Compositions and methods for inhibiting KRAS

Abstract

Provided herein are compounds, or their salts, esters, tautomers, prodrugs, zwitterionic forms, or stereoisomers, as well as pharmaceutical compositions comprising them.Also provided herein are methods of using them to modulate (e.g., inhibit) KRAS (e.g., KRAS with G12D mutation) and treat disease or disorder in subjects who need such treatment, such as cancer.In another aspect, the present disclosure provides pharmaceutical compositions comprising a compound represented by formula I or formula II, together with a pharma- ceutically acceptable carrier.

Description

[Technical Field]

[0001] Statement regarding the rights to inventions made under federal government-supported research and development. This invention was made with government support under (1) Contract No. 75N91019D00024 granted by the National Institutes of Health, and (2) Contract No. DE-AC52-07NA27344 granted by the U.S. Department of Energy. The United States Government has certain rights to this invention.

[0002] Related applications This application claims priority and benefits of U.S. Provisional Patent Application No. 63 / 150,011, filed on 16 February 2021, and U.S. Provisional Patent Application No. 63 / 246,181, filed on 20 September 2021, the entire contents of each application are incorporated herein by reference. [Background technology]

[0003] RAS mutations occur in approximately 20-30% of human cancers, including the majority of pancreatic ductal adenocarcinomas (PDAC), half of colorectal cancers, and one-third of all lung cancers. Given that RAS mutations are most frequently observed in the top three causes of cancer death in the United States (lung cancer, colorectal cancer, and pancreatic cancer), the development of anti-RAS therapies is a major priority and challenge in cancer research. The RAS protein was thought not to present a suitable pocket for drug binding, except for the GDP / GTP binding site. Unfortunately, the RAS protein binds to these nucleotides with extremely high affinity (picomolecular concentration), making the development of effective nucleotide analogs virtually impossible. Attempts to block downstream pathways of the RAS in the hope of achieving clinical efficacy in patients with RAS-related cancers have generally been disappointing. Very recently, allele-specific covalent KRASG12C inhibitors have entered clinical trials, and early clinical data show some efficacy, at least in lung cancer.

[0004] The three RAS genes (HRAS, NRAS, and KRAS) encode four proteins of 188-189 amino acids that share 82-90% amino acid sequence identity and nearly identical structure and biochemical properties. However, they are expressed differently and mutate at different frequencies in cancer. KRAS is the most frequently mutated oncogene in cancer, and KRAS mutations are generally associated with poor prognosis and treatment resistance. There is high selectivity among the RAS genes for different types of cancer. KRAS mutations are mainly found in lung cancer, colorectal cancer, and pancreatic cancer, while NRAS mutations are mainly found in cutaneous melanoma and acute myeloid leukemia, and HRAS mutations are found in bladder cancer and head and neck squamous cell carcinoma.

[0005] KRAS is activated by mutation in 94% of pancreatic cancers. Pancreatic cancer (e.g., pancreatic ductal adenocarcinoma (PDAC)) was the third leading cause of cancer death in the United States in 2016. The incidence of pancreatic cancer continues to increase and is projected to become the second leading cause of cancer death by 2020. With no biomarkers for early detection, delayed symptom onset when the cancer has already metastasized, and a five-year survival rate of only 8%, pancreatic cancer is the leading cause of cancer death in the United States.

[0006] KRAS mutations are the initiation gene stage of pancreatic cancer, but sustained function of the mutant KRAS is necessary for PDAC proliferation to be maintained. Inactivation of KRAS via RNA interference in KRASG12D-induced PDAC showed rapid regression of tumor growth. These data support the importance of mutant KRAS as a therapeutic target in PDAC. Since 40% of PDACs are induced by the KRASG12D mutant, inhibitors targeting this mutation are highly desirable. KRASG12D mutations also occur frequently in lung cancer and colorectal cancer, making KRASG12D a desirable therapeutic target for direct G12D allele-specific inhibitors. [Overview of the project] [Means for solving the problem]

[0007] In one embodiment, the present disclosure relates to a composition comprising a compound represented by formula I or formula II: [ka] or its salts, esters, tautomers, prodrugs, zwitterionic forms, or stereoisomers [wherein R, R] 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 The following is provided herein. In some embodiments, the compounds provided herein, or their salts, esters, tautomers, zwitterionic forms, or stereoisomers, can modulate the activity of KRAS proteins, such as KRAS proteins having the G12D mutation.

[0008] In another embodiment, the disclosure provides a pharmaceutical composition comprising a compound represented by formula I or formula II together with a pharmaceutically acceptable carrier.

[0009] In a further embodiment, the present disclosure provides a method for inhibiting KRAS activity in human or animal subjects for the treatment of diseases such as cancer, including pancreatic cancer (e.g., pancreatic ductal adenocarcinoma (PDAC)), colorectal cancer, and lung cancer.

[0010] In another embodiment, the disclosure provides the use of compounds provided herein, or their salts, esters, tautomers, zwitterionic forms, or stereoisomers, in the manufacture of agents for the treatment of diseases, disorders, or conditions (e.g., cancer) that are improved, treated, inhibited, or mitigated by inhibition of KRAS having a G12D mutation. In some embodiments, the disease, disorder, or condition is pancreatic cancer (e.g., pancreatic ductal adenocarcinoma (PDAC)), colorectal cancer, or lung cancer.

[0011] In further embodiments, the Disclosure provides compounds provided herein, or salts, esters, tautomers, zwitterionic forms, or stereoisomers thereof, for use as pharmaceuticals. In some embodiments, the pharmaceuticals are used to treat 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. [Modes for carrying out the invention]

[0012] This disclosure provides compounds of formulas I and II, which may possess useful KRAS inhibitory activity and can be used to treat or prevent diseases, disorders, or conditions in which KRAS plays an active role. In particular, certain compounds provided herein may have useful inhibitory activity against KRAS having the G12D mutation, in either an active (bound to GTP) or inactive (bound to GDP) conformation. This disclosure also provides pharmaceutical compositions comprising one or more of the compounds provided herein with a pharmaceutically acceptable carrier, as well as methods for preparing and using such compounds and compositions. This disclosure also provides methods for inhibiting KRAS, including KRAS having the G12D mutation, in either an active or inactive conformation. In one embodiment, this disclosure provides a method for treating a KRAS-mediated disease, comprising administering a therapeutically effective amount of the compounds or compositions provided herein to a subject in need of treatment for such a disease, comprising KRAS having the G12D mutation. This specification also provides the use of certain compounds provided herein in the manufacture of agents for the treatment of diseases, disorders, or conditions that are improved, treated, inhibited, or mitigated by inhibition of KRAS, including KRAS having the G12D mutation. In some embodiments, the disease, disorder, or condition is cancer.

[0013] When a range of values ​​is disclosed and n1 and n2 are numerical values, and the notation "n1...~n2" or "between n1 and n2" is used, unless otherwise specified, this notation is intended to include the numerical values ​​themselves and the range between them. This range can be integers or continuous values ​​between and including the final value. For example, the range "2 to 6 carbons" is intended to include 2, 3, 4, 5, and 6 carbons, since carbon is an integer unit. Compared to the range "1 to 3 μM (micromoles)", this range is intended to include 1 μM, 3 μM, and all values ​​in between, with any number of significant figures (e.g., 1.255 μM, 2.1 μM, 2.9999 μM, etc.).

[0014] As used herein, “approximately” is intended to limit the number it modifies, meaning that such value will vary within a margin of error. The term “approximately” should be understood to mean not only the range encompassing the stated value, but also the range included by rounding up or down to the number, taking significant figures into consideration, if no specific margin of error range, such as the standard deviation relative to the mean, is specified in the graph or table of data.

[0015] As used herein, “acyl” refers, alone or in combination, to an alkenyl, alkyl, aryl, cycloalkyl, heteroaryl, heterocyclic, or carbonyl group bonded to any other part such that the atom bonded to the carbonyl group is carbon. “Acetyl” group refers to the -C(O)CH3 group. “Alkylcarbonyl” or “alkanoyl” group refers to an alkyl group bonded to the parent molecule via a carbonyl group. Examples of such groups include methylcarbonyl and ethylcarbonyl. Examples of acyl groups include formyl, alkanoyl, and aroyl.

[0016] As used herein, "alkenyl" refers to a straight or branched chain hydrocarbon radical having one or more double bonds and containing 2 to 20 carbon atoms, alone or in combination. In certain embodiments, alkenyl contains 2 to 6 carbon atoms. The term "alkenylene" refers to a carbon-carbon double bond system bonded at two or more positions such as ethenylene [(-CH=CH-), (-C::C-)]. Examples of suitable alkenyl groups include ethenyl, propenyl, 2-methylpropenyl, 1,4-butadienyl, and the like. Unless otherwise specified, the term "alkenyl" may include "alkenylene" groups.

[0017] "Alkynyl" has at least two carbon atoms and at least one triple bond and refers to a straight or branched chain hydrocarbon having the indicated number of carbon atoms (i.e., C 2~6 means 2 to 6 carbons). Alkynyl is C2, C 2~3 , C 2~4 , C 2~5 , C 2~6 , C 2~7 , C 2~8 , C 2~9 , C 2~10 , C3, C 3~4 , C 3~5 , C 3~6 , C4, C 4~5 , C 4~6 , C5, C 5~6 , and may contain any number of carbons such as C6. Examples of alkynyl groups include, but are not limited to, ethynyl, propynyl, 1-butynyl, 2-butynyl, butadiynyl, 1-pentynyl, 2-pentynyl, isopentynyl, 1,3-pentadiynyl, 1,4-pentadiynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 1,3-hexadiynyl, 1,4-hexadiynyl, 1,5-hexadiynyl, 2,4-hexadiynyl, and 1,3,5-hexatriynyl.

[0018] As used herein, “alkoxy” means an alkyl ether radical, either alone or in combination, except that the term alkyl is as defined herein. Suitable examples of alkyl ether radicals include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, and tert-butoxy.

[0019] As used herein, "alkyl" refers to a linear or branched alkyl radical (e.g., C) containing 1 to 20 carbon atoms, either alone or in combination. 1~20 This refers to alkyl groups. In certain embodiments, alkyl groups contain 1 to 10 carbon atoms (for example, C 1~10 Alkyl). In further embodiments, the alkyl group contains 1 to 8 carbon atoms (e.g., C 1~8 Alkyl). In further embodiments, the alkyl group comprises 1 to 6 carbon atoms (e.g., C 1~6 Alkyl). In further embodiments, the alkyl group contains 1 to 3 carbon atoms (e.g., C 1~3 Alkyl groups are unsubstituted or substituted as defined herein. Examples of alkyl radicals include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isoamyl, hexyl, octyl, and nonyl. As used herein, the term "alkylene," alone or in combination, means a saturated aliphatic group derived from a linear or branched saturated hydrocarbon, such as methylene (-CH2-), bonded at two or more positions. Unless otherwise specified, the term "alkyl" may include an "alkylene" group.

[0020] As used herein, “alkylamino” refers to an alkyl group bonded to the parent molecule via an amino group, either alone or in combination. Suitable alkylamino groups can be monoalkylated or dialkylated to form groups such as N-methylamino, N-ethylamino, N,N-dimethylamino, and N,N-ethylmethylamino.

[0021] As used herein, “alkylthio” means, alone or in combination, an alkylthioether (RS-) radical, wherein the term alkyl is as defined herein and the sulfur may be oxidized single or double. Examples of suitable alkylthioether radicals include methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio, tert-butylthio, methanesulfonyl, and ethanesulfinyl.

[0022] As used herein, “amide” and “carbamoyl” refer to the amino groups described herein, individually or in combination, bonded to the parent molecule via a carbonyl group, or vice versa. As used herein, the “amide” group includes “C-amide” and “N-amide” groups. As used herein, the term “C-amide” refers, individually or in combination, to the -C(O)N(RR') group, where R and R' are as defined herein or as defined by the specified specifically enumerated “R” group. In some embodiments, the “amide” group may be -C(O)NH2, C 1~4 Alkylamides, and di(C) 1~4 Examples include alkylamides. When used herein, "C 1~4 The term "alkylamide" is -C(O)NH(C 1~4 (Alkyl) refers to C 1~4 Alkyl is as defined herein. As used herein, the term “N-amide” means, alone or in combination, an RC(O)N(R')- group, where R and R' are as defined herein or by the specified, specifically enumerated “R” groups. As used herein, the term “acylamino” means, alone or in combination, an acyl group attached to the parent moiety via an amino group. An example of an “acylamino” group is acetylamino (CH3C(O)NH-).

[0023] As used herein, “amino” means -NRR', either alone or in combination, where R and R' are independently selected from hydrogen, alkyl, acyl, heteroalkyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl, each of which may be unsubstituted or substituted. Furthermore, R and R' may combine to form an unsubstituted or substituted heterocycloalkyl group. The “amino” group may be a primary amine (e.g., -NH2), a secondary or disubstituted amine (e.g., -NHR where R is not hydrogen), or a tertiary or trisubstituted amine (e.g., -NRR', where neither R nor R' is hydrogen).

[0024] As used herein, “aryl” means a carbocyclic aromatic system, either alone or in combination, comprising one, two, or three rings, such polycyclic systems being condensed with each other. The term “aryl” encompasses aromatic groups such as phenyl, naphthyl, anthracenyl, and phenanthryl. The aryl moiety may contain, for example, 5 to 20 carbon atoms, for example, 5 to 12 carbon atoms, or for example, 5 or 6 carbon atoms.

[0025] As used herein, "arylalkenyl" or "aralkenyl" refers to an aryl group bonded to the parent molecule via an alkenyl group, either alone or in combination.

[0026] As used herein, "arylalkoxy" or "araloxy" refers to an aryl group bonded to the parent molecule via an alkoxy group, either individually or in combination.

[0027] As used herein, "arylalkyl" or "aralkyl" refers to an aryl group bonded to the parent molecule via an alkyl group, either alone or in combination.

[0028] As used herein, "aryloxy" refers to an aryl group, either alone or in combination, bonded to the parent molecule via oxygen.

[0029] As used herein, “carbamate” means, alone or in combination, an ester (-NHCOO-) of carbamic acid which can be attached to the parent molecule from either the nitrogen or acid terminus and is either unsubstituted or substituted as defined herein.

[0030] As used herein, “O-carbamyl” means the -OC(O)NRR' group, either alone or in combination, where R and R' are as defined herein.

[0031] As used herein, “N-carbamyl” means, alone or in combination, the ROC(O)NR'- group, where R and R' are as defined herein.

[0032] As used herein, "carbonyl" alone contains formyl [-C(O)H], and in combination with other groups, it refers to a -C(O)- group.

[0033] As used herein, “carboxyl” or “carboxy” refers to the -C(O)OH or the corresponding “carboxylate” anion, such as in carboxylate salts. The “O-carboxyl” group refers to the RC(O)O- group, where R is as defined herein. The “C-carboxyl” group refers to the -C(O)OR group, where R is as defined herein.

[0034] As used herein, "cyano," alone or in combination, refers to -CN.

[0035] As used herein, “cycloalkyl” or, in lieu thereof, “carbocyclic” means, alone or in combination, a saturated or partially saturated monocyclic, bicyclic, or tricyclic alkyl group in which each cyclic portion contains 3 to 12 carbon atom ring members, and may be unsubstituted or a benzo-condensed ring system as defined herein. Carbocyclics may include bridging ring systems and / or spiro-ring systems (e.g., systems containing two rings sharing one carbon atom). The term “cycloalkenyl” means a cycloalkyl group having one or two double bonds. In certain embodiments, the cycloalkyl (or cycloalkenyl) contains 5 to 7 carbon atoms. Examples of such groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, tetrahydronaphthyl, indanyl, octahydronaphthyl, 2,3-dihydro-1H-indenyl, and adamantyl. As used herein, “bicyclic” and “tricyclic” include both condensed ring systems such as decahydronaphthalene and octahydronaphthalene, as well as polycyclic (multi-center) saturated and partially unsaturated forms. Examples of the latter type of isomers generally include bicyclo[1,1,1]pentane, camphor, adamantane, and bicyclo[3,2,1]octane.

[0036] As used herein, "ester" refers to a carboxyl group that bridges two carbon-carbon linked moieties, either alone or in combination.

[0037] As used herein, “ether” refers to an oxy group that bridges two carbon-carbon linked moieties, either alone or in combination.

[0038] As used herein, "halogen" or "halo" refers to fluorine, chlorine, bromine, or iodine.

[0039] As used herein, "haloalkoxy" refers to a haloalkyl group bonded to a parent molecule via an oxygen atom, either alone or in combination.

[0040] As used herein, “haloalkyl” refers to an alkyl radical having the meanings set forth herein, either alone or in combination, in which one or more hydrogen atoms are substituted with halogens. Specifically, this includes monohaloalkyl, dihaloalkyl, and polyhaloalkyl radicals. For example, a monohaloalkyl radical may have an iodine, bromo, chloro, or fluoro atom within the radical. Dihalo and polyhaloalkyl radicals may have two or more identical halo atoms or combinations of different halo radicals. Examples of haloalkyl radicals include fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, and dichloropropyl. “Haloalkylene” refers to a haloalkyl group bonded at two or more positions. Examples include fluoromethylene (-CFH-), difluoromethylene (-CF2-), and chloromethylene (-CHCl-).

[0041] As used herein, “heteroalkyl” means, alone or in combination, a stable linear or branched hydrocarbon chain that is fully saturated or has 1 to 3 degrees of unsaturation, and consists of a specified number of carbon atoms and 1 to 3 selected heteroatoms selected from N, O, and S, wherein the N and S atoms may optionally be oxidized, and the N heteroatom may optionally be quaternized. The heteroatom(s) may be positioned at any internal position of the heteroalkyl group. For example, up to two heteroatoms may be consecutive, such as -CH2-NH-OCH3.

[0042] As used herein, “heteroaryl” means, alone or in combination, a 3- to 15-membered aromatic monocyclic ring, or a fused monocyclic, bicyclic, or tricyclic ring system in which at least one of the fused rings is aromatic, wherein the ring or ring system contains at least one atom selected from N, O, and S. In certain embodiments, the heteroaryl contains 1 to 4 heteroatoms as ring members. In further embodiments, the heteroaryl contains 1 to 2 heteroatoms as ring members. In certain embodiments, the alkenyl contains 5 to 7 atoms. The term also includes fused polycyclic groups in which a heterocyclic ring is fused with an aryl ring, a heteroaryl ring is fused with another heteroaryl ring, a heteroaryl ring is fused with a heterocycloalkyl ring, or a heteroaryl ring is fused with a cycloalkyl ring. Examples of heteroaryl groups include pyrrolyl, imidazolyl, pyrazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridadinyl, triazolyl, furyl, thienyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, thiadiazolyl, isothiazolyl, indolyl, isoindolyl, indolidinyl, benzimidazolyl, quinolyl, isoquinolyl, quinoxalinyl, quinazolinyl, indazolyl, benzotriazolyl, benzodioxolyl, benzopyranil, benzoxazolyl, benzoxadiazolyl, benzothiazolyl, benzothiadiazolyl, benzofuryl, benzothienyl, chromonyl, coumalinyl, benzopyranil, tetrahydroquinolinyl, tetrazolopyridazinyl, tetrahydroisoquinolinyl, thienopyridinyl, phlopyridinyl, and pyrrolopyridinyl. Examples of tricyclic heterocyclic groups include carbazolyl, phenanthrolinyl, dibenzofuranyl, acridinyl, phenanthrolinyl, and xanthenyl.

[0043] As used herein, “heterocycloalkyl” and interchangeably “heterocycle” mean a saturated, partially unsaturated, or fully unsaturated (but non-aromatic) monocyclic, bicyclic, or tricyclic heterocyclic group, either alone or in combination, comprising at least one heteroatom as a ring member, such that each heteroatom can be independently selected from nitrogen, oxygen, and sulfur. In certain embodiments, the heterocycloalkyl comprises 1 to 4 heteroatoms as ring members. In further embodiments, the heterocycloalkyl comprises 1 to 2 heteroatoms as ring members. In certain embodiments, the heterocycloalkyl comprises 3 to 8 heteroatoms per ring. In further embodiments, the heterocycloalkyl comprises 3 to 7 heteroatoms per ring. In even further embodiments, the heterocycloalkyl comprises 5 to 6 heteroatoms per ring. Heterocycles may include bridging ring systems and / or spiro-ring systems (e.g., systems comprising two rings sharing one atom, such as one carbon atom). "Heterocycloalkyl" and "heterocyclic" include sulfones, sulfoxides, N-oxides of tertiary nitrogen ring members, and condensed carbocyclic and benzo-condensed ring systems, and further, both terms include systems in which the heterocyclic is fused with an aryl group or further heterocyclic group as defined herein. Examples of heterocyclic groups include azilidinyl, azetidinyl, 1,3-benzodioxolyl, dihydroisoindolyl, dihydroisoquinolinyl, dihydrosinnolinyl, dihydrobenzodioxynyl, dihydro[1,3]oxazolo[4,5-b]pyridinyl, benzothiazolyl, dihydroindolyl, dihydropyridinyl, 1,3-dioxanyl, 1,4-dioxanyl, 1,3-dioxolanyl, isoindolinyl, morpholinyl, piperazinyl, pyrrolidinyl, tetrahydropyridinyl, piperidinyl, and thiomorpholinyl. Heterocyclic groups are either unsubstituted or substituted unless otherwise prohibited.

[0044] As used herein, "hydrazinyl" refers, either individually or in combination, to two amino groups linked by a single bond, i.e., -NN-.

[0045] As used herein, "hydroxyl" refers to -OH, either alone or in combination.

[0046] As used herein, "hydroxyalkyl" refers to an alkyl group bonded to the parent molecule via an alkyl group, either alone or in combination.

[0047] As used herein, "iminohydroxy" refers, either alone or in combination, to =N(OH) and =NO-.

[0048] As used herein, “lower amino” means -NRR', either alone or in combination, where R and R' are independently selected from hydrogen and lower alkyl, and either is unsubstituted or substituted.

[0049] As used herein, “mercaptyl” alone or in combination refers to the RS- group, where R is as defined herein.

[0050] As used herein, "nitro," either alone or in combination, refers to -NO2.

[0051] As used herein, "oxy" or "oxa" means -O-, either alone or in combination.

[0052] As used herein, "oxo" alone or in combination refers to =O.

[0053] "Perhaloalkoxy" refers to an alkoxy group in which all hydrogen atoms are replaced by halogen atoms.

[0054] As used herein, “perhaloalkyl” refers to an alkyl group, either alone or in combination, in which all hydrogen atoms are replaced by halogen atoms.

[0055] As used herein with respect to chemical structures or parts thereof, “ring” or its equivalent “cycle” means a group in which all atoms are members of a common ring structure. Unless otherwise specified, rings may be saturated or unsaturated (including aromatic) and may have 3 to 9 members. If the ring is a heterocycle, then B, N, O, S, C(O), S(O) m It may contain 1 to 4 heteroatoms or heteroatom-containing groups selected from the following. Unless otherwise prohibited, the rings are either unsubstituted or substituted. Two or more rings may be fused (e.g., two or more rings may be bonded and share two common atoms). Two or more rings may be linked to each other in a spiro configuration such that only one atom is shared between the two rings. Furthermore, or alternatively, two or more rings may be arranged in a bridged configuration such that three or more atoms are shared between the two rings.

[0056] As used herein, "sulfonate," "sulfonic acid," and "of a sulfonic acid" refer, individually or in combination, to the -SO3H group and, if the sulfonic acid is used in salt formation, to its anion.

[0057] As used herein, "sulfanil," alone or in combination, refers to -S-.

[0058] As used herein, "sulfinyl," either alone or in combination, refers to -S(O)-.

[0059] As used herein, "sulfonyl," either alone or in combination, refers to -SO2.

[0060] "N-sulfonamide" refers to the RS(=O)2NR'- group, where R and R' are as defined herein.

[0061] "S-sulfonamide" refers to the -S(=O)2NRR'- group, where R and R' are as defined herein.

[0062] As used herein, “tautomer” refers to one of two or more isomers that rapidly interconvert, either alone or in combination. Generally, this interconversion is fast enough that individual tautomers cannot be isolated in the absence of other tautomers. The ratio of tautomers may depend on the solvent composition, ionic strength, pH, and other solution parameters. The ratio of tautomers may vary in a particular solution and in the microenvironment of biomolecular binding sites in said solution. 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.

[0063] As used herein, "thia" and "thio" refer, individually or in combination, to an -S- group or ether in which oxygen is substituted with sulfur. Oxidized derivatives of the thio group, namely sulfinyl and sulfonyl, are included in the definitions of thia and thio.

[0064] As used herein, "thiol" refers to an -SH group, either alone or in combination.

[0065] As used herein, "thiocarbonyl" alone contains thioformyl-C(S)H, and in combination with other groups, it refers to a -C(S)- group.

[0066] "N-thiocarbamyl" refers to the ROC(S)NR'- group, where R and R' are as defined herein.

[0067] "O-thiocarbamyl" refers to the -OC(S)NRR' group, where R and R' are as defined herein.

[0068] "Thiocyanate" refers to the -CNS group.

[0069] Any definition used herein may be used in combination with any other definition to describe a complex structural group. By convention, the element at the end of such a definition is the element that is bonded to the parent part. For example, the complex group alkylamide represents an alkyl group bonded to the parent molecule via an amide group, and the term alkoxyalkyl represents an alkoxy group bonded to the parent molecule via an alkyl group.

[0070] As described herein, the groups may be substituted or unsubstituted (e.g., "optionally substituted"). Unless otherwise specified, any group may be substituted with one or more substituents, such as one or more substituents provided herein. Examples of substituents that can substitute a group include, but are not limited to, the following groups or certain designated groups, either alone or in combination: alkyl (e.g., C 1~20 Alkyl, for example, C 1~10 Alkyl, for example, C 1~6 Alkyl, for example, C 1~3 Alkyl), alkenyl (e.g., C 2~20 Alkenyl, for example, C 2~10 Alkenyl, for example, C 2~6 Alkenyl), Alkinyl (for example, C 2~20 Alkinyl, for example, C 2~10 Alkinyl, for example, C 2~6 Alkinyl), Alkanoyl (for example, C 1~20 Alkanoyl, for example, C 1~10 Alkanoyl, for example, C 1~6 Alkanoyl), heteroalkyl (e.g., a heteroalkyl moiety containing 1 to 20 carbon atoms and 1 to 6 heteroatoms, e.g., a heteroalkyl moiety containing 1 to 6 carbon atoms and 1 to 3 heteroatoms), haloalkyl (e.g., halosubstituted C) 1~20 Alkyl, for example, halo-substituted C 1~10 Alkyl, halo-substituted C 1~6 Alkyl), haloalkenyl (e.g., halosubstituted C) 2~20 Alkenyl, e.g., halo-substituted C 2~6 Alkenyls), haloalkynyls (e.g., halo-substituted C) 2~20Alkynyl, e.g., halo substitution C 2~6 Alkinyl), perhaloalkyl (e.g., C 1~20 Perhaloalkyl, for example, C 1~6 Perhaloalkyl, for example, C 1~3 Perhaloalkyls), perhaloalkoxys (e.g., C 1~20 Perhaloalkoxy, for example, C 1~6 Perhaloalkoxy), phenyl, aryl (e.g., C 5~20 Aryl, for example, C 5~10 Aryl, for example, C 5~6 aryl), aryloxy (for example, C 5~20 Aryloxy, for example, C 5~10 Aryloxy, for example, C 5~6 Aryloxy), alkoxy (e.g., C 1~20 Alkoxy, for example, C 1~10 Alkoxy, for example, C 1~6 Alkoxy), haloalkoxy (for example, C 1~20 Haloalkoxy, for example, C 1~10 Haloalkoxy, for example, C 1~6 Haloalkoxy), oxo, acyloxy (e.g., acyloxy groups containing 1 to 20 carbon atoms, e.g., 1 to 10 carbon atoms, e.g., 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 Alkyl carbonyl, for example, C 1~10 Alkyl carbonyl, for example, C 1~6 Alkyl carbonyl, for example, C 1~3 Alkylcarbonyl), carboxyl ester (e.g., C(O)OR, where R is, for example, alkyl (e.g., C 1~20 Alkyl, for example, C 1~10 Alkyl, for example, C 1~6 Alkyl, for example, C 1~3 Alkyl), alkenyl (e.g., (e.g., C 2~20 Alkenyl, for example, C 2~10 Alkenyl, for example, C 2~6 Alkenyl) or alkinyl (for example, C 2~20 Alkinyl, for example, C 2~10Alkynyl, such as C 2~6 Alkynyl), any of which may be substituted with any group provided herein), carboxamide, cyano (e.g., CN), hydrogen, halogen (e.g., iodine, bromine, chlorine, or fluorine), hydroxy, amino (e.g., NR’R”, provided that R’ and R” are independently, for example, hydrogen, alkyl (e.g., C 1~20 Alkyl, such as C 1~10 Alkyl, such as C 1~6 Alkyl, such as C 1~3 Alkyl), alkenyl (e.g., (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 may be substituted with any group provided herein), alkylamino (e.g., NR’R” provided that R’ is alkyl (e.g., C 1~20 Alkyl, such as C 1~10 Alkyl, such as C 1~6 Alkyl, such as C 1~3 Alkyl), and R” is, for example, hydrogen, alkyl (e.g., C 1~20 Alkyl, such as C 1~10 Alkyl, such as C 1~6 Alkyl, such as C 1~3 Alkyl), alkenyl (e.g., (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 may be substituted with any group provided herein), arylamino (e.g., NR’R”, provided that 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., C1~20 Alkyl, for example, C 1~10 Alkyl, for example, C 1~6 Alkyl, for example, C 1~3 Alkyl), alkenyl (e.g., (e.g., C 2~20 Alkenyl, for example, C 2~10 Alkenyl, for example, C 2~6 Alkenyl) or alkinyl (for example, C 2~20 Alkinyl, for example, C 2~10 Alkinyl, for example, C 2~6 Alkynnyl) and any of these may be substituted with any group provided herein), amide (e.g., C(O)NR'R'', where R' and R'' are independently, for example, hydrogen, alkyl (e.g., C 1~20 Alkyl, for example, C 1~10 Alkyl, for example, C 1~6 Alkyl, for example, C 1~3 Alkyl), alkenyl (e.g., (e.g., C 2~20 Alkenyl, for example, C 2~10 Alkenyl, for example, C 2~6 Alkenyl) or alkinyl (for example, C 2~20 Alkinyl, for example, C 2~10 Alkinyl, for example, C 2~6 Alkynyl (and any of these may 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 C substituted with alkyl groups, for example, thiol groups 1~10 C substituted with alkyl, for example, thiol groups 1~6 C substituted with alkyl, for example, thiol groups 1~3 Alkyl), haloalkylthio (for example, C 1~20 Haloalkylthio, for example, C 1~10 Haloalkylthio, for example, C 1~6 Haloalkylthio, for example, C 1~3 Haloalkylthio), perhaloalkylthio (for example, C 1~20 Perhaloalkylthio, for example, C 1~10 Perhaloalkylthio, for example, C 1~6 Perhaloalkylthio, for example, C1~3 Perhaloalkylthio), arylthiol (for example, C 5~20 Arylthiols, for example, C 5~10 Arylthiols, for example, C 5~6 Arylthiols), sulfonates (e.g., S(O)2OR, where R is, for example, alkyl (e.g., C) 1~20 Alkyl, for example, C 1~10 Alkyl, for example, C 1~6 Alkyl, for example, C 1~3 Alkyl), alkenyl (e.g., (e.g., C 2~20 Alkenyl, for example, C 2~10 Alkenyl, for example, C 2~6 Alkenyl) or alkinyl (for example, C 2~20 Alkinyl, for example, C 2~10 Alkinyl, for example, C 2~6 Alkynnyls) (any of which may be substituted with any group provided herein), sulfonic acids (e.g., S(O)2OH), trisubstituted silyls (e.g., SiR'R''R*, where R', R'', and R* are independently, for example, alkyls (e.g., C 1~20 Alkyl, for example, C 1~10 Alkyl, for example, C 1~6 Alkyl, for example, C 1~3 Alkyl), alkenyl (e.g., (e.g., C 2~20 Alkenyl, for example, C 2~10 Alkenyl, for example, C 2~6 Alkenyl) or alkinyl (for example, C 2~20 Alkinyl, for example, C 2~10 Alkinyl, for example, C 2~6Selected from alkynyls, any of which may be substituted with any group provided herein; for example, the trisubstituted silyl may be trimethylsilyl), N3, SCH3, C(O)CH3, CO2CH3, CO2H, pyridinyl, thiophene, furanyl, carbamate, and urea. Further groups may also be conceived. Where structurally possible, two substituents may bond to each other to form a condensed 5, 6, or 7-membered carbocyclic or heterocyclic ring consisting of 0 to 3 heteroatoms (e.g., N, O, S, etc.) to form, for example, methylenedioxy or ethylenedioxy. Unsubstituted or substituted 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 substituents are described without limitation with respect to substitution, both substituted and unsubstituted forms are included. When a substituent is specifically referred to as "substituted," the form of substitution is concretely intended. Furthermore, different sets of any substituents for a particular part can be defined as needed, in which case any substitution is as defined and often immediately follows the phrase "unsubstituted or substituted."

