoisomers, are capable of binding to KRAS proteins in both active ("GTP-bound") and inactive ("GDP-bound") conformations.

[0013] In another aspect, the disclosure provides a pharmaceutical composition comprising a compound as provided herein (e.g., a compound of Formula I, Ia, IA, IAl, 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, II In the present invention, the present invention further comprises a compound represented by one of the following formulae: I1, IIU, IIU, IIV, IIV, IIW, IIW, IIX, IIX, IIY, IIY, IIZ, IIZ, IIAA, IIAA, III, III', III-a, IIIA, IIIA, IIIB, IIIC, IIIC, 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 formulae listed herein, or a salt, ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof, and a pharmaceutically acceptable carrier.

[0014] In yet another aspect, the disclosure provides a method for producing a novel compound using, for example, a compound as provided herein (e.g., a compound 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, IIW, IIW1, IIX, IIX1, IIY, IIY1 In some embodiments, the present invention relates to a method of inhibiting KRAS activity in a human or animal subject by inhibiting KRAS activity in a human or animal subject for treating a disease such as cancer, including pancreatic cancer (e.g., pancreatic ductal adenocarcinoma (PDAC)), colorectal cancer, endometrial endometrioid adenocarcinoma, rectal adenocarcinoma, gastric cancer, and lung cancer. The method further comprises:

[0015] In another aspect, the disclosure provides compounds provided herein (e.g., compounds of Formula I, Ia, IA, IAl, 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, II H1, IIJ, IIJ1, IIK, IIK1, IIL, IIL1, IIM, IIM1, IIN, IIN1, IIP, IIP1, IIQ, IIQ1, IIR, IIR1, IIS, IIS1, IIT, II T1, IIU, IIU1, IIV, IIV1, IIW, IIW1, IIX, IIX1, IIY, IIY1, IIZ, IIZ1, IIAA, IIAA1, III, III', III-a, IIIA, II IA1, 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 listed herein) or a salt, ester, tautomer, zwitterionic form, or stereoisomer thereof Use of a construct for the manufacture of a medicament for treating a disease, disorder or condition (e.g., cancer) that is improved, treated, inhibited or alleviated by inhibiting KRAS, including KRAS with a mutation at codon 12 (e.g., G12D, G12V, G12C, G12S, G12A or G12R mutation), KRAS with a mutation at codon 13 (e.g., G13D mutation), KRAS with a mutation at codon 61 (e.g., Q61H mutation), or wild-type KRAS. In some embodiments, the disease, disorder or condition is pancreatic cancer (e.g., pancreatic ductal adenocarcinoma (PDAC)), colorectal cancer, or lung cancer.

[0016] In yet another aspect, the disclosure provides a compound as provided herein (e.g., a compound 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, I In some embodiments, the medicament is a compound selected from the group consisting of: IU, IIUi, IIV, IIVi, IIW, IIWi, IIX, IIXi, IIY, IIYi, IIZ, IIZi, IIAA, IIAAi, III, III', III-a, IIIA, IIIAi, IIIB, IIIC, IIICi, 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 listed herein) or a salt, ester, tautomer, zwitterionic form, or stereoisomer thereof for use as a medicament. In some embodiments, the medicament is for use in treating a disease, disorder, or condition (e.g., cancer). In some embodiments, the disease, disorder, or condition is pancreatic cancer (e.g., pancreatic ductal adenocarcinoma (PDAC)), colorectal cancer, or lung cancer. DETAILED DESCRIPTION

[0017] The present disclosure provides compounds (e.g., Formula I, Ia, IA, IA1, IA2, IB, IBl, 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, II E1, IIF, IIF1, IIG, IIG1, IIH, IIH1, IIJ, IIJ1, IIK, IIK1, IIL, IIL1, IIM, IIM1, IIN, IIN1, IIP, IIP1, IIQ, IIQ1, IIR, IIR1, II In some embodiments, the present invention relates to compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: a) compounds comprising: Specifically, certain compounds provided herein may have useful inhibitory activity against KRAS proteins having a mutation at codon 12 (e.g., G12D, G12V, G12C, G12S, G12A, or G12R mutation), KRAS proteins having a mutation at codon 13 (e.g., G13D mutation), KRAS proteins having a mutation at codon 61 (e.g., Q61H mutation), or wild-type KRAS proteins, wherein the KRAS proteins are in an active (GTP-bound) or inactive (GDP-bound) conformation. Certain compounds provided herein may be able to inhibit KRAS in both active and inactive forms. The present disclosure also provides pharmaceutical compositions comprising one or more compounds provided herein and a pharmaceutically acceptable carrier, as well as methods for preparing and using the compounds and compositions. The present disclosure also provides methods for inhibiting KRAS, including a KRAS protein having a mutation at codon 12 (e.g., a G12D, G12V, G12C, G12S, G12A, or G12R mutation), a KRAS protein having a mutation at codon 13 (e.g., a G13D mutation), a KRAS protein having a mutation at codon 61 (e.g., a Q61H mutation), or a wild-type KRAS protein, wherein KRAS is in an active or inactive conformation.In one aspect, the present disclosure provides a method for treating a KRAS-mediated disorder in a subject in need of treatment, wherein the KRAS includes a KRAS protein having a mutation at codon 12 (e.g., 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, the method comprising administering to the subject a therapeutically effective amount of a compound or composition provided herein. Also provided herein are uses of certain compounds provided herein for the manufacture of a medicament for treating a disease, condition, or disorder that is improved, treated, inhibited, or alleviated by inhibiting KRAS, including a KRAS protein having a mutation at codon 12 (e.g., G12D, G12V, G12C, G12S, G12A, or G12R mutation), a KRAS protein having a mutation at codon 13 (e.g., G13D mutation), a KRAS protein having a mutation at codon 61 (e.g., Q61H mutation), or a wild-type KRAS protein. In some embodiments, the disease, condition, or disorder is cancer (e.g., as described herein).

[0018] When a range of values ​​is disclosed and the expression "n1 ... to n2" or "between n1 ... and n2" is used, where n1 and n2 are numerical values, then unless otherwise specified, such expression is intended to include the numerical value itself and the range between the numerical values. This range between and including the end values ​​can be integers or continuous. For example, the range "2 to 6 carbons" is intended to include two, three, four, five, and six carbons, as carbon occurs in integer units. For example, comparing the range "1 to 3 μM (micromolar concentration)", the range is intended to include 1 μM, 3 μM, and any number between a number of significant figures (e.g., 1.255 μM, 2.1 μM, 2.9999 μM, etc.).

[0019] As used herein, "about" is intended to qualify the numerical value it modifies, indicating that the value may vary within a margin of error. When no specific margin of error is recited, such as the standard deviation of the mean value given in a graph or data table, the term "about" should be understood to mean that the stated range will encompass the recited value as well as the range that would be included by rounding up or down to the recited number, taking into account significant figures.

[0020] As used herein, "acyl," alone or in combination, refers to a carbonyl group attached to an alkenyl, alkyl, aryl, cycloalkyl, heteroaryl, heterocycle, or any other moiety wherein the atom attached to the carbonyl group is carbon. An "acetyl" group refers to a -C(O)CH3 group. An "alkylcarbonyl" or "alkanoyl" group refers to an alkyl group attached to the parent molecular moiety through a carbonyl group. Examples of such groups include methylcarbonyl and ethylcarbonyl. Examples of acyl groups include formyl, alkanoyl, and aroyl.

[0021] As used herein, "alkenyl" alone or in combination refers to a straight or branched hydrocarbon group having one or more double bonds and containing 2 to 20 carbon atoms. In certain embodiments, the alkenyl group will contain 2 to 6 carbon atoms. The term "alkenylene" refers to a carbon-carbon double bond system connected at two or more positions, such as vinylene [(-CH=CH-), (-C::C-)]. Examples of suitable alkenyl groups include vinyl, propenyl, 2-methylpropenyl, 1,4-butadienyl, etc. Unless otherwise specified, the term "alkenyl" may include "alkenylene" groups.

[0022] "Alkynyl" refers to a group having at least 2 carbon atoms and at least one triple bond and having the specified number of carbon atoms (i.e., C 2-6 Alkynyl refers to a straight or branched hydrocarbon chain of two to six carbon atoms. 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 Examples of alkynyl groups include, but are not limited to, ethynyl, propynyl, 1-butynyl, 2-butynyl, butadiynyl, 1-pentynyl, 2-pentynyl, isopentenyl, 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.

[0023] As used herein, "alkoxy," alone or in combination, refers to an alkyl ether radical, wherein the term alkyl is as described herein. Examples of suitable alkyl ether radicals include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, and the like.

[0024] As used herein, "alkyl," alone or in combination, refers to a straight or branched chain alkyl group containing 1 to 20 carbon atoms (e.g., C 1-20 In certain embodiments, the alkyl group will contain from 1 to 10 carbon atoms (e.g., C 1-10 In other embodiments, the alkyl group will contain from 1 to 8 carbon atoms (e.g., C 1-8 In other embodiments, the alkyl group will contain from 1 to 6 carbon atoms (e.g., C 1-6 In other embodiments, the alkyl group will contain from 1 to 3 carbon atoms (e.g., C 1-3 Alkyl). Alkyl is unsubstituted or substituted as defined herein. Examples of alkyl include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, hexyl, octyl, nonyl, etc. As used herein, the term "alkylene" alone or in combination refers to a saturated aliphatic group derived from a straight or branched saturated hydrocarbon attached at two or more positions, such as methylene (-CH2-). Unless otherwise specified, the term "alkyl" may include "alkylene" groups.

[0025] 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 groups such as N-methylamino, N-ethylamino, N,N-dimethylamino, N,N-ethylmethylamino, and the like.

[0026] As used herein, "alkylthio," alone or in combination, refers to an alkylthioether (RS-) group, wherein the term alkyl is as described herein and wherein the sulfur may be mono- or di-oxidized. Examples of suitable alkylthioether groups include methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio, tert-butylthio, methanesulfonyl, ethanesulfinyl, and the like.

[0027] 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 as defined by the specific enumerated designated "R" group. In some embodiments, an "amido" group includes -C(O)NH2, C 1-4 Alkyl amide and di(C 1-4 As used herein, the term "C 1-4 "Alkylamide" refers to -C(O)NH(C 1-4 alkyl), wherein C 1-4Alkyl is as defined herein. As used herein, the term "N-amido," alone or in combination, refers to a RC(O)N(R')- group, wherein R and R' are as defined herein or as defined by the specific enumerated designated "R" group. 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 (CH3C(O)NH-).

[0028] As used herein, "amino," alone or in combination, refers to -NRR', wherein R and R' are independently selected from hydrogen, alkyl, acyl, heteroalkyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl, any of which groups may themselves be unsubstituted or substituted. In addition, R and R' may be combined to form an unsubstituted or substituted heterocycloalkyl. An "amino" group may be a primary amine (e.g., -NH2), a secondary amine, or a disubstituted amine (e.g., -NHR, wherein R is not hydrogen), or a tertiary amine or a trisubstituted amine (e.g., -NRR', wherein neither R nor R' is hydrogen).

[0029] As used herein, "aryl" alone or in combination means a carbocyclic aromatic system containing one, two, or three rings, wherein such polycyclic ring systems are fused together. The term "aryl" encompasses aromatic groups such as phenyl, naphthyl, anthracenyl, and phenanthrenyl. The aryl moiety can include, for example, 5 to 20 carbon atoms, such as 5 to 12 carbon atoms, for example 5 or 6 carbon atoms.

[0030]

[00146] "Arylalkenyl" or "aralkenyl," as used herein, alone or in combination, refers to an aryl group attached to the parent molecular moiety through an alkenyl group.

[0031]

[00146] "Arylalkoxy" or "aralkoxy," as used herein, alone or in combination, refers to an aryl group attached to the parent molecular moiety through an alkoxy group.

[0032]

[00146] "Arylalkyl" or "aralkyl," as used herein, alone or in combination, refers to an aryl group attached to the parent molecular moiety through an alkyl group.

[0033] As used herein, "aryloxy," alone or in combination, refers to an aryl group attached to the parent molecular moiety through an oxy group.

[0034] As used herein, "carbamate," alone or in combination, refers to an ester of carbamic acid (-NHCO O-), which can be attached to the parent molecular moiety via either the nitrogen terminus or the acid terminus, and can be unsubstituted or substituted as defined herein.

[0035] As used herein, "O-carbamyl," alone or in combination, refers to a -OC(O)NRR' group, where R and R' are as defined herein.

[0036] As used herein, "N-carbamyl," alone or in combination, refers to a ROC(O)NR'- group, where R and R' are as defined herein.

[0037] As used herein, "carbonyl" alone includes formyl [-C(O)H] and in combination is a -C(O)- group.

[0038] As used herein, "carboxyl" or "carboxy" refers to -C(O)OH or the corresponding "carboxylate" anion, for example, in a carboxylate salt. An "O-carboxyl" group refers to a RC(O)O- group, where R is as defined herein. A "C-carboxyl" group refers to a -C(O)OR group, where R is as defined herein.

[0039] As used herein, "cyano," alone or in combination, refers to -CN.

[0040] As used herein, "cycloalkyl" or "carbocycle" alone or in combination refers to a saturated or partially saturated monocyclic, bicyclic or tricyclic alkyl group, wherein each cyclic moiety contains 3 to 12 carbon atom ring members, and is optionally a benzo-fused ring system as defined herein that is unsubstituted or substituted. Carbocycle may include a bridged ring system and / or a spirocyclic system (e.g., a system comprising two rings sharing a single carbon atom). The term "cycloalkenyl" refers to a cycloalkyl group with one or two double bonds. In certain embodiments, the cycloalkyl (or cycloalkenyl) will include 5 to 7 carbon atoms. Examples of such groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, tetrahydronaphthyl, dihydroindenyl, octahydronaphthyl, 2,3-dihydro-1H-indenyl, adamantyl, etc. As used herein, "bicyclic" and "tricyclic" are intended to include both fused ring systems such as decahydronaphthalene and octahydronaphthalene as well as polycyclic (multi-centered) saturated or partially unsaturated types. The latter type of isomers is generally exemplified by bicyclo[1,1,1]pentane, camphor, adamantane, and bicyclo[3,2,1]octane.

[0041] As used herein, "ester," alone or in combination, refers to a carboxyl group bridging two moieties linked at carbon atoms.

[0042] As used herein, "ether," alone or in combination, refers to an oxy group bridging two moieties linked at carbon atoms.

[0043] As used herein, "halo" or "halogen," alone or in combination, refers to fluoro, chloro, bromo or iodo.

[0044] As used herein, "haloalkoxy," alone or in combination, refers to a haloalkyl group attached to the parent molecular moiety through an oxygen atom.

[0045] As used herein, "haloalkyl" alone or in combination refers to an alkyl group with an implication as described herein, wherein one or more hydrogens are replaced by halogen. Specifically encompassing monohaloalkyl, dihaloalkyl and polyhaloalkyl. For an example, monohaloalkyl can have iodine, bromine, chlorine or fluorine atoms within the group. Dihaloalkyl and polyhaloalkyl can have a combination of two or more identical halogen atoms or different halogen groups. The example of haloalkyl includes fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl and dichloropropyl. "haloalkylene" refers to a haloalkyl group connected at two or more positions. Examples include fluoromethylene (-CFH-), difluoromethylene (-CF2-), chloromethylene (-CHCl-) etc.

[0046] As used herein, "heteroalkyl," alone or in combination, refers to a stable straight or branched hydrocarbon chain, fully saturated or containing 1 to 3 degrees of unsaturation, consisting of the specified number of carbon atoms and one to three heteroatoms selected from N, O, and S, and wherein the N and S atoms may be optionally oxidized and the N heteroatom may be optionally quaternized. The heteroatom may be located at any interior position of the heteroalkyl group. Up to two heteroatoms may be consecutive, for example, -CH2-NH-OCH3.

[0047] 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, wherein at least one of the fused rings is aromatic, whose ring or ring system contains at least one atom selected from N, O, and S. In certain embodiments, the heteroaryl group will contain 1 to 4 heteroatoms as ring members. In other embodiments, the heteroaryl group will contain 1 to 2 heteroatoms as ring members. In certain embodiments, the heteroaryl group will contain 5 to 7 atoms. The term also encompasses fused polycyclic groups in which a heterocyclic ring is fused to an aryl ring, in which a heteroaryl ring is fused to another heteroaryl ring, in which a heteroaryl ring is fused to a heterocycloalkyl ring, or in which a heteroaryl ring is fused to a cycloalkyl ring. Examples of heteroaryl groups include pyrrolyl, imidazolyl, pyrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazolyl, furanyl, thienyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, thiadiazolyl, isothiazolyl, indolyl, isoindolyl, indolizinyl, benzimidazolyl, quinolinyl, isoquinolinyl, quinoxalinyl, quinazolinyl, indazolyl, benzotriazolyl, benzodioxolyl, benzopyranyl, benzoxazolyl, benzoxadiazolyl, benzothiazolyl, benzothiadiazolyl, benzofuranyl, 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.

[0048] As used herein, "heterocycloalkyl" and "heterocycle" interchangeably, alone or in combination, each 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, wherein each of the heteroatoms is independently selected from nitrogen, oxygen and sulfur. In some embodiments, the heterocycle comprises a heteroaryl ring fused to a saturated, partially unsaturated or fully unsaturated (but non-aromatic) ring optionally containing a heteroatom. In some embodiments, the heterocycle comprises an aryl ring fused to a saturated, partially unsaturated or fully unsaturated (but non-aromatic) ring containing a heteroatom. In some embodiments, the heterocycle comprises a carbocyclic ring fused to a saturated, partially unsaturated or fully unsaturated ring containing a heteroatom. In some embodiments, the heterocycle comprises a first ring as a saturated, partially unsaturated or fully unsaturated ring containing a heteroatom and a second ring as 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 will include 1 to 4 heteroatoms as ring members. In other embodiments, the heterocycloalkyl will include 1 to 2 heteroatoms as ring members. In certain embodiments, the heterocycloalkyl will include 3 to 8 ring members in each ring. In other embodiments, the heterocycloalkyl will include 3 to 7 ring members in each ring. In other embodiments, the heterocycloalkyl will include 5 to 6 ring members in each ring. Heterocycle may include a bridged ring system and / or a spirocyclic system (for example, a system including two rings sharing a single atom, such as a single carbon atom). "Heterocycloalkyl" and "heterocycle" are intended to include N-oxides of sulfones, sulfoxides, tertiary nitrogen ring members, and carbocyclic fused rings and benzofused ring systems; In addition, the two terms also include systems in which heterocycles are fused to aryl or additional heterocyclic groups 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, isoindolyl, morpholinyl, piperazinyl, pyrrolidinyl, tetrahydropyridinyl, piperidinyl, thiomorpholinyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine, 4,5,6,7-tetrahydro-[1,2,3]triazolo[1,4 ... [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-imidofuro[3,2-b]furan, etc. Unless otherwise specified, the heterocyclic group may be unsubstituted or substituted.

[0049] As used herein, "hydrazino," alone or in combination, refers to two amino groups joined by a single bond, ie, -NN-.

[0050] As used herein, "hydroxy," alone or in combination, refers to -OH.

[0051] As used herein, "hydroxyalkyl," alone or in combination, refers to a hydroxy group attached to the parent molecular moiety through an alkyl group.

[0052] As used herein, "iminohydroxy," alone or in combination, refers to =N(OH) and =NO-.

[0053] As used herein, "lower amino," alone or in combination, refers to -NRR', wherein R and R' are independently selected from hydrogen and lower alkyl (e.g., C 1-4 alkyl), any of which is unsubstituted or substituted.

[0054] As used herein, "mercapto," alone or in combination, refers to an RS- group, where R is as defined herein.

[0055] As used herein, "nitro," alone or in combination, refers to -NO2.

[0056] As used herein, "oxy" or "oxa," alone or in combination, refers to -O-.

[0057] As used herein, "oxo," alone or in combination, means =0.

[0058] "Perhaloalkoxy" refers to an alkoxy group in which all of the hydrogen atoms are replaced by halogen atoms.

[0059] As used herein, "perhaloalkyl," alone or in combination, refers to an alkyl group in which all of the hydrogen atoms are replaced by halogen atoms.

[0060] As used herein, "ring" or equivalently "cycle" with respect to a chemical structure or portion thereof means a group in which each atom is a member of a common cyclic structure. Unless otherwise specified, the ring may be saturated or unsaturated, including aromatic, and may have from 3 to 9 members. If the ring is a heterocycle, it may contain from 1 to 4 atoms selected from B, N, O, S, C(O) and S(O). m wherein m is 0, 1 or 2. Unless otherwise prohibited, the ring is unsubstituted or substituted. Two or more rings may be fused together (e.g., the rings may share a bond and two common atoms). Two or more rings may be connected together in a spirocyclic arrangement so that only a single atom is shared between the two rings. Two or more rings may also or alternatively be constructed in a bridged arrangement so that three or more atoms are shared between the two or more rings.

[0061] As used herein, "sulfonate" and "sulfonic acid" or "sulfonic acid," alone or in combination, refer to the -SO3H group and its anion as the sulfonic acid is used to form the salt.

[0062] As used herein, "sulfanyl," alone or in combination, refers to -S-.

[0063] As used herein, "sulfinyl," alone or in combination, refers to -S(O)-.

[0064] As used herein, "sulfonyl," alone or in combination, refers to -S(O)2-.

[0065] "N-Sulfonamido" refers to an RS(=O)2NR'- group, where R and R' are as defined herein.

[0066] "S-Sulfonamido" refers to a -S(=O)2NRR' group where R and R' are as defined herein.

[0067] As used herein, " tautomer " alone or in combination refers to one of two or more isomers that rapidly interconvert. Typically, this interconversion is fast enough so that individual tautomers will not separate in the absence of another tautomer. The ratio of the amount of tautomers may depend on solvent composition, ionic strength, pH, and other solution parameters. The ratio of the amount of tautomers in a particular solution and in the microenvironment of a biomolecule binding site in the solution may be different. Examples of tautomers well known in the art include keto / enol, enamine / imine, and lactam / lactim tautomers. Examples of tautomers well known in the art also include 2-hydroxypyridine / 2 (1H)-pyridone and 2-aminopyridine / 2 (1H)-iminopyridone tautomers.

[0068] As used herein, "thia" and "thio," alone or in combination, refer to an -S- group or an ether wherein the oxygen is replaced by sulfur. The oxygenated derivatives of thio (ie, sulfinyl and sulfonyl) are included in the definition of thia and thio.

[0069] As used herein, "thiol," alone or in combination, refers to a -SH group.

[0070] As used herein, "thiocarbonyl" alone includes thioformyl -C(S)H and in combination is a -C(S)- group.

[0071] "N-Thiocarbamyl" refers to a ROC(S)NR'- group where R and R' are as defined herein.

[0072] "O-Thiocarbamyl" refers to a -OC(S)NRR' group where R and R' are as defined herein.

[0073] "Thiocyanato" refers to a -CNS group.

[0074] Any definition herein may be used in combination with any other definition to describe a composite structural group. By convention, the trailing element of any such definition is the element that is attached to the parent moiety. For example, the composite group alkylamido would represent an alkyl group attached to the parent molecule via an amide group, and the term alkoxyalkyl would represent an alkoxy group attached to the parent molecule via an alkyl group.

[0075] As described herein, a group may be substituted or unsubstituted (e.g., "optionally substituted"). Unless otherwise specified, any group may be substituted with one or more substituents, such as one or more substituents provided herein. Examples of substituents that may be substituted with a group include, but are not limited to, one or more substituents independently selected from the following groups or a group of specifically designated groups, either alone or in combination: alkyl (e.g., C 1-20 Alkyl groups, such as C 1-10 Alkyl groups, such as C 1-6Alkyl groups, such as C 1-3 alkyl), alkenyl (e.g., C 2-20 Alkenyl, such as C 2-10 Alkenyl, such as C 2-6 alkenyl), alkynyl (e.g., C 2-20 Alkynyl, such as C 2-10 Alkynyl, such as C 2-6 Alkynyl), alkanoyl (e.g., C 1-20 Alkanoyl, such as C 1-10 Alkanoyl, such as C 1-6 alkyl), heteroalkyl (e.g., heteroalkyl moieties comprising 1-20 carbon atoms and 1-6 heteroatoms, such as heteroalkyl moieties comprising 1-6 carbon atoms and 1-3 heteroatoms), haloalkyl (e.g., C 1-20 Alkyl, such as C 1-10 Alkyl, halogen-substituted C 1-6 alkyl), haloalkenyl (e.g., C 2-20 Alkenyl, such as C 2-6 alkenyl), haloalkynyl (e.g., C 2-20 Alkynyl, such as C 2-6 Alkynyl), perhaloalkyl (e.g., C 1-20 Perhalogenated alkyl, such as C 1-6 Perhalogenated alkyl, such as C 1-3 perhaloalkyl), perhaloalkoxy (e.g., C 1-20 Perhalogenated alkoxy, such as C 1-6 perhalogenated alkoxy), phenyl, aryl (e.g., C 5-20 Aryl, such as C 5-10 Aryl, such as C 5-6 Aryl), aryloxy (e.g., C 5-20 Aryloxy, such as C 5-10 Aryloxy, such as C 5-6 Aryloxy), alkoxy (e.g., C 1-20 Alkoxy, such as C 1-10 Alkoxy, such as C 1-6 Alkoxy), haloalkoxy (e.g., C 1-20 Halogenated alkoxy, such as C 1-10 Halogenated alkoxy, such as C 1-6 haloalkoxy), oxo, acyloxy (e.g., acyloxy containing 1 to 20 carbon atoms, such as 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, such as C 1-10 Alkylcarbonyl, such as C 1-6 Alkylcarbonyl, such as C 1-3alkylcarbonyl), carboxylesters (e.g., C(O)OR, where R is, for example, an alkyl group (e.g., C 1-20 Alkyl groups, such as C 1-10 Alkyl groups, such as C 1-6 Alkyl groups, such as C 1-3 alkyl), alkenyl (e.g., C 2-20 Alkenyl, such as C 2-10 Alkenyl, such as C 2-6 alkenyl) or alkynyl (e.g., C 2-20 Alkynyl, such as C 2-10 Alkynyl, such as C 2-6 alkynyl), any of which can be substituted with any group provided herein), carboxamido, cyano (e.g., CN), hydrogen, halogen (e.g., iodine, bromine, chlorine, or fluorine), hydroxyl, amino (e.g., NR'R", wherein R' and R" are independently, for example, hydrogen, alkyl (e.g., C 1-20 Alkyl groups, such as C 1-10 Alkyl groups, such as C 1-6 Alkyl groups, such as C 1-3 alkyl), alkenyl (e.g., C 2-20 Alkenyl, such as C 2-10 Alkenyl, such as C 2-6 alkenyl) or alkynyl (e.g., C 2-20 Alkynyl, such as C 2-10 Alkynyl, such as C 2-6 alkynyl), any of which can be substituted with any group provided herein), alkylamino (e.g., NR'R", where R' is alkyl (e.g., C 1-20 Alkyl groups, such as C 1-10 Alkyl groups, such as C 1-6 Alkyl groups, such as C 1-3 alkyl) and R" is, for example, hydrogen, alkyl (e.g., C 1-20 Alkyl groups, such as C 1-10 Alkyl groups, such as C 1-6 Alkyl groups, such as C 1-3 alkyl), alkenyl (e.g., C 2-20 Alkenyl, such as C 2-10 Alkenyl, such as C 2-6 alkenyl) or alkynyl (e.g., C 2-20 Alkynyl, such as C 2-10 Alkynyl, such as C 2-6 alkynyl), any of which can be substituted with any group provided herein), arylamino (e.g., NR'R", where R' is aryl (e.g., C 5-20 Aryl, such as C 5-10 Aryl, such as C 5-6 aryl) and R" is, for example, hydrogen, alkyl (e.g., C 1-20 Alkyl groups, such as C 1-10 Alkyl groups, such as C 1-6 Alkyl groups, such as C1-3 alkyl), alkenyl (e.g., C 2-20 Alkenyl, such as C 2-10 Alkenyl, such as C 2-6 alkenyl) or alkynyl (e.g., C 2-20 Alkynyl, such as C 2-10 Alkynyl, such as C 2-6 alkynyl), any of which can 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 groups, such as C 1-10 Alkyl groups, such as C 1-6 Alkyl groups, such as C 1-3 alkyl), alkenyl (e.g., C 2-20 Alkenyl, such as C 2-10 Alkenyl, such as C 2-6 alkenyl) or alkynyl (e.g., C 2-20 Alkynyl, such as C 2-10 Alkynyl, such as C 2-6 alkynyl), any of which can be substituted with any group provided herein), nitro (e.g., NO2), thiol (e.g., SH), alkylthio (e.g., C substituted with a thiol group), 1-20 Alkyl, such as C substituted with thiol 1-10 Alkyl, such as C substituted with thiol 1-6 Alkyl, such as C substituted with thiol 1-3 alkyl), haloalkylthio (e.g., C 1-20 Halogenated alkylthio, such as C 1-10 Halogenated alkylthio, such as C 1-6 Halogenated alkylthio, such as C 1-3 haloalkylthio), perhaloalkylthio (e.g., C 1-20 Perhalogenated alkylthio, such as C 1-10 Perhalogenated alkylthio, such as C 1-6 Perhalogenated alkylthio, such as C 1-3 perhalogenated alkylthio), arylthio (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)2OR, where R is, for example, an alkyl group (e.g., C 1-20 Alkyl groups, such as C 1-10 Alkyl groups, such as C 1-6 Alkyl groups, such as C 1-3 alkyl), alkenyl (e.g., C 2-20 Alkenyl, such as C 2-10 Alkenyl, such as C 2-6 alkenyl) or alkynyl (e.g., C 2-20 Alkynyl, such as C 2-10 Alkynyl, such as C2-6 alkynyl), any of which can be substituted with any group provided herein), sulfonic acid (e.g., S(O)2OH), trisubstituted silyl (e.g., SiR'R"R*, wherein R', R" and R* are independently selected from, for example, alkyl (e.g., C 1-20 Alkyl groups, such as C 1-10 Alkyl groups, such as C 1-6 Alkyl groups, such as C 1-3 alkyl), alkenyl (e.g., C 2-20 Alkenyl, such as C 2-10 Alkenyl, such as C 2-6 alkenyl) or alkynyl (e.g., C 2-20 Alkynyl, such as C 2-10 Alkynyl, such as C 2-6 In some cases, the trisubstituted silyl group may be trimethylsilyl), N3, SCH3, C(O)CH3, CO2CH3, CO2H, pyridyl, thiophene, furyl, carbamate and urea. Additional groups are also contemplated. Where structurally feasible, two substituents may be joined together to form a fused five-, six- or seven-membered carbocyclic or heterocyclic ring consisting of zero to three heteroatoms (e.g., N, O, S, etc.), such as methylenedioxy or ethylenedioxy. Unsubstituted or substituted groups may be unsubstituted (e.g., -CH2CH3), fully substituted (e.g., -CF2CF3), monosubstituted (e.g., -CH2CH2F), or substituted at any level between fully substituted and monosubstituted (e.g., -CH2CF3). Where substitution is not limited and substituents are listed, both substituted and unsubstituted forms are encompassed. Where a substituent is qualified as "substituted," the substituted form is specifically contemplated. Additionally, different sets of optional substituents may be defined for a particular moiety as desired; in these cases, the optional substitutions will be as defined, typically immediately following the phrase "unsubstituted or substituted."

[0076] Unless otherwise defined, the terms R, R', R", R*, etc., when appearing alone and without a designated number, refer to a moiety selected from hydrogen, alkyl, cycloalkyl, heteroalkyl, aryl, heteroaryl, and heterocycloalkyl, any of which is unsubstituted or substituted (e.g., as described herein). Such R and R' groups are understood to be unsubstituted or substituted as defined herein. Regardless of whether the R group has a designated number, each R group (including R, R', and R*) is a moiety selected from hydrogen, alkyl, cycloalkyl, heteroalkyl, aryl, heteroaryl, and heterocycloalkyl. n, wherein n=(1, 2, 3, ... n)), each substituent and each term should be understood to be independent of each other in terms of selection from the group. If any variable, substituent or term (e.g., aryl, heterocycle, R, etc.) appears more than once in a formula or general 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 can be attached to the parent molecule or can occupy the position of either end of the element chain. For example, an asymmetric group such as -C(O)N(R)- can be attached to the parent moiety at either carbon or nitrogen.

[0077] When the atoms joined by a bond are considered to be part of a larger substructure, "bond" refers to a covalent linkage between two atoms or two moieties. Unless otherwise specified, a bond can be a single bond, a double bond, or a triple bond. A dashed line between two atoms in a molecular diagram indicates that an additional bond may or may not be present at that position.

[0078] Asymmetric centers may be present in the compounds disclosed herein. Depending on the configuration of the substituents around the chiral carbon atom, these centers are indicated by the symbols "R" or "S". It should be understood that the present disclosure encompasses all stereochemical isomeric forms, including diastereoisomers, enantiomers, atropisomers and epimeric forms, as well as d-isomers and 1-isomers, and mixtures thereof. Individual stereoisomers of compounds can be prepared synthetically from commercially available starting materials containing chiral centers, or by preparing a mixture of enantiomeric products, followed by separation, such as conversion into a mixture of diastereoisomers, followed by separation or recrystallization, chromatography, direct separation of enantiomers on a chiral chromatographic column, or any other suitable method known in the art. The starting compound of a specific stereochemistry is commercially available or can be prepared and resolved by techniques known in the art. In addition, the compounds disclosed herein can exist as geometric isomers. The present disclosure includes all cis, trans, isomers, reverse, opposite (E) and same (Z) isomers and suitable mixtures thereof. In addition, the compounds may exist as tautomers; the present disclosure provides all tautomers. In addition, the compounds provided herein may include conformational isomers, which include groups that can be oriented in different conformations relative to another part. In addition, the compounds disclosed herein may exist in unsolvated forms as well as in solvated forms formed with pharmaceutically acceptable solvents (e.g., water, ethanol, etc.). In general, solvated forms are considered to be equivalent to unsolvated forms.

