Compounds and compositions for treating conditions associated with NLRP activity

Abstract

In one aspect, the compound having formula AA or a pharmaceutically acceptable salt thereof is characterized by: or a pharmaceutically acceptable salt thereof, wherein the variables shown in formula A may be as defined anywhere herein.

Description

Technical Field

[0001] The present disclosure features chemical entities (e.g., compounds that modulate (e.g., antagonize) NLRP3, or pharmaceutically acceptable salts and / or hydrates and / or cocrystals and / or drug combinations thereof) that can be used, for example, to treat a condition, disease, or disorder in a subject (e.g., a human), in which a decrease or increase in NLRP3 activity (e.g., an increase, e.g., a condition, disease, or disorder associated with NLRP3 signaling) contributes to the pathology and / or symptoms and / or progression of the condition, disease, or disorder. The present disclosure also features compositions and other methods of using and preparing the compositions.

[0002] This disclosure also relates in part to methods and compositions for treating anti-TNFα resistance in subjects with an NLRP3 antagonist. This disclosure further relates in part to methods, combinations, and compositions for treating TFNα-related disease and anti-TNFα resistance in subjects, said methods, combinations, and compositions comprising administration of an NLRP3 antagonist, an NLRP3 antagonist and an anti-TNFα agent, or a composition comprising an NLRP3 antagonist and an anti-TNFα agent. Background Art

[0003] The NLRP3 inflammasome is a component of the inflammatory process, and its abnormal activation is pathogenic in inherited disorders such as cryopyrin-associated periodic syndromes (CAPS). Hereditary CAPS, Muckle-Wells syndrome (MWS), familial cold autoinflammatory syndrome (FCAS), and neonatal-onset multisystem inflammatory disease (NOMID) are examples of indications that have been reported to be associated with gain-of-function mutations in NLRP3.

[0004] NLRP3 can form complexes and has been involved in the pathogenesis of a variety of complex diseases, including but not limited to metabolic disorders such as type 2 diabetes, atherosclerosis, obesity, and gout; and central nervous system diseases such as Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, and Parkinson's disease; lung diseases such as asthma, COPD, and idiopathic pulmonary fibrosis; liver diseases such as NASH syndrome, viral hepatitis, and cirrhosis; pancreatic diseases such as acute and chronic pancreatitis; kidney diseases such as acute and chronic kidney injury; intestinal diseases such as Crohn's disease and ulcerative colitis; skin diseases such as psoriasis; musculoskeletal diseases such as scleroderma; vascular disorders such as giant cell arteritis; bone disorders such as osteoarthritis, osteoporosis, and osteosclerosis; eye diseases such as glaucoma and macular degeneration; diseases caused by viral infections such as HIV and AIDS; and autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, autoimmune thyroiditis, and Addison's disease. disease), pernicious anemia, cancer, and aging.

[0005] In view of the above, it is desirable to provide compounds that regulate (e.g., antagonize) NLRP3.

[0006] Several patients with inflammatory or autoimmune diseases have been treated with anti-TNFα agents. A subgroup of these patients has developed resistance to treatment with anti-TNFα agents. It is desirable to develop methods to reduce resistance to anti-TNFα agents in these patients. Therefore, it is also desirable to provide alternative therapies (e.g., NLRP3 inflammasome inhibitors) for the treatment of inflammatory or autoimmune diseases to avoid or minimize the use of anti-TNFα agents.

[0007] Intestinal diseases (IBD) (including ulcerative colitis (UC) and Crohn's disease (CD)) are chronic diseases characterized by barrier dysfunction and uncontrolled inflammation and mucosal immune responses within the gut. Many inflammatory pathways are involved in the progression of IBD, and anti-inflammatory therapies, such as tumor necrosis factor-α (TNF-α) blockade, have shown clinical efficacy (Rutgeerts P et al. N Engl J Med [New England Journal of Medicine] 2005; 353:2462-76). However, anti-TNFα therapy has not shown complete efficacy; however, other cytokines such as IL-1β, IL-6, IL-12, IL-18, IL-21, and IL-23 have been shown to drive the inflammatory pathology of IBD (Neurath MF Nat Rev Immunol [Nature Reviews Immunology] 2014; 14; 329-42). IL-1β and IL-18 are produced by the NLRP3 inflammasome in response to pathogenic danger signals and have been shown to play a role in IBD. Anti-IL-1β therapy has been effective in patients with IBD driven by gene mutations in CARD8 or IL-10R (Mao L et al., J Clin Invest 2018; 238:1793-1806; Shouval DS et al., Gastroenterology 2016; 151:1100-1104), IL-18 genetic polymorphism has been associated with UC (Kanai T et al., Curr Drug Targets 2013; 14:1392-9), and NLRP3 inflammasome inhibitors have shown efficacy in a mouse model of IBD (Perera AP et al., Sci Rep 2018; 8:8618). Resident intestinal immune cells isolated from the lamina propria of IBD patients can produce IL-1β spontaneously or upon LPS stimulation, and this IL-1β production can be blocked by in vitro addition of NLRP3 antagonists. Based on the strong clinical and preclinical evidence showing a role for inflammasome-driven IL-1β and IL-18 in IBD pathology, it is clear that NLRP3 inflammasome inhibitors may be an effective therapeutic option for subsets of patients with UC, Crohn's disease, or IBD.These patient subgroups can be defined by the following: their peripheral or intestinal levels of inflammasome-related cytokines (IL-1β, IL-6, and IL-18), which predispose IBD patients to genetic factors with NLRP3 inflammasome activation, such as mutations in genes including ATG16L1, CARD8, IL-10R, or PTPN2 (Saitoh T et al., Nature 2008; 456:264; Spalinger MR, Cell Reports 2018; 22:1835), or other clinical baselines, such as non-response to TNF therapy.

[0008] Although anti-TNF therapy is an effective treatment option for Crohn's disease, 40% of patients remain unresponsive. One-third of unresponsive CD patients are unresponsive to anti-TNF therapy at the start of treatment, while another third lose response to treatment over time (secondary non-response). Secondary non-response may be due to the development of anti-drug antibodies or changes in the immune compartment that desensitize patients to anti-TNF (Ben-Horin S et al., Autoimmune Rev [Autoimmune Review] 2014; 13:24-30; Steenholdt C et al. Gut [Gut] 2014; 63:919-27). Anti-TNF therapy reduces inflammation in IBD by inducing apoptosis of pathogenic T cells in the gut, thereby eliminating the T-cell-mediated inflammatory response (Van den Brande et al. Gut [Gut] 2007:56:509-17). Compared with TNF-responsive patients, TNF-unresponsive Crohn's disease (CD) patients showed increased NLRP3 expression and IL-1β production in the gut (Leal RF et al., Gut [Gut] 2015; 64:233-42), indicating activation of the NLRP3 inflammasome pathway. Furthermore, expression of TNF-receptor 2 (TNF-R2), which allows TNF-mediated T cell proliferation, was increased (Schmitt H et al., Gut [Gut] 2018; 0:1-15). IL-1β signaling in the gut promotes T cell differentiation into Th1 / 17 cells that can escape anti-TNF-α-mediated apoptosis. Therefore, it is possible that NLRP3 inflammasome activation may contribute to CD patients' unresponsiveness to anti-TNF-α therapy by sensitizing pathogenic T cells in the gut to anti-TNF-α-mediated apoptosis. Experimental data from immune cells isolated from the gut of TNF-resistant Crohn's disease patients showed that these cells spontaneously released IL-1β, which could be inhibited by the addition of an NLRP3 antagonist. The anticipated use of NLRP3 inflammasome antagonists—partially by blocking IL-1β secretion—inhibits the mechanism leading to anti-TNF non-responsiveness, thereby resensitizing patients to anti-TNF therapy. In IBD patients who have not received anti-TNF therapy, treatment with NLRP3 antagonists is expected to prevent primary and secondary non-responsiveness by blocking the mechanism leading to non-responsiveness.

[0009] Locally effective NLRP3 antagonists in the gut can be effective for treating IBD, alone or in combination with anti-TNF therapy; particularly for treating TNF-resistant CD. Systemic inhibition of both IL-1β and TNF-α has been shown to increase the risk of opportunistic infections (Genovese MC et al., Arthritis Rheum 2004; 50:1412), therefore, blocking the NLRP3 inflammasome only at the site of inflammation will reduce the risk of infection inherent in either IL-1β or TNF-α. NLRP3 antagonists are potent in cellular NLRP3-inflammasome-driven cytokine secretion assays, but exhibit poor systemic bioavailability in in vitro permeability assays such as the MDCK assay, resulting in low permeability in rat or mouse pharmacokinetic studies. However, for intestinal restriction purposes, high levels of these compounds in the colon and / or small intestine may be a useful therapeutic option.

[0010] The present invention also provides alternative therapies for treating inflammatory or autoimmune diseases (including IBD) that address the above-mentioned problems associated with anti-TNFα agents. Summary of the Invention

[0011] This disclosure is characterized by chemical entities that can be used, for example, to treat conditions, diseases, or disorders (e.g., compounds that regulate (e.g., antagonize) NLRP3, or pharmaceutically acceptable salts and / or hydrates and / or cocrystals and / or drug combinations of said compounds) in which NLRP3 activity is reduced or increased (e.g., increased, for example, conditions, diseases, or disorders associated with NLRP3 signaling).

[0012] In some embodiments, compounds having the formula AA are provided herein.

[0013]

[0014] Or a pharmaceutically acceptable salt thereof, wherein the variables in formula AA may be defined as anywhere in this document.

[0015] This disclosure is further characterized by the composition and other methods of using and preparing the composition.

[0016] The present invention also relates to Applicants' discovery that inhibition of the NLRP3 inflammasome can increase a subject's sensitivity to anti-TNFα agents or can overcome resistance to anti-TNFα agents in a subject, or indeed provide an alternative therapy to anti-TNFα agents.

[0017] This article provides a method for treating a subject, the method comprising: (a) identifying a subject with cells having elevated levels of NLRP3 inflammasome activity and / or expression compared to a reference level; and (b) administering to the identified subject a therapeutically effective amount of a compound of formula I or a pharmaceutically acceptable salt, solvate or cocrystal thereof.

[0018] This article provides a method for treating inflammatory or autoimmune diseases (including IBDs such as UC and CD) in subjects in need, the method comprising administering to the subject a therapeutically effective amount of a compound of formula I or a pharmaceutically acceptable salt, solvate or cocrystal thereof, wherein the NLRP3 antagonist is an NLRP3 antagonist targeting the gut.

[0019] This article provides a method for treating subjects in need, the method comprising: (a) identifying subjects resistant to an anti-TNFα agent; and (b) administering a treatment to the identified subjects, the treatment comprising a therapeutically effective amount of a compound of formula I or a pharmaceutically acceptable salt, solvate, or cocrystal thereof.

[0020] This article provides a method for treating subjects in need, the method comprising administering treatment to subjects identified as resistant to TNFα agents, the treatment comprising a therapeutically effective amount of a compound of formula I or a pharmaceutically acceptable salt, solvate or cocrystal thereof.

[0021] This article provides a method for selecting treatment for subjects in need, the method comprising: (a) identifying subjects resistant to an anti-TNFα agent; and (b) selecting treatment for said identified subjects, said treatment comprising a therapeutically effective amount of a compound of formula I or a pharmaceutically acceptable salt, solvate or cocrystal thereof.

[0022] This article provides a method for selecting treatment for subjects in need, the method comprising: selecting treatment for subjects identified as resistant to TNFα agents, the treatment comprising a therapeutically effective amount of a compound of formula I or a pharmaceutically acceptable salt, solvate or cocrystal thereof.

[0023] In some embodiments of any of the methods described herein, the treatment further comprises, in addition to the NLRP3 antagonist, a therapeutically effective amount of an anti-TNFα agent.

[0024] "Antagonists" of NLRP3 include compounds that inhibit the ability of NLRP3 to induce the production of IL-1β and / or IL-18 by directly binding to NLRP3, or by inactivating, destabilizing, altering the distribution of NLRP3, or otherwise.

[0025] In one aspect, a pharmaceutical composition is characterized by comprising a chemical entity described herein (e.g., a compound or a pharmaceutically acceptable salt thereof or a composition containing the thereof, as generally or specifically described herein), and one or more pharmaceutically acceptable excipients.

[0026] In one aspect, a method for modulating (e.g., activating, partially activating, antagonizing) NLRP3 activity is characterized by contacting NLRP3 with a chemical entity described herein (e.g., a compound generally or specifically described herein, or a pharmaceutically acceptable salt thereof, or a composition containing the thereof). The method includes in vitro methods, such as contacting a sample containing one or more cells containing NLRP3, and in vivo methods.

[0027] In another aspect, methods for treating diseases in which NLRP3 signaling contributes to the pathology and / or symptoms and / or progression of the disease are characterized by treatment comprising administering an effective amount of the chemical entity described herein (e.g., a compound generally or specifically described herein or a pharmaceutically acceptable salt thereof or a composition containing the thereof) to a subject in need.

[0028] In another aspect, the treatment method is characterized by administering to a subject a chemical entity described herein (e.g., a compound generally or specifically described herein, or a pharmaceutically acceptable salt thereof, or a composition containing the thereof), wherein the chemical entity is administered in an amount that effectively treats the pathology and / or symptoms and / or progression of the disease that contributes to NLRP3 signaling, thereby treating the disease.

[0029] An embodiment may include one or more of the following features.

[0030] The chemical entity may be administered in combination with one or more additional therapies using one or more agents useful in treating the condition, disease, or disorder.

[0031] Examples of indications for treatment with the compounds disclosed herein include, but are not limited to, metabolic disorders such as type 2 diabetes, atherosclerosis, obesity, and gout; and diseases of the central nervous system such as Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, and Parkinson's disease; lung diseases such as asthma, COPD, and idiopathic pulmonary fibrosis; liver diseases such as NASH syndrome, viral hepatitis, and cirrhosis; pancreatic diseases such as acute and chronic pancreatitis; kidney diseases such as acute and chronic kidney injury; intestinal diseases such as Crohn's disease and ulcerative colitis; skin diseases such as psoriasis; musculoskeletal diseases such as scleroderma; vascular disorders such as giant cell arteritis; bone disorders such as osteoarthritis, osteoporosis, and osteosclerosis; eye diseases such as glaucoma and macular degeneration; diseases caused by viral infections such as HIV and AIDS; and autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, autoimmune thyroiditis, Addison's disease, pernicious anemia, cancer, and aging.

[0032] The method may further include identifying the subject.

[0033] Other embodiments include those described in the detailed embodiments and / or the claims.

[0034] Additional definition

[0035] To facilitate understanding of the disclosures set forth herein, several additional terms are defined below. Generally, the nomenclature used herein and the laboratory procedures described herein in organic chemistry, medicinal chemistry, and pharmacology are those well-known and commonly used in the art. Unless otherwise defined, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains. Every patent, application, published application, and other publication mentioned throughout this specification, as well as any appendices, is incorporated herein by reference in its entirety.

[0036] As used herein, the term "NLRP3" means, but is not limited to, nucleic acids, polynucleotides, oligonucleotides, sense and antisense polynucleotide chains, complementary sequences, peptides, polypeptides, proteins, homologous and / or orthologous NLRP3 molecules, isotypes, precursors, mutants, variants, derivatives, splice variants, alleles, different species, and their active fragments.

[0037] As used herein, the term “acceptable” in relation to formulations, compositions or ingredients means that there is no lasting adverse effect on the general health of the subject being treated.

[0038] “API” means active pharmaceutical ingredient.

[0039] As used herein, the term "effective amount" or "therapeutically effective amount" refers to a sufficient amount of a chemical entity (e.g., a compound that exhibits activity as an NLRP3 modulator, or a pharmaceutically acceptable salt and / or hydrate and / or co-crystal thereof) that, when administered, will alleviate to some extent one or more symptoms of the disease or condition being treated. Results include alleviation and / or relief of signs, symptoms, or causes of the disease or any other desired change in a biological system. For example, an "effective amount" for therapeutic use is the amount of a composition comprising a compound as disclosed herein that is required to achieve a clinically significant reduction in the symptoms of the disease. The appropriate "effective" amount in any individual case is determined using any suitable technique, such as a dose escalation study.

[0040] The term "excipient" or "pharmaceutically acceptable excipient" means a pharmaceutically acceptable material, composition, or vehicle, such as a liquid or solid filler, diluent, carrier, solvent, or encapsulating material. In one embodiment, each component is "pharmaceutically acceptable" in the sense that it is compatible with the other ingredients of the pharmaceutical formulation and is suitable for use in contact with human and animal tissues or organs without excessive toxicity, irritation, allergic response, immunogenicity, or other problems or complications commensurate with a reasonable benefit / risk ratio. See, e.g., The Science and Practice of Pharmacy [Remington: The Science and Practice of Pharmacy], 21st ed.; Lippincott Williams & Wilkins: Philadelphia, PA, 2005; Handbook of Pharmaceutical Excipients, 6th ed.; Rowe et al., eds.; The Pharmaceutical Press and the American Pharmaceutical Association: 2009; Handbook of Pharmaceutical Additives, 3rd ed.; Ash and Ash, eds.; Gower Publishing Company: 2007; Pharmaceutical Preformulation and Formulation, 2nd ed.; Gibson, ed.; CRC Press LLC: Boca Raton, FL, 2009.

[0041] The term "pharmaceutically acceptable salt" can refer to a pharmaceutically acceptable addition salt prepared from a pharmaceutically acceptable non-toxic acid (including inorganic and organic acids). In some cases, a pharmaceutically acceptable salt is obtained by reacting the compound described herein with acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, etc. The term "pharmaceutically acceptable salt" can also refer to a pharmaceutically acceptable addition salt prepared by reacting a compound having an acidic group with a base to form a salt such as ammonium salts, alkali metal salts (such as sodium or potassium salts), alkaline earth metal salts (such as calcium or magnesium salts), organic bases such as dicyclohexylamine, N-methyl-D-glucosamine, tris(hydroxymethyl)methylamine, and salts formed by reacting with amino acids such as arginine, lysine, etc. There are no particular limitations on the pharmacologically acceptable salt, as long as it can be used in a pharmaceutical. Examples of salts formed by the compounds described herein with bases include: salts with inorganic bases such as sodium, potassium, magnesium, calcium, and aluminum; salts with organic bases such as methylamine, ethylamine, and ethanolamine; salts with basic amino acids such as lysine and ornithine; and ammonium salts. The salts may be acid addition salts, specifically examples of addition salts with the following acids: inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, and phosphoric acid; organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, methanesulfonic acid, and ethanesulfonic acid; and acidic amino acids such as aspartic acid and glutamic acid.

[0042] The term "pharmaceutical composition" refers to a mixture of the compound described herein with other chemical components (collectively referred to herein as "excipients") such as carriers, stabilizers, diluents, dispersants, suspending agents, and / or thickeners. Pharmaceutical compositions facilitate the administration of compounds to a living organism. Various techniques exist in the art for administering compounds, including but not limited to: rectal, oral, intravenous, aerosol, parenteral, ocular, pulmonary, and topical administration.

[0043] The term "subject" refers to an animal, including but not limited to a primate (e.g., human), monkey, cow, pig, sheep, goat, horse, dog, cat, rabbit, rat, or mouse. The terms "subject" and "patient" are used interchangeably herein, e.g., with respect to a mammalian subject (e.g., human).

[0044] The terms "treat," "treating," and "treatment," in the context of treating a disease or disorder, are meant to include alleviating or eliminating the disorder, disease, or condition, or one or more symptoms associated with the disorder, disease, or condition; or slowing the progression, spread, or worsening of the disease, disorder, or condition, or one or more symptoms thereof.

[0045] The term “preventing” in relation to a disease or disorder refers to preventive treatment of a subject at risk of developing a condition (e.g., a specific disease or disorder or its clinical symptoms) that reduces the likelihood of the subject developing the condition.

[0046] The terms “hydrogen” and “H” are used interchangeably in this document.

[0047] The term "halogenated" refers to fluorine (F), chlorine (Cl), bromine (Br), or iodine (I).

[0048] The term "alkyl" refers to a hydrocarbon chain that can be straight or branched, saturated or unsaturated, and contains the indicated number of carbon atoms. For example, C 1-10 Indicates that the group may have from 1 to 10 (inclusive) carbon atoms in it. Non-limiting examples include methyl, ethyl, isopropyl, tert-butyl, n-hexyl.

[0049] The term "haloalkyl" refers to an alkyl group in which one or more hydrogen atoms are replaced by independently selected halo.

[0050] The term "alkoxy" refers to an -O-alkyl group (eg, -OCH3).

[0051] As used herein, the term "carbocyclic" includes aromatic or non-aromatic cyclic hydrocarbon groups having 3 to 10 carbons (unless otherwise specified), such as 3 to 8 carbons, or 3 to 7 carbons. The carbocyclic ring can be monocyclic or bicyclic, and when bicyclic, it can be a fused bicyclic, bridged bicyclic, or spirocyclic ring. Examples of carbocyclic rings include five-membered, six-membered, and seven-membered carbocyclic rings.

[0052] The term "heterocycle" refers to an aromatic or non-aromatic 5-8 membered monocyclic, 8-12 membered bicyclic, or 11-14 membered tricyclic system (e.g., carbon atom, and for monocyclic, bicyclic, or tricyclic systems, 1-3, 1-6, or 1-9 N, O, or S heteroatoms respectively) having 1-3 heteroatoms (if monocyclic), 1-6 heteroatoms (if bicyclic), or 1-9 heteroatoms (if tricyclic), wherein the heteroatoms are selected from O, N, or S, and 0, 1, 2, or 3 atoms in each ring may be substituted by substituents. When the heterocycle is bicyclic or tricyclic, any two connected rings of the bicyclic or tricyclic system may be fused bicyclic, bridged bicyclic, or spirocyclic. Examples of heterocycles include five-, six-, and seven-membered heterocycles.

[0053] As used herein, the term "cycloalkyl" includes non-aromatic cyclic, bicyclic, fused, or spiroalkyl groups having 3 to 10 carbons, such as 3 to 8 carbons, such as 3 to 7 carbons, wherein the cycloalkyl group may be optionally substituted. Examples of cycloalkyl groups include five-, six-, and seven-membered rings. Examples include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, and cyclooctyl.

[0054] The term "heterocyclic alkyl" refers to a non-aromatic 5-8 membered monocyclic, 8-12 membered bicyclic, or 11-14 membered tricyclic, fused, or spirocyclic group having 1-3 heteroatoms (if monocyclic), 1-6 heteroatoms (if bicyclic), or 1-9 heteroatoms (if tricyclic), selected from O, N, or S, wherein 0, 1, 2, or 3 atoms of each ring may be substituted with substituents. Examples of heterocyclic alkyl groups include five-, six-, and seven-membered heterocycles. Examples include piperazine, pyrrolyl, dioxyl, morpholinyl, tetrahydrofuranyl, etc.

[0055] The term "aryl" is intended to refer to an aromatic cyclic group containing 6 to 10 carbon atoms. Examples include phenyl and naphthyl.

[0056] The term "heteroaryl" is intended to refer to an aromatic ring system comprising 5 to 14 aromatic ring atoms, which may be monocyclic, consisting of two fused rings or three fused rings, wherein at least one aromatic ring atom is a heteroatom selected from, but not limited to, the group consisting of O, S, and N. Examples include furanyl, thiopheneyl, pyrroleyl, imidazolyl, oxazolyl, thiazolyl, isoxazolyl, pyrazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, etc. Examples also include carbazolyl, quinazinyl, quinolinyl, isoquinolinyl, cyclolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, triazinyl, indolyl, isoindolyl, indazole, inazinyl, purine, naphridinyl, pteridinyl, acridineyl, phenazinyl, phenothiazinyl, phenotoxazinyl, benzoxazolyl, benzothiazolyl, 1H-benzimidazolyl, imidazopyridyl, benzothiophenyl, benzofuranyl, isobenzofuran, etc.

[0057] The term "hydroxyl group" refers to the OH group.

[0058] The term "amino" refers to the NH2 group.

[0059] The term "oxo" refers to oxygen (O). As an example, replacing a CH2 group with an oxo group yields a C=O group.

[0060] As used herein, the term "Ring A" or "A" is used interchangeably to indicate the ring of Formula AA. Among them, the waveform line The bond shown as broken connects A to S(O)(NHR 3 )=N part.

[0061] As used herein, the term "Ring A'" or "A'" is used interchangeably to indicate the ring of Formula AA-1. Among them, the waveform line The bond shown as broken connects A' to S(O)(NHR 3 ) = N parts.