[0071] Unless otherwise defined, the terms R, R', R'', and R*, when used alone or without a number specified, refer to a portion selected from hydrogen, alkyl, cycloalkyl, heteroalkyl, aryl, heteroaryl, and heterocycloalkyl, any of which are either unsubstituted or substituted (e.g., as described herein). Such R and R' groups should be understood as either unsubstituted or substituted as defined herein. Regardless of whether the R group is numbered or not, R, R', R nAll R groups, all substituents, and all terms, including n=(1, 2, 3, ..., n) (wherein n=(1, 2, 3, ..., n)), should be understood as independent of one another with respect to 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 in each case is independent of its definition in all other cases. Those skilled in the art will also recognize that certain groups can be bonded to the parent molecule from either end as described or occupy a given position in the element chain. For example, an asymmetric group such as -C(O)N(R)- can be bonded to the parent moiety at either carbon or nitrogen.

[0072] "Bond" refers to a covalent bond between two atoms, or a covalent bond between two substructures when the atoms linked by the bond are considered part of a larger substructure. Unless otherwise specified, bonds can be single, double, or triple. In molecular diagrams, dashed lines between two atoms indicate whether or not there may be further bonds at that location.

[0073] The compounds disclosed herein may contain chiral centers. These centers are designated by the symbol "R" or "S" depending on the arrangement of substituents around the chiral carbon atom. It should be understood that this disclosure encompasses all stereochemical isomers, including diastereomers, enantiomers, atropisomers, and epimer forms, as well as d-isomers and l-isomers, and mixtures thereof. Individual stereoisomers of compounds can be prepared by synthesis from commercially available starting materials containing chiral centers, or by separation after preparing mixtures of enantiomer products, for example, by separation or recrystallization after conversion to a mixture of diastereomers, by chromatographic techniques, direct separation of enantiomers in a chiral chromatography column, or by other suitable methods well known in the art. Starting compounds for specific stereochemistrys are commercially available or can be prepared and divided by techniques well known in the art. Furthermore, the compounds disclosed herein may also exist as geometric isomers. This disclosure includes all cis, trans, syn, anti, entgegen (E), and tuzamen (Z) isomers, as well as suitable mixtures thereof. Furthermore, compounds may exist as tautomers, and all tautomers are provided by this disclosure. In addition, the compounds provided herein may include conformational isomers, and these compounds contain groups that can be oriented to different conformations with respect to another part. Furthermore, the compounds disclosed herein may exist in non-solvated and solvated forms with pharmaceutically acceptable solvents such as water and ethanol. Generally, the solvated form is considered equivalent to the non-solvated form.

[0074] "Combination therapy" means the administration of two or more therapeutic agents for the treatment of the therapeutic condition or disorder described herein. Such administration includes the simultaneous administration of these therapeutic agents, substantially simultaneously, for example, as a single dose unit (e.g., a capsule) having a fixed ratio of active ingredients, or as multiple separate dose units (e.g., capsules) for each active ingredient. Furthermore, such administration also includes the sequential use of each type of therapeutic agent. In any case, the treatment regimen provides the beneficial effect of the combination of drugs in the treatment of the condition or disorder described herein.

[0075] As used herein, "KRAS inhibitor" means an IC50 or less, more commonly, of approximately 50 μM or less, with respect to KRAS activity, as measured by assays commonly described herein, such as surface plasmon resonance KRAS-G12D protein binding assay and / or KRASG12D protein-effector protein interaction interference assay. 50 It is used to refer to compounds that exhibit the characteristic "IC". 50 " is the concentration of an inhibitor that reduces the activity of an enzyme (e.g., KRAS) to half of its maximum level. Certain compounds disclosed herein have been found to exhibit inhibitory activity against KRAS. In certain embodiments, when measured by the KRAS assay described herein, the compound has an IC50 or less of approximately 50 μM against KRAS (e.g., KRAS with the G12D mutation). 50 In further embodiments, the compound exhibits an IC50 of approximately 10 μM or less against KRAS (e.g., KRAS having the G12D mutation). 50 In further embodiments, the compound exhibits an IC50 of approximately 1 μM or less against KRAS (e.g., KRAS having the G12D mutation). 50 In further embodiments, the compound has an IC50 of approximately 200 nM or less against KRAS (e.g., KRAS having the G12D mutation). 50In some embodiments, the compound has an IC50 of less than approximately 50 μM against KRAS (e.g., KRAS with the G12D mutation), such as approximately 40 μM, 30 μM, 20 μM, 10 μM, 5 μM, 1 μM, 500 nM, 200 nM, 100 nM, 50 nM, or less. 50 This shows that in certain embodiments, the compound has an IC50 of less than approximately 1 μM against KRAS (e.g., KRAS with the G12D mutation). 50 This demonstrates that, in some embodiments, the inhibitory activity of a KRAS inhibitor against KRAS having the G12D mutation is greater than its inhibitory activity against KRAS having other mutations, such as G12C, G12R, G12S, G12A, or G12V mutations. For example, in some embodiments, the KRAS inhibitors provided herein have at least 2 times, 5 times, 10 times, 20 times, or more inhibitory activity against KRAS having the G12D mutation compared to KRAS having other mutations, such as the G12C mutation, such as the G12C, G12R, G12S, G12A, or G12V mutations. In some embodiments, the KRAS inhibitors provided herein have higher inhibitory activity against active KRAS having the G12D mutation than against inactive KRAS having the G12D mutation. In some embodiments, the KRAS inhibitors provided herein have lower inhibitory activity against active KRAS having the G12D mutation than against inactive KRAS having the G12D mutation. In some embodiments, the KRAS inhibitors provided herein have similar inhibitory activity against active and inactive KRAS having the G12D mutation. In some embodiments, the KRAS inhibitors provided herein have inhibitory activity against the K-RAS4a splice variant. In some embodiments, the KRAS inhibitors provided herein have inhibitory activity against the K-RAS4b splice variant. In some embodiments, the KRAS inhibitors provided herein have inhibitory activity against both the K-RAS4a and K-RAS4b splice variants.

[0076] "Therapeutic dose" refers to the amount of compound or pharmaceutical composition useful for treating or improving a specific disease, disorder, or condition, or for exhibiting a detectable therapeutic or inhibitory effect. The exact amount is determined by the therapeutic purpose and can be determined by those skilled in the art using known techniques (see, for example, Lieberman, Pharmaceutical Dosage Forms (vols. 1-3, 1992); Lloyd, The Art, Science and Technology of Pharmaceutical Compounding (1999); Pickar, Dosage Calculations (1999); and Remington: The Science and Practice of Pharmacy, 20th Edition, 2003, Gennaro, Ed., Lippincott, Williams & Wilkins).

[0077] The term "therapeutably acceptable" refers to a compound (or salt, prodrug, tautomer, zwitterionic form, etc.) that is free from excessive toxicity, irritation, and allergic reactions, has a reasonable benefit-to-risk ratio, is effective for its intended use, and is suitable for use in contact with patient tissue.

[0078] The terms “to treat,” “therapeutic,” and “treatment” refer to any sign of successful treatment or improvement of an injury, condition, or state, including any objective or subjective parameters, such as remission, remission, disappearance of symptoms or making the injury, condition, or state tolerable to the patient, slowing the rate of degeneration or decline, making the final stage of degeneration less debilitating, and / or improving the patient’s physical or mental health. Treatment or improvement of symptoms may be based on objective or subjective parameters, including the results of a physical examination, neuropsychiatric examination, and / or psychiatric assessment. Treatment may be preemptive in nature, that is, it may include prevention of disease, disorder, or state, prevention of the onset of one or more symptoms of disease, disorder, or state, and / or prevention of the worsening of disease, disorder, or state. Prevention of disease, disorder, or state may include complete protection from disease and / or prevention of disease progression (e.g., to later stages of disease, disorder, or state). For example, disease prevention may not mean completely eliminating all effects associated with the disease at all levels, but rather preventing the symptoms of the disease, disorder, or condition to a clinically significant or detectable level.

[0079] "Patient" or "Subject" means an organism that is suffering from or is likely to suffer from a disease, disorder, or condition that can be treated by administration of the compounds or pharmaceutical compositions provided herein. Non-exclusive 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 administration of the compounds or pharmaceutical compositions provided herein include, for example, rodents (e.g., rats, mice, squirrels, guinea pigs, hamsters, etc.), lagomorphs (e.g., rabbits, hares, etc.), primates (monkeys, apes, etc.), cattle (e.g., cattle), odd-toed ungulates (e.g., horses), artiodactyls (e.g., cattle, sheep, goats, pigs, etc.), and marsupials (e.g., kangaroos, wallabies, wallaroos, sugar gliders, etc.). In some embodiments, the patient or subject is a human. In some embodiments, the patient or subject is a companion animal such as a cat or a dog. In some embodiments, the patient or subject is livestock such as a goat, sheep, cattle, pig, or horse. In some embodiments, the patient or subject is a primate (e.g., a monkey), a marsupial (e.g., a kangaroo, wallaby, wallaroo, sugar glider, etc.), or an exotic animal such as an undomesticated or mixed-breed cat or dog.

[0080] As used herein, “composition” is intended to include products containing specific amounts of specific components, as well as any products obtained directly or indirectly from specific amounts of specific components in combination. “Pharmacologically acceptable” means that the carrier, diluent, or excipient is compatible with the other components of the formulation and is not harmful to its recipient.

[0081] "Pharmacologically acceptable excipients" refer to substances that assist in the administration and absorption of an activator to a subject. Useful pharmaceutical excipients in this disclosure include, but are not limited to, binders, fillers, disintegrants, lubricants, coatings, sweeteners, flavorings, and colorants. Those skilled in the art will recognize that other pharmaceutical excipients may also be useful in this disclosure.

[0082] The term "prodrug" refers to a compound that is more active in vivo. Certain compounds disclosed herein may also exist as prodrugs. Prodrugs of compounds described herein are structurally modified forms of a compound that readily undergo chemical changes under physiological conditions to yield the compound. Furthermore, prodrugs may be converted to compounds by chemical or biochemical methods in an ex vivo environment. For example, a prodrug may be slowly converted to a compound when placed in a transdermal patch reservoir with a suitable enzyme or chemical reagent. Prodrugs are often useful because, in some situations, they may be easier to administer than the compound or parent drug. For example, a prodrug may exhibit bioavailability by oral administration, even if the parent drug does not. Prodrugs may also have improved solubility in pharmaceutical compositions compared to the parent drug.

[0083] The compounds disclosed herein may exist as therapeutically acceptable salts. This disclosure includes compounds provided herein in the form of salts, including acid addition salts. Suitable salts include those formed with both organic and inorganic acids. Such acid addition salts are generally pharmaceutically acceptable. However, salts of pharmaceutically unacceptable salts may also be useful in the preparation and purification of the compounds of interest. Base addition salts are also formed and are pharmaceutically acceptable.

[0084] As used herein, the term “therapeutably acceptable salt” refers to a salt or zwitterionic form of a compound disclosed herein that is water-soluble, oil-soluble, or dispersible and therapeutically acceptable as defined herein. Salts can be prepared separately during the final isolation and purification of the compound, or by reacting a suitable compound in the form of a free base with a suitable acid. Typical acid addition salts include acetate, adipine, alginate, L-ascorbate, aspartate, benzoate, benzenesulfonate (besylate), bisulfate, butyrate, camphorate, camphorsulfonate, citrate, digluconate, formate, fumarate, gentisinate, glutarate, glycerophosphate, glycolic acid, hemisulfate, heptanoate, hexanoate, hippurate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonic acid (isethionate), lactate, maleate, and malonic acid. Examples include salts, DL-mandelate, mesitylene sulfonate, methanesulfonate, naphthylene sulfonate, nicotinate, 2-naphthalene sulfonate, oxalate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphonate, picrate, pivalate, propionate, pyroglutamate, succinate, sulfonate, tartrate, L-tartrate, trichloroacetate, trifluoroacetate, phosphate, glutamate, bicarbonate, p-toluenesulfonic acid (p-tosylate), and undecanoate. Furthermore, the basic groups of the compounds disclosed herein can be quaternized with, for example, methyl chloride, bromide, and iodide, ethyl chloride, bromide, and iodide, propyl chloride, bromide, and butyl chloride, bromide, and iodide; dimethyl sulfate, diethyl sulfate, dibutyl sulfate, and diamyl sulfate; decyl chloride, bromide, and iodide, lauryl chloride, bromide, and iodide, myristyl chloride, bromide, and steryl chloride, bromide, and iodide; and benzyl bromide and phenylethyl bromide. Examples of acids that can be used to form therapeutically acceptable addition salts include inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, and phosphoric acid, as well as organic acids such as oxalic acid, maleic acid, succinic acid, and citric acid.Salts can also be formed by the coordination of a compound with an alkali metal or alkaline earth ion. Therefore, the present disclosure includes sodium, potassium, magnesium, and calcium salts of the compounds disclosed herein.

[0085] Basic addition salts can be prepared by reacting the carboxyl group with a suitable base, such as a metal cation hydroxide, carbonate, or bicarbonate, or with ammonia or an organic primary, secondary, or tertiary amine, during the final isolation and purification of the compound. Therapeutably acceptable salt cations include lithium, sodium, potassium, calcium, magnesium, and aluminum, as well as non-toxic quaternary amine cations such as ammonium, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, triethylamine, diethylamine, ethylamine, tributylamine, pyridine, N,N-dimethylaniline, N-methylpiperidine, N-methylmorpholine, dicyclohexylamine, procaine, dibenzylamine, N,N-dibenzylphenethylamine, 1-ephenamine, and N,N'-dibenzylethylenediamine. Other representative organic amines useful for forming base addition salts include ethylenediamine, ethanolamine, diethanolamine, piperidine, and piperazine.

[0086] Salts of compounds can be prepared by reacting a suitable compound in the form of a free base with a suitable acid.

[0087] "KRASG12D-positive cancer" refers to cancer characterized by the KRASG12D mutation.

[0088] As used herein, “combined therapeutic dose” means the amount of therapeutic agents that, when administered separately (time-staggered and especially in a specific order) to a warm-blooded animal, in particular a human being treated, exhibit an additive, but preferably synergistic, interaction (combined therapeutic effect). Whether this is true can be determined, among other things, by tracking blood concentrations that indicate the presence of both compounds in the blood of the human being treated for at least a specific time interval.

[0089] As used herein, “synergistic effect” refers to the effect of at least two therapeutic agents, which may be a KRASG12D inhibitor as defined herein and an additional agent configured to treat a disease, disorder, or condition, or its symptoms. This effect may include, for example, slowing the progression of symptoms of a proliferative disorder, such as cancer, particularly lung cancer, or its symptoms. Similarly, “synergistic effective dose” refers to the amount required to obtain the synergistic effect.

[0090] When "a," "an," or "a(n)" is used herein in reference to a group of substituents or "substituents," it means at least one. For example, if a compound is substituted with "an(1)" alkyl or aryl, the compound is either unsubstituted or substituted with at least one alkyl and / or at least one aryl, each alkyl and / or aryl being different. In another example, if a compound is substituted with "a(1)" substituent, the compound is substituted with at least one substituent, each substituent being different.

[0091] compound In one embodiment, the present disclosure relates to a compound represented by formula (I): [ka] The formula provides a salt thereof (e.g., a pharmaceutically acceptable salt), an ester, a tautomer, a prodrug, a zwitterionic form, or a stereoisomer [wherein, R 1 is -OR 8A 4-6 member heterocycle containing a nitrogen atom, selected from H, wherein the heterocycle is unsubstituted or has one or more R 16 Replaced by, R 2 These are H, a 3-6 membered carbon ring, and C 1~6 Selected from alkyl groups, but with a 3-6 membered carbon ring or C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, R 3 C 1~6 Selected from alkyl, carbocyclic, and heterocyclic elements, however any C 1~6 Alkyl is one or more R 9 Substituted by, and the carbocyclic or heterocyclic ring is unsubstituted or has one or more R 10 Replaced by, Or, R 2 and R 3 This refers to the atoms to which they are bonded, and whether they are unsubstituted or have one or more R 11 Forms a heterocycle substituted with, R 4 H, halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 5 H, halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Selected from alkynyls, 3-6 membered carbon rings, 3-6 membered heterocycles, 5-6 membered heteroaryls, and phenyls, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbocyclic, heterocyclic, heteroaryl, and phenyl is either unsubstituted or has one or more R14 Replaced by, R 6 is a phenyl, monocyclic heteroaryl, bicyclic aryl, or bicyclic heteroaryl, provided that any phenyl, monocyclic heteroaryl, bicyclic aryl, and bicyclic heteroaryl is unsubstituted or has one or more R 15 Replaced by, R 7 is halogen, -OR 12 Selected from , -CN, and H, R 8 The heterocycle is selected from H, heterocycles, and alkyl heterocycles, provided that the heterocycle or alkyl heterocycle is unsubstituted or has one or more R 16 Substituted with, the alkyl portion of any alkyl heterocycle is C 1~6 Selected from alkyl groups, Each R 9 is -N(R 17 )2, -N(R 17 )C(O)C 1~6 Alkyl and -OR 17 Selected independently of, however, any C 1~6 Alkyl is either unsubstituted or has one or more R 18 Replaced by, Each R 10 Halogen, -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )2, -C(O)(C 1~6 Alkyl)N(R 19 )2, -(C 1~6 Alkyl)C(O)N(R 19 )2, -C(NR 19 )NR 19 CN, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 20 Replaced by, Each R 11 is -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )2, -C(O)(C 1~6 Alkyl)N(R19 )2, -(C 1~6 Alkyl)C(O)N(R 19 )2, -C(NR 19 )NR 19 CN, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 20 Replaced by, Each R 12 C 1~6 Alkyl, C 2~6 Alkenyl and H are selected independently, except for any C 1~6 Alkyl or C 2~6 Alkenyls are either unsubstituted or have one or more R 13 Replaced by, Each R 13 is -OR 22 -CN, -N(R 22 )2, and selected independently from halogens, Each R 14 is halogen, -OR 12 -CN, -N(R 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 15 is halogen, -OR 12 -CN, -N(R 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 16 Halogen, -N(R 12 )2, C 1~6 Alkyl, -OR 12 , and independently selected from 3- to 6-membered complex rings, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 17 C 1~6Selected independently from alkyl and H, Each R 18 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 19 C 1~6 A alkyl group, a 3- to 6-membered heterocycle, and H are independently selected, except for any C. 1~6 Alkyl is either unsubstituted or has one or more R 21 Replaced by, Each R 20 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Independently selected from alkyl, halogen, and 3-6 membered carbon rings, Each R 21 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 22 C 1~6 Alkyl, C 2~6 [Selected independently of alkenyl and H].

[0092] In some embodiments, the disclosure provides compounds of formula I or salts thereof (e.g., pharmaceutically acceptable salts).

[0093] In some embodiments, R 1 is -OR 8 In some embodiments, R 8 It is a complex algebra. In some embodiments, R 8 is an alkyl heterocycle. In some embodiments, R 8 It is an alkyl heterocycle, where the alkyl portion of the alkyl heterocycle is C 1~6 Selected from alkyl groups. In some embodiments, R 8is -CH2 (heterocycle). In some embodiments, the heterocycle or alkyl heterocycle has 4 to 8 members, including at least one heteroatom (e.g., 1 to 2 heteroatoms) selected from N, O, and S. In some embodiments, R 8 It comprises a heterocycle containing at least one nitrogen atom. In some embodiments, R 8 The heterocycle comprises a 4- to 8-membered heterocycle containing at least one nitrogen atom. In some embodiments, the heterocycle or alkyl heterocycle is a 4- to 6-membered monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the heterocycle or alkyl heterocycle is an 8-membered bicyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the heterocycle comprises one or more R 16 It is replaced by. In some embodiments, at least one R 16 is -OR 12 And, however, R 12 C 1~6 Alkyl, C 2~6 Alkenyls and H are selected independently. In some embodiments, at least one R 16 is -OCH3. In some embodiments, at least one R 16 is a halogen (e.g., F). In some embodiments, at least one R 16 is either unsubstituted or one or more R 13 C replaced by 1~6 It is alkyl. In some embodiments, each R 16 is halogen, C 1~6 Alkyl and -OR 12 Selected independently of, however, any C 1~6 Alkyl is either unsubstituted or has one or more R 13 It is replaced by. In some embodiments, each R 16 It is selected independently from -F, -CH3, -CH2CH2F, -CH2CHF2, -CH2CH2CN, -OCH3, and -OCHF2.

[0094] In some embodiments, R 1 The following can be selected: [ka] However, R a and R b Each of them is independent of halogen and C 1~6 Alkyl, -OR 12 , and H are selected, and any C 1~6 Alkyl is either unsubstituted or has one or more R 13 It is replaced by R a is a halogen. In some embodiments, R a In some embodiments, R a is either unsubstituted or one or more R 13 C replaced by 1~6 It is alkyl. In some embodiments, R a is methyl. In some embodiments, R a is, -OC 1~6 It is alkyl. In some embodiments, R a H is H. In some embodiments, R b H is H. In some embodiments, R b is a halogen. In some embodiments, R b In some embodiments, R b is either unsubstituted or one or more R 13 C replaced by 1~6 It is alkyl. In some embodiments, R b is methyl. In some embodiments, R 1 teeth, [ka] Selected from.

[0095] In some embodiments, R 1 teeth, [ka] Selected from.

[0096] In some embodiments, R 1 teeth, [ka] Selected from, However, each R a is halogen, C 1~6 Alkyl, -OR 12 , and H are selected independently, R c is C 1~6 Selected from alkyl, R a or R c C 1~6 Alkyl is either unsubstituted or has one or more R 13 It is replaced by one R. In some embodiments, one R a is halogen, C 1~6 Alkyl and -OR 12 Selected from, other R a is H. In some embodiments, one R a is a halogen (e.g., F). In some embodiments, two R a is a halogen (e.g., F). In some embodiments, one R a However, -OR 12 (For example, -OCH3 or -CHF2). In some embodiments, one R a However, C 1~6 It is an alkyl group (e.g., methyl). In some embodiments, two R a However, C 1~6 It is an alkyl group (e.g., methyl). In some embodiments, R c R is selected from -CH3, -CH2CH2F, -CH2CHF2, and -CH2CH2CN. In some embodiments, R 1 teeth, [ka] Selected from.

[0097] In some embodiments, R 1 teeth, [ka] It is selected from the group consisting of the following.

[0098] In some embodiments, R 1 teeth, [ka] Selected from.

[0099] In some embodiments, R 1 teeth, [ka] Selected from.

[0100] In some embodiments, R 1 It is a 4-6 member heterocycle containing a nitrogen atom, and the heterocycle is unsubstituted or has one or more R 16 It is replaced by R. In some such embodiments, 16 is -N(R 12 )2, C 1~6 Selected from alkyl groups and 3- to 6-membered heterocycles. In some embodiments, R 16 is -N(C 1~6 Alkyl)2, for example, -N(CH3)2. In some embodiments, R 16 C 1~6 It is an alkyl group (e.g., methyl). In some embodiments, R 16 It is a bicyclic, six-membered heterocycle having one nitrogen atom. In some embodiments, R 1 teeth, [ka] It is selected from the group consisting of the following.

[0101] In some embodiments, R 1 It is hydrogen.

[0102] In some embodiments, R 2 H is H. In some embodiments, R 2 is either unsubstituted or one or more R 13 C replaced by 1~6 It is alkyl. In some such embodiments, each R 13 is -OR 22 (For example, -OH) and -CN are selected independently. In some embodiments, R 2 C 1~6 It is alkyl. In some embodiments, R 2 R is selected from -CH3, -CH2CH3, -CH2CH2OH, -CH2CH2CN, and -CH(CH3)2. In some embodiments, R 2 is a 3-6 member carbon ring. In some embodiments, R 2 It is cyclopropyl.

[0103] In some embodiments, R 3 is C 1~6 It is alkyl, C 1~6 Alkyl is one or more R 9 It is replaced by R 3 is -N(R 17 C replaced with )2 1~6 It is alkyl, however each R 17 C 1~6 Selected independently from alkyl and H. In some embodiments, R 3 C is substituted with -NH2, -NH(CH3), or -N(CH3)2. 1~6 It is alkyl. In some embodiments, R 3 is -N(R 17 )C(O)C 1~6 C substituted with alkyl (e.g., -N(H)C(O)CH3) 1~6 It is alkyl. In some embodiments, R 3 is -OR 17 (For example, C substituted with -OH) 1~6 It is alkyl.

[0104] In some embodiments, R 3 teeth, [ka] Selected from.

[0105] In some embodiments, R 3 It is a carbon ring, and that carbon ring is either unsubstituted or has one or more R 10 It is replaced by R 3 It is a 4-6 member carbon ring, and the carbon ring is either unsubstituted or has one or more R 10 It is replaced by R 3 R is a polycyclic carbon ring (for example, a bicyclic carbon ring with 5-6 members). In some embodiments, R 3 R is a monocyclic carbon ring (for example, a 4-6 member monocyclic carbon ring). In some embodiments, R 3 is -N(R 19 )2 is a carbon ring substituted with each R 19 This is either non-substitutive or substituted C 1~6 Selected independently from alkyl and H. In some embodiments, R 3 This is a carbon ring substituted with -NH2.

[0106] In some embodiments, R 3 teeth, [ka] Selected from.

[0107] In some embodiments, R 3 is a heteroalgebra, and a heteroalgebra is either unsubstituted or has one or more R 10 It is replaced by R 3 A is a 4-8 membered heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and the heterocycle is unsubstituted or has one or more R 10It is replaced by R 3 is a polycyclic heteroalgebra (for example, a bicyclic heteroalgebra with 6 to 8 members). In some embodiments, R 3 is a monocyclic heterocycle (e.g., a monocyclic heterocycle with 4 to 6 members). In some embodiments, the heterocycle contains one or more nitrogen atoms. In some embodiments, R 3 is either unsubstituted or one or more R 10 It is a heterogeneous ring substituted with, where each R 10 Halogen, -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )2, -C(O)(C 1~6 Alkyl)N(R 19 )2, and C 1~6 Selected independently of alkyl, any C 1~6 Alkyl is either unsubstituted or has one or more R 20 It is replaced by R 3 is either unsubstituted or -F, -CH3, -CH2F, -CH2CN, -C(O)CH3, -C(O)CH2NH2, -C(O)NH2, and [ka] It is a heterocycle substituted with one or more groups selected from. In some embodiments, R 3 is -N(R 19 ) is a complex ring substituted with 2, and each R 19 This is either non-substitutive or substituted C 1~6 Selected independently from alkyl and H. In some embodiments, R 3 This is a heterocycle substituted with -NH2.

[0108] In some embodiments, R 3 teeth, [ka] Selected from, None of these are non-substituted, or one or more R 10It has been replaced with.

[0109] In some embodiments, R 3 teeth, [ka] Selected from.

[0110] In some embodiments, R 3 teeth, [ka] Selected from, None of these are non-substituted, or one or more R 10 It has been replaced with.

[0111] In some embodiments, R 2 or R 3 It includes an amino moiety (e.g., -NRR'). In some embodiments, R 2 or R 3 The amino portion is (i.e., -N(R) 17 )2 or -N(R 19 )2) is replaced.

[0112] In some embodiments, R 2 and R 3 This refers to the unsubstituted or one or more R atoms, along with the atom to which they are bonded (for example, a nitrogen atom). 11 It forms a heterocycle substituted with R. In some embodiments, R 2 and R 3 This refers to a 4-9 membered heterocycle having, together with the bonded atom (e.g., a nitrogen atom), 0-2 further heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the heterocycle is unsubstituted or has one or more R 11 It is replaced by R 2 and R 3This refers to a 4-7 membered heterocycle having 0-1 further heteroatoms independently selected from nitrogen, oxygen, and sulfur, together with the bonded atom (e.g., a nitrogen atom), wherein the heterocycle is unsubstituted or has one or more R 11 It is replaced by R 2 and R 3 This refers to a 7-9 membered heterocycle having, together with the bonded atom (e.g., a nitrogen atom), 0-2 further heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the heterocycle is unsubstituted or has one or more R 11 It is replaced by. In some such embodiments, each R 11 is -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )2, -C(O)(C 1~6 Alkyl)N(R 19 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 20 It is replaced by. In some embodiments, each R 11 -NH2, -NHCH3, -C(O)CH3, -C(O)NH2, -C(O)CH2NH2, -CH3, -CH2CH3, -CH(CH3)2, -CH2CN, -CH2C(O)NH2, -C(NH)NHCN, -CH2OH, and [ka] It is selected independently of others.

[0113] In some embodiments, R 2 and R 3 These, along with the atoms to which they are bonded, form a heterocycle selected from the following: [ka] None of these are non-substituted or one or more R 11 It has been replaced with.

[0114] In some embodiments, R 2 and R 3 These, along with the atoms to which they are bonded, form a heterocycle selected from the following: [ka]

[0115] In some embodiments, R 2 and R 3 These atoms, together with the atoms to which they are bonded, form a heterocycle with the following structure: [ka] None of these are non-substituted or one or more R 11 It is replaced by R 2 and R 3 These atoms, together with the atoms to which they are bonded, form a heterocycle with the following structure: [ka] None of these are non-substituted or one or more R 11 It is replaced by R 2 and R 3 These atoms, together with the atoms to which they are bonded, form a heterocycle with the following structure: [ka]

[0116] In some embodiments, R 2 and R 3 These atoms, together with the atoms to which they are bonded, form a heterocycle with the following structure: [ka] None of these are non-substituted or one or more R 11 It has been replaced with.

[0117] In some embodiments, R 2 and R 3 These atoms, together with the atoms to which they are bonded, form a heterocycle with the following structure: [ka]

[0118] In some embodiments, R 2 and R 3 This refers to the nitrogen atom to which they are bonded, and whether it is unsubstituted or has one or more R 11 A heterocycle is formed by substitution with a group (e.g., -N(R)) which contains a further nitrogen atom and / or an amino moiety. 19 )2) is replaced.

[0119] In some embodiments, R 4 is H. In some embodiments, R 4 is a halogen. In some embodiments, R 4 は-OR 12 In some embodiments, R 4 It is -OCH3.

[0120] In some embodiments, R 5 is either unsubstituted or one or more R 14 It is a 3-6 member carbon ring substituted with R. In some embodiments, R 5 is either unsubstituted or one or more R 14 (For example, one or more -OR 12 It is a 3-4 member carbon ring substituted with (or -CN). In some embodiments, R 5 is either unsubstituted or one or more R 14 A 3-6 membered heterocycle substituted with (for example, a 3-6 membered heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur). In some embodiments, R 5 is either unsubstituted or one or more R 14It is a 5 or 6-membered aryl or heteroaryl moiety substituted with R. In some embodiments, R 5 R is phenyl. In some embodiments, R 5 is either unsubstituted or one or more R 14 (For example, C 1~6 It is a 5-6 member heteroaryl substituted with alkyl. In some embodiments, R 5 is pyridyl, furanyl, or imidazolyl, each unsubstituted or with one or more R 14 (For example, C 1~6 It is substituted with alkyl. In some embodiments, R 5 It is furanyl.

[0121] In some embodiments, R 5 is either unsubstituted or one or more R 13 C replaced by 1~6 Selected from alkyl groups. In some embodiments, R 5 This is an unsubstituted C such as methyl or ethyl. 1~6 Selected from alkyl groups. In some embodiments, R 5 C is a C substituted with one or more halogens or -CN. 1~6 Selected from alkyl groups. In some embodiments, R 5 R is selected from -CF3, -CF2H, and -CH2CN. In some embodiments, R 5 The following are selected from -CH3, -CH2CH3, -CF2H, -CF3, -CF2CH3, and -CH2CN.

[0122] In some embodiments, R 5 C 2~6 It is an alkenyl. In some embodiments, R 5 C 2~6 This is an alkynyl (for example, ethynyl).

[0123] In some embodiments, R 5 is -OR 12 Selected from, however, R 12is either unsubstituted or one or more R 13 C replaced by 1~6 Selected from alkyl groups. In some embodiments, R 5 It is -OCH3, -OCF3, or -OCF2H.

[0124] In some embodiments, R 5 It is -CN.

[0125] In some embodiments, R 5 is a halogen. In some embodiments, R 5 It is either Cl or F.

[0126] In some embodiments, R 5 It is hydrogen.

[0127] In some embodiments, R 7 is a halogen. In some embodiments, R 7 is Cl or F. In some embodiments, R 7 is -OR 12 And, however, R 12 is H and unsubstituted or one or more R 13 C replaced by 1~6 Selected from alkyl groups. In some embodiments, R 7 is -OH, -OCH3, or -OCH2CF3. In some embodiments, R 7 is -CN. In some embodiments, R 7 It is hydrogen.

[0128] In some embodiments, R 5 and R 7 Both are halogens. In some embodiments, R 5 and R 7 Both are selected from Cl and F. In some embodiments, R 4 , R 5 , and R 7 Each of these is independently a halogen. In some embodiments, R 4 , R5 , and R 7 These are selected from Cl and F, respectively.