[0079] "Combination therapy" means the administration of two or more therapeutic agents to treat the therapeutic conditions or disorders described herein. Such administration encompasses co-administration of these therapeutic agents in a substantially simultaneous manner, for example, in a single dosage unit (e.g., one capsule) having a fixed ratio of active ingredients or in multiple separate dosage units (e.g., multiple capsules) for each active ingredient. In addition, such administration also encompasses the use of each type of therapeutic agent in a sequential manner. In either case, the treatment regimen will provide a beneficial effect of the drug combination in treating the conditions or disorders described herein.

[0080] "KRAS inhibitor" is used herein to refer to an inhibitor that exhibits an IC <RTI ID=0.0>0.001< / RTI> for KRAS activity as measured in the assays generally described herein. 50 No greater than about 100 μM, and more typically no greater than about 50 μM, of a compound in an assay 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. "IC 50 " is the concentration that reduces the activity of an enzyme (e.g., KRAS) to half-maximal levels. Certain compounds disclosed herein have been found to exhibit inhibitory effects on KRAS. In certain embodiments, the compound exhibits an IC of 0.05 with respect to KRAS (e.g., a KRAS protein having a mutation at codon 12 (e.g., G12D, G12V, G12C, G12S, G12A, or G12R mutation), a KRAS protein having a mutation at codon 13 (e.g., G13D mutation), a KRAS protein having a mutation at codon 61 (e.g., Q61H mutation), or a wild-type KRAS protein). 50 In other embodiments, the compound exhibits an IC of no greater than about 50 μM with respect to KRAS (e.g., a KRAS protein having a mutation at codon 12 (e.g., 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). 50In other embodiments, the compound exhibits an IC of no greater than about 10 μM with respect to KRAS (e.g., a KRAS protein having a mutation at codon 12 (e.g., 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). 50 In other embodiments, the compound exhibits an IC of no greater than about 1 μM with respect to KRAS (e.g., a KRAS protein having a mutation at codon 12 (e.g., 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). 50 No greater than about 200 nanomolar concentrations (nM) as measured in a KRAS assay described herein. In some embodiments, the compound exhibits an IC of 0.05 or less with respect to KRAS (e.g., a KRAS protein having a mutation at codon 12 (e.g., G12D, G12V, G12C, G12S, G12A, or G12R mutation), a KRAS protein having a mutation at codon 13 (e.g., G13D mutation), a KRAS protein having a mutation at codon 61 (e.g., Q61H mutation), or a wild-type KRAS protein). 50 Less than about 50 μM, for example, less than about 40 μM, 30 μM, 20 μM, 10 μM, 9 μM, 8 μM, 7 μM, 6 μM, 5 μM, 4 μM, 3 μM, 2 μM, 1 μM, 900 nM, 800 nM, 700 nM, 600 nM, 500 nM, 400 nM, 300 nM, 200 nM, 100 nM, 90 nM, 80 nM, 70 nM, 60 nM, 50 nM, 40 nM, 30 nM, 20 nM, 10 nM, 9 nM, 8 nM, 7 nM, 6 nM, 5 nM, 4 nM, 3 nM, 2 nM, 1 nM or less. In certain embodiments, the IC exhibited by the compound 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) is 2. 50In some embodiments, the compound exhibits an IC of less than about 1 μM for KRAS with a G12D mutation. 50 In some embodiments, the compound exhibits an IC of less than about 50 μM, for example, 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, for example, 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, for example, 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, for example, 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, for example, 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, for example, 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, for example, 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, for example, 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 Less than about 50 μM, for example, 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.

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

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

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

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

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

[0086] In some embodiments, the inhibitory activity of the KRAS inhibitor against KRAS with a G12A mutation exceeds its inhibitory activity against KRAS with another mutation, such as Q61H, G12C, G12D, G12S, G12R, G12V, or G13D mutation. For example, in some embodiments, the KRAS inhibitors provided herein have at least two-fold, five-fold, ten-fold, twenty-fold, thirty-fold, forty-fold, fifty-fold, one hundred-fold, or greater inhibitory activity against KRAS with a G12A mutation relative to KRAS with another mutation, such as Q61H, G12C, G12D, G12S, G12R, G12V, or G13D mutation.

[0087] In some embodiments, the inhibitory activity of the KRAS inhibitor against KRAS with a G13D mutation exceeds its inhibitory activity against KRAS with another mutation, such as Q61H, G12C, G12D, G12S, G12R, G12V, or G12A mutation. For example, in some embodiments, the KRAS inhibitors provided herein have at least two-fold, five-fold, ten-fold, twenty-fold, thirty-fold, forty-fold, fifty-fold, one hundred-fold, or greater inhibitory activity against KRAS with a G13D mutation relative to KRAS with another mutation, such as Q61H, G12C, G12D, G12S, G12R, G12V, or G12A mutation.

[0088] In some embodiments, the inhibitory activity of the KRAS inhibitor against KRAS with the Q61H mutation exceeds its inhibitory activity against KRAS with another mutation, such as G13D, G12C, G12D, G12S, G12R, G12V, or G12A mutation. For example, in some embodiments, the KRAS inhibitors provided herein have at least two-fold, five-fold, ten-fold, twenty-fold, thirty-fold, forty-fold, fifty-fold, one hundred-fold, or greater inhibitory activity against KRAS with the Q61H mutation relative to KRAS with another mutation, such as G13D, G12C, G12D, G12S, G12R, G12V, or G12A mutation.

[0089] In some embodiments, the inhibitory activity of the KRAS inhibitor against wild-type KRAS exceeds its inhibitory activity against KRAS with a Q61H, G13D, G12C, G12D, G12S, G12R, G12V, or G12A mutation. For example, in some embodiments, the KRAS inhibitors provided herein have at least two-fold, five-fold, ten-fold, twenty-fold, thirty-fold, forty-fold, fifty-fold, one hundred-fold, or greater inhibitory activity against wild-type KRAS relative to KRAS with a Q61H, G13D, G12C, G12D, G12S, G12R, G12V, or G12A mutation.

[0090] In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS with Q61H, G13D, G12D, G12S, G12R, G12V or G12A mutations 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.

[0091] In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS with a G12D mutation than against KRAS with a G12C mutation. In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS with a G12D mutation than against KRAS with a G12R mutation. In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS with a G12D mutation than against KRAS with a G12S mutation. In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS with a G12D mutation than against KRAS with a G12A mutation. In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS with a G12D mutation than against KRAS with a G12V mutation. In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS with a G12D mutation than against KRAS with a G13D mutation. In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS having a G12D mutation than against KRAS having a Q61H mutation.

[0092] In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS with a G12V mutation than against KRAS with a G12C mutation. In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS with a G12V mutation than against KRAS with a G12R mutation. In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS with a G12V mutation than against KRAS with a G12S mutation. In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS with a G12V mutation than against KRAS with a G12A mutation. In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS with a G12V mutation than against KRAS with a G12D mutation. In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS with a G12V mutation than against KRAS with a G13D mutation. In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS having a G12V mutation than against KRAS having a Q61H mutation.

[0093] In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS with a G12R mutation than against KRAS with a G12C mutation. In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS with a G12R mutation than against KRAS with a G12D mutation. In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS with a G12R mutation than against KRAS with a G12S mutation. In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS with a G12R mutation than against KRAS with a G12A mutation. In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS with a G12R mutation than against KRAS with a G12V mutation. In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS with a G12R mutation than against KRAS with a G13D mutation. In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against KRAS having a G12R mutation than against KRAS having a Q61H mutation.

[0094] In some embodiments, the KRAS inhibitors provided herein have greater inhibitory activity against active ("GTP-bound") KRAS having a Q61H, G12D, G12V, G12R, G12A, G12S, G12C, or G13D mutation or wild-type KRAS than against inactive ("GDP-bound") KRAS having a Q61H, G12D, G12V, G12R, G12A, G12S, G12C, or G13D mutation or wild-type KRAS. In some embodiments, the KRAS inhibitors provided herein have less 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 inhibitory activity against active ("GTP-bound") and 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 similar inhibitory activity against active ("GTP-bound") and inactive ("GDP-bound") KRAS or wild-type KRAS with Q61H, G12D, G12V, G12R, G12A, G12S, G12C, or G13D mutations. In some embodiments, the KRAS inhibitors provided herein have inhibitory activity against K-RAS4a splice variants. In some embodiments, the KRAS inhibitors provided herein have inhibitory activity against K-RAS4b splice variants. In some embodiments, the KRAS inhibitors provided herein have inhibitory activity against both K-RAS4a and K-RAS4b splice variants.

[0095] "Therapeutically effective amount" refers to the amount of a compound or pharmaceutical composition that can be used to treat or ameliorate an identified disease, disorder, or condition, or that can be used to exhibit a detectable therapeutic or inhibitory effect. The exact amount will depend on the purpose of the treatment and can be determined by those skilled in the art using known techniques (see, for example, Lieberman, Pharmaceutical Dosage Forms (Volumes 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).

[0096] The term "therapeutically acceptable" refers to those compounds (or salts, prodrugs, tautomers, zwitterionic forms, etc.) that are suitable for contact with patient tissues without excessive toxicity, irritation and allergic response, commensurate with a reasonable benefit / risk ratio, and effective for their intended use.

[0097] "Treatment" refers to any sign of success in treating or ameliorating an injury, lesion, disease, condition, or illness, including any objective or subjective parameter, such as elimination; remission; alleviation of symptoms or rendering the patient more tolerant to the injury, lesion, disease, condition, or illness; slowing the rate of degeneration or decline; making the end point of degeneration less debilitating; and / or improving the patient's physical or mental well-being. Treatment or amelioration of symptoms may be based on objective or subjective parameters, including the results of a physical examination, neuropsychiatric examination, and / or psychiatric evaluation. Treatment may also be preemptive in nature; that is, treatment may include preventing the disease, condition, or illness, preventing the onset of one or more symptoms of the disease, condition, or illness, and / or preventing the escalation of the disease, condition, or illness. Prevention of a disease, condition, or illness may involve complete protection from the disease and / or preventing the progression of the disease (e.g., progression to a later stage of the disease, condition, or illness). For example, prevention of a disease may not mean completely eliminating any effects associated with the disease at any level, but may mean preventing the symptoms of the disease, condition, or illness from reaching a clinically significant or detectable level.

[0098] "Patient" or "subject" refers to a living organism suffering from or susceptible to a disease, illness or condition that can be treated by administering a compound or pharmaceutical composition as provided herein. Non-limiting examples include humans, rats, mice, rabbits, hamsters, guinea pigs, cats, dogs, non-human primates (e.g., monkeys), goats, pigs, sheep, cattle, deer, horses and other non-mammals. Examples of mammals that can be treated by administering a compound or pharmaceutical composition as provided herein include, for example, rodents (e.g., rats, mice, squirrels, guinea pigs, hamsters, etc.), lagomorphs (e.g., rabbits, hares, etc.), primates (e.g., monkeys, apes, etc.), bovines (e.g., cattle), odd-toed ungulates (e.g., horses), even-toed ungulates (e.g., bovines such as cattle, ovines such as sheep, goats such as goats, swine such as pigs, etc.) and marsupials (e.g., kangaroos, wallabies, large kangaroos, 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 farm animal such as a goat, sheep, cattle, pig, or horse. In some embodiments, the patient or subject is an exotic animal such as a primate (e.g., monkey), a marsupial (e.g., kangaroo, wallaby, wallaby, sugar glider, etc.), or a non-domesticated or hybrid cat or dog.

[0099] As used herein, "composition" is intended to encompass a product comprising the specified ingredients in the specified amounts, as well as any product which results, directly or indirectly, from combination of the specified ingredients in the specified amounts. "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.

[0100] A "pharmaceutically acceptable excipient" refers to a substance that facilitates the administration of an active agent to a subject and its absorption by a subject. Pharmaceutical excipients that can be used in the present disclosure include, but are not limited to, binders, fillers, disintegrants, lubricants, coatings, sweeteners, flavorings, and coloring agents. One skilled in the art will recognize that other pharmaceutical excipients can be used in the present disclosure.

[0101] The term "prodrug" refers to a compound that becomes 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 provide the compounds. Additionally, prodrugs can be converted to compounds by chemical or biochemical methods in an ex vivo environment. For example, when a prodrug is placed in a transdermal patch reservoir with a suitable enzyme or chemical reagent, the prodrug can be slowly converted to the compound. Prodrugs are often useful because, in some cases, they may be easier to administer than the compound or parent drug. The prodrug may, for example, be bioavailable by oral administration, whereas the parent drug is not. The solubility of the prodrug in a pharmaceutical composition may also be improved compared to the parent drug.

[0102] The compounds disclosed herein may exist as therapeutically acceptable salts (also referred to herein as "pharmaceutically acceptable salts"). The present disclosure includes the compounds provided herein in the form of salts, including acid addition salts. Suitable salts include those formed with organic and inorganic acids. Such acid addition salts will generally be pharmaceutically acceptable. However, non-pharmaceutically acceptable salts may be used to prepare and purify the compounds in question. Base addition salts may also be formed and are pharmaceutically acceptable.

[0103] As used herein, the terms "therapeutically acceptable salts" and "pharmaceutically acceptable salts" refer to salts or zwitterionic forms of the compounds disclosed herein that are water-soluble or oil-soluble or dispersible and are therapeutically acceptable as defined herein. Salts can be prepared during the final isolation and purification of the compound, or independently prepared by reacting the appropriate compound in free base form with a suitable acid. Representative acid addition salts include acetate, adipate, alginate, L-ascorbate, aspartate, benzoate, benzenesulfonate (benzenesulfonate / besylate), bisulfate, butyrate, camphorate, camphorsulfonate, citrate, digluconate, formate, fumarate, gentisate, glutarate, glycerophosphate, glycolate, hemisulfate, heptanoate, hexanoate, hippurate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonate (hydroxyethyl sulfonate), lactate, cis- The compounds disclosed herein may be quaternized with methyl, ethyl, propyl, and butyl chlorides, bromides, and iodides; dimethyl, diethyl, dibutyl, and diamyl sulfates; decyl, lauryl, myristoyl, and stearoyl chlorides, bromides, and iodides; and benzyl and phenethyl bromides. 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 compound with an alkali metal or alkaline earth metal ion. Thus, the present disclosure encompasses sodium, potassium, magnesium, and calcium salts of the compounds disclosed herein.

[0104] Base addition salts can be prepared by reacting the carboxyl group with a suitable base (e.g., hydroxide, carbonate, or bicarbonate of a metal cation) or with ammonia or an organic primary, secondary, or tertiary amine during the final separation and purification of the compound. The cation of the therapeutically acceptable salt includes lithium, sodium, potassium, calcium, magnesium, and aluminum, and nontoxic quaternary ammonium cations, such as ammonium, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, triethylamine, diethylamine, ethylamine, tributylamine, pyridine, N,N-dimethylaniline, N-methylpiperidine, N-methylmorpholine, dicyclohexylamine, procaine, benzhydrylamine, N,N-dibenzylphenethylamine, 1-diphenylhydroxymethylamine (1-ephenamine) and N,N'-dibenzylethylenediamine. Other representative organic amines that can be used to form base addition salts include ethylenediamine, ethanolamine, diethanolamine, piperidine, and piperazine.

[0105] Salts of the compounds can be prepared by reacting the appropriate compound in its free base form with an appropriate acid.

[0106] "KRAS-positive cancer" refers to a cancer characterized by a KRAS mutation, such as a KRAS Q61H, G12C, G12D, G12R, G12A, G12S, G12V, or G13D mutation, and / or characterized by amplification of wild-type KRAS activity. In some embodiments, "KRAS-positive cancer" refers to a cancer that can benefit from inhibition of KRAS, such as wild-type KRAS or KRAS with a Q61H, G12C, G12D, G12R, G12A, G12S, G12V, or G13D mutation.

[0107] "KRAS G12C-positive cancer" refers to a cancer characterized by the KRAS G12C mutation.

[0108] "KRAS G12D-positive cancer" refers to a cancer characterized by a KRAS G12D mutation.

[0109] "KRAS G12R-positive cancer" refers to a cancer characterized by a KRAS G12R mutation.

[0110] "KRAS G12V-positive cancer" refers to a cancer characterized by the KRAS G12V mutation.

[0111] "KRAS G12A-positive cancer" refers to a cancer characterized by a KRAS G12A mutation.

[0112] "KRAS G12S-positive cancer" refers to a cancer characterized by a KRAS G12S mutation.

[0113] "KRAS G13D-positive cancer" refers to a cancer characterized by a KRAS G13D mutation.

[0114] "KRAS Q61H-positive cancer" refers to a cancer characterized by the KRAS Q61H mutation.

[0115] As used herein, "combined therapeutically effective amount" means an amount of the therapeutic agents that, when administered separately (in a time-staggered manner, in particular in a sequence-specific manner) to a warm-blooded animal, in particular to a human to be treated, shows (additive, but preferably synergistic) interaction (combined therapeutic effect). Whether this is the case can be determined, in particular, by tracking blood levels to show that both compounds are present in the blood of the human to be treated at least during certain time intervals.

[0116] 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 can be an agent configured to treat a disease, disorder or condition, or a symptom thereof. The effect can be, for example, a reduction in symptomatic progression of a proliferative disease (e.g., cancer, particularly lung cancer), or a symptom thereof. Similarly, a "synergistically effective amount" refers to the amount required to achieve a synergistic effect.

[0117] "A / an / a(n)" when used to refer to a group of substituents or a "substituent group" herein means at least one. For example, when a compound is substituted with "an" alkyl or aryl group, the compound is unsubstituted or substituted with at least one alkyl and / or at least one aryl group, wherein each alkyl and / or aryl group is optionally different. In another example, when a compound is substituted with "a" substituent group, the compound is substituted with at least one substituent group, wherein each substituent group is optionally different.

[0118] Compound

[0119] In one aspect, the present disclosure provides compounds represented by Formula I:

[0120]

[0121] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof, wherein:

[0122] R 1 Select from -OR 8 and

[0123] R 2 Selected from H and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0124] R 3 is unsubstituted or substituted with one or more R 10substituted 3-11 membered carbocyclic ring;

[0125] R 4 is H;

[0126] R 5 Selected from H, halogen, -CN, -OR 12 , 3-6 membered heterocyclic ring, 5-6 membered heteroaryl and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0127] R 6 For one or more R 15 substituted bicyclic heteroaryl;

[0128] R 7 is selected from halogen, -CN and H;

[0129] R 8 is selected from heterocycle and alkylheterocycle, wherein any heterocycle contains 4-8 members and is unsubstituted or substituted by one or more R a or R b substituted, and wherein the alkyl portion of any alkyl heterocycle is selected from C 1-6 alkyl;

[0130] Each R 10 Independently selected from -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 group is unsubstituted or substituted with one or more R 20 replace;

[0131] Each R 12 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H, wherein any C 1-6 Alkyl or C 2-6 The alkenyl group is unsubstituted or substituted with one or more R 13 replace;

[0132] Each R 13 Independently selected from -OR 14 、-CN、-N(R 14 )2 and halogen;

[0133] Each R14 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H;

[0134] Each R 15 are independently selected from deuterium, halogen, -N(R 12 )2, -CN and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0135] Each R 20 Independently selected from -OH, -OC 1-6 Alkyl, -CN, -NH2, -NHC 1-6 Alkyl and halogen;

[0136] R 27 is a 3-6 membered heterocyclic ring including one or more heteroatoms selected from N, O and S, wherein the heterocyclic ring is unsubstituted or replaced by one or more R 28 replace;

[0137] Each R 28 Independently selected from C 1-6 alkyl and halogen; and

[0138] R a and R b are each independently selected from deuterium, halogen, C 1-6 Alkyl, 3-6 membered carbocyclic ring, -OR 12 and H, where R a and R b are optionally linked together to form a 3-6 membered carbocyclic or heterocyclic ring, and wherein any C 1-6 Alkyl or 3-6 membered carbocyclic or heterocyclic ring is unsubstituted or replaced by one or more R 13 replace.

[0139] In some embodiments, the present disclosure provides a compound of Formula I or a salt (eg, a pharmaceutically acceptable salt) thereof.

[0140] In some embodiments, the present disclosure provides compounds of Formula I, wherein:

[0141] R 1 Select from -OR 8 and

[0142] R 2 Selected from H and C 1-6 alkyl;

[0143] R 3 is selected from unsubstituted or substituted by one or more R 10substituted 3-11 membered carbocyclic ring;

[0144] R 4 is H;

[0145] R 5 Selected from H, halogen, -CN, -OR 12 , 5-6 membered heteroaryl and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0146] R 6 For one or more R 15 substituted bicyclic heteroaryl;

[0147] R 7 is selected from halogen, -CN and H;

[0148] R 8 is an alkyl heterocycle, wherein any heterocycle contains 4 to 8 members and is unsubstituted or substituted by one or more R a or R b substituted, and wherein the alkyl portion of any alkyl heterocycle is selected from C 1-6 alkyl;

[0149] Each R 10 Independently selected from -OR 12 、-C(O)N(R 14 )2. Halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace;

[0150] Each R 12 Independently selected from C 1-6 Alkyl and H, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0151] Each R 13 independently selected from halogen;

[0152] Each R 14 Independently selected from C 1-6 alkyl;

[0153] Each R 15 are independently selected from halogen, -N(R 12 )2 and -CN;

[0154] Each R 20 Independently selected from -OH, -OC 1-6 Alkyl and -CN;

[0155] R 27 is a 3-6 membered heterocyclic ring including one or more heteroatoms selected from N, O and S, wherein the heterocyclic ring is unsubstituted or replaced by one or more R 28 replace;

[0156] Each R 28 are independently selected from halogen; and

[0157] R a and R b are each independently selected from halogen, C 1-6 Alkyl, -OR 12 and H, where any C 1-6 The alkyl group is unsubstituted.

[0158] In some embodiments, the present disclosure provides compounds of Formula I, wherein the compound has Formula Ia:

[0159]

[0160] or a salt (eg, a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof, wherein R 2 and R 3 As defined above for Formula I and described in classes and subclasses herein, individually and in combination. In some embodiments, the disclosure provides a compound of Formula Ia or a salt (eg, a pharmaceutically acceptable salt) thereof.

[0161] In some embodiments of the compound according to Formula I or Ia, R 3 is selected from unsubstituted 3-11 membered carbocyclic rings. 3 Selected from one or more R 10 In some embodiments, R 3 is selected from unsubstituted 3-8 membered carbocyclic rings. 3 Selected from one or more R 10 In some embodiments, R 3 is unsubstituted or replaced by one or more R 10 In some embodiments, R 3 is an unsubstituted 3-6 membered carbocyclic ring. 3 For one or more R 10 In some embodiments, R 3 For 1-4 R 10 In some embodiments, R 3 For 0-4 R 10In some embodiments, R 3 For 1-4 R 10 In some embodiments, R 3 For one or more R 10 Substituted cyclopropyl, wherein one or more R 10 At least one of the is unsubstituted or replaced by one or more R 20 Substituted C 1-6 In some embodiments, R 3 For 0-4 R 10 In some embodiments, R 3 For 1-4 R 10 In some embodiments, R 3 For 0-4 R 10 In some embodiments, R 3 For 1-4 R 10 In some embodiments, R 3 For 0-4 R 10 In some embodiments, R 3 For 1-4 R 10 In some embodiments, R 3 For one or more R 10 a substituted 3-6 membered carbocyclic ring (e.g., cyclopropane, cyclobutane, cyclopentane, or cyclohexane), wherein at least one R 10 Select from -OR 12 and C substituted by -OH 1-6 In some embodiments, R 3 For one or more R 10 a substituted 3-6 membered carbocyclic ring (e.g., cyclopropane, cyclobutane, cyclopentane, or cyclohexane), wherein at least one R 10 For-OR 12 In some embodiments, R 3 For one or more R 10 a substituted 3-6 membered carbocyclic ring (e.g., cyclopropane, cyclobutane, cyclopentane, or cyclohexane), wherein at least one R 10 C substituted by -OH 1-6 In some embodiments, R 3 For one or more R 10 a substituted 3-6 membered carbocyclic ring (e.g., cyclopropane, cyclobutane, cyclopentane, or cyclohexane), wherein at least one R 10 -C(O)N(R 14 )2. In some embodiments, R 3 For one or more R10 Substituted cyclopentane, wherein at least one R 10 -C(O)N(R 14 )2. In some embodiments, R 3 For one or more R 10 a substituted 3-6 membered carbocyclic ring (e.g., cyclopropane, cyclobutane, cyclopentane, or cyclohexane), wherein at least one R 10 For unsubstituted C 1-6 alkyl.

[0162] In some embodiments of the compound according to Formula I or Ia, R 3 is unsubstituted or replaced by one or more R 10 In some embodiments, R 3 is unsubstituted or replaced by one or more R 10 In some embodiments, R 3 is unsubstituted or replaced by one or more R 10 In some embodiments, R 3 is unsubstituted or replaced by one or more R 10 In some embodiments, R 3 is unsubstituted or replaced by one or more R 10 In some embodiments, R 3 is unsubstituted or replaced by one or more R 10 In some embodiments, R 3 is unsubstituted or replaced by one or more R 10 In some embodiments, R 3 is unsubstituted or replaced by one or more R 10 In some embodiments, R 3 is unsubstituted or replaced by one or more R 10 Substituted spiro ring, wherein one or more R 10 At least one of them is -OR 12 In some embodiments, R 3 is unsubstituted or replaced by one or more R 10Substituted spiro ring, wherein the spiro ring comprises a 4-membered ring (e.g., cyclobutane) and a 5-membered ring (e.g., cyclopentane), and the one or more R 10 At least one of them is -OR 12 .

[0163] In some embodiments of the compound according to Formula I or Ia, R 3 is unsubstituted or replaced by one or more R 10 In some embodiments, R 3 is unsubstituted or replaced by one or more R 10 In some embodiments, R 3 is unsubstituted or replaced by one or more R 10 In some embodiments, R 3 is unsubstituted or replaced by one or more R 10 In some embodiments, R 3 is unsubstituted or replaced by one or more R 10 A substituted bridged carbocyclic ring wherein one or more R 10 is unsubstituted or replaced by one or more R 20 Substituted C 1-6 alkyl.

[0164] In some embodiments of the compound according to Formula I or Ia, when R 10 -C(O)N(R 14 )2, then at least one R 14 is not H. In some embodiments, when R 10 -C(O)N(R 14 )2, then each R 14 C 1-6 Alkyl (eg, methyl or ethyl).

[0165] In some embodiments of the compound according to Formula I or Ia, R 3 Selected from:

[0166]

[0167]

[0168] Any of which is optionally further represented by one or more R 10 replace.

[0169] In some embodiments, the compound is according to Formula IA, IB, IC, ID, IE, or IF:

[0170]

[0171] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof, wherein:

[0172] R 1 Select from -OR 8 and

[0173] R 2 Selected from H and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0174] R 4 H when present;

[0175] R 5 Selected from H, halogen, -CN, -OR 12 , 3-6 membered heterocyclic ring, 5-6 membered heteroaryl and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0176] R 6 For one or more R 15 substituted bicyclic heteroaryl;

[0177] R 7 is selected from halogen, -CN and H;

[0178] R 8 is selected from heterocycle and alkylheterocycle, wherein any heterocycle contains 4-8 members and is unsubstituted or substituted by one or more R a or R b substituted, and wherein the alkyl portion of any alkyl heterocycle is selected from C 1-6 alkyl;

[0179] Each R 12 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H, wherein any C 1-6 Alkyl or C 2-6 The alkenyl group is unsubstituted or substituted with one or more R 13 replace;

[0180] Each R 13 Independently selected from -OR 14、-CN、-N(R 14 )2 and halogen;

[0181] Each R 14 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H;

[0182] Each R 15 are independently selected from deuterium, halogen, -N(R 12 )2, -CN and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0183] Each R 20 Independently selected from -OH, -OC 1-6 Alkyl, -CN, -NH2, -NHC 1-6 Alkyl and halogen;

[0184] R 27 is a 3-6 membered heterocyclic ring including one or more heteroatoms selected from N, O and S, wherein the heterocyclic ring is unsubstituted or replaced by one or more R 28 replace;

[0185] Each R 28 Independently selected from C 1-6 Alkyl and halogen;

[0186] R a and R b are each independently selected from deuterium, halogen, C 1-6 Alkyl, -OR 12 and H, where R a and R b are optionally linked together to form a 3-6 membered carbocyclic or heterocyclic ring, and wherein any C 1-6 Alkyl or 3-6 membered carbocyclic or heterocyclic ring is unsubstituted or replaced by one or more R 13 replace; and

[0187] Each R d Independently selected from 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 group is unsubstituted or substituted with one or more R 20 replace.

[0188] In some embodiments, the compound is a compound according to formula IA or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IB or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IC or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula ID or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IE or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to Formula IF or a salt (eg, a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof.

[0189] In some embodiments, the compound is a compound according to Formula IA or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to Formula IB or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to Formula IC or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to Formula ID or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to Formula IE or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to Formula IF or a salt thereof (e.g., a pharmaceutically acceptable salt).

[0190] In some embodiments, for compounds according to any one of Formula I, IA, IB, IC, ID, IE, and IF, R 6 Selected from:

[0191]

[0192] wherein X is selected from N and C-CN; Y is selected from O and S; R 23 Selected from -N(R 12 )2、C 1-6 Alkyl and C 1-6 Alkyl-N(R 14 )2, where any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 Replace; and R24 、R 25 and R 26 independently selected from H, deuterium, halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with 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, Y is S, and R 23 -N(R 12 )2. In some embodiments, X is C-CN, Y is S, and R 23 In some embodiments, R 24 is halogen (eg, fluorine). In some embodiments, R 26 For deuterium.

[0193] In some embodiments, for compounds according to any one of Formula I, IA, IB, IC, ID, IE, and IF, R 6 Selected from:

[0194]

[0195] Any of which is represented by one or more R 15 replace.

[0196] In some embodiments, for compounds according to any one of Formula I, IA, IB, IC, ID, IE, and IF, R 6 Selected from:

[0197]

[0198] In some embodiments, for compounds according to any one of Formula I, IA, IB, IC, ID, IE, and IF, R 6 Selected from:

[0199]

[0200] In some embodiments, for compounds according to any one of Formula I, IA, IB, IC, ID, IE, and IF, R 6 for

[0201] In some embodiments, the compound is according to Formula IA1, IB1, IC1, ID1, IE1, and Formula IF1:

[0202]

[0203] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof, wherein:

[0204] R 1 Select from -OR 8 and

[0205] R 2 Selected from H and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0206] R 4 H when present;

[0207] R 5 Selected from H, halogen, -CN, -OR 12 , 3-6 membered heterocyclic ring, 5-6 membered heteroaryl and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0208] R 7 is selected from halogen, -CN and H;

[0209] R 8 is selected from heterocycle and alkylheterocycle, wherein any heterocycle contains 4-8 members and is unsubstituted or substituted by one or more R a or R b substituted, and wherein the alkyl portion of any alkyl heterocycle is selected from C 1-6 alkyl;

[0210] Each R 12 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H, wherein any C 1-6 Alkyl or C 2-6 The alkenyl group is unsubstituted or substituted with one or more R 13 replace;

[0211] Each R 13 Independently selected from -OR 14 、-CN、-N(R 14 )2 and halogen;

[0212] Each R 14 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H;

[0213] Each R 20Independently selected from -OH, -OC 1-6 Alkyl, -CN, -NH2, -NHC 1-6 Alkyl and halogen;

[0214] R 27 is a 3-6 membered heterocyclic ring including one or more heteroatoms selected from N, O and S, wherein the heterocyclic ring is unsubstituted or replaced by one or more R 28 replace;

[0215] Each R 28 Independently selected from C 1-6 Alkyl and halogen;

[0216] R a and R b are each independently selected from deuterium, halogen, C 1-6 Alkyl, -OR 12 and H, where R a and R b are optionally linked together to form a 3-6 membered carbocyclic or heterocyclic ring, and wherein any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0217] Each R d Independently selected from 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 group is unsubstituted or substituted with one or more R 20 replace;

[0218] X is selected from N and C-CN;

[0219] Y is selected from O and S;

[0220] R 23 Selected from -N(R 12 )2、C 1-6 Alkyl and C 1-6 Alkyl-N(R 14 )2, where any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; and

[0221] R 24 、R 25 and R 26independently selected from H, deuterium, halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace.

[0222] In some embodiments, the compound is a compound according to formula IA1 or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IB1 or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IC1 or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula ID1 or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IE1 or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to Formula IF1 or a salt (eg, a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof.

[0223] In some embodiments, the compound is a compound according to Formula IA1 or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to Formula IB1 or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to Formula IC1 or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to Formula ID1 or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to Formula IE1 or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to Formula IF1 or a salt thereof (e.g., a pharmaceutically acceptable salt).