[0062] As used herein, the term "Ring A'" or "A'" is used interchangeably to refer to the rings in Formula AA-2, Formula AA-3, and Formula AA-4. Among them, the waveform line The bond shown as broken connects A″ to S(O)(NHR 3 ) = N parts.

[0063] As used herein, the term "Ring B" or "B" is used interchangeably to indicate a ring in Formula AA. Among them, the waveform line The bond shown as broken connects B to the NHC(O) group of formula AA.

[0064] As used herein, the term "Ring B'" or "B'" is used interchangeably to indicate the ring of Formula AA-4. Among them, the waveform line The bond shown as broken connects B' to the NHC(O) group of formula AA-4.

[0065] As used herein, the terms "Ring B" or "B" are used interchangeably to indicate the ring in Formula AA-5. Among them, the waveform line The bond shown as broken connects B" to the NHC(O) group of formula AA-5.

[0066] As used herein, the term "optionally substituted ring A" is used to indicate that the ring A in formula AA Among them, the waveform line The bond shown as broken connects A to S(O)(NHR 3 )=N part.

[0067] As used herein, the term "optionally substituted ring A'" is used to indicate that the ring in formula AA-1 Among them, the waveform line The bond shown as broken connects A' to S(O)(NHR 3 )=N part.

[0068] As used herein, the term "optionally substituted Ring A" is used to indicate that the ring in Formula AA-2 In formula AA-3 In the Japanese AA-4 Among them, the waveform line The bond shown as broken connects A″ to S(O)(NHR 3 )=N part.

[0069] As used herein, the term "substituted ring B" is used in the indicative AA. In the formula AA-1 Among them, the waveform line The bond shown as broken connects B to the NHC(O) group of Formula AA and Formula AA-1.

[0070] As used herein, the term "substituted ring B'" is used in indicator AA-4. Among them, the waveform line The bond shown as broken connects B' to the NHC(O) group of formula AA-4.

[0071] As used herein, the term "substituted ring B" is used in indicator AA-5. Among them, the waveform line The bond shown as broken connects B" to the NHC(O) group of formula AA-5.

[0072] As used herein, the expression "S(O2)", alone or as part of a larger expression, refers to the group.

[0073] Furthermore, the atoms constituting the compounds of embodiments of the present invention are intended to include all isotopic forms of such atoms. As used herein, isotopes include those atoms with the same number of atoms but different mass numbers. By way of example and not limitation, isotopes of hydrogen include tritium and deuterium, and isotopes of carbon include 13 C and 14 C.

[0074] The scope of compounds disclosed herein includes tautomer forms of compounds. Therefore, as examples, compounds containing the following moiety are represented.

[0075]

[0076] Also intended to include tautomeric forms containing the moiety

[0077] Furthermore, as an example, compounds containing the following components are represented.

[0078]

[0079] Also intended to include tautomeric forms containing the moiety

[0080]

[0081] Non-limiting illustrative compounds having the formulas described herein comprise a stereosulfur atom and optionally one or more stereocarbon atoms. This disclosure provides examples of stereoisomer mixtures (e.g., racemic or semi-racemic mixtures of enantiomers; mixtures of diastereomers). This disclosure also describes and illustrates methods for separating individual components of said stereoisomer mixtures (e.g., resolving enantiomers of racemic mixtures). In the case of compounds containing only a stereosulfur atom, the resolved enantiomers are graphically represented using one of two forms: Formula A / B (hash and solid wedge three-dimensional representation); and Formula C (“having…”). * -The planar structure of marked stereosulfur).

[0082]

[0083] In reaction schemes showing the resolution of racemic mixtures, Formulas A / B and C are intended only to convey that the constituent enantiomers are resolved into enantiomerically pure forms (about 98% ee or greater). The use of Formula A / B forms to show the schemes of the resolved products is not intended to disclose or imply any correlation between absolute configuration and elution order.

[0084] Similar formulas apply to compounds containing both steric sulfur and carbon atoms.

[0085] Some compounds shown in the table below are represented graphically using Formula A / B. However, unless otherwise specified (e.g., when the compound is synthesized from an enantiomer-enriched starting material (see, for example, compound 964a, example 573), the stereochemistry shown at the sulfur location for each listed compound in Formula A / B form is provisional and analogous to the absolute stereochemistry specified for compound 162bb herein (see...). Figure 5 ).

[0086] In some embodiments, for S(O)NHR 3 Two enantiomers or two epimers of the compound of formula AA differ in the stereochemical configuration at the sulfur atom of the (=N) moiety, and one of the two enantiomers or epimers has greater NLRP3 antagonistic activity than the other.

[0087] In some embodiments, when R 3 When =H, for S(O)NHR 3Two enantiomers or two epimers of a compound of formula AA that differ in stereochemical configuration at the sulfur atom of the (=N) moiety, the enantiomer or epimer having the (R)-stereochemical configuration at the sulfur atom having greater NLRP3 antagonistic activity than the enantiomer or epimer having the (S)-stereochemical configuration at the sulfur atom. For example, the enantiomer or epimer having the (R)-stereochemical configuration at the sulfur atom exhibits a lower IC in the hTHP-1 assay described herein. 50 value.

[0088] Details of one or more embodiments of the present invention are set forth in the accompanying drawings and the description below. Further features and advantages of the invention will become apparent from the specification, the drawings, and the claims. Attached Figure Description

[0089] Figure 1 Expression levels of RNA encoding NLRP3 in Crohn's disease patients who responded to and did not respond to infliximab.

[0090] Figure 2 Expression levels of RNA encoding IL-1β in Crohn's disease patients who responded to and did not respond to infliximab.

[0091] Figure 3 Expression levels of RNA encoding NLRP3 in patients with ulcerative colitis (UC) who responded to and did not respond to infliximab.

[0092] Figure 4 Expression levels of RNA encoding IL-1β in patients with ulcerative colitis (UC) who responded to and did not respond to infliximab.

[0093] Figure 5 Ball-and-stick representations of two crystallographically independent molecules of compound 162bb in the asymmetric unit are depicted. Detailed Implementation

[0094] In one respect, this article provides compounds having the formula AA.

[0095]

[0096] in

[0097] m = 0, 1, or 2;

[0098] n = 0, 1, or 2;

[0099] o = 1 or 2;

[0100] p = 0, 1, 2 or 3; where the sum of o and p ranges from 1 to 4;

[0101] in

[0102] A is a 5- to 10-membered heteroaryl or a C6-C 10 aryl;

[0103] B is a 6-membered heteroaromatic ring containing 1-3 N atoms, or its N oxide;

[0104] At least one of the R 6 It is located in the ortho position of the bond that links the B ring to the NHC(O) group of formula AA;

[0105] R 1 and R 2 Each is independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halogen, CN, NO2, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10 Aryl, 5- to 10-membered heteroaryl, NR 8 R 9 、C(O)R 13 、CONR 8 R 9 SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, S(O2)NR 11 R 12 S(O)C1-C6 alkyl, C3-C7 cycloalkyl and 3 to 7-membered heterocyclic alkyl,

[0106] The C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C6-C 10 The aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl, and 3- to 7-membered heterocycloalkyl groups are optionally substituted by one or more substituents, each independently selected from the following: hydroxyl, halogen, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, R 15 NR 8 R 9 、=NR 10 、COOC1-C6 alkyl、CONR 8 R 9 3 to 7-membered heterocyclic alkyl groups, C6-C 10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), and OCO (3- to 7-membered heterocyclic alkyl);

[0107] wherein R 1or R 2 C3-C7 cycloalkyl or said R 1 or R 2 Each C1-C6 alkyl substituent and each C1-C6 alkoxy substituent of the 3- to 7-membered heterocycloalkyl group is further optionally and independently substituted with one to three hydroxyl groups, -O(C0-C3 alkylene)C6-C 10 Aryl, halogenated, NR 8 R 9 , or oxo-substituted;

[0108] wherein the 3 to 7 membered heterocycloalkyl, C6-C 10 Aryl, and 5- to 10-membered heteroaryl are each optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;

[0109] or a pair of R located on adjacent atoms 1 and R 2 Together with the atoms that connect them, they independently form at least one monocyclic or bicyclic C4-C 12 carbocyclic ring or at least one monocyclic or bicyclic 5- to 12-membered heterocyclic ring, wherein:

[0110] a) When each of the adjacent atoms is a carbon atom, the heterocycle contains from 1 to 3 heteroatoms and / or heteroatom groups independently selected from the group consisting of O, NH, NR 13 , S, S(O), and S(O)2; and

[0111] b) When one or two of the adjacent atoms are nitrogen atoms, the heterocyclic ring contains from 0 to 2 heteroatoms and / or heteroatom groups independently selected from the following: O, NH, NR 13 S, S(O), and S(O)2 (except for the aforementioned connection to R) 1 and / or R 2 one or more nitrogen atoms), and

[0112] The carbocyclic or heterocyclic ring is optionally and independently substituted by one or more substituents, each independently selected from the following: hydroxyl, halogenated, oxo-substituted, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, OC3-C 10 Cycloalkyl, NR 8 R 9 、=NR 10 、CN、COOC1-C6 alkyl、OS(O2)C6-C 10 Aryl, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10Cycloalkyl, 3- to 10-membered heterocycloalkyl, and CONR 8 R 9 ,

[0113] wherein the C1-C6 alkyl, C1-C6 alkoxy, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, and 3 to 10 membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from the group consisting of hydroxy, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 alkyl, C4-C6 alkyl, C6-C6 alkyl, C7-C6 alkyl, C8-C6 alkyl, C9-C6 alkyl, C10-C6 alkyl, C11-C6 alkyl, C12-C6 alkyl, C13-C6 alkyl, C14-C6 alkyl, C15-C6 alkyl, C16-C6 alkyl, C17-C6 alkyl, C18-C6 alkyl, C19-C6 alkyl, C21-C6 alkyl, C22-C6 alkyl, C23-C6 alkyl, C24-C6 alkyl, C25-C6 alkyl, C2 10 Cycloalkyl, C1-C6 alkoxy, oxo, NR 8 R 9 、=NR 10 COOC1-C6 alkyl, C6-C 10 Aryl and CONR 8 R 9 ;

[0114] R 6 and R 7 Each is independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halogen, hydroxyl, oxo, CN, NO2, COC1-C6 alkyl, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10 Aryl, 5- to 10-membered heteroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, CONR 8 R 9 SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, C3-C 10 Cycloalkyl and 3- to 10-membered heterocycloalkyl, and C2-C6 alkenyl,

[0115] Where R 6 and R 7 Each may optionally be substituted by one or more substituents independently selected from the following: hydroxyl, halogen, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR. 8 R 9 、=NR 10 、COOC1-C6 alkyl、CONR 8 R 9 3 to 7-membered heterocyclic alkyl groups, C6-C 10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10 aryloxy, and S(O2)C1-C6 alkyl; and wherein substituted R 6 or R 7 The C1-C6 alkyl or C1-C6 alkoxy group is optionally surrounded by one or more hydroxyl groups, C6-C 10 Aryl or NR 8 R 9 Replace, or where R 6 or R 7 optionally fused to a five- to seven-membered carbocyclic or heterocyclic ring containing one or two heteroatoms independently selected from oxygen, sulfur, and nitrogen;

[0116] wherein the 3 to 7 membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, NHCOC6-C 10 Aryl, NHCO(5- to 10-membered heteroaryl), and NHCO(3- to 7-membered heterocycloalkyl) are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;

[0117] Or at least one pair of R atoms located on adjacent atoms 6 and R 7 Together with the atoms that connect them, they independently form at least one C4-C8 carbon ring or at least one 5- to 8-membered heterocycle, said heterocycle containing one or two atoms independently selected from O, NH, and NR. 13 The heteroatom of S, wherein the carbocyclic or heterocyclic ring is optionally and independently substituted by one or more substituents independently selected from: hydroxyl, hydroxymethyl, halogenated, oxo-substituted, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, NR 8 R 9 CH2NR 8 R 9 、=NR 10 、COOH、COOC1-C6 alkyl、C6-C 10 Aryl and CONR 8 R 9 ;

[0118] R 10 It is a C1-C6 alkyl group;

[0119] R 8 and R 9 Each of these elements is independently selected from hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C3-C7 cycloalkyl, C1-C6 haloalkyl, (C=NR) each time it appears. 13 )NR 11 R12 、S(O2)C1-C6 alkyl、S(O2)NR 11 R 12 COR 13 CO2R 13 and CONR 11 R 12 wherein the C1-C6 alkyl group is optionally substituted by one or more hydroxyl groups, halo groups, C1-C6 alkoxy groups, C6-C 10 aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl, 3- to 7-membered heterocycloalkyl, or NR 11 R 12 ;

[0120] or R 8 and R 9 Together with the nitrogen atoms to which they are attached, they form 3- to 10-membered monocyclic or bicyclic rings optionally containing one or more heteroatoms other than the nitrogen atoms to which they are attached, wherein said rings are optionally substituted by one or more substituents independently selected from: halogenated, C-shaped, etc. 1- C6 alkyl, C 1- C6 haloalkyl, C1-C6 alkoxy, oxo, N(C1-C6 alkyl)2, NH2, NH(C1-C6 alkyl), and hydroxy;

[0121] R 13 is C1-C6 alkyl, C1-C6 haloalkyl, or -(Z 1 -Z 2 ) a1 -Z 3 ;

[0122] R 11 and R 12 Each of these elements is independently selected from hydrogen, C1-C6 alkyl groups, and -(Z) each time it appears. 1 -Z 2 ) a1 -Z 3 ;

[0123] a1 is an integer selected from 0-10 (e.g., 0-5);

[0124] Each Z 1 Independently, it is a C1-C6 alkylene group optionally substituted with one or more substituents independently selected from oxo, halogenated, and hydroxyl groups;

[0125] Each Z 2 is independently a bond, NH, N(C1-C6 alkyl), -O-, -S-, or a 5-10 membered heteroarylene group;

[0126] Z 3 Independently C 6-C 10 Aryl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C 10 cycloalkyl, 5- to 10-membered heteroaryl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from the group consisting of halo, C1-C6 alkyl, C 1-6 Haloalkyl, C1-C6 alkoxy, oxo, N(C1-C6 alkyl)2, NH2, NH(C1-C6 alkyl), and hydroxy;

[0127] R 3 Selected from hydrogen, cyano, hydroxyl, CO2C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkyl, and The C1-C2 alkylene groups are optionally substituted with oxo groups;

[0128] R 14 is hydrogen, C1-C6 alkyl, 5- to 10-membered monocyclic or bicyclic heteroaryl, or C6-C 10 Monocyclic or bicyclic aryl, wherein each C1-C6 alkyl, aryl or heteroaryl is optionally independently replaced by 1 or 2 R 6 replace;

[0129] R 15 Yes - (Z 4 -Z 5 ) a2 -Z 6 ;

[0130] a2 is an integer selected from 1 to 10 (e.g., 1 to 5 (e.g., 2 to 5));

[0131] Each Z 4 Independently selected from -O-, -S-, -NH-, and -N(C1-C3 alkyl)-;

[0132] The prerequisite is a direct connection to R. 1 or R 2 Z 4 The radical is -O- or -S-;

[0133] Each Z 5 is independently C1-C6 alkylene optionally substituted by one or more substituents independently selected from oxo, halo, and hydroxy; and

[0134] Z 6 is OH, OC1-C6 alkyl, NH2, NH(C1-C6 alkyl), N(C1-C6 alkyl)2, NHC(O)(C1-C6 alkyl), NHC(O)(C1-C6 alkoxy), or an optionally substituted group selected from the group consisting of:

[0135] C6- C 10 Aryl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C 10 cycloalkyl, 5- to 10-membered heteroaryl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from the group consisting of halo, C1-C6 alkyl, C 1-6 Haloalkyl, C1-C6 alkoxy, oxo, N(C1-C6 alkyl)2, NH2, NH(C1-C6 alkyl), and hydroxy;

[0136] The condition is that the compound having formula AA is not a compound selected from the group consisting of:

[0137]

[0138] or a pharmaceutically acceptable salt thereof.

[0139] In one respect, this article provides compounds having the formula AA:

[0140]

[0141]

[0142] in

[0143] m = 0, 1, or 2;

[0144] n = 0, 1, or 2;

[0145] o = 1 or 2;

[0146] p = 0, 1, 2 or 3; where the sum of o and p ranges from 1 to 4;

[0147] in

[0148] A is a 5- to 10-membered heteroaryl or a C6-C 10 aryl;

[0149] B is a 6-membered heteroaromatic ring containing 1-3 N atoms, or its N oxide;

[0150] At least one of the R 6 It is located in the ortho position of the bond that links the B ring to the NHC(O) group of formula AA;

[0151] R 1 and R 2 Each is independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halogen, CN, NO2, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C 10Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10 Aryl, 5- to 10-membered heteroaryl, NR 8 R 9 、C(O)R 13 、CONR 8 R 9 SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, S(O2)NR 11 R 12 S(O)C1-C6 alkyl, C3-C7 cycloalkyl and 3 to 7-membered heterocyclic alkyl,

[0152] The C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C6-C 10 The aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl, and 3- to 7-membered heterocycloalkyl groups are optionally substituted by one or more substituents, each independently selected from the following: hydroxyl, halogen, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, R 15 NR 8 R 9 、=NR 10 、COOC1-C6 alkyl、CONR 8 R 9 3 to 7-membered heterocyclic alkyl groups, C6-C 10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), and OCO (3- to 7-membered heterocyclic alkyl);

[0153] wherein R 1 or R 2 C3-C7 cycloalkyl or said R 1 or R 2 Each C1-C6 alkyl substituent and each C1-C6 alkoxy substituent of the 3- to 7-membered heterocycloalkyl group is further optionally and independently substituted with one to three hydroxyl groups, -O(C0-C3 alkylene)C6-C 10 Aryl, halogenated, NR 8 R 9 , or oxo-substituted;

[0154] wherein the 3 to 7 membered heterocycloalkyl, C6-C 10 Aryl, and 5- to 10-membered heteroaryl are each optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;

[0155] or a pair of R located on adjacent atoms 1 and R 2Together with the atoms that connect them, they independently form at least one monocyclic or bicyclic C4-C 12 carbocyclic ring or at least one monocyclic or bicyclic 5- to 12-membered heterocyclic ring, wherein:

[0156] a) When each of the adjacent atoms is a carbon atom, the heterocycle contains from 1 to 3 heteroatoms and / or heteroatom groups independently selected from the group consisting of O, NH, NR 13 , S, S(O), and S(O)2; and

[0157] b) When one or two of the adjacent atoms are nitrogen atoms, the heterocyclic ring contains from 0 to 2 heteroatoms and / or heteroatom groups independently selected from the following: O, NH, NR 13 S, S(O), and S(O)2 (except for the aforementioned connection to R) 1 and / or R 2 one or more nitrogen atoms), and

[0158] The carbocyclic or heterocyclic ring is optionally and independently substituted by one or more substituents, each independently selected from the following: hydroxyl, halogenated, oxo-substituted, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, OC3-C 10 Cycloalkyl, NR 8 R 9 、=NR 10 、CN、COOC1-C6 alkyl、OS(O2)C6-C 10 Aryl, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, 3- to 10-membered heterocycloalkyl, and CONR 8 R 9 ,

[0159] wherein the C1-C6 alkyl, C1-C6 alkoxy, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, and 3 to 10 membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from the group consisting of hydroxy, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 alkyl, C4-C6 alkyl, C6-C6 alkyl, C7-C6 alkyl, C8-C6 alkyl, C9-C6 alkyl, C10-C6 alkyl, C11-C6 alkyl, C12-C6 alkyl, C13-C6 alkyl, C14-C6 alkyl, C15-C6 alkyl, C16-C6 alkyl, C17-C6 alkyl, C18-C6 alkyl, C19-C6 alkyl, C21-C6 alkyl, C22-C6 alkyl, C23-C6 alkyl, C24-C6 alkyl, C25-C6 alkyl, C2 10 Cycloalkyl, C1-C6 alkoxy, oxo, NR 8 R 9 、=NR 10 COOC1-C6 alkyl, C6-C 10 Aryl and CONR 8 R9 ;

[0160] R 6 and R 7 Each is independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halogen, CN, NO2, COC1-C6 alkyl, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10 Aryl, 5- to 10-membered heteroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, CONR 8 R 9 SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, C3-C 10 Cycloalkyl and 3- to 10-membered heterocycloalkyl, and C2-C6 alkenyl,

[0161] Where R 6 and R 7 Each may optionally be substituted by one or more substituents independently selected from the following: hydroxyl, halogen, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR. 8 R 9 、=NR 10 、COOC1-C6 alkyl、CONR 8 R 9 3 to 7-membered heterocyclic alkyl groups, C6-C 10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10 aryloxy, and S(O2)C1-C6 alkyl; and wherein substituted R 6 or R 7 The C1-C6 alkyl or C1-C6 alkoxy group is optionally surrounded by one or more hydroxyl groups, C6-C 10 Aryl or NR 8 R 9 Replace, or where R 6 or R 7 optionally fused to a five- to seven-membered carbocyclic or heterocyclic ring containing one or two heteroatoms independently selected from oxygen, sulfur, and nitrogen;

[0162] wherein the 3 to 7 membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, NHCOC6-C 10Aryl, NHCO(5- to 10-membered heteroaryl), and NHCO(3- to 7-membered heterocycloalkyl) are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;

[0163] Or at least one pair of R atoms located on adjacent atoms 6 and R 7 Together with the atoms that connect them, they independently form at least one C4-C8 carbon ring or at least one 5- to 8-membered heterocycle, said heterocycle containing one or two atoms independently selected from O, NH, and NR. 13 The heteroatom of S, wherein the carbocyclic or heterocyclic ring is optionally and independently substituted by one or more substituents independently selected from: hydroxyl, hydroxymethyl, halogenated, oxo-substituted, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, NR 8 R 9 CH2NR 8 R 9 、=NR 10 、COOH、COOC1-C6 alkyl、C6-C 10 Aryl and CONR 8 R 9 ;

[0164] R 10 It is a C1-C6 alkyl group;

[0165] R 8 and R 9 Each of these elements is independently selected from hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C3-C7 cycloalkyl, C1-C6 haloalkyl, (C=NR) each time it appears. 13 )NR 11 R 12 、S(O2)C1-C6 alkyl、S(O2)NR 11 R 12 COR 13 CO2R 13 and CONR 11 R 12 wherein the C1-C6 alkyl group is optionally substituted by one or more hydroxyl groups, halo groups, C1-C6 alkoxy groups, C6-C 10 aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl, 3- to 7-membered heterocycloalkyl, or NR 11 R 12 ;

[0166] or R 8 and R 9Together with the nitrogen atoms to which they are attached, they form 3- to 10-membered monocyclic or bicyclic rings optionally containing one or more heteroatoms other than the nitrogen atoms to which they are attached, wherein said rings are optionally substituted by one or more substituents independently selected from: halogenated, C-shaped, etc. 1- C6 alkyl, C 1- C6 haloalkyl, C1-C6 alkoxy, oxo, N(C1-C6 alkyl)2, NH2, NH(C1-C6 alkyl), and hydroxy;

[0167] R 13 is C1-C6 alkyl, C1-C6 haloalkyl, or -(Z 1 -Z 2 ) a1 -Z 3 ;

[0168] R 11 and R 12 Each of these elements is independently selected from hydrogen, C1-C6 alkyl groups, and -(Z) each time it appears. 1 -Z 2 ) a1 -Z 3 ;

[0169] a1 is an integer selected from 0-10 (e.g., 0-5);

[0170] Each Z 1 Independently, it is a C1-C6 alkylene group optionally substituted with one or more substituents independently selected from oxo, halogenated, and hydroxyl groups;

[0171] Each Z 2 is independently a bond, NH, N(C1-C6 alkyl), -O-, -S-, or a 5-10 membered heteroarylene group;

[0172] Z 3 Independently C 6- C 10 Aryl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C 10 cycloalkyl, 5- to 10-membered heteroaryl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from the group consisting of halo, C1-C6 alkyl, C 1-6 Haloalkyl, C1-C6 alkoxy, oxo, N(C1-C6 alkyl)2, NH2, NH(C1-C6 alkyl), and hydroxy;

[0173] R 3 Selected from hydrogen, cyano, hydroxyl, CO2C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkyl, and The C1-C2 alkylene groups are optionally substituted with oxo groups;

[0174] R 14 is hydrogen, C1-C6 alkyl, 5- to 10-membered monocyclic or bicyclic heteroaryl, or C6-C 10 Monocyclic or bicyclic aryl, wherein each C1-C6 alkyl, aryl or heteroaryl is optionally independently replaced by 1 or 2 R 6 replace;

[0175] R 15 Yes - (Z 4 -Z 5 ) a2 -Z 6 ;

[0176] a2 is an integer selected from 1 to 10 (e.g., 1 to 5 (e.g., 2 to 5));

[0177] Each Z 4 Independently selected from -O-, -S-, -NH-, and -N(C1-C3 alkyl)-;

[0178] The prerequisite is a direct connection to R. 1 or R 2 Z 4 The radical is -O- or -S-;

[0179] Each Z 5 is independently C1-C6 alkylene optionally substituted by one or more substituents independently selected from oxo, halo, and hydroxy; and

[0180] Z 6 is OH, OC1-C6 alkyl, NH2, NH(C1-C6 alkyl), N(C1-C6 alkyl)2, NHC(O)(C1-C6 alkyl), NHC(O)(C1-C6 alkoxy), or an optionally substituted group selected from the group consisting of:

[0181] C 6- C 10 Aryl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C 10 cycloalkyl, 5- to 10-membered heteroaryl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from the group consisting of halo, C1-C6 alkyl, C 1-6 Haloalkyl, C1-C6 alkoxy, oxo, N(C1-C6 alkyl)2, NH2, NH(C1-C6 alkyl), and hydroxy;

[0182] The condition is that the compound having formula AA is not a compound selected from the group consisting of:

[0183]

[0184] or a pharmaceutically acceptable salt thereof.