[0129] In some embodiments, R 6 is a bicyclic aryl or bicyclic heteroaryl, wherein the aryl or heteroaryl is unsubstituted or has one or more R 15 It is replaced by R 6 is a bicyclic aryl or bicyclic heteroaryl, where the aryl or heteroaryl is one or more R 15 It has been replaced with.

[0130] In some embodiments, R 6 is one or more R 15 It is a biring aryl substituted with R. In some embodiments, R 6 is one or more R 15 It is naphthyl substituted with R. In some embodiments, 6 teeth, [ka] Selected from.

[0131] In some embodiments, R 6 is either unsubstituted or one or more R 15 It is a 9-10 member heteroaryl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur substituted with R. In some embodiments, R 6 is one or more R 15 It is a bicyclic heteroaryl substituted with R. In some embodiments, R 6 is one or more R 15 A nine-membered heteroaryl having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, substituted with R. In some such embodiments, at least one R 15 is -N(R 12 )2 (for example, -NH2). In some embodiments, at least one R 15is a halogen (e.g., F). In some embodiments, each R 15 These are halogen, -CN, and -N(R) 12 )2 is selected independently. In some embodiments, R 6 is at least two R 15 (For example, it is substituted with at least halogen and -NH2)

[0132] In some embodiments, R 6 teeth, [ka] Selected from, None of these are non-substituted or one or more R 15 It has been replaced with.

[0133] In some embodiments, R 6 teeth, [ka] Selected from.

[0134] In some embodiments, R 6 teeth, [ka] Selected from.

[0135] In some embodiments, R 6 teeth: [ka]

[0136] In some embodiments, R 6 teeth, [ka] That is the case.

[0137] In some embodiments, R 6 is phenyl or heteroaryl, where the phenyl or heteroaryl is unsubstituted or has one or more R 15 It has been replaced with.

[0138] In some embodiments, R 6 is unsubstituted or one or more R 15 It is a phenyl substituted with R. In some such embodiments, each R 15 is halogen, -OR 12 -CN, and -N(R 12 )2 is selected independently. In some embodiments, R 6 teeth, [ka] Selected from.

[0139] In some embodiments, R 6 is unsubstituted or one or more R 15 It is a monocyclic 5-6 member heteroaryl substituted with R. In some embodiments, R 6 is unsubstituted or one or more R 15 It is pyridyl substituted with. In some embodiments, each R 15 N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 It is replaced by R 6 teeth, [ka] That is the case.

[0140] In some embodiments, (i)R 2 is C 1~6 Selected from alkyl and 3- to 6-membered carbon rings, however, C 1~6 Alkyl and 3-6 membered carbon rings are unsubstituted or have one or more R 13(ii)R is replaced by 3 The elements are selected from carbocyclic and heterocyclic rings, and the carbocyclic or heterocyclic ring is either unsubstituted or has one or more R components. 10 It is replaced by R 4 is H. In some embodiments, R 7 is a halogen (e.g., F). In some embodiments, R 5 C 1~6 Selected from alkyl, halogen, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle are unsubstituted or have one or more R 14 It is replaced by R 6 is one or more R 15 It is a bicyclic heteroaryl substituted with R. In some embodiments, R 6 teeth, [ka] That is the case.

[0141] In some embodiments, R 1 は-OR 8 And R 8 is a heterocycle or alkyl heterocycle. In some embodiments, R 1 teeth, [ka] Selected from.

[0142] In some embodiments, R 1 teeth, [ka] Selected from.

[0143] In some embodiments, (i)R 2 is either unsubstituted or one or more R 13 C replaced by 1~6Selected from alkyl (e.g., methyl or ethyl), (ii)R 3 is either unsubstituted or one or more R 10 Selected from carbon rings substituted with . In some embodiments, (i)R 2 is either unsubstituted or one or more R 13 C replaced by 1~6 Selected from alkyl (e.g., methyl or ethyl), (ii)R 3 is either unsubstituted or one or more R 10 Selected from a complex ring substituted with . In some embodiments, (i)R 2 is either unsubstituted or one or more R 13 A 3-6 membered carbon ring (e.g., cyclopropyl) substituted with (ii)R 3 is either unsubstituted or one or more R 10 Selected from carbon rings substituted with . In some embodiments, (i)R 2 is either unsubstituted or one or more R 13 A 3-6 membered carbon ring (e.g., cyclopropyl) substituted with (ii)R 3 is either unsubstituted or one or more R 10 It is selected from a complex ring substituted with .

[0144] In one embodiment, the present disclosure relates to a compound represented by formula IA: [ka] or provides salts thereof (e.g., pharmaceutically acceptable salts), esters, tautomers, prodrugs, zwitterionic forms, or stereoisomers, provided that R 1 , R 3 , R 4 , R 5 , R 6 , and R 7 The compounds of formula I are as defined above and are described herein as classes and subclasses, both individually and in combination. In some embodiments, the disclosure provides compounds of formula IA or salts thereof (e.g., pharmaceutically acceptable salts).

[0145] In some embodiments, the present disclosure provides compounds of formula IA [wherein, R 1 is -OR 8 A 4-6 member heterocycle containing a nitrogen atom, selected from H, wherein the heterocycle is unsubstituted or has one or more R 16 Replaced by, R 3 C 1~6 Selected from alkyl, carbocyclic, and heterocyclic elements, however any C 1~6 Alkyl is one or more R 9 Substituted by, and the carbocyclic or heterocyclic ring is unsubstituted or has one or more R 10 Replaced by, R 4 H, halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 5 H, halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 6 is one or more R 15 It is a bicyclic heteroaryl substituted with, R 7 is halogen, -OR 12 Selected from , -CN, and H, R 8The component is selected from heterocycles and alkyl heterocycles, and either is unsubstituted or has one or more R 16 Substituted with, the alkyl portion of any alkyl heterocycle is C 1~6 Selected from alkyl groups, Each R 9 is -N(R 17 )2, -N(R 17 )C(O)C 1~6 Alkyl and -OR 17 Selected independently of, however, any C 1~6 Alkyl is either unsubstituted or has one or more R 18 Replaced by, Each R 10 is -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )2, -C(O)(C 1~6 Alkyl)N(R 19 )2, -(C 1~6 Alkyl)C(O)N(R 19 )2, -C(NR 19 )NR 19 CN, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 20 Replaced by, Each R 12 C 1~6 Alkyl, C 2~6 Alkenyl and H are selected independently, except for any C 1~6 Alkyl or C 2~6 Alkenyls are either unsubstituted or have one or more R 13 Replaced by, Each R 13 is -OR 22 -CN, -N(R 22 )2, and selected independently from halogens, Each R 14 Halogen, N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 15 Halogen, N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 16 Halogen, -N(R 12 )2, and C 1~6 Alkyl and -OR 12 Selected independently of, however, any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 17 C 1~6 Selected independently from alkyl and H, Each R 18 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 19 C 1~6 Selected independently from alkyl and H, except for any C 1~6 Alkyl is either unsubstituted or has one or more R 21 Replaced by, Each R 20 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 21 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 22 C 1~6 Alkyl, C 2~6 [Selected independently of alkenyl and H].

[0146] In some embodiments, R 3The carbon ring and heterocycle are selected, provided that the carbon ring or heterocycle is unsubstituted or has one or more R 10 It is replaced by R 3 is either unsubstituted or one or more R 10 It is a 3- to 6-membered carbon ring or heterocycle substituted with R. In some embodiments, R 3 is either unsubstituted or one or more R 10 It is a 3- to 7-membered carbon ring substituted with R. In some embodiments, R 3 is either unsubstituted or one or more R 10 It is a 3- to 7-member complex ring substituted with .

[0147] In some embodiments, R 3 It is a carbon ring, and the carbon ring is either unsubstituted or has one or more R 10 It is replaced by R 3 It is a polycyclic carbon ring. In some embodiments, R 3 It is a monocyclic carbon ring. In some embodiments, R 3 is -N(R 19 A carbon ring substituted with )2, where each R 19 This is either non-substitutive or substituted C 1~6 Selected independently from alkyl and H. In some embodiments, R 3 This is a carbon ring substituted with -NH2.

[0148] In some embodiments, R 3 is a heteroalgebra, and a heteroalgebra is either unsubstituted or has one or more R 10 It is replaced by R 3 It is a polycyclic heteroalgebra. In some embodiments, R 3 It is a monocyclic heterocycle. In some embodiments, the heterocycle contains one or more nitrogen atoms. In some embodiments, R 3 is -N(R 19 ) is a heterogeneous ring substituted with 2, where each R 19 This is either non-substitutive or substituted C 1~6Selected independently from alkyl and H. In some embodiments, R 3 This is a heterocycle substituted with -NH2.

[0149] In some embodiments, R 3 teeth, [ka] Selected from, None of these are non-substituted or one or more R 10 It has been replaced with.

[0150] In some embodiments, R 3 teeth, [ka] Selected from, None of these are non-substituted or one or more R 10 It has been replaced with.

[0151] In some embodiments, R 3 teeth, [ka] Selected from, None of these are non-substituted or one or more R 10 It has been replaced with.

[0152] In some embodiments, R 3 is one or more R 9 C replaced by 1~6 Selected from alkyl groups. In some embodiments, R 3 C 1~6 alkyl-N(R 17 ) Selected from 2, however each R 17 C 1~6 Selected independently from alkyl and H. In some embodiments, R 3 C is substituted with -NH2. 1~6 It is alkyl.

[0153] In some embodiments, R 3 teeth, [ka] Selected from.

[0154] In some embodiments, R 3 It includes an amino moiety (e.g., -NRR'). In some embodiments, the amino moiety is a component of a heterocycle. In some embodiments, the amino moiety is added to a carbocyclic or heterocycle. In some embodiments, the amino moiety is a primary amine (e.g., -NH2). In some embodiments, the amino moiety is a secondary amine (e.g., -NHR).

[0155] In some embodiments, R 1 It is hydrogen.

[0156] In some embodiments, R 1 is -OR 8 In some embodiments, R 8 It is a complex algebra. In some embodiments, R 8 It is an alkyl heterocycle.

[0157] In some embodiments, R 8 is either unsubstituted or one or more R 16 It includes a 3- to 6-membered heterocycle substituted with . In some embodiments, the heterocycle or alkyl heterocycle comprises 4- to 8 members including at least one heteroatom selected from N, O, and S. In some embodiments, R 8 It comprises a heterocycle containing at least one nitrogen atom. In some embodiments, the heterocycle is one or more R 16 Includes substituents. In some embodiments, at least one R 16 is -OR 12 And, however, R 12 C 1~6 Alkyl, C 2~6Alkenyls and H are selected independently. In some embodiments, at least one R 16 It is -OCH3.

[0158] In some embodiments, R 1 teeth, [ka] Selected from, However, R a and R b Each of them is independent of halogen and C 1~6 Alkyl, -OR 12 , and H are selected, and any C 1~6 Alkyl is either unsubstituted or has one or more R 13 It is replaced by R a is a halogen. In some embodiments, R a In some embodiments, R a is either unsubstituted or one or more R 13 C replaced by 1~6 It is alkyl. In some embodiments, R a is, -OC 1~6 It is alkyl. In some embodiments, R a H is H. In some embodiments, R b H is H. In some embodiments, R b is a halogen. In some embodiments, R b In some embodiments, R b is either unsubstituted or one or more R 13 C replaced by 1~6 It is alkyl. In some embodiments, R 1 teeth, [ka] Selected from.

[0159] In some embodiments, R 1 teeth, [ka] Selected from.

[0160] In some embodiments, R 1 teeth, [ka] Selected from, However, each R a is halogen, C 1~6 Alkyl, -OR 12 , and H are selected independently, R c is C 1~6 Selected from alkyl, however C 1~6 Alkyl is either unsubstituted or has one or more R 13 It is replaced by R 1 teeth, [ka] Selected from.

[0161] In some embodiments, R 1 teeth, [ka] Selected from.

[0162] In some embodiments, R 1 teeth, [ka] Selected from.

[0163] In some embodiments, R 1 teeth, [ka] Selected from.

[0164] In some embodiments, R 1The heteroalgebra is either unsubstituted or has one or more R 16 It is a 4- to 6-membered heterocycle containing nitrogen atoms substituted with R. In some embodiments, R 1 teeth, [ka] Selected from.

[0165] In some embodiments, R 6 teeth, [ka] Selected from.

[0166] [ka] Selected from.

[0167] In some embodiments, R 6 teeth, [ka] That is the case.

[0168] In some embodiments, R 4 is H. In some embodiments, R 4 It is a halogen.

[0169] In some embodiments, R 5 is a 3-6 member carbon ring. In some embodiments, R 5 R is a 3- to 6-membered complex ring. In some embodiments, R 5 is a 5 or 6-membered aryl or heteroaryl portion. In some embodiments, R 5 It is Fran.

[0170] In some embodiments, R 5 is a halogen. In some embodiments, R 5is Cl or F. In some embodiments, R 7 is a halogen. In some embodiments, R 7 is Cl or F. In some embodiments, R 5 and R 7 Both are halogens. In some embodiments, R 5 and R 7 Both are selected from Cl and F. In some embodiments, R 4 , R 5 , and R 7 Each of these is independently a halogen. In some embodiments, R 4 , R 5 , and R 7 These are selected from Cl and F, respectively.

[0171] In some embodiments, (i)R 3 A is a 4 or 5-membered heterocycle containing one nitrogen atom, and the heterocycle is unsubstituted or has one or more R 10 (ii)R is replaced by 1 は-OR 8 And, however, R 8 (iii)R 4 is hydrogen. In some embodiments, (iv)R 7 is a halogen. In some embodiments, R 3 teeth, [ka] Selected from, None of these are non-substituted or one or more R 10 It is replaced by R 1 teeth, [ka] Selected from, However, each R a and Rb is independently selected from halogen, C 1~6 alkyl, -OR 12 , and H. In some embodiments, R 1 is

Chemical formula

[0172] In some embodiments, R 7 is F. In some embodiments, R 6 is

Chemical formula

[0173] In some embodiments, R 5 is selected from -CF3, -Cl, -CH2CN, furan, and phenyl. In some embodiments, (i) R 3 is a 4-member heterocyclic ring containing one nitrogen atom (e.g., azetidine), and the heterocyclic ring is unsubstituted or substituted with one or more R 10 , (ii) R 1 is -OR 8 , provided that R 8 is an alkyl heterocyclic ring, and the heterocyclic ring is an 8-membered ring system containing one nitrogen atom, (iii) R 4 is H, (iv) R 7 is halogen. In some embodiments, (i) R 3 is a 5-member heterocyclic ring containing one nitrogen atom (e.g., azetidine), and the heterocyclic ring is unsubstituted or substituted with one or more R 10 , (ii) R 1 is -OR 8 , provided that R 8 is an alkyl heterocyclic ring, and the heterocyclic ring is an 8-membered ring system containing one nitrogen atom, (iii) R 4 is H, (iv) R 7 is halogen.

[0174] In some embodiments, (i) R3 is a 4- or 5-membered heterocyclic ring containing one nitrogen atom, and the heterocyclic ring is unsubstituted or substituted with one or more R 10 , (ii) R 1 is -OR 8 , provided that R 8 is a heterocyclic ring or an alkyl heterocyclic ring, and the heterocyclic ring of the heterocyclic ring or alkyl heterocyclic ring is a 4- to 8-membered ring system such as a 5-membered ring system containing one nitrogen atom. In some embodiments, (iii) R 4 is H. In some embodiments, (iv) R 7 is a halogen. In some embodiments, R 3 is [[ID=1,8]]

Chem.

Chem.

Chem.

[0175] In some embodiments, R 7 is F. In some embodiments, R 6 is

Chem.

[0176] In some embodiments, R 5 (i)R 3 It is a four-membered heterocycle containing one nitrogen atom (e.g., azetidine), and the heterocycle is unsubstituted or has one or more R atoms. 10 (ii)R is replaced by 1 は-OR 8 And, however, R 8 (iii)R is an alkyl heterocycle, and a heterocycle is a five-membered ring system containing one nitrogen atom. 4 (iv)R 7 is a halogen. In some embodiments, (i)R 3 It is a five-membered heterocycle containing one nitrogen atom (e.g., pyrrolidine), and the heterocycle is unsubstituted or has one or more R 10 (ii)R is replaced by 1 は-OR 8 And, however, R 8 (iii)R is an alkyl heterocycle, and a heterocycle is a five-membered ring system containing one nitrogen atom. 4 (iv)R 7 It is a halogen.

[0177] In some embodiments, (i)R 3 is either unsubstituted or one or more R 10 A bridged carbocyclic or heterocyclic system substituted with (ii)R 1 は-OR 8 And, however, R 8 (iii)R 4 is H. In some embodiments, (iv)R 7 is a halogen. In some embodiments, (i)R 3 is either unsubstituted or one or more R 10 (ii)R is a heterogeneous system substituted with 1 は-OR8 And, however, R 8 (i)R 3 is either unsubstituted or one or more R 10 A carbocyclic system substituted with (ii)R 1 は-OR 8 And, however, R 8 R is a heterocycle or alkyl heterocycle, and the heterocycle of the heterocycle or alkyl heterocycle is a 4- to 8-membered ring system containing one nitrogen atom. In some embodiments, R 3 teeth, [ka] Selected from.

[0178] In some embodiments, R 1 teeth, [ka] Selected from, However, each R a and R b is halogen, C 1~6 Alkyl, -OR 12 , and H are selected independently, R c is C 1~6 Selected from alkyl, however C 1~6 Alkyl is either unsubstituted or has one or more R 13 It is replaced by R 1 teeth, [ka] Selected from.

[0179] In some embodiments, R 1 teeth, [ka] is selected from.

[0180] In some embodiments, R 7 is F. In some embodiments, R 5 is -CF3. In some embodiments, R 6 is

Chemical formula

[0181] In some embodiments, (i) R 3 is an unsubstituted or crosslinked heterocyclic ring system substituted with one or more R 10 , (ii) R 1 is -OR 8 , provided that R 8 is an alkyl heterocycle, and the heterocycle is a 4- to 8-membered ring system containing one nitrogen atom, (iii) R 4 is H, (iv) R 7 is a halogen.

[0182] In some embodiments, (i) R 3 is selected from C 1~6 alkyl-N(R 17 )2, (ii) R 1 is -OR 8 , provided that R 8 is an alkyl heterocycle, and the heterocycle is a 4- to 8-membered ring system containing one nitrogen atom. In some embodiments, (iii) R 4 is H. In some embodiments, (iv) R 7 is a halogen. In some embodiments, R 3 is

Chemical formula

[0183] In some embodiments, (i) R 3 is selected from C2 alkyl-N(R 17 )2, (ii) R 1 is -OR8 And, however, R 8 (iii)R is an alkyl heterocycle, and a heterocycle is a 4-8 membered ring system containing one nitrogen atom. 4 (iv)R 7 is a halogen. In some embodiments, R 6 teeth, [ka] That is the case.

[0184] In some embodiments, the present disclosure relates to compounds of formula IA1: [ka] or provides salts thereof (e.g., pharmaceutically acceptable salts), esters, tautomers, prodrugs, zwitterionic forms, or stereoisomers, provided that R 3 , R 4 , R 5 , R 6 , and R 7 The compounds are as defined above for formula I and are described herein as classes and subclasses, both individually and in combination. In some embodiments, the present disclosure provides compounds of formula IA1 or salts thereof (e.g., pharmaceutically acceptable salts).

[0185] In some embodiments, the present disclosure provides compounds according to formula IA1 [wherein, R 3 C 1~6 Selected from alkyl, carbocyclic, and heterocyclic elements, however any C 1~6 Alkyl is one or more R 9 Substituted by, and the carbocyclic or heterocyclic ring is unsubstituted or has one or more R 10 Replaced by, R 4 H, halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 5 is halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 6 is one or more R 15 It is a bicyclic heteroaryl substituted with, R 7 is halogen, -OR 12 Selected from , -CN, and H, Each R 9 is -N(R 17 )2, -N(R 17 )C(O)C 1~6 Alkyl and -OR 17 Selected independently of, however, any C 1~6 Alkyl is either unsubstituted or has one or more R 18 Replaced by, Each R 10 is -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )2, -C(O)(C 1~6 Alkyl)N(R 19 )2, -(C 1~6 Alkyl)C(O)N(R 19 )2, -C(NR 19 )NR 19 CN, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R20 Replaced by, Each R 11 is -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )2, -C(O)(C 1~6 Alkyl)N(R 19 )2, -(C 1~6 Alkyl)C(O)N(R 19 )2, -C(NR 19 )NR 19 CN, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 20 Replaced by, Each R 12 C 1~6 Alkyl, C 2~6 Alkenyl and H are selected independently, except for any C 1~6 Alkyl or C 2~6 Alkenyls are either unsubstituted or have one or more R 13 Replaced by, Each R 13 is -OR 22 -CN, -N(R 22 )2, and selected independently from halogens, Each R 14 Halogen, N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 15 Halogen, N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 17 C 1~6 Selected independently from alkyl and H, Each R 18 -OH, -OC 1~6Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 19 C 1~6 Selected independently from alkyl and H, except for any C 1~6 Alkyl is either unsubstituted or has one or more R 21 Replaced by, Each R 20 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 21 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 22 C 1~6 Alkyl, C 2~6 [Selected independently of alkenyl and H].

[0186] In some embodiments, R 3 The carbon ring and heterocycle are selected, provided that the carbon ring or heterocycle is unsubstituted or has one or more R 10 It is replaced by R 3 is either unsubstituted or one or more R 10 It is a 3- to 6-membered carbon ring or heterocycle substituted with R. In some embodiments, R 3 is either unsubstituted or one or more R 10 It is a 3- to 7-membered carbon ring substituted with R. In some embodiments, R 3 is either unsubstituted or one or more R 10 It is a 3- to 7-member complex ring substituted with .

[0187] In some embodiments, R 3 teeth, [ka] Selected from, none of these are non-substituted or one or more R 10 It has been replaced with.

[0188] In some embodiments, R 3 teeth, [ka] Selected from, None of these are non-substituted or one or more R 10 It has been replaced with.

[0189] In some embodiments, R 3 teeth, [ka] Selected from, None of these are non-substituted or one or more R 10 It has been replaced with.

[0190] In some embodiments, R 3 is one or more R 9 C replaced by 1~6 Selected from alkyl groups. In some embodiments, R 3 C 1~6 alkyl-N(R 17 ) Selected from 2, however each R 17 C 1~6 Selected independently from alkyl and H. In some embodiments, R 3 C is substituted with -NH2. 1~6 It is alkyl.

[0191] In some embodiments, R 3 teeth, [ka] Selected from.

[0192] In some embodiments, R 3It includes an amino moiety (e.g., -NRR'). In some embodiments, the amino moiety is a component of a heterocycle. In some embodiments, the amino moiety is added to a carbocyclic or heterocycle. In some embodiments, the amino moiety is a primary amine (e.g., -NH2). In some embodiments, the amino moiety is a secondary amine (e.g., -NHR).

[0193] In some embodiments, R 6 teeth, [ka] Selected from.

[0194] In some embodiments, R 6 teeth, [ka] Selected from.

[0195] In some embodiments, R 6 teeth, [ka] That is the case.

[0196] In some embodiments, R 4 is H. In some embodiments, R 4 It is a halogen.

[0197] In some embodiments, R 5 is a 3-6 member carbon ring. In some embodiments, R 5 R is a 3- to 6-membered complex ring. In some embodiments, R 5 is a 5 or 6-membered aryl or heteroaryl portion. In some embodiments, R 5 It is Fran.

[0198] In some embodiments, R 5 is a halogen. In some embodiments, R5 is Cl or F. In some embodiments, R 7 is a halogen. In some embodiments, R 7 is Cl or F. In some embodiments, R 5 and R 7 Both are halogens. In some embodiments, R 5 and R 7 Both are selected from Cl and F. In some embodiments, R 4 , R 5 , and R 7 Each of these is independently a halogen. In some embodiments, R 4 , R 5 , and R 7 These are selected from Cl and F, respectively.

[0199] In some embodiments, the present disclosure relates to compounds of formula IA2: [ka] or provides salts thereof (e.g., pharmaceutically acceptable salts), esters, tautomers, prodrugs, zwitterionic forms, or stereoisomers, provided that R 3 , R 4 , R 5 , R 6 , R 7 , and R 8 The compounds are as defined above for formula I and are described herein as classes and subclasses, both individually and in combination. In some embodiments, the present disclosure provides compounds of formula IA2 or salts thereof (e.g., pharmaceutically acceptable salts).

[0200] In some embodiments, the present disclosure provides compounds of formula IA2 [wherein, R 3 C 1~6 Selected from alkyl, carbocyclic, and heterocyclic elements, however any C 1~6 Alkyl is one or more R 9 Substituted by, and the carbocyclic or heterocyclic ring is unsubstituted or has one or more R 10Replaced by, R 4 H, halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 5 is halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 6 is one or more R 15 It is a bicyclic heteroaryl substituted with, R 7 is halogen, -OR 12 Selected from , -CN, and H, R 8 The component is selected from heterocycles and alkyl heterocycles, and either is unsubstituted or has one or more R 16 Replaced by, Each R 9 is -N(R 17 )2, -N(R 17 )C(O)C 1~6 Alkyl and -OR 17 Selected independently of, however, any C 1~6 Alkyl is either unsubstituted or has one or more R 18 Replaced by, Each R 10 is -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19)2, -C(O)(C 1~6 Alkyl)N(R 19 )2, -(C 1~6 Alkyl)C(O)N(R 19 )2, -C(NR 19 )NR 19 CN, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 20 Replaced by, Each R 12 C 1~6 Alkyl, C 2~6 Alkenyl and H are selected independently, except for any C 1~6 Alkyl or C 2~6 Alkenyls are either unsubstituted or have one or more R 13 Replaced by, Each R 13 is -OR 22 -CN, -N(R 22 )2, and selected independently from halogens, Each R 14 Halogen, N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 15 Halogen, N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 16 Halogen, -N(R 12 )2, and C 1~6 Alkyl and -OR 12 Selected independently of, however, any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 17 C 1~6 Selected independently from alkyl and H, Each R 18 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 19 C 1~6 Selected independently from alkyl and H, except for any C 1~6 Alkyl is either unsubstituted or has one or more R 21 Replaced by, Each R 20 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 21 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 22 C 1~6 Alkyl, C 2~6 [Selected independently of alkenyl and H].

[0201] In some embodiments, R 8 is either unsubstituted or one or more R 16 It includes 3- to 6-membered complex rings substituted with .

[0202] In some embodiments, -OR 8 teeth, [ka] Selected from.

[0203] In some embodiments, -OR 8 teeth, [ka] Selected from.

[0204] In some embodiments, R 3 The carbon ring and heterocycle are selected, provided that the carbon ring or heterocycle is unsubstituted or has one or more R 10 It is replaced by R 3 is either unsubstituted or one or more R 10 It is a 3- to 6-membered carbon ring or heterocycle substituted with R. In some embodiments, R 3 teeth, [ka] Selected from, None of these are non-substituted or one or more R 10 It has been replaced with.

[0205] In some embodiments, R 3 teeth, [ka] Selected from, None of these are non-substituted or one or more R 10 It has been replaced with.

[0206] In some embodiments, R 3 is one or more R 9 C replaced by 1~6 Selected from alkyl groups. In some embodiments, R 3 C 1~6 alkyl-N(R 17 ) Selected from 2. In some embodiments, R 3 teeth, [ka] Selected from.

[0207] In some embodiments, R 3 It contains an amino portion (e.g., -NRR').

[0208] In some embodiments, R 6 teeth, [ka] Selected from.

[0209] In some embodiments, R 6 teeth, [ka] Selected from.

[0210] In some embodiments, R 6 teeth, [ka] That is the case.

[0211] In some embodiments, R 4 is H. In some embodiments, R 4 It is a halogen.

[0212] In some embodiments, R 5 is a 3-6 member carbon ring. In some embodiments, R 5 R is a 3- to 6-membered complex ring. In some embodiments, R 5 is a 5 or 6-membered aryl or heteroaryl portion. In some embodiments, R 5 It is Fran.

[0213] In some embodiments, R 5 is a halogen. In some embodiments, R 5 is Cl or F. In some embodiments, R 7 is a halogen. In some embodiments, R 7 is Cl or F. In some embodiments, R 5 and R 7 Both are halogens. In some embodiments, R 5 and R7 Both are selected from Cl and F. In some embodiments, R 4 , R 5 , and R 7 Each of these is independently a halogen. In some embodiments, R 4 , R 5 , and R 7 These are selected from Cl and F, respectively.

[0214] In another aspect, this disclosure relates to compounds of formula IB: [ka] or provides salts thereof (e.g., pharmaceutically acceptable salts), esters, tautomers, prodrugs, zwitterionic forms, or stereoisomers, provided that R 1 , R 4 , R 5 , R 6 , and R 7 The elements are as defined above for formula I, and are described herein as classes and subclasses, both individually and in combination, and ring A is either unsubstituted or has one or more R 11 It is a heterocycle substituted with . In some embodiments, the present disclosure provides compounds of formula IB or salts thereof (e.g., pharmaceutically acceptable salts).

[0215] In some embodiments, the present disclosure provides compounds of formula IB [wherein, R 1 is -OR 8 A 4-6 member heterocycle containing a nitrogen atom, selected from H, wherein the heterocycle is unsubstituted or has one or more R 16 Replaced by, Ring A is either unsubstituted or contains one or more R 11 It is a complex ring substituted with, R 4 H, halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 5 is halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 6 is one or more R 15 It is a bicyclic heteroaryl substituted with, R 7 is halogen, -OR 12 Selected from , -CN, and H, R 8 The component is selected from heterocycles and alkyl heterocycles, and either is unsubstituted or has one or more R 16 Replaced by, Each R 11 is -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )2, -C(O)(C 1~6 Alkyl)N(R 19 )2, -(C 1~6 Alkyl)C(O)N(R 19 )2, -C(NR 19 )NR 19 CN, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 20 Replaced by, Each R 12 C 1~6 Alkyl, C 2~6Alkenyl and H are selected independently, except for any C 1~6 Alkyl or C 2~6 Alkenyls are either unsubstituted or have one or more R 13 Replaced by, Each R 13 is -OR 22 -CN, -N(R 22 )2, and selected independently from halogens, Each R 14 Halogen, N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 15 Halogen, N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 16 Halogen, -N(R 12 )2, and C 1~6 Alkyl and -OR 12 Selected independently of, however, any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 19 C 1~6 Selected independently from alkyl and H, except for any C 1~6 Alkyl is either unsubstituted or has one or more R 21 Replaced by, Each R 20 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 21 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R22 C 1~6 Alkyl, C 2~6 [Selected independently of alkenyl and H].

[0216] In some embodiments, ring A is unsubstituted or has one or more R 11 It is a monocyclic heterocyclic ring substituted with R. In some embodiments, ring A is unsubstituted or has one or more R 11 It is a polycyclic heterocyclic ring substituted with R. In some embodiments, ring A is unsubstituted or has one or more R 11 It is a 4- to 10-membered heteroring substituted with R. In some embodiments, ring A is unsubstituted or has one or more R 11 It is a 4- to 6-membered heterocycle substituted with . In some embodiments, ring A contains at least one nitrogen atom. In some embodiments, ring A has the following structure: [ka] None of these are non-substituted or one or more R 11 It is replaced by the following. In some embodiments, ring A has the following structure: [ka] (The ring is either unsubstituted or has one or more R 11 (It is replaced by...). In some embodiments, ring A has the following structure: [ka] (The ring is either unsubstituted or has one or more R 11 (It is replaced by...). In some embodiments, ring A has the following structure: [ka]

[0217] In some embodiments, ring A has the following structure: [ka]

[0218] In some embodiments, ring A is a 4- to 10-membered heterocycle containing at least two nitrogen atoms (e.g., an amino moiety (e.g., -NR-)) and / or substituted with a group containing an amino moiety (e.g., -NRR'). In some embodiments, ring A is a 4- to 6-membered heterocycle containing at least two nitrogen atoms (e.g., an amino moiety (e.g., -NR-)) and / or substituted with a group containing an amino moiety (e.g., -NRR').

[0219] In some embodiments, R 1 It is hydrogen.

[0220] In some embodiments, R 1 is -OR 8 In some embodiments, R 8 It is a complex algebra. In some embodiments, R 8 is an alkyl heterocycle. In some embodiments, the heterocycle or the heterocycle of the alkyl heterocycle comprises 4 to 8 members, including at least one heteroatom selected from N, O, and S. In some embodiments, R 8 It comprises a heterocycle containing at least one nitrogen atom. In some embodiments, R 8 It comprises a 4- to 8-membered heterocycle containing at least one nitrogen atom. In some embodiments, the heterocycle is one or more R 16 Includes substituents. In some embodiments, at least one R 16 is -OR 12 And, however, R 12 C 1~6 Alkyl, C 2~6 Alkenyls and H are selected independently. In some embodiments, at least one R 16 It is -OCH3.