[0224] In some embodiments, for compounds 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, Y is S, and R 23 -N(R 12 )2. In some embodiments, X is C-CN, Y is S, and R23 In some embodiments, X is C-CN, Y is S, and R 23 -N(R 12 )2, and R 24 In some embodiments, X is C-CN, Y is S, and R 23 -N(R 12 )2, and R 24 、R 25 and R 26 One or more of is halogen (eg, F). In some embodiments, R 26 For deuterium.

[0225] In some embodiments, for compounds according to any one of Formula I, IA, IAl, IB, IBl, IC, IC1, ID, ID1, IE, IE1, IF, and IF1, R 1 Select from -OR 8 , where R 8 is selected from heterocycle and alkylheterocycle, wherein any heterocycle contains 4-8 members and is unsubstituted or substituted by one or more R a or R b substituted, and wherein the alkyl portion of any alkyl heterocycle is selected from C 1-6 In some embodiments, R 8 is a heterocycle or an alkylheterocycle, wherein any heterocycle contains 4 to 8 members and is surrounded by one or more R a or R b In some embodiments, R 8 is unsubstituted or replaced by one or more R a or R b In some embodiments, R 8 is unsubstituted or replaced by one or more R a or R b In some embodiments, R 8 is -CH2(heterocycle), wherein the heterocycle is unsubstituted or replaced by one or more R a or R b In some embodiments, the heterocyclic ring 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 heterocyclic ring 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 heterocyclic ring of the heterocycle or alkylheterocycle is replaced by one or more R a or R b Substituted, wherein one or more R a or R bis halogen (eg, F). In some embodiments, the heterocyclic ring of the heterocyclic or alkylheterocyclic ring is replaced by one or more R a or R b Substituted, wherein one or more R a or R b C 1-6 In some embodiments, the heterocyclic ring or the heterocyclic ring of the alkylheterocyclic ring is replaced by one or more R a or R b Substituted, wherein one or more R a or R b For-OR 12 (e.g., -OCH3). In some embodiments, the heterocyclic ring or the heterocyclic ring of the alkylheterocyclic ring is replaced by one or more R a or R b Substituted, wherein one or more R a or R b is a 3-6 membered carbocyclic ring (eg, cyclopropane). In some embodiments, the heterocyclic ring or the heterocyclic ring of the alkyl heterocyclic ring is replaced by one or more R a or R b Substituted, wherein one or more R a or R b For deuterium.

[0226] In some embodiments, for compounds according to any one of Formula I, IA, IAl, IB, IBl, IC, IC1, ID, ID1, IE, IE1, IF, and IF1, R 1 Selected from:

[0227]

[0228] where R a and R b are each independently selected from halogen, C 1-6 Alkyl, -OR 12 and H, where any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 In some embodiments, R a In some embodiments, R a is F. In some embodiments, R a is unsubstituted or replaced by one or more R 13 Substituted C 1-6 In some embodiments, R a In some embodiments, R a For-OC 1-6 In some embodiments, R a is H. In some embodiments, R bis H. In some embodiments, R b In some embodiments, R b is F. In some embodiments, R b is unsubstituted or replaced by one or more R 13 Substituted C 1-6 In some embodiments, R b In some embodiments, R a and R b Each of is F. In some embodiments, R a and R b In some embodiments, each of R 1 Selected from:

[0229]

[0230] In some embodiments, for compounds according to any one of Formula I, IA, IAl, IB, IBl, IC, IC1, ID, ID1, IE, IE1, IF, and IF1, R 1 Selected from:

[0231]

[0232]

[0233] In some embodiments, for compounds according to any one of Formula I, IA, IAl, IB, IBl, IC, IC1, ID, ID1, IE, IE1, IF, and IF1, R 1 Selected from:

[0234]

[0235] In some embodiments, R a is unsubstituted or replaced by one or more R 13 Substituted C 1-6 In some embodiments, R a In some embodiments, R 1 Selected from:

[0236]

[0237] In some embodiments, for compounds according to any one of Formula I, IA, IAl, IB, IBl, IC, IC1, ID, ID1, IE, IE1, IF, and IF1, R 1 Selected from:

[0238]

[0239] Each R a and R b independently selected from halogen, C 1-6 Alkyl, -OR 12 and H; and R c Selected from C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 substituted, and wherein R a and R b or R c are optionally linked together to form a 3-6 membered carbocyclic or heterocyclic ring. a and R b independently selected from halogen, C 1-6 Alkyl, -OR 12 and H; and R c Selected from C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 substituted, and wherein R attached to the same carbon atom a and R b are linked together to form a 3-6 membered carbocyclic ring. a and R b independently selected from halogen, C 1-6 Alkyl, -OR 12 and H, where R a and R c are linked together to form a 3-6 membered heterocyclic ring. a and R b independently selected from halogen, C 1-6 Alkyl, -OR 12 and H; and R c Selected from C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 In some embodiments, one R a or R b Selected from halogen, C 1-6 Alkyl and -OR 12 , and other R a and R b The group is H. In some embodiments, one R a or R b is halogen (eg, F). In some embodiments, two R a Group, two R b Group or R a and Rb is halogen (eg, F). In some embodiments, one R a or R b For-OR 12 (e.g., -OCH3 or -CHF2). In some embodiments, one R a or R b C 1-6 In some embodiments, two R a Group, two R b Group or R a and R b C 1-6 In some embodiments, R c is selected from -CH3, -CH2CH2F, -CH2CHF2 and -CH2CH2CN. In some embodiments, R a and R b are linked together to form a 3-6 membered carbocyclic ring, such as cyclopropane. In some embodiments, R a and R b are linked together to form a 3-6 membered carbon ring, such as cyclopropane. a and R c are linked together to form a 3-6 membered heterocyclic ring. 1 Selected from:

[0240]

[0241] In some embodiments, for compounds according to any one of Formula I, IA, IAl, IB, IBl, IC, IC1, ID, ID1, IE, IE1, IF, and IF1, R 1 Selected from:

[0242]

[0243] In some embodiments, for compounds according to any one of Formula I, IA, IAl, IB, IBl, IC, IC1, ID, ID1, IE, IE1, IF, and IF1, R 1 Selected from:

[0244]

[0245] In some embodiments, the compound is according to Formula IA2, IB2, IC2, ID2, IE2, or IF2:

[0246]

[0247] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof, wherein:

[0248] R 2 Selected from H and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0249] R 4 H when present;

[0250] R 5 Selected from H, halogen, -CN, -OR 12 , 3-6 membered heterocyclic ring, 5-6 membered heteroaryl and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0251] R 7 is selected from halogen, -CN and H;

[0252] Each R 12 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H, wherein any C 1-6 Alkyl or C 2-6 The alkenyl group is unsubstituted or substituted with one or more R 13 replace;

[0253] Each R 13 Independently selected from -OR 14 、-CN、-N(R 14 )2 and halogen;

[0254] Each R 14 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H;

[0255] Each R 20 Independently selected from -OH, -OC 1-6 Alkyl, -CN, -NH2, -NHC 1-6 Alkyl and halogen;

[0256] R a and R b are each independently selected from halogen, C 1-6 Alkyl, -OR 12 and H, where any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0257] Each Rd Independently selected from 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 group is unsubstituted or substituted with one or more R 20 replace;

[0258] X is selected from N and C-CN;

[0259] Y is selected from O and S;

[0260] R 23 Selected from -N(R 12 )2、C 1-6 Alkyl and C 1-6 Alkyl-N(R 14 )2, where any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; and

[0261] R 24 、R 25 and R 26 independently selected from H, deuterium, halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace.

[0262] In some embodiments, the compound is a compound according to formula IA2 or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IB2 or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IC2 or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula ID2 or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IE2 or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to Formula IF2 or a salt (eg, a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof.

[0263] In some embodiments, the compound is a compound according to formula IA2 or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to formula IB2 or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to formula IC2 or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to formula ID2 or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to formula IE2 or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to formula IF2 or a salt thereof (e.g., a pharmaceutically acceptable salt).

[0264] In some embodiments, for compounds 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, Y is S, and R 23 -N(R 12 )2. 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 -N(R 12 )2, and R 24In some embodiments, X is C-CN, Y is S, and R 23 -N(R 12 )2, and R 24 、R 25 and R 26 One or more of is halogen (eg, F). In some embodiments, R 26 For deuterium.

[0265] In some embodiments, for compounds according to any one of Formula IA2, IB2, IC2, ID2, IE2, and IF2, R a In some embodiments, R a is F. In some embodiments, R a is unsubstituted or replaced by one or more R 13 Substituted C 1-6 In some embodiments, R a In some embodiments, R a For-OC 1-6 In some embodiments, R a is H. In some embodiments, R b is H. In some embodiments, R b In some embodiments, R b is F. In some embodiments, R b is unsubstituted or replaced by one or more R 13 Substituted C 1-6 In some embodiments, R b In some embodiments, R a and R b Each of is F. In some embodiments, R a and R b Each of is methyl.

[0266] In some embodiments, for compounds according to any of Formula IA, IAl, IA2, IB, IB1, IB2, IC, IC1, IC2, ID, ID1, ID2, IE, IE1, IE2, IF, IF1, and IF2, at least one R d Select from -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 1-6Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 In some embodiments, at least one R d Select from -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 replaced by one or more R 20 Substituted C 1-6 In some embodiments, at least one R d Select from -OR 12 、-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 replaced by one or more R 20 Substituted C 1-6 In some embodiments, at least one R d Select from -OR 12 and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 In some embodiments, at least one R d In some embodiments, at least one R d is halogen (eg, F). In some embodiments, at least one R d -C(O)N(R 14 ) 2. In some embodiments, at least one R d -C(O)N(R 14 )2, where each R 14 Independently selected from C 1-6 In some embodiments, at least one R d is -C(O)N(CH3)2. In some embodiments, when R d -C(O)N(R 14 )2, then at least one R 14 is not H. In some embodiments, when R d -C(O)N(R 14 )2, then each R 14 C 1-6In some embodiments, each R d For H.

[0267] In some embodiments, for compounds according to any one of Formula 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 replaced by one or more R 13 Substituted C 1-6 In some embodiments, R 2 For unsubstituted C 1-6 In some embodiments, R 2 For one or more R 13 Substituted C 1-6 In some embodiments, R 2 is unsubstituted or replaced by one or more R 13 Substituted C 1-2 In some embodiments, R 2 For unsubstituted C 1-2 In some embodiments, R 2 For one or more R 13 Substituted C 1-2 In some embodiments, R 2 In some embodiments, R 2 For ethyl.

[0268] In some embodiments, for compounds according to any one of Formula 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 (eg, F or Cl). In some embodiments, R 5 In some embodiments, R 5 is F. In some embodiments, R 5 In some embodiments, R 5 For-OR 12 , where R 12 Selected from C 1-6 Alkyl and H. In some embodiments, R 5 In some embodiments, R 5 In some embodiments, R 5is unsubstituted or substituted with one or more R 13 Substituted C 1-6 In some embodiments, R 5 is unsubstituted or substituted with one or more R 13 Substituted C 1-2 In some embodiments, R 5 Selected from unsubstituted C 1-6 In some embodiments, R 5 Selected from C substituted by one or more halogen or -CN 1-6 In some embodiments, R 5 is C substituted by one or more halogens, such as one or more fluorines 1-6 In some embodiments, R 5 In some embodiments, R 5 In some embodiments, R 5 is selected from -CF2H, -CF3, -CH2CN and -CH2CH3. In some embodiments, R 5 is selected from -CH3, -CH2CH3, -CF2H, -CF3, -CF2CH3 and -CH2CN. In some embodiments, R 5 For one or more R 13 Substituted C 1-6 Alkyl, where each R 13 Independently selected from -OR 14 , -CN and -N(R 14 )2. In some embodiments, R 5 In some embodiments, R 5 is a 3-6 membered heterocyclic ring. 5 is a 5-6 membered heteroaryl group, for example, furan.

[0269] In some embodiments, for compounds according to any one of Formula 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 (eg, F or Cl). In some embodiments, R 7 In some embodiments, R 7 is F. In some embodiments, R 7 It is -CN.

[0270] In another aspect, the present disclosure provides a compound represented by Formula II':

[0271]

[0272] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof, wherein:

[0273] R 1 Select from -OR 8 and

[0274] R 2 Selected from H, C 1-6 Alkyl and 3-6 membered carbon ring, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0275] R 3 is selected from unsubstituted or substituted by one or more R 10 substituted 4-9 membered heterocycle;

[0276] R 4 is H;

[0277] R 5 Selected from H, halogen, -CN, -OR 12 , 3-6 membered heterocyclic ring, 5-6 membered heteroaryl and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0278] R 6 is a monocyclic or bicyclic heteroaryl group, wherein the heteroaryl group is separated by one or more R 15 replace;

[0279] R 7 selected from halogen;

[0280] R 8 is selected from heterocycle and alkylheterocycle, wherein any heterocycle contains 4-8 members and is unsubstituted or substituted by one or more R a or R b substituted, and wherein the alkyl portion of any alkyl heterocycle is selected from C 1-6 alkyl;

[0281] Each R 10 Independently selected from 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 1-6alkyl), -C(O)(3-6 membered carbocyclic ring), -C(O)(3-8 membered heterocyclic ring), -C(O)(5-6 membered heteroaryl), -C(O)O(3-6 membered carbocyclic ring), -C(O)O(3-6 membered heterocyclic ring), -C(O)O(C 1-6 Alkylene)(3-6 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, 3-6 membered heterocyclic ring and C 1-6 Alkyl, any C 1-6 The alkyl group is optionally deuterated and unsubstituted or substituted with one or more R 20 substituted, wherein any 3-6 membered carbocyclic ring, 5-6 membered heteroaryl ring or 3-6 membered or 3-8 membered heterocyclic ring is unsubstituted or replaced by one or more R 12 or R 20 Replace, and two R 10 are optionally joined together to form, together with the atoms to which they are attached, a 3-6 membered carbocyclic or heterocyclic ring;

[0282] Each R 12 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H, wherein any C 1-6 Alkyl or C 2-6 The alkenyl group is unsubstituted or substituted with one or more R 13 replace;

[0283] Each R 13 Independently selected from -OR 14 、-CN、-N(R 14 )2 and halogen;

[0284] Each R 14 independently selected from 3-6 membered carbocyclic ring, 3-6 membered heterocyclic ring, C 1-6 Alkyl, C 2-6 alkenyl and H, wherein any C 1-6 The alkyl group is optionally deuterated;

[0285] Each R 15 are independently selected from deuterium, halogen, -N(R 12 )2, -CN and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0286] Each R 20 Independently selected from -OH, -OC 1-6 Alkyl, -OC 1-6Haloalkyl, =O, -CN, -NH2, -NHC 1-6 Alkyl, -C(O)(C 1-6 alkyl), 3-6 membered carbocyclic ring, phenyl and halogen;

[0287] R 27 is a 3-6 membered heterocyclic ring including one or more heteroatoms selected from N, O and S, wherein the heterocyclic ring is unsubstituted or replaced by one or more R 28 replace;

[0288] Each R 28 Independently selected from C 1-6 alkyl and halogen; and

[0289] R a and R b are each independently selected from deuterium, halogen, C 1-6 Alkyl, 3-6 membered carbocyclic ring, -OR 12 and H, where R a and R b are optionally linked together to form a 3-6 membered carbocyclic or heterocyclic ring, and wherein any C 1-6 Alkyl or 3-6 membered carbocyclic or heterocyclic ring is unsubstituted or replaced by one or more R 13 replace.

[0290] In some embodiments, the present disclosure provides a compound of Formula II' or a salt (eg, a pharmaceutically acceptable salt) thereof.

[0291] In another aspect, the present disclosure provides a compound represented by Formula II:

[0292]

[0293] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof, wherein:

[0294] R 1 Select from -OR 8 and

[0295] R 2 Selected from H, C 1-6 Alkyl and 3-6 membered carbon ring, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0296] R 3 is selected from unsubstituted or substituted by one or more R 10 substituted 4-9 membered heterocycle, provided that (i) when the heterocycle contains a nitrogen atom, the nitrogen atom is replaced by R 10substituted, or (ii) the heterocycle does not contain an -NH- moiety;

[0297] R 4 is H;

[0298] R 5 Selected from H, halogen, -CN, -OR 12 , 3-6 membered heterocyclic ring, 5-6 membered heteroaryl and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0299] R 6 is a monocyclic or bicyclic heteroaryl group, wherein the heteroaryl group is separated by one or more R 15 replace;

[0300] R 7 selected from halogen;

[0301] R 8 is selected from heterocycle and alkylheterocycle, wherein any heterocycle contains 4-8 members and is unsubstituted or substituted by one or more R a or R b substituted, and wherein the alkyl portion of any alkyl heterocycle is selected from C 1-6 alkyl;

[0302] Each R 10 Independently selected from 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)(3-6 membered carbocyclic ring), -C(O)(3-8 membered heterocyclic ring), -C(O)(5-6 membered heteroaryl), -C(O)O(3-6 membered carbocyclic ring), -C(O)O(3-6 membered heterocyclic ring), -C(O)O(C 1-6 Alkylene)(3-6 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 group is optionally deuterated and unsubstituted or substituted with one or more R 20 wherein any 3-6 membered carbocyclic ring, 5-6 membered heteroaryl ring or 3-6 membered or 3-8 membered heterocyclic ring is unsubstituted or replaced by one or more R 12 or R 20 Replace; and two R10 are optionally joined together to form, together with the atoms to which they are attached, a 3-6 membered carbocyclic or heterocyclic ring;

[0303] Each R 12 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H, wherein any C 1-6 Alkyl or C 2-6 The alkenyl group is unsubstituted or substituted with one or more R 13 replace;

[0304] Each R 13 Independently selected from -OR 14 、-CN、-N(R 14 )2 and halogen;

[0305] Each R 14 independently selected from 3-6 membered carbocyclic ring, 3-6 membered heterocyclic ring, C 1-6 Alkyl, C 2-6 alkenyl and H, wherein any C 1-6 The alkyl group is optionally deuterated;

[0306] Each R 15 are independently selected from deuterium, halogen, -N(R 12 )2, -CN and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0307] Each R 20 Independently selected from -OH, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, =O, -CN, -NH2, -NHC 1-6 Alkyl, -C(O)(C 1-6 alkyl), 3-6 membered carbocyclic ring, phenyl and halogen;

[0308] R 27 is a 3-6 membered heterocyclic ring including one or more heteroatoms selected from N, O and S, wherein the heterocyclic ring is unsubstituted or replaced by one or more R 28 replace;

[0309] Each R 28 Independently selected from C 1-6 alkyl and halogen; and

[0310] R a and R b are each independently selected from deuterium, halogen, C 1-6 Alkyl, -OR 12 , 3-6 membered carbon ring and H, wherein R aand R b are optionally linked together to form a 3-6 membered carbocyclic or heterocyclic ring, and wherein any C 1-6 Alkyl or 3-6 membered carbocyclic or heterocyclic ring is unsubstituted or replaced by one or more R 13 replace.

[0311] In some embodiments, the present disclosure provides a compound of Formula II or a salt (eg, a pharmaceutically acceptable salt) thereof.

[0312] In some embodiments, the present disclosure provides a compound of Formula II, wherein:

[0313] R 1 For-OR 8 ;

[0314] R 2 Selected from C 1-6 Alkyl and 3-6 membered carbon ring, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0315] R 3 is selected from unsubstituted or substituted by one or more R 10 substituted 4-9 membered heterocycle, provided that (i) when the heterocycle contains a nitrogen atom, the nitrogen atom is replaced by R 10 substituted, or (ii) the heterocycle does not contain an -NH- moiety;

[0316] R 4 is H;

[0317] R 5 Selected from halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0318] R 6 is a bicyclic heteroaryl group, wherein the heteroaryl group is separated by one or more R 15 replace;

[0319] R 7 is a halogen;

[0320] R 8 is an alkyl heterocycle, wherein any heterocycle contains 4 to 8 members and is unsubstituted or substituted by one or more R a or R b substituted, and wherein the alkyl portion of any alkyl heterocycle is selected from C 1-6 alkyl;

[0321] Each R 10 Independently selected from 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)(3-6 membered carbocyclic ring), -C(O)(3-8 membered heterocyclic ring), -C(O)(5-6 membered heteroaryl), -C(O)O(3-6 membered carbocyclic ring), -C(O)O(3-6 membered heterocyclic ring), -C(O)O(C 1-6 Alkylene)(3-6 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 group is optionally deuterated and unsubstituted or substituted with one or more R 20 wherein any 3-6 membered carbocyclic ring, 5-6 membered heteroaryl ring or 3-6 membered or 3-8 membered heterocyclic ring is unsubstituted or replaced by one or more R 12 or R 20 replace;

[0322] Each R 12 Independently selected from C 1-6 Alkyl and H, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0323] Each R 13 independently selected from halogen;

[0324] Each R 14 independently selected from 3-6 membered carbocyclic ring, 3-6 membered heterocyclic ring, C 1-6 Alkyl and H;

[0325] Each R 15 are independently selected from halogen, -N(R 12 )2 and -CN;

[0326] Each R 20 Independently selected from -OH, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, -CN, -C(O)(C 1-6 alkyl), 3-6 membered carbocyclic ring, phenyl and halogen; and

[0327] R a and R b are each independently selected from deuterium, halogen, C 1-6 Alkyl, -OR 12 and H, where R a and Rb are optionally linked together to form a 3-6 membered carbocyclic ring.

[0328] In some embodiments, the present disclosure provides compounds of Formula II' or II, wherein the compound has Formula II-a:

[0329]

[0330] or a salt (eg, a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof, wherein R 2 and R 3 As defined above for Formula II and described in classes and subclasses herein, individually and in combination. In some embodiments, R 2 and R 3 As defined above for Formula II' and described in classes and subclasses herein, individually and in combination. In some embodiments, the present disclosure provides a compound of Formula II-a or a salt (eg, a pharmaceutically acceptable salt) thereof.

[0331] In some embodiments, for compounds according to any one of Formula II, II', and II-a, R 3 is a 4-6 membered heterocyclic ring including one or more heteroatoms selected from O, S and N, wherein the heterocyclic ring is unsubstituted or substituted by one or more R 10 In some embodiments, R 3 is a 4-6 membered heterocyclic ring including one or more heteroatoms selected from O, S and N, wherein the heterocyclic ring is unsubstituted or substituted by one or more R 10 substituted, provided that when the heterocyclic ring contains a nitrogen atom, the nitrogen atom is replaced by R 10 In some embodiments, R 3 is a 4-6 membered heterocyclic ring including one heteroatom selected from O and S, wherein the heterocyclic ring is unsubstituted or replaced by one or more R 10 In some embodiments, R 3 is a 4-6 membered heterocyclic ring including one heteroatom selected from O, S and N, wherein the heterocyclic ring is unsubstituted or replaced by one or more R 10 substituted, provided that when the heterocyclic ring contains a nitrogen atom, the nitrogen atom is replaced by R 10 In some embodiments, R 3 is a 4-6 membered heterocyclic ring including one heteroatom selected from O, S and N, wherein the heterocyclic ring is surrounded by 1-4 R 10 substituted, provided that when the heterocyclic ring contains a nitrogen atom, the nitrogen atom is replaced by R 10 In some embodiments, R 3 is a 4-6 membered heterocyclic ring including a nitrogen atom, wherein the heterocyclic ring is surrounded by 1-4 R10 substituted, provided that the nitrogen atom is replaced by R 10 In some embodiments, R 3 is a 4-6 membered heterocyclic ring including a sulfur atom, wherein the heterocyclic ring is surrounded by 1-4 R 10 In some embodiments, R 3 is a 4-6 membered heterocyclic ring including an oxygen atom, wherein the heterocyclic ring is surrounded by 1-4 R 10 In some embodiments, R 3 For 0-4 R 10 Substituted pyrrolidine, provided that the nitrogen atom of the heterocyclic ring is replaced by R 10 In some embodiments, R 3 For 1-4 R 10 Substituted pyrrolidine, provided that the nitrogen atom of the heterocyclic ring is replaced by R 10 In some embodiments, R 3 For 0-4 R 10 In some embodiments, R 3 For 1-4 R 10 In some embodiments, R 3 For 0-4 R 10 In some embodiments, R 3 For 1-4 R 10 In some embodiments, R 3 For one or more R 10 A substituted 4-6 membered heterocyclic ring, wherein at least one R 10 Select from -OR 12 and C substituted by -OH 1-6 alkyl, provided that when the heterocyclic ring contains a nitrogen atom, the nitrogen atom is replaced by R 10 In some embodiments, R 3 For one or more R 10 A substituted 4-6 membered heterocyclic ring, wherein at least one R 10 For unsubstituted C 1-6 alkyl, provided that when the heterocyclic ring contains a nitrogen atom, the nitrogen atom is replaced by R 10 In some embodiments, R 3 Selected from one or more R 10 substituted 4-6 membered heterocycle, provided that when the heterocycle contains a nitrogen atom, the nitrogen atom is replaced by R 10 Substitute, where each R 10 Independently selected from -OR 12 ,=O,-C(O)(C 1-6Alkylene)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 replaced by one or more R 20 Substituted C 1-6 In some embodiments, R 3 Selected from one or more R 10 substituted 4-6 membered heterocycle, provided that when the heterocycle contains a nitrogen atom, the nitrogen atom is replaced by R 10 Substitute, where each R 10 Independently selected from -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)(3-6 membered carbocyclic ring), -C(O)(3-7 membered heterocyclic ring), -C(O)(5-6 membered heteroaryl), -C(O)O(3-6 membered heterocyclic ring), -C(O)O(C 1-6 Alkylene)(3-6 membered heterocycle), -C(O)OR 14 、-S(O)2(C 1-6 alkyl), halogen, 3-6 membered carbocyclic ring and unsubstituted or substituted by one or more R 20 Substituted C 1-6 Alkyl, wherein any 3-6 membered carbocyclic ring, 5-6 membered heteroaryl ring or 3-6 membered heterocyclic ring is unsubstituted or replaced by one or more R 12 or R 20 In some embodiments, R 3 Selected from one or more R 10 substituted 4-6 membered heterocycle, provided that when the heterocycle contains a nitrogen atom, the nitrogen atom is replaced by R 10 Replace, and each R 10 independently selected from -C(O)(C 1-6 alkyl), -C(O)(3-6 membered carbocyclic ring), -C(O)O(C 1-6 alkyl), halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 substituted, and any 3-6 membered carbocyclic ring is unsubstituted or replaced by one or more R 12 or R 20 In some embodiments, R 3 Selected from one or more R 10substituted 4-6 membered heterocycle, provided that when the heterocycle contains a nitrogen atom, the nitrogen atom is replaced by R 10 substituted, wherein at least one R 10 Selected from -C(O)(C 1-6 alkyl) and -C(O)O(C 1-6 In some embodiments, two R 10 are joined together to form a 3-6 membered carbocyclic or heterocyclic ring together with the atoms to which they are attached. In some embodiments, two R 10 are joined together to form a 3-6 membered carbocyclic or heterocyclic ring together with the atoms to which they are attached. In some embodiments, two R 10 are joined together to form a 5-6 membered heterocyclic ring, such as pyrrolidine or oxazolidine. 10 The 3-6 membered carbocyclic or heterocyclic ring formed by the connection is formed by one or more R 10 In some embodiments, the two R 10 The 5-6 membered heterocyclic ring formed by the connection is 10 In some embodiments, the two R 10 The 5-6 membered heterocyclic ring (eg, pyrrolidine or oxazolidine) is substituted with =0. In some embodiments, each R 10 Independently selected from -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)(3-6 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 group is unsubstituted or substituted with one or more R 20 Replace, and two R 10 are optionally linked together to form a 3-6 membered carbocyclic or heterocyclic ring together with the atoms to which they are attached. 10 Independently selected from -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)(3-6 membered carbocyclic ring), -C(O)N(R 14 )2、-S(O)2(C 1-6 alkyl), halogen and C 1-6Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 In some embodiments, each R 10 Independently selected from -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 group is unsubstituted or substituted with one or more R 20 In some embodiments, each R 10 independently selected from -C(O)(C 1-6 alkyl), -C(O)(3-6 membered carbocyclic ring), -C(O)O(C 1-6 alkyl), halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 substituted, and any 3-6 membered carbocyclic ring is unsubstituted or replaced by one or more R 12 or R 20 replace.

[0332] In some embodiments, for compounds according to any one of Formula II, II', and II-a, R 3 is a 7-9 membered heterocyclic ring including one or more heteroatoms selected from O, S and N, wherein the heterocyclic ring is unsubstituted or replaced by one or more R 10 In some embodiments, R 3 is a 7-9 membered heterocyclic ring including one or more heteroatoms selected from O, S and N, wherein the heterocyclic ring is unsubstituted or replaced by one or more R 10 substituted, provided that (i) when the heterocyclic ring contains a nitrogen atom, the nitrogen atom is replaced by R 10 In some embodiments, R 3 is a 7-9 membered heterocyclic ring including one or more heteroatoms selected from O, S and N, wherein the heterocyclic ring is unsubstituted or replaced by one or more R 10 substituted, provided that (i) when the heterocyclic ring contains a nitrogen atom, the nitrogen atom is replaced by R 10 or (ii) when the heterocycle contains a single ring, the heterocycle does not contain an -NH- moiety. 3 is a 7-9 membered bridged heterocycle comprising one or more heteroatoms selected from O, S and N, wherein the bridged heterocycle is unsubstituted or substituted by one or more R 10 In some embodiments, R3 is a 7-9 membered bridged heterocycle comprising one or more heteroatoms selected from O, S and N, wherein the bridged heterocycle is unsubstituted or substituted by one or more R 10 substituted, provided that (i) when the bridged heterocycle contains a nitrogen atom, the nitrogen atom is replaced by R 10 In some embodiments, R 3 is unsubstituted or replaced by one or more R 10 In some embodiments, R 3 is unsubstituted or replaced by one or more R 10 In some embodiments, R 3 For one or more R 10 In some embodiments, R 3 is a 7-9 membered heterocyclic ring containing a fused ring system including one or more heteroatoms selected from O, S and N, wherein the heterocyclic ring is unsubstituted or replaced by one or more R 10 In some embodiments, R 3 is a 7-9 membered heterocyclic ring containing a fused ring system including one or more heteroatoms selected from O, S and N, wherein the heterocyclic ring is unsubstituted or replaced by one or more R 10 substituted, provided that (i) when the heterocyclic ring contains a nitrogen atom, the nitrogen atom is replaced by R 10 In some embodiments, R 3 is a 7-9 membered heterocyclic ring comprising a fused ring system containing two rings, wherein the heterocyclic ring includes one or more heteroatoms selected from O, S and N, and the heterocyclic ring is unsubstituted or replaced by one or more R 10 In some embodiments, R 3 is a 7-9 membered heterocyclic ring comprising a fused ring system containing two rings, wherein the heterocyclic ring includes one or more heteroatoms selected from O, S and N, and the heterocyclic ring is unsubstituted or replaced by one or more R 10 substituted, provided that (i) when the heterocyclic ring contains a nitrogen atom, the nitrogen atom is replaced by R 10 In some embodiments, R 3 Contains a fused ring system containing two rings, at least one of which is unsubstituted or substituted with one or more R 10 In some embodiments, R 3 Contains a fused ring system containing two rings, at least one of which is unsubstituted or substituted with one or more R 10In some embodiments, R 3 Contains a fused ring system containing two rings, each of which is unsubstituted or substituted with one or more R 10 In some embodiments, R 3 Contains a fused ring system containing two rings, one of which is unsubstituted or substituted with one or more R 10 substituted 5-membered heterocyclic ring and the second ring is unsubstituted or replaced by one or more R 10 In some embodiments, R 3 Contains a fused ring system containing two rings, one of which is unsubstituted or substituted with one or more R 10 substituted pyrrolidine and the second ring is unsubstituted or replaced by one or more R 10 In some embodiments, the fused ring system is replaced by at least one R 10 substituted, wherein at least one R 10 Selected from =O and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace.

[0333] In some embodiments, when R 10 -C(O)N(R 14 )2, then at least one R 14 is not H. In some embodiments, when R 10 -C(O)N(R 14 )2, then each R 14 C 1-6 Alkyl (eg, methyl or ethyl).

[0334] In some embodiments, for compounds according to Formula II' or II-a, R 3 Selected from:

[0335]

[0336] Any of which is optionally further represented by one or more R 10 replace.

[0337] In some embodiments, for compounds according to any one of Formula II', II, and II-a, R 3 Selected from:

[0338]

[0339]

[0340]

[0341]

[0342]

[0343]

[0344]

[0345] Any of which is optionally further represented by one or more R 10 replace.

[0346] In some embodiments, for compounds according to Formula II' or II, R 3 Selected from:

[0347]

[0348] Any of which is optionally further represented by one or more R 10 replace.