[0185] In one respect, this article provides compounds having the formula AA.

[0186]

[0187] in

[0188] m = 0, 1, or 2;

[0189] n = 0, 1, or 2;

[0190] o = 1 or 2;

[0191] p = 0, 1, 2 or 3;

[0192] The sum of o and p ranges from 1 to 4;

[0193] in

[0194] A is a 5- to 10-membered heteroaryl or a C6-C 10 aryl;

[0195] B is a 6-membered heteroaromatic ring containing 1-3 N atoms, or its N oxide;

[0196] in

[0197] At least one R 6 It is located in the ortho position of the bond that links the B ring to the NHC(O) group of formula AA;

[0198] R 1 and R 2 Each is independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halogen, CN, NO2, COC1-C6 alkyl, CO-C6-C 10 Aryl, CO (5- to 10-membered heteroaryl), CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10 Aryl, 5- to 10-membered heteroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, NHCOC1-C6 alkyl, NHCOC6-C 10 Aryl, NHCO (5- to 10-membered heteroaryl), NHCO (3- to 7-membered heterocyclic alkyl), NHCOC2-C6 ynyl, NHCOOC1-C6 alkyl, NH-(C=NR) 13 )NR 11 R 12 、CONR 8 R9 SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, S(O2)NR 11 R 12 S(O)C1-C6 alkyl, C3-C7 cycloalkyl and 3 to 7-membered heterocyclic alkyl,

[0199] The C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, and 3- to 7-membered heterocyclic alkyl groups are optionally substituted by one or more substituents, each independently selected from the following: hydroxyl, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR. 8 R 9 、=NR 10 、COOC1-C6 alkyl、CONR 8 R 9 3 to 7-membered heterocyclic alkyl groups, C6-C 10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocyclic alkyl), NHCOC1-C6 alkyl, NHCOC6-C 10 Aryl, NHCO (5- to 10-membered heteroaryl), NHCO (3- to 7-membered heterocyclic alkyl), and NHCOC2-C6 alkynyl;

[0200] wherein R 1 or R 2 C3-C7 cycloalkyl or said R 1 or R 2 Each C1-C6 alkyl substituent and each C1-C6 alkoxy substituent of the 3- to 7-membered heterocyclic alkyl group may further optionally be independently replaced by one to three hydroxyl, halogenated, or NR-substituted groups. 8 R 9 , or oxo-substituted;

[0201] wherein the 3 to 7 membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, NHCOC6-C 10 Aryl, NHCO(5- to 10-membered heteroaryl), and NHCO(3- to 7-membered heterocycloalkyl) are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;

[0202] or a pair of R located on adjacent atoms 1 and R 2 Together with the atoms that connect them, they independently form a monocyclic or bicyclic C4-C ring. 12A carbon ring or a monocyclic or bicyclic 5- to 12-membered heterocycle, wherein a) when each of the adjacent atoms is a carbon atom, the heterocycle comprises 1 to 3 heteroatoms and / or heteroatom groups independently selected from: O, NH, NR 13 S, S(O), and S(O)2; and b) when one or both of the adjacent atoms are nitrogen atoms, the heterocycle comprises 0-2 heteroatoms and / or heteroatom groups independently selected from: O, NH, NR 13 S, S(O), and S(O)2 (except for the aforementioned connection to R) 1 and / or R 2 (excluding one or more nitrogen atoms), and wherein the carbocyclic or heterocyclic ring is optionally independently substituted by one or more substituents each independently selected from the following: hydroxyl, halogen, oxo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, OC3-C 10 Cycloalkyl, NR 8 R 9 、=NR 10 、CN、COOC1-C6 alkyl、OS(O2)C6-C 10 Aryl, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, 3- to 10-membered heterocycloalkyl, and CONR 8 R 9 The C1-C6 alkyl, C1-C6 alkoxy, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, and 3 to 10 membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from the group consisting of hydroxy, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 alkyl, C4-C6 alkyl, C6-C6 alkyl, C7-C6 alkyl, C8-C6 alkyl, C9-C6 alkyl, C10-C6 alkyl, C11-C6 alkyl, C12-C6 alkyl, C13-C6 alkyl, C14-C6 alkyl, C15-C6 alkyl, C16-C6 alkyl, C17-C6 alkyl, C18-C6 alkyl, C19-C6 alkyl, C21-C6 alkyl, C22-C6 alkyl, C23-C6 alkyl, C24-C6 alkyl, C25-C6 alkyl, C2 10 Cycloalkyl, C1-C6 alkoxy, oxo, NR 8 R 9 、=NR 10 COOC1-C6 alkyl, C6-C 10 Aryl and CONR 8 R 9 ;

[0203] R 6 and R 7Each is independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halogen, CN, NO2, COC1-C6 alkyl, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10 Aryl, 5- to 10-membered heteroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, CONR 8 R 9 SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, C3-C 10 Cycloalkyl and 3- to 10-membered heterocycloalkyl, and C2-C6 alkenyl,

[0204] Where R 6 and R 7 Each may optionally be substituted by one or more substituents independently selected from the following: hydroxyl, halogen, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR. 8 R 9 、=NR 10 、COOC1-C6 alkyl、CONR 8 R 9 3 to 7-membered heterocyclic alkyl groups, C6-C 10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocyclic alkyl), NHCOC1-C6 alkyl, NHCOC6-C 10 Aryl, NHCO (5- to 10-membered heteroaryl), NHCO (3- to 7-membered heterocycloalkyl), NHCOC2-C6 ynyl, C6-C 10 aryloxy, and S(O2)C1-C6 alkyl; and wherein substituted R 6 or R 7 The C1-C6 alkyl or C1-C6 alkoxy group is optionally surrounded by one or more hydroxyl groups, C6-C 10 Aryl or NR 8 R 9 Replace, or where R 6 or R 7 optionally fused to a five- to seven-membered carbocyclic or heterocyclic ring containing one or two heteroatoms independently selected from oxygen, sulfur, and nitrogen;

[0205] wherein the 3 to 7 membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, NHCOC6-C 10Aryl, NHCO(5- to 10-membered heteroaryl), and NHCO(3- to 7-membered heterocycloalkyl) are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;

[0206] or a pair of R located on adjacent atoms 6 and R 7 Together with the atoms connecting them, they independently form at least one C4-C8 carbon ring or at least one 5- to 8-membered heterocycle, said heterocycle containing one or two heteroatoms and / or heteroatom groups independently selected from: O, NH, NR. 13 S, S(O), and S(O)2, wherein the carbocyclic or heterocyclic ring is optionally and independently substituted by one or more substituents independently selected from the following: hydroxyl, hydroxymethyl, halogenated, oxo-substituted, C1-C6 alkyl, C1-C6 alkoxy, NR 8 R 9 CH2NR 8 R 9 、=NR 10 COOC1-C6 alkyl, C6-C 10 Aryl and CONR 8 R 9 ;

[0207] R 10 It is a C1-C6 alkyl group;

[0208] R 8 and R 9 Each of these terms is independently selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, (C=NR) each time it appears. 13 )NR 11 R 12 、S(O2)C1-C6 alkyl、S(O2)NR 11 R 12 COR 13 CO2R 13 and CONR 11 R 12 wherein the C1-C6 alkyl group is optionally substituted by one or more hydroxyl groups, halo groups, C1-C6 alkoxy groups, C6-C 10 aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl, or 3- to 7-membered heterocycloalkyl; or R 8 and R 9 taken together with the nitrogen to which they are attached to form a 3- to 7-membered ring optionally containing one or more heteroatoms in addition to the nitrogen to which they are attached;

[0209] R 13 It is a C1-C6 alkyl, C1-C6 haloalkyl, C6-C 10aryl, or 5- to 10-membered heteroaryl;

[0210] R 11 and R 12 Each of these terms is independently selected from hydrogen and C1-C6 alkyl groups each time it appears;

[0211] and

[0212] R 3 Selected from hydrogen, cyano, hydroxyl, CO2C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkyl, and The C1-C2 alkylene groups are optionally substituted with oxo groups;

[0213] R 14 is hydrogen, C1-C6 alkyl, 5- to 10-membered monocyclic or bicyclic heteroaryl, or C6-C 10 Monocyclic or bicyclic aryl, wherein each C1-C6 alkyl, aryl or heteroaryl is optionally independently replaced by 1 or 2 R 6 replace;

[0214] The condition is that the compound having formula AA is not a compound selected from the group consisting of:

[0215]

[0216] or a pharmaceutically acceptable salt thereof.

[0217] In another aspect, this article provides compounds having the formula AA.

[0218]

[0219]

[0220] wherein the compound of formula AA is selected from

[0221]

[0222] in

[0223] m = 0, 1, or 2;

[0224] n = 0, 1, or 2;

[0225] m' = 0, 1, or 2;

[0226] n' = 0, 1, or 2; where the sum of m' and n' is 0, 1, or 3; m” = 0, 1, or 2;

[0227] n” = 0, 1 or 2; where the sum of m” and n” is 2;

[0228] m”'=1;

[0229] n”'=1;

[0230] o = 1 or 2;

[0231] p = 0, 1, 2 or 3; where the sum of o and p ranges from 1 to 4;

[0232] in

[0233] A' is selected from:

[0234] 6 to 10 yuan of mixed aromatic compounds,

[0235] C6-C 10 Aryl,

[0236] Five-membered heteroaryl groups containing two or more heteroatoms

[0237] Includes 1 selected from N, NH, and NR 1 5-membered heteroaryl groups of heteroatoms or heteroatom groups, and

[0238] A 5-membered heteroaryl group comprising one heteroatom selected from O and S, wherein the heteroatom is not bonded to S(O)(NHR) 3 Positional bonding of N parts;

[0239] A” is a 5-membered heteroaryl group containing one heteroatom selected from O and S, wherein the heteroatom is bonded to the heteroaryl group to S(O)(NHR). 3 )=position bonding of N part;

[0240] B is a 6-membered heteroaromatic ring containing 1-3 N atoms, or its N oxide;

[0241] B' is 2-pyridinyl, 3-pyridinyl, or its N-oxide;

[0242] B” is 4-pyridinyl or its N-oxide;

[0243] in

[0244] At least one R 6 It is located in the ortho position of the bond that links the B ring to the NHC(O) group of formula AA-2, formula AA-3, and formula AA-4;

[0245] At least one R 6’ It is located in the ortho position of the bond that links the B ring to the NHC(O) group of formula AA-5;

[0246] At least one R 6” It is located in the ortho position of the bond that links the B ring to the NHC(O) group of formula AA-1;

[0247] R 1 and R2 Each is independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halogen, CN, NO2, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10 Aryl, 5- to 10-membered heteroaryl, NR 8 R 9 、C(O)R 13 、CONR 8 R 9 SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, S(O2)NR 11 R 12 S(O)C1-C6 alkyl, C3-C7 cycloalkyl and 3 to 7-membered heterocyclic alkyl,

[0248] The C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C6-C 10 The aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl, and 3- to 7-membered heterocycloalkyl groups are optionally substituted by one or more substituents, each independently selected from the following: hydroxyl, halogen, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, R 15 NR 8 R 9 、=NR 10 、COOC1-C6 alkyl、CONR 8 R 9 3 to 7-membered heterocyclic alkyl groups, C6-C 10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), and OCO (3- to 7-membered heterocyclic alkyl);

[0249] wherein R 1 or R 2 C3-C7 cycloalkyl or said R 1 or R 2 Each C1-C6 alkyl substituent and each C1-C6 alkoxy substituent of the 3- to 7-membered heterocycloalkyl group is further optionally and independently substituted with one to three hydroxyl groups, -O(C0-C3 alkylene)C6-C 10 Aryl, halogenated, NR 8 R 9 , or oxo-substituted;

[0250] wherein the 3 to 7 membered heterocycloalkyl, C6-C 10Aryl, and 5- to 10-membered heteroaryl are each optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;

[0251] or a pair of R located on adjacent atoms 1 and R 2 Together with the atoms that connect them, they independently form a monocyclic or bicyclic C4-C ring. 12 A carbon ring or a single or double ring of 5 to 12-membered heterocyclic rings, wherein:

[0252] a) When each of the adjacent atoms is a carbon atom, the heterocycle contains from 1 to 3 heteroatoms and / or heteroatom groups independently selected from the group consisting of O, NH, NR 13 , S, S(O), and S(O)2; and

[0253] b) When one or two of the adjacent atoms are nitrogen atoms, the heterocyclic ring contains from 0 to 2 heteroatoms and / or heteroatom groups independently selected from the following: O, NH, NR 13 S, S(O), and S(O)2 (except for the aforementioned connection to R) 1 and / or R 2 one or more nitrogen atoms), and

[0254] The carbocyclic or heterocyclic ring is optionally and independently substituted by one or more substituents, each independently selected from the following: hydroxyl, halogenated, oxo-substituted, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, OC3-C 10 Cycloalkyl, NR 8 R 9 、=NR 10 、CN、COOC1-C6 alkyl、OS(O2)C6-C 10 Aryl, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, 3- to 10-membered heterocycloalkyl, and CONR 8 R 9 ,

[0255] wherein the C1-C6 alkyl, C1-C6 alkoxy, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, and 3 to 10 membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from the group consisting of hydroxy, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 alkyl, C4-C6 alkyl, C6-C6 alkyl, C7-C6 alkyl, C8-C6 alkyl, C9-C6 alkyl, C10-C6 alkyl, C11-C6 alkyl, C12-C6 alkyl, C13-C6 alkyl, C14-C6 alkyl, C15-C6 alkyl, C16-C6 alkyl, C17-C6 alkyl, C18-C6 alkyl, C19-C6 alkyl, C21-C6 alkyl, C22-C6 alkyl, C23-C6 alkyl, C24-C6 alkyl, C25-C6 alkyl, C210 Cycloalkyl, C1-C6 alkoxy, oxo, NR 8 R 9 、=NR 10 COOC1-C6 alkyl, C6-C 10 Aryl and CONR 8 R 9 ;

[0256] R 1’ and R 2’ Each is independently selected from C2-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, Cl, Br, I, CN, NO2, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10 Aryl, 5- to 10-membered heteroaryl, NR 8 R 9 、C(O)R 13 、CONR 8 R 9 SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, S(O2)NR 11 R 12 S(O)C1-C6 alkyl, C3-C7 cycloalkyl and 3 to 7-membered heterocyclic alkyl,

[0257] The C2-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C6-C 10 The aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl, and 3- to 7-membered heterocycloalkyl groups are optionally substituted by one or more substituents, each independently selected from the following: hydroxyl, halogen, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, R 15 NR 8 R 9 、=NR 10 、COOC1-C6 alkyl、CONR 8 R 9 3 to 7-membered heterocyclic alkyl groups, C6-C 10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), and OCO (3- to 7-membered heterocyclic alkyl);

[0258] wherein R 1’ or R 2’ C3-C7 cycloalkyl or said R 1’ or R 2’Each C1-C6 alkyl substituent and each C1-C6 alkoxy substituent of the 3- to 7-membered heterocycloalkyl group is further optionally and independently substituted with one to three hydroxyl groups, -O(C0-C3 alkylene)C6-C 10 Aryl, halogenated, NR 8 R 9 , or oxo-substituted;

[0259] wherein the 3 to 7 membered heterocycloalkyl, C6-C 10 Aryl, and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;

[0260] or a pair of R located on adjacent atoms 1’ and R 2’ Together with the atoms that connect them, they independently form a monocyclic or bicyclic C4-C ring. 12 A carbon ring or a monocyclic or bicyclic 5- to 12-membered heterocycle, said heterocycle comprising 1 to 3 heteroatoms and / or heteroatom groups independently selected from the following: O, NH, NR. 13 S, S(O), and S(O)2, and

[0261] The carbocyclic or heterocyclic ring is optionally and independently substituted by one or more substituents independently selected from the following: hydroxyl, halogenated, oxo-substituted, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, OC3-C 10 Cycloalkyl, NR 8 R 9 、=NR 10 、CN、COOC1-C6 alkyl、OS(O2)C6-C 10 Aryl, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, 3- to 10-membered heterocycloalkyl, and CONR 8 R 9 ,

[0262] wherein the C1-C6 alkyl, C1-C6 alkoxy, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, and 3 to 10 membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from the group consisting of hydroxy, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 alkyl, C4-C6 alkyl, C6-C6 alkyl, C7-C6 alkyl, C8-C6 alkyl, C9-C6 alkyl, C10-C6 alkyl, C11-C6 alkyl, C12-C6 alkyl, C13-C6 alkyl, C14-C6 alkyl, C15-C6 alkyl, C16-C6 alkyl, C17-C6 alkyl, C18-C6 alkyl, C19-C6 alkyl, C21-C6 alkyl, C22-C6 alkyl, C23-C6 alkyl, C24-C6 alkyl, C25-C6 alkyl, C2 10 Cycloalkyl, C1-C6 alkoxy, oxo, NR 8 R9 、=NR 10 COOC1-C6 alkyl, C6-C 10 Aryl and CONR 8 R 9 ;

[0263] R 2” It is F or CH3; or

[0264] When the compound having formula AA is a compound having formula AA-4, a pair of R atoms located on adjacent atoms 1 and R 2” Together with the atoms that connect them, they independently form a monocyclic or bicyclic C4-C ring. 12 A carbon ring or a monocyclic or bicyclic 5- to 12-membered heterocycle, said heterocycle comprising 1 to 3 heteroatoms and / or heteroatom groups independently selected from the following: O, NH, NR. 13 S, S(O), and S(O)2, and

[0265] The carbocyclic or heterocyclic ring is optionally and independently substituted by one or more substituents independently selected from the following: hydroxyl, halogenated, oxo-substituted, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, OC3-C 10 Cycloalkyl, NR 8 R 9 、=NR 10 、CN、COOC1-C6 alkyl、OS(O2)C6-C 10 Aryl, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, 3- to 10-membered heterocycloalkyl, and CONR 8 R 9 ,

[0266] wherein the C1-C6 alkyl, C1-C6 alkoxy, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, and 3 to 10 membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from the group consisting of hydroxy, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 alkyl, C4-C6 alkyl, C6-C6 alkyl, C7-C6 alkyl, C8-C6 alkyl, C9-C6 alkyl, C10-C6 alkyl, C11-C6 alkyl, C12-C6 alkyl, C13-C6 alkyl, C14-C6 alkyl, C15-C6 alkyl, C16-C6 alkyl, C17-C6 alkyl, C18-C6 alkyl, C19-C6 alkyl, C21-C6 alkyl, C22-C6 alkyl, C23-C6 alkyl, C24-C6 alkyl, C25-C6 alkyl, C2 10 Cycloalkyl, C1-C6 alkoxy, oxo, NR 8 R 9 、=NR 10 COOC1-C6 alkyl, C6-C 10 Aryl and CONR8 R 9 ;

[0267] R 6 and R 7 Each is independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halogen, hydroxyl, oxo, CN, NO2, COC1-C6 alkyl, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10 Aryl, 5- to 10-membered heteroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, CONR 8 R 9 SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, C3-C 10 Cycloalkyl and 3- to 10-membered heterocycloalkyl, and C2-C6 alkenyl,

[0268] Where R 6 and R 7 Each may optionally be substituted by one or more substituents independently selected from the following: hydroxyl, halogen, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR. 8 R 9 、=NR 10 、COOC1-C6 alkyl、CONR 8 R 9 3 to 7-membered heterocyclic alkyl groups, C6-C 10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10 aryloxy, and S(O2)C1-C6 alkyl; and wherein substituted R 6 or R 7 The C1-C6 alkyl or C1-C6 alkoxy group is optionally surrounded by one or more hydroxyl groups, C6-C 10 Aryl or NR 8 R 9 Replace, or where R 6 or R 7 optionally fused to a five- to seven-membered carbocyclic or heterocyclic ring containing one or two heteroatoms independently selected from oxygen, sulfur, and nitrogen;

[0269] wherein the 3 to 7 membered heterocycloalkyl, C6-C 10Aryl, and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;

[0270] or a pair of R located on adjacent atoms 6 and R 7 Together with the atoms connecting them, they independently form at least one C4-C8 carbon ring or at least one 5- to 8-membered heterocycle, said heterocycle containing one or two heteroatoms and / or heteroatom groups independently selected from: O, NH, NR. 13 S, S(O), and S(O)2, wherein the carbocyclic or heterocyclic ring is optionally and independently substituted by one or more substituents independently selected from the following: hydroxyl, hydroxymethyl, halogenated, oxo-substituted, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, NR 8 R 9 CH2NR 8 R 9 、=NR 10 、COOH、COOC1-C6 alkyl、C6-C 10 Aryl and CONR 8 R 9 ;

[0271] R 6’ and R 7’ Each is independently selected from non-branched C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halogen, hydroxyl, oxo, CN, NO2, COC1-C6 alkyl, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10 Aryl, 5- to 10-membered heteroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, CONR 8 R 9 SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, C3-C 10 Cycloalkyl and 3- to 10-membered heterocycloalkyl, and C2-C6 alkenyl,

[0272] Where R 6’ and R 7’ Each is optionally substituted with one or more substituents independently selected from the group consisting of hydroxy, halo, CN, oxo, C1-C6 alkoxy, NR 8 R 9 、=NR 10 、COOC1-C6 alkyl、CONR 8 R9 3 to 7-membered heterocyclic alkyl groups, C6-C 10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10 aryloxy, and S(O2)C1-C6 alkyl; and wherein substituted R 6’ or R 7’ The C1-C6 alkoxy group is optionally replaced by one or more hydroxyl groups, C6-C 10 Aryl or NR 8 R 9 Replace, or where R 6’ or R 7’ optionally fused to a five- to seven-membered carbocyclic or heterocyclic ring containing one or two heteroatoms independently selected from oxygen, sulfur, and nitrogen;

[0273] wherein the 3 to 7 membered heterocycloalkyl, C6-C 10 Aryl, and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;

[0274] or a pair of R located on adjacent atoms 6’ and R 7’ Together with the atoms connecting them, they independently form at least one C4-C8 carbon ring or at least one 5- to 8-membered heterocycle, said heterocycle containing one or two heteroatoms and / or heteroatom groups independently selected from: O, NH, NR. 13 S, S(O), and S(O)2, wherein the carbocyclic or heterocyclic ring is optionally and independently substituted by one or more substituents independently selected from the following: hydroxyl, hydroxymethyl, halogenated, oxo-substituted, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, NR 8 R 9 CH2NR 8 R 9 、=NR 10 、COOH、COOC1-C6 alkyl、C6-C 10 Aryl and CONR 8 R 9 ;

[0275] R 6” Selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, hydroxy, oxo, NO2, COC1-C6 alkyl, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C 10Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10 Aryl, 5- to 10-membered heteroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, CONR 8 R 9 SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, C3-C 10 Cycloalkyl, 3- to 10-membered heterocyclic alkyl, and C2-C6 alkenyl,