[0221] In some embodiments, R 1 teeth, [ka] Selected from, However, R a and R b Each of them is independent of halogen and C 1~6 Alkyl, -OR 12 , and H are selected, and any C 1~6 Alkyl is either unsubstituted or has one or more R 13 It is replaced by R a is a halogen. In some embodiments, R a In some embodiments, R a is either unsubstituted or one or more R 13 C replaced by 1~6 It is alkyl. In some embodiments, R a is, -OC 1~6 It is alkyl. In some embodiments, R a H is H. In some embodiments, R b H is H. In some embodiments, R b is a halogen. In some embodiments, R b In some embodiments, R b is either unsubstituted or one or more R 13 C replaced by 1~6 It is alkyl. In some embodiments, R 1 teeth, [ka] Selected from.

[0222] In some embodiments, R 1 teeth, [ka] Selected from.

[0223] In some embodiments, R 1 teeth, [ka] Selected from, However, each R a is halogen, C 1~6 Alkyl, -OR 12 , and H are selected independently, R c is C 1~6 Selected from alkyl, R a or R c C 1~6 Alkyl is either unsubstituted or has one or more R 13 It is replaced by R 1 teeth, [ka] Selected from.

[0224] In some embodiments, R 1 teeth, [ka] Selected from.

[0225] In some embodiments, R 1 teeth, [ka] Selected from.

[0226] In some embodiments, R 1 teeth, [ka] Selected from.

[0227] In some embodiments, R 1 The heteroalgebra is either unsubstituted or has one or more R 16It is a 4- to 6-membered heterocycle containing nitrogen atoms substituted with R. In some embodiments, R 1 teeth, [ka] Selected from.

[0228] In some embodiments, R 6 teeth, [ka] Selected from.

[0229] In some embodiments, R 6 teeth, [ka] Selected from.

[0230] In some embodiments, R 6 teeth, [ka] That is the case.

[0231] In some embodiments, R 4 is H. In some embodiments, R 4 It is a halogen.

[0232] In some embodiments, R 5 is a 3-6 member carbon ring. In some embodiments, R 5 R is a 3- to 6-membered complex ring. In some embodiments, R 5 is a 5 or 6-membered aryl or heteroaryl portion. In some embodiments, R 5 It is Fran.

[0233] In some embodiments, R 5is a halogen. In some embodiments, R 5 is Cl or F. In some embodiments, R 7 is a halogen. In some embodiments, R 7 is Cl or F. In some embodiments, R 5 and R 7 Both are halogens. In some embodiments, R 5 and R 7 Both are selected from Cl and F. In some embodiments, R 4 , R 5 , and R 7 Each of these is independently a halogen. In some embodiments, R 4 , R 5 , and R 7 These are selected from Cl and F, respectively.

[0234] In some embodiments, the present disclosure relates to compounds according to formula IB1: [ka] or provides salts thereof (e.g., pharmaceutically acceptable salts), esters, tautomers, prodrugs, zwitterionic forms, or stereoisomers, provided that R 4 , R 5 , R 6 , and R 7 The elements are as defined above for formula I, and are described herein as classes and subclasses, both individually and in combination, and ring A is either unsubstituted or has one or more R 11 It is a heterocycle substituted with . In some embodiments, the present disclosure provides compounds of formula IB1 or salts thereof (e.g., pharmaceutically acceptable salts).

[0235] In some embodiments, the present disclosure provides compounds of formula IB1 [wherein, Ring A is either unsubstituted or contains one or more R 11 It is a complex ring substituted with, R 4 H, halogen, -OR 12,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 5 is halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 6 is one or more R 15 It is a bicyclic heteroaryl substituted with, R 7 is halogen, -OR 12 Selected from , -CN, and H, Each R 11 is -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )2, -C(O)(C 1~6 Alkyl)N(R 19 )2, -(C 1~6 Alkyl)C(O)N(R 19 )2, -C(NR 19 )NR 19 CN, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 20 Replaced by, Each R 12 C 1~6 Alkyl, C 2~6 Alkenyl and H are selected independently, except for any C 1~6Alkyl or C 2~6 Alkenyls are either unsubstituted or have one or more R 13 Replaced by, Each R 13 is -OR 22 -CN, -N(R 22 )2, and selected independently from halogens, Each R 14 Halogen, N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 15 Halogen, N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 19 C 1~6 Selected independently from alkyl and H, except for any C 1~6 Alkyl is either unsubstituted or has one or more R 21 Replaced by, Each R 20 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 21 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 22 C 1~6 Alkyl, C 2~6 [Selected independently of alkenyl and H].

[0236] In some embodiments, ring A is unsubstituted or has one or more R 11 It is a monocyclic heterocyclic ring substituted with R. In some embodiments, ring A is unsubstituted or has one or more R 11It is a polycyclic heterocyclic ring substituted with R. In some embodiments, ring A is unsubstituted or has one or more R 11 It is a 4- to 10-membered heteroring substituted with R. In some embodiments, ring A is unsubstituted or has one or more R 11 It is a 4- to 6-membered heterocycle substituted with . In some embodiments, ring A contains at least one nitrogen atom. In some embodiments, ring A has the following structure: [ka] It has, None of these are non-substituted or one or more R 11 It is replaced by the following. In some embodiments, ring A has the following structure: [ka] (The ring is either unsubstituted or has one or more R 11 (It is replaced by...). In some embodiments, ring A has the following structure: [ka] (The ring is either unsubstituted or has one or more R 11 (It has been replaced with...) In some embodiments, ring A has the following structure: [ka]

[0237] In some embodiments, ring A has the following structure: [ka]

[0238] In some embodiments, ring A is a 4- to 10-membered heterocycle containing at least two nitrogen atoms (e.g., an amino moiety (e.g., -NR-)) and / or substituted with a group containing an amino moiety (e.g., -NRR'). In some embodiments, ring A is a 4- to 6-membered heterocycle containing at least two nitrogen atoms (e.g., an amino moiety (e.g., -NR-)) and / or substituted with a group containing an amino moiety (e.g., -NRR').

[0239] In some embodiments, R 6 teeth, [ka] Selected from.

[0240] In some embodiments, R 6 teeth, [ka] Selected from.

[0241] In some embodiments, R 6 teeth, [ka] That is the case.

[0242] In some embodiments, R 4 is H. In some embodiments, R 4 It is a halogen.

[0243] In some embodiments, R 5 is a 3-6 member carbon ring. In some embodiments, R 5 R is a 3- to 6-membered complex ring. In some embodiments, R 5 is a 5 or 6-membered aryl or heteroaryl portion. In some embodiments, R 5 It is Fran.

[0244] In some embodiments, R5 is a halogen. In some embodiments, R 5 is Cl or F. In some embodiments, R 7 is a halogen. In some embodiments, R 7 is Cl or F. In some embodiments, R 5 and R 7 Both are halogens. In some embodiments, R 5 and R 7 Both are selected from Cl and F. In some embodiments, R 4 , R 5 , and R 7 Each of these is independently a halogen. In some embodiments, R 4 , R 5 , and R 7 These are selected from Cl and F, respectively.

[0245] In some embodiments, (i) ring A is unsubstituted or has one or more R 11 It is a piperazine or diazepane substituted with. In some embodiments, (ii)R 7 is a halogen. In some embodiments, (iii)R 4 is H. In some embodiments, ring A is [ka] Selected from, However, each R g H and C 1~6 Selected independently of alkyl, R h H, C 1~6 Alkyl, -C(O)NH2, and -C(O)C 1~6 Selected from alkylNH2. In some embodiments, at least one R g C 1~6 Alkyl, for example, C1 alkyl. In some embodiments, R h is H. In some embodiments, ring A is an unsubstituted piperazine or diazepane. In some embodiments, ring A is [ka] Selected from.

[0246] In some embodiments, R 7 is F. In some embodiments, R 5 Halogen, -CN, C 1~6 Selected from alkyl groups and 3-6 membered carbon rings, carbon ring or C 1~6 Alkyl is either unsubstituted or has one or more R 13 It is replaced by R 6 teeth, [ka] That is the case.

[0247] In some embodiments, ring A is unsubstituted or has one or more R 11 It is a piperazine substituted with R. In some embodiments, ring A is unsubstituted or has one or more R 11 This is a diazepane substituted with [the specified compound].

[0248] In some embodiments, (i) ring A is unsubstituted or has one or more R 11 It is a bridged heterocyclic ring system that is substituted with. In some embodiments, (ii)R 7 is a halogen. In some embodiments, (iii)R 4 is H. In some embodiments, ring A is [ka] Selected from, (a)R g1 and R g3 or (b)R g2 and R g3 These elements bond to each other to form a second ring containing 4-6 members, and R is not part of the second ring. g1 , R g2 , R g3 , and R g4 Either H or C 1~6Selected independently of alkyl, R h H, C 1~6 Alkyl, -C(O)NH2, and -C(O)C 1~6 Selected from alkylNH2. In some embodiments, R g1 , R g2 , R g3 , and R g4 At least one of them is C 1~6 Alkyl, for example, C1 alkyl. In some embodiments, R h H is H. In some embodiments, ring A is [ka] Selected from, However, R g2 and R g4 These two elements bond to each other to form a second ring containing 4 to 6 members, R g1 , R g3 , and R g5 H and C 1~6 Selected independently of alkyl, R h H, C 1~6 Alkyl, -C(O)NH2, and -C(O)C 1~6 Selected from alkylNH2. In some embodiments, R g1 , R g3 , and R g5 At least one of them is C 1~6 Alkyl, for example, C1 alkyl. In some embodiments, R h is H. In some embodiments, R h is -C(O)NH2. In some embodiments, ring A is [ka] Selected from.

[0249] In some embodiments, R 7 is F. In some embodiments, R 5 Halogen, -CN, C 1~6 Selected from alkyl groups and 3-6 membered carbon rings, carbon ring or C1~6 Alkyl is either unsubstituted or has one or more R 13 It is replaced by R 6 teeth, [ka] That is the case.

[0250] In some embodiments, (i) ring A is unsubstituted or has one or more R 11 A bridged heterocyclic ring system substituted with (ii)R 7 (iii)R 4 H is H.

[0251] In some embodiments, the present disclosure relates to compounds according to formula IB2: [ka] or provides salts thereof (e.g., pharmaceutically acceptable salts), esters, tautomers, prodrugs, zwitterionic forms, or stereoisomers, provided that R 4 , R 5 , R 6 , R 7 , and R 8 The elements are as defined above for formula I, and are described herein as classes and subclasses, both individually and in combination, and ring A is either unsubstituted or has one or more R 11 It is a heterocycle substituted with . In some embodiments, the present disclosure provides compounds of formula IB2 or salts thereof (e.g., pharmaceutically acceptable salts).

[0252] In some embodiments, the present disclosure provides compounds of formula IB2 [wherein, Ring A is either unsubstituted or contains one or more R 11 It is a complex ring substituted with, R 4 H, halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 5 is halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 6 is one or more R 15 It is a bicyclic heteroaryl substituted with, R 7 is halogen, -OR 12 Selected from , -CN, and H, R 8 The component is selected from heterocycles and alkyl heterocycles, and either is unsubstituted or has one or more R 16 Replaced by, Each R 11 is -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )2, -C(O)(C 1~6 Alkyl)N(R 19 )2, -(C 1~6 Alkyl)C(O)N(R 19 )2, -C(NR 19 )NR 19 CN, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 20 Replaced by, Each R 12 C 1~6 Alkyl, C 2~6Alkenyl and H are selected independently, except for any C 1~6 Alkyl or C 2~6 Alkenyls are either unsubstituted or have one or more R 13 Replaced by, Each R 13 is -OR 22 -CN, -N(R 22 )2, and selected independently from halogens, Each R 14 Halogen, N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 15 Halogen, N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 16 Halogen, -N(R 12 )2, and C 1~6 Alkyl and -OR 12 Selected independently of, however, any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 19 C 1~6 Selected independently from alkyl and H, except for any C 1~6 Alkyl is either unsubstituted or has one or more R 21 Replaced by, Each R 20 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 21 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R22 C 1~6 Alkyl, C 2~6 [Selected independently of alkenyl and H].

[0253] In some embodiments, ring A is unsubstituted or has one or more R 11 It is a monocyclic heterocyclic ring substituted with R. In some embodiments, ring A is unsubstituted or has one or more R 11 It is a polycyclic heterocyclic ring substituted with R. In some embodiments, ring A is unsubstituted or has one or more R 11 It is a 4- to 10-membered heteroring substituted with R. In some embodiments, ring A is unsubstituted or has one or more R 11 It is a 4- to 6-membered heterocycle substituted with . In some embodiments, ring A contains at least one nitrogen atom. In some embodiments, ring A has the following structure: [ka] It has, None of these are non-substituted or one or more R 11 It is replaced by the following. In some embodiments, ring A has the following structure: [ka] (The ring is either unsubstituted or has one or more R 11 (It is replaced by...). In some embodiments, ring A has the following structure: [ka] (The ring is either unsubstituted or has one or more R 11 (It is replaced by...). In some embodiments, ring A has the following structure: [ka]

[0254] In some embodiments, ring A has the following structure: [ka]

[0255] In some embodiments, ring A is a 4- to 10-membered heterocycle containing at least two nitrogen atoms (e.g., an amino moiety (e.g., -NR-)) and / or substituted with a group containing an amino moiety (e.g., -NRR'). In some embodiments, ring A is a 4- to 6-membered heterocycle containing at least two nitrogen atoms (e.g., an amino moiety (e.g., -NR-)) and / or substituted with a group containing an amino moiety (e.g., -NRR').

[0256] In some embodiments, R 8 It is a complex algebra. In some embodiments, R 8 is an alkyl heterocycle. In some embodiments, the heterocycle or the heterocycle of the alkyl heterocycle comprises 4 to 8 members, including at least one heteroatom selected from N, O, and S. In some embodiments, R 8 It comprises a heterocycle containing at least one nitrogen atom. In some embodiments, R 8 It comprises a 4- to 8-membered heterocycle containing at least one nitrogen atom. In some embodiments, R 8 is either unsubstituted or one or more R 16 It includes a 3- to 6-membered heteroring substituted with R. In some embodiments, the heteroring is one or more R 16 Includes substituents. In some embodiments, at least one R 16 is -OR 12 And, however, R 12 C 1~6 Alkyl, C 2~6 Alkenyls and H are selected independently. In some embodiments, at least one R 16 It is -OCH3.

[0257] In some embodiments, -OR 8 teeth, [ka] Selected from, However, R a and R b Each of them is independent of halogen and C 1~6 Alkyl, -OR 12 , and H are selected, and any C 1~6 Alkyl is either unsubstituted or has one or more R 13 It is replaced by R a is a halogen. In some embodiments, R a In some embodiments, R a is either unsubstituted or one or more R 13 C replaced by 1~6 It is alkyl. In some embodiments, R a is, -OC 1~6 It is alkyl. In some embodiments, R a H is H. In some embodiments, R b H is H. In some embodiments, R b is a halogen. In some embodiments, R b In some embodiments, R b is either unsubstituted or one or more R 13 C replaced by 1~6 It is alkyl. In some embodiments, -OR 8 teeth, [ka] Selected from.

[0258] In some embodiments, -OR 8 teeth, [ka] Selected from.

[0259] In some embodiments, -OR 8 teeth, [ka] Selected from, However, each R a is halogen, C 1~6 Alkyl, -OR 12 , and H are selected independently, R c is C 1~6 Selected from alkyl, R a or R c C 1~6 Alkyl is either unsubstituted or has one or more R 13 It has been replaced with. In some embodiments, -OR 8 teeth, [ka] Selected from.

[0260] In some embodiments, -OR 8 teeth, [ka] Selected from.

[0261] In some embodiments, -OR 8 teeth, [ka] Selected from.

[0262] In some embodiments, -OR 8 teeth, [ka] Selected from.

[0263] In some embodiments, R 6 teeth, [ka] Selected from.

[0264] In some embodiments, R 6 teeth, [ka] Selected from.

[0265] In some embodiments, R 6 teeth, [ka] That is the case.

[0266] In some embodiments, R 4 is H. In some embodiments, R 4 It is a halogen.

[0267] In some embodiments, R 5 is a 3-6 member carbon ring. In some embodiments, R 5 R is a 3- to 6-membered complex ring. In some embodiments, R 5 is a 5 or 6-membered aryl or heteroaryl portion. In some embodiments, R 5 It is Fran.

[0268] In some embodiments, R 5 is a halogen. In some embodiments, R 5 is Cl or F. In some embodiments, R 7 is a halogen. In some embodiments, R 7 is Cl or F. In some embodiments, R 5 and R 7 Both are halogens. In some embodiments, R 5 and R 7 Both are selected from Cl and F. In some embodiments, R 4 , R 5 , and R 7Each of these is independently a halogen. In some embodiments, R 4 , R 5 , and R 7 These are selected from Cl and F, respectively.

[0269] In some embodiments, (i) ring A is unsubstituted or has one or more R 11 It is a piperazine or diazepane substituted with. In some embodiments, (ii)R 7 is a halogen. In some embodiments, (iii)R 4 is H. In some embodiments, ring A is [ka] Selected from, However, each R g H and C 1~6 Selected independently of alkyl, R h H, C 1~6 Alkyl, -C(O)NH2, and -C(O)C 1~6 Selected from alkylNH2. In some embodiments, at least one R g C 1~6 Alkyl, for example, C1 alkyl. In some embodiments, R h is H. In some embodiments, ring A is [ka] Selected from.

[0270] In some embodiments, R 8 is an alkyl heterocycle. In some embodiments, -OR 8 teeth, [ka] Selected from.

[0271] In some embodiments, -OR 8 teeth, [ka] Selected from.

[0272] In some embodiments, R 7 is F. In some embodiments, R 5 Halogen, -CN, C 1~6 Selected from alkyl groups and 3-6 membered carbon rings, carbon ring or C 1~6 Alkyl is either unsubstituted or has one or more R 13 It is replaced by R 6 teeth, [ka] That is the case.

[0273] In some embodiments, (i)R 8 (ii) is an alkyl heterocycle, and ring A is unsubstituted or has one or more R 11 It is a piperazine substituted with. In some embodiments, (i)R 8 (ii) is an alkyl heterocycle, and ring A is unsubstituted or has one or more R 11 It is a diazepane substituted with. In some embodiments, (i)R 8 (ii) is an alkyl heterocycle, and ring A is an unsubstituted piperazine or diazepane.

[0274] In some embodiments, (i) ring A is unsubstituted or has one or more R 11 It is a bridged heterocyclic ring system that is substituted with. In some embodiments, (ii)R 7 is a halogen. In some embodiments, (iii)R 4 is H. In some embodiments, ring A is [ka] Selected from, (a)R g1 and R g3or (b)R g2 and R g3 These elements bond to each other to form a second ring containing 4-6 members, and R is not part of the second ring. g1 , R g2 , R g3 , and R g4 Either H or C 1~6 Selected independently of alkyl, R h H, C 1~6 Alkyl, -C(O)NH2, and -C(O)C 1~6 Selected from alkylNH2. In some embodiments, R g1 , R g2 , R g3 , and R g4 At least one of them is C 1~6 Alkyl, for example, C1 alkyl. In some embodiments, R h is H. In some embodiments, ring A is [ka] Selected from, However, R g2 and R g4 These two elements bond to each other to form a second ring containing 4 to 6 members, R g1 , R g3 , and R g5 H and C 1~6 Selected independently of alkyl, R h H, C 1~6 Alkyl, -C(O)NH2, and -C(O)C 1~6 Selected from alkylNH2. In some embodiments, R g1 , R g3 , and R g5 At least one of them is C 1~6 Alkyl, for example, C1 alkyl. In some embodiments, R h is H. In some embodiments, R h is -C(O)NH2. In some embodiments, ring A is [ka] Selected from.

[0275] In some embodiments, R 8 is an alkyl heterocycle. In some embodiments, -OR 8 teeth, [ka] Selected from.

[0276] In some embodiments, -OR 8 teeth, [ka] Selected from.

[0277] In some embodiments, R 7 is F. In some embodiments, R 5 Halogen, -CN, C 1~6 Selected from alkyl groups and 3-6 membered carbon rings, carbon ring or C 1~6 Alkyl is either unsubstituted or has one or more R 13 It is replaced by R 6 teeth, [ka] That is the case.

[0278] In some embodiments, (i)R 8 (ii) is an alkyl heterocycle, and ring A is unsubstituted or has one or more R 11 A bridged heterocyclic ring system substituted with (iii)R 7 (iv)R is a halogen, 4 H is H.

[0279] In another aspect, this disclosure relates to compounds of formula IC: [ka] or provides salts thereof (e.g., pharmaceutically acceptable salts), esters, tautomers, prodrugs, zwitterionic forms, or stereoisomers, provided that R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 The compounds of formula I are as defined above and are described herein as classes and subclasses, both individually and in combination. In some embodiments, the present disclosure provides compounds of formula IC or salts thereof (e.g., pharmaceutically acceptable salts).

[0280] In some embodiments, the present disclosure provides compounds of formula IC [wherein, R 2 H and C 1~6 Selected from alkyl groups, R 3 C 1~6 Selected from alkyl, carbocyclic, and heterocyclic elements, however any C 1~6 Alkyl is one or more R 9 Substituted by, and the carbocyclic or heterocyclic ring is unsubstituted or has one or more R 10 Replaced by, Or, R 2 and R 3 This refers to the atoms to which they are bonded, and whether they are unsubstituted or have one or more R 11 Forms a heterocycle substituted with, R 4 H, halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 5 is halogen, -OR 12 ,-CN,C 1~6 Alkyl, C2~6 Alkenil, C 2~6 Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 6 is one or more R 15 It is a bicyclic heteroaryl substituted with, R 7 is halogen, -OR 12 Selected from , -CN, and H, Each R 9 is -N(R 17 )2, -N(R 17 )C(O)C 1~6 Alkyl and -OR 17 Selected independently of, however, any C 1~6 Alkyl is either unsubstituted or has one or more R 18 Replaced by, Each R 10 is -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )2, -C(O)(C 1~6 Alkyl)N(R 19 )2, -(C 1~6 Alkyl)C(O)N(R 19 )2, -C(NR 19 )NR 19 CN, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 20 Replaced by, Each R 11 is -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )2, -C(O)(C 1~6 Alkyl)N(R 19 )2, -(C 1~6 Alkyl)C(O)N(R 19 )2, -C(NR 19)NR 19 CN, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 20 Replaced by, Each R 12 C 1~6 Alkyl, C 2~6 Alkenyl and H are selected independently, except for any C 1~6 Alkyl or C 2~6 Alkenyls are either unsubstituted or have one or more R 13 Replaced by, Each R 13 is -OR 22 -CN, -N(R 22 )2, and selected independently from halogens, Each R 14 Halogen, N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 15 Halogen, N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 17 C 1~6 Selected independently from alkyl and H, Each R 18 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 19 C 1~6 Selected independently from alkyl and H, except for any C 1~6 Alkyl is either unsubstituted or has one or more R 21 Replaced by, Each R 20 -OH, -OC 1~6Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 21 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 22 C 1~6 Alkyl, C 2~6 [Selected independently of alkenyl and H].

[0281] In some embodiments, R 2 is H. In some embodiments, R 2 is C 1~6 It is alkyl. In some embodiments, R 2 is a 3-6 member carbon ring. In some embodiments, R 2 It is cyclopropyl.

[0282] In some embodiments, R 3 It is a carbon ring, and the carbon ring is either unsubstituted or has one or more R 10 It is replaced by R 3 It is a polycyclic carbon ring. In some embodiments, R 3 It is a monocyclic carbon ring. In some embodiments, R 3 is -N(R 19 A carbon ring substituted with )2, where each R 19 This is either non-substitutive or substituted C 1~6 Selected independently from alkyl and H. In some embodiments, R 3 This is a carbon ring substituted with -NH2.

[0283] In some embodiments, R 3 is a heteroalgebra, and a heteroalgebra is either unsubstituted or has one or more R 10 It is replaced by R 3 It is a polycyclic heteroalgebra. In some embodiments, R 3It is a monocyclic heterocycle. In some embodiments, the heterocycle contains one or more nitrogen atoms. In some embodiments, R 3 is -N(R 19 ) is a heterogeneous ring substituted with 2, where each R 19 This is either non-substitutive or substituted C 1~6 Selected independently from alkyl and H. In some embodiments, R 3 This is a heterocycle substituted with -NH2.

[0284] In some embodiments, R 3 teeth, [ka] Selected from, None of these are non-substituted or one or more R 10 It has been replaced with.

[0285] In some embodiments, R 3 teeth, [ka] Selected from, None of these are non-substituted or one or more R 10 It has been replaced with.

[0286] In some embodiments, R 3 teeth, [ka] Selected from, None of these are non-substituted or one or more R 10 It has been replaced with.

[0287] In some embodiments, R 3 is one or more R 9 C replaced by 1~6 Selected from alkyl groups. In some embodiments, R 3 C 1~6 alkyl-N(R 17) Selected from 2, however each R 17 C 1~6 Selected independently from alkyl and H. In some embodiments, R 3 C is substituted with -NH2. 1~6 It is alkyl.

[0288] In some embodiments, R 3 teeth, [ka] Selected from.

[0289] In some embodiments, R 3 It includes an amino moiety (e.g., -NRR'). In some embodiments, the amino moiety is a component of a heterocycle. In some embodiments, the amino moiety is added to a carbocyclic or heterocycle. In some embodiments, the amino moiety is a primary amine (e.g., -NH2). In some embodiments, the amino moiety is a secondary amine (e.g., -NHR).

[0290] In some embodiments, R 3 is one or more R 9 C replaced by 1~6 Selected from alkyl groups. In some embodiments, R 3 is -N(R 17 C replaced with )2 1~6 It is alkyl, however each R 17 C 1~6 Selected independently from alkyl and H. In some embodiments, R 3 C is substituted with -NH2. 1~6 It is alkyl. In some embodiments, R 3 teeth, [ka] Selected from.

[0291] In some embodiments, R 2 or R 3It contains an amino portion (e.g., -NRR').

[0292] In some embodiments, R 2 and R 3 This refers to the atoms to which they are bonded, and whether they are unsubstituted or have one or more R 11 It forms a monocyclic heterocyclic ring substituted with R. In some embodiments, R 2 and R 3 This refers to the atoms to which they are bonded, and whether they are unsubstituted or have one or more R 11 It forms a polycyclic heterocyclic ring substituted with R. In some embodiments, R 2 and R 3 This refers to the atoms to which they are bonded, and whether they are unsubstituted or have one or more R 11 It forms a 4- to 10-membered heteroring substituted with R. In some embodiments, R 2 and R 3 This refers to the atoms to which they are bonded, and whether they are unsubstituted or have one or more R 11 It forms a 4- to 6-membered heteroring substituted with R. In some embodiments, R 2 and R 3 This means that together with the atoms to which they are bonded, they form a structure containing at least one nitrogen atom. In some embodiments, R 2 and R 3 These atoms, together with the atoms to which they are bonded, form a heterocycle with the following structure: [ka] (None of these are non-substituted or one or more R 11 (It has been replaced with...) In some embodiments, R 2 and R 3 These atoms, together with the atoms to which they are bonded, form a heterocycle with the following structure: [ka] (The ring is either unsubstituted or has one or more R 11 (It is replaced by R) In some embodiments, 2 and R3 These atoms, together with the atoms to which they are bonded, form a heterocycle with the following structure: [ka] (The ring is either unsubstituted or has one or more R 11 (It has been replaced with...) In some embodiments, R 2 and R 3 These atoms, together with the atoms to which they are bonded, form a heterocycle with the following structure: [ka]

[0293] In some embodiments, R 2 and R 3 These atoms, together with the atoms to which they are bonded, form a heterocycle with the following structure: [ka]

[0294] In some embodiments, R 2 and R 3 This refers to a 4- to 10-membered heterocycle that, together with the bonded atoms, contains at least two nitrogen atoms (e.g., an amino moiety (e.g., -NR-)) and / or is substituted with a group containing an amino moiety (e.g., -NRR'). In some embodiments, R 2 and R 3 These atoms, along with the bonded atoms, form a 4- to 6-membered heterocycle that contains at least two nitrogen atoms (e.g., an amino moiety (e.g., -NR-)) and / or is substituted with a group containing an amino moiety (e.g., -NRR').

[0295] In some embodiments, R 6 teeth, [ka] Selected from.

[0296] In some embodiments, R 6 teeth, [ka] Selected from.

[0297] In some embodiments, R 6 teeth, [ka] That is the case.

[0298] In some embodiments, R 4 is H. In some embodiments, R 4 It is a halogen.

[0299] In some embodiments, R 5 is a 3-6 member carbon ring. In some embodiments, R 5 R is a 3- to 6-membered complex ring. In some embodiments, R 5 is a 5 or 6-membered aryl or heteroaryl portion. In some embodiments, R 5 It is Fran.

[0300] In some embodiments, R 5 is a halogen. In some embodiments, R 5 is Cl or F. In some embodiments, R 7 is a halogen. In some embodiments, R 7 is Cl or F. In some embodiments, R 5 and R 7 Both are halogens. In some embodiments, R 5 and R 7 Both are selected from Cl and F. In some embodiments, R 4 , R 5 , and R 7 Each of these is independently a halogen. In some embodiments, R 4 , R 5 , and R 7These are selected from Cl and F, respectively.

[0301] In another aspect, this disclosure relates to compounds by formula ID or ID': [ka] or provides salts thereof (e.g., pharmaceutically acceptable salts), esters, tautomers, prodrugs, zwitterionic forms, or stereoisomers, provided that R 1 , R 2 , R 3 , R 4 , R 5 , and R 7 This is as defined above for formula I, and is described herein as a class and a subclass, both individually and in combination, and R 23 is -N(R 12 )2 and C 1~6 alkyl-N(R 12 ) Selected from 2, R 24 , R 25 , and R 26 H, halogen, -OR 12 , and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 11 It is substituted with. In some embodiments, the disclosure provides compounds of formula ID or salts thereof (e.g., pharmaceutically acceptable salts). In some embodiments, the disclosure provides compounds of formula ID' or salts thereof (e.g., pharmaceutically acceptable salts).

[0302] In some embodiments, the present disclosure provides compounds of formula ID or ID' [wherein, R 1 is -OR 8 A 4-6 member heterocycle containing a nitrogen atom, selected from H, wherein the heterocycle is unsubstituted or has one or more R 16 Replaced by, R 2 H and C 1~6 Selected from alkyl groups, R3 C 1~6 Selected from alkyl, carbocyclic, and heterocyclic elements, however any C 1~6 Alkyl is one or more R 9 Substituted by, and the carbocyclic or heterocyclic ring is unsubstituted or has one or more R 10 Replaced by, Or, R 2 and R 3 This refers to the atoms to which they are bonded, and whether they are unsubstituted or have one or more R 11 Forms a heterocycle substituted with, R 4 H, halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 5 is halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 7 is halogen, -OR 12 Selected from , -CN, and H, R 8 The component is selected from heterocycles and alkyl heterocycles, and either is unsubstituted or has one or more R 16 Replaced by, Each R 9 is -N(R 17 )2, -N(R 17 )C(O)C 1~6Alkyl and -OR 17 Selected independently of, however, any C 1~6 Alkyl is either unsubstituted or has one or more R 18 Replaced by, Each R 10 is -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )2, -C(O)(C 1~6 Alkyl)N(R 19 )2, -(C 1~6 Alkyl)C(O)N(R 19 )2, -C(NR 19 )NR 19 CN, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 20 Replaced by, Each R 11 is -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )2, -C(O)(C 1~6 Alkyl)N(R 19 )2, -(C 1~6 Alkyl)C(O)N(R 19 )2, -C(NR 19 )NR 19 CN, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 20 Replaced by, Each R 12 C 1~6 Alkyl, C 2~6 Alkenyl and H are selected independently, except for any C 1~6 Alkyl or C 2~6 Alkenyls are either unsubstituted or have one or more R 13 Replaced by, Each R 13 is -OR 22 -CN, -N(R 22 )2, and selected independently from halogens, Each R 14Halogen, N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 16 Halogen, -N(R 12 )2, and C 1~6 Alkyl and -OR 12 Selected independently of, however, any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 17 C 1~6 Selected independently from alkyl and H, Each R 18 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 19 C 1~6 Selected independently from alkyl and H, except for any C 1~6 Alkyl is either unsubstituted or has one or more R 21 Replaced by, Each R 20 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 21 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 22 C 1~6 Alkyl, C 2~6 [Selected independently of alkenyl and H]. R 23 is -N(R 12 )2 and C 1~6 alkyl-N(R 12 ) Selected from 2. R 24 , R 25, and R 26 H, halogen, -OR 12 , and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 11 It has been replaced with.

[0303] In some embodiments, R 2 is H. In some embodiments, R 2 is C 1~6 It is alkyl. In some embodiments, R 2 is a 3-6 member carbon ring. In some embodiments, R 2 It is cyclopropyl.

[0304] In some embodiments, R 3 It is a carbon ring, and the carbon ring is either unsubstituted or has one or more R 10 It is replaced by R 3 It is a polycyclic carbon ring. In some embodiments, R 3 It is a monocyclic carbon ring. In some embodiments, R 3 is -N(R 19 A carbon ring substituted with )2, where each R 19 This is either non-substitutive or substituted C 1~6 Selected independently from alkyl and H. In some embodiments, R 3 This is a carbon ring substituted with -NH2.