[0349] In some embodiments, the compound is according to 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:

[0350]

[0351]

[0352] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof, wherein:

[0353] R 1 Select from -OR 8 and

[0354] R 2 Selected from H, C 1-6 Alkyl and 3-6 membered carbon ring, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0355] R 4 H when present;

[0356] R 5 Selected from H, halogen, -CN, -OR 12, 3-6 membered heterocyclic ring, 5-6 membered heteroaryl and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0357] R 6 is a monocyclic or bicyclic heteroaryl group, wherein the heteroaryl group is separated by one or more R 15 replace;

[0358] R 7 selected from halogen;

[0359] R 8 is selected from heterocycle and alkylheterocycle, wherein any heterocycle contains 4-8 members and is unsubstituted or substituted by one or more R a or R b substituted, and wherein the alkyl portion of any alkyl heterocycle is selected from C 1-6 alkyl;

[0360] Each R 12 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H, wherein any C 1-6 Alkyl or C 2-6 The alkenyl group is unsubstituted or substituted with one or more R 13 replace;

[0361] Each R 13 Independently selected from -OR 14 、-CN、-N(R 14 )2 and halogen;

[0362] Each R 14 independently selected from 3-6 membered carbocyclic ring, 3-6 membered heterocyclic ring, C 1-6 Alkyl, C 2-6 alkenyl and H, wherein any C 1-6 The alkyl group is optionally deuterated;

[0363] Each R 15 are independently selected from deuterium, halogen, -N(R 12 )2, -CN and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0364] Each R 20 Independently selected from -OH, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, =O, -CN, -NH2, -NHC 1-6 Alkyl, -C(O)(C 1-6alkyl), 3-6 membered carbocyclic ring, phenyl and halogen;

[0365] R 27 is a 3-6 membered heterocyclic ring including one or more heteroatoms selected from N, O and S, wherein the heterocyclic ring is unsubstituted or replaced by one or more R 28 replace;

[0366] Each R 28 Independently selected from C 1-6 Alkyl and halogen;

[0367] R a and R b are each independently selected from deuterium, halogen, C 1-6 Alkyl, -OR 12 , 3-6 membered carbon ring and H, wherein R a and R b are optionally linked together to form a 3-6 membered carbocyclic or heterocyclic ring, and wherein any C 1-6 Alkyl or 3-6 membered carbocyclic or heterocyclic ring is unsubstituted or replaced by one or more R 13 replace;

[0368] Each R d Independently selected from 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)(3-6 membered carbocyclic ring), -S(O)2(C 1-6 alkyl), halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 substituted, and any 3-6 membered carbocyclic ring is unsubstituted or replaced by one or more R 12 or R 20 replace;

[0369] R e When present, selected from -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 carbocyclic ring), -C(O)(3-8 membered heterocyclic ring), -C(O)(5-6 membered heteroaryl), -C(O)O(3-6 membered carbocyclic ring), -C(O)O(3-6 membered heterocyclic ring), -C(O)O(C 1-6Alkylene)(3-6 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 group is optionally deuterated and unsubstituted or substituted with one or more R 20 substituted, and any 3-6 membered carbocyclic ring, 5-6 membered heteroaryl ring or 3-6 membered or 3-8 membered heterocyclic ring is unsubstituted or replaced by one or more R 12 or R 20 replace; and

[0370] Each R f Optionally absent and when present is selected from ═O, —NH 2 , —NHC 1-6 Alkyl and -N(C 1-6 Alkyl)2.

[0371] In some embodiments, the compound is a compound according to formula IIA or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIB or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIC or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IID or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIE or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIF or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIG or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIH or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIJ or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIK or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIL or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIM or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIN or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIP or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIQ or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer.In some embodiments, the compound is a compound according to formula IIR or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIS or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIT or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIU or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIV or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIW or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIX or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIY or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIZ or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer.

[0372] In some embodiments, the compound is a compound according to Formula IIA or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to Formula IIB or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to Formula IIC or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to Formula IID or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to Formula IIE or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to Formula IIF or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to Formula IIG or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to Formula IIH or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to Formula IIJ or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to Formula IIK or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to formula IIL or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to formula IIM or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to formula IIN or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to formula IIP or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to formula IIQ or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to formula IIR or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to formula IIS or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to formula IIT or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to formula IIU or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to formula IIV or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to Formula IIW or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to Formula IIX or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to Formula IIY or a salt thereof (e.g., a pharmaceutically acceptable salt).In some embodiments, the compound is a compound according to Formula IIZ or a salt (eg, a pharmaceutically acceptable salt) thereof.

[0373] In some embodiments, the compound is according to Formula IIAA:

[0374]

[0375] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof, wherein:

[0376] R 1 Select from -OR 8 and

[0377] R 2 Selected from H, C 1-6 Alkyl and 3-6 membered carbon ring, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0378] R 4 is H;

[0379] R 5 Selected from H, halogen, -CN, -OR 12 , 3-6 membered heterocyclic ring, 5-6 membered heteroaryl and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0380] R 6 is a monocyclic or bicyclic heteroaryl group, wherein the heteroaryl group is separated by one or more R 15 replace;

[0381] R 7 selected from halogen;

[0382] R 8 is selected from heterocycle and alkylheterocycle, wherein any heterocycle contains 4-8 members and is unsubstituted or substituted by one or more R a or R b substituted, and wherein the alkyl portion of any alkyl heterocycle is selected from C 1-6 alkyl;

[0383] Each R 12 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H, wherein any C 1-6 Alkyl or C 2-6 The alkenyl group is unsubstituted or substituted with one or more R 13 replace;

[0384] Each R 13 Independently selected from -OR 14 、-CN、-N(R 14 )2 and halogen;

[0385] Each R 14 independently selected from 3-6 membered carbocyclic ring, 3-6 membered heterocyclic ring, C 1-6 Alkyl, C 2-6 alkenyl and H, wherein any C 1-6 The alkyl group is optionally deuterated;

[0386] Each R 15 are independently selected from deuterium, halogen, -N(R 12 )2, -CN and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0387] Each R 20 Independently selected from -OH, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, =O, -CN, -NH2, -NHC 1-6 Alkyl, -C(O)(C 1-6 alkyl), 3-6 membered carbocyclic ring, phenyl and halogen;

[0388] R 27 is a 3-6 membered heterocyclic ring including one or more heteroatoms selected from N, O and S, wherein the heterocyclic ring is unsubstituted or replaced by one or more R 28 replace;

[0389] Each R 28 Independently selected from C 1-6 Alkyl and halogen;

[0390] R a and R b are each independently selected from deuterium, halogen, C 1-6 Alkyl, -OR 12 , 3-6 membered carbon ring and H, wherein R a and R b are optionally linked together to form a 3-6 membered carbocyclic or heterocyclic ring, and wherein any C 1-6 Alkyl or 3-6 membered carbocyclic or heterocyclic ring is unsubstituted or replaced by one or more R 13 replace;

[0391] Each R d Independently selected from H, deuterium, -OR 12 ,=O,-C(O)(C 1-6Alkylene)CN, -C(O)(C 1-6 Alkylene)OH, -C(O)(C 1-6 Alkyl), -C(O)(3-6 membered carbocyclic ring), -S(O)2(C 1-6 alkyl), halogen, 3-6 membered carbocyclic ring, 3-6 membered heterocyclic ring and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 substituted, wherein any 3-6 membered carbocyclic ring or 3-6 membered heterocyclic ring is unsubstituted or replaced by one or more R 12 or R 20 replace; and

[0392] (i)R q1 、R q2 and R p2 Each independently selected from R d , and R e and R p1 Together with the atoms to which it is attached, it forms an unsubstituted or substituted atom or atoms. d a substituted 5-6 membered heterocycle; or

[0393] (ii)R p1 、R p2 and R q2 Each independently selected from R d , and R e and R q1 Together with the atoms to which it is attached, it forms an unsubstituted or substituted with one or more R d Substituted 5-6 membered heterocycle.

[0394] In some embodiments, the compound is a compound according to Formula IIAA or a salt (eg, a pharmaceutically acceptable salt) thereof.

[0395] In some embodiments, for compounds according to any one of Formula 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 For one or more R 15 In some embodiments, R 6 For one or more R 15 In some embodiments, at least one R 15 Selected from C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R13 In some embodiments, at least one R 15 -N(R 12 )2. In some embodiments, R 6 Selected from Any of which is optionally replaced by one or more R 15 In some embodiments, R 6 for

[0396] In some embodiments, for compounds according to any one of Formula 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 For one or more R 15 In some embodiments, R 6 Selected from:

[0397]

[0398] wherein X is selected from N and C-CN; Y is selected from O and S; R 23 Selected from -N(R 12 )2、C 1-6 Alkyl and C 1-6 Alkyl-N(R 14 )2, where any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 Replace; and R 24 、R 25 and R 26 independently selected from H, deuterium, halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with 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, Y is S, and R 23 -N(R 12 )2. In some embodiments, X is C-CN, Y is S, and R 23 In some embodiments, R 24 is halogen (eg, fluorine). In some embodiments, R 26 For deuterium.

[0399] In some embodiments, for compounds according to any one of Formula 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 Selected from:

[0400]

[0401] Any of which is represented by one or more R 15 replace.

[0402] In some embodiments, for compounds according to any one of Formula 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 Selected from:

[0403]

[0404]

[0405] In some embodiments, for compounds according to any one of Formula 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 Selected from:

[0406]

[0407] In some embodiments, for compounds according to any one of Formula 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 for

[0408] In some embodiments, the compound is according to 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:

[0409]

[0410]

[0411]

[0412] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof, wherein:

[0413] R 1 Select from -OR 8 and

[0414] R 2 Selected from H, C 1-6 Alkyl and 3-6 membered carbon ring, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0415] R 4 H when present;

[0416] R 5 Selected from H, halogen, -CN, -OR 12 , 3-6 membered heterocyclic ring, 5-6 membered heteroaryl and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0417] R 7 selected from halogen;

[0418] R 8 is selected from heterocycle and alkylheterocycle, wherein any heterocycle contains 4-8 members and is unsubstituted or substituted by one or more R a or R b substituted, and wherein the alkyl portion of any alkyl heterocycle is selected from C 1-6 alkyl;

[0419] Each R 12 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H, wherein any C 1-6Alkyl or C 2-6 The alkenyl group is unsubstituted or substituted with one or more R 13 replace;

[0420] Each R 13 Independently selected from -OR 14 、-CN、-N(R 14 )2 and halogen;

[0421] Each R 14 independently selected from 3-6 membered carbocyclic ring, 3-6 membered heterocyclic ring, C 1-6 Alkyl, C 2-6 alkenyl and H, wherein any C 1-6 The alkyl group is optionally deuterated;

[0422] Each R 20 Independently selected from -OH, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, =O, -CN, -NH2, -NHC 1-6 Alkyl, -C(O)(C 1-6 alkyl), 3-6 membered carbocyclic ring, phenyl and halogen;

[0423] R 27 is a 3-6 membered heterocyclic ring including one or more heteroatoms selected from N, O and S, wherein the heterocyclic ring is unsubstituted or replaced by one or more R 28 replace;

[0424] Each R 28 Independently selected from C 1-6 Alkyl and halogen;

[0425] R a and R b are each independently selected from deuterium, halogen, C 1-6 Alkyl, -OR 12 , 3-6 membered carbon ring and H, wherein R a and R b are optionally linked together to form a 3-6 membered carbocyclic or heterocyclic ring, and wherein any C 1-6 Alkyl or 3-6 membered carbocyclic or heterocyclic ring is unsubstituted or replaced by one or more R 13 replace;

[0426] Each R d Independently selected from 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)(3-6 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 group is unsubstituted or substituted with one or more R 20 substituted, and any 3-6 membered carbocyclic ring is unsubstituted or replaced by one or more R 12 or R 20 replace;

[0427] R e When present, selected from -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 carbon ring), -C(O)N(R 14 )2, -C(O)(3-8 membered heterocyclic ring), -C(O)(5-6 membered heteroaryl), -C(O)O(3-6 membered carbocyclic ring), -C(O)O(3-6 membered heterocyclic ring), -C(O)O(C 1-6 Alkylene)(3-6 membered heterocycle), -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 group is optionally deuterated and unsubstituted or substituted with one or more R 20 substituted, and any 3-6 membered carbocyclic ring, 5-6 membered heteroaryl ring or 3-6 membered or 3-8 membered heterocyclic ring is unsubstituted or replaced by one or more R 12 or R 20 replace;

[0428] Each R f Optionally absent and when present is selected from ═O, —NH 2 , —NHC 1-6 Alkyl and -N(C 1-6 Alkyl)2;

[0429] X is selected from N and C-CN;

[0430] Y is selected from O and S;

[0431] R 23 Selected from -N(R 12 )2、C 1-6 Alkyl and C 1-6 Alkyl-N(R 14 )2, where any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; and

[0432] R 24 、R 25 and R 26 independently selected from H, deuterium, halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace.

[0433] In some embodiments, the compound is a compound according to Formula IIA1 or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer. In some embodiments, the compound is a compound according to Formula IIB1 or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer. In some embodiments, the compound is a compound according to Formula IIC1 or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer. In some embodiments, the compound is a compound according to Formula IID1 or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer. In some embodiments, the compound is a compound according to Formula IIE1 or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer. In some embodiments, the compound is a compound according to formula IIF1 or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIG1 or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIH1 or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIJ1 or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIK1 or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIL1 or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIM1 or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIN1 or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIP1 or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer.In some embodiments, the compound is a compound according to formula IIQ1 or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIR1 or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIS1 or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIT1 or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIU1 or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIV1 or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIW1 or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIX1 or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIY1 or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer. In some embodiments, the compound is a compound according to formula IIZ1 or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form or stereoisomer.

[0434] In some embodiments, the compound is a compound according to Formula IIA1 or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to Formula IIB1 or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to Formula IIC1 or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to Formula IID1 or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to Formula IIE1 or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to Formula IIF1 or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to Formula IIG1 or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to Formula IIH1 or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to Formula IIJ1 or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to formula IIK1 or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to formula IIL1 or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to formula IIM1 or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to formula IIN1 or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to formula IIP1 or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to formula IIQ1 or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to formula IIR1 or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to formula IIS1 or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to formula IIT1 or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to formula IIU1 or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to formula IIV1 or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to formula IIW1 or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to formula IIIX1 or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the compound is a compound according to formula IIY1 or a salt thereof (e.g., a pharmaceutically acceptable salt).In some embodiments, the compound is a compound according to Formula IIZ1 or a salt (eg, a pharmaceutically acceptable salt) thereof.

[0435] In some embodiments, the compound is according to Formula IIAA1:

[0436]

[0437] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof, wherein:

[0438] R 1 Select from -OR 8 and

[0439] R 2 Selected from H, C 1-6 Alkyl and 3-6 membered carbon ring, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0440] R 4 is H;

[0441] R 5 Selected from H, halogen, -CN, -OR 12 , 3-6 membered heterocyclic ring, 5-6 membered heteroaryl and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0442] R 7 selected from halogen;

[0443] R 8 is selected from heterocycle and alkylheterocycle, wherein any heterocycle contains 4-8 members and is unsubstituted or substituted by one or more R a or R b substituted, and wherein the alkyl portion of any alkyl heterocycle is selected from C 1-6 alkyl;

[0444] Each R 12 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H, wherein any C 1-6 Alkyl or C 2-6 The alkenyl group is unsubstituted or substituted with one or more R 13 replace;

[0445] Each R 13 Independently selected from -OR 14 、-CN、-N(R14 )2 and halogen;

[0446] Each R 14 independently selected from 3-6 membered carbocyclic ring, 3-6 membered heterocyclic ring, C 1-6 Alkyl, C 2-6 alkenyl and H, wherein any C 1-6 The alkyl group is optionally deuterated;

[0447] Each R 20 Independently selected from -OH, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, =O, -CN, -NH2, -NHC 1-6 Alkyl, -C(O)(C 1-6 alkyl), 3-6 membered carbocyclic ring, phenyl and halogen;

[0448] R 27 is a 3-6 membered heterocyclic ring including one or more heteroatoms selected from N, O and S, wherein the heterocyclic ring is unsubstituted or replaced by one or more R 28 replace;

[0449] Each R 28 Independently selected from C 1-6 Alkyl and halogen;

[0450] R a and R b are each independently selected from deuterium, halogen, C 1-6 Alkyl, -OR 12 , 3-6 membered carbon ring and H, wherein R a and R b are optionally linked together to form a 3-6 membered carbocyclic or heterocyclic ring, and wherein any C 1-6 Alkyl or 3-6 membered carbocyclic or heterocyclic ring is unsubstituted or replaced by one or more R 13 replace;

[0451] Each R d Independently selected from 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)(3-6 membered carbocyclic ring), -C(O)N(R 14 )2、-S(O)2(C 1-6 alkyl), 3-6 membered carbocyclic ring, 3-6 membered heterocyclic ring, halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20substituted, and any 3-6 membered carbocyclic ring or 3-6 membered heterocyclic ring is unsubstituted or replaced by one or more R 12 or R 20 replace;

[0452] X is selected from N and C-CN;

[0453] Y is selected from O and S;

[0454] R 23 Selected from -N(R 12 )2、C 1-6 Alkyl and C 1-6 Alkyl-N(R 14 )2, where any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0455] R 24 、R 25 and R 26 independently selected from H, deuterium, halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; and

[0456] (i)R q1 、R q2 and R p2 Each independently selected from R d , and R e and R p1 Together with the atoms to which it is attached, it forms an unsubstituted or substituted with one or more R d a substituted 5-6 membered heterocycle; or

[0457] (ii)R p1 、R p2 and R q2 Each independently selected from R d , and R e and R q1 Together with the atoms to which it is attached, it forms an unsubstituted or substituted with one or more R d Substituted 5-6 membered heterocycle.

[0458] In some embodiments, the compound is a compound according to Formula IIA1 or a salt (eg, a pharmaceutically acceptable salt) thereof.

[0459] In some embodiments, for compounds according to Formula IIAA or IIAA1, R q1 、R q2 and R p2 Each independently selected from R d , and R eand R p1 Together with the atoms to which it is attached, it forms an unsubstituted or substituted atom or atoms. d In some embodiments, R e and R p1 Together with the atoms to which it is attached, it forms an unsubstituted or substituted atom or atoms. d In some embodiments, R e and R p1 Together with the atoms to which it is attached, it forms an unsubstituted or substituted atom or atoms. d In some embodiments, R e and R p1 Together with the atoms to which they are attached, they form an unsubstituted 5-6 membered heterocyclic ring. e and R p1 Together with the atoms to which it is attached, it forms a d substituted 5-6 membered heterocycle, provided that at least one R d is not H. In some embodiments, R e and R p1 Together with the atoms to which it is attached, it forms an unsubstituted or substituted atom or atoms. d In some embodiments, R e and R p1 Together with the atoms to which it is attached, it forms an unsubstituted or substituted atom or atoms. d In some embodiments, R p2 For H.

[0460] In some embodiments, for compounds according to Formula IIAA or IIAA1, R p1 、R p2 and R q2 Each independently selected from R d , and R e and R q1 Together with the atoms to which it is attached, it forms an unsubstituted or substituted atom or atoms. d In some embodiments, R e and R q1 Together with the atoms to which it is attached, it forms an unsubstituted or substituted atom or atoms. d In some embodiments, R e and R q1 Together with the atoms to which it is attached, it forms an unsubstituted or substituted atom or atoms. d In some embodiments, Re and R q1 Together with the atoms to which they are attached, they form an unsubstituted 5-6 membered heterocyclic ring. e and R q1 Together with the atoms to which it is attached, it forms a d substituted 5-6 membered heterocycle, provided that at least one R d is not H. In some embodiments, R e and R q1 Together with the atoms to which it is attached, it forms an unsubstituted or substituted with one or more R d In some embodiments, R e and R p1 Together with the atoms to which it is attached, it forms an unsubstituted or substituted with one or more R d In some embodiments, R q2 For H.

[0461] In some embodiments, for compounds 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, Y is S, and R 23 -N(R 12 )2. 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 -N(R 12 )2, and R 24 In some embodiments, X is C-CN, Y is S, and R 23 -N(R 12 )2, and R 24 、R 25 and R 26 One or more of is halogen (eg, F). In some embodiments, R 26 For deuterium.

[0462] In some embodiments, for compounds according to any one of Formula IIC, IIC1, IIE, IIE1, IIL, IIL1, IIM, IIM1, IIQ, IIQ1, IIS, IIS1, IIY, IIY1, IIZ, and IIZ1, each R f =0. In some embodiments, each R f is optionally absent and, when present, is =0. In some embodiments, each R f Does not exist.

[0463] In some embodiments, for a compound of any one of Formula 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 Select from -OR 12 and C substituted by -OH 1-6 In some embodiments, each R d Independently selected from 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 replaced by one or more R 20 Substituted C 1-6 It should be understood that when R d When it is =O, other R on the same carbon atom d is absent so that the carbon has the appropriate valence.

[0464] In some embodiments, for compounds 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 Selected from -C(O)(C 1-6 Alkylene)CN, -C(O)(C 1-6Alkylene)OH, -C(O)(C 1-6 alkyl), -C(O)(3-6 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 The alkyl group is unsubstituted or substituted with one or more R 20 substituted and wherein any 3-6 membered carbocyclic ring is unsubstituted or replaced by one or more R 12 or R 20 In some embodiments, R e Selected from -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 carbocyclic ring), -C(O)(3-7 membered heterocyclic ring), -C(O)(5-6 membered heteroaryl), -C(O)O(3-6 membered heterocyclic ring) and -C(O)O(C 1-6 Alkylene) (3-6 membered heterocyclic ring), wherein any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 substituted, and any 3-6 membered carbocyclic ring, 5-6 membered heteroaryl ring or 3-6 membered heterocyclic ring is unsubstituted or replaced by one or more R 12 or R 20 In some embodiments, R e Selected from -C(O)(3-6 membered carbocyclic ring), -C(O)(3-7 membered heterocyclic ring), -C(O)(5-6 membered heteroaryl), -C(O)O(3-6 membered heterocyclic ring) and -C(O)O(C 1-6 Alkylene) (3-6 membered heterocyclic ring), wherein any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 substituted, and any 3-6 membered carbocyclic ring, 5-6 membered heteroaryl ring or 3-6 membered heterocyclic ring is unsubstituted or replaced by one or more R 12 or R 20 In some embodiments, R e Selected from -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 C1-6 The alkyl group is unsubstituted or substituted with one or more R 20 In some embodiments, R e Selected from -C(O)(C 1-6 alkyl), -C(O)(3-6 membered carbocyclic ring) and -C(O)O(C 1-6 alkyl), wherein any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 substituted, and any 3-6 membered carbocyclic ring is unsubstituted or replaced by one or more R 12 or R 20 In some embodiments, R e is unsubstituted or replaced by one or more R 20 Substituted C 1-6 In some embodiments, R e For one or more R 20 Substituted C 1-6 In some embodiments, R e For one or more R 20 Substituted C 1-6 Alkyl, where each R 20 Independently selected from -OH, -OC 1-6 In some embodiments, R e Selected from -C(O)(C 1-6 alkyl), wherein any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 In some embodiments, R e Selected from -C(O)(C 1-6 alkyl), wherein any C 1-6 Alkyl is unsubstituted. In some embodiments, R e Selected from -C(O)(C 1-6 alkyl), wherein any C 1-6 The alkyl group is replaced by one or more R 20 Substituted, wherein one or more R 20 Independently selected from -OC 1-6 In some embodiments, R e Selected from -C(O)(C 1-6 Alkylene)CN, wherein any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 In some embodiments, R e Selected from -C(O)(C 1-6 Alkylene)OH, wherein any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20In some embodiments, R e Selected from -C(O)N(R 14 )2. In some embodiments, R e Selected from -C(O)N(R 14 )2, where each R 14 independently selected from 3-6 membered carbocyclic ring, 3-6 membered heterocyclic ring, C 1-6 Alkyl and H. In some embodiments, R e Selected from -C(O)N(R 14 )2, where each R 14 Independently selected from C 1-6 alkyl and H. In some embodiments, when R e -C(O)N(R 14 )2, then at least one R 14 is not H. In some embodiments, when R e -C(O)N(R 14 )2, then each R 14 C 1-6 In some embodiments, R e Selected from -C(O)OR 14 In some embodiments, R e Selected from -C(O)OR 14 , where R 14 Selected from 3-6 membered carbocyclic ring, 3-6 membered heterocyclic ring, C 1-6 Alkyl and C 2-6 Alkenyl, any C 1-6 In some embodiments, R e Selected from -C(O)OR 14 , where R 14 is selected from 3-6 membered carbocyclic rings and 3-6 membered heterocyclic rings. e -S(O)2(C 1-6 alkyl), wherein the C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 In some embodiments, R e Selected from -C(O)(3-6 membered carbocyclic ring), wherein the 3-6 membered carbocyclic ring is unsubstituted or substituted with one or more R 12 or R 20 In some embodiments, R e is unsubstituted -C(O)(3-6 membered carbocyclic ring). e Selected from -C(O)(3-6 membered carbocyclic ring), wherein the 3-6 membered carbocyclic ring is replaced by one or more R 12 or R 20In some embodiments, R e Selected from -C(O)(3-6 membered carbocyclic ring), wherein the 3-6 membered carbocyclic ring is cyclopropane or cyclobutane, and wherein the 3-6 membered carbocyclic ring is unsubstituted or substituted by one or more R 12 or R 20 In some embodiments, R e In some embodiments, R e Selected from -C(O)(cyclopropane), wherein the cyclopropane is replaced by one or more R 12 or R 20 (e.g., one or more fluorine) substitutions. In some embodiments, R e Selected from -C(O)(3-8 membered heterocycle), wherein the 3-8 membered heterocycle is unsubstituted or replaced by one or more R 12 or R 20 In some embodiments, R e is selected from -C(O)(3-8 membered heterocycle), wherein the 3-8 membered heterocycle is unsubstituted. In some embodiments, R e Selected from -C(O)(3-8 membered heterocycle), wherein the 3-8 membered heterocycle is replaced by one or more R 12 or R 20 In some embodiments, R e Selected from -C(O)(3-7 membered heterocycle), wherein the 3-7 membered heterocycle is unsubstituted or replaced by one or more R 12 or R 20 In some embodiments, R e is selected from -C(O)(3-7 membered heterocycle), wherein the 3-7 membered heterocycle is unsubstituted. In some embodiments, R e Selected from -C(O)(3-7 membered heterocycle), wherein the 3-7 membered heterocycle is replaced by one or more R 12 or R 20 In some embodiments, R e is selected from -C(O)(3-7 membered heterocycle), wherein the 3-7 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 wherein the 3-7 membered heterocycle is unsubstituted or replaced by one or more R 12 or R 20 In some embodiments, R e is selected from -C(O)(3-7 membered heterocycle), wherein the 3-7 membered heterocycle is oxetane, azetidine, pyrrolidine, morpholine, tetrahydropyran, piperidine or piperazine, and wherein the 3-7 membered heterocycle is unsubstituted or replaced by one or more R 12 or R20 In some embodiments, R e Selected from -C(O)(3-7 membered heterocycle), wherein the 3-7 membered heterocycle is morpholine or a bridged morpholine, and wherein the morpholine or the bridged morpholine is unsubstituted or replaced by one or more R 12 or R 20 In some embodiments, R e Selected from -C(O)(3-7 membered heterocycle), wherein the 3-7 membered heterocycle is selected from wherein the bridged morpholine is unsubstituted or substituted with one or more R 12 or R 20 In some embodiments, R e Selected from -C(O)(3-7 membered heterocycle), wherein the 3-7 membered heterocycle is replaced by one or more R 12 or R 20 Substitute, where each R 12 Independently selected from C 1-6 Alkyl and each R 20 Independently selected from -OC 1-6 Alkyl, -C(O)(C 1-6 In some embodiments, R e Selected from -C(O)(5-6 membered heteroaryl), wherein the 5-6 membered heteroaryl is unsubstituted or substituted by 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. In some embodiments, R e Selected from -C(O)(5-6 membered heteroaryl), wherein the 5-6 membered heteroaryl is replaced by 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 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)(5-6 membered heteroaryl), wherein the 5-6 membered heteroaryl is oxazole or isoxazole, and wherein the oxazole or the isoxazole is unsubstituted or replaced by one or more R 12 or R 20 In some embodiments, R eSelected from -C(O)O(3-6 membered carbocyclic ring), wherein the 3-6 membered carbocyclic ring is unsubstituted or substituted by one or more R 12 or R 20 In some embodiments, R e is selected from -C(O)O(3-6 membered carbocyclic ring), wherein the 3-6 membered carbocyclic ring is unsubstituted. In some embodiments, R e Selected from -C(O)O(3-6 membered carbocyclic ring), wherein the 3-6 membered carbocyclic ring is replaced by one or more R 12 or R 20 In some embodiments, R e Selected from -C(O)O(3-6 membered carbocyclic ring), wherein the 3-6 membered carbocyclic ring is cyclopropane or cyclobutane, and wherein the 3-6 membered carbocyclic ring is unsubstituted or substituted by one or more R 12 or R 20 In some embodiments, R e Selected from -C(O)O(3-6 membered heterocycle), wherein the 3-6 membered heterocycle is unsubstituted or replaced by one or more R 12 or R 20 In some embodiments, R e is selected from -C(O)O(3-6 membered heterocycle), wherein the 3-6 membered heterocycle is unsubstituted. In some embodiments, R e Selected from -C(O)O(3-6 membered heterocycle), wherein the 3-6 membered heterocycle is replaced by one or more R 12 or R 20 In some embodiments, R e Selected from -C(O)O(3-6 membered heterocycle), wherein the 3-6 membered heterocycle is oxetane, tetrahydrofuran, tetrahydropyran or pyrrolidine, and wherein the 3-6 membered heterocycle is unsubstituted or replaced by one or more R 12 or R 20 In some embodiments, R e Selected from -C(O)O(C 1-6 Alkylene) (3-6 membered heterocyclic ring), wherein the 3-6 membered heterocyclic ring is unsubstituted or substituted by one or more R 12 or R 20 In some embodiments, R e Selected from -C(O)O(C 1-6 alkylene) (3-6 membered heterocyclic ring), wherein the 3-6 membered heterocyclic ring is unsubstituted. In some embodiments, R e Selected from -C(O)O(C 1-6 Alkylene) (3-6 membered heterocyclic ring), wherein the 3-6 membered heterocyclic ring is replaced by one or more R 12 or R 20 In some embodiments, Re is a 3-6 membered carbocyclic ring, wherein the 3-6 membered carbocyclic ring is unsubstituted or substituted by one or more R 12 or R 20 In some embodiments, R e is a 3-6 membered carbocyclic ring, wherein the 3-6 membered carbocyclic ring is unsubstituted. In some embodiments, R e is a 3-6 membered carbon ring, wherein the 3-6 membered carbon ring is surrounded by one or more R 12 or R 20 In some embodiments, R e is a 5-6 membered heteroaryl group, wherein the 5-6 membered heteroaryl group is unsubstituted or substituted by one or more R 12 or R 20 In some embodiments, R e is a 5-6 membered heteroaryl, wherein the 5-6 membered heteroaryl is unsubstituted. e is a 5-6 membered heteroaryl group, wherein the 3-6 membered carbocyclic ring is surrounded by one or more R 12 or R 20 replace.

[0465] In some embodiments, for compounds of any one of Formula IID, IID1, IIR, and IIR1, is a structure selected from the following:

[0466]

[0467]

[0468]

[0469]

[0470]

[0471]

[0472]

[0473] In some embodiments, for a compound of any one of Formula 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 replaced by one or more R 13 Substituted C 1-6 In some embodiments, R 2 For unsubstituted C 1-6 In some embodiments, R 2 For one or more R 13 Substituted C 1-6 In some embodiments, R 2 is unsubstituted or replaced by one or more R 13 Substituted C 1-2 In some embodiments, R 2 For unsubstituted C 1-2 In some embodiments, R 2 For one or more R 13 Substituted C 1-2 In some embodiments, R 2 In some embodiments, R 2 For ethyl.

[0474] In some embodiments, for compounds of any one of Formula 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 Select from -OR 8, where R 8 is selected from heterocycle and alkylheterocycle, wherein any heterocycle contains 4-8 members and is unsubstituted or substituted by one or more R a or R b substituted, and wherein the alkyl portion of any alkyl heterocycle is selected from C 1-6 In some embodiments, R 8 is a heterocycle or an alkylheterocycle, wherein any heterocycle contains 4 to 8 members and is surrounded by one or more R a or R b In some embodiments, R 8 is unsubstituted or replaced by one or more R a or R b In some embodiments, R 8 is unsubstituted or replaced by one or more R a or R b In some embodiments, R 8 is -CH2(heterocycle), wherein the heterocycle is unsubstituted or replaced by one or more R a or R b In some embodiments, the heterocyclic ring 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 heterocyclic ring 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 heterocyclic ring of the heterocycle or alkylheterocycle is replaced by one or more R a or R b Substituted, wherein one or more R a or R b is halogen (eg, F). In some embodiments, the heterocyclic ring of the heterocyclic or alkylheterocyclic ring is replaced by one or more R a or R b Substituted, wherein one or more R a or R b C 1-6 In some embodiments, the heterocyclic ring or the heterocyclic ring of the alkylheterocyclic ring is replaced by one or more R a or R b Substituted, wherein one or more R a or R b For-OR 12 (e.g., -OCH3). In some embodiments, the heterocyclic ring or the heterocyclic ring of the alkylheterocyclic ring is replaced by one or more R a or R b Substituted, wherein one or more R a or R bis a 3-6 membered carbocyclic ring (eg, cyclopropane). In some embodiments, the heterocyclic ring or the heterocyclic ring of the alkyl heterocyclic ring is replaced by one or more R a or R b Substituted, wherein one or more R a or R b For deuterium.