[0276] Where R 6” Optionally substituted by one or more substituents independently selected from the following: hydroxyl, halogen, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR 8 R 9 、=NR 10 、COOC1-C6 alkyl、CONR 8 R 9 3 to 7-membered heterocyclic alkyl groups, C6-C 10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10 Aryloxy, and S(O2)C1-C6 alkyl; and

[0277] where R is substituted 6” The C1-C6 alkyl or C1-C6 alkoxy group is optionally surrounded by one or more hydroxyl groups, C6-C 10 Aryl or NR 8 R 9 Replace, or where R 6” optionally fused to a five- to seven-membered carbocyclic or heterocyclic ring containing one or two heteroatoms independently selected from oxygen, sulfur, and nitrogen;

[0278] wherein the 3 to 7 membered heterocycloalkyl, C6-C 10 Aryl, and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;

[0279] or a pair of R located on adjacent atoms 6” and R 7 Together with the atoms connecting them, they independently form at least one C4-C8 carbon ring or at least one 5- to 8-membered heterocycle, said heterocycle containing one or two heteroatoms and / or heteroatom groups independently selected from: O, NH, NR. 13S, S(O), and S(O)2, wherein the carbocyclic or heterocyclic ring is optionally and independently substituted by one or more substituents independently selected from the following: hydroxyl, hydroxymethyl, halogenated, oxo-substituted, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, NR 8 R 9 CH2NR 8 R 9 、=NR 10 、COOH、COOC1-C6 alkyl、C6-C 10 Aryl and CONR 8 R 9 ;

[0280] R 10 It is a C1-C6 alkyl group;

[0281] R 8 and R 9 Each of these elements is independently selected from hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C3-C7 cycloalkyl, C1-C6 haloalkyl, (C=NR) each time it appears. 13 )NR 11 R 12 、S(O2)C1-C6 alkyl、S(O2)NR 11 R 12 COR 13 CO2R 13 and CONR 11 R 12 wherein the C1-C6 alkyl group is optionally substituted by one or more hydroxyl groups, halo groups, C1-C6 alkoxy groups, C6-C 10 aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl, 3- to 7-membered heterocycloalkyl, or NR 11 R 12 ;

[0282] or R 8 and R 9 Together with the nitrogen atoms to which they are attached, they form 3- to 10-membered monocyclic or bicyclic rings optionally containing one or more heteroatoms other than the nitrogen atoms to which they are attached, wherein said rings are optionally substituted by one or more substituents independently selected from: halogenated, C-shaped, etc. 1- C6 alkyl, C 1- C6 haloalkyl, C1-C6 alkoxy, oxo, N(C1-C6 alkyl)2, NH2, NH(C1-C6 alkyl), and hydroxy;

[0283] R 13 is C1-C6 alkyl, C1-C6 haloalkyl, or -(Z 1 -Z 2 )a1 -Z 3 ;

[0284] R 11 and R 12 Each of these elements is independently selected from hydrogen, C1-C6 alkyl groups, and -(Z) each time it appears. 1 -Z 2 ) a1 -Z 3 ;

[0285] a1 is an integer selected from 0-10 (e.g., 0-5);

[0286] Each Z 1 Independently, it is a C1-C6 alkylene group optionally substituted with one or more substituents independently selected from oxo, halogenated, and hydroxyl groups;

[0287] Each Z 2 is independently a bond, NH, N(C1-C6 alkyl), -O-, -S-, or a 5-10 membered heteroarylene group;

[0288] Z 3 Independently C 6- C 10 Aryl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C 10 cycloalkyl, 5- to 10-membered heteroaryl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from the group consisting of halo, C1-C6 alkyl, C 1-6 Haloalkyl, C1-C6 alkoxy, oxo, N(C1-C6 alkyl)2, NH2, NH(C1-C6 alkyl), and hydroxy;

[0289] R 3 Selected from hydrogen, cyano, hydroxyl, CO2C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkyl, and The C1-C2 alkylene groups are optionally substituted with oxo groups;

[0290] R 14 is hydrogen, C1-C6 alkyl, 5- to 10-membered monocyclic or bicyclic heteroaryl, or C6-C 10 Monocyclic or bicyclic aryl, wherein each C1-C6 alkyl, aryl or heteroaryl is optionally independently replaced by 1 or 2 R 6 replace;

[0291] R 15 Yes - (Z 4 -Z 5 ) a2 -Z 6 ;

[0292] a2 is an integer selected from 1 to 10 (e.g., 1 to 5 (e.g., 2 to 5));

[0293] Each Z 4 Independently selected from -O-, -S-, -NH-, and -N(C1-C3 alkyl)-;

[0294] The prerequisite is a direct connection to R. 1 or R 2 Z 4 The radical is -O- or -S-;

[0295] Each Z 5 is independently C1-C6 alkylene optionally substituted by one or more substituents independently selected from oxo, halo, and hydroxy; and

[0296] Z 6 is OH, OC1-C6 alkyl, NH2, NH(C1-C6 alkyl), N(C1-C6 alkyl)2, NHC(O)(C1-C6 alkyl), NHC(O)(C1-C6 alkoxy), or an optionally substituted group selected from the group consisting of:

[0297] C 6- C 10 Aryl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C 10 cycloalkyl, 5- to 10-membered heteroaryl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from the group consisting of halo, C1-C6 alkyl, C 1-6 Haloalkyl, C1-C6 alkoxy, oxo, N(C1-C6 alkyl)2, NH2, NH(C1-C6 alkyl), and hydroxy;

[0298] or a pharmaceutically acceptable salt thereof.

[0299] In another aspect, provided herein is a compound having the formula AA:

[0300]

[0301] wherein the compound of formula AA is selected from

[0302]

[0303]

[0304] in

[0305] m = 0, 1, or 2;

[0306] n = 0, 1, or 2;

[0307] m' = 0, 1, or 2;

[0308] n' = 0, 1, or 2; where the sum of m' and n' is 0, 1, or 3;

[0309] m" = 0, 1, or 2;

[0310] n” = 0, 1 or 2; where the sum of m” and n” is 2;

[0311] m”'=1;

[0312] n”'=1;

[0313] o = 1 or 2;

[0314] p = 0, 1, 2 or 3; where the sum of o and p ranges from 1 to 4;

[0315] in

[0316] A' is selected from:

[0317] 6 to 10 yuan of mixed aromatic compounds,

[0318] C6-C 10 Aryl,

[0319] Five-membered heteroaryl groups containing two or more heteroatoms

[0320] Includes 1 selected from N, NH, and NR 1 5-membered heteroaryl groups of heteroatoms or heteroatom groups, and

[0321] A 5-membered heteroaryl group comprising one heteroatom selected from O and S, wherein the heteroatom is not bonded to S(O)(NHR) 3 )=position bonding of N part;

[0322] A” is a 5-membered heteroaryl group containing one heteroatom selected from O and S, wherein the heteroatom is bonded to the heteroaryl group to S(O)(NHR). 3 )=position bonding of N part;

[0323] B is a 6-membered heteroaromatic ring containing 1-3 N atoms, or its N oxide;

[0324] B' is 2-pyridinyl, 3-pyridinyl, or its N-oxide;

[0325] B” is 4-pyridinyl or its N-oxide;

[0326] in

[0327] At least one R 6 It is located in the ortho position of the bond that links the B ring to the NHC(O) group of formula AA-2, formula AA-3, and formula AA-4;

[0328] At least one R 6’ It is located in the ortho position of the bond that links the B ring to the NHC(O) group of formula AA-5;

[0329] At least one R 6” It is located in the ortho position of the bond that links the B ring to the NHC(O) group of formula AA-1;

[0330] R 1 and R 2 Each is independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halogen, CN, NO2, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10 Aryl, 5- to 10-membered heteroaryl, NR 8 R 9 、C(O)R 13 、CONR 8 R 9 SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, S(O2)NR 11 R 12 S(O)C1-C6 alkyl, C3-C7 cycloalkyl and 3 to 7-membered heterocyclic alkyl,

[0331] The C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C6-C 10 The aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl, and 3- to 7-membered heterocycloalkyl groups are optionally substituted by one or more substituents, each independently selected from the following: hydroxyl, halogen, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, R 15 NR 8 R 9 、=NR 10 、COOC1-C6 alkyl、CONR 8 R 9 3 to 7-membered heterocyclic alkyl groups, C6-C 10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), and OCO (3- to 7-membered heterocyclic alkyl);

[0332] wherein R 1 or R 2 C3-C7 cycloalkyl or said R 1 or R2 Each C1-C6 alkyl substituent and each C1-C6 alkoxy substituent of the 3- to 7-membered heterocycloalkyl group is further optionally and independently substituted with one to three hydroxyl groups, -O(C0-C3 alkylene)C6-C 10 Aryl, halogenated, NR 8 R 9 , or oxo-substituted;

[0333] wherein the 3 to 7 membered heterocycloalkyl, C6-C 10 Aryl, and 5- to 10-membered heteroaryl are each optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;

[0334] or a pair of R located on adjacent atoms 1 and R 2 Together with the atoms that connect them, they independently form a monocyclic or bicyclic C4-C ring. 12 A carbon ring or a single or double ring of 5 to 12-membered heterocyclic rings, wherein:

[0335] a) When each of the adjacent atoms is a carbon atom, the heterocycle contains from 1 to 3 heteroatoms and / or heteroatom groups independently selected from the group consisting of O, NH, NR 13 , S, S(O), and S(O)2; and

[0336] b) When one or two of the adjacent atoms are nitrogen atoms, the heterocyclic ring contains from 0 to 2 heteroatoms and / or heteroatom groups independently selected from the following: O, NH, NR 13 S, S(O), and S(O)2 (except for the aforementioned connection to R) 1 and / or R 2 one or more nitrogen atoms), and

[0337] The carbocyclic or heterocyclic ring is optionally and independently substituted by one or more substituents, each independently selected from the following: hydroxyl, halogenated, oxo-substituted, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, OC3-C 10 Cycloalkyl, NR 8 R 9 、=NR 10 、CN、COOC1-C6 alkyl、OS(O2)C6-C 10 Aryl, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, 3- to 10-membered heterocycloalkyl, and CONR 8 R 9 ,

[0338] wherein the C1-C6 alkyl, C1-C6 alkoxy, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, and 3 to 10 membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from the group consisting of hydroxy, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 alkyl, C4-C6 alkyl, C6-C6 alkyl, C7-C6 alkyl, C8-C6 alkyl, C9-C6 alkyl, C10-C6 alkyl, C11-C6 alkyl, C12-C6 alkyl, C13-C6 alkyl, C14-C6 alkyl, C15-C6 alkyl, C16-C6 alkyl, C17-C6 alkyl, C18-C6 alkyl, C19-C6 alkyl, C21-C6 alkyl, C22-C6 alkyl, C23-C6 alkyl, C24-C6 alkyl, C25-C6 alkyl, C2 10 Cycloalkyl, C1-C6 alkoxy, oxo, NR 8 R 9 、=NR 10 COOC1-C6 alkyl, C6-C 10 Aryl and CONR 8 R 9 ;

[0339] R 1’ and R 2’ Each is independently selected from C2-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, Cl, Br, I, CN, NO2, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10 Aryl, 5- to 10-membered heteroaryl, NR 8 R 9 、C(O)R 13 、CONR 8 R 9 SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, S(O2)NR 11 R 12 S(O)C1-C6 alkyl, C3-C7 cycloalkyl and 3 to 7-membered heterocyclic alkyl,

[0340] The C2-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C6-C 10 The aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl, and 3- to 7-membered heterocycloalkyl groups are optionally substituted by one or more substituents, each independently selected from the following: hydroxyl, halogen, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, R 15 NR 8 R 9 、=NR 10 、COOC1-C6 alkyl、CONR 8 R 93 to 7-membered heterocyclic alkyl groups, C6-C 10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), and OCO (3- to 7-membered heterocyclic alkyl);

[0341] wherein R 1’ or R 2’ C3-C7 cycloalkyl or said R 1’ or R 2’ Each C1-C6 alkyl substituent and each C1-C6 alkoxy substituent of the 3- to 7-membered heterocycloalkyl group is further optionally and independently substituted with one to three hydroxyl groups, -O(C0-C3 alkylene)C6-C 10 Aryl, halogenated, NR 8 R 9 , or oxo-substituted;

[0342] wherein the 3 to 7 membered heterocycloalkyl, C6-C 10 Aryl, and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;

[0343] or a pair of R located on adjacent atoms 1’ and R 2’ Together with the atoms that connect them, they independently form a monocyclic or bicyclic C4-C ring. 12 A carbon ring or a monocyclic or bicyclic 5- to 12-membered heterocycle, said heterocycle comprising 1 to 3 heteroatoms and / or heteroatom groups independently selected from the following: O, NH, NR. 13 S, S(O), and S(O)2, and

[0344] The carbocyclic or heterocyclic ring is optionally and independently substituted by one or more substituents independently selected from the following: hydroxyl, halogenated, oxo-substituted, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, OC3-C 10 Cycloalkyl, NR 8 R 9 、=NR 10 、CN、COOC1-C6 alkyl、OS(O2)C6-C 10 Aryl, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, 3- to 10-membered heterocycloalkyl, and CONR 8 R 9 ,

[0345] wherein the C1-C6 alkyl, C1-C6 alkoxy, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, and 3 to 10 membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from the group consisting of hydroxy, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 alkyl, C4-C6 alkyl, C6-C6 alkyl, C7-C6 alkyl, C8-C6 alkyl, C9-C6 alkyl, C10-C6 alkyl, C11-C6 alkyl, C12-C6 alkyl, C13-C6 alkyl, C14-C6 alkyl, C15-C6 alkyl, C16-C6 alkyl, C17-C6 alkyl, C18-C6 alkyl, C19-C6 alkyl, C21-C6 alkyl, C22-C6 alkyl, C23-C6 alkyl, C24-C6 alkyl, C25-C6 alkyl, C2 10 Cycloalkyl, C1-C6 alkoxy, oxo, NR 8 R 9 、=NR 10 COOC1-C6 alkyl, C6-C 10 Aryl and CONR 8 R 9 ;

[0346] R 2” It is F or CH3; or

[0347] When the compound having formula AA is a compound having formula AA-4, a pair of R atoms located on adjacent atoms 1 and R 2” Together with the atoms that connect them, they independently form a monocyclic or bicyclic C4-C ring. 12 A carbon ring or a monocyclic or bicyclic 5- to 12-membered heterocycle, said heterocycle comprising 1 to 3 heteroatoms and / or heteroatom groups independently selected from the following: O, NH, NR. 13 S, S(O), and S(O)2, and

[0348] The carbocyclic or heterocyclic ring is optionally and independently substituted by one or more substituents independently selected from the following: hydroxyl, halogenated, oxo-substituted, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, OC3-C 10 Cycloalkyl, NR 8 R 9 、=NR 10 、CN、COOC1-C6 alkyl、OS(O2)C6-C 10 Aryl, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, 3- to 10-membered heterocycloalkyl, and CONR 8 R 9 ,

[0349] wherein the C1-C6 alkyl, C1-C6 alkoxy, S(O2)C6-C 10 Aryl, C6-C 10Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, and 3 to 10 membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from the group consisting of hydroxy, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 alkyl, C4-C6 alkyl, C6-C6 alkyl, C7-C6 alkyl, C8-C6 alkyl, C9-C6 alkyl, C10-C6 alkyl, C11-C6 alkyl, C12-C6 alkyl, C13-C6 alkyl, C14-C6 alkyl, C15-C6 alkyl, C16-C6 alkyl, C17-C6 alkyl, C18-C6 alkyl, C19-C6 alkyl, C21-C6 alkyl, C22-C6 alkyl, C23-C6 alkyl, C24-C6 alkyl, C25-C6 alkyl, C2 10 Cycloalkyl, C1-C6 alkoxy, oxo, NR 8 R 9 、=NR 10 COOC1-C6 alkyl, C6-C 10 Aryl and CONR 8 R 9 ;

[0350] R 6 and R 7 Each is independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halogen, CN, NO2, COC1-C6 alkyl, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10 Aryl, 5- to 10-membered heteroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, CONR 8 R 9 SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, C3-C 10 Cycloalkyl and 3- to 10-membered heterocycloalkyl, and C2-C6 alkenyl,

[0351] Where R 6 and R 7 Each may optionally be substituted by one or more substituents independently selected from the following: hydroxyl, halogen, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR. 8 R 9 、=NR 10 、COOC1-C6 alkyl、CONR 8 R 9 3 to 7-membered heterocyclic alkyl groups, C6-C 10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10 aryloxy, and S(O2)C1-C6 alkyl; and wherein substituted R 6 or R 7The C1-C6 alkyl or C1-C6 alkoxy group is optionally surrounded by one or more hydroxyl groups, C6-C 10 Aryl or NR 8 R 9 Replace, or where R 6 or R 7 optionally fused to a five- to seven-membered carbocyclic or heterocyclic ring containing one or two heteroatoms independently selected from oxygen, sulfur, and nitrogen;

[0352] wherein the 3 to 7 membered heterocycloalkyl, C6-C 10 Aryl, and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;

[0353] or a pair of R located on adjacent atoms 6 and R 7 Together with the atoms connecting them, they independently form at least one C4-C8 carbon ring or at least one 5- to 8-membered heterocycle, said heterocycle containing one or two heteroatoms and / or heteroatom groups independently selected from: O, NH, NR. 13 S, S(O), and S(O)2, wherein the carbocyclic or heterocyclic ring is optionally and independently substituted by one or more substituents independently selected from the following: hydroxyl, hydroxymethyl, halogenated, oxo-substituted, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, NR 8 R 9 CH2NR 8 R 9 、=NR 10 、COOH、COOC1-C6 alkyl、C6-C 10 Aryl and CONR 8 R 9 ;

[0354] R 6’ and R 7’ Each independently selected from the group consisting of unbranched C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, NO2, COC1-C6 alkyl, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10 Aryl, 5- to 10-membered heteroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, CONR 8 R 9 SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, C3-C 10Cycloalkyl and 3- to 10-membered heterocycloalkyl, and C2-C6 alkenyl,

[0355] Where R 6’ and R 7’ Each is optionally substituted with one or more substituents independently selected from the group consisting of hydroxy, halo, CN, oxo, C1-C6 alkoxy, NR 8 R 9 、=NR 10 、COOC1-C6 alkyl、CONR 8 R 9 3 to 7-membered heterocyclic alkyl groups, C6-C 10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10 aryloxy, and S(O2)C1-C6 alkyl; and wherein substituted R 6’ or R 7’ The C1-C6 alkoxy group is optionally replaced by one or more hydroxyl groups, C6-C 10 Aryl or NR 8 R 9 Replace, or where R 6’ or R 7’ optionally fused to a five- to seven-membered carbocyclic or heterocyclic ring containing one or two heteroatoms independently selected from oxygen, sulfur, and nitrogen;

[0356] wherein the 3 to 7 membered heterocycloalkyl, C6-C 10 Aryl, and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;

[0357] or a pair of R located on adjacent atoms 6’ and R 7’ Together with the atoms connecting them, they independently form at least one C4-C8 carbon ring or at least one 5- to 8-membered heterocycle, said heterocycle containing one or two heteroatoms and / or heteroatom groups independently selected from: O, NH, NR. 13 S, S(O), and S(O)2, wherein the carbocyclic or heterocyclic ring is optionally and independently substituted by one or more substituents independently selected from the following: hydroxyl, hydroxymethyl, halogenated, oxo-substituted, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, NR 8 R 9 CH2NR 8 R 9 、=NR 10 、COOH、COOC1-C6 alkyl、C6-C10 Aryl and CONR 8 R 9 ;

[0358] R 6” Selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halogen, NO2, COC1-C6 alkyl, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10 Aryl, 5- to 10-membered heteroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, CONR 8 R 9 SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, C3-C 10 Cycloalkyl, 3- to 10-membered heterocyclic alkyl, and C2-C6 alkenyl,

[0359] Where R 6” Optionally substituted by one or more substituents independently selected from the following: hydroxyl, halogen, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR 8 R 9 、=NR 10 、COOC1-C6 alkyl、CONR 8 R 9 3 to 7-membered heterocyclic alkyl groups, C6-C 10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10 Aryloxy, and S(O2)C1-C6 alkyl; and

[0360] where R is substituted 6” The C1-C6 alkyl or C1-C6 alkoxy group is optionally surrounded by one or more hydroxyl groups, C6-C 10 Aryl or NR 8 R 9 Replace, or where R 6” optionally fused to a five- to seven-membered carbocyclic or heterocyclic ring containing one or two heteroatoms independently selected from oxygen, sulfur, and nitrogen;

[0361] wherein the 3 to 7 membered heterocycloalkyl, C6-C 10 Aryl, and 5- to 10-membered heteroaryl are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;

[0362] or a pair of R located on adjacent atoms 6” and R 7 Together with the atoms connecting them, they independently form at least one C4-C8 carbon ring or at least one 5- to 8-membered heterocycle, said heterocycle containing one or two heteroatoms and / or heteroatom groups independently selected from: O, NH, NR. 13 S, S(O), and S(O)2, wherein the carbocyclic or heterocyclic ring is optionally and independently substituted by one or more substituents independently selected from the following: hydroxyl, hydroxymethyl, halogenated, oxo-substituted, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, NR 8 R 9 CH2NR 8 R 9 、=NR 10 、COOH、COOC1-C6 alkyl、C6-C 10 Aryl and CONR 8 R 9 ;

[0363] R 10 It is a C1-C6 alkyl group;

[0364] R 8 and R 9 Each of these elements is independently selected from hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C3-C7 cycloalkyl, C1-C6 haloalkyl, (C=NR) each time it appears. 13 )NR 11 R 12 、S(O2)C1-C6 alkyl、S(O2)NR 11 R 12 COR 13 CO2R 13 and CONR 11 R 12 wherein the C1-C6 alkyl group is optionally substituted by one or more hydroxyl groups, halo groups, C1-C6 alkoxy groups, C6-C 10 aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl, 3- to 7-membered heterocycloalkyl, or NR 11 R 12 ;

[0365] or R 8 and R 9 Together with the nitrogen atoms to which they are attached, they form 3- to 10-membered monocyclic or bicyclic rings optionally containing one or more heteroatoms other than the nitrogen atoms to which they are attached, wherein said rings are optionally substituted by one or more substituents independently selected from: halogenated, C-shaped, etc. 1- C6 alkyl, C1- C6 haloalkyl, C1-C6 alkoxy, oxo, N(C1-C6 alkyl)2, NH2, NH(C1-C6 alkyl), and hydroxy;

[0366] R 13 is C1-C6 alkyl, C1-C6 haloalkyl, or -(Z 1 -Z 2 ) a1 -Z 3 ;

[0367] R 11 and R 12 Each of these elements is independently selected from hydrogen, C1-C6 alkyl groups, and -(Z) each time it appears. 1 -Z 2 ) a1 -Z 3 ;

[0368] a1 is an integer selected from 0-10 (e.g., 0-5);

[0369] Each Z 1 Independently, it is a C1-C6 alkylene group optionally substituted with one or more substituents independently selected from oxo, halogenated, and hydroxyl groups;

[0370] Each Z 2 is independently a bond, NH, N(C1-C6 alkyl), -O-, -S-, or a 5-10 membered heteroarylene group;

[0371] Z 3 Independently C 6- C 10 Aryl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C 10 cycloalkyl, 5- to 10-membered heteroaryl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from the group consisting of halo, C1-C6 alkyl, C 1-6 Haloalkyl, C1-C6 alkoxy, oxo, N(C1-C6 alkyl)2, NH2, NH(C1-C6 alkyl), and hydroxy;

[0372] R 3 Selected from hydrogen, cyano, hydroxyl, CO2C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkyl, and The C1-C2 alkylene groups are optionally substituted with oxo groups;

[0373] R 14 is hydrogen, C1-C6 alkyl, 5- to 10-membered monocyclic or bicyclic heteroaryl, or C6-C 10Monocyclic or bicyclic aryl, wherein each C1-C6 alkyl, aryl or heteroaryl is optionally independently replaced by 1 or 2 R 6 replace;

[0374] R 15 Yes - (Z 4 -Z 5 ) a2 -Z 6 ;

[0375] a2 is an integer selected from 1 to 10 (e.g., 1 to 5 (e.g., 2 to 5));

[0376] Each Z 4 Independently selected from -O-, -S-, -NH-, and -N(C1-C3 alkyl)-;

[0377] The prerequisite is a direct connection to R. 1 or R 2 Z 4 The radical is -O- or -S-;

[0378] Each Z 5 is independently C1-C6 alkylene optionally substituted by one or more substituents independently selected from oxo, halo, and hydroxy; and

[0379] Z 6 is OH, OC1-C6 alkyl, NH2, NH(C1-C6 alkyl), N(C1-C6 alkyl)2, NHC(O)(C1-C6 alkyl), NHC(O)(C1-C6 alkoxy), or an optionally substituted group selected from the group consisting of:

[0380] C 6- C 10 Aryl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C 10 cycloalkyl, 5- to 10-membered heteroaryl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from the group consisting of halo, C1-C6 alkyl, C 1-6 Haloalkyl, C1-C6 alkoxy, oxo, N(C1-C6 alkyl)2, NH2, NH(C1-C6 alkyl), and hydroxy;

[0381] or a pharmaceutically acceptable salt thereof.