[0305] In some embodiments, R 3 is a heteroalgebra, and a heteroalgebra is either unsubstituted or has one or more R 10 It is replaced by R 3 It is a polycyclic heteroalgebra. In some embodiments, R 3 It is a monocyclic heterocycle. In some embodiments, the heterocycle contains one or more nitrogen atoms. In some embodiments, R 3 is -N(R 19 ) is a heterogeneous ring substituted with 2, where each R 19This is either non-substitutive or substituted C 1~6 Selected independently from alkyl and H. In some embodiments, R 3 This is a heterocycle substituted with -NH2.

[0306] In some embodiments, R 3 teeth, [ka] Selected from, (None of these are non-substituted or one or more R 10 (It has been replaced with...)

[0307] In some embodiments, R 3 teeth, [ka] Selected from, (None of these are non-substituted or one or more R 10 (It has been replaced with...)

[0308] In some embodiments, R 3 teeth, [ka] Selected from, (None of these are non-substituted or one or more R 10 (It has been replaced with...)

[0309] In some embodiments, R 3 is one or more R 9 C replaced by 1~6 Selected from alkyl groups. In some embodiments, R 3 C 1~6 alkyl-N(R 17 ) Selected from 2, however each R 17 C 1~6 Selected independently from alkyl and H. In some embodiments, R 3 C is substituted with -NH2. 1~6 It is alkyl.

[0310] In some embodiments, R 3 teeth, [ka] Selected from.

[0311] In some embodiments, R 3 It includes an amino moiety (e.g., -NRR'). In some embodiments, the amino moiety is a component of a heterocycle. In some embodiments, the amino moiety is added to a carbocyclic or heterocycle. In some embodiments, the amino moiety is a primary amine (e.g., -NH2). In some embodiments, the amino moiety is a secondary amine (e.g., -NHR).

[0312] In some embodiments, R 3 is one or more R 9 C replaced by 1~6 Selected from alkyl groups. In some embodiments, R 3 is -N(R 17 C replaced with )2 1~6 It is alkyl, however each R 17 C 1~6 Selected independently from alkyl and H. In some embodiments, R 3 C is substituted with -NH2. 1~6 It is alkyl. In some embodiments, R 3 teeth, [ka] Selected from.

[0313] In some embodiments, R 2 or R 3 It contains an amino portion (e.g., -NRR').

[0314] In some embodiments, R 2 and R 3 This refers to the atoms to which they are bonded, and whether they are unsubstituted or have one or more R11 It forms a monocyclic heterocyclic ring substituted with R. In some embodiments, R 2 and R 3 This refers to the atoms to which they are bonded, and whether they are unsubstituted or have one or more R 11 It forms a polycyclic heterocyclic ring substituted with R. In some embodiments, R 2 and R 3 This refers to the atoms to which they are bonded, and whether they are unsubstituted or have one or more R 11 It forms a 4- to 10-membered heteroring substituted with R. In some embodiments, R 2 and R 3 This refers to the atoms to which they are bonded, and whether they are unsubstituted or have one or more R 11 It forms a 4- to 6-membered heteroring substituted with R. In some embodiments, R 2 and R 3 This means that together with the atoms to which they are bonded, they form a structure containing at least one nitrogen atom. In some embodiments, R 2 and R 3 These atoms, together with the atoms to which they are bonded, form a heterocycle with the following structure: [ka] (None of these are non-substituted or one or more R 11 (It is replaced by R) In some embodiments, 2 and R 3 These atoms, together with the atoms to which they are bonded, form a heterocycle with the following structure: [ka] (The ring is either unsubstituted or has one or more R 11 (It is replaced by R) In some embodiments, 2 and R 3 These atoms, together with the atoms to which they are bonded, form a heterocycle with the following structure: [ka] (The ring is either unsubstituted or has one or more R 11 (It is replaced by R) In some embodiments, 2 and R 3 These atoms, together with the atoms to which they are bonded, form a heterocycle with the following structure: [ka]

[0315] In some embodiments, R 2 and R 3 These atoms, together with the atoms to which they are bonded, form a heterocycle with the following structure: [ka]

[0316] In some embodiments, R 2 and R 3 This refers to a 4- to 10-membered heterocycle that, together with the bonded atoms, contains at least two nitrogen atoms (e.g., an amino moiety (e.g., -NR-)) and / or is substituted with a group containing an amino moiety (e.g., -NRR'). In some embodiments, R 2 and R 3 These atoms, along with the bonded atoms, form a 4- to 6-membered heterocycle that contains at least two nitrogen atoms (e.g., an amino moiety (e.g., -NR-)) and / or is substituted with a group containing an amino moiety (e.g., -NRR').

[0317] In some embodiments, R 1 It is hydrogen.

[0318] In some embodiments, R 1 is -OR 8 In some embodiments, R 8 It is a complex algebra. In some embodiments, R 8is an alkyl heterocycle. In some embodiments, the heterocycle or the heterocycle of the alkyl heterocycle comprises 4 to 8 members, including at least one heteroatom selected from N, O, and S. In some embodiments, R 8 It comprises a heterocycle containing at least one nitrogen atom. In some embodiments, R 8 It comprises a 4- to 8-membered heterocycle containing at least one nitrogen atom. In some embodiments, R 8 is either unsubstituted or one or more R 16 It includes a 3- to 6-membered heteroring substituted with R. In some embodiments, the heteroring is one or more R 16 Includes substituents. In some embodiments, at least one R 16 is -OR 12 And, however, R 12 C 1~6 Alkyl, C 2~6 Alkenyls and H are selected independently. In some embodiments, at least one R 16 It is -OCH3.

[0319] In some embodiments, R 1 teeth, [ka] Selected from, However, R a and R b Each of them is independent of halogen and C 1~6 Alkyl, -OR 12 , and H are selected, and any C 1~6 Alkyl is either unsubstituted or has one or more R 13 It is replaced by R a is a halogen. In some embodiments, R a In some embodiments, R a is either unsubstituted or one or more R 13 C replaced by 1~6 It is alkyl. In some embodiments, R a is, -OC 1~6It is alkyl. In some embodiments, R a H is H. In some embodiments, R b H is H. In some embodiments, R b is a halogen. In some embodiments, R b In some embodiments, R b is either unsubstituted or one or more R 13 C replaced by 1~6 It is alkyl. In some embodiments, R 1 teeth, [ka] Selected from.

[0320] In some embodiments, R 1 teeth, [ka] Selected from.

[0321] In some embodiments, R 1 teeth, [ka] Selected from, however each R a is halogen, C 1~6 Alkyl, -OR 12 , and H are selected independently, R c is C 1~6 Selected from alkyl, R a or R c C 1~6 Alkyl is either unsubstituted or has one or more R 13 It has been replaced with. In some embodiments, R 1 teeth, [ka] Selected from.

[0322] [Chemical formula] selected from the following.

[0323] In some embodiments, R 1 is [Chemical formula] selected from the following.

[0324] In some embodiments, R 1 is [Chemical formula] selected from the following.

[0325] In some embodiments, R 1 is a 4- to 6-membered heterocyclic ring in which the heterocyclic ring is unsubstituted or contains a nitrogen atom substituted with one or more R 16 In some embodiments, R 1 is [Chemical formula] selected from the following.

[0326] In some embodiments, R 4 is H. In some embodiments, R 4 is halogen.

[0327] In some embodiments, R 5 is a 3- to 6-membered carbocyclic ring. In some embodiments, R 5 is a 3- to 6-membered heterocyclic ring. In some embodiments, R 5 is a 5- or 6-membered aryl or heteroaryl moiety. In some embodiments, R 5 is furan.

[0328] In some embodiments, R5 is a halogen. In some embodiments, R 5 is Cl or F. In some embodiments, R 7 is a halogen. In some embodiments, R 7 is Cl or F. In some embodiments, R 5 and R 7 Both are halogens. In some embodiments, R 5 and R 7 Both are selected from Cl and F. In some embodiments, R 4 , R 5 , and R 7 Each of these is independently a halogen. In some embodiments, R 4 , R 5 , and R 7 These are selected from Cl and F, respectively.

[0329] In some embodiments, R 23 is -N(R 12 )2. In some embodiments, R 23 It is -NH2.

[0330] In some embodiments, R 24 is a halogen. In some embodiments, R 24 is Cl or F. In some embodiments, R 24 is F. In some embodiments, R 24 H is H.

[0331] In some embodiments, R 25 and R 26 is H. In some embodiments, R 25 is H. In some embodiments, R 26 H is H.

[0332] In one embodiment, the present disclosure relates to a compound represented by formula IE: [ka] or provides salts thereof (e.g., pharmaceutically acceptable salts), esters, tautomers, prodrugs, zwitterionic forms, or stereoisomers, provided that R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 This is as defined above for formula I, and is described herein as a class and a subclass, both individually and in combination, and R a and R b is halogen, -OR 12 , C 1~6 A alkyl group and H are independently selected, except for any C. 1~6 Alkyl is either unsubstituted or has one or more R 13 It is substituted with. In some embodiments, the present disclosure provides compounds of formula IE or salts thereof (e.g., pharmaceutically acceptable salts).

[0333] In some embodiments, the present disclosure provides compounds of formula IE [wherein, R 2 These are H, a 3-6 membered carbon ring, and C 1~6 Selected from alkyl groups, but with a 3-6 membered carbon ring or C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, R 3 C 1~6 Selected from alkyl, carbocyclic, and heterocyclic elements, however any C 1~6 Alkyl is one or more R 9 Substituted by, and the carbocyclic or heterocyclic ring is unsubstituted or has one or more R 10 Replaced by, Or, R 2 and R 3 This refers to the atoms to which they are bonded, and whether they are unsubstituted or have one or more R 11 Forms a heterocycle substituted with, R 4 H, halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6Alkenil, C 2~6 Alkynnyls, 3-6 membered carbon rings, and 3-6 membered heterorings, where any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 5 is halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 6 is one or more R 15 It is a bicyclic heteroaryl substituted with, R 7 is halogen, -OR 12 Selected from , -CN, and H, Each R 9 is -N(R 17 )2, -N(R 17 )C(O)C 1~6 Alkyl and -OR 17 Selected independently of, however, any C 1~6 Alkyl is either unsubstituted or has one or more R 18 Replaced by, Each R 10 is -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )2, -C(O)(C 1~6 Alkyl)N(R 19 )2, -(C 1~6 Alkyl)C(O)N(R 19 )2, -C(NR 19 )NR 19 CN, and C 1~6 Selected independently of alkyl, however any C 1~6Alkyl is either unsubstituted or has one or more R 20 Replaced by, Each R 11 is -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )2, -C(O)(C 1~6 Alkyl)N(R 19 )2, -(C 1~6 Alkyl)C(O)N(R 19 )2, -C(NR 19 )NR 19 CN, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 20 Replaced by, Each R 12 C 1~6 Alkyl, C 2~6 Alkenyl and H are selected independently, except for any C 1~6 Alkyl or C 2~6 Alkenyls are either unsubstituted or have one or more R 13 Replaced by, Each R 13 is -OR 22 -CN, -N(R 22 )2, and selected independently from halogens, Each R 14 Halogen, N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 15 Halogen, N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 17 C 1~6 Selected independently from alkyl and H, Each R 18 -OH, -OC1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 19 C 1~6 Selected independently from alkyl and H, except for any C 1~6 Alkyl is either unsubstituted or has one or more R 21 Replaced by, Each R 20 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 21 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 22 C 1~6 Alkyl, C 2~6 Alkenyl and H are selected independently. R a and R b is halogen, -OR 12 , C 1~6 Alkyl and H are independently selected, and any C 1~6 Alkyl is either unsubstituted or has one or more R 13 [It has been replaced by...]

[0334] In some embodiments, R a is a halogen. In some embodiments, R a In some embodiments, R a is either unsubstituted or one or more R 13 C replaced by 1~6 It is alkyl. In some embodiments, R a is, -OC 1~6 It is alkyl. In some embodiments, R a H is H. In some embodiments, R b H is H. In some embodiments, R b is a halogen. In some embodiments, Rb is F. In some embodiments, R b is unsubstituted or is C 13 alkyl substituted with one or more R 1~6 . In some embodiments, R a and R b are both halogen. In some embodiments, R a and R b are both F. In some embodiments, R a and R b are both unsubstituted or are C 13 alkyl substituted with one or more R 1~6 . In some embodiments, R a and R b are both methyl. In some embodiments, R a and R b are both H. In some embodiments, R a is -OC 1~6 alkyl and R b is H.

[0335] In some embodiments, R 2 is H. In some embodiments, R 2 is C 1~6 alkyl. In some embodiments, R 2 is a 3- to 6-membered carbocycle. In some embodiments, R 2 is cyclopropyl.

[0336] In some embodiments, R 3 is C 1~6 alkyl and C 1~6 alkyl is substituted with one or more R<� 9 . In some embodiments, R 3 is C 17 alkyl substituted with -N(R 1~6 )2, provided that each R 17 is independently selected from C 1~6 alkyl and H. In some embodiments, R 3 is C1~6 It is alkyl.

[0337] In some embodiments, R 3 teeth, [ka] Selected from.

[0338] In some embodiments, R 3 It includes an amino moiety (e.g., -NRR'). In some embodiments, the amino moiety is a component of a heterocycle. In some embodiments, the amino moiety is added to a carbocyclic or heterocycle. In some embodiments, the amino moiety is a primary amine (e.g., -NH2). In some embodiments, the amino moiety is a secondary amine (e.g., -NHR).

[0339] In some embodiments, R 3 It is a carbon ring, and the carbon ring is either unsubstituted or has one or more R 10 It is replaced by R 3 It is a polycyclic carbon ring. In some embodiments, R 3 It is a monocyclic carbon ring. In some embodiments, R 3 is -N(R 19 A carbon ring substituted with )2, where each R 19 This is either non-substitutive or substituted C 1~6 Selected independently from alkyl and H. In some embodiments, R 3 This is a carbon ring substituted with -NH2.

[0340] In some embodiments, R 3 is a heteroalgebra, and a heteroalgebra is either unsubstituted or has one or more R 10 It is replaced by R 3 It is a polycyclic heteroalgebra. In some embodiments, R 3 It is a monocyclic heterocycle. In some embodiments, the heterocycle contains one or more nitrogen atoms. In some embodiments, R 3 is -N(R19 ) is a heterogeneous ring substituted with 2, where each R 19 This is either non-substitutive or substituted C 1~6 Selected independently from alkyl and H. In some embodiments, R 3 is a heterocycle substituted with -NH2. In some embodiments, R 3 It is a bridged heterocyclic ring system. In some embodiments, R 3 It is a monoring. In some embodiments, R 3 is either unsubstituted or one or more R 10 It is an azetidine or pyrrolidine substituted with [the specified compound].

[0341] In some embodiments, R 3 teeth, [ka] Selected from, none of these are non-substituted or one or more R 10 It has been replaced with.

[0342] In some embodiments, R 3 teeth, [ka] Selected from, none of these are non-substituted or one or more R 10 It has been replaced with.

[0343] In some embodiments, R 3 teeth, [ka] Selected from, none of these are non-substituted or one or more R 10 It has been replaced with.

[0344] In some embodiments, R 2 and R 3This refers to the atoms to which they are bonded, and whether they are unsubstituted or have one or more R 11 It forms a monocyclic heterocyclic ring substituted with R. In some embodiments, R 2 and R 3 This refers to the atoms to which they are bonded, and whether they are unsubstituted or have one or more R 11 It forms a polycyclic heterocyclic ring substituted with R. In some embodiments, R 2 and R 3 This refers to the atoms to which they are bonded, and whether they are unsubstituted or have one or more R 11 It forms a 4- to 10-membered heteroring substituted with R. In some embodiments, R 2 and R 3 This refers to the atoms to which they are bonded, and whether they are unsubstituted or have one or more R 11 It forms a 4- to 6-membered heteroring substituted with R. In some embodiments, R 2 and R 3 This means that, together with the atoms to which they are bonded, they form a structure containing at least one nitrogen atom. In some embodiments, R 2 and R 3 These atoms, together with the atoms to which they are bonded, form a heterocycle with the following structure: [ka] (None of these are non-substituted or one or more R 11 (It is replaced by R) In some embodiments, 2 and R 3 These atoms, together with the atoms to which they are bonded, form a heterocycle with the following structure: [ka] (The ring is either unsubstituted or has one or more R 11 (It is replaced by R) In some embodiments, 2 and R 3 These atoms, together with the atoms to which they are bonded, form a heterocycle with the following structure: [ka] (The ring is either unsubstituted or has one or more R 11 (It is replaced by R) In some embodiments, 2 and R 3 These atoms, together with the atoms to which they are bonded, form a heterocycle with the following structure: [ka]

[0345] In some embodiments, R 2 and R 3 These atoms, together with the atoms to which they are bonded, form a heterocycle with the following structure: [ka]

[0346] In some embodiments, R 2 and R 3 This refers to a 4- to 10-membered heterocycle that, together with the bonded atoms, contains at least two nitrogen atoms (e.g., an amino moiety (e.g., -NR-)) and / or is substituted with a group containing an amino moiety (e.g., -NRR'). In some embodiments, R 2 and R 3 These atoms, along with the bonded atoms, form a 4- to 6-membered heterocycle that contains at least two nitrogen atoms (e.g., an amino moiety (e.g., -NR-)) and / or is substituted with a group containing an amino moiety (e.g., -NRR').

[0347] In some embodiments, R 4 is H. In some embodiments, R 4 is a halogen. In some embodiments, R 4 は-OR 12 In some embodiments, R 4 It is -OCH3.

[0348] In some embodiments, R 5 is a 3-6 member carbon ring. In some embodiments, R 5 R is a 3- to 6-membered complex ring. In some embodiments, R 5 is a 5 or 6-membered aryl or heteroaryl portion. In some embodiments, R 5 It is Fran.

[0349] In some embodiments, R 5 is either unsubstituted or one or more R 13 C replaced by 1~6 Selected from alkyl groups. In some embodiments, R 5 This is an unsubstituted C such as methyl or ethyl. 1~6 Selected from alkyl groups. In some embodiments, R 5 C is a C substituted with one or more halogens or -CN. 1~6 Selected from alkyl groups. In some embodiments, R 5 R is selected from -CF3, -CF2H, and -CH2CN. In some embodiments, R 5 is -OR 12 Selected from, however, R 12 is either unsubstituted or one or more R 13 C replaced by 1~6 Selected from alkyl groups. In some embodiments, R 5 It is -OCH3, -OCF3, or -OCF2H.

[0350] In some embodiments, R 5 is a halogen. In some embodiments, R 5 is Cl or F. In some embodiments, R 7 is a halogen. In some embodiments, R 7 is Cl or F. In some embodiments, R 5 and R 7 Both are halogens. In some embodiments, R 5 and R 7 Both are selected from Cl and F. In some embodiments, R4 , R 5 , and R 7 Each of these is independently a halogen. In some embodiments, R 4 , R 5 , and R 7 These are selected from Cl and F, respectively.

[0351] In some embodiments, R 6 is one or more R 15 It is a biring aryl substituted with R. In some embodiments, R 6 teeth, [ka] Selected from.

[0352] In some embodiments, R 6 is one or more R 15 It is a bicyclic heteroaryl substituted with R. In some embodiments, R 6 teeth, [ka] Selected from.

[0353] In some embodiments, R 6 teeth, [ka] Selected from.

[0354] In some embodiments, R 6 teeth, [ka]

[0355] In some embodiments, (i)R 6 is one or more R 15 It is a bicyclic heteroaryl substituted with (ii)R 2 and R 3This refers to the unsubstituted or one or more R atoms, along with the atom to which they are bonded (for example, a nitrogen atom). 11 It forms a heterocycle substituted with R. In some embodiments, R 6 teeth, [ka] Selected from.

[0356] In some embodiments, R 2 and R 3 These atoms, together with the atoms to which they are bonded, form a heterocycle with the following structure: [ka] (None of these are non-substituted or one or more R 11 (It is replaced by R) In some embodiments, 2 and R 3 These atoms, together with the atoms to which they are bonded, form a heterocycle with the following structure: [ka] (None of these are non-substituted or one or more R 11 (It has been replaced with...) In some embodiments, R 2 and R 3 These atoms, together with the atoms to which they are bonded, form a heterocycle with the following structure: [ka]

[0357] In some embodiments, R 4 is H. In some embodiments, R 7 is a halogen (e.g., F). In some embodiments, (i)R 6 is one or more R 15 It is a bicyclic heteroaryl substituted with (ii)R2 and R 3 This refers to the unsubstituted or one or more R atoms, along with the atom to which they are bonded (for example, a nitrogen atom). 11 It forms a bridged heterocyclic ring system substituted with. In some embodiments, (i)R 6 is one or more R 15 It is a bicyclic heteroaryl substituted with (ii)R 2 and R 3 This refers to the fact that together with the atoms to which they are bonded (e.g., nitrogen atoms), they form a bridged heterocyclic ring system containing a piperazine ring, and the bridged heterocyclic ring system is either unsubstituted or has one or more R 11 It is replaced by (i)R 6 is one or more R 15 It is a bicyclic heteroaryl substituted with (ii)R 2 and R 3 This refers to the unsubstituted or one or more R atoms, along with the atom to which they are bonded (for example, a nitrogen atom). 11 It forms a piperazine ring substituted with [a specific compound].

[0358] In some embodiments, (i)R 6 is one or more R 15 It is a bicyclic heteroaryl substituted with (ii)R 2 H, C 1~6 Selected from alkyl groups and 3- to 6-membered carbon rings, however, C 1~6 Alkyl or 3-6 membered carbon rings are unsubstituted or have one or more R 13 (iii)R is replaced by 3 C 1~6 It is alkyl, C 1~6 Alkyl is one or more R 9 It is replaced by R 3 C is substituted with -NH2. 1~6 It is alkyl. In some embodiments, R 2 H is H. In some embodiments, R 2 is either unsubstituted or one or more R 13 C replaced by 1~6 It is alkyl. In some embodiments, R2 is either unsubstituted or one or more R 13 It is a 3- to 6-membered carbon ring substituted with a specific compound.

[0359] In some embodiments, (i)R 6 is one or more R 15 It is a bicyclic heteroaryl substituted with (ii)R 2 H, C 1~6 Selected from alkyl groups and 3- to 6-membered carbon rings, however, C 1~6 Alkyl or 3-6 membered carbon rings are unsubstituted or have one or more R 13 (iii)R is replaced by 3 It is a carbon ring, and the carbon ring is either unsubstituted or has one or more R 10 It is replaced by R 3 is either unsubstituted or one or more R 10 It is cyclobutyl substituted with R. In some embodiments, 3 is -N(R 19 A carbon ring substituted with )2, where each R 19 This is either non-substitutive or substituted C 1~6 Selected independently from alkyl and H. In some embodiments, R 3 is a carbon ring substituted with -NH2. In some embodiments, R 2 H is H. In some embodiments, R 2 is either unsubstituted or one or more R 13 C replaced by 1~6 It is alkyl. In some embodiments, R 2 is either unsubstituted or one or more R 13 It is a 3- to 6-membered carbon ring substituted with a specific compound.

[0360] In some embodiments, (i)R 6 is one or more R 15 It is a bicyclic heteroaryl substituted with (ii)R 2 H, C 1~6 Selected from alkyl groups and 3- to 6-membered carbon rings, however, C 1~6Alkyl or 3-6 membered carbon rings are unsubstituted or have one or more R 13 (iii)R is replaced by 3 is a heteroalgebra, and a heteroalgebra is either unsubstituted or has one or more R 10 It is substituted with. In some embodiments, the heterocycle contains one or more nitrogen atoms. In some embodiments, R 3 is -N(R 19 ) is a heterogeneous ring substituted with 2, where each R 19 This is either non-substitutive or substituted C 1~6 Selected independently from alkyl and H. In some embodiments, R 3 is a heterocycle substituted with -NH2. In some embodiments, R 3 It is a bridged heterocyclic ring system. In some embodiments, R 3 It is a monoring. In some embodiments, R 3 is either unsubstituted or one or more R 10 It is an azetidine or pyrrolidine substituted with R. In some embodiments, R 3 teeth, [ka] Selected from, None of these are non-substituted or one or more R 10 It is replaced by R 2 H is H. In some embodiments, R 2 is either unsubstituted or one or more R 13 C replaced by 1~6 It is alkyl. In some embodiments, R 2 is either unsubstituted or one or more R 13 It is a 3- to 6-membered carbon ring substituted with a specific compound.

[0361] In one embodiment, the present disclosure relates to a compound represented by formula IF: [ka] or provides salts thereof (e.g., pharmaceutically acceptable salts), esters, tautomers, prodrugs, zwitterionic forms, or stereoisomers, provided that R 1 , R 4 , R 5 , R 6 , and R 7 This is as defined above for formula I, and is described herein as a class and a subclass, both individually and in combination, and R g1 , R g2 , R g3 , and R g4 H and C 1~6 Each alkyl is independently selected, or (a)R g1 and R g3 or (b)R g2 and R g3 These elements bond to each other to form a second ring containing 4-6 members, and R is not part of the second ring. g1 , R g2 , R g3 , and R g4 Either H or C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced with R h H, C 1~6 Alkyl, -C(O)NH2, and -C(O)C 1~6 Selected from alkylNH2. In some embodiments, the present disclosure provides compounds of formula IF or salts thereof (e.g., pharmaceutically acceptable salts).

[0362] In some embodiments, the present disclosure provides compounds of formula IF [wherein, R 1 is -OR 8 A 4-6 member heterocycle containing a nitrogen atom, selected from H, wherein the heterocycle is unsubstituted or has one or more R 16 Replaced by, R g1 , R g2 , R g3 , and R g4 H and C 1~6Each alkyl is independently selected, or (a)R g1 and R g3 or (b)R g2 and R g3 These elements bond to each other to form a second ring containing 4-6 members, and R is not part of the second ring. g1 , R g2 , R g3 , and R g4 Either H or C 1~6 Selected independently of alkyl, any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, R h H, C 1~6 Alkyl, -C(O)NH2, and -C(O)C 1~6 Selected from alkylNH2, R 4 H, halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 5 is halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 6 is one or more R 15 It is a bicyclic heteroaryl substituted with, R 7 is halogen, -OR 12Selected from , -CN, and H, Each R 12 C 1~6 Alkyl, C 2~6 Alkenyl and H are selected independently, except for any C 1~6 Alkyl or C 2~6 Alkenyls are either unsubstituted or have one or more R 13 Replaced by, Each R 13 is -OR 22 -CN, -N(R 22 )2, and selected independently from halogens, Each R 14 Halogen, N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 15 Halogen, N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 22 C 1~6 Alkyl, C 2~6 [Selected independently of alkenyl and H].

[0363] In some embodiments, R 1 is -OR 8 In some embodiments, R 8 It is a complex algebra. In some embodiments, R 8 is an alkyl heterocycle. In some embodiments, the heterocycle or the heterocycle of the alkyl heterocycle comprises 4 to 8 members, including at least one heteroatom selected from N, O, and S. In some embodiments, R 8 It comprises a heterocycle containing at least one nitrogen atom. In some embodiments, R 8It comprises a 4- to 8-membered heterocycle containing at least one nitrogen atom. In some embodiments, the heterocycle is one or more R 16 Includes substituents. In some embodiments, at least one R 16 is -OR 12 And, however, R 12 C 1~6 Alkyl, C 2~6 Alkenyls and H are selected independently. In some embodiments, at least one R 16 It is -OCH3.

[0364] In some embodiments, R 1 teeth, [ka] Selected from, However, R a and R b Each of them is independent of halogen and C 1~6 Alkyl, -OR 12 Selected from , and H. In some embodiments, R a and R b Each of them is independent of halogen and C 1~6 Alkyl, -OR 12 , and H are selected, and any C 1~6 Alkyl is either unsubstituted or has one or more R 13 It is replaced by R a is a halogen. In some embodiments, R a In some embodiments, R a is either unsubstituted or one or more R 13 C replaced by 1~6 It is alkyl. In some embodiments, R a is, -OC 1~6 It is alkyl. In some embodiments, R a H is H. In some embodiments, R b H is H. In some embodiments, R b is a halogen. In some embodiments, R bIn some embodiments, R b is either unsubstituted or one or more R 13 C replaced by 1~6 It is alkyl. In some embodiments, R 1 teeth, [ka] Selected from.

[0365] In some embodiments, R 1 teeth, [ka] Selected from.

[0366] In some embodiments, R 1 teeth, [ka] Selected from, however each R a is halogen, C 1~6 Alkyl, -OR 12 , and H are selected independently, R c is C 1~6 Selected from alkyl, R a or R c C 1~6 Alkyl is either unsubstituted or has one or more R 13 It has been replaced with. In some embodiments, R 1 teeth, [ka] Selected from.

[0367] In some embodiments, R 1 teeth, [ka] Selected from.

[0368] In some embodiments, R 1 teeth, [ka] Selected from.

[0369] In some embodiments, R 1 teeth, [ka] Selected from.

[0370] In some embodiments, R 1 It is a 4-6 member heterocycle containing a nitrogen atom, and the heterocycle is unsubstituted or has one or more R 16 It is replaced by R 1 teeth, [ka] Selected from.

[0371] In some embodiments, R 1 It is hydrogen.

[0372] In some embodiments, R 4 is H. In some embodiments, R 4 is a halogen. In some embodiments, R 4 は-OR 12 In some embodiments, R 4 It is -OCH3.

[0373] In some embodiments, R 5 is a 3-6 member carbon ring. In some embodiments, R 5 R is a 3- to 6-membered complex ring. In some embodiments, R 5 is a 5 or 6-membered aryl or heteroaryl portion. In some embodiments, R 5 It is Fran.

[0374] In some embodiments, R 5 is either unsubstituted or one or more R 13 C replaced by 1~6 Selected from alkyl groups. In some embodiments, R 5 This is an unsubstituted C such as methyl or ethyl. 1~6 Selected from alkyl groups. In some embodiments, R 5 C is a C substituted with one or more halogens or -CN. 1~6 Selected from alkyl groups. In some embodiments, R 5 R is selected from -CF3, -CF2H, and -CH2CN. In some embodiments, R 5 is -OR 12 Selected from, however, R 12 is either unsubstituted or one or more R 13 C replaced by 1~6 Selected from alkyl groups. In some embodiments, R 5 It is -OCH3, -OCF3, or -OCF2H.

[0375] In some embodiments, R 5 is a halogen. In some embodiments, R 5 is Cl or F. In some embodiments, R 7 is a halogen. In some embodiments, R 7 is Cl or F. In some embodiments, R 5 and R 7 Both are halogens. In some embodiments, R 5 and R 7 Both are selected from Cl and F. In some embodiments, R 4 , R 5 , and R 7 Each of these is independently a halogen. In some embodiments, R 4 , R 5 , and R 7 These are selected from Cl and F, respectively.

[0376] In some embodiments, R 6 is one or more R 15 It is a biring aryl substituted with R. In some embodiments, R 6 teeth, [ka] Selected from.

[0377] In some embodiments, R 6 is one or more R 15 It is a bicyclic heteroaryl substituted with R. In some embodiments, R 6 teeth, [ka] Selected from.

[0378] In some embodiments, R 6 teeth, [ka] Selected from.

[0379] In some embodiments, R 6 teeth, [ka] Selected from.

[0380] In some embodiments, R g1 C 1~6 Selected from alkyl (e.g., methyl). In some embodiments, R g2 C 1~6 Selected from alkyl (e.g., methyl). In some embodiments, R g3 C 1~6 Selected from alkyl (e.g., methyl). In some embodiments, R g4 C 1~6 Selected from alkyl (e.g., methyl). In some embodiments, Rg1 and R g2 C 1~6 Selected from alkyl (e.g., methyl). In some embodiments, R g1 and R g2 Both are methyl. In some embodiments, R g1 and R g3 C 1~6 Selected from alkyl (e.g., methyl). In some embodiments, R g1 and R g3 Both are methyl. In some embodiments, R g1 and R g4 C 1~6 Selected from alkyl (e.g., methyl). In some embodiments, R g1 and R g4 Both are methyl. In some embodiments, R g2 and R g3 C 1~6 Selected from alkyl (e.g., methyl). In some embodiments, R g2 and R g3 Both are methyl.

[0381] In some embodiments, R g1 and R g3 These combine with each other to form a second ring containing 4 to 6 members. In some embodiments, R g2 and R g3 These combine with each other to form a second ring containing 4 to 6 members. In some embodiments, R h H is H.

[0382] In some embodiments, the compound has the following structure: [ka]

[0383] In some embodiments of the compound according to formula (IF1) or (IF2), R g1 and R g4Each of these is H. In some embodiments of the compound according to formula (IF3) or (IF4), R g2 and R g4 Each of these is H. In some embodiments of the compounds according to formula (IF1), (IF2), (IF3), or (IF4), R h is H. In some embodiments of the compound according to formula (IF1), (IF2), (IF3), or (IF4), R 1 teeth, [ka] Selected from, However, R a and R b Each of them is independent of halogen and C 1~6 Alkyl, -OR 12 , and H are selected, and any C 1~6 Alkyl is either unsubstituted or has one or more R 13 It is substituted with. In some embodiments of the compound by formula (IF1), (IF2), (IF3), or (IF4), R 6 teeth, [ka] Selected from.