[0475] In some embodiments, for compounds according to any one of Formula 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 Selected from:

[0476]

[0477] where R a1 、R a2 、R b1 and R b2 are each independently selected from deuterium, halogen, C 1-6 Alkyl, -OR 12 and H, where R a1 and R b1 and / or R a2 and R b2 may be optionally linked together to form a 3-6 membered carbocyclic ring, and wherein any C 1-6 Alkyl or 3-6 membered carbon ring is unsubstituted or substituted by one or more R 13 In some embodiments, R a1 and / or R a2 In some embodiments, R a1 and / or R a2 is F. In some embodiments, R a1 and / or R a2 is unsubstituted or replaced by one or more R 13 Substituted C 1-6 In some embodiments, R a1 and / or R a2 In some embodiments, R a1 and / or R a2 For-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 In some embodiments, R b1 and / or R b2 is F. In some embodiments, R b1 and / or R b2 is unsubstituted or replaced by one or more R 13 Substituted C 1-6 In some embodiments, R b1 and / or R b2 In some embodiments, R a1 and R b1 Each of 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 3-6 membered carbocyclic ring (e.g., cyclopropane), which is optionally substituted by one or more R 13 In some embodiments, R a1 and R b1 are linked together to form a 3-6 membered carbocyclic ring (e.g., cyclopropane). 1 Selected from:

[0478]

[0479] In some embodiments, for compounds of any one of Formula 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 Selected from:

[0480]

[0481] where R a and Rb are each independently selected from halogen, C 1-6 Alkyl, -OR 12 and H, where any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 In some embodiments, R a In some embodiments, R a is F. In some embodiments, R a is unsubstituted or replaced by one or more R 13 Substituted C 1-6 In some embodiments, R a In some embodiments, R a For-OC 1-6 In some embodiments, R a is H. In some embodiments, R b is H. In some embodiments, R b In some embodiments, R b is F. In some embodiments, R b is unsubstituted or replaced by one or more R 13 Substituted C 1-6 In some embodiments, R b In some embodiments, R a and R b Each of is F. In some embodiments, R a and R b In some embodiments, each of R 1 Selected from:

[0482]

[0483] In some embodiments, for compounds of any one of Formula 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 Selected from:

[0484]

[0485] In some embodiments, for compounds of any one of Formula 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 Selected from:

[0486]

[0487] In some embodiments, R a is unsubstituted or replaced by one or more R 13 Substituted C 1-6 In some embodiments, R a In some embodiments, R 1 Selected from:

[0488]

[0489] In some embodiments, for compounds of any one of Formula 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 Selected from:

[0490]

[0491] Each R a and R b independently selected from halogen, C 1-6 Alkyl, -OR 12 and H; and R c Selected from C 1-6 Alkyl, where Ra and R b or R c are optionally linked together to form a 3-6 membered carbocyclic or heterocyclic ring, and wherein any C 1-6 Alkyl or 3-6 membered carbocyclic or heterocyclic ring is unsubstituted or replaced by one or more R 13 In some embodiments, each R a and R b independently selected from halogen, C 1-6 Alkyl, -OR 12 and H; and R c Selected from C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 substituted, and wherein R attached to the same carbon atom a and R b are linked together to form a 3-6 membered carbocyclic ring. a and R b independently selected from halogen, C 1-6 Alkyl, -OR 12 and H; and wherein R a and R c are linked together to form a 3-6 membered heterocyclic ring. a and R b independently selected from halogen, C 1-6 Alkyl, -OR 12 and H; and R c Selected from C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 In some embodiments, one R a or R b Selected from halogen, C 1-6 Alkyl and -OR 12 , and other R a and R b The group is H. In some embodiments, one R a or R b is halogen (eg, F). In some embodiments, two R a Group, two R b Group or R a and R b is halogen (eg, F). In some embodiments, one R a or R b For-OR 12 (e.g., -OCH3 or -CHF2). In some embodiments, one R a or Rb C 1-6 In some embodiments, two R a Group, two R b Group or R a and R b C 1-6 In some embodiments, R c is selected from -CH3, -CH2CH2F, -CH2CHF2 and -CH2CH2CN. In some embodiments, R a and R b are linked together to form a 3-6 membered carbocyclic ring, such as cyclopropane. In some embodiments, R a and R b are linked together to form a 3-6 membered carbon ring, such as cyclopropane. a and R c are linked together to form a 3-6 membered heterocyclic ring. 1 Selected from:

[0492]

[0493]

[0494] In some embodiments, for compounds of any one of Formula 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 Selected from:

[0495]

[0496] In some embodiments, for compounds of any one of Formula 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 Selected from:

[0497]

[0498] In some embodiments, for compounds of any one of Formula 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 is halogen (eg, F or Cl). In some embodiments, R 5 In some embodiments, R 5 is F. In some embodiments, R 5 In some embodiments, R 5 For-OR 12 , where R 12 Selected from C 1-6 Alkyl and H. In some embodiments, R 5 In some embodiments, R 5 In some embodiments, R 5 is unsubstituted or substituted with one or more R 13 Substituted C 1-6 In some embodiments, R 5 is unsubstituted or substituted with one or more R 13 Substituted C 1-2In some embodiments, R 5 Selected from unsubstituted C 1-6 In some embodiments, R 5 Selected from C substituted by one or more halogen or -CN 1-6 In some embodiments, R 5 is C substituted by one or more halogens, such as one or more fluorines 1-6 In some embodiments, R 5 In some embodiments, R 5 In some embodiments, R 5 is selected from -CF2H, -CF3, -CH2CN and -CH2CH3. In some embodiments, R 5 is selected from -CH3, -CH2CH3, -CF2H, -CF3, -CF2CH3 and -CH2CN. In some embodiments, R 5 For one or more R 13 Substituted C 1-6 Alkyl, where each R 13 Independently selected from -OR 14 , -CN and -N(R 14 )2. In some embodiments, R 5 In some embodiments, R 5 is a 3-6 membered heterocyclic ring. 5 is a 5-6 membered heteroaryl group, for example, furan.

[0499] In some embodiments, for compounds of any one of Formula 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 In some embodiments, R 7 For F.

[0500] In some embodiments, for a compound of any one of Formula 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 thereof.

[0501] Table 1.

[0502]

[0503]

[0504]

[0505] In another aspect, the present disclosure provides a compound represented by Formula III':

[0506]

[0507] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof, wherein:

[0508] R 1 Select from -OR 8 and

[0509] R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms an unsubstituted or substituted 11 substituted 4-10 membered heterocycle;

[0510] R 4 is H;

[0511] R 5 Selected from halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0512] R 6is a monocyclic or bicyclic heteroaryl group, wherein the heteroaryl group is separated by one or more R 15 replace;

[0513] R 7 selected from halogen;

[0514] R 8 is selected from heterocycle and alkylheterocycle, wherein any heterocycle contains 4-8 members and is unsubstituted or substituted by one or more R a or R b substituted, and wherein the alkyl portion of any alkyl heterocycle is selected from C 1-6 alkyl;

[0515] Each R 11 Independently selected from 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)(3-6 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, 3-6 membered carbocyclic or heterocyclic ring, 5-6 membered heteroaryl and C 1-6 Alkyl, any C 1-6 Alkyl, carbocyclic, heterocyclic or heteroaryl groups are unsubstituted or replaced by one or more R 20 replace;

[0516] Each R 12 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H, wherein any C 1-6 Alkyl or C 2-6 The alkenyl group is unsubstituted or substituted with one or more R 13 replace;

[0517] Each R 13 Independently selected from -OR 14 、-CN、-N(R 14 )2 and halogen;

[0518] Each R 14 Independently selected from C 1-6 Alkyl, C2-6 alkenyl and H;

[0519] Each R 15 are independently selected from deuterium, halogen, -N(R 12 )2, -CN and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0520] Each R 20 Independently selected from -OH, -OC 1-6 Alkyl, -CN, -NH2, -NHC 1-6 Alkyl and halogen;

[0521] R 27 is a 3-6 membered heterocyclic ring including one or more heteroatoms selected from N, O and S, wherein the heterocyclic ring is unsubstituted or replaced by one or more R 28 replace;

[0522] Each R 28 Independently selected from C 1-6 Alkyl and halogen;

[0523] R a and R b are each independently selected from deuterium, halogen, C 1-6 Alkyl, 3-6 membered carbocyclic ring, -OR 12 and H, where R a and R b are optionally linked together to form a 3-6 membered carbocyclic or heterocyclic ring, and wherein any C 1-6 Alkyl or 3-6 membered carbocyclic or heterocyclic ring is unsubstituted or replaced by one or more R 13 replace.

[0524] In some embodiments, the present disclosure provides a compound of Formula III' or a salt (eg, a pharmaceutically acceptable salt) thereof.

[0525] In another aspect, the present disclosure provides compounds represented by Formula III:

[0526]

[0527] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof, wherein:

[0528] R 1 Select from -OR 8 and

[0529] R 2 and R 3Together with the nitrogen atom to which it is attached, it forms an unsubstituted or substituted 11 substituted 4-10 membered heterocycles, provided that (i) when the heterocycle contains an additional nitrogen atom, the additional nitrogen atom is replaced by R 11 substituted, or (ii) the heterocycle does not contain an -NH- moiety;

[0530] R 4 is H;

[0531] R 5 Selected from halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0532] R 6 is a monocyclic or bicyclic heteroaryl group, wherein the heteroaryl group is separated by one or more R 15 replace;

[0533] R 7 selected from halogen;

[0534] R 8 is selected from heterocycle and alkylheterocycle, wherein any heterocycle contains 4-8 members and is unsubstituted or substituted by one or more R a or R b substituted, and wherein the alkyl portion of any alkyl heterocycle is selected from C 1-6 alkyl;

[0535] Each R 11 Independently selected from 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)(3-6 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, 3-6 membered carbocyclic or heterocyclic ring, 5-6 membered heteroaryl and C 1-6 Alkyl, any C 1-6 Alkyl, carbocyclic, heterocyclic or heteroaryl groups are unsubstituted or replaced by one or more R 20replace;

[0536] Each R 12 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H, wherein any C 1-6 Alkyl or C 2-6 The alkenyl group is unsubstituted or substituted with one or more R 13 replace;

[0537] Each R 13 Independently selected from -OR 14 、-CN、-N(R 14 )2 and halogen;

[0538] Each R 14 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H;

[0539] Each R 15 are independently selected from deuterium, halogen, -N(R 12 )2, -CN and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0540] Each R 20 Independently selected from -OH, -OC 1-6 Alkyl, -CN, -NH2, -NHC 1-6 Alkyl and halogen;

[0541] R 27 is a 3-6 membered heterocyclic ring including one or more heteroatoms selected from N, O and S, wherein the heterocyclic ring is unsubstituted or replaced by one or more R 28 replace;

[0542] Each R 28 Independently selected from C 1-6 Alkyl and halogen;

[0543] R a and R b are each independently selected from deuterium, halogen, C 1-6 Alkyl, 3-6 membered carbocyclic ring, -OR 12 and H, where R a and R b are optionally linked together to form a 3-6 membered carbocyclic or heterocyclic ring, and wherein any C 1-6 Alkyl or 3-6 membered carbocyclic or heterocyclic ring is unsubstituted or replaced by one or more R 13 replace.

[0544] In some embodiments, the present disclosure provides a compound of Formula III or a salt (eg, a pharmaceutically acceptable salt) thereof.

[0545] In some embodiments, the present disclosure provides compounds of Formula III, wherein:

[0546] R 1 Select from -OR 8 ;

[0547] R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms an unsubstituted or substituted 11 substituted 4-10 membered heterocycles, provided that (i) when the heterocycle contains an additional nitrogen atom, the additional nitrogen atom is replaced by R 11 substituted, or (ii) the heterocycle does not contain an -NH- moiety;

[0548] R 4 is H;

[0549] R 5 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0550] R 6 is a monocyclic or bicyclic heteroaryl group, wherein the heteroaryl group is separated by one or more R 15 replace;

[0551] R 7 selected from halogen;

[0552] R 8 is an alkyl heterocycle, wherein any heterocycle contains 4 to 8 members and is unsubstituted or substituted by one or more R a or R b substituted, and wherein the alkyl portion of any alkyl heterocycle is selected from C 1-6 alkyl;

[0553] Each R 11 Independently selected from 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)(3-6 membered carbocyclic or heterocyclic ring), -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 , halogen, -CN, 3-6 membered carbocyclic or heterocyclic ring, 5-6 membered heteroaryl and C 1-6 Alkyl, any C 1-6 Alkyl, carbocyclic, heterocyclic or heteroaryl groups are unsubstituted or replaced by one or more R 20 replace;

[0554] Each R 12 Independently selected from C 1-6 Alkyl and H, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0555] Each R 13 independently selected from halogen;

[0556] Each R 14 Independently selected from C 1-6 Alkyl and H;

[0557] Each R 15 are independently selected from deuterium, halogen, -N(R 12 )2, -CN and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0558] Each R 20 Independently selected from -OH, -OC 1-6 Alkyl, -CN and halogen;

[0559] R a and R b are each independently selected from deuterium, halogen, C 1-6 Alkyl and H, where R a and R b are optionally linked together to form a 3-6 membered carbocyclic ring, and wherein any C 1-6 Alkyl or 3-6 membered carbon ring is unsubstituted or substituted by one or more R 13 replace.

[0560] In some embodiments, the present disclosure provides compounds of Formula III' or III, wherein the compound has Formula III-a:

[0561]

[0562] or a salt (eg, a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof, wherein R 2 and R 3 As defined above for Formula III and described in classes and subclasses herein, individually and in combination. In some embodiments, R 2 and R 3 As defined above for Formula III' and described in classes and subclasses herein, individually and in combination. In some embodiments, the present disclosure provides a compound of Formula III-a or a salt (eg, a pharmaceutically acceptable salt) thereof.

[0563] 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 it is attached, it forms an unsubstituted or substituted 11 In some embodiments, R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms an unsubstituted or substituted 11 substituted 4-7 membered heterocycles, provided that (i) when the heterocycle contains an additional nitrogen atom, the additional nitrogen atom is replaced by R 11 In some embodiments, R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms an unsubstituted or substituted 11 substituted 4-7 membered heterocycles, provided that (i) when the heterocycle contains an additional nitrogen atom, the additional nitrogen atom is replaced by R 11 or (ii) when the heterocycle comprises a monocyclic ring, the heterocycle does not comprise an -NH- moiety. 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a 4-7 membered heterocyclic ring comprising a monocyclic ring, wherein the heterocyclic ring is unsubstituted or substituted by one or more R 11 In some embodiments, R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms an unsubstituted or substituted 11 In some embodiments, R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms an unsubstituted or substituted 11 substituted 4-6 membered heterocycles, provided that (i) when the heterocycle contains an additional nitrogen atom, the additional nitrogen atom is replaced by R 11In some embodiments, R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms an unsubstituted or substituted 11 substituted 4-6 membered heterocycles, provided that (i) when the heterocycle contains an additional nitrogen atom, the additional nitrogen atom is replaced by R 11 or (ii) when the heterocycle comprises a single ring, the heterocycle does not comprise an -NH- moiety. 2 and R 3 Together with the nitrogen atom to which it is attached, it forms an unsubstituted 4-6 membered heterocyclic ring, provided that the 4-6 membered heterocyclic ring does not contain an -NH- moiety. In some embodiments, R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms an unsubstituted 7-membered heterocyclic ring, provided that the 7-membered heterocyclic ring does not contain an -NH- moiety. In some embodiments, R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a 11 substituted 4-6 membered heterocycles, provided that (i) when the heterocycle contains an additional nitrogen atom, the additional nitrogen atom is replaced by R 11 In some embodiments, R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a 4-6 membered heterocyclic ring including 1 or 2 heteroatoms selected from O, S and N, wherein the heterocyclic ring is unsubstituted or substituted by one or more R 11 substituted, provided that (i) when the heterocyclic ring contains an additional nitrogen atom, the additional nitrogen atom is replaced by R 11 In some embodiments, R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a 4-6 membered heterocyclic ring including 1 or 2 heteroatoms selected from O, S and N, wherein the heterocyclic ring is surrounded by 1-4 R 11 substituted, provided that (i) when the heterocyclic ring contains an additional nitrogen atom, the additional nitrogen atom is replaced by R 11 In some embodiments, R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a group consisting of 0-4 R 11 In some embodiments, R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a group consisting of 0-4 R 11 In some embodiments, R2 and R 3 Together with the nitrogen atom to which it is attached, it forms a group consisting of 0-4 R 11 In some embodiments, R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a group consisting of 0-4 R 11 substituted piperazines, provided that the additional nitrogen atom of the piperazine is replaced by R 11 In some embodiments, R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a group consisting of 0-4 R 11 In some embodiments, R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a 11 substituted 4-6 membered heterocycles, provided that (i) when the heterocycle contains an additional nitrogen atom, the additional nitrogen atom is replaced by R 11 substituted, or (ii) the heterocycle does not contain an -NH- moiety, wherein at least one R 11 Select from -OR 12 and C substituted by -OH 1-6 In some embodiments, R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a 11 substituted 4-6 membered heterocycles, provided that (i) when the heterocycle contains an additional nitrogen atom, the additional nitrogen atom is replaced by R 11 substituted, or (ii) the heterocycle does not contain an -NH- moiety, wherein at least one R 11 For unsubstituted C 1-6 In some embodiments, R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a 7-membered heterocyclic ring including 1 to 3 heteroatoms selected from O, S and N, wherein the heterocyclic ring is unsubstituted or replaced by one or more R 11 In some embodiments, R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a 7-membered heterocyclic ring including 1 to 3 heteroatoms selected from O, S and N, wherein the heterocyclic ring is unsubstituted or replaced by one or more R 11 substituted, provided that (i) when the heterocyclic ring contains an additional nitrogen atom, the additional nitrogen atom is replaced by R 11 In some embodiments, R 2 and R 3Together with the nitrogen atom to which it is attached, it forms a 7-membered heterocyclic ring including 1-3 heteroatoms selected from O, S and N, wherein the heterocyclic ring is surrounded by 1-4 R 11 In some embodiments, R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a 7-membered heterocyclic ring including 1-3 heteroatoms selected from O, S and N, wherein the heterocyclic ring is surrounded by 1-4 R 11 substituted, provided that (i) when the heterocyclic ring contains an additional nitrogen atom, the additional nitrogen atom is replaced by R 11 In some embodiments, R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a 7-membered heterocyclic ring including the nitrogen atom. 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a 7-membered heterocyclic ring including nitrogen and oxygen atoms. 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a 7-membered heterocyclic ring including a nitrogen atom and a sulfur atom, which is optionally substituted with two oxo moieties. 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a 7-membered heterocyclic ring including two nitrogen atoms. 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a 7-membered heterocyclic ring including one additional nitrogen atom, provided that the additional nitrogen atom is replaced by R 11 replace.

[0564] 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 it is attached, it forms an unsubstituted or substituted 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 it is attached, it forms an unsubstituted or substituted 11 substituted bridged heterocycles, provided that (i) when the heterocycle contains an additional nitrogen atom, the additional nitrogen atom is replaced by R 11 In some embodiments, R 2 and R 3Together with the nitrogen atom to which it is attached, it forms a 7-9 membered bridged heterocyclic ring including 1 or 2 heteroatoms selected from O, S and N, wherein the bridged heterocyclic ring is unsubstituted or substituted by one or more R 11 substituted, provided that (i) when the heterocyclic ring contains an additional nitrogen atom, the additional nitrogen atom is replaced by R 11 In some embodiments, R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a 7-9 membered bridged heterocyclic ring including 1 or 2 heteroatoms selected from O, S and N, wherein the bridged heterocyclic ring is supported by 1-4 R 11 substituted, provided that (i) when the heterocyclic ring contains an additional nitrogen atom, the additional nitrogen atom is replaced by R 11 In some embodiments, R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a group consisting of 0-4 R 11 In some embodiments, R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a group consisting of 0-4 R 11 substituted bridged piperazines, provided that (i) the additional nitrogen atom of the piperazine is replaced by R 11 In some embodiments, R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a group consisting of 0-4 R 11 In some embodiments, R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a 11 substituted bridged heterocycles, provided that (i) when the heterocycle contains an additional nitrogen atom, the additional nitrogen atom is replaced by R 11 substituted, or (ii) the heterocycle does not contain an -NH- moiety, wherein at least one R 11 Select from -OR 12 and C substituted by -OH 1-6 In some embodiments, R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a 11 substituted bridged heterocycles, provided that (i) when the heterocycle contains an additional nitrogen atom, the additional nitrogen atom is replaced by R 11 substituted, or (ii) the heterocycle does not contain an -NH- moiety, wherein at least one R 11 For unsubstituted C 1-6 alkyl.

[0565] 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 it is attached, it forms an unsubstituted or substituted 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 it is attached, it forms an unsubstituted or substituted 11 substituted spirocycles, provided that (i) when the spirocycle contains an additional nitrogen atom, the additional nitrogen atom is replaced by R 11 In some embodiments, R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms an unsubstituted spirocycle, provided that the spirocycle does not include an -NH- moiety. In some embodiments, R 2 and R 3 Together with the atoms to which it is attached, it forms a 11 substituted spirocycles, provided that (i) when the spirocycle contains an additional nitrogen atom, the additional nitrogen atom is replaced by R 11 In some embodiments, R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a spirocycle comprising a 4-membered ring and a 3-membered ring. 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a spirocycle comprising two 4-membered rings. 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a spirocycle comprising a 4-membered ring and a 5-membered ring. 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a spirocycle comprising a 4-membered ring and a 6-membered ring. 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a spirocycle comprising a 6-membered ring and a 5-membered ring. 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a spirocycle containing two 5-membered rings.

[0566] In some embodiments, for compounds according to Formula III, III' or III-a, R 2 and R 3Together with the nitrogen atom to which it is attached, it forms a fused ring system comprising at least two rings, wherein the fused ring system is unsubstituted or substituted by one or more R 11 In some embodiments, R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a fused ring system comprising at least two rings, wherein the fused ring system is unsubstituted or substituted by one or more R 11 In some embodiments, R 2 and R 3 The fused ring system comprises at least two rings, wherein at least one of the rings is 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 wherein the fused ring system is unsubstituted or substituted with one or more R 11 In some embodiments, R 2 and R 3 The fused ring system comprises at least two rings, wherein at least one of the rings is 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 wherein the fused ring system is unsubstituted or substituted with one or more R 11 In some embodiments, R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a fused ring system comprising two 5-membered rings. 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a fused ring system comprising a 5-membered ring and a 6-membered ring. 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a fused ring system comprising a 5-membered ring and a 4-membered ring. 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a fused ring system comprising a 6-membered ring and a 3-membered ring. 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a fused ring system comprising a 7-membered ring and a 5-membered ring. 2 and R 3 Together with the nitrogen atom to which it is attached, R forms a fused ring system comprising at least two rings, wherein the fused ring system is unsubstituted.2 and R 3 Together with the nitrogen atom to which it is attached, it forms a fused ring system comprising at least two rings, wherein the fused ring system is unsubstituted, provided that 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 it is attached, it forms a fused ring system comprising at least two rings, wherein the fused ring system is surrounded by one or more R 11 In some embodiments, R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a fused ring system comprising at least two rings, wherein the fused ring system is surrounded by one or more R 11 substituted, provided that (i) when the fused ring system contains an additional nitrogen atom, the additional nitrogen atom is replaced by R 11 In some embodiments, R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a fused ring system comprising at least two rings, wherein the fused ring system is surrounded by 1-4 R 11 In some embodiments, R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a fused ring system comprising at least two rings, wherein the fused ring system is surrounded by 1-4 R 11 substituted, provided that (i) when the fused ring system contains an additional nitrogen atom, the additional nitrogen atom is replaced by R 11 substituted, or (ii) the fused ring system does not contain an -NH- moiety.

[0567] 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 it is attached, it forms an unsubstituted or substituted 11 a substituted 4-10 membered heterocyclic ring, wherein each R 11 Independently selected from 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)(3-6 membered carbocyclic or heterocyclic ring), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6 alkyl), -N(R14 )C(O)(C 1-6 alkylene)OR 14 , halogen, -CN, 3-6 membered carbocyclic or heterocyclic ring and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 In some embodiments, each R 11 Independently selected from 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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 In some embodiments, each R 11 Independently selected from -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 , halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 In some embodiments, each R 11 Independently selected from deuterium, -OR 12 、-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. Halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 In some embodiments, at least one R 11 is -C(O)(3-6 membered carbocyclic or heterocyclic ring), wherein any carbocyclic or heterocyclic ring is unsubstituted or replaced by one or more R 20 In some embodiments, at least one R 11 is -C(O)(3-6 membered carbocyclic ring), wherein the carbocyclic ring is unsubstituted or substituted with one or more R 20 In some embodiments, at least one R 11 is -C(O)(3-6 membered heterocycle), wherein the heterocycle is unsubstituted or substituted by one or more R 20 In some embodiments, at least one R 11 -C(O)N(R 14 ) 2. In some embodiments, at least one R 11 =0. In some embodiments, when R 11 -C(O)N(R 14 )2, then at least one R 14 is not H. In some embodiments, when R 11 -C(O)N(R 14 )2, then each R 14 C 1-6 Alkyl (eg, methyl or ethyl).

[0568] 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 it is attached, it forms an unsubstituted or substituted 11 substituted 4-10 membered heterocycle, provided that when the heterocycle contains an additional nitrogen atom, the additional nitrogen atom is replaced by R 11 Substituted, wherein one or more R 11 Independently selected from -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 1-6alkylene)OR 14 , halogen and unsubstituted or replaced by one or more R 20 Substituted C 1-6 In some embodiments, R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms an unsubstituted or substituted 11 substituted 4-10 membered heterocycles, provided that (i) when the heterocycle contains an additional nitrogen atom, the additional nitrogen atom is replaced by R 11 substituted, or (ii) the heterocycle does not contain an -NH- moiety, wherein the one or more R 11 Independently selected from 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)(3-6 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, 3-6 membered carbocyclic or heterocyclic rings and unsubstituted or substituted by one or more R 20 Substituted C 1-6 In some embodiments, R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms an unsubstituted or substituted 11 substituted 4-10 membered heterocycles, provided that (i) when the heterocycle contains an additional nitrogen atom, the additional nitrogen atom is replaced by R 11 substituted, or (ii) the heterocycle does not contain an -NH- moiety, wherein the one or more R 11 Independently selected from 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)(3-6 membered carbocyclic or heterocyclic ring), -S(O)2(C 1-6 alkyl), -N(R 14 )C(O)(C 1-6alkyl), -N(R 14 )C(O)(C 1-6 alkylene)OR 14 , halogen, -CN, 3-6 membered carbocyclic or heterocyclic ring, 5-6 membered heteroaryl and unsubstituted or replaced by one or more R 20 Substituted C 1-6 alkyl.

[0569] 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 it is attached, it forms a structure selected from the following:

[0570]

[0571]

[0572]

[0573]

[0574]

[0575] Any of which is optionally further represented by one or more R 11 replace.

[0576] In some embodiments, the compound is according to Formula IIIA:

[0577]

[0578] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof, wherein:

[0579] R 1 Select from -OR 8 and

[0580] R 5 Selected from halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0581] R 6 is a monocyclic or bicyclic heteroaryl group, wherein the heteroaryl group is separated by one or more R 15 replace;

[0582] R 7 selected from halogen;

[0583] R8 is selected from heterocycle and alkylheterocycle, wherein any heterocycle contains 4-8 members and is unsubstituted or substituted by one or more R a or R b substituted, and wherein the alkyl portion of any alkyl heterocycle is selected from C 1-6 alkyl;

[0584] Each R 12 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H, wherein any C 1-6 Alkyl or C 2-6 The alkenyl group is unsubstituted or substituted with one or more R 13 replace;

[0585] Each R 13 Independently selected from -OR 14 、-CN、-N(R 14 )2 and halogen;

[0586] Each R 14 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H;

[0587] Each R 15 are independently selected from deuterium, halogen, -N(R 12 )2, -CN and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0588] Each R 20 Independently selected from -OH, -OC 1-6 Alkyl, -CN, -NH2, -NHC 1-6 Alkyl and halogen;

[0589] R 27 is a 3-6 membered heterocyclic ring including one or more heteroatoms selected from N, O and S, wherein the heterocyclic ring is unsubstituted or replaced by one or more R 28 replace;

[0590] Each R 28 Independently selected from C 1-6 Alkyl and halogen;

[0591] R a and R b are each independently selected from deuterium, halogen, C 1-6 Alkyl, 3-6 membered carbocyclic ring, -OR 12 and H, where R a and R bare optionally linked together to form a 3-6 membered carbocyclic or heterocyclic ring, and wherein any C 1-6 Alkyl or 3-6 membered carbocyclic or heterocyclic ring is unsubstituted or replaced by one or more R 13 replace;

[0592] Each R e independently selected from 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 and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace; and

[0593] R f and R g are each independently selected from 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 , halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 Replace, or

[0594] R f and R g are linked together to form a 3-6 membered carbocyclic or heterocyclic ring which is unsubstituted or substituted with one or more substituents selected from: -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 , halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace.

[0595] In some embodiments, the present disclosure provides a compound of Formula IIIA or a salt (eg, a pharmaceutically acceptable salt) thereof.

[0596] In some embodiments, for compounds according to Formula IIIA, each R e 、R f and R g are independently selected from 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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 In some embodiments, each R e 、R f and R g are independently selected from 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)OR14 , halogen and unsubstituted or replaced by one or more R 20 Substituted C 1-6 It should be understood that when R e 、R f or R g When it is =O, other R on the same carbon atom e 、R f or R g In some embodiments, each R e is independently hydrogen. In some embodiments, each R e 、R f and R g are independently hydrogen.

[0597] In some embodiments, for compounds according to Formula IIIA, R f and R g are linked together to form a 3-6 membered carbocyclic or heterocyclic ring which is unsubstituted or substituted with one or more substituents selected from: -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 In some embodiments, R f and R g are linked together to form an unsubstituted 3-6 membered carbocyclic or heterocyclic ring. f and R g are linked together to form a 3-6 membered carbocyclic or heterocyclic ring substituted with one or more substituents selected from: -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 1-6alkyl), -N(R 14 )C(O)(C 1-6 alkylene)OR 14 , halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 In some embodiments, R f and R g are linked together to form a 3-6 membered carbon ring which is unsubstituted or substituted with one or more substituents selected from: -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 In some embodiments, R f and R g linked together to form a cyclopropane which is unsubstituted or substituted with one or more substituents selected from: -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 In some embodiments, R f and R g linked together to form a cyclobutane which is unsubstituted or substituted with one or more substituents selected from: -OR 12 ,=O,-C(O)(C 1-6Alkylene)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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 In some embodiments, R f and R g are linked together to form a 3-6 membered heterocyclic ring which is unsubstituted or substituted with one or more substituents selected from: -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 In some embodiments, R f and R g linked together to form an oxetane which is unsubstituted or substituted with one or more substituents selected from: -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R20 replace.

[0598] In some embodiments, for compounds according to Formula IIIA, is a structure selected from the following:

[0599]

[0600] In some embodiments, the compound is according to Formula IIIA1:

[0601]

[0602] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof, wherein:

[0603] R 1 Select from -OR 8 and

[0604] R 5 Selected from halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0605] R 6 is a monocyclic or bicyclic heteroaryl group, wherein the heteroaryl group is separated by one or more R 15 replace;

[0606] R 7 selected from halogen;

[0607] R 8 is selected from heterocycle and alkylheterocycle, wherein any heterocycle contains 4-8 members and is unsubstituted or substituted by one or more R a or R b substituted, and wherein the alkyl portion of any alkyl heterocycle is selected from C 1-6 alkyl;

[0608] Each R 12 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H, wherein any C 1-6 Alkyl or C 2-6 The alkenyl group is unsubstituted or substituted with one or more R 13 replace;

[0609] Each R 13 Independently selected from -OR 14 、-CN、-N(R 14 )2 and halogen;

[0610] Each R 14 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H;

[0611] Each R 15 are independently selected from deuterium, halogen, -N(R 12 )2, -CN and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0612] Each R 20 Independently selected from -OH, -OC 1-6 Alkyl, -CN, -NH2, -NHC 1-6 Alkyl and halogen;

[0613] R 27 is a 3-6 membered heterocyclic ring including one or more heteroatoms selected from N, O and S, wherein the heterocyclic ring is unsubstituted or replaced by one or more R 28 replace;

[0614] Each R 28 Independently selected from C 1-6 Alkyl and halogen;

[0615] R a and R b are each independently selected from deuterium, halogen, C 1-6 Alkyl, 3-6 membered carbocyclic ring, -OR 12 and H, where R a and R b are optionally linked together to form a 3-6 membered carbocyclic or heterocyclic ring, and wherein any C 1-6 Alkyl or 3-6 membered carbocyclic or heterocyclic ring is unsubstituted or replaced by one or more R 13 replace;

[0616] Each R e independently selected from 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)(3-6 membered carbocyclic ring), -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace; and

[0617] R f and R g are linked together to form a 3-6 membered carbocyclic or heterocyclic ring which is unsubstituted or substituted with one or more substituents selected from: -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)(3-6 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 C 1-6 Alkyl, any C 1-6 The alkyl, carbocyclic or heterocyclic ring is unsubstituted or substituted with one or more R 20 replace.

[0618] In some embodiments, the present disclosure provides a compound of Formula IIIA1 or a salt (eg, a pharmaceutically acceptable salt) thereof.

[0619] In some embodiments, for compounds according to Formula IIIA1, each R e are independently selected from 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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R20 In some embodiments, for compounds according to Formula IIIA1, each R e are independently selected from 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 replaced by one or more R 20 Substituted C 1-6 It should be understood that when R e Connected to also with R f or R g When connected to carbon, R e Not =O or =N(R 14 ), and when R e =O or =N(R 14 ), other R on the same carbon atom e In some embodiments, each R e are independently hydrogen.