[0382] In another aspect, this paper describes compounds having the formula AA.

[0383]

[0384] wherein the compound of formula AA is selected from

[0385]

[0386]

[0387] in

[0388] m = 0, 1, or 2;

[0389] n = 0, 1, or 2;

[0390] m' = 0, 1, or 2;

[0391] n' = 0, 1, or 2;

[0392] The sum of m' and n' is 0, 1, or 3;

[0393] m" = 0, 1, or 2;

[0394] n" = 0, 1 or 2;

[0395] The sum of m” and n” is 2;

[0396] m”'=1;

[0397] n”'=1;

[0398] o = 1 or 2;

[0399] p = 0, 1, 2 or 3;

[0400] The sum of o and p ranges from 1 to 4;

[0401] in

[0402] A' is selected from:

[0403] 6 to 10 yuan of mixed aromatic compounds,

[0404] C6-C 10 Aryl,

[0405] Five-membered heteroaryl groups containing two or more heteroatoms

[0406] Includes 1 selected from N, NH, and NR 1 5-membered heteroaryl groups of heteroatoms or heteroatom groups, and

[0407] A 5-membered heteroaryl group comprising one heteroatom selected from O and S, wherein the heteroatom is not bonded to S(O)(NHR) 3 )=position bonding of N part;

[0408] A” is a 5-membered heteroaryl group containing one heteroatom selected from O and S, wherein the heteroatom is bonded to the heteroaryl group to S(O)(NHR). 3 )=position bonding of N part;

[0409] B is a 6-membered heteroaromatic ring containing 1-3 N atoms, or its N oxide;

[0410] B' is 2-pyridinyl, 3-pyridinyl, or its N-oxide;

[0411] B” is 4-pyridinyl or its N-oxide;

[0412] in

[0413] At least one R 6 It is located in the ortho position of the bond that links the B ring to the NHC(O) group of formula AA-2, formula AA-3, and formula AA-4;

[0414] At least one R 6’ It is located in the ortho position of the bond that links the B ring to the NHC(O) group of formula AA-5;

[0415] At least one R 6” It is located in the ortho position of the bond that links the B ring to the NHC(O) group of formula AA-1;

[0416] R 1 and R 2 Each is independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halogen, CN, NO2, COC1-C6 alkyl, CO-C6-C 10 Aryl, CO (5- to 10-membered heteroaryl), CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10 Aryl, 5- to 10-membered heteroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, NHCOC1-C6 alkyl, NHCOC6-C 10 Aryl, NHCO (5- to 10-membered heteroaryl), NHCO (3- to 7-membered heterocyclic alkyl), NHCOC2-C6 ynyl, NHCOOC1-C6 alkyl, NH-(C=NR) 13 )NR 11 R 12 、CONR 8 R 9 SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, S(O2)NR 11 R 12 S(O)C1-C6 alkyl, C3-C7 cycloalkyl and 3 to 7-membered heterocyclic alkyl,

[0417] The C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, and 3- to 7-membered heterocyclic alkyl groups are optionally substituted by one or more substituents, each independently selected from the following: hydroxyl, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR. 8 R 9 、=NR 10 、COOC1-C6 alkyl、CONR 8 R 9 3 to 7-membered heterocyclic alkyl groups, C6-C 10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocyclic alkyl), NHCOC1-C6 alkyl, NHCOC6-C 10 Aryl, NHCO (5- to 10-membered heteroaryl), NHCO (3- to 7-membered heterocyclic alkyl), and NHCOC2-C6 alkynyl;

[0418] wherein R 1 or R 2 C3-C7 cycloalkyl or said R 1 or R 2 Each C1-C6 alkyl substituent and each C1-C6 alkoxy substituent of the 3- to 7-membered heterocyclic alkyl group may further optionally be independently replaced by one to three hydroxyl, halogenated, or NR-substituted groups. 8 R 9 , or oxo-substituted;

[0419] wherein the 3 to 7 membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, NHCOC6-C 10 Aryl, NHCO(5- to 10-membered heteroaryl), and NHCO(3- to 7-membered heterocycloalkyl) are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;

[0420] or a pair of R located on adjacent atoms 1 and R 2 Together with the atoms that connect them, they independently form a monocyclic or bicyclic C4-C ring. 12 A carbon ring or a monocyclic or bicyclic 5- to 12-membered heterocycle, wherein a) when each of the adjacent atoms is a carbon atom, the heterocycle comprises 1 to 3 heteroatoms and / or heteroatom groups independently selected from: O, NH, NR 13 S, S(O), and S(O)2; and b) when one or both of the adjacent atoms are nitrogen atoms, the heterocycle comprises 0-2 heteroatoms and / or heteroatom groups independently selected from: O, NH, NR13 S, S(O), and S(O)2 (except for the aforementioned connection to R) 1 and / or R 2 (excluding one or more nitrogen atoms), and wherein the carbocyclic or heterocyclic ring is optionally independently substituted by one or more substituents independently selected from the following: hydroxyl, halogen, oxo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, OC3-C 10 Cycloalkyl, NR 8 R 9 、=NR 10 、CN、COOC1-C6 alkyl、OS(O2)C6-C 10 Aryl, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, 3- to 10-membered heterocycloalkyl, and CONR 8 R 9 The C1-C6 alkyl, C1-C6 alkoxy, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, and 3 to 10 membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from the group consisting of hydroxy, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 alkyl, C4-C6 alkyl, C6-C6 alkyl, C7-C6 alkyl, C8-C6 alkyl, C9-C6 alkyl, C10-C6 alkyl, C11-C6 alkyl, C12-C6 alkyl, C13-C6 alkyl, C14-C6 alkyl, C15-C6 alkyl, C16-C6 alkyl, C17-C6 alkyl, C18-C6 alkyl, C19-C6 alkyl, C21-C6 alkyl, C22-C6 alkyl, C23-C6 alkyl, C24-C6 alkyl, C25-C6 alkyl, C2 10 Cycloalkyl, C1-C6 alkoxy, oxo, NR 8 R 9 、=NR 10 COOC1-C6 alkyl, C6-C 10 Aryl and CONR 8 R 9 ;

[0421] R 1’ and R 2’ Each is independently selected from C2-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, Cl, Br, I, CN, NO2, COC1-C6 alkyl, CO-C6-C 10 Aryl, CO (5- to 10-membered heteroaryl), CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10Aryl, 5- to 10-membered heteroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, NHCOC1-C6 alkyl, NHCOC6-C 10 Aryl, NHCO (5- to 10-membered heteroaryl), NHCO (3- to 7-membered heterocyclic alkyl), NHCOC2-C6 ynyl, NHCOOC1-C6 alkyl, NH-(C=NR) 13 )NR 11 R 12 、CONR 8 R 9 SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, S(O2)NR 11 R 12 S(O)C1-C6 alkyl, C3-C7 cycloalkyl and 3 to 7-membered heterocyclic alkyl,

[0422] wherein the C2-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl and 3 to 7 membered heterocycloalkyl are optionally substituted by one or more substituents each independently selected from the group consisting of hydroxy, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR 8 R 9 、=NR 10 、COOC1-C6 alkyl、CONR 8 R 9 3 to 7-membered heterocyclic alkyl groups, C6-C 10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocyclic alkyl), NHCOC1-C6 alkyl, NHCOC6-C 10 Aryl, NHCO (5- to 10-membered heteroaryl), NHCO (3- to 7-membered heterocyclic alkyl), and NHCOC2-C6 alkynyl;

[0423] wherein R 1’ or R 2’ C3-C7 cycloalkyl or said R 1’ or R 2’ Each C1-C6 alkyl substituent and each C1-C6 alkoxy substituent of the 3- to 7-membered heterocyclic alkyl group may further optionally be independently replaced by one to three hydroxyl, halogenated, or NR-substituted groups. 8 R 9 , or oxo-substituted;

[0424] wherein the 3 to 7 membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, NHCOC6-C 10Aryl, NHCO(5- to 10-membered heteroaryl), and NHCO(3- to 7-membered heterocycloalkyl) are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;

[0425] or a pair of R located on adjacent atoms 1’ and R 2’ Together with the atoms that connect them, they independently form a monocyclic or bicyclic C4-C ring. 12 A carbon ring or a monocyclic or bicyclic 5- to 12-membered heterocycle, said heterocycle comprising 1 to 3 heteroatoms and / or heteroatom groups independently selected from the following: O, NH, NR. 13 S, S(O), and S(O)2, wherein the carbocyclic or heterocyclic ring is optionally and independently substituted by one or more substituents independently selected from the following: hydroxyl, halogenated, oxo-substituted, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, OC3-C 10 Cycloalkyl, NR 8 R 9 、=NR 10 、CN、COOC1-C6 alkyl、OS(O2)C6-C 10 Aryl, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, 3- to 10-membered heterocycloalkyl, and CONR 8 R 9 The C1-C6 alkyl, C1-C6 alkoxy, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, and 3 to 10 membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from the group consisting of hydroxy, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 alkyl, C4-C6 alkyl, C6-C6 alkyl, C7-C6 alkyl, C8-C6 alkyl, C9-C6 alkyl, C10-C6 alkyl, C11-C6 alkyl, C12-C6 alkyl, C13-C6 alkyl, C14-C6 alkyl, C15-C6 alkyl, C16-C6 alkyl, C17-C6 alkyl, C18-C6 alkyl, C19-C6 alkyl, C21-C6 alkyl, C22-C6 alkyl, C23-C6 alkyl, C24-C6 alkyl, C25-C6 alkyl, C2 10 Cycloalkyl, C1-C6 alkoxy, oxo, NR 8 R 9 、=NR 10 COOC1-C6 alkyl, C6-C 10 Aryl and CONR 8 R 9 ;

[0426] R 2” It is F or CH3;

[0427] Alternatively, when the compound having formula AA is a compound having formula AA-4, a pair of R atoms located on adjacent atoms 1and R 2” Together with the atoms that connect them, they independently form a monocyclic or bicyclic C4-C ring. 12 A carbon ring or a monocyclic or bicyclic 5- to 12-membered heterocycle, said heterocycle comprising 1 to 3 heteroatoms and / or heteroatom groups independently selected from the following: O, NH, NR. 13 S, S(O), and S(O)2, wherein the carbocyclic or heterocyclic ring is optionally and independently substituted by one or more substituents independently selected from the following: hydroxyl, halogenated, oxo-substituted, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, OC3-C 10 Cycloalkyl, NR 8 R 9 、=NR 10 、CN、COOC1-C6 alkyl、OS(O2)C6-C 10 Aryl, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, 3- to 10-membered heterocycloalkyl, and CONR 8 R 9 The C1-C6 alkyl, C1-C6 alkoxy, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, and 3 to 10 membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from the group consisting of hydroxy, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 alkyl, C4-C6 alkyl, C6-C6 alkyl, C7-C6 alkyl, C8-C6 alkyl, C9-C6 alkyl, C10-C6 alkyl, C11-C6 alkyl, C12-C6 alkyl, C13-C6 alkyl, C14-C6 alkyl, C15-C6 alkyl, C16-C6 alkyl, C17-C6 alkyl, C18-C6 alkyl, C19-C6 alkyl, C21-C6 alkyl, C22-C6 alkyl, C23-C6 alkyl, C24-C6 alkyl, C25-C6 alkyl, C2 10 Cycloalkyl, C1-C6 alkoxy, oxo, NR 8 R 9 、=NR 10 COOC1-C6 alkyl, C6-C 10 Aryl and CONR 8 R 9 ;

[0428] R 6 and R 7 Each is independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halogen, CN, NO2, COC1-C6 alkyl, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10Aryl, 5- to 10-membered heteroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, CONR 8 R 9 SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, C3-C 10 Cycloalkyl and 3- to 10-membered heterocycloalkyl, and C2-C6 alkenyl,

[0429] Where R 6 and R 7 Each may optionally be substituted by one or more substituents independently selected from the following: hydroxyl, halogen, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR. 8 R 9 、=NR 10 、COOC1-C6 alkyl、CONR 8 R 9 3 to 7-membered heterocyclic alkyl groups, C6-C 10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocyclic alkyl), NHCOC1-C6 alkyl, NHCOC6-C 10 Aryl, NHCO (5- to 10-membered heteroaryl), NHCO (3- to 7-membered heterocycloalkyl), NHCOC2-C6 ynyl, C6-C 10 aryloxy, and S(O2)C1-C6 alkyl; and wherein substituted R 6 or R 7 The C1-C6 alkyl or C1-C6 alkoxy group is optionally surrounded by one or more hydroxyl groups, C6-C 10 Aryl or NR 8 R 9 Replace, or where R 6 or R 7 optionally fused to a five- to seven-membered carbocyclic or heterocyclic ring containing one or two heteroatoms independently selected from oxygen, sulfur, and nitrogen;

[0430] wherein the 3 to 7 membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, NHCOC6-C 10 Aryl, NHCO(5- to 10-membered heteroaryl), and NHCO(3- to 7-membered heterocycloalkyl) are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;

[0431] or a pair of R located on adjacent atoms 6 and R 7Together with the atoms connecting them, they independently form at least one C4-C8 carbon ring or at least one 5- to 8-membered heterocycle, said heterocycle containing one or two heteroatoms and / or heteroatom groups independently selected from: O, NH, NR. 13 S, S(O), and S(O)2, wherein the carbocyclic or heterocyclic ring is optionally and independently substituted by one or more substituents independently selected from the following: hydroxyl, hydroxymethyl, halogenated, oxo-substituted, C1-C6 alkyl, C1-C6 alkoxy, NR 8 R 9 CH2NR 8 R 9 、=NR 10 COOC1-C6 alkyl, C6-C 10 Aryl and CONR 8 R 9 ;

[0432] R 6’ and R 7’ Each independently selected from the group consisting of unbranched C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, NO2, COC1-C6 alkyl, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10 Aryl, 5- to 10-membered heteroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, CONR 8 R 9 SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, C3-C 10 Cycloalkyl and 3- to 10-membered heterocycloalkyl, and C2-C6 alkenyl,

[0433] Where R 6’ and R 7’ Each is optionally substituted with one or more substituents independently selected from the group consisting of hydroxy, halo, CN, oxo, C1-C6 alkoxy, NR 8 R 9 、=NR 10 、COOC1-C6 alkyl、CONR 8 R 9 3 to 7-membered heterocyclic alkyl groups, C6-C 10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocyclic alkyl), NHCOC1-C6 alkyl, NHCOC6-C 10Aryl, NHCO (5- to 10-membered heteroaryl), NHCO (3- to 7-membered heterocycloalkyl), NHCOC2-C6 ynyl, C6-C 10 aryloxy, and S(O2)C1-C6 alkyl; and wherein substituted R 6’ or R 7’ The C1-C6 alkoxy group is optionally replaced by one or more hydroxyl groups, C6-C 10 Aryl or NR 8 R 9 Replace, or where R 6’ or R 7’ optionally fused to a five- to seven-membered carbocyclic or heterocyclic ring containing one or two heteroatoms independently selected from oxygen, sulfur, and nitrogen;

[0434] wherein the 3 to 7 membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, NHCOC6-C 10 Aryl, NHCO(5- to 10-membered heteroaryl), and NHCO(3- to 7-membered heterocycloalkyl) are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;

[0435] or a pair of R located on adjacent atoms 6’ and R 7’ Together with the atoms connecting them, they independently form at least one C4-C8 carbon ring or at least one 5- to 8-membered heterocycle, said heterocycle containing one or two heteroatoms and / or heteroatom groups independently selected from: O, NH, NR. 13 S, S(O), and S(O)2, wherein the carbocyclic or heterocyclic ring is optionally and independently substituted by one or more substituents independently selected from the following: hydroxyl, hydroxymethyl, halogenated, oxo-substituted, C1-C6 alkyl, C1-C6 alkoxy, NR 8 R 9 CH2NR 8 R 9 、=NR 10 COOC1-C6 alkyl, C6-C 10 Aryl and CONR 8 R 9 ;

[0436] R 6” Selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halogen, NO2, COC1-C6 alkyl, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C10 Aryl, 5- to 10-membered heteroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, CONR 8 R 9 SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, C3-C 10 Cycloalkyl, 3- to 10-membered heterocyclic alkyl, and C2-C6 alkenyl,

[0437] Where R 6” Optionally substituted by one or more substituents independently selected from the following: hydroxyl, halogen, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR 8 R 9 、=NR 10 、COOC1-C6 alkyl、CONR 8 R 9 3 to 7-membered heterocyclic alkyl groups, C6-C 10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocyclic alkyl), NHCOC1-C6 alkyl, NHCOC6-C 10 Aryl, NHCO (5- to 10-membered heteroaryl), NHCO (3- to 7-membered heterocycloalkyl), NHCOC2-C6 ynyl, C6-C 10 aryloxy, and S(O2)C1-C6 alkyl; and wherein substituted R 6” The C1-C6 alkyl or C1-C6 alkoxy group is optionally surrounded by one or more hydroxyl groups, C6-C 10 Aryl or NR 8 R 9 Replace, or where R 6” optionally fused to a five- to seven-membered carbocyclic or heterocyclic ring containing one or two heteroatoms independently selected from oxygen, sulfur, and nitrogen;

[0438] wherein the 3 to 7 membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, NHCOC6-C 10 Aryl, NHCO(5- to 10-membered heteroaryl), and NHCO(3- to 7-membered heterocycloalkyl) are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;

[0439] or a pair of R located on adjacent atoms 6” and R 7Together with the atoms connecting them, they independently form at least one C4-C8 carbon ring or at least one 5- to 8-membered heterocycle, said heterocycle containing one or two heteroatoms and / or heteroatom groups independently selected from: O, NH, NR. 13 S, S(O), and S(O)2, wherein the carbocyclic or heterocyclic ring is optionally and independently substituted by one or more substituents independently selected from the following: hydroxyl, hydroxymethyl, halogenated, oxo-substituted, C1-C6 alkyl, C1-C6 alkoxy, NR 8 R 9 CH2NR 8 R 9 、=NR 10 COOC1-C6 alkyl, C6-C 10 Aryl and CONR 8 R 9 ;

[0440] R 10 It is a C1-C6 alkyl group;

[0441] R 8 and R 9 Each of these terms is independently selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, (C=NR) each time it appears. 13 )NR 11 R 12 、S(O2)C1-C6 alkyl、S(O2)NR 11 R 12 COR 13 CO2R 13 and CONR 11 R 12 wherein the C1-C6 alkyl group is optionally substituted by one or more hydroxyl groups, halo groups, C1-C6 alkoxy groups, C6-C 10 aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl, or 3- to 7-membered heterocycloalkyl; or R 8 and R 9 taken together with the nitrogen to which they are attached to form a 3- to 7-membered ring optionally containing one or more heteroatoms in addition to the nitrogen to which they are attached;

[0442] R 13 It is a C1-C6 alkyl, C1-C6 haloalkyl, C6-C 10 aryl, or 5- to 10-membered heteroaryl;

[0443] R 11 and R 12 Each of these terms is independently selected from hydrogen and C1-C6 alkyl groups each time it appears;

[0444] and

[0445] R 3 Selected from hydrogen, cyano, hydroxyl, CO2C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkyl, and The C1-C2 alkylene groups are optionally substituted with oxo groups;

[0446] R 14 is hydrogen, C1-C6 alkyl, 5- to 10-membered monocyclic or bicyclic heteroaryl, or C6-C 10 Monocyclic or bicyclic aryl, wherein each C1-C6 alkyl, aryl or heteroaryl is optionally independently replaced by 1 or 2 R 6 replace;

[0447] or a pharmaceutically acceptable salt thereof.

[0448] Formula AA

[0449] In some embodiments, Formula AA is Formula AA-1

[0450]

[0451] In some embodiments, Formula AA is Formula AA-2

[0452]

[0453] In some embodiments, Formula AA is Formula AA-3

[0454]

[0455] In some embodiments, Formula AA is Formula AA-4

[0456]

[0457] In some embodiments, Formula AA is Formula AA-5

[0458]

[0459] In some embodiments, the variables shown in the formulas herein are as follows:

[0460] Variables m, m', m", n, n', and n"

[0461] In some embodiments, m=0, 1, or 2.

[0462] In some embodiments, m=0 or 1.

[0463] In some embodiments, m=1 or 2.

[0464] In some embodiments, m=0 or 2.

[0465] In some embodiments, m = 0.

[0466] In some embodiments, m = 1.

[0467] In some embodiments, m = 2.

[0468] In some embodiments, n = 0, 1, or 2.

[0469] In some embodiments, n = 0 or 1.

[0470] In some embodiments, n = 1 or 2.

[0471] In some embodiments, n = 0 or 2.

[0472] In some embodiments, n = 0.

[0473] In some embodiments, n = 1.

[0474] In some embodiments, n = 2.

[0475] In some embodiments, m = 0 and n = 0.

[0476] In some embodiments, m = 1 and n = 0.

[0477] In some embodiments, m = 1 and n = 1.

[0478] In some embodiments of compounds having formula AA-1, m = 1 and n = 0.

[0479] In some embodiments of compounds having formula AA-1, m=1, and n=1.

[0480] In some embodiments, m' = 0, 1, or 2.

[0481] In some embodiments, m' = 0 or 1.

[0482] In some embodiments, m' = 1 or 2.

[0483] In some embodiments, m' = 0 or 2.

[0484] In some embodiments, m' = 0.

[0485] In some embodiments, m' = 1.

[0486] In some embodiments, m' = 2.

[0487] In some embodiments, n' = 0, 1, or 2.

[0488] In some embodiments, n' = 0 or 1.

[0489] In some embodiments, n' = 1 or 2.

[0490] In some embodiments, n' = 0 or 2.

[0491] In some embodiments, n' = 0.

[0492] In some embodiments, n' = 1.

[0493] In some embodiments, n' = 2.

[0494] In some embodiments, m' = 0 and n' = 0.

[0495] In some embodiments, m' = 1 and n' = 0.

[0496] In some embodiments, m' = 2 and n' = 1.

[0497] In some embodiments, m' = 1 and n' = 2.

[0498] The sum of m' and n' is 0, 1, or 3.

[0499] In some embodiments of the compound having formula AA-2, m' = 1 and n' = 0.

[0500] In some embodiments, m” = 0, 1 or 2.

[0501] In some embodiments, m” = 0 or 1.

[0502] In some embodiments, m” = 1 or 2.

[0503] In some embodiments, m” = 0 or 2.

[0504] In some embodiments, m” = 0.

[0505] In some embodiments, m” = 1.

[0506] In some embodiments, m″=2.

[0507] In some embodiments, n” = 0, 1 or 2.

[0508] In some embodiments, n” = 0 or 1.

[0509] In some embodiments, n” = 1 or 2.

[0510] In some embodiments, n” = 0 or 2.

[0511] In some embodiments, n” = 0.

[0512] In some embodiments, n” = 1.

[0513] In some embodiments, n″=2.

[0514] In some embodiments, m"=0 and n"=2.

[0515] In some embodiments, m"=2 and n"=0.

[0516] In some embodiments, m” = 1 and n” = 1.

[0517] The sum of m' and n' is 2.

[0518] In some embodiments of compounds having formula AA-3, m″=1 and n″=1.

[0519] Rings A, A' and A" and substitutions on rings A, A' and A"

[0520] Ring A

[0521] In some embodiments, A is a 5- to 10-membered heteroaryl or a C7-C 10 Aryl.

[0522] In some embodiments, A is a 5-membered heteroaryl.

[0523] In some embodiments, A is a 6- to 10-membered heteroaryl.

[0524] In some embodiments, A is a 6-membered heteroaryl.

[0525] In some embodiments, A is C6-C 10 Aryl.

[0526] In some embodiments, A is a member comprising one selected from N, NH, and NR 1 A 5-membered heteroaryl group of heteroatoms or heteroatom groups.