[0384] In some embodiments of the compound according to formula (IF1), (IF2), (IF3), or (IF4), R 4 is H. In some embodiments of the compounds according to formula (IF1), (IF2), (IF3), or (IF4), R 7 is a halogen (e.g., F). In some embodiments of the compounds according to formula (IF1), (IF2), (IF3), or (IF4), R 5 This includes halogens, -CN, 3-6 membered carbon rings, 3-6 membered heterocycles, or unsubstituted or one or more R atoms. 13 C is replaced by 1~6 It is alkyl.

[0385] In another embodiment, the present disclosure relates to a compound of formula II: [ka] The formula provides a salt thereof (e.g., a pharmaceutically acceptable salt), an ester, a tautomer, a prodrug, a zwitterionic form, or a stereoisomer [wherein, R 1 is -OR 8 A 4-6 member heterocycle containing a nitrogen atom, selected from H, wherein the heterocycle is unsubstituted or has one or more R 16 Replaced by, R 2 These are H, a 3-6 membered carbon ring, and C 1~6 Selected from alkyl groups, but with a 3-6 membered carbon ring or C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, R 3 C 1~6 Selected from alkyl, carbocyclic, and heterocyclic elements, however any C 1~6 Alkyl is one or more R 9 Substituted by, and the carbocyclic or heterocyclic ring is unsubstituted or has one or more R 10 Replaced by, Or, R 2 and R 3 This refers to the atoms to which they are bonded, and whether they are unsubstituted or have one or more R 11 Forms a heterocycle substituted with, R 4 H, halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 6is a phenyl, monocyclic heteroaryl, bicyclic aryl, or bicyclic heteroaryl, provided that any phenyl, monocyclic heteroaryl, bicyclic aryl, and bicyclic heteroaryl is unsubstituted or has one or more R 15 Replaced by, R 7 is halogen, -OR 12 Selected from , -CN, and H, R 8 The heterocycle is selected from H, heterocycles, and alkyl heterocycles, provided that the heterocycle or alkyl heterocycle is unsubstituted or has one or more R 16 Substituted with, the alkyl portion of any alkyl heterocycle is C 1~6 Selected from alkyl groups, Each R 9 is -N(R 17 )2, -N(R 17 )C(O)C 1~6 Alkyl and -OR 17 Selected independently of, however, any C 1~6 Alkyl is either unsubstituted or has one or more R 18 Replaced by, Each R 10 Halogen, -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )2, -C(O)(C 1~6 Alkyl)N(R 19 )2, -(C 1~6 Alkyl)C(O)N(R 19 )2, -C(NR 19 )NR 19 CN, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 20 Replaced by, Each R 11 is -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )2, -C(O)(C 1~6 Alkyl)N(R 19 )2, -(C 1~6 Alkyl)C(O)N(R19 )2, -C(NR 19 )NR 19 CN, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 20 Replaced by, Each R 12 C 1~6 Alkyl, C 2~6 Alkenyl and H are selected independently, except for any C 1~6 Alkyl or C 2~6 Alkenyls are either unsubstituted or have one or more R 13 Replaced by, Each R 13 is -OR 22 -CN, -N(R 22 )2, and selected independently from halogens, Each R 14 is halogen, -OR 12 -CN, -N(R 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 15 is halogen, -OR 12 -CN, -N(R 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 16 Halogen, -N(R 12 )2, C 1~6 Alkyl, -OR 12 , and independently selected from 3- to 6-membered complex rings, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 17 C 1~6 Selected independently from alkyl and H, Each R 18-OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 19 C 1~6 A alkyl group, a 3- to 6-membered heterocycle, and H are independently selected, except for any C. 1~6 Alkyl is either unsubstituted or has one or more R 21 Replaced by, Each R 20 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Independently selected from alkyl, halogen, and 3-6 membered carbon rings, Each R 21 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 22 C 1~6 Alkyl, C 2~6 [Selected independently of alkenyl and H].

[0386] In some embodiments, the present disclosure provides compounds of formula II or salts thereof (e.g., pharmaceutically acceptable salts).

[0387] In some embodiments, the present disclosure provides compounds of formula II [wherein, R 1 is -OR 8 A 4-6 member heterocycle containing a nitrogen atom, selected from H, wherein the heterocycle is unsubstituted or has one or more R 16 Replaced by, R 2 H and C 1~6 Selected from alkyl groups, R 3 C 1~6 Selected from alkyl, carbocyclic, and heterocyclic elements, however any C 1~6 Alkyl is one or more R 9 Substituted by, and the carbocyclic or heterocyclic ring is unsubstituted or has one or more R 10Replaced by, Or, R 2 and R 3 This refers to the atoms to which they are bonded, and whether they are unsubstituted or have one or more R 11 Forms a heterocycle substituted with, R 4 H, halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 6 is one or more R 15 It is a bicyclic heteroaryl substituted with, R 7 is halogen, -OR 12 Selected from , -CN, and H, R 8 The component is selected from heterocycles and alkyl heterocycles, and either is unsubstituted or has one or more R 16 Replaced by, Each R 9 is -N(R 17 )2, -N(R 17 )C(O)C 1~6 Alkyl and -OR 17 Selected independently of, however, any C 1~6 Alkyl is either unsubstituted or has one or more R 18 Replaced by, Each R 10 is -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )2, -C(O)(C 1~6 Alkyl)N(R 19 )2, -(C 1~6 Alkyl)C(O)N(R 19 )2, -C(NR 19 )NR 19 CN, and C 1~6Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 20 Replaced by, Each R 11 is -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )2, -C(O)(C 1~6 Alkyl)N(R 19 )2, -(C 1~6 Alkyl)C(O)N(R 19 )2, -C(NR 19 )NR 19 CN, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 20 Replaced by, Each R 12 C 1~6 Alkyl, C 2~6 Alkenyl and H are selected independently, except for any C 1~6 Alkyl or C 2~6 Alkenyls are either unsubstituted or have one or more R 13 Replaced by, Each R 13 is -OR 22 -CN, -N(R 22 )2, and selected independently from halogens, Each R 14 is halogen, -OR 12 -CN, -N(R 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 15 Halogen, N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 16 Halogen, -N(R12 )2, and C 1~6 Alkyl and -OR 12 Selected independently of, however, any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 17 C 1~6 Selected independently from alkyl and H, Each R 18 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 19 C 1~6 Selected independently from alkyl and H, except for any C 1~6 Alkyl is either unsubstituted or has one or more R 21 Replaced by, Each R 20 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 21 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 22 C 1~6 Alkyl, C 2~6 [Selected independently of alkenyl and H].

[0388] In some embodiments, R 3 The carbon ring and heterocycle are selected, provided that the carbon ring or heterocycle is unsubstituted or has one or more R 10 It is replaced by R 3 is either unsubstituted or one or more R 10 It is a 3- to 6-membered carbon ring or heterocycle substituted with R. In some embodiments, R 3 It is a 4-6 member carbon ring, and the carbon ring is either unsubstituted or has one or more R 10It is replaced by R 3 A is a 4-8 membered heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and the heterocycle is unsubstituted or has one or more R 10 It is replaced by R 3 is unsubstituted or one or more R 10 It is an azetidine substituted with R. In some embodiments, R 3 teeth, [ka] Selected from, none of these are non-substituted or one or more R 10 It has been replaced with.

[0389] In some embodiments, R 3 is one or more R 9 C replaced by 1~6 Selected from alkyl groups. In some embodiments, R 3 C 1~6 alkyl-N(R 17 ) Selected from 2. In some embodiments, R 3 is -CH2CH2NH2. In some embodiments, R 3 teeth, [ka] Selected from.

[0390] In some embodiments, R 2 or R 3 It includes an amino moiety (e.g., -NRR'). In some embodiments, R 2 or R 3 The amino portion is (i.e., -N(R) 17 )2 or -N(R 19 )2) is replaced.

[0391] In some embodiments, R 2 and R 3This refers to the atoms to which they are bonded, and whether they are unsubstituted or have one or more R 11 It forms a 4- to 6-membered heteroring substituted with R. In some embodiments, R 2 and R 3 This refers to a 4-9 membered heterocycle having, together with the bonded atom (e.g., a nitrogen atom), 0-2 further heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the heterocycle is unsubstituted or has one or more R 11 It is replaced by R 2 and R 3 This refers to a 4-7 membered heterocycle having 0-1 further heteroatoms independently selected from nitrogen, oxygen, and sulfur, together with the bonded atom (e.g., a nitrogen atom), wherein the heterocycle is unsubstituted or has one or more R 11 It is replaced by R 2 and R 3 These, together with the atoms to which they are bonded (for example, a nitrogen atom), form piperazine. In some embodiments, R 2 and R 3 This refers to a 7-9 membered heterocycle having, together with the bonded atom (e.g., a nitrogen atom), 0-2 further heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the heterocycle is unsubstituted or has one or more R 11 It has been replaced with. In some embodiments, R 2 and R 3 These atoms, together with the atoms to which they are bonded, form a heterocycle with the following structure: [ka] (The ring is either unsubstituted or has one or more R 11 (It is replaced by R) In some embodiments, 2 and R 3 These atoms, together with the atoms to which they are bonded, form a heterocycle with the following structure: [ka]

[0392] In some embodiments, R 2 and R 3 This refers to the nitrogen atom to which they are bonded, and whether it is unsubstituted or has one or more R 11 A heterocycle is formed by substitution with a group containing a further nitrogen atom (e.g., an amino moiety (e.g., -NR-)) and / or a group containing an amino moiety (e.g., -N(R 19 )2) is replaced.

[0393] In some embodiments, R 1 It is hydrogen.

[0394] In some embodiments, R 1 is -OR 8 In some embodiments, R 1 は-OR 8 And R 8 is a heterocycle or alkyl heterocycle. In some embodiments, R 8 is either unsubstituted or one or more R 14 It includes a 3- to 6-membered heteroring substituted with R. In some embodiments, R 8 It is a complex algebra. In some embodiments, R 8 is an alkyl heterocycle. In some embodiments, R 8 It is an alkyl heterocycle, where the alkyl portion of the alkyl heterocycle is C 1~6 Selected from alkyl groups. In some embodiments, R 8 is -CH2 (heterocyclic). In some embodiments, the heterocyclic or alkyl heterocyclic heterocyclic comprises 4 to 8 members, including at least one heteroatom selected from N, O, and S. In some embodiments, R 8 It comprises a heterocycle containing at least one nitrogen atom. In some embodiments, R 8The heterocycle comprises a 4- to 8-membered heterocycle containing at least one nitrogen atom. In some embodiments, the heterocycle or alkyl heterocycle is a 4- to 6-membered monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the heterocycle or alkyl heterocycle is an 8-membered bicyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the heterocycle comprises one or more R 16 It is replaced by. In some embodiments, at least one R 16 is -OR 12 And, however, R 12 C 1~6 Alkyl, C 2~6 Alkenyls and H are selected independently. In some embodiments, at least one R 16 is -OCH3. In some embodiments, at least one R 16 is a halogen (e.g., F). In some embodiments, at least one R 16 is either unsubstituted or one or more R 13 C replaced by 1~6 It is alkyl.

[0395] In some embodiments, R 1 teeth, [ka] Selected from.

[0396] In some embodiments, R 1 teeth, [ka] Selected from.

[0397] In some embodiments, R 1 The heteroalgebra is either unsubstituted or has one or more R 16It is a 4- to 6-membered heterocycle containing nitrogen atoms substituted with R. In some such embodiments, R 16 is -N(R 12 )2, C 1~6 Selected from alkyl groups and 3- to 6-membered heterocycles. In some embodiments, R 16 is -N(C 1~6 Alkyl)2, for example, -N(CH3)2. In some embodiments, R 16 C 1~6 It is an alkyl group (e.g., methyl). In some embodiments, R 16 It is a bicyclic, six-membered heterocycle having one nitrogen atom. In some embodiments, R 1 teeth, [ka] Selected from.

[0398] In some embodiments, R 6 is one or more R 15 It is a biring aryl substituted with R. In some embodiments, R 6 is one or more R 15 This is naphthyl substituted with [another compound].

[0399] In some embodiments, R 6 is either unsubstituted or one or more R 15 It is a 9-10 member heteroaryl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur substituted with R. In some embodiments, R 6 is one or more R 15 It is a bicyclic heteroaryl substituted with R. In some embodiments, R 6 is one or more R 15 A nine-membered heteroaryl having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, substituted with R. In some such embodiments, at least one R 15 is -N(R 12 )2 (for example, -NH2). In some embodiments, at least one R 15is a halogen (e.g., F). In some embodiments, each R 15 These are halogen, -CN, and -N(R) 12 )2 is selected independently. In some embodiments, R 6 is at least two R 15 (For example, it is substituted with at least halogen and -NH2)

[0400] In some embodiments, R 6 teeth, [ka] Selected from, none of these are non-substituted or one or more R 15 It has been replaced with.

[0401] In some embodiments, R 6 teeth, [ka] Selected from.

[0402] In some embodiments, R 6 teeth, [ka] Selected from.

[0403] In some embodiments, R 6 teeth, [ka] That is the case.

[0404] In some embodiments, R 6 is unsubstituted or one or more R 15 It is a phenyl substituted with R. In some such embodiments, each R 15 is halogen, -OR 12-CN, and -N(R 12 ) Selected independently from 2.

[0405] In some embodiments, R 6 is unsubstituted or one or more R 15 It is a monocyclic 5-6 member heteroaryl substituted with R. In some embodiments, R 6 is unsubstituted or one or more R 15 It is pyridyl substituted with. In some embodiments, each R 15 N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 It has been replaced with.

[0406] In some embodiments, R 4 is H. In some embodiments, R 4 is a halogen. In some embodiments, R 4 is -OR 12 In some embodiments, R 4 It is -OCH3.

[0407] In some embodiments, R 7 is a halogen. In some embodiments, R 7 is Cl or F. In some embodiments, R 7 is -OR 12 And, however, R 12 is H and unsubstituted or one or more R 13 C replaced by 1~6 Selected from alkyl groups. In some embodiments, R 7 is -OH, -OCH3, or -OCH2CF3. In some embodiments, R 7 is -CN. In some embodiments, R 7 It is hydrogen.

[0408] In some embodiments, R 4 and R7 Both are halogens. In some embodiments, R 4 and R 7 Both are selected from Cl or F.

[0409] In some embodiments, the compound is represented by a formula included in any of Tables 2 to 9. In some embodiments, the disclosure provides a compound or salt (e.g., a pharmaceutically acceptable salt thereof) selected from any one of Tables 2, 3, 4, 5, 7, 8, and 9. In some embodiments, the disclosure provides a compound or salt (e.g., a pharmaceutically acceptable salt thereof) selected from any one of Tables 2, 3, 4, 7, 8, and 9.

[0410] Furthermore, compounds selected from any of Tables 2-9 or any of the examples shown herein, or their salts, esters, tautomers, prodrugs, zwitterionic forms, or stereoisomers, are also provided herein. The compounds described herein may be provided and / or utilized in any available form (e.g., in the form of salts), and it will be recognized that all such forms are conceived by this disclosure. This disclosure also conceives of forms such as esters, tautomers, prodrugs, zwitterionic forms, and stereoisomers of the compounds provided herein.

[0411] In some embodiments, the compounds provided are provided and / or utilized in the form of salts (e.g., pharmaceutically acceptable salts). References to the compounds provided herein are understood to include references to their salts unless otherwise indicated.

[0412] Furthermore, embodiments are also provided herein that allow any embodiment described herein to be combined with any one or more of these embodiments, provided that the combinations are not mutually exclusive. Two embodiments are “mutually exclusive” if one is defined as being different from the other, as used herein. For example, an embodiment in which two groups are bonded to form a ring is mutually exclusive with an embodiment in which one group is ethyl and the other is hydrogen. Similarly, an embodiment in which one group is CH2 is mutually exclusive with an embodiment in which the same group is NH.

[0413] composition This disclosure also provides compounds provided herein (e.g., formulas I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II), or their salts, esters, tautomers, prodrugs, zwitterionic forms, or stereoisomers. In some embodiments, the provided compositions include compounds provided herein, or pharmaceutically acceptable salts thereof. For example, this disclosure includes compounds provided herein (e.g., formulas I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II), or their salts, esters, tautomers, prodrugs, zwitterionic forms, or stereoisomers, together with a pharmaceutically acceptable carrier. In some embodiments, the provided pharmaceutical compositions include compounds provided herein, or pharmaceutically acceptable salts thereof, together with a pharmaceutically acceptable carrier.

[0414] In some embodiments, the pharmaceutical composition is formulated for oral administration. In some embodiments, the oral pharmaceutical formulation is selected from tablets and capsules.

[0415] In some embodiments, the pharmaceutical composition is formulated for parenteral administration. In some embodiments, the pharmaceutical composition is formulated for intravenous administration. In some embodiments, the pharmaceutical composition is formulated for subcutaneous administration.

[0416] Certain compounds provided herein (e.g., any one of the compounds of formula I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II), or their salts, esters, tautomers, prodrugs, zwitterionic forms, or stereoisomers, can be administered as unprocessed chemicals, but the compounds can also be provided in addition to or instead in a pharmaceutical formulation. Accordingly, this specification provides pharmaceutical compositions comprising one or more of the compounds disclosed herein (e.g., any one of the compounds of formula I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II), or one or more pharmaceutically acceptable salts, esters, prodrugs, amides, or solvates thereof, together with one or more pharmaceutically acceptable carriers and optionally one or more other therapeutic components. The carrier(s) must be “acceptable” in the sense that they are compatible with the other components of the formulation and are not harmful to its recipient. The appropriate formulation is determined by the chosen route of administration. Any known technology, carrier, and excipient can be used as appropriate, as understood in the art. The pharmaceutical compositions disclosed herein can be prepared by any known suitable method, for example, by conventional mixing, dissolution, granulation, sugar-coated tablet production, polishing, emulsification, encapsulation, sealing, or compression processes.

[0417] The pharmaceutical formulations provided herein may be suitable for oral, parenteral (including subcutaneous, intradermal, intramuscular, intravenous, intra-articular, and intra-bone marrow), intraperitoneal, transmucosal, transdermal, rectal, and topical (including cutaneous, buccal, sublingual, and intraocular) administration. The most suitable route may be determined, for example, by the condition and disorder of the subject to whom the pharmaceutical formulation is administered. The pharmaceutical formulations may be provided in unit dosage forms. The pharmaceutical formulations may be prepared by any suitable method. Methods for preparing the pharmaceutical formulations may include contacting one or more pharmaceutically acceptable carriers (e.g., auxiliary components) of a compound provided herein (e.g., any one of the compounds of formula I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II) or a pharmaceutically acceptable salt, ester, amide, prodrug, or solvate thereof ("active component") with one or more pharmaceutically acceptable carriers (e.g., auxiliary components). Generally, formulations are prepared by uniformly and closely contacting an active ingredient with a liquid carrier, a pulverized solid carrier, or both, and then, if necessary, shaping the product into the desired formulation.

[0418] The compounds provided herein (for example, any one of the compounds of formulas I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II in any available form (e.g., salt, ester, tautomer, prodrug, zwitterionic form, stereoisomer, etc.)) may be provided as separate units. For example, formulations suitable for oral administration may be provided as capsules, cachets, and / or tablets containing a predetermined amount of any suitable form of the compound (e.g., the active ingredient), as a solution or suspension in a solvent (e.g., aqueous or non-aqueous solvent), as an emulsion (oil-in-water emulsion or water-in-oil emulsion), or as a powder or granules. In addition to or instead of the above, the active ingredient may be provided as a bolus, lick, or paste.

[0419] Pharmaceutical formulations suitable for oral administration include tablets, push-fit capsules formed from gelatin, and soft, sealed capsules formed from gelatin and plasticizers such as glycerol or sorbitol. Tablets can be prepared, for example, by compression or molding, and may use one or more auxiliary components, such as one or more pharmaceutically acceptable excipients. Compressed tablets can be prepared by compressing a free-flowing active ingredient, such as a powder or granules, mixed with a binder, lubricant, inert diluent, lubricating surfactant, or dispersant, as needed, using a suitable machine. Molded tablets can be prepared by molding a mixture of powdered compounds moistened with an inert liquid diluent, using a suitable machine. Tablets may be coated or scored as needed, and can be formulated to release the active ingredient therein in a sustained or controlled manner. All formulations for oral administration must be in a dosage suitable for such administration. The push-fit capsule may contain an active ingredient mixed with, for example, one or more fillers such as lactose, one or more binders such as one or more starches, and / or one or more lubricants such as talc or magnesium stearate, and optionally one or more stabilizers. In the case of a soft capsule, the active compound(s) may be dissolved or suspended in a suitable liquid such as fatty oil, liquid paraffin, or liquid polyethylene glycol. Stabilizers and other components may also be added. The sugar-coated tablet core may be given a suitable coating. For this purpose, a concentrated sugar solution may be used, which may optionally include gum, gelling agents, polymers, solvents, or combinations thereof. Dyes or pigments may be added to the tablet or sugar-coated tablet coating for identification purposes or to characterize different combinations of active compound doses.

[0420] Pharmaceutical compositions comprising compounds provided herein (e.g., any one of the compounds of formulas I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II) or any predetermined form thereof (e.g., salts, esters, tautomers, prodrugs, zwitterionic forms, stereoisomers, etc.) can be formulated for parenteral administration by injection, e.g., bolus injection or continuous infusion. Formulations for injection can be provided in unit dosage forms, e.g., in ampoules, vials, or multi-dose containers with added preservatives. Compositions can be in the form of suspensions, solutions, or emulsions in oily or aqueous solvents and may contain compounding agents such as suspending agents, stabilizers, and / or dispersants. Formulations may also be provided in unit or multi-dose containers, e.g., in sealed ampoules and vials, and may be stored in powder form or freeze-dried state, requiring only the addition of a sterile liquid carrier, e.g., physiological saline or sterile pyrogen-free water, before use (e.g., immediately before use). Immediate injection solutions and suspensions can be prepared from the above-mentioned types of sterile powders, granules, and tablets.

[0421] Pharmaceutical compositions comprising the compounds provided herein (e.g., any one of the compounds of formulas I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II) or a predetermined form thereof (e.g., salts, esters, tautomers, prodrugs, zwitterionic forms, stereoisomers, etc.) can be formulated as injection solutions, which may be aqueous or non-aqueous (oil-based) sterile solutions and may contain one or more antioxidants, thickeners, suspending agents, buffers, solutes, and / or bacteriostatic agents. By adding one or more such additives, the formulation can be made isotonic with the blood of the intended recipient (e.g., subject or patient). Suitable lipophilic solvents or vehicles include fatty oils such as sesame oil, or synthetic fatty acid esters such as ethyl oleate or triglycerides, or liposomes. Aqueous injection suspensions may contain substances that increase the viscosity of the suspension, such as sodium carboxymethylcellulose, sorbitol, or dextran. If necessary, such suspensions may contain appropriate stabilizers or agents to increase the solubility of the compound, enabling the preparation of highly concentrated solutions.

[0422] In addition to the formulations described elsewhere in this Specification, the compounds provided herein (e.g., any one of the compounds of formulas I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II) can also be formulated as depot preparations in any suitable form (e.g., salts, esters, tautomers, prodrugs, zwitterionic forms, stereoisomers, etc.). Such long-acting formulations can be administered by implantation (e.g., subcutaneous or intramuscular) or intramuscular injection. Thus, for example, the compounds can be formulated with a suitable polymer or hydrophobic material (e.g., as an emulsion in an acceptable oil) or an ion exchange resin, or as a sparingly soluble derivative, such as a sparingly soluble salt.

[0423] Pharmaceutical compositions comprising compounds provided herein (e.g., any one of the compounds of formulas I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II) or a predetermined form thereof (e.g., salts, esters, tautomers, prodrugs, zwitterionic forms, stereoisomers, etc.) suitable for oral or sublingual administration may be in the form of tablets, lozenges, troches, or gels. Such compositions may contain the active ingredient in a flavored base such as sucrose and acacia, or in tragacanth. Pharmaceutical compositions comprising compounds provided herein or a predetermined form thereof (e.g., salts, esters, tautomers, prodrugs, zwitterionic forms, stereoisomers, etc.) suitable for rectal administration may be formulated as suppositories or retained enemas and may contain a medium such as cocoa butter, polyethylene glycol, or other glycerides.

[0424] Certain compounds provided herein (e.g., any one of the compounds of formulas I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II) or their prescribed forms (e.g., salts, esters, tautomers, prodrugs, zwitterionic forms, stereoisomers, etc.) can be formulated for non-systemic administration, such as topical administration. This includes application of the compounds or their prescribed forms disclosed herein to the outer surface of the epidermis or cheek cavity, as well as dropping the compounds or their prescribed forms into the ears, eyes, and noses, in such a way that large amounts of the compounds or their prescribed forms do not enter the bloodstream. Systemic administration, in contrast, refers to oral, intravenous, intraperitoneal, and intramuscular administration.

[0425] Formulations suitable for topical administration include liquid or semi-liquid formulations suitable for penetration through the skin into the site of inflammation, such as gels, liniments, lotions, creams, ointments, or pastes, and drops suitable for administration to the eyes, ears, or nose. The active ingredient for topical administration may constitute, for example, 0.001% by weight to 10% by weight of the formulation. In certain embodiments, the active ingredient may constitute an amount of 10% by weight. In other embodiments, the active ingredient may constitute less than 5% by weight. In certain embodiments, the active ingredient may constitute 2% by weight to 5% by weight. In other embodiments, the active ingredient may constitute 0.1% by weight to 1% by weight of the formulation.

[0426] For administration by inhalation, the compound (e.g., any one compound from formulas I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II) or a predetermined form of the compound (e.g., salt, ester, tautomer, prodrug, zwitterionic form, stereoisomer, etc.) can be conveniently delivered by an inhaler, nebulizer pressurized pack, or other convenient means of delivering an aerosol spray. The pressurized pack may contain a suitable propellant such as dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide, or other suitable gas. In the case of a pressurized aerosol, the dose unit can be determined by providing a valve that dispenses a measured amount. Alternatively, for administration by inhalation or inhalation, the compounds provided herein may be in the form of a dry powder composition, for example, a powder mixture of the compound and a suitable powder base such as lactose or starch. The powder composition may be provided in unit dosage forms such as capsules, cartridges, gelatin, or blister packs from which the powder can be administered using an inhaler or inhaler.

[0427] A preferred unit dose formulation contains, for example, an effective dose or appropriate proportion thereof of the active ingredient (e.g., any one of the compounds provided herein (e.g., any one of the compounds of formulas I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II), or its salts, esters, tautomers, prodrugs, zwitterionic forms, or stereoisomers).

[0428] In addition to the ingredients described in detail elsewhere in this specification, the formulations described herein may contain other useful agents depending on the type of formulation being intended. For example, those suitable for oral administration may contain flavoring agents.

[0429] The compound (e.g., any one compound from formulas I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II) or a predetermined form of the compound (e.g., salt, ester, tautomer, prodrug, zwitterionic form, stereoisomer, etc.) may be administered orally or by injection at doses of 0.1 to 500 mg / kg / day. The dose range for adults is generally 5 mg to 2 g / day. Tablets or other forms of provision provided in separate units may conveniently contain units containing one or more compounds in amounts effective at that dose or multiple doses, for example, 5 mg to 500 mg, usually about 10 mg to 200 mg.

[0430] The amount of active ingredient that can be combined with a carrier material to create a single dosage form may vary depending on the host being treated and the specific method of administration.

[0431] method This disclosure also provides methods for modulating KRAS (e.g., KRAS having the G12D mutation), comprising contacting KRAS with a compound provided herein (e.g., any one of the compounds of formulas I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II), or a salt, ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof. For example, this disclosure may provide methods for modifying cellular phenotype, cell proliferation, KRAS activity, biochemical output resulting from active or inactive KRAS, KRAS expression, and / or the binding of KRAS to its natural binding partner. Any such properties can be monitored and modified by contacting KRAS with a compound provided herein or a predetermined form thereof. Methods for modulating KRAS (e.g., KRAS having the G12D mutation) may include therapies for diseases, disorders, or conditions (e.g., cancer), biological assays, cytoassays, biochemical assays, etc.

[0432] This disclosure also provides methods for treating a disease, disorder, or condition in a subject requiring treatment of the disease, disorder, or condition, using a compound provided herein (e.g., any one of the compounds of formula I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II), or a salt, ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof. For example, this disclosure provides a method comprising administering (e.g., giving) an effective amount of a compound provided herein (e.g., any one of the compounds of formula I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II), or a salt, ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof to a subject (e.g., a patient). This disclosure also provides a method for treating a disease, disorder, or condition in a subject requiring treatment of the disease, disorder, or condition, using a pharmaceutical composition comprising a compound provided herein (e.g., any one of the compounds of formula I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II), or a salt, ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof. For example, this disclosure provides a method comprising administering (e.g., giving) an effective amount of a pharmaceutical composition comprising a subject (e.g., a patient) requiring treatment of a pharmaceutical composition comprising an effective amount of a compound provided herein (e.g., any one of the compounds of formula I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II), or a salt, ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof. In some embodiments, the subject is known to have a disease, disorder, or condition such as cancer (e.g., previously diagnosed). The disease, disorder, or condition may be a KRAS-mediated disease, such as cancer characterized by the G12D mutation in KRAS. In some embodiments, the compounds administered to subjects requiring the compounds herein, according to the methods described herein, are the compounds described herein, or their stereoisomers or pharmaceutically acceptable salts, as described in the embodiments, examples, figures, or tables herein.

[0433] This disclosure also provides pharmaceutical compositions comprising any of the compounds provided herein (e.g., any one of the compounds of formula I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II), or their salts, esters, tautomers, prodrugs, zwitterionic forms, or stereoisomers, or any of the above compounds, with pharmaceutically acceptable excipients, for use as a drug, such as a drug for treating a disease, disorder, or condition (e.g., cancer). This disclosure also provides pharmaceutical compositions comprising any of the compounds provided herein (e.g., any one of the compounds of formula I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II), or their salts, esters, tautomers, prodrugs, zwitterionic forms, or stereoisomers, or any of the above compounds, with pharmaceutically acceptable excipients, for use in the manufacture of a drug for treating a target disease, disorder, or condition (e.g., cancer).

[0434] This disclosure also provides the use of a pharmaceutical composition comprising any of the compounds provided herein (e.g., any one of the compounds of formulas I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II), or a salt, ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof, or any of the above compounds, with a pharmaceutically acceptable excipient, for treating a target disease, disorder, or condition (e.g., cancer) requiring treatment of the disease, disorder, or condition.

[0435] The present disclosure also provides the use of a pharmaceutical composition comprising a compound provided herein (e.g., a compound of any one of Formula I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II), or a salt, ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof, or any of the above compounds, and a pharmaceutically acceptable excipient, for use in the manufacture of a medicament for treating a disease, disorder, or condition (e.g., cancer) of a subject in need of treatment of the disease, disorder, or condition.

[0436] The present disclosure also provides a method of inhibiting KRAS (e.g., KRAS having a G12D mutation) (e.g., in a subject in need of inhibition of KRAS), the method comprising contacting KRAS with a pharmaceutical composition comprising a compound provided herein (e.g., a compound of any one of Formula I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II), or a salt, ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof, or any of the above compounds, and a pharmaceutically acceptable excipient.

[0437] The disclosure also provides pharmaceutical compositions comprising any of the compounds provided herein (e.g., any one of the compounds of formulas I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II), or a salt, ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof, or any of the above compounds, with pharmaceutically acceptable excipients, for use in inhibiting KRAS (e.g., KRAS having the G12D mutation) in subjects requiring KRAS inhibition. The disclosure also provides pharmaceutical compositions comprising any of the compounds provided herein (e.g., any one of the compounds of formula I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II), or a salt, ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof, or any of the above compounds, with pharmaceutically acceptable excipients, for use in the manufacture of agents that inhibit KRAS (e.g., KRAS having the G12D mutation) in subjects requiring KRAS inhibition.

[0438] This disclosure also provides the use of a pharmaceutical composition comprising any of the compounds provided herein (e.g., any one of the compounds of formula I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II), or a salt, ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof, or any of the above compounds, with a pharmaceutically acceptable excipient, for inhibiting KRAS (e.g., KRAS having the G12D mutation) in subjects requiring KRAS inhibition.

[0439] This disclosure also provides the use of a pharmaceutical composition comprising any of the compounds provided herein (e.g., any one of the compounds of formula I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II), or a salt, ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof, or any of the above compounds, with a pharmaceutically acceptable excipient, in the manufacture of a drug for inhibiting KRAS (e.g., KRAS having the G12D mutation) in subjects requiring KRAS inhibition.

[0440] This disclosure also provides a method of alleviating, reducing, eliminating, stopping, or improving one or more symptoms of a subject (e.g., a patient) by administering a therapeutically effective amount of any of the compounds provided herein (e.g., any one of the compounds of formula I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II), or its salts, esters, tautomers, prodrugs, zwitterionic forms, or stereoisomers thereof, thereby alleviating, reducing, eliminating, stopping, or improving one or more symptoms of a subject, such as one or more symptoms of a disease, disorder, or condition (e.g., cancer). In some embodiments, administering a therapeutically effective amount of any of the compounds provided herein (e.g., any one of the compounds of formula I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II), or its salts, esters, tautomers, prodrugs, zwitterionic forms, or stereoisomers thereof, slows or prevents tumor growth. In some embodiments, administration of a therapeutically effective amount of any of the compounds provided herein (e.g., any one of the compounds of formulas I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II), or its salts, esters, tautomers, prodrugs, zwitterionic forms, or stereoisomers results in tumor reduction (e.g., tumor regression).