[0620] In some embodiments, for compounds according to Formula IIIA1, R f and R g are linked together to form an unsubstituted 3-6 membered carbocyclic or heterocyclic ring. f and R g are linked together to form a 3-6 membered carbocyclic or heterocyclic ring substituted with one or more substituents selected from: -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)(3-6 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)(C1-6 alkylene)OR 14 , halogen and C 1-6 Alkyl, any C 1-6 The alkyl, carbocyclic or heterocyclic ring is unsubstituted or substituted with one or more R 20 In some embodiments, R f and R g are linked together to form a 3-6 membered carbocyclic or heterocyclic ring substituted with one or more substituents selected from: -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)(3-6 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 C 1-6 Alkyl, any C 1-6 The alkyl, carbocyclic or heterocyclic ring is unsubstituted or substituted with one or more R 20 In some embodiments, R f and R g are linked together to form a 3-6 membered carbocyclic or heterocyclic ring substituted with one or more substituents selected from: -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)(3-6 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 replaced by one or more R 20 Substituted C 1-6 Alkyl, wherein any carbocyclic or heterocyclic ring is unsubstituted or replaced by one or more R 20 In some embodiments, R f and R g are linked together to form a pyrrolidine substituted with one or more substituents selected from: -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)(3-6 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 C 1-6 Alkyl, any C 1-6 The alkyl, carbocyclic or heterocyclic ring is unsubstituted or substituted with one or more R 20 In some embodiments, R f and R g are linked together to form a pyrrolidine substituted with one or more substituents selected from: -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)(3-6 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 C 1-6 Alkyl, any C 1-6 The alkyl, carbocyclic or heterocyclic ring is unsubstituted or substituted with one or more R 20 In some embodiments, when R f and R g The ring formed by the connection is -C(O)N(R 14 )2 substituted, at least one R 14 C 1-6 alkyl.

[0621] In some embodiments, for the compound according to Formula IIIA1, is a structure selected from the following:

[0622]

[0623] In some embodiments, the compound is according to Formula IIIB:

[0624]

[0625] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof, wherein:

[0626] R 1 Select from -OR 8 and

[0627] R 5 Selected from halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0628] R 6 is a monocyclic or bicyclic heteroaryl group, wherein the heteroaryl group is separated by one or more R 15 replace;

[0629] R 7 selected from halogen;

[0630] R 8 is selected from heterocycle and alkylheterocycle, wherein any heterocycle contains 4-8 members and is unsubstituted or substituted by one or more R a or R b substituted, and wherein the alkyl portion of any alkyl heterocycle is selected from C 1-6 alkyl;

[0631] Each R 12 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H, wherein any C 1-6 Alkyl or C 2-6 The alkenyl group is unsubstituted or substituted with one or more R 13 replace;

[0632] Each R 13 Independently selected from -OR 14 、-CN、-N(R 14 )2 and halogen;

[0633] Each R 14 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H;

[0634] Each R 15 are independently selected from deuterium, halogen, -N(R 12 )2, -CN and C 1-6Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0635] Each R 20 Independently selected from -OH, -OC 1-6 Alkyl, -CN, -NH2, -NHC 1-6 Alkyl and halogen;

[0636] R 27 is a 3-6 membered heterocyclic ring including one or more heteroatoms selected from N, O and S, wherein the heterocyclic ring is unsubstituted or replaced by one or more R 28 replace;

[0637] Each R 28 Independently selected from C 1-6 Alkyl and halogen;

[0638] R a and R b are each independently selected from deuterium, halogen, C 1-6 Alkyl, 3-6 membered carbocyclic ring, -OR 12 and H, where R a and R b are optionally linked together to form a 3-6 membered carbocyclic or heterocyclic ring, and wherein any C 1-6 Alkyl or 3-6 membered carbocyclic or heterocyclic ring is unsubstituted or replaced by one or more R 13 replace; and

[0639] Each R e independently selected from 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 and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace.

[0640] In some embodiments, the present disclosure provides a compound of Formula IIIB or a salt (eg, a pharmaceutically acceptable salt) thereof.

[0641] In some embodiments, for compounds according to Formula IIIB, each R e In some embodiments, at least one R e For-OR 12 In some embodiments, each R e are independently selected from 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 replaced by one or more R 20 Substituted C 1-6 It should be understood that when R e When it is =O, other R on the same carbon atom e is absent so that the carbon has the appropriate valence.

[0642] In some embodiments, the compound is according to Formula IIIC:

[0643]

[0644] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof, wherein:

[0645] R 1 Select from -OR 8 and

[0646] R 5 Selected from halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0647] R 6 is a monocyclic or bicyclic heteroaryl group, wherein the heteroaryl group is separated by one or more R 15 replace;

[0648] R 7 selected from halogen;

[0649] R 8 is selected from heterocycle and alkylheterocycle, wherein any heterocycle contains 4-8 members and is unsubstituted or substituted by one or more R a or R b substituted, and wherein the alkyl portion of any alkyl heterocycle is selected from C 1-6 alkyl;

[0650] Each R 12 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H, wherein any C 1-6 Alkyl or C 2-6 The alkenyl group is unsubstituted or substituted with one or more R 13 replace;

[0651] Each R 13 Independently selected from -OR 14 、-CN、-N(R 14 )2 and halogen;

[0652] Each R 14 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H;

[0653] Each R 15 are independently selected from deuterium, halogen, -N(R 12 )2, -CN and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0654] Each R 20 Independently selected from -OH, -OC 1-6 Alkyl, -CN, -NH2, -NHC 1-6 Alkyl and halogen;

[0655] R 27 is a 3-6 membered heterocyclic ring including one or more heteroatoms selected from N, O and S, wherein the heterocyclic ring is unsubstituted or replaced by one or more R 28 replace;

[0656] Each R 28 Independently selected from C 1-6 Alkyl and halogen;

[0657] R a and R b are each independently selected from deuterium, halogen, C 1-6 Alkyl, 3-6 membered carbocyclic ring, -OR 12 and H, where R aand R b are optionally linked together to form a 3-6 membered carbocyclic or heterocyclic ring, and wherein any C 1-6 Alkyl or 3-6 membered carbocyclic or heterocyclic ring is unsubstituted or replaced by one or more R 13 replace; and

[0658] Each R e independently selected from 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 group is unsubstituted or substituted with one or more R 20 replace.

[0659] In some embodiments, the present disclosure provides a compound of Formula IIIC or a salt (eg, a pharmaceutically acceptable salt) thereof.

[0660] In some embodiments, for compounds according to Formula IIIC, is a structure selected from the following:

[0661]

[0662] In some embodiments, the compound is according to Formula IIIC1:

[0663]

[0664] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof, wherein:

[0665] R 1 Select from -OR 8 and

[0666] R 5 Selected from halogen and C 1-6 Alkyl, any C 1-6The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0667] R 6 is a monocyclic or bicyclic heteroaryl group, wherein the heteroaryl group is separated by one or more R 15 replace;

[0668] R 7 selected from halogen;

[0669] R 8 is selected from heterocycle and alkylheterocycle, wherein any heterocycle contains 4-8 members and is unsubstituted or substituted by one or more R a or R b substituted, and wherein the alkyl portion of any alkyl heterocycle is selected from C 1-6 alkyl;

[0670] Each R 12 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H, wherein any C 1-6 Alkyl or C 2-6 The alkenyl group is unsubstituted or substituted with one or more R 13 replace;

[0671] Each R 13 Independently selected from -OR 14 、-CN、-N(R 14 )2 and halogen;

[0672] Each R 14 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H;

[0673] Each R 15 are independently selected from deuterium, halogen, -N(R 12 )2, -CN and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0674] Each R 20 Independently selected from -OH, -OC 1-6 Alkyl, -CN, -NH2, -NHC 1-6 Alkyl and halogen;

[0675] R 27 is a 3-6 membered heterocyclic ring including one or more heteroatoms selected from N, O and S, wherein the heterocyclic ring is unsubstituted or replaced by one or more R 28 replace;

[0676] Each R28 Independently selected from C 1-6 Alkyl and halogen;

[0677] R a and R b are each independently selected from deuterium, halogen, C 1-6 Alkyl, 3-6 membered carbocyclic ring, -OR 12 and H, where R a and R b are optionally linked together to form a 3-6 membered carbocyclic or heterocyclic ring, and wherein any C 1-6 Alkyl or 3-6 membered carbocyclic or heterocyclic ring is unsubstituted or replaced by one or more R 13 replace;

[0678] Each R e independently selected from 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 and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace; and

[0679] R f 、R g and R h are each independently selected from 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 , halogen and C 1-6 Alkyl, any C1-6 The alkyl group is unsubstituted or substituted with one or more R 20 substituted, optionally wherein

[0680] (i)R f and R g are linked together to form a 3-6 membered carbocyclic or heterocyclic ring or a 5-6 membered heteroaryl group which is unsubstituted or substituted with one or more substituents selected from: -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace; or

[0681] (ii)R g and R h are linked together to form a 3-6 membered carbocyclic or heterocyclic ring or a 5-6 membered heteroaryl group which is unsubstituted or substituted with one or more substituents selected from: -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace.

[0682] In some embodiments, the present disclosure provides a compound of Formula IIIC1 or a salt (eg, a pharmaceutically acceptable salt) thereof.

[0683] In some embodiments, for compounds according to Formula IIIC or IIIC1, each R eIn some embodiments, at least one R e Select from -OR 12 , halogen and unsubstituted or replaced by one or more R 20 Substituted C 1-6 Alkyl (e.g., C substituted with -OH) 1-6 In some embodiments, each R e are independently selected from 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 replaced by one or more R 20 Substituted C 1-6 It should be understood that when R e When it is =O, other R on the same carbon atom e 、R f 、R g or R h is absent so that the carbon has the appropriate valence.

[0684] 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 to form a 3-6 membered carbocyclic or heterocyclic ring which is unsubstituted or substituted with one or more substituents selected from: -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20In some embodiments, R f and R g are linked together to form a 3-6 membered carbocyclic or heterocyclic ring which is unsubstituted or substituted with one or more substituents selected from: -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 In some embodiments, R g and R h are linked together to form a 3-6 membered carbocyclic or heterocyclic ring which is unsubstituted or substituted with one or more substituents selected from: -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 In some embodiments, (i) R f and R g or (ii) R g and R h are joined together to form an unsubstituted 3-6 membered carbocyclic or heterocyclic ring. f and R g or (ii) R g and R h are linked together to form a 3-6 membered carbocyclic or heterocyclic ring substituted with one or more substituents selected from: -OR 12 ,=O,-C(O)(C1-6 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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with 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 a 3-6 membered heterocyclic ring which is unsubstituted or substituted with one or more substituents selected from: -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 In some embodiments, (i) R f and R g or (ii) R g and R h linked together to form tetrahydrofuran which is unsubstituted or substituted with one or more substituents selected from: -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)(C1-6 alkylene)OR 14 , halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with 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 a pyrrolidine which is unsubstituted or substituted with one or more substituents selected from: -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with 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 to form a 5-6 membered heteroaryl group which is unsubstituted or substituted with one or more substituents selected from: -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 In some embodiments, R f and R gare linked together to form a 5-6 membered heteroaryl group which is unsubstituted or substituted with one or more substituents selected from: -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 In some embodiments, R g and R h are linked together to form a 5-6 membered heteroaryl group which is unsubstituted or substituted with one or more substituents selected from: -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with 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 (eg, pyridine). In some embodiments, (i) R f and R g or (ii) R g and R h are linked together to form a 5-6 membered heteroaryl group substituted with one or more substituents selected from: -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 , halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 In some embodiments, when (i) R f and R g or (ii) R g and R h When linked together, the ring formed does not contain an -NH- moiety. e 、R f 、R g or R h When ═O, another optional substituent on the same carbon atom is not otherwise present so that the carbon has the appropriate valence.

[0685] In some embodiments, for the compound according to Formula IIIC1, is a structure selected from the following:

[0686]

[0687] In some embodiments, the compound is according to Formula IIID:

[0688]

[0689] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof, wherein:

[0690] R 1 Select from -OR 8 and

[0691] R 5 Selected from halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0692] R 6 is a monocyclic or bicyclic heteroaryl group, wherein the heteroaryl group is separated by one or more R 15 replace;

[0693] R7 selected from halogen;

[0694] R 8 is selected from heterocycle and alkylheterocycle, wherein any heterocycle contains 4-8 members and is unsubstituted or substituted by one or more R a or R b substituted, and wherein the alkyl portion of any alkyl heterocycle is selected from C 1-6 alkyl;

[0695] Each R 11 Independently selected from 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)(3-6 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, 3-6 membered carbocyclic or heterocyclic ring, 5-6 membered heteroaryl and C 1-6 Alkyl, any C 1-6 Alkyl, carbocyclic, heterocyclic or heteroaryl groups are unsubstituted or replaced by one or more R 20 replace;

[0696] Each R 12 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H, wherein any C 1-6 Alkyl or C 2-6 The alkenyl group is unsubstituted or substituted with one or more R 13 replace;

[0697] Each R 13 Independently selected from -OR 14 、-CN、-N(R 14 )2 and halogen;

[0698] Each R 14 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H;

[0699] Each R 15are independently selected from deuterium, halogen, -N(R 12 )2, -CN and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0700] Each R 20 Independently selected from -OH, -OC 1-6 Alkyl, -CN, -NH2, -NHC 1-6 Alkyl and halogen;

[0701] R 27 is a 3-6 membered heterocyclic ring including one or more heteroatoms selected from N, O and S, wherein the heterocyclic ring is unsubstituted or replaced by one or more R 28 replace;

[0702] Each R 28 Independently selected from C 1-6 Alkyl and halogen;

[0703] R a and R b are each independently selected from deuterium, halogen, C 1-6 Alkyl, 3-6 membered carbocyclic ring, -OR 12 and H, where R a and R b are optionally linked together to form a 3-6 membered carbocyclic or heterocyclic ring, and wherein any C 1-6 Alkyl or 3-6 membered carbocyclic or heterocyclic ring is unsubstituted or replaced by one or more R 13 replace;

[0704] Q is selected from CR h R j NR g , O, S and SO2;

[0705] Each R e and R f Independently selected from R 11 and hydrogen, of which:

[0706] (i)R e and R f may optionally be linked together to form a 4-6 membered ring;

[0707] (ii) The first R connected to the adjacent atom f and the second R f may optionally be linked together to form a 3-5 membered ring;

[0708] (iii) The first R connected to the adjacent atom e and the second R emay optionally be linked together to form a 3-5 membered ring; or

[0709] (iv) The first R attached to the same atom f and the second R f may optionally be linked together to form a 3-5 membered ring,

[0710] where one or more R e and / or one or more R f Any ring formed is unsubstituted or replaced by one or more R 11 replace;

[0711] R g R when present 11 ;and

[0712] R h and R j When present, each independently selected from R 11 and hydrogen, or may be optionally linked together to form a 3-4 membered carbocyclic or heterocyclic ring which is unsubstituted or substituted with one or more substituents 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 , halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 Substitution, or R h and R e or R h and R f Optionally linked together to form unsubstituted or substituted with one or more R 11 Substituted 3-6 membered ring.

[0713] In some embodiments, the present disclosure provides a compound of Formula IIID or a salt (eg, a pharmaceutically acceptable salt) thereof.

[0714] In some embodiments, for compounds according to Formula IIID, Q is NR g In some embodiments, Rg Selected from -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 group is unsubstituted or substituted with one or more R 20 In some embodiments, R g Selected from -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 substituted by one or more R 20 Substituted C 1-6 alkyl.

[0715] In some embodiments, for compounds according to Formula IIID, Q is O, S, or SO 2 . In some embodiments, Q is O. In some embodiments, Q is S. In some embodiments, Q is SO 2 .

[0716] In some embodiments, for compounds 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 4-6 membered ring. In some embodiments, when Q is CR h R j And R e and R f When linked together to form a 4-6 membered ring, R h and R j are not linked together to form a 3-4 membered carbocyclic or heterocyclic ring. In some embodiments, Q is CR h R j And R h and R j are linked together to form a 3-4 membered carbocyclic or heterocyclic ring. In some embodiments, when Q is CR h R j And R h and R j When connected together to form a 3-4 membered carbocyclic or heterocyclic ring, there is no R e and R fIn some embodiments, when Q is CR h R j And R h and R j When linked together to form a 3-4 membered carbocyclic or heterocyclic ring, one or more R e 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 , R h is hydrogen, and R j Selected from 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 , halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 In some embodiments, Q is CR h R j , R h is hydrogen, and R j Select from -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20In some embodiments, Q is CR h R j , R h is hydrogen, and R j Select from -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 replaced by one or more R 20 Substituted C 1-6 In some embodiments, Q is CR h R j , R j is hydrogen, and R h and R e or R h and R f Optionally linked together to form unsubstituted or substituted with one or more R 11 Substituted 3-6 membered rings (eg, pyridine).

[0717] In some embodiments, for compounds according to Formula IIID, R h and R j Independently selected from R 11 In some embodiments, each R 11 Independently selected from -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 replaced by one or more R 20 Substituted C 1-6 In some embodiments, R h and R j At least one of them is -OR 12or unsubstituted or replaced by one or more R 20 Substituted C 1-6 Alkyl (e.g., C unsubstituted or substituted with -OH or -CN) 1-6 In some embodiments, R h and R j It should be understood that when R h or R j When =O, R on the same carbon atom h or R j is absent so that the carbon has the appropriate valence.

[0718] In some embodiments, for compounds according to Formula IIID, R h and R j are linked together to form a 3-4 membered carbocyclic or heterocyclic ring which is unsubstituted or substituted with one or more substituents selected from: -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 replaced by one or more R 20 Substituted C 1-6 In some embodiments, R h and R j At least one of them is -OR 12 or unsubstituted or replaced by one or more R 20 Substituted C 1-6 Alkyl (e.g., C unsubstituted or substituted with -OH or -CN) 1-6 In some embodiments, R h and R j are hydrogen. It should be understood that when R h or R j When it is =O, other R on the same carbon atom h or R j is absent so that the carbon has the appropriate valence.

[0719] In some embodiments, for the compound according to Formula IIID, each R e and R f Independently selected from R 11In some embodiments, each R 11 Independently selected from 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 replaced by one or more R 20 Substituted C 1-6 In some embodiments, R e and R f At least one of them is -OR 12 or unsubstituted or replaced by one or more R 20 Substituted 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 selected from hydrogen and R 11 , where each R 11 Independently selected from -OR 12 , halogen, 5-6 membered heteroaryl and unsubstituted or substituted by one or more R 20 Substituted C 1-6 In some embodiments, each R e In some embodiments, each R f In some embodiments, each R e and R f It should be understood that when R e or R f When it is =O, other R on the same carbon atom e or R f is absent so that the carbon has the appropriate valence.

[0720] In some embodiments, the compound is according to Formula IIIE:

[0721]

[0722] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof, wherein:

[0723] R 1 Select from -OR 8 and

[0724] R 5 Selected from halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0725] R 6 is a monocyclic or bicyclic heteroaryl group, wherein the heteroaryl group is separated by one or more R 15 replace;

[0726] R 7 selected from halogen;

[0727] R 8 is selected from heterocycle and alkylheterocycle, wherein any heterocycle contains 4-8 members and is unsubstituted or substituted by one or more R a or R b substituted, and wherein the alkyl portion of any alkyl heterocycle is selected from C 1-6 alkyl;

[0728] Each R 11 Independently selected from 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 group is unsubstituted or substituted with one or more R 20 replace;

[0729] Each R 12 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H, wherein any C 1-6 Alkyl or C2-6 The alkenyl group is unsubstituted or substituted with one or more R 13 replace;

[0730] Each R 13 Independently selected from -OR 14 、-CN、-N(R 14 )2 and halogen;

[0731] Each R 14 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H;

[0732] Each R 15 are independently selected from deuterium, halogen, -N(R 12 )2, -CN and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0733] Each R 20 Independently selected from -OH, -OC 1-6 Alkyl, -CN, -NH2, -NHC 1-6 Alkyl and halogen;

[0734] R 27 is a 3-6 membered heterocyclic ring including one or more heteroatoms selected from N, O and S, wherein the heterocyclic ring is unsubstituted or replaced by one or more R 28 replace;

[0735] Each R 28 Independently selected from C 1-6 Alkyl and halogen;

[0736] R a and R b are each independently selected from deuterium, halogen, C 1-6 Alkyl, 3-6 membered carbocyclic ring, -OR 12 and H, where R a and R b are optionally linked together to form a 3-6 membered carbocyclic or heterocyclic ring, and wherein any C 1-6 Alkyl or 3-6 membered carbocyclic or heterocyclic ring is unsubstituted or replaced by one or more R 13 replace;

[0737] Each R e and R f Independently selected from R 11 and hydrogen, of which:

[0738] (i)R e and R fmay optionally be linked together to form a 4-6 membered ring;

[0739] (ii) The first R connected to the adjacent atom f and the second R f may optionally be linked together to form a 3-5 membered ring;

[0740] (iii) The first R connected to the adjacent atom e and the second R e may optionally be linked together to form a 3-5 membered ring; or

[0741] (iv) The first R attached to the same atom f and the second R f may optionally be linked together to form a 3-5 membered ring,

[0742] where one or more R e and / or one or more R f Any ring formed is unsubstituted or replaced by one or more R 11 replace; and

[0743] R h and R j Each independently selected from R 11 and hydrogen, or may be optionally linked together to form a 3-4 membered carbocyclic or heterocyclic ring which is unsubstituted or substituted with one or more substituents selected from: -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 Substitution, or R h and R e or R h and R f Optionally linked together to form unsubstituted or substituted with one or more R 11 Substituted 3-6 membered ring.

[0744] In some embodiments, the present disclosure provides a compound of Formula IIIE or a salt (eg, a pharmaceutically acceptable salt) thereof.

[0745] In some embodiments, for compounds according to Formula IIIE, R h and R j Independently selected from R 11 In some embodiments, each R 11 Independently selected from -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 replaced by one or more R 20 Substituted C 1-6 In some embodiments, R h and R j At least one of them is -OR 12 or unsubstituted or replaced by one or more R 20 Substituted 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 R 11 In some embodiments, R h and R j It should be understood that when R h or R j When =O, R on the same carbon atom h or R j is absent so that the carbon has the appropriate valence. In some embodiments, R h and R j Independently selected from R 11 and hydrogen, and (i) R e and R f linked together to form a 4-6 membered ring; (ii) the first R f and the second R f can be optionally linked together to form a 3-5 membered ring; (iii) the first R e and the second R e are optionally linked together to form a 3-5 membered ring; or (iv) linked to the first Rf and the second R f may be optionally linked together to form a 3-5 membered ring, wherein one or more R e and / or one or more R f Any ring formed is unsubstituted or replaced by one or more R 11 replace.

[0746] In some embodiments, for compounds according to Formula IIIE, R h and R j are linked together to form a 3-4 membered carbocyclic or heterocyclic ring which is unsubstituted or substituted with one or more substituents selected from: -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 In some embodiments, for compounds according to Formula III-IE, R h and R j are linked together to form a 3-4 membered carbocyclic or heterocyclic ring which is unsubstituted or substituted with one or more substituents selected from: -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 replaced by one or more R 20 Substituted C 1-6 In some embodiments, when R h and R j When connected together to form a 3-4 membered carbocyclic or heterocyclic ring, there is no R e and Rf In some embodiments, when R h and R j When linked together to form a 3-4 membered carbocyclic or heterocyclic ring, one or more R e and / or one or more R f In some embodiments, R h and R j are linked together to form an unsubstituted 3-4 membered carbocyclic or heterocyclic ring. h and R j are linked together to form a 3-4 membered carbocyclic or heterocyclic ring substituted with one or more substituents selected from: -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 In some embodiments, R h and R j are linked together to form a 3-4 membered carbon ring which is unsubstituted or substituted with one or more substituents selected from: -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 In some embodiments, R h and R jlinked together to form a cyclopropane which is unsubstituted or substituted with one or more substituents selected from: -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 In some embodiments, R h and R j linked together to form a cyclobutane which is unsubstituted or substituted with one or more substituents selected from: -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 In some embodiments, R h and R j are linked together to form a 3-4 membered heterocyclic ring which is unsubstituted or substituted with one or more substituents selected from: -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 1-6alkylene)OR 14 , halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 In some embodiments, R j is hydrogen, and R h and R e or R h and R f Optionally linked together to form unsubstituted or substituted with one or more R 11 Substituted 3-6 membered rings (eg, pyridine).

[0747] In some embodiments of the compound according to Formula IIIE, each R e and R f Independently selected from R 11 In some embodiments, each R 11 Independently selected from 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 replaced by one or more R 20 Substituted C 1-6 In some embodiments, R e and R f At least one of them is -OR 12 or unsubstituted or replaced by one or more R 20 Substituted 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 selected from hydrogen and R 11 , where each R 11 Independently selected from -OR 12 , halogen, 5-6 membered heteroaryl and unsubstituted or substituted by one or more R 20 Substituted C 1-6 In some embodiments, each Re and R f It should be understood that when R e or R f When it is =O, other R on the same carbon atom e or R f is absent so that the carbon has the appropriate valence.

[0748] In some embodiments, for compounds according to Formula IIIE, is a structure selected from the following:

[0749]

[0750]

[0751] In some embodiments, the compound is according to Formula IIIF, IIIG, or IIIH:

[0752]

[0753] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof, wherein:

[0754] R 1 Select from -OR 8 and

[0755] R 5 Selected from halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0756] R 6 is a monocyclic or bicyclic heteroaryl group, wherein the heteroaryl group is separated by one or more R 15 replace;

[0757] R 7 selected from halogen;

[0758] R 8 is selected from heterocycle and alkylheterocycle, wherein any heterocycle contains 4-8 members and is unsubstituted or substituted by one or more R a or R b substituted, and wherein the alkyl portion of any alkyl heterocycle is selected from C 1-6 alkyl;

[0759] Each R 11 Independently selected from deuterium, -OR 12 、=O、=N(R 14 )、-C(O)(C 1-6Alkylene)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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace;

[0760] Each R 12 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H, wherein any C 1-6 Alkyl or C 2-6 The alkenyl group is unsubstituted or substituted with one or more R 13 replace;

[0761] Each R 13 Independently selected from -OR 14 、-CN、-N(R 14 )2 and halogen;

[0762] Each R 14 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H;

[0763] Each R 15 are independently selected from deuterium, halogen, -N(R 12 )2, -CN and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0764] Each R 20 Independently selected from -OH, -OC 1-6 Alkyl, -CN, -NH2, -NHC 1-6 Alkyl and halogen;

[0765] R 27 is a 3-6 membered heterocyclic ring including one or more heteroatoms selected from N, O and S, wherein the heterocyclic ring is unsubstituted or replaced by one or more R 28 replace;

[0766] Each R 28 Independently selected from C1-6 Alkyl and halogen;

[0767] R a and R b are each independently selected from deuterium, halogen, C 1-6 Alkyl, 3-6 membered carbocyclic ring, -OR 12 and H, where R a and R b are optionally linked together to form a 3-6 membered carbocyclic or heterocyclic ring, and wherein any C 1-6 Alkyl or 3-6 membered carbocyclic or heterocyclic ring is unsubstituted or replaced by one or more R 13 replace; and

[0768] Each R e and R f Independently selected from R 11 and hydrogen, of which:

[0769] (i)R e and R f may optionally be linked together to form a 4-6 membered ring;

[0770] (ii) The first R connected to the adjacent atom f and the second R f may optionally be linked together to form a 3-5 membered ring;

[0771] (iii) The first R connected to the adjacent atom e and the second R e may optionally be linked together to form a 3-5 membered ring; or

[0772] (iv) The first R attached to the same atom f and the second R f may optionally be linked together to form a 3-5 membered ring,

[0773] where one or more R e and / or one or more R f Any ring formed is unsubstituted or replaced by one or more R 11 replace.

[0774] In some embodiments, the compound is a compound according to formula IIIF or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer. In some embodiments, the compound is a compound according to formula IIIG or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer. In some embodiments, the compound is a compound according to formula IIIH or a salt thereof (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer.

[0775] In some embodiments, the present disclosure provides a compound of formula IIIF or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the present disclosure provides a compound of formula IIIG or a salt thereof (e.g., a pharmaceutically acceptable salt). In some embodiments, the present disclosure provides a compound of formula IIIH or a salt thereof (e.g., a pharmaceutically acceptable salt).

[0776] In some embodiments, for compounds according to Formula IIIF, IIIG, or IIIH, each R e and R f Independently selected from R 11 In some embodiments, each R 11 Independently selected from 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 replaced by one or more R 20 Substituted C 1-6 In some embodiments, R e and R f At least one of them is -OR 12 or unsubstituted or replaced by one or more R 20 Substituted C 1-6 Alkyl (e.g., C unsubstituted or substituted with -OH or -CN) 1-6 In some embodiments, each R e In some embodiments, each Rf In some embodiments, each R e and R f It should be understood that when R e or R f When it is =O, other R on the same carbon atom e or R f is absent so that the carbon has the appropriate valence.

[0777] In some embodiments, for compounds according to Formula IIIF, IIIG, or IIIH, is a structure selected from the following:

[0778]

[0779]

[0780] In some embodiments, the compound is according to Formula IIIJ:

[0781]

[0782] or a salt (e.g., a pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof, wherein:

[0783] R 1 Select from -OR 8 and

[0784] R 5 Selected from halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0785] R 6 is a monocyclic or bicyclic heteroaryl group, wherein the heteroaryl group is separated by one or more R 15 replace;

[0786] R 7 selected from halogen;

[0787] R 8 is selected from heterocycle and alkylheterocycle, wherein any heterocycle contains 4-8 members and is unsubstituted or substituted by one or more R a or R b substituted, and wherein the alkyl portion of any alkyl heterocycle is selected from C 1-6 alkyl;

[0788] Each R 11 Independently selected from deuterium, -OR 12 、=O、=N(R14 )、-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)(3-6 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, 3-6 membered carbocyclic or heterocyclic ring and C 1-6 Alkyl, any C 1-6 The alkyl, carbocyclic or heterocyclic ring is unsubstituted or substituted with one or more R 20 replace;

[0789] Each R 12 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H, wherein any C 1-6 Alkyl or C 2-6 The alkenyl group is unsubstituted or substituted with one or more R 13 replace;

[0790] Each R 13 Independently selected from -OR 14 、-CN、-N(R 14 )2 and halogen;

[0791] Each R 14 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H;

[0792] Each R 15 are independently selected from deuterium, halogen, -N(R 12 )2, -CN and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace;

[0793] Each R 20 Independently selected from -OH, -OC 1-6 Alkyl, -CN, -NH2, -NHC 1-6 Alkyl and halogen;

[0794] R 27is a 3-6 membered heterocyclic ring including one or more heteroatoms selected from N, O and S, wherein the heterocyclic ring is unsubstituted or replaced by one or more R 28 replace;

[0795] Each R 28 Independently selected from C 1-6 Alkyl and halogen;

[0796] R a and R b are each independently selected from deuterium, halogen, C 1-6 Alkyl, 3-6 membered carbocyclic ring, -OR 12 and H, where R a and R b are optionally linked together to form a 3-6 membered carbocyclic or heterocyclic ring, and wherein any C 1-6 Alkyl or 3-6 membered carbocyclic or heterocyclic ring is unsubstituted or replaced by one or more R 13 replace;

[0797] Each R e and R f Independently selected from R 11 and hydrogen, of which:

[0798] (i)R e and R f may optionally be linked together to form a 4-6 membered ring;

[0799] (ii) The first R connected to the adjacent atom f and the second R f may optionally be linked together to form a 3-5 membered ring;

[0800] (iii) The first R connected to the adjacent atom e and the second R e may optionally be linked together to form a 3-5 membered ring; or

[0801] (iv) The first R attached to the same atom f and the second R f may optionally be linked together to form a 3-5 membered ring,

[0802] where one or more R e and / or one or more R f Any ring formed is unsubstituted or replaced by one or more R 11 replace; and

[0803] R g R 11 , or R g and R e or R g and Rf Optionally linked together to form unsubstituted or substituted with one or more R 11 Substituted 3-6 membered ring.

[0804] In some embodiments, the present disclosure provides a compound of Formula IIIJ or a salt (eg, a pharmaceutically acceptable salt) thereof.

[0805] In some embodiments, for compounds according to Formula IIIJ, each R e and R f Independently selected from R 11 In some embodiments, each R 11 Independently selected from 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 replaced by one or more R 20 Substituted C 1-6 In some embodiments, each R 11 Independently selected from 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 alk...