[0527] In some embodiments, A is a 5-membered heteroaryl group comprising one heteroatom selected from O and S, wherein the heteroatom is not bonded to a S(O)(NHR 3 )=N part is bonded at the position.

[0528] In some embodiments, A is not a portion selected from the group consisting of: R at the ortho position of the bond connecting the phenyl group to the S(O)(NH) moiety. 1 or R 2 Monosubstituted pyrazolyl, 2-thienyl, 2-furyl, or phenyl.

[0529] In some embodiments, A is selected from the group consisting of: 3-furanyl, 3-thienyl, pyrroleyl, imidazolyl, triazolyl, thiazolyl, thiadiazolyl, oxadiazolyl, oxazolyl, pyridyl, pyrimidinyl, triazinyl, benzimidazolyl, benzothiophene, benzofuranyl, indazoleyl, benzotriazolyl, benzotriazolyl, quinolinyl, quinazolinyl, and benzotriazinyl.

[0530] In some embodiments, A is a thiophene group.

[0531] In some embodiments, A is a thiazolyl group.

[0532] In some embodiments, A is a pyrazolyl group.

[0533] In some embodiments, A is imidazolyl.

[0534] In some embodiments, A is pyrrolyl.

[0535] In some embodiments, A is an oxazolyl group.

[0536] In some embodiments, A is a furanyl group.

[0537] In some embodiments, A is isoxazolyl.

[0538] In some embodiments, A is isothiazolyl.

[0539] In some embodiments, A is a triazolyl group (e.g., 1,2,3-triazolyl or 1,2,4-triazolyl).

[0540] In some embodiments, A is a pyridyl group.

[0541] In some embodiments, A is pyrimidinyl.

[0542] In some embodiments, A is pyrazinyl.

[0543] In some embodiments, A is a pyridazinyl group.

[0544] In some embodiments, A is a triazine group.

[0545] In some embodiments, A is phenyl.

[0546] In some embodiments, A is optionally represented by 1 or 2 Rs. 1 and optionally substituted with 1 or 2 R 2 Substituted phenyl groups.

[0547] In some embodiments, A is optionally replaced by 1 or 2 R 1 Replaced and optionally by 1 or 2 R 2 Substituted naphthyl group.

[0548] In some embodiments, A is optionally replaced by 1 or 2 R 1 Replaced and optionally by 1 R 2 Substituted furyl.

[0549] In some embodiments, A is optionally represented by 1 R 1 and optionally substituted with 1 or 2 R 2 Substituted furanyl group.

[0550] In some embodiments, A is optionally replaced by 1 or 2 R 1 and optionally substituted with 1 or 2 R 2 Substituted thienyl.

[0551] In some embodiments, A is optionally replaced by 1 or 2 R 1 and optionally substituted with 1 or 2 R 2 Substituted oxazolyl.

[0552] In some embodiments, A is optionally replaced by 1 or 2 R 1 and optionally substituted with 1 or 2 R 2 Substituted thiazole group.

[0553] In some embodiments, A is optionally represented by two Rs. 1 substituted or optionally substituted by 2 R 2 Substituted oxazolyl.

[0554] In some embodiments, A is optionally replaced by 2 R 1 Replace or optionally be 2 R 2 Substituted thiazole group.

[0555] In some embodiments, A is optionally replaced by 1 or 2 R 1 and optionally substituted with 1 or 2 R 2 Substituted pyrazolyl.

[0556] In some embodiments, A is optionally replaced by 1 R 1 and optionally substituted with 1 or 2 R 2 Substituted pyrazol group.

[0557] In some embodiments, A is optionally replaced by 1 or 2 R 1 Replaced and optionally by 1 R 2 Substituted pyrazol group.

[0558] In some embodiments, A is optionally replaced by 1 or 2 R 1 and optionally substituted with 1 or 2 R 2 Substituted pyridinyl group.

[0559] In some embodiments, A is optionally replaced by 1 or 2 R1 and optionally substituted with 1 or 2 R 2 Substituted indazole group.

[0560] In some embodiments, A is optionally replaced by 1 or 2 R 1 and optionally substituted with 1 or 2 R 2 Substituted imidazole group.

[0561] In some embodiments, A is optionally replaced by 1 or 2 R 1 and optionally substituted with 1 or 2 R 2 Substituted pyrrole group.

[0562] In some embodiments, A is optionally replaced by 1 or 2 R 1 and optionally substituted with 1 or 2 R 2 Substituted oxazolyl.

[0563] In some embodiments, A is optionally replaced by 1 or 2 R 1 and optionally substituted with 1 or 2 R 2 Substituted furanyl group.

[0564] In some embodiments, A is optionally replaced by 1 or 2 R 1 and optionally substituted with 1 or 2 R 2 Substituted isoxazolyl group.

[0565] In some embodiments, A is optionally replaced by 1 or 2 R 1 and optionally substituted with 1 or 2 R 2 Substituted isothiazol group.

[0566] In some embodiments, A is optionally replaced by 1 R 1 Replaced and optionally by 1 R 2 Substituted triazole group (e.g., 1,2,3-triazole or 1,2,4-triazole).

[0567] In some embodiments, A is optionally replaced by 1 or 2 R 1 and optionally substituted with 1 or 2 R 2 Substituted pyridinyl group.

[0568] In some embodiments, A is optionally replaced by 1 or 2 R 1 and optionally substituted with 1 or 2 R 2 Substituted pyrimidine group.

[0569] In some embodiments, A is optionally replaced by 1 or 2 R 1 and optionally substituted with 1 or 2 R 2 Substituted pyrazinyl group.

[0570] In some embodiments, A is optionally replaced by 1 or 2 R 1 and optionally substituted with 1 or 2 R 2 Substituted pyridazinyl group.

[0571] In some embodiments, A is optionally replaced by 1 or 2 R 1 and optionally substituted with 1 or 2 R 2 Substituted triazine group.

[0572] In some embodiments, A is controlled by 1 R 1 Replaced and optionally by 1 R 2 Substituted phenyl groups.

[0573] In some embodiments, A is controlled by 1 R 1 Replaced and optionally by 1 R 2 Substituted naphthyl group.

[0574] In some embodiments, A is controlled by 1 R 1 Replaced and optionally by 1 R 2 Substituted furanyl group.

[0575] In some embodiments, A is controlled by 1 R 1 Replaced and optionally by 1 R 2 Substituted thienyl.

[0576] In some embodiments, A is controlled by 1 R 1 Replaced and optionally by 1 R 2 Substituted oxazolyl.

[0577] In some embodiments, A is controlled by 1 R 1 Replaced and optionally by 1 R 2 Substituted thiazole group.

[0578] In some embodiments, A is controlled by 1 R 1 Replaced and optionally by 1 R 2 Substituted pyrazol group.

[0579] In some embodiments, A is controlled by 1 R 1 Replaced and optionally by 1 R 2 Substituted pyridinyl group.

[0580] In some embodiments, A is optionally replaced by 1 R 1 Replaced and optionally by 1 R 2 Substituted indazole group.

[0581] In some embodiments, A is controlled by 1 R 1 Replaced and by 1 R 2 Substituted phenyl groups.

[0582] In some embodiments, A is controlled by 1 R 1 Replaced and by 1 R 2 Substituted furanyl group.

[0583] In some embodiments, A is controlled by 1 R 1 Replaced and by 1 R 2 Substituted thienyl.

[0584] In some embodiments, A is controlled by 1 R 1 Replaced and by 1 R 2 Substituted oxazolyl.

[0585] In some embodiments, A is controlled by 1 R 1 Replaced and by 1 R 2 Substituted thiazole group.

[0586] In some embodiments, A is controlled by 1 R 1 Replaced and by 1 R 2 Substituted pyrazol group.

[0587] In some embodiments, A is controlled by 1 R 1 Replaced and by 1 R 2 Substituted pyridinyl group.

[0588] In some embodiments, A is controlled by 1 R 1 Replaced and by 1 R 2 Substituted imidazole group.

[0589] In some embodiments, A is controlled by 1 R 1 Replaced and by 1 R 2 Substituted pyrrole group.

[0590] In some embodiments, A is controlled by 1 R 1 Replaced and by 1 R 2 Substituted oxazolyl.

[0591] In some embodiments, A is controlled by 1 R 1 Replaced and by 1 R 2 Substituted furanyl group.

[0592] In some embodiments, A is controlled by 1 R 1 Replaced and by 1 R 2 Substituted isoxazolyl group.

[0593] In some embodiments, A is controlled by 1 R 1 Replaced and by 1 R 2 Substituted isothiazol group.

[0594] In some embodiments, A is controlled by 1 R 1Replaced and by 1 R 2 Substituted triazole group (e.g., 1,2,3-triazole or 1,2,4-triazole).

[0595] In some embodiments, A is controlled by 1 R 1 Replaced and by 1 R 2 Substituted pyrimidine group.

[0596] In some embodiments, A is controlled by 1 R 1 Replaced and by 1 R 2 Substituted pyrazinyl group.

[0597] In some embodiments, A is controlled by 1 R 1 Replaced and by 1 R 2 Substituted pyridazinyl group.

[0598] In some embodiments, A is controlled by 1 R 1 Replaced and by 1 R 2 Substituted triazine group.

[0599] In some embodiments, A is phenyl, m is 0 or 1, and n is 0, 1, or 2.

[0600] In some embodiments, A is furanyl, m is 0 or 1, and n is 0, 1, or 2.

[0601] In some embodiments, A is a thiophene group, m is 0 or 1, and n is 0, 1, or 2.

[0602] In some embodiments, A is an oxazolyl group, m is 0 or 1, and n is 0, 1, or 2.

[0603] In some embodiments, A is a thiazolyl group, m is 0 or 1, and n is 0, 1, or 2.

[0604] In some embodiments, A is a pyrazolyl group, m is 0 or 1, and n is 0, 1, or 2.

[0605] In some embodiments, A is pyridyl, m is 0 or 1, and n is 0, 1, or 2.

[0606] In some embodiments, A is an indazole group, m is 0 or 1, and n is 0, 1, or 2.

[0607] In some embodiments, A is phenyl, m is 0, and n is 0 or 1.

[0608] In some embodiments, A is furanyl, m is 0, and n is 0 or 1.

[0609] In some embodiments, A is a thiophene group, m is 0, and n is 0 or 1.

[0610] In some embodiments, A is oxazolyl, m is 0, and n is 0 or 1.

[0611] In some embodiments, A is a thiazolyl group, m is 0, and n is 0 or 1.

[0612] In some embodiments, A is pyrazolyl, m is 0, and n is 0 or 1.

[0613] In some embodiments, A is pyridyl, m is 0, and n is 0 or 1.

[0614] In some embodiments, A is thiazolyl, m is 1, and n is 1.

[0615] In some embodiments, A is a pyrazolyl group, m is 1 or 2, and n is 1 or 2.

[0616] In some embodiments, A is imidazolyl, m is 1 or 2, and n is 1 or 2.

[0617] In some embodiments, A is a pyrrole group, m is 1 or 2, and n is 1 or 2.

[0618] In some embodiments, A is an oxazolyl group, m is 1, and n is 1.

[0619] In some embodiments, A is furanyl, m is 1 or 2, and n is 1 or 2.

[0620] In some embodiments, A is isoxazolyl, m is 1, and n is 1.

[0621] In some embodiments, A is isothiazolyl, m is 1, and n is 1.

[0622] In some embodiments, A is triazolyl (eg, 1,2,3-triazolyl or 1,2,4-triazolyl), m is 1, and n is 1.

[0623] In some embodiments, A is pyridyl, m is 1 or 2, and n is 1 or 2.

[0624] In some embodiments, A is a pyrimidinyl group, m is 1 or 2, and n is 1 or 2.

[0625] In some embodiments, A is pyrazinyl, m is 1 or 2, and n is 1 or 2.

[0626] In some embodiments, A is pyridazinyl, m is 1 or 2, and n is 1 or 2.

[0627] In some embodiments, A is triazinyl, m is 1, and n is 1.

[0628] In some embodiments, A is one of the rings disclosed below optionally substituted as disclosed below, wherein in each case, the ring represented by the wavy line The bond shown as broken connects A to S(O)(NHR 3 )=N part.

[0629] In some embodiments, the optionally substituted ring A yes

[0630] In some embodiments, the optionally substituted Ring A is

[0631] In some embodiments, the optionally substituted Ring A is

[0632] In some embodiments, the optionally substituted ring A is

[0633] In some embodiments, the optionally substituted Ring A is

[0634] In some embodiments, the optionally substituted ring A is

[0635] In some embodiments, the optionally substituted Ring A is

[0636] In some embodiments, the optionally substituted Ring A is

[0637] In some embodiments, the optionally substituted ring A is

[0638] In some embodiments, the optionally substituted ring A is

[0639] In some embodiments, the optionally substituted Ring A is

[0640] In some embodiments, the optionally substituted ring A is

[0641] In some embodiments, the optionally substituted Ring A is

[0642] In some embodiments, the optionally substituted ring A is

[0643] In some embodiments, the optionally substituted Ring A is

[0644] In some embodiments, the optionally substituted Ring A is

[0645] In some embodiments, the optionally substituted Ring A is

[0646] In some embodiments, the optionally substituted Ring A is

[0647] In some embodiments, the optionally substituted Ring A is

[0648] In some embodiments, the optionally substituted Ring A is

[0649] In some embodiments, the optionally substituted Ring A is

[0650] In some embodiments, the optionally substituted Ring A is

[0651] In some embodiments, the optionally substituted Ring A is

[0652] In some embodiments, the optionally substituted Ring A is

[0653] In some embodiments, the optionally substituted Ring A is

[0654] In some embodiments, the optionally substituted Ring A is

[0655] In some embodiments, the optionally substituted Ring A is

[0656] In some embodiments, the optionally substituted Ring A is

[0657] In some embodiments, the optionally substituted Ring A is

[0658] In some embodiments, the optionally substituted Ring A is

[0659] In some embodiments, the optionally substituted Ring A is

[0660] In some embodiments, the replaced ring A is

[0661] In some embodiments, the substituted Ring A is

[0662] In some embodiments, the substituted Ring A is

[0663] In some embodiments, the substituted Ring A is

[0664] In some embodiments, the substituted Ring A is

[0665] In some embodiments, the optionally substituted Ring A is

[0666] In some embodiments, the optionally substituted Ring A is

[0667] In some embodiments, the optionally substituted Ring A is

[0668] In some embodiments, the optionally substituted Ring A is

[0669] In some embodiments, the optionally substituted Ring A is

[0670] In some embodiments, the optionally substituted Ring A is

[0671] In some embodiments, the optionally substituted Ring A is

[0672] In some embodiments, the optionally substituted Ring A is

[0673] In some embodiments, the optionally substituted Ring A is

[0674] In some embodiments, the optionally substituted Ring A is

[0675] In some embodiments, the optionally substituted Ring A is

[0676] In some embodiments, the optionally substituted Ring A is

[0677] In some embodiments, the optionally substituted Ring A is

[0678] In some embodiments, the optionally substituted Ring A is

[0679] In some embodiments, the optionally substituted Ring A is

[0680] In some embodiments, the optionally substituted Ring A is

[0681] In some embodiments, the optionally substituted Ring A is

[0682] In some embodiments, the optionally substituted Ring A is

[0683] In some embodiments, the optionally substituted Ring A is

[0684] In some embodiments, the optionally substituted Ring A is

[0685] In some embodiments, the optionally substituted Ring A is

[0686] In some embodiments, the optionally substituted Ring A is

[0687] In some embodiments, the optionally substituted Ring A is

[0688] In some embodiments, the optionally substituted Ring A is

[0689] In some embodiments, the optionally substituted Ring A is

[0690] In some embodiments, the optionally substituted Ring A is

[0691] In some embodiments, the optionally substituted Ring A is

[0692] In some embodiments, the optionally substituted Ring A is

[0693] In some embodiments, the optionally substituted Ring A is

[0694] In some embodiments, the optionally substituted Ring A is

[0695] In some embodiments, the optionally substituted Ring A is

[0696] In some embodiments, the optionally substituted Ring A is

[0697] In some embodiments, the optionally substituted Ring A is

[0698] In some embodiments, the optionally substituted Ring A is

[0699] In some embodiments, the optionally substituted Ring A is

[0700] In some embodiments, the optionally substituted Ring A is

[0701] In some embodiments, the optionally substituted Ring A is

[0702] In some embodiments, the optionally substituted Ring A is

[0703] In some embodiments, the optionally substituted Ring A is

[0704] In some embodiments, the optionally substituted Ring A is

[0705] In some embodiments, the optionally substituted Ring A is

[0706] In some embodiments, the optionally substituted Ring A is

[0707] In some embodiments, the optionally substituted Ring A is

[0708] In some embodiments, the optionally substituted Ring A is

[0709] In some embodiments, the optionally substituted Ring A is

[0710] In some embodiments, the optionally substituted Ring A is

[0711] In some embodiments, the optionally substituted Ring A is

[0712] In some embodiments, the optionally substituted Ring A is

[0713] In some embodiments, the optionally substituted Ring A is

[0714] In some embodiments, the optionally substituted Ring A is

[0715] In some embodiments, the optionally substituted Ring A is

[0716] In some embodiments, the optionally substituted Ring A is

[0717] In some embodiments, the optionally substituted Ring A is

[0718] In some embodiments, the optionally substituted Ring A is

[0719] In some embodiments, the optionally substituted Ring A is

[0720] In some embodiments, the optionally substituted Ring A is

[0721] In some embodiments, the optionally substituted Ring A is

[0722] In some embodiments, the optionally substituted Ring A is

[0723] In some embodiments, the optionally substituted Ring A is

[0724] In some embodiments, the optionally substituted Ring A is

[0725] In some embodiments, the optionally substituted Ring A is

[0726] In some embodiments, the optionally substituted Ring A is

[0727] In some embodiments, the optionally substituted Ring A is

[0728] In some embodiments, the optionally substituted Ring A is

[0729] In some embodiments, the optionally substituted Ring A is

[0730] In some embodiments, the optionally substituted Ring A is

[0731] In some embodiments, the optionally substituted Ring A is

[0732] In some embodiments, the optionally substituted Ring A is

[0733] In some embodiments, the optionally substituted Ring A is

[0734] In some embodiments, the optionally substituted Ring A is

[0735] In some embodiments, the optionally substituted Ring A is

[0736] In some embodiments, the optionally substituted Ring A is

[0737] In some embodiments, the optionally substituted Ring A is

[0738] In some embodiments, the optionally substituted Ring A is

[0739] In some embodiments, the optionally substituted Ring A is

[0740] In some embodiments, the optionally substituted Ring A is

[0741] In some embodiments, the optionally substituted Ring A is

[0742] In some embodiments, the substituted Ring A is

[0743] In some embodiments, the substituted Ring A is

[0744] In some embodiments, the substituted Ring A is

[0745] In some embodiments, the substituted Ring A is

[0746] In some embodiments, the substituted Ring A is

[0747] In some embodiments, the substituted Ring A is

[0748] In some embodiments, the substituted Ring A is

[0749] In some embodiments, the substituted Ring A is

[0750] In some embodiments, the substituted Ring A is

[0751] In some embodiments, the substituted Ring A is

[0752] In some embodiments, the substituted Ring A is

[0753] In some embodiments, the substituted Ring A is

[0754] In some embodiments, the substituted Ring A is

[0755] In some embodiments, the substituted Ring A is

[0756] In some embodiments, the substituted Ring A is

[0757] In some embodiments, the optionally substituted Ring A is

[0758] In some embodiments, the optionally substituted Ring A is

[0759] In some embodiments, the optionally substituted Ring A is

[0760] In some embodiments, the optionally substituted Ring A is

[0761] In some embodiments, the optionally substituted Ring A is

[0762] In some embodiments, the optionally substituted Ring A is

[0763] In some embodiments, the optionally substituted Ring A is

[0764] In some embodiments, the optionally substituted Ring A is

[0765] In some embodiments, the optionally substituted Ring A is

[0766] In some embodiments, the optionally substituted Ring A is

[0767] In some embodiments, the optionally substituted Ring A is

[0768] In some embodiments, the optionally substituted Ring A is

[0769] In some embodiments, the optionally substituted Ring A is

[0770] In some embodiments, the optionally substituted Ring A is

[0771] In some embodiments, the optionally substituted Ring A is

[0772] In some embodiments, the optionally substituted Ring A is

[0773] In some embodiments, the optionally substituted Ring A is

[0774] In some embodiments, the optionally substituted Ring A is

[0775] In some embodiments, the optionally substituted Ring A is

[0776] In some embodiments, the optionally substituted Ring A is

[0777] In some embodiments, the optionally substituted Ring A is

[0778] In some embodiments, the optionally substituted Ring A is

[0779] In some embodiments, the optionally substituted Ring A is

[0780] In some embodiments, the optionally substituted Ring A is

[0781] In some embodiments, the optionally substituted Ring A is

[0782] In some embodiments, the optionally substituted Ring A is

[0783] In some embodiments, the optionally substituted Ring A is

[0784] In some embodiments, the optionally substituted Ring A is

[0785] In some embodiments, the optionally substituted ring A is selected from the group consisting of:

[0786]

[0787]

[0788] In some embodiments, the optionally substituted ring A is selected from the group consisting of:

[0789]

[0790] In some embodiments, the optionally substituted Ring A is selected from the group consisting of:

[0791]

[0792] In some embodiments, the optionally substituted ring A is selected from the group consisting of:

[0793]

[0794] In some embodiments, the optionally substituted ring A is selected from the group consisting of:

[0795]

[0796] In some embodiments, the optionally substituted ring A is selected from the following:

[0797]

[0798] In some embodiments of compounds having the formula AA, when ring A is phenyl, then R 1 and R 2 Each is independently selected from C3 alkyl, C5-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, F, I, CN, NO2, COC2-C6 alkyl, CO-C6-C 10 Aryl, CO (5- to 10-membered heteroaryl), CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC2-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10 Aryl, 5- to 10-membered heteroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, NHCOC1-C6 alkyl, NHCOC6-C 10Aryl, NHCO (5- to 10-membered heteroaryl), NHCO (3- to 7-membered heterocyclic alkyl), NHCOC2-C6 ynyl, NHCOOC1-C6 alkyl, NH-(C=NR) 13 )NR 11 R 12 、CONR 8 R 9 SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, S(O2)NR 11 R 12 S(O)C1-C6 alkyl, C3-C7 cycloalkyl and 3 to 7-membered heterocyclic alkyl,

[0799] The C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, and 3- to 7-membered heterocyclic alkyl groups are optionally substituted by one or more substituents, each independently selected from the following: hydroxyl, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR. 8 R 9 、=NR 10 、COOC1-C6 alkyl、CONR 8 R 9 3 to 7-membered heterocyclic alkyl groups, C6-C 10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocyclic alkyl), NHCOC1-C6 alkyl, NHCOC6-C 10 Aryl, NHCO (5- to 10-membered heteroaryl), NHCO (3- to 7-membered heterocyclic alkyl), and NHCOC2-C6 alkynyl;

[0800] wherein R 1 or R 2 C3-C7 cycloalkyl or said R 1 or R 2 Each C1-C6 alkyl substituent and each C1-C6 alkoxy substituent of the 3- to 7-membered heterocyclic alkyl group may further optionally be independently replaced by one to three hydroxyl, halogenated, or NR-substituted groups. 8 R 9 , or oxo-substituted;

[0801] wherein the 3 to 7 membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, NHCOC6-C 10 Aryl, NHCO(5- to 10-membered heteroaryl), and NHCO(3- to 7-membered heterocycloalkyl) are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;

[0802] or a pair of R located on adjacent atoms 1 and R 2 Together with the atoms that connect them, they independently form a monocyclic or bicyclic C4 or C6-C 12 A carbon ring or a monocyclic or bicyclic 5- to 12-membered heterocycle, said heterocycle comprising 1 to 3 heteroatoms and / or heteroatom groups independently selected from the following: O, NH, NR. 13 S, S(O), and S(O)2, wherein the carbocyclic or heterocyclic ring is optionally and independently substituted by one or more substituents independently selected from the following: hydroxyl, halogenated, oxo-substituted, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, OC3-C 10 Cycloalkyl, NR 8 R 9 、=NR 10 、CN、COOC1-C6 alkyl、OS(O2)C6-C 10 Aryl, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, 3- to 10-membered heterocycloalkyl, and CONR 8 R 9 The C1-C6 alkyl, C1-C6 alkoxy, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, and 3 to 10 membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from the group consisting of hydroxy, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 alkyl, C4-C6 alkyl, C6-C6 alkyl, C7-C6 alkyl, C8-C6 alkyl, C9-C6 alkyl, C10-C6 alkyl, C11-C6 alkyl, C12-C6 alkyl, C13-C6 alkyl, C14-C6 alkyl, C15-C6 alkyl, C16-C6 alkyl, C17-C6 alkyl, C18-C6 alkyl, C19-C6 alkyl, C21-C6 alkyl, C22-C6 alkyl, C23-C6 alkyl, C24-C6 alkyl, C25-C6 alkyl, C2 10 Cycloalkyl, C1-C6 alkoxy, oxo, NR 8 R 9 、=NR 10 COOC1-C6 alkyl, C6-C 10 Aryl and CONR 8 R 9 .