[0441] In some embodiments of any of the methods, uses, and agents provided herein, the disease, disorder, or condition is cancer. In some embodiments, cancer is pancreatic cancer (e.g., ductal adenocarcinoma), lung cancer (e.g., non-small cell lung cancer), colorectal cancer (CRC), endometrial cancer, uterine carcinosarcoma, Ewing's sarcoma, osteosarcoma, rhabdomyosarcoma, adrenocortical carcinoma, neuroblastoma, Wilms' tumor, retinoblastoma, skin cancer, breast cancer, prostate cancer, head and neck cancer, or ovarian cancer. In some embodiments, cancer is pancreatic cancer (e.g., ductal adenocarcinoma), lung cancer (e.g., non-small cell lung adenocarcinoma), or colorectal cancer (CRC). In some embodiments, cancer is pancreatic cancer (e.g., ductal adenocarcinoma). In some embodiments, cancer is non-small cell lung adenocarcinoma. In some embodiments, cancer is colorectal cancer (CRC). In some embodiments, cancer is a solid tumor or comprises a solid tumor.

[0442] In some embodiments, the disease, disorder, or condition is related to KRAS, such as a disorder associated with a mutation in KRAS or a dysregulation of KRAS. In some embodiments, the disease, disorder, or condition is related to the KRAS gene, such as a disease, disorder, or condition associated with a mutation in the KRAS gene or a dysregulation of the KRAS gene. KRAS or KRAS mutations or dysregulations may include mutations or dysregulations of human K-Ras4a and / or human K-Ras4b. In some embodiments, the disease, disorder, or condition is related to KRAS (e.g., human K-Ras4a or K-Ras4b) signaling pathway activity, such as a disease, disorder, or condition associated with abnormal KRAS signaling pathway activity. In some embodiments, the disease, disorder, or condition is related to mutations or dysregulations of human K-Ras4b. In some embodiments, the disease, disorder, or condition is related to abnormal K-Ras4b signaling pathway activity. In some embodiments, the disease, disorder, or condition is related to mutations or dysregulations of human K-Ras4a. In some embodiments, the disease, disorder, or condition is associated with abnormal K-Ras4a signaling pathway activity.

[0443] Administration and combination therapy The compounds provided herein (e.g., any one of the compounds of formulas I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II) and their prescribed forms (e.g., salts, esters, tautomers, prodrugs, zwitterionic forms, stereoisomers, etc.), or compositions containing them (e.g., pharmaceutical compositions) can be administered by various means (e.g., orally, topically, or by injection). The amount of the active ingredient (e.g., the compounds provided herein in any suitable form) administered to the subject (e.g., a patient) is the responsibility of the attending physician. A specific dose level for a particular subject (e.g., a patient) depends on a variety of factors, including, for example, the activity of the active ingredient being administered; the subject's physical attributes (e.g., age, weight, height, BMI, general health status, comorbidities, sex, etc.); other characteristics of the subject (e.g., diet, exercise level, country of origin, ethnicity, etc.); time of administration; route of administration; rate of excretion; concomitant medications; disease, disorder, or condition being treated; and the severity of disease, disorder, or condition being treated.

[0444] In some embodiments, the compounds provided herein (e.g., any one of the compounds of formula I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II) or a predetermined form thereof (e.g., salts, esters, tautomers, prodrugs, zwitterionic forms, stereoisomers, etc.) are administered in combination with additional agents, such as additional therapeutic agents. For example, if a subject experiences side effects such as hypertension when administered the compounds provided herein or a predetermined form thereof, it may be appropriate to administer additional agents effective in managing these side effects, such as antihypertensives. In another example, the therapeutic effect of the compounds provided herein (e.g., any one of the compounds of formula I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II) or a predetermined form thereof can be enhanced by the administration of an adjuvant, which may have only minimal therapeutic effect on its own, but can provide an enhanced overall therapeutic effect to the subject when used in combination with another therapeutic agent. In further examples, the therapeutic effect of a compound provided herein (e.g., any one of the compounds of formula I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II), or a predetermined form thereof, can be enhanced by the administration of the compound or another form thereof with additional agents (which may include additional treatment regimens) that also provide a therapeutic effect. For example, a compound provided herein (e.g., any one of the compounds of formula I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II), or a predetermined form thereof, can be administered in combination with additional agents that may be effective in treating diseases, disorders, or conditions such as cancer. In general, a combination of a compound provided herein (e.g., any one of the compounds of formula I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II) and one or more additional agents (e.g., therapeutic agents) can enhance the overall effect that the subject obtains from any of the individual components. In some embodiments, the effects may be additive. In some embodiments, the effects may be synergistic.

[0445] In some embodiments, the compounds provided herein (e.g., any one of the compounds of formulas I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II), or a predetermined form thereof (e.g., salts, esters, tautomers, prodrugs, zwitterionic forms, stereoisomers, etc.) are administered in combination with an anticancer agent (e.g., a chemotherapeutic agent). The anticancer agent may be, for example, an alkylating agent, a mitotic inhibitor, a checkpoint inhibitor, an antimetabolite, a plant alkaloid, a terpenoid, a cytotoxic agent, an antibiotic, a topoisomerase inhibitor, an aromatase inhibitor, angiogenesis inhibitor, an antisteroid, an antiandrogen, an mTOR inhibitor, a monoclonal antibody, or a tyrosine kinase inhibitor. The alkylating agent may be, for example, alumustine, chlorambucil (LEUKERAN), cisplatin (PLATIN), carboplatin (PARAPLATIN), oxaliplatin (ELOXATIN), streptozocin (ZANOSAR), busulfan (MYLERAN), dacarbazine, ifosfamide, lomustine (CCNU), melphalan (ALKERAN), procarbazine (MATULAN), temozolomide (TEMODAR), thiotepa, or cyclophosphamide (ENDOXAN). Antimetabolites may include, for example, cladribine (LEUSTATIN), mercaptopurine (PURINETHOL), thioguanine, pentostatin (NIPENT), cytosine arabinoside (Cytarabine, ARA-C), gemcitabine (GEMZAR), fluorouracil (5-FU, CARAC), capecitabine (XELODA), leucovorin (FUSILEY), methotrexate (RHEUMATREX), or larcitrexed. Antimitotic agents may include, for example, taxanes such as docetaxel (TAXITERE) or paclitaxel (ABRAXANE, TAXOL), or vinca alkaloids such as vincristine (ONCOVIN), vinblastine, vindesine, or vinorelbine (NAVELBINE).Checkpoint inhibitors may be anti-PD-1 or anti-PD-L1 antibodies such as pembrolizumab (KEYTRUDA), nivolumab (OPDIVO), MEDI4736, or MPDL3280A; anti-CTLA-4 antibody ipilimumab (YERVOY); or agents targeting LAG3 (lymphocyte activation gene 3 protein), KIR (killer cell immunoglobulin-like receptor), 4-1BB (tumor necrosis factor receptor superfamily member 9), TIM3 (T cell immunoglobulin and mucin domain-3), or 0X40 (tumor necrosis factor receptor superfamily member 4). Topoisomerase inhibitors may be, for example, camptothecin (CTP), irinotecan (CAMPTOSAR), topotecan (HYCAMTIN), teniposide (VUMON), or etoposide (EPOSIN). Cytotoxic antibiotics may include, for example, actinomycin D (dactinomycin, COSMEGEN), bleomycin (BLENOXANE), doxorubicin (ADRIAMYCIN), daunorubicin (CERUBIDINE), epirubicin (ELLENCE), fludarabine (FLUDARA), idarubicin, mitomycin (MITOSOL), mitoxantrone (NOYANTRONE), or plicamycin. Aromatase inhibitors may include, for example, aminoglutethimide, anastrozole (ARIMIDEX), letrozole (FEMARA), borozole (RIYIZOR), or exemestane (AROMASIN). Angiogenesis inhibitors may include, for example, genistein, sunitinib (SUTENT), or bevacizumab (AYASTIN). Antisteroids or antiandrogens may include, for example, aminoglutethimide (CYTADREN), bicalutamide (CASODEX), cyproterone, flutamide (EULEXIN), or nilutamide (NILANDRON). Tyrosine kinase inhibitors may include, for example, imatinib (GLEEVEC), erlotinib (TARCEVA), afatinib (GILOTRIF), lapatinib (TYKERB), sorafenib (NEXAVAR), or axitinib (INLYTA).The mTOR inhibitor may be, for example, everolimus, temsirolimus (TORISEL), or sirolimus. The monoclonal antibody may be, for example, trastuzumab (HERCEPTIN) or rituximab (RITUXAN). Further examples of agents that may be useful in combination with the compounds provided herein or their alternative forms include, but are not limited to, amsacrin; Bacillus Calmette-Guerin (BCG) vaccine; buserelin (ETILAMIDE); chloroquine (ARALEN); clodronate, pamidronate, and other bisphosphonates; colchicine; demethoxypyridine; dichloroacetate; estramustine; filgrastim (NEUPOGEN); fludrocortisone (FLORINEF); goserelin (ZOLADEX); interferon; leucovorin; leuprolide (LUPRON); levamisole; ronidamine; mesna; metformin; mitotane (o,r'-DD) Examples include D, lysodren; nocodazole; octreotide (sandostatin); perifosin; porfimers (especially in combination with phototherapy and radiotherapy); suramin; tamoxifen; titanocene dichloride; tretinoin; anabolic steroids such as fluoxymesterone (halotestin); estrogens such as estradiol, diethylstilbestrol (DES), and dienestrol; progestins such as medroxyprogesterone acetate (MPA) and megestrol; and testosterone.

[0446] Two or more therapeutic agents, one of which is a compound provided herein (e.g., formula I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II) or a predetermined form thereof, may be administered in any order or simultaneously. When administered simultaneously, the multiple therapeutic agents may be given in a single integrated form or in multiple forms (e.g., as one pill or as two separate pills). One therapeutic agent may be administered in multiple doses, or both may be administered in multiple doses. When not administered simultaneously, the timing between doses may be any period ranging from a few minutes to four weeks.

[0447] Accordingly, in another aspect, the present disclosure provides a method for treating a disease, disorder, or condition (e.g., cancer) in a subject (e.g., a human or animal subject) that requires treatment of the disease, disorder, or condition, the method comprising administering to the subject a predetermined amount of a compound provided herein (e.g., any one compound from formulas I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II), or a predetermined form thereof (e.g., a salt, ester, tautomer, prodrug, zwitterionic form, stereoisomer, etc.), in combination with at least one additional agent for the treatment of the disease, disorder, or condition. In related embodiments, the Disclosure provides a composition (e.g., a pharmaceutical composition) comprising a compound provided herein (e.g., any one of the compounds of formulas I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II) or a predetermined form thereof (e.g., a salt, ester, tautomer, prodrug, zwitterionic form, stereoisomer, etc.) and at least one additional agent for use in the treatment of a disease, disorder, or condition (e.g., cancer).

[0448] In some embodiments, the methods provided herein are used to treat a disease, disorder, or condition (e.g., cancer) and include administering a therapeutically effective amount of one compound of formula I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II, or a pharmaceutically acceptable salt thereof, to a subject in need of treatment for the disease, disorder, or condition, wherein the disease, disorder, or condition is cancer that has acquired resistance to one or more chemotherapeutic agents and / or ionizing radiation. In some embodiments, the methods provided herein are used to treat a disease, disorder, or condition (e.g., cancer) and include administering a therapeutically effective amount of one compound of formula I, IA, IA1, IA2, IB, IB1, IB2, IC, ID, ID', IE, IF, or II, or a pharmaceutically acceptable salt thereof, in combination with additional agents, to a subject in need of treatment for the disease, disorder, or condition, wherein the disease, disorder, or condition is cancer that has acquired resistance to one or more chemotherapeutic agents and / or ionizing radiation.

[0449] The compounds, compositions, and methods disclosed herein are useful for treating diseases, disorders, or conditions such as cancer. In certain embodiments, the disease is one of the dysregulated cell proliferations, including cancer. The cancer may be hormone-dependent or hormone-resistant, as in the case of breast cancer. In certain embodiments, the cancer is or comprises a solid tumor. In other embodiments, the cancer is lymphoma or leukemia. In certain embodiments, the cancer is a drug-resistant phenotype of cancer disclosed herein or otherwise known. Tumor invasion, tumor growth, tumor metastasis, and angiogenesis can also be treated using the compositions and methods disclosed herein. In some embodiments, the compounds, compositions, and methods provided herein are also useful for treating precancerous tumors.

[0450] Cancers treatable by the methods disclosed herein include, but are not limited to, pancreatic cancer, colon cancer, rectal cancer, colorectal cancer, breast cancer, ovarian cancer, endometrial cancer, lung cancer, and prostate cancer; cancers of the oral cavity and pharynx (lips, tongue, mouth, larynx, pharynx), esophagus, stomach, small intestine, large intestine, colon, rectum, liver, and biliary tract; cancers of the pancreas, bone, connective tissue, skin, cervix, uterus, endometrium, testes, bladder, kidney, and other urinary tissues, including renal cell carcinoma (RCC); cancers of the eye, brain, spinal cord, and other components of the central and peripheral nervous systems, as well as cancers of related structures such as the meninges; and cancers of the thyroid and other endocrine glands. The term "cancer" includes cancers that do not necessarily form solid tumors, including Hodgkin's disease, non-Hodgkin lymphoma, multiple myeloma, and hematopoietic malignancies, such as leukemia (chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia) (CML), acute myeloid leukemia (AML), and lymphomas, including lymphocytic, granulocytic, and monocytic lymphomas. Further types of cancer that can be treated with the compounds and methods provided herein include, but are not limited to, adenocarcinoma, angiosarcoma, astrocytoma, acoustic neuroma, undifferentiated astrocytoma, basal cell carcinoma, blastoma, chondrosarcoma, choriocarcinoma, chordoma, craniopharyngioma, cutaneous melanoma, cystadenocarcinoma, endosarcoma, embryonal carcinoma, ependymoma, Ewing's tumor, epithelial carcinoma, fibrosarcoma, gastric cancer, genitourinary cancer, glioblastoma multiforme, head and neck cancer, angioblastoma, hepatocellular carcinoma, liver cancer, Kaposi's sarcoma, large cell carcinoma, leiomyosarcoma, leukemia, liposarcoma, and phosphate Examples include P-type carcinomas, lymphomas, lymphangiosarcomas, intralymphatic sarcomas, medullary thyroid carcinomas, medulloblastomas, meningiomas, mesotheliomas, myelomas, myxosarcomas, neuroblastomas, neurofibrosarcomas, oligodendrogliomas, osteogenic sarcomas, epithelial ovarian cancers, papillary carcinomas, papillary adrenocortical carcinomas, paragangliomas, parathyroid tumors, pheochromocytomas, pineal glandomas, plasmacytomas, retinoblastomas, rhabdomyosarcomas, sebaceous gland carcinomas, seminomas, skin cancers, melanomas, small cell lung cancers, non-small cell lung cancers, squamous cell carcinomas, sweat gland carcinomas, synoviomas, thyroid cancers, uveal melanomas, and Wilms' tumors.Further diseases and disorders treatable by the methods disclosed herein include, but are not limited to, KRAS-related diseases or disorders, such as diseases or disorders associated with mutations in KRAS or dysregulation of KRAS, and KRAS gene-related diseases or disorders, such as diseases or disorders associated with mutations in the KRAS gene or dysregulation of the KRAS gene.

[0451] In some embodiments, the compounds, compositions, and methods provided herein are useful for preventing and / or reducing tumor invasion, growth, and / or metastasis.

[0452] The compounds, compositions, and methods provided herein may be useful for the treatment of humans, as well as for the veterinary treatment of non-human animals, including companion animals such as mammals (e.g., those described herein), rodents, exotic animals, and livestock. For example, the compounds, compositions, and methods provided herein may be useful for the treatment of horses, dogs, or cats.

[0453] List of embodiments Embodiment I-1. Compound represented by formula I: [ka] or its salts (e.g., pharmaceutically acceptable salts), esters, tautomers, prodrugs, zwitterionic forms, or stereoisomers [in the formula, R 1 is -OR 8 A 4-6 member heterocycle containing a nitrogen atom, selected from H, wherein the heterocycle is unsubstituted or has one or more R 16 Replaced by, R 2 H and C 1~6 Selected from alkyl groups, R 3 C 1~6 Selected from alkyl, carbocyclic, and heterocyclic elements, however any C 1~6 Alkyl is one or more R 9Substituted by, and the carbocyclic or heterocyclic ring is unsubstituted or has one or more R 10 Replaced by, Or, R 2 and R 3 This refers to the atoms to which they are bonded, and whether they are unsubstituted or have one or more R 11 Forms a heterocycle substituted with, R 4 H, halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 5 is halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 6 is one or more R 15 It is a bicyclic heteroaryl substituted with, R 7 is halogen, -OR 12 Selected from , -CN, and H, R 8 The component is selected from heterocycles and alkyl heterocycles, and either is unsubstituted or has one or more R 16 Replaced by, Each R 9 is -N(R 17 )2, -N(R 17 )C(O)C 1~6 Alkyl and -OR 17Selected independently of, however, any C 1~6 Alkyl is either unsubstituted or has one or more R 18 Replaced by, Each R 10 is -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )2, -C(O)(C 1~6 Alkyl)N(R 19 )2, -(C 1~6 Alkyl)C(O)N(R 19 )2, -C(NR 19 )NR 19 CN, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 20 Replaced by, Each R 11 is -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )2, -C(O)(C 1~6 Alkyl)N(R 19 )2, -(C 1~6 Alkyl)C(O)N(R 19 )2, -C(NR 19 )NR 19 CN, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 20 Replaced by, Each R 12 C 1~6 Alkyl, C 2~6 Alkenyl and H are selected independently, except for any C 1~6 Alkyl or C 2~6 Alkenyls are either unsubstituted or have one or more R 13 Replaced by, Each R 13 is -OR 22 -CN, -N(R 22 )2, and selected independently from halogens, Each R 14 Halogen, N(R) 12)2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 15 Halogen, N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 16 Halogen, -N(R 12 )2, and C 1~6 Alkyl and -OR 12 Selected independently of, however, any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 17 C 1~6 Selected independently from alkyl and H, Each R 18 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 19 C 1~6 Selected independently from alkyl and H, except for any C 1~6 Alkyl is either unsubstituted or has one or more R 21 Replaced by, Each R 20 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 21 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 22 C 1~6 Alkyl, C 2~6 [Selected independently of alkenyl and H].

[0454] Embodiment I-2.R 1 However, -OR 8 The compound of Embodiment I-1.

[0455] Embodiment I-3.R 8 However, the compound of Embodiment I-2 is a heterocyclic compound.

[0456] Embodiment I-4.R 8 However, the compound of Embodiment I-3 is an alkyl heterocycle.

[0457] Embodiment I-5.R 8 A compound of Embodiment I-3 or I-4, comprising a heterocycle containing at least one nitrogen atom.

[0458] Embodiment I-6. The complex ring is one or R 16 A compound comprising a substituent, one of any one of embodiments I-3 to I-5.

[0459] Embodiment I-7. At least one R 16 ga-OR 12 And, however, R 12 C 1~6 Alkyl, C 2~6 Compounds of Embodiments I-6, independently selected from alkenyl and H.

[0460] Embodiment I-8. At least one R 16 However, the compound of Embodiment I-7 is -OCH3.

[0461] Embodiment I-9.R 1 but, [ka] A compound of Embodiment I-1, selected from the above.

[0462] Embodiment I-10.R 1 but, [ka] A compound of Embodiment I-1, selected from the above.

[0463] Embodiment I-11.R 1 However, it is a 4-6 member heterocycle containing a nitrogen atom, and the heterocycle is unsubstituted or has one or more R 16 The compound of Embodiment I-1, which is substituted with [the compound].

[0464] Embodiment I-12.R 1 but, [ka] A compound of Embodiment I-11, selected from the above.

[0465] Embodiment I-13.R 1 However, the compound of Embodiment I-1 is H.

[0466] Embodiment I-14.R 2 A compound from any one of embodiments I-1 to I-13, wherein is H.

[0467] Embodiment I-15.R 2 However, C 1~6 A compound that is alkyl, one of the compounds from Embodiments I-1 to I-13.

[0468] Embodiment I-16.R 3 C 1~6 It is alkyl, C 1~6 Alkyl is one or more R 9 A compound from any one of embodiments I-1 to I-15, which is substituted with [the compound].

[0469] Embodiment I-17.R 3 However, -N(R 17 C replaced with )2 1~6 It is alkyl, however each R 17 C 1~6 A compound of Embodiment I-16, independently selected from alkyl and H.

[0470] Embodiment I-18.R 3However, C substituted with -NH2 1~6 The compound of Embodiment I-17, which is alkyl.

[0471] Embodiment I-19.R 3 but, [ka] Compounds of embodiments I-1 to I-15, selected from the above.

[0472] Embodiment I-20.R 3 is a carbon ring, and the carbon ring is unsubstituted or has one or more R 10 A compound from any one of embodiments I-1 to I-15, which is substituted with [the compound].

[0473] Embodiment I-21.R 3 However, -N(R 19 A carbon ring substituted with )2, where each R 19 This is either non-substitutive or substituted C 1~6 Compounds of Embodiment I-20, independently selected from alkyl and H.

[0474] Embodiment I-22.R 3 However, the compound of Embodiment I-21 is a carbon ring substituted with -NH2.

[0475] Embodiment I-23.R 3 However, C 1~6 alkyl-N(R 17 )C(O)C 1~6 Alkyl N(R) 17 One compound selected from )2, which is one of the compounds from Embodiments I-1 to I-15.

[0476] Embodiment I-24.R 3 The complex ring is a complex ring, and the complex ring is unsubstituted or has one or more R 10 A compound from any one of embodiments I-1 to I-15, which is substituted with [the compound].

[0477] Embodiment I-25. The compound of Embodiment I-24, wherein the heterocycle contains one or more nitrogen atoms.

[0478] Embodiment I-26.R 3 However, -N(R 19 ) is a heterogeneous ring substituted with 2, where each R 19 This is either non-substitutive or substituted C 1~6 A compound of Embodiment I-24 or I-25, independently selected from alkyl and H.

[0479] Embodiment I-27.R 3 However, the compound of Embodiment I-26 is a heterocycle substituted with -NH2.

[0480] Embodiment I-28.R 3 but, [ka] Selected from, none of these are non-substituted or one or more R 10 A compound from any one of embodiments I-1 to I-15, which is substituted with [the compound].

[0481] Embodiment I-29.R 2 or R 3 However, one of the compounds from Embodiments I-15 to I-28, which contains an amino portion.

[0482] Embodiment I-30.R 2 and R 3 and together with the atom to which they are bonded (for example, a nitrogen atom), they are either unsubstituted or have one or more R 11 A compound from any one of embodiments I-1 to I-13 that forms a heterocycle substituted with .

[0483] Embodiment I-31.R 2 and R 3 And, together with the atoms to which they are bonded, form the following structure: [ka] A heterocycle is formed having any of these, and none of them are substituted or one or more R 11The compound of Embodiment I-30, which is substituted with [the compound].

[0484] Embodiment I-32.R 2 and R 3 And, together with the atoms to which they are bonded, form the following structure: [ka] A compound of Embodiment I-30 that forms a heterocycle having [a specific component].

[0485] Embodiment I-33.R 2 and R 3 A compound from any one of Embodiments I-30 to I-32, wherein the nitrogen atom to which they are bonded forms a heterocycle that is (i) substituted with an additional nitrogen atom or (ii) substituted with a group containing an amino moiety.

[0486] Embodiment I-34.R 4 A compound from any one of embodiments I-1 to I-33, wherein the compound is hydrogen.

[0487] Embodiment I-35.R 4 A compound from any one of embodiments I-1 to I-33, wherein the compound is hydrogen.

[0488] Embodiment I-36.R 5 A compound from any one of embodiments I-1 to I-35, wherein the compound is hydrogen.

[0489] Embodiment I-37.R 7 A compound from any one of embodiments I-1 to I-36, wherein the compound is hydrogen.

[0490] Embodiment I-38.R 6 but, [ka] A compound selected from any one of embodiments I-1 to I-37.

[0491] Embodiment I-39.R 6 but, [ka] A compound of Embodiment I-38, selected from the above.

[0492] Embodiment I-40.R 6 but, [ka] A compound of Embodiment I-39, selected from the above.

[0493] Embodiment I-41. Compound represented by formula IA: [ka] or its salts (e.g., pharmaceutically acceptable salts), esters, tautomers, prodrugs, zwitterionic forms, or stereoisomers [in the formula, R 1 is -OR 8 A 4-6 member heterocycle containing a nitrogen atom, selected from H, wherein the heterocycle is unsubstituted or has one or more R 16 Replaced by, R 2 H is, R 3 C 1~6 Selected from alkyl, carbocyclic, and heterocyclic elements, however any C 1~6 Alkyl is one or more R 9 Substituted by, and the carbocyclic or heterocyclic ring is unsubstituted or has one or more R 10 Replaced by, R 4 H, halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R5 is halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 6 is one or more R 15 It is a bicyclic heteroaryl substituted with, R 7 is halogen, -OR 12 Selected from , -CN, and H, R 8 The component is selected from heterocycles and alkyl heterocycles, and either is unsubstituted or has one or more R 16 Replaced by, Each R 9 is -N(R 17 )2, -N(R 17 )C(O)C 1~6 Alkyl and -OR 17 Selected independently of, however, any C 1~6 Alkyl is either unsubstituted or has one or more R 18 Replaced by, Each R 10 is -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )2, -C(O)(C 1~6 Alkyl)N(R 19 )2, -(C 1~6 Alkyl)C(O)N(R 19 )2, -C(NR 19 )NR 19 CN, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 20 Replaced by, Each R 12 C 1~6 Alkyl, C2~6 Alkenyl and H are selected independently, except for any C 1~6 Alkyl or C 2~6 Alkenyls are either unsubstituted or have one or more R 13 Replaced by, Each R 13 is -OR 22 -CN, -N(R 22 )2, and selected independently from halogens, Each R 14 Halogen, N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 15 Halogen, N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 16 Halogen, -N(R 12 )2, and C 1~6 Alkyl and -OR 12 Selected independently of, however, any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 17 C 1~6 Selected independently from alkyl and H, Each R 18 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 19 C 1~6 Selected independently from alkyl and H, except for any C 1~6 Alkyl is either unsubstituted or has one or more R 21 Replaced by, Each R 20 -OH, -OC 1~6Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 21 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 22 C 1~6 Alkyl, C 2~6 [Selected independently of alkenyl and H].

[0494] Embodiment I-42.R 3 However, selected from carbocyclic and heterocyclic rings, wherein the carbocyclic or heterocyclic ring is unsubstituted or has one or more R 10 The compound of Embodiment I-41, which is substituted with [the compound].

[0495] Embodiment I-43.R 3 However, it is either unsubstituted or one or more R 10 The compounds of Embodiment I-42, which are 3- to 6-membered carbocyclic or heterocyclic rings substituted with .

[0496] Embodiment I-44.R 3 but, [ka] Selected from, none of these are non-substituted or one or more R 10 The compound of Embodiment I-43, which is substituted with [the compound].

[0497] Embodiment I-45.R 3 However, one or more R 9 C replaced by 1~6 Compounds of Embodiment I-41, selected from alkyl groups.

[0498] Embodiment I-46.R 3 However, C 1~6 alkyl-N(R 17 A compound of Embodiments I-45, selected from )2.

[0499] Embodiment I-47.R 3 but, [ka] A compound of embodiment I-45 or I-46, selected from the above.

[0500] Embodiment I-48.R 3 However, C 1~6 alkyl-N(R 17 )C(O)C 1~6 Alkyl N(R) 17 A compound of Embodiments I-45, selected from )2.

[0501] Embodiment I-49.R 3 A compound from any one of embodiments I-41 to I-48, wherein the compound contains an amino portion.

[0502] Embodiment I-50.R 1 A compound from any one of embodiments I-41 to I-49, wherein is H.

[0503] Embodiment I-51.R 1 ga-OR 8 The compound is one of any of embodiments I-41 to I-50.

[0504] Embodiment I-52.R 8 However, it is either unsubstituted or one or more R 14 Compounds of Embodiment I-51 comprising a 3- to 6-membered heterocycle substituted with .

[0505] Embodiment I-53.R 1 but, [ka] A compound of embodiment I-51 or I-52, selected from the above.

[0506] Embodiment I-54.R 1 but, [ka] A compound of embodiment I-51 or I-52, selected from the above.

[0507] Embodiment I-55.R 1 However, it is either unsubstituted or one or more R 16 A compound from any one of embodiments I-41 to I-54, which is a 4- to 6-membered heterocycle containing a nitrogen atom substituted with .

[0508] Embodiment I-56.R 1 but, [ka] A compound of Embodiment I-55, selected from the above.

[0509] Embodiment I-57.R 6 but, [ka] A compound selected from any one of embodiments I-41 to I-56.

[0510] Embodiment I-58.R 6 but, [ka] A compound of Embodiment I-57, selected from the above.

[0511] Embodiment I-59.R 6 but, [ka] A compound of Embodiment I-58, selected from the above.

[0512] Embodiment I-60.R 4 A compound from any one of embodiments I-41 to I-59, wherein is H.

[0513] Embodiment I-61.R 4 A compound from any one of embodiments I-41 to I-59, wherein is a halogen.

[0514] Embodiment I-62.R 5 A compound from any one of embodiments I-41 to I-61, wherein is a halogen.

[0515] Embodiment I-63.R 7 A compound from any one of embodiments I-41 to I-62, wherein is a halogen.

[0516] Embodiment I-64. Compound according to formula IA1: [ka] or its salts (e.g., pharmaceutically acceptable salts), esters, tautomers, prodrugs, zwitterionic forms, or stereoisomers [in the formula, R 1 H is, R 2 H is, R 3 C 1~6 Selected from alkyl, carbocyclic, and heterocyclic elements, however any C 1~6 Alkyl is one or more R 9 Substituted by, and the carbocyclic or heterocyclic ring is unsubstituted or has one or more R 10 Replaced by, R 4 H, halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 5 is halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 6 is one or more R 15 It is a bicyclic heteroaryl substituted with, R 7 is halogen, -OR 12 Selected from , -CN, and H, Each R 9 is -N(R 17 )2, -N(R 17 )C(O)C 1~6 Alkyl and -OR 17 Selected independently of, however, any C 1~6 Alkyl is either unsubstituted or has one or more R 18 Replaced by, Each R 10 is -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )2, -C(O)(C 1~6 Alkyl)N(R 19 )2, -(C 1~6 Alkyl)C(O)N(R 19 )2, -C(NR 19 )NR 19 CN, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 20 Replaced by, Each R 11 is -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )2, -C(O)(C 1~6 Alkyl)N(R 19 )2, -(C 1~6 Alkyl)C(O)N(R 19 )2, -C(NR 19 )NR 19 CN, and C 1~6Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 20 Replaced by, Each R 12 C 1~6 Alkyl, C 2~6 Alkenyl and H are selected independently, except for any C 1~6 Alkyl or C 2~6 Alkenyls are either unsubstituted or have one or more R 13 Replaced by, Each R 13 is -OR 22 -CN, -N(R 22 )2, and selected independently from halogens, Each R 14 Halogen, N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 15 Halogen, N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 17 C 1~6 Selected independently from alkyl and H, Each R 18 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 19 C 1~6 Selected independently from alkyl and H, except for any C 1~6 Alkyl is either unsubstituted or has one or more R 21 Replaced by, Each R 20 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6Selected independently from alkyl and halogen, Each R 21 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 22 C 1~6 Alkyl, C 2~6 [Selected independently of alkenyl and H].

[0517] Embodiment I-65.R 3 However, selected from carbocyclic and heterocyclic rings, wherein the carbocyclic or heterocyclic ring is unsubstituted or has one or more R 10 The compound of Embodiment I-64, which is substituted with [the compound].

[0518] Embodiment I-66.R 3 but, [ka] Selected from, none of these are non-substituted or one or more R 10 The compound of Embodiment I-65, which is substituted with [the compound].

[0519] Embodiment I-67.R 3 However, one or more R 9 C replaced by 1~6 Compounds of Embodiment I-64, selected from alkyl groups.

[0520] Embodiment I-68.R 3 but, [ka] A compound of Embodiment I-67, selected from the above.

[0521] Embodiment I-69.R 3 However, C 1~6 alkyl-N(R 17 )C(O)C 1~6 Alkyl N(R) 17 A compound of Embodiment I-64, selected from )2.

[0522] Embodiment I-70.R 3 A compound from any one of embodiments I-64 to I-68, wherein the compound contains an amino portion.

[0523] Embodiment I-71.R 6 but, [ka] One compound selected from any of embodiments I-62 to I-70.

[0524] Embodiment I-72.R 6 but, [ka] A compound of Embodiment I-71, selected from the above.