Claims

1. A compound represented by formula II': or a salt thereof (e.g., a pharmaceutically acceptable salt), wherein: R 1 Select from -OR 8 and R 2 Selected from H, C 1-6 Alkyl and 3-6 membered carbocyclic ring, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; R 3 is selected from unsubstituted or substituted with one or more R 10 substituted 4-9 membered heterocycle; R 4 is H; R 5 Selected from H, halogen, -CN, -OR 12 , 3-6 membered heterocyclic ring, 5-6 membered heteroaryl and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; R 6 is a monocyclic or bicyclic heteroaryl group, wherein the heteroaryl group is surrounded by one or more R 15 replace; R 7 is selected from halogen; R 8 is selected from heterocycle and alkylheterocycle, wherein any heterocycle contains 4 to 8 members and is unsubstituted or substituted by one or more R a or R b substituted, and wherein the alkyl portion of any alkyl heterocycle is selected from C 1-6 alkyl; Each R 10 are independently selected from 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)(3-6 membered carbocyclic ring), -C(O)(3-8 membered heterocyclic ring), -C(O)(5-6 membered heteroaryl), -C(O)O(3-6 membered carbocyclic ring), -C(O)O(3-6 membered heterocyclic ring), -C(O)O(C 1-6 Alkylene)(3-6 membered heterocyclic ring), -S(O)2(C 1-6 alkyl), halogen, 5-6 membered heteroaryl, 3-6 membered carbocyclic ring, 3-6 membered heterocyclic ring and C 1-6 Alkyl, any C 1-6 The alkyl group is optionally deuterated and unsubstituted or substituted with one or more R 20 substituted, wherein any 3-6 membered carbocyclic ring, 5-6 membered heteroaryl ring or 3-6 membered or 3-8 membered heterocyclic ring is unsubstituted or replaced by one or more R 12 or R 20 Replace, and two R 10 are optionally joined together to form, together with the atoms to which they are attached, a 3-6 membered carbocyclic or heterocyclic ring; Each R 12 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H, any C 1-6 Alkyl or C 2-6 The alkenyl group is unsubstituted or substituted with one or more R 13 replace; Each R 13 Independently selected from -OR 14 、-CN、-N(R 14 )2 and halogen; Each R 14 independently selected from 3-6 membered carbocyclic ring, 3-6 membered heterocyclic ring, C 1-6 Alkyl, C 2-6 alkenyl and H, any C 1-6 The alkyl group is optionally deuterated; Each R 15 are independently selected from deuterium, halogen, -N(R 12 )2. -CN and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; Each R 20 Independently selected from -OH, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, =O, -CN, -NH2, -NHC 1-6 Alkyl, -C(O)(C 1-6 alkyl), 3-6 membered carbocyclic ring, phenyl and halogen; R 27 is a 3-6 membered heterocyclic ring including one or more heteroatoms selected from N, O and S, wherein the heterocyclic ring is unsubstituted or substituted with one or more R 28 replace; Each R 28 Independently selected from C 1-6 Alkyl and halogen; and R a and R b are each independently selected from deuterium, halogen, C 1-6 Alkyl, 3-6 membered carbocyclic ring, -OR 12 and H, where R a and R b are optionally linked together to form a 3-6 membered carbocyclic or heterocyclic ring, and any C 1-6 Alkyl or 3-6 membered carbocyclic or heterocyclic ring is unsubstituted or substituted by one or more R 13 replace.

2. A compound represented by formula II: or a salt thereof (e.g., a pharmaceutically acceptable salt), wherein: R 1 Select from -OR 8 and R 2 Selected from H, C 1-6 Alkyl and 3-6 membered carbocyclic ring, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; R 3 is selected from unsubstituted or substituted with one or more R 10 substituted 4-9 membered heterocyclic ring, provided that (i) when the heterocyclic ring contains a nitrogen atom, the nitrogen atom is replaced by R 10 substituted, or (ii) the heterocyclic ring does not contain an -NH- moiety; R 4 is H; R 5 Selected from H, halogen, -CN, -OR 12 , 3-6 membered heterocyclic ring, 5-6 membered heteroaryl and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; R 6 is a monocyclic or bicyclic heteroaryl group, wherein the heteroaryl group is surrounded by one or more R 15 replace; R 7 is selected from halogen; R 8 is selected from heterocycle and alkylheterocycle, wherein any heterocycle contains 4 to 8 members and is unsubstituted or substituted by one or more R a or R b substituted, and wherein the alkyl portion of any alkyl heterocycle is selected from C 1-6 alkyl; Each R 10 are independently selected from 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)(3-6 membered carbocyclic ring), -C(O)(3-8 membered heterocyclic ring), -C(O)(5-6 membered heteroaryl), -C(O)O(3-6 membered carbocyclic ring), -C(O)O(3-6 membered heterocyclic ring), -C(O)O(C 1-6 Alkylene)(3-6 membered heterocyclic ring), -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 group is optionally deuterated and unsubstituted or substituted with one or more R 20 substituted, wherein any 3-6 membered carbocyclic ring, 5-6 membered heteroaryl ring or 3-6 membered or 3-8 membered heterocyclic ring is unsubstituted or replaced by one or more R 12 or R 20 Replace, and two R 10 are optionally joined together to form, together with the atoms to which they are attached, a 3-6 membered carbocyclic or heterocyclic ring; Each R 12 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H, any C 1-6 Alkyl or C 2-6 The alkenyl group is unsubstituted or substituted with one or more R 13 replace; Each R 13 Independently selected from -OR 14 、-CN、-N(R 14 )2 and halogen; Each R 14 independently selected from 3-6 membered carbocyclic ring, 3-6 membered heterocyclic ring, C 1-6 Alkyl, C 2-6 alkenyl and H, any C 1-6 The alkyl group is optionally deuterated; Each R 15 are independently selected from deuterium, halogen, -N(R 12 )2. -CN and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; Each R 20 Independently selected from -OH, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, =O, -CN, -NH2, -NHC 1-6 Alkyl, -C(O)(C 1-6 alkyl), 3-6 membered carbocyclic ring, phenyl and halogen; R 27 is a 3-6 membered heterocyclic ring including one or more heteroatoms selected from N, O and S, wherein the heterocyclic ring is unsubstituted or substituted with one or more R 28 replace; Each R 28 Independently selected from C 1-6 Alkyl and halogen; and R a and R b are each independently selected from deuterium, halogen, C 1-6 Alkyl, 3-6 membered carbocyclic ring, -OR 12 and H, where R a and R b are optionally linked together to form a 3-6 membered carbocyclic or heterocyclic ring, and any C 1-6 Alkyl or 3-6 membered carbocyclic or heterocyclic ring is unsubstituted or substituted by one or more R 13 replace.

3. The compound of claim 1 or 2, wherein the compound has formula II-a: or a salt thereof (eg, a pharmaceutically acceptable salt).

4. A compound as described in any one of claims 1 to 3, wherein R 3 is a 4-6 membered heterocyclic ring including one heteroatom selected from O, S and N.

5. The compound as claimed in claim 4, wherein R 3 is a 4-6 membered heterocyclic ring including 1 heteroatom selected from O, S and N, wherein the heterocyclic ring is surrounded by 1-4 R 10 substituted, provided that when the heterocyclic ring contains a nitrogen atom, the nitrogen atom is replaced by R 10 replace.

6. A compound as described in any one of claims 1 to 5, wherein R 3 For 0-4 R 10 substituted pyrrolidine, provided that the nitrogen atom is replaced by R 10 replace.

7. A compound as described in any one of claims 1 to 5, wherein R 3 For 0-4 R 10 Substituted oxetanes or thieetanes.

8. A compound as described in any one of claims 1 to 5, wherein R 3 For 0-4 R 10 Substituted tetrahydrofuran or tetrahydrothiophene.

9. The compound of any one of claims 1 to 5, wherein R 3 For one or more R 10 substituted 4-6 membered heterocyclic ring, provided that when the heterocyclic ring contains a nitrogen atom, the nitrogen atom is replaced by R 10 Replace, and each R 10 are independently selected from -C(O)(C 1-6 alkyl), -C(O)(3-6 membered carbocyclic ring), -C(O)O(C 1-6 alkyl), halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 substituted, and any 3-6 membered carbocyclic ring is unsubstituted or replaced by one or more R 12 or R 20 replace.

10. The compound of any one of claims 1 to 5, wherein R 3 For one or more R 10 A substituted 4-6 membered heterocyclic ring, wherein at least one R 10 Select from -OR 12 and C substituted by -OH 1-6 alkyl.

11. The compound of any one of claims 1 to 10, wherein R 3 For one or more R 10 A substituted 4-6 membered heterocyclic ring, wherein at least one R 10 For unsubstituted C 1-6 alkyl.

12. A compound as described in any one of claims 1 to 11, wherein R 3 Selected from: Any of which is optionally further represented by one or more R 10 replace.

13. A compound as described in any one of claims 1 to 3, wherein R 3 is a 7-9 membered heterocyclic ring including one or more heteroatoms selected from O, S and N, wherein the heterocyclic ring is unsubstituted or substituted with one or more R 10 replace.

14. The compound of claim 13, wherein R 3 is a 7-9 membered heterocyclic ring including one or more heteroatoms selected from O, S and N, wherein the heterocyclic ring is unsubstituted or substituted with one or more R 10 substituted, provided that (i) when the heterocyclic ring contains a nitrogen atom, the nitrogen atom is replaced by R 10 substituted, or (ii) the heterocycle does not contain an -NH- moiety.

15. The compound of claim 13 or 14, wherein R 3 is a 7-9 membered bridged heterocyclic ring including one or more heteroatoms selected from O, S and N, wherein the bridged heterocyclic ring is unsubstituted or substituted with one or more R 10 replace.

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

17. A compound as described in any one of claims 1, 2, 3 or 13-16, wherein R 3 Selected from: Any of which is optionally further represented by one or more R 10 replace.

18. The compound of any one of claims 1-17, wherein the compound is according to 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: or a salt thereof (e.g., a pharmaceutically acceptable salt), wherein: Each R d Independently selected from 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 carbon ring), -S(O)2(C 1-6 alkyl), halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 substituted, and any 3-6 membered carbocyclic ring is unsubstituted or replaced by one or more R 12 or R 20 replace; R e When present, selected from -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)(3-6 membered carbocyclic ring), -C(O)(3-8 membered heterocyclic ring), -C(O)(5-6 membered heteroaryl), -C(O)O(3-6 membered carbocyclic ring), -C(O)O(3-6 membered heterocyclic ring), -C(O)O(C 1-6 Alkylene)(3-6 membered heterocyclic ring), -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 group is optionally deuterated and unsubstituted or substituted with one or more R 20 substituted, and any 3-6 membered carbocyclic ring, 5-6 membered heteroaryl ring or 3-6 membered or 3-8 membered heterocyclic ring is unsubstituted or replaced by one or more R 12 or R 20 replace; and Each R f Optionally absent and when present is selected from =O, -NH2, -NHC 1-6 Alkyl and -N(C 1-6 Alkyl)2.

19. The compound of any one of claims 1 to 17, wherein the compound is a compound according to formula IIAA: or a salt thereof (e.g., a pharmaceutically acceptable salt), wherein: Each R d Independently selected from 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)(3-6 membered carbocyclic ring), -S(O)2(C 1-6 alkyl), halogen, 3-6 membered carbocyclic ring, 3-6 membered heterocyclic ring and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 substituted, wherein any 3-6 membered carbocyclic ring or 3-6 membered heterocyclic ring is unsubstituted or replaced by one or more R 12 or R 20 replace; and (i)R q1 , R q2 and R p2 Each independently selected from R d , and R e and R p1 Together with the atoms to which they are attached, they are unsubstituted or replaced by one or more R d a substituted 5-6 membered heterocycle; or (ii) R p1 , R p2 and R q2 Each independently selected from R d , and R e and R q1 Together with the atoms to which they are attached, they are unsubstituted or replaced by one or more R d Substituted 5-6 membered heterocyclic ring.

20. The compound of any one of claims 1 to 19, wherein R 6 For one or more R 15 Substituted monocyclic heteroaryl.

21. The compound of claim 20, wherein R 6 For one or more R 15 Substituted pyridines.

22. The compound of claim 21, wherein R 6 With structure 23. A compound as described in any one of claims 1 to 19, wherein R 6 For one or more R 15 Substituted bicyclic heteroaryl.

24. The compound of claim 23, wherein R 6 Selected from: in: X is selected from N and C-CN; Y is selected from O and S; R 23 Selected from -N(R 12 2. C 1-6 Alkyl and C 1-6 Alkyl-N(R 14 )2, where any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; and R 24 , R 25 and R 26 independently selected from H, deuterium, halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace.

25. The compound of claim 23 or 24, wherein R 6 Selected from: Any of which is one or more R 15 replace.

26. A compound as described in any one of claims 23-25, wherein R 6 Selected from:

27. A compound as described in any one of claims 23-26, wherein R 6 Selected from:

28. The compound of any one of claims 1-27, wherein the compound is according to 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: or a salt thereof (e.g., a pharmaceutically acceptable salt), wherein: Each R d Independently selected from 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 carbon ring), -S(O)2(C 1-6 alkyl), halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 substituted, and any 3-6 membered carbocyclic ring is unsubstituted or replaced by one or more R 12 or R 20 replace; R e When present, selected from -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)(3-6 membered carbocyclic ring), -C(O)(3-8 membered heterocyclic ring), -C(O)(5-6 membered heteroaryl), -C(O)O(3-6 membered carbocyclic ring), -C(O)O(3-6 membered heterocyclic ring), -C(O)O(C 1-6 Alkylene)(3-6 membered heterocyclic ring), -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 group is optionally deuterated and unsubstituted or substituted with one or more R 20 substituted, and any 3-6 membered carbocyclic ring, 5-6 membered heteroaryl ring or 3-6 membered or 3-8 membered heterocyclic ring is unsubstituted or replaced by one or more R 12 or R 20 replace; Each R f Optionally absent and when present is selected from =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 Selected from -N(R 12 2. C 1-6 Alkyl and C 1-6 Alkyl-N(R 14 )2, where any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; and R 24 , R 25 and R 26 independently selected from H, deuterium, halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace.

29. The compound of any one of claims 1 to 27, wherein the compound is according to formula IIAA1: or a salt thereof (e.g., a pharmaceutically acceptable salt), wherein: Each R d Independently selected from 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)(3-6 membered carbocyclic ring), -C(O)N(R 14 )2、-S(O)2(C 1-6 alkyl), 3-6 membered carbocyclic ring, 3-6 membered heterocyclic ring, halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 substituted, and any 3-6 membered carbocyclic ring or 3-6 membered heterocyclic ring is unsubstituted or replaced by one or more R 12 or R 20 replace; X is selected from N and C-CN; Y is selected from O and S; R 23 Selected from -N(R 12 2. C 1-6 Alkyl and C 1-6 Alkyl-N(R 14 )2, where any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; R 24 , R 25 and R 26 independently selected from H, deuterium, halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; and (i)R q1 , R q2 and R p2 Each independently selected from R d , and R e and R p1 Together with the atoms to which they are attached, they are unsubstituted or replaced by one or more R d a substituted 5-6 membered heterocycle; or (ii) R p1 , R p2 and R q2 Each independently selected from R d , and R e and R q1 Together with the atoms to which they are attached, they are unsubstituted or replaced by one or more R d Substituted 5-6 membered heterocyclic ring.

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

31. A compound as described in any one of claims 28-30, wherein R 24 , R 25 and R 26 One or more of the is halogen (eg, F).

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

33. The compound of claim 18 or 28, wherein each R f Does not exist.

34. The compound of claim 18 or 28, wherein R e is unsubstituted or replaced by one or more R 20 Substituted C 1-6 alkyl.

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

36. The compound of claim 18 or 28, wherein R e Selected from -C(O)(C 1-6 alkyl), -C(O)(3-6 membered carbocyclic ring) and -C(O)O(C 1-6 alkyl), any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 substituted, and any 3-6 membered carbocyclic ring is unsubstituted or replaced by one or more R 12 or R 20 replace.

37. A compound as described in any one of claims 18-36, wherein each R d For H.

38. A compound as described in any one of claims 18-36, wherein at least one R d Select from -OR 12 and C substituted by -OH 1-6 alkyl.

39. A compound as described in any one of claims 1 to 38, wherein R 2 For H.

40. A compound as described in any one of claims 1-38, wherein R 2 is selected from unsubstituted or substituted with one or more R 13 Substituted C 1-6 alkyl.

41. The compound of claim 40, wherein R 2 Selected from C 1-2 alkyl.

42. A compound as described in any one of claims 1-38, wherein R 2 is selected from 3-6 membered carbon rings.

43. A compound as described in any one of claims 1-42, wherein R 1 Select from -OR 8 .

44. The compound of claim 43, wherein R 1 Selected from: Where R a1 , R a2 , R b1 and R b2 are each independently selected from deuterium, halogen, C 1-6 Alkyl, -OR 12 and H, where R a2 and R b2 may be optionally linked together to form a 3-6 membered carbocyclic ring, and wherein any C 1-6 Alkyl or 3-6 membered carbocyclic ring is unsubstituted or substituted with one or more R 13 replace.

45. The compound of claim 44, wherein R 1 Selected from:

46. ​​The compound of claim 43, wherein R 1 Selected from: Where R a and R b are each independently selected from halogen, C 1-6 Alkyl, -OR 12 and H, where any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace.

47. The compound of claim 46, wherein R 1 Selected from:

48. The compound of claim 43, wherein R 1 Selected from: Each R a and R b independently selected from halogen, C 1-6 Alkyl, -OR 12 and H; and R c Selected from C 1-6 Alkyl, where R a and R b or R c are optionally linked together to form a 3-6 membered carbocyclic or heterocyclic ring, and any C 1-6 Alkyl or 3-6 membered carbocyclic or heterocyclic ring is unsubstituted or substituted by one or more R 13 replace.

49. The compound of claim 48, wherein R 1 Selected from:

50. A compound as described in any one of claims 1-42, wherein R 1 Selected from 51. A compound as described in any one of claims 1-50, wherein R 5 For H.

52. A compound as described in any one of claims 1-50, wherein R 5 is a halogen (eg, F or Cl).

53. A compound as described in any one of claims 1-50, wherein R 5 is selected from unsubstituted or substituted with one or more R 13 Substituted C 1-6 alkyl.

54. The compound of claim 53, wherein R 5 is selected from C substituted by one or more halogen or -CN 1-6 alkyl.

55. The compound of claim 54, wherein R 5 Selected from -CF2H, -CF3, -CH2CN and -CH2CH3.

56. The compound of claim 55, wherein R 5 It is -CF3.

57. A compound as described in any one of claims 1-56, wherein the compound is not a compound included in Table 1.

58. A compound represented by formula III': or a salt thereof (e.g., a pharmaceutically acceptable salt), wherein: R 1 Select from -OR 8 and R 2 and R 3 Together with the nitrogen atom to which it is attached, it is unsubstituted or replaced by one or more R 11 substituted 4-10 membered heterocycle; R 4 is H; R 5 Selected from halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; R 6 is a monocyclic or bicyclic heteroaryl group, wherein the heteroaryl group is surrounded by one or more R 15 replace; R 7 is selected from halogen; R 8 is selected from heterocycle and alkylheterocycle, wherein any heterocycle contains 4 to 8 members and is unsubstituted or substituted by one or more R a or R b substituted, and wherein the alkyl portion of any alkyl heterocycle is selected from C 1-6 alkyl; Each R 11 are independently selected from 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)(3-6 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, 3-6 membered carbocyclic or heterocyclic ring, 5-6 membered heteroaryl and C 1-6 Alkyl, any C 1-6 The alkyl, carbocyclic, heterocyclic or heteroaryl groups are unsubstituted or substituted with one or more R 20 replace; Each R 12 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H, any C 1-6 Alkyl or C 2-6 The alkenyl group is unsubstituted or substituted with one or more R 13 replace; Each R 13 Independently selected from -OR 14 、-CN、-N(R 14 )2 and halogen; Each R 14 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H; Each R 15 are independently selected from deuterium, halogen, -N(R 12 )2. -CN and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; Each R 20 Independently selected from -OH, -OC 1-6 Alkyl, -CN, -NH2, -NHC 1-6 Alkyl and halogen; R 27 is a 3-6 membered heterocyclic ring including one or more heteroatoms selected from N, O and S, wherein the heterocyclic ring is unsubstituted or substituted with one or more R 28 replace; Each R 28 Independently selected from C 1-6 Alkyl and halogen; and R a and R b are each independently selected from deuterium, halogen, C 1-6 Alkyl, 3-6 membered carbocyclic ring, -OR 12 and H, where R a and R b are optionally linked together to form a 3-6 membered carbocyclic or heterocyclic ring, and any C 1-6 Alkyl or 3-6 membered carbocyclic or heterocyclic ring is unsubstituted or substituted by one or more R 13 replace.

59. A compound represented by formula III: or a salt thereof (e.g., a pharmaceutically acceptable salt), wherein: R 1 Select from -OR 8 and R 2 and R 3 Together with the nitrogen atom to which it is attached, it is unsubstituted or replaced by one or more R 11 substituted 4-10 membered heterocyclic ring, provided that when the heterocyclic ring contains an additional nitrogen atom, the additional nitrogen atom is replaced by R 11 replace; R 4 is H; R 5 Selected from halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; R 6 is a monocyclic or bicyclic heteroaryl group, wherein the heteroaryl group is surrounded by one or more R 15 replace; R 7 is selected from halogen; R 8 is selected from heterocycle and alkylheterocycle, wherein any heterocycle contains 4 to 8 members and is unsubstituted or substituted by one or more R a or R b substituted, and wherein the alkyl portion of any alkyl heterocycle is selected from C 1-6 alkyl; Each R 11 are independently selected from 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)(3-6 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, 3-6 membered carbocyclic or heterocyclic ring, 5-6 membered heteroaryl and C 1-6 Alkyl, any C 1-6 The alkyl, carbocyclic, heterocyclic or heteroaryl groups are unsubstituted or substituted with one or more R 20 replace; Each R 12 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H, any C 1-6 Alkyl or C 2-6 The alkenyl group is unsubstituted or substituted with one or more R 13 replace; Each R 13 Independently selected from -OR 14 、-CN、-N(R 14 )2 and halogen; Each R 14 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H; Each R 15 are independently selected from deuterium, halogen, -N(R 12 )2. -CN and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; Each R 20 Independently selected from -OH, -OC 1-6 Alkyl, -CN, -NH2, -NHC 1-6 Alkyl and halogen; R 27 is a 3-6 membered heterocyclic ring including one or more heteroatoms selected from N, O and S, wherein the heterocyclic ring is unsubstituted or substituted with one or more R 28 replace; Each R 28 Independently selected from C 1-6 Alkyl and halogen; and R a and R b are each independently selected from deuterium, halogen, C 1-6 Alkyl, 3-6 membered carbocyclic ring, -OR 12 and H, where R a and R b are optionally linked together to form a 3-6 membered carbocyclic or heterocyclic ring, and any C 1-6 Alkyl or 3-6 membered carbocyclic or heterocyclic ring is unsubstituted or substituted by one or more R 13 replace.

60. The compound of claim 58 or 59, wherein the compound has the formula III-a: or a salt thereof (eg, a pharmaceutically acceptable salt).

61. A compound as described in any one of claims 58-60, wherein R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a 4-7 membered heterocyclic ring.

62. The compound of claim 61, wherein R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a 4-7 membered heterocyclic ring including 1 or 2 heteroatoms selected from O, S and N.

63. The compound of claim 62, wherein R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a 4-7 membered heterocyclic ring including 1 or 2 heteroatoms selected from O, S and N, wherein the heterocyclic ring is surrounded by 1-4 R 11 replace.

64. A compound as described in any one of claims 58-63, wherein R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a group consisting of 0-4 R 11 Substituted pyrrolidines.

65. A compound as described in any one of claims 58-63, wherein R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a group consisting of 0-4 R 11 Substituted azetidines.

66. A compound as described in any one of claims 58-63, wherein R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a group consisting of 0-4 R 11 Substituted piperidines.

67. A compound as described in any one of claims 58-63, wherein R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a group consisting of 0-4 R 11 Substituted piperazines.

68. A compound as described in any one of claims 58-63, wherein R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a group consisting of 0-4 R 11 Substituted morpholine or thiomorpholine.

69. A compound as described in any one of claims 58-63, wherein R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a 7-membered heterocyclic ring including 1 to 3 heteroatoms selected from O, S and N.

70. A compound as described in any one of claims 58-69, wherein R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a 11 A substituted 4-7 membered heterocyclic ring, wherein at least one R 11 Select from -OR 12 and C substituted by -OH 1-6 alkyl.

71. A compound as described in any one of claims 58-70, wherein R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a 11 A substituted 4-7 membered heterocyclic ring, wherein at least one R 11 For unsubstituted C 1-6 alkyl.

72. A compound as described in any one of claims 58-69, wherein R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms an unsubstituted 4-7 membered heterocyclic ring.

73. A compound as described in any one of claims 58-60, wherein R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a bridged heterocyclic ring.

74. The compound of claim 73, wherein R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a 7-9 membered bridged heterocyclic ring including 1 or 2 heteroatoms selected from O, S and N.

75. The compound of claim 74, wherein R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a 7-9 membered bridged heterocyclic ring including 1 or 2 heteroatoms selected from O, S and N, wherein the bridged heterocyclic ring is supported by 1-4 R 11 replace.

76. A compound as described in any one of claims 73-75, wherein R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a group consisting of 0-4 R 11 Substituted Bridged Piperidines.

77. A compound as described in any one of claims 73-75, wherein R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a group consisting of 0-4 R 11 Substituted Bridged Piperazines.

78. A compound as described in any one of claims 73-75, wherein R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a group consisting of 0-4 R 11 Substituted bridged morpholine or thiomorpholine.

79. A compound as described in any one of claims 73-78, wherein R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a 11 A substituted bridged heterocycle, wherein at least one R 11 Select from -OR 12 and C substituted by -OH 1-6 alkyl.

80. A compound as described in any one of claims 73-79, wherein R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a 11 A substituted bridged heterocycle, wherein at least one R 11 For unsubstituted C 1-6 alkyl.

81. A compound as described in any one of claims 73-78, wherein R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms an unsubstituted bridged heterocyclic ring.

82. A compound as described in any one of claims 58-60, wherein R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a spiro ring.

83. A compound as described in any one of claims 58-60, wherein R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a fused ring system comprising at least two rings.

84. A compound as described in any one of claims 58-71, 73-80, 82 and 83, wherein R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a 11 substituted 4-10 membered heterocyclic ring, wherein one or more R 11 are independently selected from 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 substituted with one or more R 20 Substituted C 1-6 alkyl.

85. The compound of claim 84, wherein R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a 11 substituted 4-10 membered heterocyclic ring, wherein one or more R 11 Independently selected from -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 substituted with one or more R 20 Substituted C 1-6 alkyl.

86. A compound as described in any one of claims 58-85, wherein R 2 and R 3 Together with the nitrogen atom to which it is attached, it forms a structure selected from the following: Any of which is optionally further represented by one or more R 11 replace.

87. The compound of any one of claims 58-86, wherein the compound is according to formula IIIA: or a salt thereof (e.g., a pharmaceutically acceptable salt), wherein: Each R e are independently selected from 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 , halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace; and R f and R g are each independently selected from 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 , halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 Replace, or R f and R g are linked together to form a 3-6 membered carbocyclic or heterocyclic ring which is unsubstituted or substituted with one or more substituents selected from: -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace.

88. The compound of claim 87, wherein each R e , R f and R g are independently selected from 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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace.

89. The compound of claim 87, wherein each R e , R f and R g are independently selected from 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 substituted with one or more R 20 Substituted C 1-6 alkyl.

90. The compound of any one of claims 87-89, wherein each R e For hydrogen.

91. A compound as described in any one of claims 87-90, wherein R f and R g are linked together to form a 3-6 membered carbocyclic or heterocyclic ring which is unsubstituted or substituted with one or more substituents selected from: -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace.

92. The compound of claim 91, wherein R f and R g are linked together to form an unsubstituted 3-6 membered carbocyclic or heterocyclic ring.

93. The compound of claim 91, wherein R f and R g are linked together to form a 3-6 membered carbocyclic or heterocyclic ring substituted with one or more substituents selected from: -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace.

94. The compound of claim 91, wherein R f and R g are linked together to form a 3-6 membered carbon ring which is unsubstituted or substituted with one or more substituents selected from: -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace.

95. The compound of claim 94, wherein R f and R g are linked together to form a cyclopropane which is unsubstituted or substituted with one or more substituents selected from: -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace.

96. The compound of claim 91, wherein R f and R g are linked together to form a 3-6 membered heterocyclic ring which is unsubstituted or substituted with one or more substituents selected from: -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace.

97. The compound of claim 96, wherein R f and R g are linked together to form an oxetane which is unsubstituted or substituted with one or more substituents selected from: -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace.

98. The compound of any one of claims 58-86, wherein the compound is according to formula IIIB: or a salt thereof (e.g., a pharmaceutically acceptable salt), wherein: Each R e are independently selected from 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 and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace.

99. The compound of claim 98, wherein each R e For hydrogen.

100. The compound of any one of claims 58-86, wherein the compound is according to formula IIIC: or a salt thereof (e.g., a pharmaceutically acceptable salt), wherein: Each R e are independently selected from 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 group is unsubstituted or substituted with one or more R 20 replace.

101. The compound of claim 100, wherein each R e For hydrogen.

102. The compound of any one of claims 58-86, wherein the compound is according to formula IIIC1: or a salt thereof (e.g., a pharmaceutically acceptable salt), wherein: Each R e are independently selected from 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 and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace; and R f , R g and R h are each independently selected from 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 , halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 Replace, optionally wherein (i)R f and R g are connected together to form a 3-6 membered carbocyclic or heterocyclic ring or a 5-6 membered heteroaryl group which is unsubstituted or substituted with one or more substituents selected from: -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace; or (ii) R g and R h are connected together to form a 3-6 membered carbocyclic or heterocyclic ring or a 5-6 membered heteroaryl group which is unsubstituted or substituted with one or more substituents selected from: -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace.

103. The compound of claim 102, wherein each R e For hydrogen.

104. The compound of claim 102 or 103, wherein R f and R g are linked together to form a 3-6 membered carbocyclic or heterocyclic ring which is unsubstituted or substituted with one or more substituents selected from: -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace.

105. The compound of claim 104, wherein R f and R g are linked together to form a 3-6 membered carbon ring which is unsubstituted or substituted with one or more substituents selected from: -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace.

106. The compound of claim 104, wherein R f and R g are linked together to form a 3-6 membered heterocyclic ring which is unsubstituted or substituted with one or more substituents selected from: -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace.

107. The compound of claim 102 or 103, wherein R g and R h are linked together to form a 3-6 membered carbocyclic or heterocyclic ring which is unsubstituted or substituted with one or more substituents selected from: -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace.

108. The compound of claim 107, wherein R g and R h are linked together to form a 3-6 membered carbon ring which is unsubstituted or substituted with one or more substituents selected from: -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace.

109. The compound of claim 107, wherein R g and R h are linked together to form a 3-6 membered heterocyclic ring which is unsubstituted or substituted with one or more substituents selected from: -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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace.

110. The compound of any one of claims 58-86, wherein the compound is according to formula IIID: or a salt thereof (e.g., a pharmaceutically acceptable salt), wherein: Q is selected from CR h R j NR g , O, S and SO2; Each R e and R f Independently selected from R 11 and hydrogen, of which: (i)R e and R f may be optionally linked together to form a 4-6 membered ring; (ii) The first R connected to the adjacent atom f and the second R f may be optionally linked together to form a 3-5 membered ring; (iii) The first R connected to the adjacent atom e and the second R e may be optionally linked together to form a 3-5 membered ring; or (iv) The first R connected to the same atom f and the second R f may be optionally linked together to form a 3-5 membered ring, One or more R e and / or one or more R f Any ring formed is unsubstituted or replaced by one or more R 11 replace; R g When present, it is R 11 ;and R h and R j When present, independently selected from R 11 and hydrogen, or may be optionally linked together to form a 3-4 membered carbocyclic or heterocyclic ring which is unsubstituted or substituted by one or more substituents 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 , halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 Substitution, or R h and R e or R h and R f Optionally linked together to form unsubstituted or substituted with one or more R 11 Substituted 3-6 membered ring.

111. The compound of claim 110, wherein Q is NR g , and R g Selected from -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 group is unsubstituted or substituted with one or more R 20 replace.

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

113. The compound of claim 110, wherein the compound is according to formula IIIE: or a salt thereof (eg, a pharmaceutically acceptable salt).

114. The compound of claim 113, wherein R e and R f Linked together to form a 4-6 membered ring.

115. The compound of claim 113 or 114, wherein R h and R j Independently selected from R 11 and hydrogen.

116. A compound as described in any one of claims 113-115, wherein R h and / or R j Selected from 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 , halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace.

117. A compound as described in any one of claims 113-115, wherein R h and R j Each is hydrogen.

118. The compound of claim 113, wherein R h and R j They are linked together to form a 3-4 membered carbocyclic or heterocyclic ring.

119. The compound of claim 118, wherein R h and R j are linked together to form an unsubstituted 3-4 membered carbocyclic or heterocyclic ring.

120. The compound of claim 118, wherein R h and R j are linked together to form a 3-4 membered carbocyclic or heterocyclic ring substituted with one or more substituents selected from: -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 substituted with one or more R 20 Substituted C 1-6 alkyl.

121. A compound as described in any one of claims 118-120, wherein there is no one or more R e and / or one or more R f The combinations are connected together to form a ring.

122. A compound as described in any one of claims 118-121, wherein each R e and R f For hydrogen.

123. The compound of claim 110, wherein the compound is according to formula IIIF, IIIG or IIIH: or a salt thereof (eg, a pharmaceutically acceptable salt).

124. The compound of claim 123, wherein each R e and R f Independently selected from R 11 and hydrogen.

125. The compound of claim 123, wherein R e and R f Linked together to form a 4-6 membered ring.

126. The compound of claim 110, wherein the compound is according to formula IIIJ: or a salt thereof (eg, a pharmaceutically acceptable salt).