[0803] In some embodiments of compounds of formula AA, when Ring A is pyridinyl, then R 1 and R 2 Each is independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halogen, CN, NO2, COC1-C6 alkyl, CO-C6-C 10Aryl, CO (5- to 10-membered heteroaryl), CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10 Aryl, 5- to 10-membered heteroaryl, NH2, NHC2-C6 alkyl, N(C1-C6 alkyl)2, NHCOC1-C6 alkyl, NHCOC6-C 10 Aryl, NHCO (5- to 10-membered heteroaryl), NHCO (3- to 7-membered heterocyclic alkyl), NHCOC2-C6 ynyl, NHCOOC1-C6 alkyl, NH-(C=NR) 13 )NR 11 R 12 、CONR 8 R 9 SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, S(O2)NR 11 R 12 S(O)C1-C6 alkyl, C3-C7 cycloalkyl, and 3- to 7-membered heterocyclic alkyl,

[0804] The C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, and 3- to 7-membered heterocyclic alkyl groups are optionally substituted by one or more substituents, each independently selected from the following: hydroxyl, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR. 8 R 9 、=NR 10 、COOC1-C6 alkyl、CONR 8 R 9 , 3 to 5 membered heterocycloalkyl, 5 membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocyclic alkyl), NHCOC1-C6 alkyl, NHCOC6-C 10 Aryl, NHCO (5- to 10-membered heteroaryl), NHCO (3- to 7-membered heterocyclic alkyl), and NHCOC2-C6 alkynyl;

[0805] wherein R 1 or R 2 C3-C7 cycloalkyl or said R 1 or R 2 Each C1-C6 alkyl substituent and each C1-C6 alkoxy substituent of the 3- to 7-membered heterocyclic alkyl group may further optionally be independently replaced by one to three hydroxyl, halogenated, or NR-substituted groups. 8 R 9 , or oxo-substituted;

[0806] wherein the 3 to 7 membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, NHCOC6-C 10 Aryl, NHCO(5- to 10-membered heteroaryl), and NHCO(3- to 7-membered heterocycloalkyl) are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;

[0807] or a pair of R located on adjacent atoms 1 and R 2 Together with the atoms that connect them, they independently form a monocyclic or bicyclic C4-C ring. 12 A carbon ring or a monocyclic or bicyclic 5- to 12-membered heterocycle, said heterocycle comprising 1 to 3 heteroatoms and / or heteroatom groups independently selected from the following: O, NH, NR. 13 S, S(O), and S(O)2, wherein the carbocyclic or heterocyclic ring is optionally and independently substituted by one or more substituents each independently selected from the following: hydroxyl, halogenated, oxo-substituted, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, OC3-C 10 Cycloalkyl, NR 8 R 9 、=NR 10 、CN、COOC1-C6 alkyl、OS(O2)C6-C 10 Aryl, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, 3- to 10-membered heterocycloalkyl, and CONR 8 R 9 The C1-C6 alkyl, C1-C6 alkoxy, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, and 3 to 10 membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from the group consisting of hydroxy, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 alkyl, C4-C6 alkyl, C6-C6 alkyl, C7-C6 alkyl, C8-C6 alkyl, C9-C6 alkyl, C10-C6 alkyl, C11-C6 alkyl, C12-C6 alkyl, C13-C6 alkyl, C14-C6 alkyl, C15-C6 alkyl, C16-C6 alkyl, C17-C6 alkyl, C18-C6 alkyl, C19-C6 alkyl, C21-C6 alkyl, C22-C6 alkyl, C23-C6 alkyl, C24-C6 alkyl, C25-C6 alkyl, C2 10 Cycloalkyl, C1-C6 alkoxy, oxo, NR 8 R 9 、=NR 10 COOC1-C6 alkyl, C6-C 10 Aryl and CONR 8 R 9 .

[0808] When the formula AA is the ring A' of the formula AA-1

[0809] In some embodiments, A' is a 6 to 10-membered (e.g., 6-membered) heteroaryl or C6-C 10 (For example, C6) monocyclic or bicyclic aryl, such as phenyl.

[0810] In some embodiments, A' is a 6 to 10-membered (e.g., 6-membered) heteroaryl or C7-C 10 (e.g., C6) monocyclic or bicyclic aryl.

[0811] In some embodiments, A' is a 6 to 10-membered (e.g., 6-membered) heteroaryl group.

[0812] In some embodiments of compounds having the formula AA-1, A' is C6-C. 10 Aryl.

[0813] In some embodiments, A' is a 5-membered heteroaryl group containing 2 or more heteroatoms.

[0814] In some embodiments, A' is a subset selected from N, NH, and NR. 1 5-membered heteroaryl groups of heteroatoms and / or heteroatom groups.

[0815] In some embodiments, A' is a 5-membered heteroaryl group comprising one heteroatom selected from O and S, wherein the heteroatom is not bonded to S(O)(NHR) by the heteroaryl group. 3 )=N part is bonded at the position.

[0816] In some embodiments, A' is a 5-membered heteroaryl group containing sulfur and optionally one or more nitrogen atoms.

[0817] In some embodiments, A' is C6-C 10 Aryl.

[0818] In some embodiments, A' is not a pyrazolyl group.

[0819] In some embodiments, A' is a thiophene group (e.g., thiophene-3-yl).

[0820] In some embodiments, A' is a thiazolyl group (e.g., thiazolyl-2-yl or thiazolyl-3-yl).

[0821] In some embodiments, A' is a pyrazolyl group (e.g., pyrazol-2-yl).

[0822] In some embodiments, A' is an imidazole group (e.g., imidazole-2-yl).

[0823] In some embodiments, A' is naphthyl.

[0824] In some embodiments, A' is furanyl.

[0825] In some embodiments, A' is pyridyl.

[0826] In some embodiments, A' is an indazole group.

[0827] In some embodiments, A' is phenyl, m is 0 or 1, and n is 0, 1, or 2.

[0828] In some embodiments, A' is furanyl, m is 0 or 1, and n is 0, 1, or 2.

[0829] In some embodiments, A′ is thienyl, m is 0 or 1, and n is 0, 1, or 2.

[0830] In some embodiments, A′ is thiazolyl, m is 0 or 1, and n is 0, 1, or 2.

[0831] In some embodiments, A′ is pyrazolyl, m is 0 or 1, and n is 0, 1, or 2.

[0832] In some embodiments, A′ is pyridyl, m is 0 or 1, and n is 0, 1, or 2.

[0833] In some embodiments, A′ is indazolyl, m is 0 or 1, and n is 0, 1, or 2.

[0834] In some embodiments, A' is a thiazolyl group, m is 1, and n is 1.

[0835] In some embodiments, A' is pyrazolyl, m is 1 or 2, and n is 1 or 2.

[0836] In some embodiments, A′ is imidazolyl, m is 1 or 2, and n is 1 or 2.

[0837] In some embodiments, A' is a pyrrole group, m is 1 or 2, and n is 1 or 2.

[0838] In some embodiments, A' is oxazolyl, m is 1, and n is 1.

[0839] In some embodiments, A' is furanyl, m is 1 or 2, and n is 1 or 2.

[0840] In some embodiments, A' is an isoxazolyl group, m is 1, and n is 1.

[0841] In some embodiments, A' is an isothiazolyl group, m is 1, and n is 1.

[0842] In some embodiments, A' is a triazolyl group (e.g., 1,2,3-triazolyl or 1,2,4-triazolyl), m is 1, and n is 1.

[0843] In some embodiments, A' is pyridyl, m is 1 or 2, and n is 1 or 2.

[0844] In some embodiments, A' is a pyrimidinyl group, m is 1 or 2, and n is 1 or 2.

[0845] In some embodiments, A' is pyrazinyl, m is 1 or 2, and n is 1 or 2.

[0846] In some embodiments, A' is pyridazinyl, m is 1 or 2, and n is 1 or 2.

[0847] In some embodiments, A' is triazine, m is 1, and n is 1.

[0848] In some embodiments, A' is optionally one of the rings disclosed below, as disclosed below, wherein in each case, it is formed by a waveform line. The bond shown as broken connects A to S(O)(NHR 3 )=N part.

[0849] In some embodiments, the optionally substituted ring A' yes

[0850] In some embodiments, the optionally substituted ring A' is

[0851] In some embodiments, the optionally substituted ring A' is

[0852] In some embodiments, the optionally substituted ring A' is

[0853] In some embodiments, the optionally substituted ring A' is

[0854] In some embodiments, the optionally substituted ring A' is

[0855] In some embodiments, the optionally substituted ring A' is

[0856] In some embodiments, the optionally substituted ring A' is

[0857] In some embodiments, the optionally substituted ring A' is

[0858] In some embodiments, the optionally substituted ring A' is

[0859] In some embodiments, the optionally substituted ring A' is

[0860] In some embodiments, the optionally substituted ring A' is

[0861] In some embodiments, the optionally substituted ring A' is

[0862] In some embodiments, the optionally substituted ring A' is

[0863] In some embodiments, the optionally substituted ring A' is

[0864] In some embodiments, the optionally substituted ring A' is

[0865] In some embodiments, the optionally substituted ring A' is

[0866] In some embodiments, the optionally substituted ring A' is

[0867] In some embodiments, the optionally substituted ring A' is

[0868] In some embodiments, the optionally substituted ring A' is

[0869] In some embodiments, the optionally substituted ring A' is

[0870] In some embodiments, the optionally substituted ring A' is

[0871] In some embodiments, the optionally substituted ring A' is

[0872] In some embodiments, the optionally substituted ring A' is

[0873] In some embodiments, the optionally substituted ring A' is

[0874] In some embodiments, the optionally substituted ring A' is

[0875] In some embodiments, the optionally substituted ring A' is

[0876] In some embodiments, the optionally substituted ring A' is

[0877] In some embodiments, the optionally substituted ring A' is

[0878] In some embodiments, the optionally substituted ring A' is

[0879] In some embodiments, the optionally substituted ring A' is

[0880] In some embodiments, the optionally substituted ring A' is

[0881] In some embodiments, the replaced ring A' is

[0882] In some embodiments, the replaced ring A' is

[0883] In some embodiments, the replaced ring A' is

[0884] In some embodiments, the replaced ring A' is

[0885] In some embodiments, the substituted ring A' is

[0886] In some embodiments, the optionally substituted ring A' is

[0887] In some embodiments, the optionally substituted ring A' is

[0888] In some embodiments, the optionally substituted ring A' is

[0889] In some embodiments, the optionally substituted ring A' is

[0890] In some embodiments, the optionally substituted ring A' is

[0891] In some embodiments, the optionally substituted ring A' is

[0892] In some embodiments, the optionally substituted ring A' is

[0893] In some embodiments, the optionally substituted ring A' is

[0894] In some embodiments, the optionally substituted ring A' is

[0895] In some embodiments, the optionally substituted ring A' is

[0896] In some embodiments, the optionally substituted ring A' is

[0897] In some embodiments, the optionally substituted ring A' is

[0898] In some embodiments, the optionally substituted ring A' is

[0899] In some embodiments, the optionally substituted ring A' is

[0900] In some embodiments, the optionally substituted ring A' is

[0901] In some embodiments, the optionally substituted ring A' is

[0902] In some embodiments, the optionally substituted ring A' is

[0903] In some embodiments, the optionally substituted ring A' is

[0904] In some embodiments, the optionally substituted ring A' is

[0905] In some embodiments, the optionally substituted ring A' is

[0906] In some embodiments, the optionally substituted ring A' is

[0907] In some embodiments, the optionally substituted ring A' is

[0908] In some embodiments, the optionally substituted ring A' is

[0909] In some embodiments, the optionally substituted ring A' is

[0910] In some embodiments, the optionally substituted ring A' is

[0911] In some embodiments, the optionally substituted ring A' is

[0912] In some embodiments, the optionally substituted ring A' is

[0913] In some embodiments, the optionally substituted ring A' is

[0914] In some embodiments, the optionally substituted ring A' is

[0915] In some embodiments, the optionally substituted ring A' is

[0916] In some embodiments, the optionally substituted ring A' is

[0917] In some embodiments, the optionally substituted ring A' is

[0918] In some embodiments, the optionally substituted ring A' is

[0919] In some embodiments, the optionally substituted ring A' is

[0920] In some embodiments, the optionally substituted ring A' is

[0921] In some embodiments, the optionally substituted ring A' is

[0922] In some embodiments, the optionally substituted ring A' is

[0923] In some embodiments, the optionally substituted ring A' is

[0924] In some embodiments, the optionally substituted ring A' is

[0925] In some embodiments, the optionally substituted ring A' is

[0926] In some embodiments, the optionally substituted ring A' is

[0927] In some embodiments, the optionally substituted ring A' is

[0928] In some embodiments, the optionally substituted ring A' is

[0929] In some embodiments, the optionally substituted ring A' is

[0930] In some embodiments, the optionally substituted ring A' is

[0931] In some embodiments, the optionally substituted ring A' is

[0932] In some embodiments, the optionally substituted ring A' is

[0933] In some embodiments, the optionally substituted ring A' is

[0934] In some embodiments, the optionally substituted ring A' is

[0935] In some embodiments, the optionally substituted ring A' is

[0936] In some embodiments, the substituted ring A' is

[0937] In some embodiments, the substituted ring A' is

[0938] In some embodiments, the substituted ring A' is

[0939] In some embodiments, the substituted ring A' is

[0940] In some embodiments, the substituted ring A' is

[0941] In some embodiments, the substituted ring A' is

[0942] In some embodiments, the substituted ring A' is

[0943] In some embodiments, the substituted ring A' is

[0944] In some embodiments, the substituted ring A' is

[0945] In some embodiments, the substituted ring A' is

[0946] In some embodiments, the substituted ring A' is

[0947] In some embodiments, the substituted ring A' is

[0948] In some embodiments, the substituted ring A' is

[0949] In some embodiments, the optionally substituted ring A' is

[0950] In some embodiments, the optionally substituted ring A' is

[0951] In some embodiments, the optionally substituted ring A' is

[0952] In some embodiments, the optionally substituted ring A' is

[0953] In some embodiments, the optionally substituted ring A' is

[0954] In some embodiments, the optionally substituted ring A' is

[0955] In some embodiments, the optionally substituted ring A' is

[0956] In some embodiments, the optionally substituted ring A' is

[0957] In some embodiments, the optionally substituted ring A' is

[0958] In some embodiments, the optionally substituted ring A' is

[0959] In some embodiments, the optionally substituted ring A' is

[0960] In some embodiments, the optionally substituted ring A' is

[0961] In some embodiments, the optionally substituted ring A' is

[0962] In some embodiments, the optionally substituted ring A' is

[0963] In some embodiments, the optionally substituted ring A' is

[0964] In some embodiments, the optionally substituted ring A' is

[0965] In some embodiments, the optionally substituted ring A' is

[0966] In some embodiments, the optionally substituted ring A' is

[0967] In some embodiments, the optionally substituted ring A' is

[0968] In some embodiments, the optionally substituted ring A' is

[0969] In some embodiments, the optionally substituted ring A' is

[0970] In some embodiments, the optionally substituted ring A' is

[0971] In some embodiments, the optionally substituted ring A' is

[0972] In some embodiments, the optionally substituted ring A' is

[0973] In some embodiments, the optionally substituted ring A' is

[0974] In some embodiments, the optionally substituted ring A' is selected from the group consisting of:

[0975]

[0976] In some embodiments, the optionally substituted ring A' is selected from the group consisting of:

[0977]

[0978] In some embodiments, the optionally substituted Ring A' is selected from the group consisting of:

[0979]

[0980] In some embodiments, the optionally substituted ring A' is selected from the group consisting of:

[0981] In some embodiments, the optionally substituted ring A' is selected from the group consisting of: as well as

[0982] In some embodiments, the optionally substituted ring A' is selected from the following:

[0983]

[0984] In some embodiments of compounds having formula AA-1, when ring A' is phenyl, then R 1 and R 2 Each is independently selected from C3 alkyl, C5-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, F, I, CN, NO2, COC2-C6 alkyl, CO-C6-C 10 Aryl, CO (5- to 10-membered heteroaryl), CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC2-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10 Aryl, 5- to 10-membered heteroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, NHCOC1-C6 alkyl, NHCOC6-C 10 Aryl, NHCO (5- to 10-membered heteroaryl), NHCO (3- to 7-membered heterocyclic alkyl), NHCOC2-C6 ynyl, NHCOOC1-C6 alkyl, NH-(C=NR) 13 )NR 11 R 12 、CONR 8 R 9 SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, S(O2)NR 11 R 12 S(O)C1-C6 alkyl, C3-C7 cycloalkyl and 3 to 7-membered heterocyclic alkyl,

[0985] The C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, and 3- to 7-membered heterocyclic alkyl groups are optionally substituted by one or more substituents, each independently selected from the following: hydroxyl, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR. 8 R 9 、=NR 10 、COOC1-C6 alkyl、CONR 8 R 9 3 to 7-membered heterocyclic alkyl groups, C6-C10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocyclic alkyl), NHCOC1-C6 alkyl, NHCOC6-C 10 Aryl, NHCO (5- to 10-membered heteroaryl), NHCO (3- to 7-membered heterocyclic alkyl), and NHCOC2-C6 alkynyl;

[0986] wherein R 1 or R 2 C3-C7 cycloalkyl or said R 1 or R 2 Each C1-C6 alkyl substituent and each C1-C6 alkoxy substituent of the 3- to 7-membered heterocyclic alkyl group may further optionally be independently replaced by one to three hydroxyl, halogenated, or NR-substituted groups. 8 R 9 , or oxo-substituted;

[0987] wherein the 3 to 7 membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, NHCOC6-C 10 Aryl, NHCO(5- to 10-membered heteroaryl), and NHCO(3- to 7-membered heterocycloalkyl) are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;

[0988] or a pair of R located on adjacent atoms 1 and R 2 Together with the atoms that connect them, they independently form a monocyclic or bicyclic C4 or C6-C 12 A carbon ring or a monocyclic or bicyclic 5- to 12-membered heterocycle, said heterocycle comprising 1 to 3 heteroatoms and / or heteroatom groups independently selected from the following: O, NH, NR. 13 S, S(O), and S(O)2, wherein the carbocyclic or heterocyclic ring is optionally and independently substituted by one or more substituents independently selected from the following: hydroxyl, halogenated, oxo-substituted, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, OC3-C 10 Cycloalkyl, NR 8 R 9 、=NR 10 、CN、COOC1-C6 alkyl、OS(O2)C6-C 10 Aryl, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, 3- to 10-membered heterocycloalkyl, and CONR8 R 9 The C1-C6 alkyl, C1-C6 alkoxy, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, and 3 to 10 membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from the group consisting of hydroxy, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 alkyl, C4-C6 alkyl, C6-C6 alkyl, C7-C6 alkyl, C8-C6 alkyl, C9-C6 alkyl, C10-C6 alkyl, C11-C6 alkyl, C12-C6 alkyl, C13-C6 alkyl, C14-C6 alkyl, C15-C6 alkyl, C16-C6 alkyl, C17-C6 alkyl, C18-C6 alkyl, C19-C6 alkyl, C21-C6 alkyl, C22-C6 alkyl, C23-C6 alkyl, C24-C6 alkyl, C25-C6 alkyl, C2 10 Cycloalkyl, C1-C6 alkoxy, oxo, NR 8 R 9 、=NR 10 COOC1-C6 alkyl, C6-C 10 Aryl and CONR 8 R 9 .

[0989] In some embodiments of compounds having formula AA-1, when ring A is pyridyl, then R 1 and R 2 Each is independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halogen, CN, NO2, COC1-C6 alkyl, CO-C6-C 10 Aryl, CO (5- to 10-membered heteroaryl), CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10 Aryl, 5- to 10-membered heteroaryl, NH2, NHC2-C6 alkyl, N(C1-C6 alkyl)2, NHCOC1-C6 alkyl, NHCOC6-C 10 Aryl, NHCO (5- to 10-membered heteroaryl), NHCO (3- to 7-membered heterocyclic alkyl), NHCOC2-C6 ynyl, NHCOOC1-C6 alkyl, NH-(C=NR) 13 )NR 11 R 12 、CONR 8 R 9 SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, S(O2)NR 11 R 12 S(O)C1-C6 alkyl, C3-C7 cycloalkyl, and 3- to 7-membered heterocyclic alkyl,

[0990] The C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, and 3- to 7-membered heterocyclic alkyl groups are optionally substituted by one or more substituents, each independently selected from the following: hydroxyl, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR. 8 R 9 、=NR 10 、COOC1-C6 alkyl、CONR 8 R 9 , 3 to 5 membered heterocycloalkyl, 5 membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocyclic alkyl), NHCOC1-C6 alkyl, NHCOC6-C 10 Aryl, NHCO (5- to 10-membered heteroaryl), NHCO (3- to 7-membered heterocyclic alkyl), and NHCOC2-C6 alkynyl;

[0991] wherein R 1 or R 2 C3-C7 cycloalkyl or said R 1 or R 2 Each C1-C6 alkyl substituent and each C1-C6 alkoxy substituent of the 3- to 7-membered heterocyclic alkyl group may further optionally be independently replaced by one to three hydroxyl, halogenated, or NR-substituted groups. 8 R 9 , or oxo-substituted;

[0992] wherein the 3 to 7 membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, NHCOC6-C 10 Aryl, NHCO(5- to 10-membered heteroaryl), and NHCO(3- to 7-membered heterocycloalkyl) are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;

[0993] or a pair of R located on adjacent atoms 1 and R 2 Together with the atoms that connect them, they independently form a monocyclic or bicyclic C4-C ring. 12 A carbon ring or a monocyclic or bicyclic 5- to 12-membered heterocycle, said heterocycle comprising 1 to 3 heteroatoms and / or heteroatom groups independently selected from the following: O, NH, NR. 13 S, S(O), and S(O)2, wherein the carbocyclic or heterocyclic ring is optionally and independently substituted by one or more substituents each independently selected from the following: hydroxyl, halogenated, oxo-substituted, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, OC3-C 10 Cycloalkyl, NR8 R 9 、=NR 10 、CN、COOC1-C6 alkyl、OS(O2)C6-C 10 Aryl, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, 3- to 10-membered heterocycloalkyl, and CONR 8 R 9 The C1-C6 alkyl, C1-C6 alkoxy, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, and 3 to 10 membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from the group consisting of hydroxy, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 alkyl, C4-C6 alkyl, C6-C6 alkyl, C7-C6 alkyl, C8-C6 alkyl, C9-C6 alkyl, C10-C6 alkyl, C11-C6 alkyl, C12-C6 alkyl, C13-C6 alkyl, C14-C6 alkyl, C15-C6 alkyl, C16-C6 alkyl, C17-C6 alkyl, C18-C6 alkyl, C19-C6 alkyl, C21-C6 alkyl, C22-C6 alkyl, C23-C6 alkyl, C24-C6 alkyl, C25-C6 alkyl, C2 10 Cycloalkyl, C1-C6 alkoxy, oxo, NR 8 R 9 、=NR 10 COOC1-C6 alkyl, C6-C 10 Aryl and CONR 8 R 9 .

[0994] When equation AA is the ring A when equation AA-2”

[0995] In some embodiments, A” is a 5-membered heteroaryl group comprising one heteroatom selected from O and S, wherein the heteroatom is bonded to the heteroaryl group to S(O)(NHR). 3 )=N part is bonded at the position.

[0996] In some embodiments, A” is thiophene-2-yl.

[0997] In some embodiments, A” is furan-2-yl.

[0998] In some embodiments, A” is optionally one of the rings disclosed below, as disclosed below, wherein in each case, it is formed by the waveform line. The bond shown as broken connects A to S(O)(NHR 3 )=N part.