[0525] Embodiment I-73.R 6 but, [ka] A compound of Embodiment I-72, selected from the above.

[0526] Embodiment I-74.R 4 A compound from any one of embodiments I-64 to I-73, wherein is H.

[0527] Embodiment I-75.R 4 A compound from any one of embodiments I-64 to I-73, wherein is a halogen.

[0528] Embodiment I-76.R 5 A compound from any one of embodiments I-64 to I-75, wherein is a halogen.

[0529] Embodiment I-77.R 7 A compound from any one of embodiments I-64 to I-76, wherein is a halogen.

[0530] Embodiment I-78. Compound according to formula IA2: [ka] or its salts (e.g., pharmaceutically acceptable salts), esters, tautomers, prodrugs, zwitterionic forms, or stereoisomers [in the formula, R 1は -OR 8 and; R 2 H is, R 3 C 1~6 Selected from alkyl, carbocyclic, and heterocyclic elements, however any C 1~6 Alkyl is one or more R 9 Substituted by, and the carbocyclic or heterocyclic ring is unsubstituted or has one or more R 10 Replaced by, R 4 H, halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 5 is halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 6 is one or more R 15 It is a bicyclic heteroaryl substituted with, R 7 is halogen, -OR12 Selected from , -CN, and H, R 8 The component is selected from heterocycles and alkyl heterocycles, and either is unsubstituted or has one or more R 16 Replaced by, Each R 9 is -N(R 17 )2, -N(R 17 )C(O)C 1~6 Alkyl and -OR 17 Selected independently of, however, any C 1~6 Alkyl is either unsubstituted or has one or more R 18 Replaced by, Each R 10 is -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )2, -C(O)(C 1~6 Alkyl)N(R 19 )2, -(C 1~6 Alkyl)C(O)N(R 19 )2, -C(NR 19 )NR 19 CN, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 20 Replaced by, Each R 12 C 1~6 Alkyl, C 2~6 Alkenyl and H are selected independently, except for any C 1~6 Alkyl or C 2~6 Alkenyls are either unsubstituted or have one or more R 13 Replaced by, Each R 13 is -OR 22 -CN, -N(R 22 )2, and selected independently from halogens, Each R 14 Halogen, N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13Replaced by, Each R 15 Halogen, N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 16 Halogen, -N(R 12 )2, and C 1~6 Alkyl and -OR 12 Selected independently of, however, any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 17 C 1~6 Selected independently from alkyl and H, Each R 18 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 19 C 1~6 Selected independently from alkyl and H, except for any C 1~6 Alkyl is either unsubstituted or has one or more R 21 Replaced by, Each R 20 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 21 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 22 C 1~6 Alkyl, C 2~6 [Selected independently of alkenyl and H].

[0531] Embodiment I-79.R 8 However, it is either unsubstituted or one or more R 14Compounds of Embodiment I-78 comprising a 3- to 6-membered heterocycle substituted with .

[0532] Embodiment I-80.R 1 but, [ka] A compound of Embodiment I-78, selected from the above.

[0533] Embodiment I-81.R 1 but, [ka] A compound of Embodiment I-78, selected from the above.

[0534] Embodiment I-82.R 3 However, selected from carbocyclic and heterocyclic rings, wherein the carbocyclic or heterocyclic ring is unsubstituted or has one or more R 10 A compound from any one of embodiments I-78 to I-81, which is substituted with [the specified compound].

[0535] Embodiment I-83.R 3 but, [ka] Selected from, none of these are non-substituted or one or more R 10 The compound of Embodiment I-82, which is substituted with [the compound].

[0536] Embodiment I-84.R 3 However, one or more R 9 C replaced by 1~6 A compound selected from alkyl groups, one of any of embodiments I-78 to I-83.

[0537] Embodiment I-85.R 3 but, [ka] A compound of Embodiment I-84, selected from the above.

[0538] Embodiment I-86.R 3 However, C 1~6 alkyl-N(R 17 )C(O)C 1~6 Alkyl N(R) 17 One compound selected from )2, which is one of the compounds from Embodiments I-78 to I-85.

[0539] Embodiment I-87.R 3 A compound from any one of embodiments I-78 to I-86, wherein the compound contains an amino portion.

[0540] Embodiment I-88.R 6 but, [ka] A compound selected from any one of embodiments I-78 to I-87.

[0541] Embodiment I-89.R 6 but, [ka] A compound of Embodiment I-88, selected from the above.

[0542] Embodiment I-90.R 6 but, [ka] A compound of Embodiments I-89, selected from the above.

[0543] Embodiment I-91.R 4 A compound from any one of embodiments I-78 to I-90, wherein is H.

[0544] Embodiment I-92.R 4 A compound from any one of embodiments I-78 to I-90, wherein is a halogen.

[0545] Embodiment I-93.R 5A compound from any one of embodiments I-78 to I-92, wherein is a halogen.

[0546] Embodiment I-94.R 7 A compound from any one of embodiments I-78 to I-93, wherein is a halogen.

[0547] Embodiment I-95. Compound according to formula IB: [ka] or its salts (e.g., pharmaceutically acceptable salts), esters, tautomers, prodrugs, zwitterionic forms, or stereoisomers [in the formula, R 1 is -OR 8 A 4-6 member heterocycle containing a nitrogen atom, selected from H, wherein the heterocycle is unsubstituted or has one or more R 16 Replaced by, Ring A is either unsubstituted or contains one or more R 11 It is a complex ring substituted with, R 4 H, halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 5 is halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 6 is one or more R 15 It is a bicyclic heteroaryl substituted with, R 7 is halogen, -OR 12 Selected from , -CN, and H, R 8 The component is selected from heterocycles and alkyl heterocycles, and either is unsubstituted or has one or more R 16 Replaced by, Each R 11 is -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )2, -C(O)(C 1~6 Alkyl)N(R 19 )2, -(C 1~6 Alkyl)C(O)N(R 19 )2, -C(NR 19 )NR 19 CN, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 20 Replaced by, Each R 12 C 1~6 Alkyl, C 2~6 Alkenyl and H are selected independently, except for any C 1~6 Alkyl or C 2~6 Alkenyls are either unsubstituted or have one or more R 13 Replaced by, Each R 13 is -OR 22 -CN, -N(R 22 )2, and selected independently from halogens, Each R 14 Halogen, N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 15 Halogen, N(R) 12 )2, and C 1~6Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 16 Halogen, -N(R 12 )2, and C 1~6 Alkyl and -OR 12 Selected independently of, however, any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 19 C 1~6 Selected independently from alkyl and H, except for any C 1~6 Alkyl is either unsubstituted or has one or more R 21 Replaced by, Each R 20 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 21 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 22 C 1~6 Alkyl, C 2~6 [Selected independently of alkenyl and H].

[0548] Embodiment I-96. Ring A is unsubstituted or has one or more R 11 The compound of Embodiment I-95 is a 4- to 6-membered heterocycle substituted with .

[0549] Embodiment I-97. Compound of Embodiment I-95, wherein ring A has the following structure: [ka] (The ring is either unsubstituted or has one or more R 11 (It has been replaced with...)

[0550] Embodiment I-98. Compound of Embodiment I-95, wherein ring A has the following structure: [ka]

[0551] Embodiment I-99. Any one of the compounds from Embodiments I-95 to I-98, wherein ring A contains at least two nitrogen atoms and / or is substituted with a group containing an amino moiety.

[0552] Embodiment I-100.R 1 A compound from any one of embodiments I-95 to I-99, wherein is H.

[0553] Embodiment I-101.R 1 ga-OR 8 The compound is one of any two of the embodiments I-95 to I-99.

[0554] Embodiment I-102.R 8 However, it is either unsubstituted or one or more R 14 Compounds of Embodiment I-101 comprising a 3- to 6-membered heterocycle substituted with .

[0555] Embodiment I-103.R 1 but, [ka] A compound of Embodiment I-101, selected from the above.

[0556] Embodiment I-104.R 1 but, [ka] Compounds of application form I-101, selected from the above.

[0557] Embodiment I-105.R 1 However, it is either unsubstituted or one or more R 16 A compound from any one of embodiments I-95 to I-99, which is a 4- to 6-membered heterocycle containing a nitrogen atom substituted with .

[0558] Embodiment I-106.R 1 but, [ka] A compound of Embodiment I-105, selected from the above.

[0559] Embodiment I-107.R 6 but, [ka] One compound selected from any of embodiments I-95 to I-106.

[0560] Embodiment I-108.R 6 but, [ka] A compound of Embodiment I-107, selected from the above.

[0561] Embodiment I-109.R 6 but, [ka] A compound of Embodiment I-108, selected from the above.

[0562] Embodiment I-110.R 4 A compound from any one of embodiments I-95 to I-109, wherein is H.

[0563] Embodiment I-111.R 4 A compound from any one of embodiments I-95 to I-109, wherein is a halogen.

[0564] Embodiment I-112.R 5 A compound from any one of embodiments I-95 to I-111, wherein is a halogen.

[0565] Embodiment I-113.R 7A compound from any one of embodiments I-95 to I-112, wherein is a halogen.

[0566] Embodiment I-114. Compound according to formula IB1: [ka] or its salts (e.g., pharmaceutically acceptable salts), esters, tautomers, prodrugs, zwitterionic forms, or stereoisomers [in the formula, Ring A is either unsubstituted or contains one or more R 11 It is a complex ring substituted with, R 4 H, halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 5 is halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 6 is one or more R 15 It is a bicyclic heteroaryl substituted with, R 7 is halogen, -OR 12 Selected from , -CN, and H, Each R 11 is -N(R 19 )2, -C(O)R 19 ,-C(O)N(R19 )2, -C(O)(C 1~6 Alkyl)N(R 19 )2, -(C 1~6 Alkyl)C(O)N(R 19 )2, -C(NR 19 )NR 19 CN, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 20 Replaced by, Each R 12 C 1~6 Alkyl, C 2~6 Alkenyl and H are selected independently, except for any C 1~6 Alkyl or C 2~6 Alkenyls are either unsubstituted or have one or more R 13 Replaced by, Each R 13 is -OR 22 -CN, -N(R 22 )2, and selected independently from halogens, Each R 14 Halogen, N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 15 Halogen, N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 19 C 1~6 Selected independently from alkyl and H, except for any C 1~6 Alkyl is either unsubstituted or has one or more R 21 Replaced by, Each R 20 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6Selected independently from alkyl and halogen, Each R 21 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 22 C 1~6 Alkyl, C 2~6 [Selected independently of alkenyl and H].

[0567] Embodiment I-115. Ring A is unsubstituted or has one or more R 11 The compound of Embodiment I-114 is a 4- to 6-membered heterocycle substituted with .

[0568] Embodiment I-116. The compound of Embodiment I-114, wherein ring A has the following structure: [ka] (The ring is either unsubstituted or has one or more R 11 (It has been replaced with...)

[0569] Embodiment I-117. The compound of Embodiment I-114, wherein ring A has the following structure: [ka]

[0570] Embodiment I-118. Any one of the compounds from Embodiments I-114 to I-117, wherein ring A contains at least two nitrogen atoms and / or is substituted with a group containing an amino moiety.

[0571] Embodiment I-119.R 6 but, [ka] One compound selected from any of embodiments I-114 to I-118.

[0572] Embodiment I-120.R 6but, [ka] A compound of Embodiment I-119, selected from the above.

[0573] Embodiment I-121.R 6 but, [ka] A compound of Embodiment I-120, selected from the above.

[0574] Embodiment I-122.R 4 A compound from any one of embodiments I-114 to I-121, wherein is H.

[0575] Embodiment I-123.R 4 A compound from any one of embodiments I-114 to I-121, wherein is a halogen.

[0576] Embodiment I-124.R 5 A compound from any one of embodiments I-114 to I-123, wherein is a halogen.

[0577] Embodiment I-125.R 7 A compound from any one of embodiments I-114 to I-124, wherein is a halogen.

[0578] Embodiment I-126. Compound according to formula IB2: [ka] or its salts (e.g., pharmaceutically acceptable salts), esters, tautomers, prodrugs, zwitterionic forms, or stereoisomers [in the formula, R 1 は-OR 8 and; Ring A is either unsubstituted or contains one or more R 11 It is a complex ring substituted with, R 4 H, halogen, -OR 12 ,-CN,C1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkynnyls, 3-6 membered carbon rings, and 3-6 membered heterorings, where any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 5 is halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 6 is one or more R 15 It is a bicyclic heteroaryl substituted with, R 7 is halogen, -OR 12 Selected from , -CN, and H, R 8 The component is selected from heterocycles and alkyl heterocycles, and either is unsubstituted or has one or more R 16 Replaced by, Each R 11 is -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )2, -C(O)(C 1~6 Alkyl)N(R 19 )2, -(C 1~6 Alkyl)C(O)N(R 19 )2, -C(NR 19 )NR 19 CN, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 20 Replaced by, Each R 12C 1~6 Alkyl, C 2~6 Alkenyl and H are selected independently, except for any C 1~6 Alkyl or C 2~6 Alkenyls are either unsubstituted or have one or more R 13 Replaced by, Each R 13 is -OR 22 -CN, -N(R 22 )2, and selected independently from halogens, Each R 14 Halogen, N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 15 Halogen, N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 16 Halogen, -N(R 12 )2, and C 1~6 Alkyl and -OR 12 Selected independently of, however, any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 19 C 1~6 Selected independently from alkyl and H, except for any C 1~6 Alkyl is either unsubstituted or has one or more R 21 Replaced by, Each R 20 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 21 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6Selected independently from alkyl and halogen, Each R 22 C 1~6 Alkyl, C 2~6 [Selected independently of alkenyl and H].

[0579] Embodiment I-127. Ring A is unsubstituted or has one or more R 11 The compound of Embodiment I-126, which is a 4- to 6-membered heterocycle substituted with .

[0580] Embodiment I-128. The compound of Embodiment I-126, wherein ring A has the following structure: [ka] (The ring is either unsubstituted or has one or more R 11 (It has been replaced with...)

[0581] Embodiment I-129. The compound of Embodiment I-126, wherein ring A has the following structure: [ka]

[0582] Embodiment I-130. Any one of the compounds from Embodiments I-126 to I-129, wherein ring A contains at least two nitrogen atoms and / or is substituted with a group containing an amino moiety.

[0583] Embodiment I-131.R 8 However, it is either unsubstituted or one or more R 14 A compound from any one of embodiments I-126 to I-130, comprising a 3- to 6-membered heterocycle substituted with .

[0584] Embodiment I-132.R 1 but, [ka] One compound selected from any of embodiments I-126 to I-131.

[0585] Embodiment I-133.R 1 but, [ka] One compound selected from any of embodiments I-126 to I-131.

[0586] Embodiment I-134.R 6 but, [ka] One compound selected from any of embodiments I-126 to I-133.

[0587] Embodiment I-135.R 6 but, [ka] A compound of Embodiment I-134, selected from the above.

[0588] Embodiment I-136.R 6 but, [ka] A compound of Embodiment I-135, selected from the above.

[0589] Embodiment I-137.R 4 A compound from any one of embodiments I-126 to I-136, wherein is H.

[0590] Embodiment I-138.R 4 A compound from any one of embodiments I-126 to I-136, wherein is a halogen.

[0591] Embodiment I-139.R 5 A compound from any one of embodiments I-126 to I-138, wherein is a halogen.

[0592] Embodiment I-140.R 7A compound from any one of embodiments I-126 to I-139, wherein is a halogen.

[0593] Embodiment I-141. Compounds based on formula IC: [ka] or its salts (e.g., pharmaceutically acceptable salts), esters, tautomers, prodrugs, zwitterionic forms, or stereoisomers [in the formula, R 2 H and C 1~6 Selected from alkyl groups, R 3 C 1~6 Selected from alkyl, carbocyclic, and heterocyclic elements, however any C 1~6 Alkyl is one or more R 9 Substituted by, and the carbocyclic or heterocyclic ring is unsubstituted or has one or more R 10 Replaced by, Or, R 2 and R 3 This refers to the atoms to which they are bonded, and whether they are unsubstituted or have one or more R 11 Forms a heterocycle substituted with, R 4 H, halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkynnyls, 3-6 membered carbon rings, and 3-6 membered heterorings, where any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 5 is halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 6 is one or more R 15 It is a bicyclic heteroaryl substituted with, R 7 is halogen, -OR 12 Selected from , -CN, and H, Each R 9 is -N(R 17 )2, -N(R 17 )C(O)C 1~6 Alkyl and -OR 17 Selected independently of, however, any C 1~6 Alkyl is either unsubstituted or has one or more R 18 Replaced by, Each R 10 is -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )2, -C(O)(C 1~6 Alkyl)N(R 19 )2, -(C 1~6 Alkyl)C(O)N(R 19 )2, -C(NR 19 )NR 19 CN, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 20 Replaced by, Each R 11 is -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )2, -C(O)(C 1~6 Alkyl)N(R 19 )2, -(C 1~6 Alkyl)C(O)N(R 19 )2, -C(NR 19 )NR 19 CN, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 20 Replaced by, Each R 12 C 1~6 Alkyl, C 2~6 Alkenyl and H are selected independently, except for any C 1~6 Alkyl or C 2~6 Alkenyls are either unsubstituted or have one or more R 13 Replaced by, Each R 13 is -OR 22 -CN, -N(R 22 )2, and selected independently from halogens, Each R 14 Halogen, N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 15 Halogen, N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 17 C 1~6 Selected independently from alkyl and H, Each R 18 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 19 C 1~6 Selected independently from alkyl and H, except for any C 1~6 Alkyl is either unsubstituted or has one or more R 21 Replaced by, Each R 20 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 21 -OH, -OC 1~6Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 22 C 1~6 Alkyl, C 2~6 [Selected independently of alkenyl and H].

[0594] Embodiment I-142.R 3 However, selected from carbocyclic and heterocyclic rings, wherein the carbocyclic or heterocyclic ring is unsubstituted or has one or more R 10 The compound of Embodiment I-141, which is substituted with [the compound].

[0595] Embodiment I-143.R 3 but, [ka] Selected from, none of these are non-substituted or one or more R 10 The compound of Embodiment I-141, which is substituted with [the compound].

[0596] Embodiment I-144.R 3 However, one or more R 9 C replaced by 1~6 A compound selected from alkyl groups, one of embodiments I-141 to I-143.

[0597] Embodiment I-145.R 3 but, [ka] A compound of Embodiment I-144, selected from the above.

[0598] Embodiment I-146.R 3 However, C 1~6 alkyl-N(R 17 )C(O)C 1~6 Alkyl N(R) 17 One compound selected from )2, which is one of embodiments I-141 to I-145.

[0599] Embodiment I-147.R 3 A compound from any one of embodiments I-141 to I-146, wherein the compound contains an amino portion.

[0600] Embodiment I-148.R 2 and R 3 and, together with the atom to which they are bonded, are unsubstituted or have one or more R 11 The compound of Embodiment I-141, which forms a 4- to 6-membered heterocycle substituted with .

[0601] Embodiment I-149.R 2 and R 3 The compounds of Embodiment 1-141, in which these atoms, together with the atoms to which they are bonded, form a heterocycle having the following structure: [ka] (The ring is either unsubstituted or has one or more R 11 (It has been replaced with...)

[0602] Embodiment I-150.R 2 and R 3 The compounds of Embodiment 1-141, in which these atoms, together with the atoms to which they are bonded, form a heterocycle having the following structure: [ka]

[0603] Embodiment I-151.R 2 and R 3 A compound of any one of Embodiments I-148 to I-150, wherein the atoms to which they are bonded form a heterocycle that (i) contains an additional nitrogen atom or (ii) is substituted with a group containing an amino moiety.

[0604] Embodiment I-152.R 6 but, [ka] One compound selected from any of embodiments I-141 to I-151.

[0605] Embodiment I-153.R 6 but, [ka] A compound of Embodiment I-152, selected from the above.

[0606] Embodiment I-154.R 6 but, [ka] A compound of Embodiment I-153, selected from the above.

[0607] Embodiment I-155.R 4 A compound from any one of embodiments I-141 to I-154, wherein is H.

[0608] Embodiment I-156.R 4 A compound from any one of embodiments I-141 to I-154, wherein is a halogen.

[0609] Embodiment I-157.R 5 A compound from any one of embodiments I-141 to I-156, wherein is a halogen.

[0610] Embodiment I-158.R 7 A compound from any one of embodiments I-141 to I-157, wherein is a halogen.

[0611] Embodiment I-159. Compound according to formula ID: [ka] or its salts (e.g., pharmaceutically acceptable salts), esters, tautomers, prodrugs, zwitterionic forms, or stereoisomers [in the formula, R 1 is -OR8 A 4-6 member heterocycle containing a nitrogen atom, selected from H, wherein the heterocycle is unsubstituted or has one or more R 16 Replaced by, R 2 H and C 1~6 Selected from alkyl groups, R 3 C 1~6 Selected from alkyl, carbocyclic, and heterocyclic elements, however any C 1~6 Alkyl is one or more R 9 Substituted by, and the carbocyclic or heterocyclic ring is unsubstituted or has one or more R 10 Replaced by, Or, R 2 and R 3 This refers to the atoms to which they are bonded, and whether they are unsubstituted or have one or more R 11 Forms a heterocycle substituted with, R 4 H, halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 5 is halogen, -OR 12 ,-CN,C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Selected from alkynyls, 3-6 membered carbon rings, and 3-6 membered heterocycles, provided that any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Substituted with, any carbon ring and heterocycle is either unsubstituted or has one or more R 14 Replaced by, R 7 is halogen, -OR 12 Selected from , -CN, and H, R 8The component is selected from heterocycles and alkyl heterocycles, and either is unsubstituted or has one or more R 16 Replaced by, Each R 9 is -N(R 17 )2, -N(R 17 )C(O)C 1~6 Alkyl and -OR 17 Selected independently of, however, any C 1~6 Alkyl is either unsubstituted or has one or more R 18 Replaced by, Each R 10 is -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )2, -C(O)(C 1~6 Alkyl)N(R 19 )2, -(C 1~6 Alkyl)C(O)N(R 19 )2, -C(NR 19 )NR 19 CN, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 20 Replaced by, Each R 11 is -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )2, -C(O)(C 1~6 Alkyl)N(R 19 )2, -(C 1~6 Alkyl)C(O)N(R 19 )2, -C(NR 19 )NR 19 CN, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 20 Replaced by, Each R 12 C 1~6 Alkyl, C 2~6 Alkenyl and H are selected independently, except for any C 1~6 Alkyl or C 2~6Alkenyls are either unsubstituted or have one or more R 13 Replaced by, Each R 13 is -OR 22 -CN, -N(R 22 )2, and selected independently from halogens, Each R 14 Halogen, N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 15 Halogen, N(R) 12 )2, and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 16 Halogen, -N(R 12 )2, and C 1~6 Alkyl and -OR 12 Selected independently of, however, any C 1~6 Alkyl is either unsubstituted or has one or more R 13 Replaced by, Each R 17 C 1~6 Selected independently from alkyl and H, Each R 18 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 19 C 1~6 Selected independently from alkyl and H, except for any C 1~6 Alkyl is either unsubstituted or has one or more R 21 Replaced by, Each R 20 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R21 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 Selected independently from alkyl and halogen, Each R 22 C 1~6 Alkyl, C 2~6 [Selected independently of alkenyl and H]. R 23 is -N(R 12 )2 and C 1~6 alkyl-N(R 12 ) Selected from 2, R 24 , R 25 , and R 26 H, halogen, -OR 12 , and C 1~6 Selected independently of alkyl, however any C 1~6 Alkyl is either unsubstituted or has one or more R 11 Replaced by, Each R 27 -OH, -OC 1~6 Alkyl, -CN, -NH2, -NHC 1~6 [Selected independently from alkyl and halogen elements.]

[0612] Embodiment I-160.R 3 However, selected from carbocyclic and heterocyclic rings, wherein the carbocyclic or heterocyclic ring is unsubstituted or has one or more R 10 The compound of Embodiment I-159, which is substituted with [the compound].

[0613] Embodiment I-161.R 3 but, [ka] Selected from, none of these are non-substituted or one or more R 10 The compound of Embodiment I-159, which is substituted with [the c...

Claims

1. Compound represented by formula ID': 【Chemistry 1】 or a pharmaceutically acceptable salt thereof (in the formula, R １ teeth, 【Chemistry 2】 And, R ２ and R ３ This refers to the atoms to which they are bonded, and which are either unsubstituted or have one or more R １１ It forms a 4- to 6-membered heterocycle by substitution, R ４ H is, R ５ is selected from halogen, -CN, and C １～６ alkyl, and the C １～６ alkyl is unsubstituted or substituted with one or more R １３ groups, R ７ It is selected from halogen and H, Each R １１ is -N(R １９ ) ２ , -C(O)R １９ , -C(O)N(R １９ ) ２ , -C(O)(C １～６ Alkyl)N(R １９ ) ２ , - (C １～６ Alkyl)C(O)N(R １９ ) ２ , -C(NR １９ ) NR １９ CN, and C １～６ Selected independently of alkyl, the C １～６ Alkyl is either unsubstituted or has one or more R ２０ Replaced by, Each R １２ C １～６ Alkyl, C ２～６ Alkenyl and H are independently selected, and C １～６ Alkyl or C ２～６ Alkenyls are either unsubstituted or have one or more R １３ Replaced by, Each R １３ It is independently a halogen, Each R １９ C １～６ A C is independently selected from alkyl and H. １～６ Alkyl is either unsubstituted or has one or more R ２１ Replaced by, Each R ２０ is -OH, -OC １～６ Alkyl, -CN, -NH ２ , - NHC １～６ Selected independently from alkyl and halogen, Each R ２１ is -OH, -OC １～６ Alkyl, -CN, -NH ２ , - NHC １～６ Selected independently from alkyl and halogen, R ２３ is -NH 2, R ２４ , R ２５ , and R ２６ It is selected independently of H and halogen, Ra and Rb are each independently selected from halogens, C1-6 alkyl groups, -OR12, and H, where the C1-6 alkyl groups are either unsubstituted or substituted with one or more R13 groups.

2. R1 is 【Transformation 3】 A compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the above.

3. R １ but, 【Chemistry 4】 The compound according to claim 1 or a pharmaceutically acceptable salt thereof.

4. R ２ and R ３ Together with the atoms to which they are bonded, they form a 4-6 membered heterocycle having 0-2 further heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the heterocycle is unsubstituted or has one or more R １１ A compound according to claim 1 or a pharmaceutically acceptable salt thereof, which is substituted with.

5. Each R １１ However, -N(R １９ ) ２ , -C(O)R １９ , -C(O)N(R １９ ) ２ , -C(O)(C １～６ Alkyl)N(R １９ ) ２ , and C １～６ Selected independently of alkyl, the C １～６ Alkyl is either unsubstituted or has one or more R ２０ A compound according to claim 1 or a pharmaceutically acceptable salt thereof, which is substituted with.

6. R ２ and R ３ And, along with the atoms to which they are bonded, 【Transformation 5】 A compound according to claim 1 or a pharmaceutically acceptable salt thereof, which forms a 4- to 6-membered heterocycle selected from the above.

7. R2 and R3, together with the atom to which they are bonded, 【Transformation 6】 A compound according to claim 1 or a pharmaceutically acceptable salt thereof, which forms a 4- to 6-membered heterocycle selected from the above.

8. R2 and R3, together with the atom to which they are bonded, 【Transformation 7】 A compound according to claim 1 or a pharmaceutically acceptable salt thereof, which forms a 4- to 6-membered heterocycle selected from the above.

9. R2 and R3, together with the atom to which they are bonded, 【Transformation 8】 A compound according to claim 1 or a pharmaceutically acceptable salt thereof, which forms [a specific compound].

10. The following formula 【Chemistry 9】 but, 【Chemistry 10】 The compound according to claim 1 or a pharmaceutically acceptable salt thereof.

11. R ５ The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein the halogen is present.

12. R ５ However, it is either unsubstituted or has one or more R １３ C replaced by １～６ A compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein the compound is alkyl.

13. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R5 is a C1-6 alkyl group substituted with one or more F groups.

14. R ７ The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein the halogen is present.

15. Compound represented by formula ID': 【Chemistry 11】 or a pharmaceutically acceptable salt thereof (in the formula, R 1 is, 【Chemistry 12】 And, 【Chemistry 9】 teeth, 【Chemistry 10】 And, R2 and R3, along with the atom to which they are bonded, 【Chemistry 13】 Form a complex ring selected from, R 4 is H, R5 is a halogen or a C1-6 alkyl substituted with one or more halogens. R7 is halogen, Ra and Rb are each independently selected from halogens, C1-6 alkyls, and H.

16. R1 is 【Chemistry 14】 A compound according to claim 15 or a pharmaceutically acceptable salt thereof, selected from the above.

17. R1 is, 【Chemistry 15】 The compound according to claim 16 or a pharmaceutically acceptable salt thereof.

18. R2 and R3, together with the atom to which they are bonded, 【Chemistry 16】 A compound according to claim 15 or a pharmaceutically acceptable salt thereof, which forms [a specific compound].

19. The compound according to claim 15 or a pharmaceutically acceptable salt thereof, wherein R5 is a C1-6 alkyl group substituted with one or more halogens.

20. The compound according to claim 15 or a pharmaceutically acceptable salt thereof, wherein R7 is a halogen.

21. The following structure: 【Chemistry 17】 A compound represented by or a pharmaceutically acceptable salt thereof.

22. A pharmaceutical composition comprising a compound according to any one of claims 1 to 21 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

23. A composition for use as a pharmaceutical agent, comprising a compound according to any one of claims 1 to 21 or a pharmaceutically acceptable salt thereof.

24. A composition for use in the manufacture of a pharmaceutical product, comprising a compound according to any one of claims 1 to 21 or a pharmaceutically acceptable salt thereof.

25. The composition according to claim 23 or 24, wherein the agent is useful for treating a disease, disorder, or condition that is improved by inhibition of KRAS having a G12D mutation.

26. The composition according to claim 23, wherein the drug is useful for treating cancer.

27. ​​The composition according to claim 24, wherein the drug is useful for treating cancer.

28. The composition according to claim 25, wherein the disease, disorder, or condition is cancer.

29. A composition comprising a compound according to any one of claims 1 to 21 or a pharmaceutically acceptable salt thereof, for use in the treatment of a disease, disorder, or condition.

30. The composition according to claim 29, wherein the disease, disorder, or condition is cancer.

31. The composition according to claim 26, wherein the cancer is selected from the group consisting of pancreatic cancer, colorectal cancer, and lung cancer.

32. The composition according to claim 27, wherein the cancer is selected from the group consisting of pancreatic cancer, colorectal cancer, and lung cancer.

33. The composition according to claim 28, wherein the cancer is selected from the group consisting of pancreatic cancer, colorectal cancer, and lung cancer.

34. The composition according to claim 30, wherein the cancer is selected from the group consisting of pancreatic cancer, colorectal cancer, and lung cancer.

35. A composition characterized by comprising administering a pharmaceutical composition containing a compound according to any one of claims 1 to 21 or a pharmaceutically acceptable salt thereof to a subject requiring such administration.

36. The composition according to claim 35, wherein the subject has a disease, disorder, or condition that is improved by inhibition of KRAS having a G12D mutation.

37. The composition according to claim 35 or 36, wherein the subject has cancer.

38. The composition according to claim 37, wherein the subject has been diagnosed with the cancer in advance.

39. The composition according to claim 37, wherein the subject has previously undergone the cancer treatment regimen.

40. The composition according to claim 37, wherein the subject is in remission from the cancer beforehand.

41. The composition according to claim 37, wherein the cancer is selected from the group consisting of pancreatic cancer, colorectal cancer, and lung cancer.

42. The composition according to claim 37, wherein the compound or a pharmaceutically acceptable salt thereof is administered in combination with an additional therapeutic agent.

43. Use of a compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 21 in the manufacture of a pharmaceutical product.

44. The use according to claim 43, wherein the drug is for the treatment of cancer.

45. The use according to claim 44, wherein the cancer is selected from the group consisting of pancreatic cancer, colorectal cancer, and lung cancer.

46. A composition comprising a compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 21, for use in a method comprising contacting a KRAS protein with a compound or a pharmaceutically acceptable salt thereof.

47. The composition according to claim 46, wherein contacting the KRAS protein with the compound modulates KRAS.

48. The composition according to claim 46, wherein the KRAS protein has the G12D mutation.

49. The composition according to claim 47, wherein the KRAS protein has a G12D mutation.

50. The composition according to claim 46, wherein the KRAS protein is in an active state.

51. The composition according to claim 47, wherein the KRAS protein is in an active state.

52. The composition according to claim 48, wherein the KRAS protein is in an active state.

53. The composition according to claim 49, wherein the KRAS protein is in an active state.

54. The composition according to claim 46, wherein the KRAS protein is in an inactive state.

55. The composition according to claim 47, wherein the KRAS protein is in an inactive state.

56. The composition according to claim 48, wherein the KRAS protein is in an inactive state.

57. The composition according to claim 49, wherein the KRAS protein is in an inactive state.

58. Compounds selected from the structures shown in the following table, or their pharmaceutically acceptable salts: Table 1 Table 2

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