127. The compound of claim 126, wherein each R e and R f Independently selected from R 11 and hydrogen.

128. The compound of claim 126, wherein R e and R f Linked together to form a 4-6 membered ring.

129. The compound of any one of claims 110-128, wherein the compound is according to Formula IIIK, IIIL, IIIM, IIIN, IIIP, IIIQ or IIIR: or a salt (e.g., a pharmaceutically acceptable salt), wherein: Each R e and R f Independently selected from R 11 and hydrogen; R g When present, it is R 11 ;and R h and R j When present, each is independently selected from R 11 and hydrogen.

130. The compound of claim 129, wherein Q is selected from CR h R j NR g and O.

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

132. The compound of claim 131, wherein R h and R j When present, each is independently selected from R 11 and hydrogen, where each R 11 are independently selected from 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)(3-6 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, 3-6 membered carbocyclic or heterocyclic ring and C 1-6 Alkyl, any C 1-6 The alkyl, carbocyclic or heterocyclic ring is unsubstituted or substituted with one or more R 20 replace.

133. The compound of claim 132, wherein R h and / or R j When present, each is independently 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 , halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace.

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

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

136. The compound of claim 135, wherein R g Selected from -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 group is unsubstituted or substituted with one or more R 20 replace.

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

138. The compound of claim 129, wherein Q is S or SO2.

139. The compound of any one of claims 129-138, wherein each R e and R f Independently selected from R 11 and hydrogen, where each R 11 are independently selected from 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)(3-6 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, 3-6 membered carbocyclic or heterocyclic ring and C 1-6 Alkyl, any C 1-6 The alkyl, carbocyclic or heterocyclic ring is unsubstituted or substituted with one or more R 20 replace.

140. The compound of claim 139, wherein each R e and / or R f are independently selected from 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 substituted with one or more R 20 Substituted C 1-6 alkyl.

141. The compound of claim 140, wherein each R e and R f For hydrogen.

142. The compound of any one of claims 58-86, wherein the compound is according to formula IIIS: or a salt (e.g., a pharmaceutically acceptable salt), wherein: Q 1 Selected from NR g1 , O, SR h 2 and CR i R j ; Q 2 Selected from NR g2 ,O,SR h 2 and CR i R j ; R g1 and R g2 When present, independently selected from hydrogen, -C(O)(C 1-6 Alkyl) and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace; Each R h not present or, when present, independently selected from =O, =N(R 14 ) and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace; Each R i and R j When present, independently selected from 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 and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace; and Each R e1 , R e2 , R e3 and R e4 are independently selected from 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 and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace, in (i)R e2 and R e3 are optionally linked together to form a 5-6 membered ring; or (ii) When Q 2 NR g2 When R g2 and R e3 The atoms to which they are attached are optionally linked together to form an unsubstituted or substituted with one or more R 11 A substituted 5-membered heterocyclic or heteroaryl group, wherein each R 11 are independently selected from 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 C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace.

143. The compound of claim 142, wherein Q 1 and Q 2 Each is CR i R j .

144. The compound of claim 143, wherein at least one R e1 , R e2 , R e3 or R e4 Select 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 , halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace.

145. The compound of claim 144, wherein each R e1 , R e2 , R e3 and R e4 For hydrogen.

146. The compound of claim 143, wherein R e2 and R e3 Linked together to form a 5-6 membered ring.

147. The compound of claim 142, wherein Q 1 CR i R j And Q 2 NR g2 .

148. The compound of claim 147, wherein R g2 and R e3 and the atoms to which they are attached to form an unsubstituted or substituted with one or more R 11 Substituted 5-membered heterocyclic or heteroaryl.

149. The compound of claim 147, wherein R g2 Selected from hydrogen, -C(O)(C 1-6 Alkyl) and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace.

150. The compound of claim 142, wherein Q 2 CR i R j And Q 1 NR g1 .

151. The compound of claim 150, wherein R g1 Selected from hydrogen, -C(O)(C 1-6 Alkyl) and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace.

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

153. The compound of claim 142, wherein (i) Q 1 CR i R j And Q 2 is O, or (ii) Q 2 CR i R j And Q 1 is O.

154. The compound of claim 153, wherein each R e1 , R e2 , R e3 and R e4 For hydrogen.

155. The compound of claim 153, wherein R e2 and R e3 Linked together to form a 5-6 membered ring.

156. The compound of claim 142, wherein (i) Q 1 CR i R j And Q 2 For SR h 2, or (ii) Q 2 CR i R j And Q 1 For SR h 2.

157. The compound of claim 156, wherein each R e1 , R e2 , R e3 and R e4 For hydrogen.

158. The compound of claim 156, wherein R e2 and R e3 Linked together to form a 5-6 membered ring.

159. A compound as described in any one of claims 156-158, wherein each R h is =O.

160. A compound as described in any one of claims 142-159, wherein each R i and R j For hydrogen.

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

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

163. The compound of claim 161, wherein R e2 and R e3 Linked together to form a 5-6 membered ring.

164. The compound of any one of claims 161-163, wherein each R h is =O.

165. The compound of any one of claims 59-86, wherein the compound is according to formula IIIT: or a salt (e.g., a pharmaceutically acceptable salt), wherein: The dashed lines represent single or double bonds, so that 1 , Q 2 , Q 3 and Q 4 The ring is aromatic; Q 1 , Q 2 , Q 3 and Q 4 are independently selected from C, N, O and S, wherein Q 1 , Q 2 , Q 3 and Q 4 At least one of is N; Each R e and R f Independently selected from R 11 and hydrogen; and Each R g Not present or independently selected from R 11 and hydrogen.

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

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

168. The compound of claim 165, wherein Q 1 is N.

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

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

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

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

173. The compound of claim 165, wherein Having a structure selected from the following:

174. A compound as described in any one of claims 165-173, wherein each R g is hydrogen or absent.

175. A compound as described in any one of claims 58-174, wherein R 6 For one or more R 15 Substituted bicyclic heteroaryl.

176. The compound of claim 175, wherein R 6 Selected from: in: X is selected from N and C-CN; Y is selected from O and S; R 23 Selected from -N(R 12 2. C 1-6 Alkyl and C 1-6 Alkyl-N(R 14 )2, where any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; and R 24 , R 25 and R 26 independently selected from H, deuterium, halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace.

177. The compound of claim 175 or 176, wherein R 6 Selected from: Any of which is one or more R 15 replace.

178. A compound as described in any one of claims 175-177, wherein R 6 Selected from:

179. A compound as described in any one of claims 175-178, wherein R 6 Selected from:

180. A compound as described in any one of claims 58-174, wherein R 6 For one or more R 15 Substituted monocyclic heteroaryl.

181. The compound of claim 180, wherein R 6 For one or more R 15 Substituted pyridines.

182. The compound of claim 181, wherein R 6 With structure 183. A compound as described in any one of claims 58-182, wherein R 1 Select from -OR 8 .

184. The compound of claim 183, wherein R 1 Selected from: Where R a1 , R a2 , R b1 and R b2 are each independently selected from deuterium, halogen, C 1-6 Alkyl, -OR 12 and H, where R a2 and R b2 may be optionally linked together to form a 3-6 membered carbocyclic ring, and wherein any C 1-6 Alkyl or 3-6 membered carbocyclic ring is unsubstituted or substituted with one or more R 13 replace.

185. The compound of claim 184, wherein R 1 Selected from:

186. The compound of claim 183, wherein R 1 Selected from: Where R a and R b are each independently selected from halogen, C 1-6 Alkyl, -OR 12 and H, where any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace.

187. The compound of claim 186, wherein R 1 Selected from:

188. The compound of claim 183, wherein R 1 Selected from: Each R a and R b independently selected from halogen, C 1-6 Alkyl, -OR 12 and H; and R c Selected from C 1-6 Alkyl, where R a and R b or R c are optionally linked together to form a 3-6 membered carbocyclic or heterocyclic ring, and any C 1-6 Alkyl or 3-6 membered carbocyclic or heterocyclic ring is unsubstituted or substituted by one or more R 13 replace.

189. The compound of claim 188, wherein R 1 Selected from:

190. A compound as described in any one of claims 58-182, wherein R 1 Selected from 191. A compound as described in any one of claims 58-190, wherein each R 11 Independently selected from -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 substituted with one or more R 20 Substituted C 1-6 alkyl.

192. A compound as described in any one of claims 58-191, wherein R 5 is a halogen (eg, F or Cl).

193. A compound as described in any one of claims 58-191, wherein R 5 is selected from unsubstituted or substituted with one or more R 13 Substituted C 1-6 alkyl.

194. The compound of claim 193, wherein R 5 is selected from C substituted by one or more halogen or -CN 1-6 alkyl.

195. The compound of claim 194, wherein R 5 Selected from -CF2H, -CF3, -CH2CN and -CH2CH3.

196. The compound of claim 195, wherein R 5 It is -CF3.

197. A compound as described in any one of claims 58-196, wherein the compound is not a compound included in Table 2.

198. A compound represented by formula I: or a salt thereof (e.g., a pharmaceutically acceptable salt), wherein: R 1 Select from -OR 8 and R 2 Selected from H and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; R 3 is selected from unsubstituted or substituted with one or more R 10 Substituted 3-11 membered carbocyclic ring; R 4 is H; R 5 Selected from H, halogen, -CN, -OR 12 , 3-6 membered heterocyclic ring, 5-6 membered heteroaryl and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; R 6 For one or more R 15 substituted bicyclic heteroaryl; R 7 is selected from halogen, -CN and H; R 8 is selected from heterocycle and alkylheterocycle, wherein any heterocycle contains 4 to 8 members and is unsubstituted or substituted by one or more R a or R b substituted, and wherein the alkyl portion of any alkyl heterocycle is selected from C 1-6 alkyl; Each R 10 Independently selected from -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 group is unsubstituted or substituted with one or more R 20 replace; Each R 12 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H, any C 1-6 Alkyl or C 2-6 The alkenyl group is unsubstituted or substituted with one or more R 13 replace; Each R 13 Independently selected from -OR 14 、-CN、-N(R 14 )2 and halogen; Each R 14 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H; Each R 15 are independently selected from deuterium, halogen, -N(R 12 )2. -CN and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; Each R 20 Independently selected from -OH, -OC 1-6 Alkyl, -CN, -NH2, -NHC 1-6 Alkyl and halogen; R 27 is a 3-6 membered heterocyclic ring including one or more heteroatoms selected from N, O and S, wherein the heterocyclic ring is unsubstituted or substituted with one or more R 28 replace; Each R 28 Independently selected from C 1-6 Alkyl and halogen; and R a and R b are each independently selected from deuterium, halogen, C 1-6 Alkyl, 3-6 membered carbocyclic ring, -OR 12 and H, where R a and R b are optionally linked together to form a 3-6 membered carbocyclic or heterocyclic ring, and any C 1-6 Alkyl or 3-6 membered carbocyclic or heterocyclic ring is unsubstituted or substituted by one or more R 13 replace.

199. The compound of claim 198, wherein the compound has Formula Ia: or a salt thereof (eg, a pharmaceutically acceptable salt).

200. The compound of claim 198 or 199, wherein R 3 is unsubstituted or replaced by one or more R 10 Substituted 3-6 membered carbocyclic ring.

201. The compound of claim 200, wherein R 3 For 1-4 R 10 Substituted 3-6 membered carbocyclic ring.

202. The compound of claim 200, wherein R 3 For 0-4 R 10 Substituted cyclopropanes.

203. The compound of claim 200, wherein R 3 For 0-4 R 10 Substituted cyclobutanes.

204. The compound of claim 200, wherein R 3 For 0-4 R 10 Substituted cyclopentanes.

205. The compound of claim 200, wherein R 3 For 0-4 R 10 Substituted cyclohexanes.

206. A compound as described in any one of claims 198-200, wherein R 3 is unsubstituted or replaced by one or more R 10 Substituted spiro ring.

207. A compound as described in any one of claims 198-200, wherein R 3 is unsubstituted or replaced by one or more R 10 Substituted bridged carbocyclic ring.

208. A compound as described in any one of claims 198-207, wherein R 3 By one or more R 10 Substituted, wherein at least one R 10 Select from -OR 12 and C substituted by -OH 1-6 alkyl.

209. The compound of any one of claims 198-208, wherein R 3 By one or more R 10 Substituted, wherein at least one R 10 For unsubstituted C 1-6 alkyl.

210. The compound of any one of claims 198-209, wherein the compound is according to Formula IA, IB, IC, ID, IE or IF: or a salt thereof (e.g., a pharmaceutically acceptable salt), wherein: Each R d Independently selected from 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 group is unsubstituted or substituted with one or more R 20 replace.

211. The compound of claim 210, wherein at least one R d Select from -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 group is unsubstituted or substituted with one or more R 20 replace.

212. The compound of claim 211, wherein at least one R d Select from -OR 12 and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace.

213. A compound as described in any one of claims 198-212, wherein R 6 Selected from: in: X is selected from N and C-CN; Y is selected from O and S; R 23 Selected from -N(R 12 2. C 1-6 Alkyl and C 1-6 Alkyl-N(R 14 )2, where any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; and R 24 , R 25 and R 26 independently selected from H, deuterium, halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace.

214. A compound as described in any one of claims 198-213, wherein R 6 Selected from: Any of which is one or more R 15 replace.

215. A compound as described in any one of claims 198-214, wherein R 6 Selected from:

216. A compound as described in any one of claims 198-215, wherein R 6 Selected from:

217. The compound of any one of claims 198-216, wherein the compound is a compound according to Formula IA1, IB1, IC1, ID1, IE1 or IF1: or a salt thereof (e.g., a pharmaceutically acceptable salt), wherein: Each R d Independently selected from 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 group is unsubstituted or substituted with one or more R 20 replace; X is selected from N and C-CN; Y is selected from O and S; R 23 Selected from -N(R 12 2. C 1-6 Alkyl and C 1-6 Alkyl-N(R 14 )2, where any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; and R 24 , R 25 and R 26 independently selected from H, deuterium, halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace.

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

219. The compound of claim 217 or 218, wherein R 24 , R 25 and R 26 One or more of the is halogen (eg, F).

220. A compound as described in any one of claims 198-219, wherein R 1 Select from -OR 8 .

221. The compound of claim 220, wherein R 1 Selected from: Where R a and R b are each independently selected from halogen, C 1-6 Alkyl, -OR 12 and H, where any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace.

222. The compound of claim 221, wherein R 1 Selected from:

223. The compound of claim 220, wherein R 1 Selected from: Each R a and R b independently selected from halogen, C 1-6 Alkyl, -OR 12 and H; and R c Selected from C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 substituted, and wherein R a and R b or R c Optionally linked together to form a 3-6 membered carbocyclic or heterocyclic ring.

224. The compound of claim 223, wherein R 1 Selected from:

225. A compound as described in any one of claims 198-219, wherein R 1 Selected from 226. The compound of any one of claims 198-225, wherein the compound is a compound according to Formula IA2, IB2, IC2, ID2, IE2 or IF2: or a salt thereof (e.g., a pharmaceutically acceptable salt), wherein: R a and R b are each independently selected from halogen, C 1-6 Alkyl, -OR 12 and H, where any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; Each R d Independently selected from 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 group is unsubstituted or substituted with one or more R 20 replace; X is selected from N and C-CN; Y is selected from O and S; R 23 Selected from -N(R 12 2. C 1-6 Alkyl and C 1-6 Alkyl-N(R 14 )2, where any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; and R 24 , R 25 and R 26 independently selected from H, deuterium, halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace.

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

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

229. A compound as described in any one of claims 226-228, wherein X is C-CN, Y is S, and R 23 -N(R 12 )2.

230. A compound as described in any one of claims 226-229, wherein R 24 , R 25 and R 26 One or more of the is halogen (eg, F).

231. A compound as described in any one of claims 198-230, wherein R 2 For H.

232. A compound as described in any one of claims 198-230, wherein R 2 is selected from unsubstituted or substituted with one or more R 13 Substituted C 1-6 alkyl.

233. The compound of claim 232, wherein R 2 Selected from C 1-2 alkyl.

234. A compound as described in any one of claims 198-223, wherein R 5 For H.

235. A compound as described in any one of claims 198-223, wherein R 5 is a halogen (eg, F or Cl).

236. A compound as described in any one of claims 198-223, wherein R 5 is selected from unsubstituted or substituted with one or more R 13 Substituted C 1-6 alkyl.

237. The compound of claim 236, wherein R 5 is selected from C substituted by one or more halogen or -CN 1-6 alkyl.

238. The compound of claim 237, wherein R 5 Selected from -CF2H, -CF3, -CH2CN and -CH2CH3.

239. The compound of claim 238, wherein R 5 It is -CF3.

240. A compound as described in any one of claims 198-239, wherein R 7 For H.

241. A compound as described in any one of claims 198-239, wherein R 7 is a halogen (eg, F or Cl).

242. A compound as described in any one of claims 198-239, wherein R 7 It is -CN.

243. A compound represented by formula IV: or a salt thereof (e.g., a pharmaceutically acceptable salt), wherein: R 1 Select from -OR 8 and R 2 Selected from H, C 1-6 Alkyl and 3-6 membered carbocyclic ring, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; R 3 is selected from unsubstituted or substituted with one or more R 10 Substituted C 1-6 alkyl; R 4 is H; R 5 Selected from H, halogen, -CN, -OR 12 , 3-6 membered heterocyclic ring, 5-6 membered heteroaryl and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; R 6 For one or more R 15 substituted bicyclic heteroaryl; R 7 is selected from halogen, -CN and H; R 8 is selected from heterocycle and alkylheterocycle, wherein any heterocycle contains 4 to 8 members and is unsubstituted or substituted by one or more R a or R b substituted, and wherein the alkyl portion of any alkyl heterocycle is selected from C 1-6 alkyl; Each R 10 Independently selected from -OR 14 , =O, -CN, -N(R 14 )2, 3-6 membered carbocyclic ring, 3-6 membered heterocyclic ring, 5-6 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, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 substituted, any 3-6 membered carbocyclic ring is unsubstituted or replaced by one or more R 12 substituted, and any 3-6 membered heterocyclic or 5-6 membered heteroaryl is unsubstituted or replaced by one or more =O, R 12 or R 13 replace; Each R 12 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H, any C 1-6 Alkyl or C 2-6 The alkenyl group is unsubstituted or substituted with one or more R 13 replace; Each R 13 Independently selected from -OR 14 、-CN、-N(R 14 )2 and halogen; Each R 14 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H; Each R 15 are independently selected from deuterium, halogen, -N(R 12 )2. -CN and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; Each R 20 Independently selected from -OH, -OC 1-6 Alkyl, -CN, -NH2, -NHC 1-6 Alkyl and halogen; R 27 is a 3-6 membered heterocyclic ring including one or more heteroatoms selected from N, O and S, wherein the heterocyclic ring is unsubstituted or substituted with one or more R 28 replace; Each R 28 Independently selected from C 1-6 Alkyl and halogen; and R a and R b are each independently selected from halogen, C 1-6 Alkyl, -OR 12 and H, where any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 substituted, and wherein R a and R b Optionally linked together to form a 3-6 membered carbocyclic or heterocyclic ring.

244. The compound of claim 243, wherein the compound has formula IV-a: or a salt thereof (eg, a pharmaceutically acceptable salt).

245. The compound of claim 243 or 244, wherein the compound is according to formula IVA: or a salt thereof (e.g., a pharmaceutically acceptable salt), wherein: Each R i and R h Independently selected from H and R 10 .

246. The compound of claim 245, wherein each R i and R h Independently selected from H and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace.

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

248. A compound as described in any one of claims 243-247, wherein R 6 Selected from: in: X is selected from N and C-CN; Y is selected from O and S; R 23 Selected from -N(R 12 2. C 1-6 Alkyl and C 1-6 Alkyl-N(R 14 )2, where any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; and R 24 , R 25 and R 26 independently selected from H, deuterium, halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace.

249. The compound of any one of claims 243-248, wherein R 6 Selected from: Any of which is one or more R 15 replace.

250. A compound as described in any one of claims 243-249, wherein R 6 Selected from:

251. A compound as described in any one of claims 243-250, wherein R 6 Selected from:

252. The compound of claim 243, wherein the compound is according to Formula IVB: or a salt thereof (e.g., a pharmaceutically acceptable salt), wherein: X is selected from N and C-CN; Y is selected from O and S; R 23 Selected from -N(R 12 2. C 1-6 Alkyl and C 1-6 Alkyl-N(R 14 )2, where any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; and R 24 , R 25 and R 26 are independently selected from H, deuterium, halogen, -OR 12 and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace.

253. A compound as described in any one of claims 243-252, wherein R 1 Select from -OR 8 .

254. The compound of claim 253, wherein R 1 Selected from: Where R a and R b are each independently selected from halogen, C 1-6 Alkyl, -OR 12 and H, where any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace.

255. The compound of claim 254, wherein R 1 Selected from:

256. The compound of claim 253, wherein R 1 Selected from: Each R a and R b independently selected from halogen, C 1-6 Alkyl, -OR 12 and H; and R c Selected from C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 substituted, and wherein R a and R b or R c Optionally linked together to form a 3-6 membered carbocyclic or heterocyclic ring.

257. The compound of claim 256, wherein R 1 Selected from:

258. A compound as described in any one of claims 243-252, wherein R 1 Selected from 259. The compound of any one of claims 243-258, wherein the compound is according to formula IVC: or a salt thereof (e.g., a pharmaceutically acceptable salt), wherein: R a and R b are each independently selected from halogen, C 1-6 Alkyl, -OR 12 and H, where any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; X is selected from N and C-CN; Y is selected from O and S; R 23 Selected from -N(R 12 2. C 1-6 Alkyl and C 1-6 Alkyl-N(R 14 )2, where any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; and R 24 , R 25 and R 26 are independently selected from H, deuterium, halogen, -OR 12 and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace.

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

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

262. A compound as described in any one of claims 252-261, wherein X is C-CN, Y is S, and R 23 Selected from -N(R 12 )2.

263. A compound as described in any one of claims 252-262, wherein R 24 , R 25 and R 26 At least one of them is a halogen (eg, F).

264. A compound as described in any one of claims 243, 244 and 252-263, wherein R 3 is selected from unsubstituted or substituted with one or more R 10 Substituted C 1-3 alkyl.

265. The compound of claim 264, wherein each R 10 Independently selected from -OR 14 , =O, -CN, -NH(R 16 )、-N(R 16 )2, 3-6 membered carbon ring, C 1-6 Alkyl and halogen, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 substituted, wherein any 3-6 membered carbocyclic ring is unsubstituted or replaced by one or more R 12 Replace, and each R 16 Independently selected from C 1-6 Alkyl and C 2-6 Alkenyl.

266. The compound of claim 265, wherein each R 10 Independently selected from -OR 14 、-CN、C 1-6 Alkyl and halogen, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace.

267. The compound of claim 266, wherein each R 10 are independently selected from halogen.

268. The compound of claim 264, wherein R 3 Select from unsubstituted C 1-3 alkyl.

269. A compound as described in any one of claims 243, 244 and 252-263, wherein the moiety Selected from: Any of which is optionally further represented by one or more R 10 replace.

270. The compound of any one of claims 243-269, wherein R 2 For H.

271. A compound as described in any one of claims 243-269, wherein R 2 is selected from unsubstituted or substituted with one or more R 13 Substituted C 1-6 alkyl.

272. The compound of claim 271, wherein R 2 Select from unsubstituted C 1-2 alkyl.

273. The compound of any one of claims 243-269, wherein R 2 It is a 3-6 membered carbon ring.

274. The compound of any one of claims 243-273, wherein R 5 For H.

275. The compound of any one of claims 243-273, wherein R 5 is a halogen (eg, F or Cl).

276. A compound as described in any one of claims 243-273, wherein R 5 is selected from unsubstituted or substituted with one or more R 13 Substituted C 1-6 alkyl.

277. The compound of claim 276, wherein R 5 is selected from C substituted by one or more halogen or -CN 1-6 alkyl.

278. The compound of claim 277, wherein R 5 Selected from -CF2H, -CF3, -CH2CN and -CH2CH3.

279. The compound of claim 278, wherein R 5 It is -CF3.

280. A compound as described in any one of claims 243-279, wherein R 7 For H.

281. A compound as described in any one of claims 243-279, wherein R 7 is a halogen (eg, F or Cl).

282. A compound as described in any one of claims 243-279, wherein R 7 It is -CN.

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

284. A compound represented by formula V: or a salt thereof (e.g., a pharmaceutically acceptable salt), wherein: R 1 Select from -OR 8 and R m Selected from hydrogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; R 4 is H; R 5 Selected from halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; R 6 is a monocyclic or bicyclic heteroaryl group, wherein the heteroaryl group is surrounded by one or more R 15 replace; R 7 is selected from halogen; R 8 is selected from heterocycle and alkylheterocycle, wherein any heterocycle contains 4 to 8 members and is unsubstituted or substituted by one or more R a or R b substituted, and wherein the alkyl portion of any alkyl heterocycle is selected from C 1-6 alkyl; Each R 12 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H, any C 1-6 Alkyl or C 2-6 The alkenyl group is unsubstituted or substituted with one or more R 13 replace; Each R 13 Independently selected from -OR 14 、-CN、-N(R 14 )2 and halogen; Each R 14 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H; Each R 15 are independently selected from deuterium, halogen, -N(R 12 )2. -CN and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; R 27 is a 3-6 membered heterocyclic ring including one or more heteroatoms selected from N, O and S, wherein the heterocyclic ring is unsubstituted or substituted with one or more R 28 replace; Each R 28 Independently selected from C 1-6 Alkyl and halogen; and R a and R b are each independently selected from deuterium, halogen, C 1-6 Alkyl, 3-6 membered carbocyclic ring, -OR 12 and H, where R a and R b are optionally linked together to form a 3-6 membered carbocyclic or heterocyclic ring, and any C 1-6 Alkyl or 3-6 membered carbocyclic or heterocyclic ring is unsubstituted or substituted by one or more R 13 replace.

285. A compound represented by formula VI: or a salt thereof (e.g., a pharmaceutically acceptable salt), wherein: R 1 Select from -OR 8 and R 2 Selected from H, C 1-6 Alkyl and 3-6 membered carbocyclic ring, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; R 4 is H; R 5 Selected from H, halogen, -CN, -OR 12 , 3-6 membered heterocyclic ring, 5-6 membered heteroaryl and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; R 6 is a monocyclic or bicyclic heteroaryl group, wherein the heteroaryl group is surrounded by one or more R 15 replace; R 7 is selected from H and halogen; R 8 is selected from heterocycle and alkylheterocycle, wherein any heterocycle contains 4 to 8 members and is unsubstituted or substituted by one or more R a or R b substituted, and wherein the alkyl portion of any alkyl heterocycle is selected from C 1-6 alkyl; Each R 12 Independently selected from C 1-6 Alkyl, C 2-6 alkenyl and H, any C 1-6 Alkyl or C 2-6 The alkenyl group is unsubstituted or substituted with one or more R 13 replace; Each R 13 Independently selected from -OR 14 、-CN、-N(R 14 )2 and halogen; Each R 14 independently selected from 3-6 membered carbocyclic ring, 3-6 membered heterocyclic ring, C 1-6 Alkyl, C 2-6 alkenyl and H, any C 1-6 The alkyl group is optionally deuterated; Each R 15 are independently selected from deuterium, halogen, -N(R 12 )2. -CN and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 13 replace; Each R 20 Independently selected from -OH, -OC 1-6 Alkyl, =O, -CN, -NH2, -NHC 1-6 Alkyl, -C(O)(C 1-6 alkyl), 3-6 membered carbocyclic ring, 5-6 membered aryl and halogen; R 27 is a 3-6 membered heterocyclic ring including one or more heteroatoms selected from N, O and S, wherein the heterocyclic ring is unsubstituted or substituted with one or more R 28 replace; Each R 28 Independently selected from C 1-6 Alkyl and halogen; R a and R b are each independently selected from deuterium, halogen, C 1-6 Alkyl, -OR 12 , 3-6 membered carbon ring and H, wherein R a and R b are optionally linked together to form a 3-6 membered carbocyclic or heterocyclic ring, and any C 1-6 Alkyl or 3-6 membered carbocyclic or heterocyclic ring is unsubstituted or substituted by one or more R 13 replace; Each R d are independently selected from H, halogen and C 1-6 Alkyl, any C 1-6 The alkyl group is unsubstituted or substituted with one or more R 20 replace; R e Selected from R f Selected from H, halogen and C 1-6 alkyl; R g and R h Independently selected from H and C 1-6 Alkyl; and R j Selected from C 1-6 alkyl, The condition is R e Not for 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 (eg, a pharmaceutically acceptable salt) thereof.

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

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

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

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

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

293. A pharmaceutical composition comprising a compound or salt thereof (e.g., a pharmaceutically acceptable salt) as described in any one of claims 1-292, and a pharmaceutically acceptable excipient.

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

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

296. The compound of claim 295, wherein the medicament is useful for preventing or treating a disease, disorder, or condition that is ameliorated by inhibition of wild-type KRAS.

297. The compound of claim 295, wherein the agent is useful for preventing or treating a disease, disorder, or condition ameliorated by inhibiting KRAS having a G12D, G12R, or G12V mutation.

298. The compound of any one of claims 294-296, wherein the agent is useful for preventing or treating cancer.

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

300. A compound or salt (eg, a pharmaceutically acceptable salt) of any one of claims 1-292 for use in treating a disease, disorder, or condition.

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

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

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

304. A compound or salt (e.g., a pharmaceutically acceptable salt) of any one of claims 1-292 for use in the manufacture of a medicament.

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

306. The compound of claim 305, wherein the medicament is useful for preventing or treating a disease, disorder, or condition that is ameliorated by inhibition of wild-type KRAS.

307. The compound of claim 305, wherein the agent is useful for preventing or treating a disease, disorder, or condition ameliorated by inhibiting KRAS having a G12D, G12R, or G12V mutation.

308. The compound of any one of claims 304-307, wherein the agent is useful for treating cancer.

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

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

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

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

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

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

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

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

317. The method of claim 315 or 316, wherein the subject has previously entered remission of the cancer.

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

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

320. Use of a compound or a salt (eg, a pharmaceutically acceptable salt) of any one of claims 1-292 for the manufacture of a medicament for treating cancer.

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

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

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

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. 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 322-325, wherein the KRAS protein is in an active (GTP bound) state.

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

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

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

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

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

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

333. A method of inhibiting the function of a wild-type KRAS protein or a KRAS protein having a Q61H, G13D, G12D, G12V, G12C, G12S, G12A or G12R mutation, the method comprising contacting the KRAS protein with a compound or a salt thereof (e.g., a pharmaceutically acceptable salt) as described in any one of claims 1-292.

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

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

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 333-336, wherein the KRAS protein is in an active (GTP bound) state.

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

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

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

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

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

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 with Q61H, G13D, G12D, G12V, G12C, G12S, G12A or G12R mutations in both active (GTP-bound) and inactive (GDP-bound) states.

345. The compound of claim 344, wherein the compound: (i) In the assay of Biological Example 1 (e.g., protein:protein interaction (PPI) homogeneous time-resolved fluorescence (HTRF) analysis of 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 RBD-3xFLAG), IC 50 ≤0.1μM, 0.1μM <IC 50 ≤1μM, 1μM <IC 50 ≤10μM or 10μM <IC 50 ; and / or (ii) in an assay of Biological Example 2 or 4 (e.g., a cell-based pERK HTRF assay in GP2d (G12D) or SW620 (G12V) cells), IC 50 ≤0.1μM, 0.1μM <IC 50 ≤1μM or IC 50 >1 μM; and / or (iii) in an 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 RBD (51-131)-Avi protein:protein interaction (PPI) homogeneous time-resolved fluorescence (HTRF) analysis), IC 50 ≤0.1μM, 0.1μM <IC 50 ≤1μM, 1μM <IC 50 ≤10μM or 10μM <IC 50 ; and / or (iv) 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), IC 50 ≤0.1μM, 0.1μM <IC 50 ≤1μM or IC 50 >1 μM; and / or (v) 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), IC 50 ≤0.1μM, 0.1μM <IC 50 ≤1μM or IC 50 >1μM.

346. The compound of claim 345, wherein the compound: (i) In the assay of Biological Example 1 (e.g., protein:protein interaction (PPI) homogeneous time-resolved fluorescence (HTRF) analysis of 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 RBD-3xFLAG), IC 50 ≤0.1μM or 0.1μM <IC 50 ≤1μM; and / or (ii) in the assay of Biological Example 2 or 4 (e.g., the cell-based pERK HTRF assay in GP2d (G12D) and SW620 (G12V) cells), IC 50 ≤0.1μM or 0.1μM <IC 50 ≤1μM; and / or (iii) in an 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 RBD (51-131)-Avi protein:protein interaction (PPI) homogeneous time-resolved fluorescence (HTRF) analysis), IC 50 ≤0.1μM or 0.1μM <IC 50 ≤1μM; and / or (iv) in an assay of Biological Example 5 (e.g., a cell-based pERK HTR assay in AsPC-1, SW1900, HPAC, Capan-2, RKN, H358, HCT116, KP-2, H1573, A549, MKN1, or HT1080 cells), IC 50 ≤0.1μM or 0.1μM <IC 50 ≤1μM; and / or (v) 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), IC 50 ≤0.1μM or 0.1μM <IC 50 ≤1μM.

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

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

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

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