[0999] In some embodiments, the optionally substituted ring A” yes

[1000] In some embodiments, the optionally substituted ring A is

[1001] In some embodiments, the optionally substituted ring A is

[1002] In some embodiments, the optionally substituted ring A is

[1003] In some embodiments, the optionally substituted ring A is

[1004] In some embodiments, the optionally substituted ring A is

[1005] In some embodiments, the optionally substituted ring A is

[1006] In some embodiments, the optionally substituted ring A is

[1007] In some embodiments, the optionally substituted ring A is

[1008] When equation AA is the ring A of equation AA-3

[1009] In some embodiments, A” is a 5-membered heteroaryl group comprising one heteroatom selected from O and S, wherein the heteroatom is bonded to the heteroaryl group to S(O)(NHR). 3 )=N part is bonded at the position.

[1010] In some embodiments, A” is thiophene-2-yl.

[1011] In some embodiments, A” is furan-2-yl.

[1012] In some embodiments, A" is composed of 2 R 1’ Substituted furan-2-yl.

[1013] In some embodiments, A” is defined by 2 Rs 2’ Substituted furan-2-yl.

[1014] In some embodiments, A” is a function of 1 R 1’ Replaced and by 1 R 2’ Substituted furan-2-yl.

[1015] In some embodiments, A” is defined by 2 Rs 1’ Substituted thiophene-2-yl.

[1016] In some embodiments, A” is defined by 2 Rs 2’ Substituted thiophen-2-yl.

[1017] In some embodiments, A” is a function of 1 R 1’ Replaced and by 1 R 2’ Substituted thiophen-2-yl.

[1018] In some embodiments, A” is optionally one of the rings disclosed below, as disclosed below, wherein in each case, it is formed by the waveform line. The broken bond is shown to connect A” to S(O)(NHR) of formula AA. 3 )=N part.

[1019] In some embodiments, the optionally substituted ring A yes

[1020] In some embodiments, the optionally substituted ring A is

[1021] In some embodiments, the optionally substituted ring A is

[1022] In some embodiments, the optionally substituted ring A is

[1023] In some embodiments, the optionally substituted ring A is

[1024] In some embodiments, the optionally substituted ring A is

[1025] In some embodiments, the optionally substituted ring A is

[1026] In some embodiments, the optionally substituted ring A is selected from the group consisting of:

[1027] In some embodiments, the optionally substituted Ring A is

[1028] When the compound is a compound having the formula AA-4, the ring A”

[1029] In some embodiments, A” is a 5-membered heteroaryl group comprising one heteroatom selected from O and S, wherein the heteroatom is bonded to the heteroaryl group to S(O)(NHR). 3 )=N part is bonded at the position.

[1030] In some embodiments, A” is thiophene-2-yl.

[1031] In some embodiments, A” is furan-2-yl.

[1032] In some embodiments, A” is optionally one of the rings disclosed below, as disclosed below, wherein in each case, it is formed by the waveform line. The bond shown as broken connects A to S(O)(NHR 3 )=N part.

[1033] In some embodiments, the optionally substituted ring A yes

[1034] In some embodiments, the optionally substituted ring A is

[1035] In some embodiments, the optionally substituted ring A is

[1036] In some embodiments, the optionally substituted ring A is

[1037] In some embodiments, the optionally substituted ring A is

[1038] In some embodiments, the optionally substituted ring A is

[1039] In some embodiments, the optionally substituted ring A is

[1040] In some embodiments, the optionally substituted ring A is

[1041] In some embodiments, the optionally substituted ring A is

[1042] In some embodiments, the optionally substituted ring A is

[1043] When the formula AA is the ring of the formula AA-5

[1044] In some embodiments, yes

[1045] In some embodiments, yes

[1046] In some embodiments, yes

[1047] In some embodiments, yes

[1048] In some embodiments, yes

[1049] In some embodiments, yes

[1050] In some embodiments, yes

[1051] Group R 1 、R 1’ 、R 2 、R 2’ and R 2”

[1052] Group R 1 and R 2

[1053] In some embodiments, R 1 When present, it is independently selected from the group consisting of: C1-C6 alkyl groups optionally substituted with one or more hydroxyl groups, optionally substituted with one or more halogenated, oxo-, C1-C6 alkoxy, or NR groups. 8 R 9 Substituted C1-C6 alkyl; optionally with one or more hydroxyl, halogenated, oxo-, C1-C6 alkoxy, C1-C6 alkyl, or NR 8 R 9 Substituted C3-C7 cycloalkyl groups, wherein the C1-C6 alkoxy or C1-C6 alkyl group is further optionally substituted with one to three hydroxyl groups, halogenated, or NR-substituted. 8 R 9 , or oxo-substituted; optionally substituted with one or more hydroxyl, halogen, oxo, C1-C6 alkyl, or NR 8 R 9 Substituted 3- to 7-membered heterocyclic alkyl groups, wherein the C1-C6 alkoxy or C1-C6 alkyl group is further optionally substituted with one to three hydroxyl groups, halogenated, or NR-substituted. 8 R 9 Or oxy-substituted; C1-C6 haloalkyl; C1-C6 alkoxy; C1-C6 haloalkoxy; halogenated; CN; CO-C1-C6 alkyl; CO-C6-C 10 Aryl; CO (5- to 10-membered heteroaryl); CO2C1-C6 alkyl; CO2C3-C8 cycloalkyl; OCOC1-C6 alkyl; OCOC6-C 10 Aryl; OCO (5- to 10-membered heteroaryl); OCO (3- to 7-membered heterocycloalkyl); C6-C 10Aryl; 5- to 10-membered heteroaryl; NH2; NHC1-C6 alkyl; N(C1-C6 alkyl)2; CONR 8 R 9 ;SF5;S(O2)NR 11 R 12 ;S(O)C1-C6 alkyl; and S(O2)C1-C6 alkyl.

[1054] In some embodiments, R 1 When present, it is independently selected from the group consisting of: optionally substituted with one or more hydroxyl groups, halogenated, or NR. 8 R 9 Substituted C1-C6 alkyl groups.

[1055] In some embodiments, R 1 When present, select from the group consisting of: 1-hydroxy-2-methylpropyl-2-yl; 1,2-dihydroxy-2-propyl; methyl; ethyl; difluoromethyl; isopropyl; 2-hydroxy-2-propyl; hydroxymethyl; 1-hydroxyethyl; 2-hydroxyethyl; 1-hydroxy-2-propyl; 1-hydroxy-1-cyclopropyl; 1-hydroxy-1-cyclobutyl; 1-hydroxy-1-cyclopentyl; 1-hydroxy-1-cyclohexyl; morpholinyl; 1,3-dioxolanecyclo-2-yl; COCH3; COCH2CH3; 2-methoxy-2-propyl; (dimethylamino)methyl; (methylamino)methyl; 1-(dimethylamino)ethyl; fluorine; chlorine; phenyl; pyridyl; pyrazolyl; S(O2)CH3; and S(O2)NR 11 R 12 .

[1056] In some embodiments, R1, when present, is selected from the group consisting of: 1-hydroxy-2-methylpropyl-2-yl; methyl; difluoromethyl; isopropyl; 2-hydroxy-2-propyl; hydroxymethyl; 1-hydroxyethyl; 2-hydroxyethyl; 1-hydroxy-2-propyl; 1-hydroxy-1-cyclopropyl; 1-hydroxy-1-cyclobutyl; 1-hydroxy-1-cyclopentyl; 1-hydroxy-1-cyclohexyl; morpholinyl; 1,3-dioxolanecyclo-2-yl; COCH3; COCH2CH3; 2-methoxy-2-propyl; (dimethylamino)methyl; 1-(dimethylamino)ethyl; fluorine; chlorine; phenyl; pyridyl; pyrazolyl; S(O2)CH3; and S(O2)NR. 11 R 12 .

[1057] In some embodiments, R 1 When present, it is selected from the group consisting of: methyl; difluoromethyl; 2-hydroxy-2-propyl; hydroxymethyl; (dimethylamino)methyl; and fluorine. For example, R 1 It is 2-hydroxy-2-propyl. For example, R 1It's fluorine.

[1058] In some embodiments, R 1 When present, it is selected from the group consisting of: methyl; ethyl; difluoromethyl; 2-hydroxy-2-propyl; 1,2-dihydroxy-2-propyl; hydroxymethyl; (dimethylamino)methyl; (methylamino)methyl; and fluorine. For example, R 1 It is 2-hydroxy-2-propyl or 1,2-dihydroxy-2-propyl (e.g., R 1 It is 2-hydroxy-2-propyl; or R 1 It is 1,2-dihydroxy-2-propyl).

[1059] In some embodiments, R 2 When present, it is independently selected from the group consisting of: C1-C6 alkyl groups optionally substituted with one or more hydroxyl groups, optionally substituted with one or more halogenated, oxo-, C1-C6 alkoxy, or NR groups. 8 R 9 Substituted C1-C6 alkyl; optionally with one or more hydroxyl, halogenated, oxo-, C1-C6 alkoxy, C1-C6 alkyl, or NR 8 R 9 Substituted C3-C7 cycloalkyl groups, wherein the C1-C6 alkoxy or C1-C6 alkyl group is further optionally substituted with one to three hydroxyl groups, halogenated, or NR-substituted. 8 R 9 , or oxo-substituted; a 3- to 7-membered heterocyclic alkyl group optionally substituted with one or more hydroxyl, halogen, oxo, C1-C6 alkyl, or NR8R9, wherein the C1-C6 alkoxy or C1-C6 alkyl group is further optionally substituted with one to three hydroxyl, halogen, NR8R9, or oxo-substituted; C1-C6 haloalkyl; C1-C6 alkoxy; C1-C6 haloalkoxy; halogen; CN; CO-C1-C6 alkyl; CO-C6-C 10 Aryl; CO (5- to 10-membered heteroaryl); CO2C1-C6 alkyl; CO2C3-C8 cycloalkyl; OCOC1-C6 alkyl; OCOC6-C 10 Aryl; OCO (5- to 10-membered heteroaryl); OCO (3- to 7-membered heterocycloalkyl); C6-C 10 Aryl; 5- to 10-membered heteroaryl; NH2; NHC1-C6 alkyl; N(C1-C6 alkyl)2; CONR 8 R 9 ;SF5;S(O2)NR 11 R 12 ;S(O)C1-C6 alkyl; and S(O2)C1-C6 alkyl.

[1060] In some embodiments, R 2When present, it is independently selected from the group consisting of: optionally substituted with one or more hydroxyl groups, halogenated, or NR. 8 R 9 Substituted C1-C6 alkyl groups.

[1061] In some embodiments, R 2 When present, select from the group consisting of: 1-hydroxy-2-methylpropyl-2-yl; 1,2-dihydroxy-2-propyl; methyl; ethyl; difluoromethyl; isopropyl; 2-hydroxy-2-propyl; hydroxymethyl; 1-hydroxyethyl; 2-hydroxyethyl; 1-hydroxy-2-propyl; 1-hydroxy-1-cyclopropyl; 1-hydroxy-1-cyclobutyl; 1-hydroxy-1-cyclopentyl; 1-hydroxy-1-cyclohexyl; morpholinyl; 1,3-dioxolanecyclo-2-yl; COCH3; COCH2CH3; 2-methoxy-2-propyl; (dimethylamino)methyl; (methylamino)methyl; 1-(dimethylamino)ethyl; fluorine; chlorine; phenyl; pyridyl; pyrazolyl; S(O2)CH3; and S(O2)NR 11 R 12 .

[1062] In some embodiments, R 2 When present, select from the group consisting of: 1-hydroxy-2-methylpropyl-2-yl; methyl; difluoromethyl; isopropyl; 2-hydroxy-2-propyl; hydroxymethyl; 1-hydroxyethyl; 2-hydroxyethyl; 1-hydroxy-2-propyl; 1-hydroxy-1-cyclopropyl; 1-hydroxy-1-cyclobutyl; 1-hydroxy-1-cyclopentyl; 1-hydroxy-1-cyclohexyl; morpholinyl; 1,3-dioxolanecyclo-2-yl; COCH3; COCH2CH3; 2-methoxy-2-propyl; (dimethylamino)methyl; 1-(dimethylamino)ethyl; fluorine; chlorine; phenyl; pyridyl; pyrazolyl; S(O2)CH3; and S(O2)NR 11 R 12 .

[1063] In some embodiments, R 2 When present, the following groups are selected: methyl; ethyl; difluoromethyl; 2-hydroxy-2-propyl; hydroxymethyl; 1,2-dihydroxy-2-propyl; (dimethylamino)methyl; (methylamino)methyl; and fluorine.

[1064] In some embodiments, R 2 When present, the following groups are selected: methyl; difluoromethyl; 2-hydroxy-2-propyl; hydroxymethyl; (dimethylamino)methyl; and fluorine.

[1065] In some embodiments, one or more R 1 When present, it is independently a C1-C6 alkyl group substituted with one or more hydroxyl groups.

[1066] In some of these embodiments, one or more R 1 Independently selected from 1-hydroxy-2-methylpropan-2-yl; 2-hydroxy-2-propyl; hydroxymethyl; 1-hydroxyethyl; 2-hydroxyethyl; 1-hydroxy-2-propyl; 1,2-dihydroxy-2-propyl; and 1,2,3-trihydroxy-2-propyl.

[1067] In some embodiments, one or more R 1 When present, it is independently substituted by one or more hydroxyl groups and further substituted by one or more (e.g., one) NR 8 R 9 Substituted C1-C6 alkyl groups.

[1068] In some of these embodiments, one or more R 1 Independently selected from 1-amino-2-hydroxy-propan-2-yl; 1-acetamido-2-hydroxy-propan-2-yl; and 1-(tert-butoxycarbonyl)amino-2-hydroxy-propan-2-yl.

[1069] In some embodiments, one or more R 1 When present, it is independently substituted by one or more hydroxyl groups and further by one or more (e.g., one) R 15 Substituted C1-C6 alkyl groups.

[1070] In some of these embodiments (e.g., a2 = 1 or 2), one or more R 1 It is independently selected from 1-(2-hydroxyethoxy)-2-hydroxy-2-propyl; 1-(2-benzyloxyethoxy)-2-hydroxy-2-propyl; and 1-(2-methoxyethoxy)-2-hydroxy-2-propyl.

[1071] In some of these embodiments (e.g., a2 = 1), one or more R 1 It is independently selected from 1-(2-hydroxyethoxy)-2-hydroxy-2-propyl and 1-(2-methoxyethyl)-2-hydroxy-2-propyl.

[1072] In some embodiments (e.g., a2 = 1), one or more R 1 Independently selected from:

[1073]

[1074] In some embodiments (e.g., a2>1), one or more R 1 yes

[1075] In some embodiments, one or more R 1 Independently is controlled by one or more (e.g., one) NR8 R 9 C1-C6 alkyl substituted and further optionally substituted with one or more halo.

[1076] In some of these embodiments, one or more R 1 Independently selected from: (methylamino)methyl; (2,2-difluoroethyl-1-yl)(methyl)aminomethyl; (2,2,2-trifluoroethyl-1-yl)(methyl)aminomethyl; (dimethylamino)methyl; 1-(dimethylamino)ethyl; 2-((methyl)aminomethyl)-propyl-2-yl; 2-((methyl)amino)-propyl-2-yl; (methyl)(cyclopropylmethyl)aminomethyl; (methyl)(2-(dimethylamino)ethyl-1-yl)aminomethyl; (cyclobutyl)(methyl)aminomethyl; 1-(cyclobutyl)amino-ethyl-1-yl; isopropylaminomethyl; (cyclobutyl)aminomethyl ; cycloheptylaminomethyl; tetrahydropyranylaminomethyl; sec-butylaminomethyl; ethylaminomethyl; allylaminomethyl; (2,2-difluoroeth-1-yl)aminomethyl; (2-methoxy-eth-1-yl)aminomethyl; (2-methoxy-eth-1-yl)(methyl)aminomethyl; 2-fluoro-1-dimethylamino-eth-1-yl; 1-dimethylamino-2,2-difluoroeth-1-yl; 1-dimethylamino-2,2,2-trifluoroeth-1-yl; 1-dimethylamino-2,2,2-trimethyleth-1-yl; and dimethylamino(cyclopropyl)methyl (e.g., one or more R 1 is dimethylaminomethyl or methylaminomethyl).

[1077] In some embodiments, one or more R 1 is C1-C6 alkyl optionally substituted by one or more halo. In certain of these embodiments, one or more R 1 is a C2-C6 alkyl group optionally substituted with one or more halogen groups. As a non-limiting example, R 1 It is ethyl or difluoromethyl.

[1078] In some embodiments, one or more R 1 When present, it is a 3 to 7 membered heterocycloalkyl group optionally substituted with one or more oxo groups and further optionally substituted with one or more C1-C6 alkyl groups. For example, R 1 It is 5-methyl-oxazolidin-2-one-5-yl.

[1079] In R 1 Any of the foregoing embodiments wherein one or more R 2 Independently selected from C1-C6 alkyl, C1-C6 alkyl optionally substituted with one or more hydroxyl groups, C1-C6 alkyl optionally substituted with one or more C1-C6 alkoxy groups, and halo.

[1080] In some embodiments, R 1 and R 2 Located on adjacent atoms, and together with the atoms connecting them, independently forming a monocyclic or bicyclic C4-C ring. 12 A carbon ring (e.g., a C5 or C6 carbon ring) or a monocyclic or bicyclic 5- to 12-membered heterocycle, wherein a) when each of the adjacent atoms is a carbon atom, the heterocycle comprises 1 to 3 heteroatoms and / or heteroatom groups independently selected from: O, NH, NR 13 S, S(O), and S(O)2; and b) when one or both of the adjacent atoms are nitrogen atoms, the heterocycle comprises 0-2 heteroatoms and / or heteroatom groups independently selected from: O, NH, NR 13 S, S(O), and S(O)2 (except for the aforementioned connection to R) 1 and / or R 2 (excluding one or more nitrogen atoms), and wherein the carbocyclic or heterocyclic ring is optionally independently substituted by one or more substituents each independently selected from: hydroxyl, halogen, oxo, C1-C6 alkyl (e.g., methyl), C2-C6 alkenyl, C2-C6 alkoxy (e.g., isopropoxy), C1-C6 alkoxy (e.g., isopropoxy), OC3-C 10 Cycloalkyl, NR 8 R 9 、=NR 10 CN, COOC1-C6 alkyl, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, 3- to 10-membered heterocycloalkyl (eg, azetidinyl or oxetanyl), and CONR 8 R 9 The C1-C6 alkyl, C1-C6 alkoxy, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 The cycloalkyl and 3- to 10-membered heterocycloalkyl groups are optionally substituted by one or more substituents, each independently selected from the following: hydroxyl, halogen (e.g., fluorine), C1-C6 alkyl, C2-C6 alkenyl, C2-C6 ynyl, C3-C 10 Cycloalkyl, C1-C6 alkoxy, oxo, NR 8 R 9 (e.g., amino, methylamino, or dimethylamino), =NR 10 COOC1-C6 alkyl, C6-C 10 Aryl and CONR8 R 9 .

[1081] In some embodiments, R 1 and R 2 Located on adjacent atoms and together with the atoms connecting them, independently forming a monocyclic or bicyclic C5-C6 carbon ring, said carbon ring optionally and independently being substituted by one or more substituents each independently selected from the following: hydroxyl, halogen, oxo, methyl, isopropoxy, aziridine, oxetidine, wherein said methyl, isopropoxy, aziridine, and oxetidine are optionally substituted by one or more substituents each independently selected from the following: hydroxyl, fluorine, amino, methylamino, and dimethylamino; or

[1082] R 1 and R 2 Located on adjacent atoms, and formed together independently. Each of these substituents is optionally substituted by one or more substituents independently selected from the following: hydroxyl, halogen, oxo, methyl, isopropoxy, aziridine, oxetidine, wherein the methyl, isopropoxy, aziridine, and oxetidine are optionally substituted by one or more substituents independently selected from the following: hydroxyl, fluorine, amino, methylamino, and dimethylamino; wherein the asterisk indicates a connection point with a carbon atom; and the Indicates the connection point with a carbon or nitrogen atom.

[1083] In some embodiments, R 1 and R 2 Located on adjacent atoms, and taken together with the atoms connecting them, independently form at least one bicyclic spiro C4-C 12 A carbon ring, wherein the carbon ring is optionally substituted by one or more substituents each independently selected from the following: hydroxyl, halogen, oxo, methyl, isopropoxy, aziridine, oxetidine, wherein the methyl, isopropoxy, aziridine, and oxetidine are optionally substituted by one or more substituents each independently selected from the following: hydroxyl, fluorine, amino, methylamino, and dimethylamino.

[1084] In some embodiments, R 1 and R 2 Located on adjacent atoms, and taken together with the atoms connecting them, independently form at least one bicyclic spirocyclic 5- to 12-membered heterocycle, wherein a) when each of the adjacent atoms is a carbon atom, the heterocycle contains from 1 to 3 heteroatoms and / or heteroatom groups independently selected from the following: O, NH, NR 13S, S(O), and S(O)2; and b) when one or both of the adjacent atoms are nitrogen atoms, the heterocycle comprises 0-2 heteroatoms and / or heteroatom groups independently selected from: O, NH, NR 13 S, S(O), and S(O)2 (except for the aforementioned connection to R) 1 and / or R 2 wherein the carbocyclic or heterocyclic ring is optionally substituted with one or more substituents each independently selected from the group consisting of hydroxy, halo, oxo, methyl, isopropoxy, azetidinyl, oxetanyl, wherein the methyl, isopropoxy, azetidinyl, and oxetanyl are optionally substituted with one or more substituents each independently selected from the group consisting of hydroxy, fluoro, amino, methylamino, and dimethylamino.

[1085] In some embodiments, R 1 and R 2 are different.

[1086] In some embodiments, R 1 and R 2 They are the same.

[1087] In some embodiments, R 1 Located in R 2 The opposite or intermediate position.

[1088] In some embodiments, R 1 Located in R 2 para or ortho position.

[1089] In some embodiments, R 1 Located in R 2 ortho or meta position.

[1090] In some embodiments, R 1 Located in R 2 counterpoint.

[1091] In some embodiments, R 1 Located in R 2 The position of the interval.

[1092] In some embodiments, R 1 Located in R 2 The adjacent position.

[1093] When the formula AA is the group R of the formula AA-1 1 and R 2

[1094] In some embodiments, R 1When present, it is independently selected from the group consisting of: C1-C6 alkyl groups optionally substituted with one or more hydroxyl groups, optionally substituted with one or more halogenated, oxo-, C1-C6 alkoxy, or NR groups. 8 R 9 Substituted C1-C6 alkyl; optionally with one or more hydroxyl, halogenated, oxo-, C1-C6 alkoxy, C1-C6 alkyl, or NR 8 R 9 Substituted C3-C7 cycloalkyl groups, wherein the C1-C6 alkoxy or C1-C6 alkyl group is further optionally substituted with one to three hydroxyl groups, halogenated, or NR-substituted. 8 R 9 , or oxo-substituted; a 3- to 7-membered heterocyclic alkyl group optionally substituted with one or more hydroxyl, halogen, oxo, C1-C6 alkyl, or NR8R9, wherein the C1-C6 alkoxy or C1-C6 alkyl group is further optionally substituted with one to three hydroxyl, halogen, NR8R9, or oxo-substituted; C1-C6 haloalkyl; C1-C6 alkoxy; C1-C6 haloalkoxy; halogen; CN; CO-C1-C6 alkyl; CO-C6-C 10 Aryl; CO (5- to 10-membered heteroaryl); CO2C1-C6 alkyl; CO2C3-C8 cycloalkyl; OCOC1-C6 alkyl; OCOC6-C 10 Aryl; OCO (5- to 10-membered heteroaryl); OCO (3- to 7-membered heterocycloalkyl); C6-C 10 Aryl; 5- to 10-membered heteroaryl; NH2; NHC1-C6 alkyl; N(C1-C6 alkyl)2; CONR 8 R 9 ;SF5;S(O2)NR 11 R 12 ;S(O)C1-C6 alkyl; and S(O2)C1-C6 alkyl.

[1095] In some embodiments, R 1 When present, it is independently selected from the group consisting of: optionally substituted with one or more hydroxyl groups, halogenated, or NR. 8 R 9 Substituted C1-C6 alkyl groups.

[1096] In some embodiments, R 1When present, select from the group consisting of: 1-hydroxy-2-methylpropyl-2-yl; 1,2-dihydroxy-2-propyl; methyl; ethyl; difluoromethyl; isopropyl; 2-hydroxy-2-propyl; hydroxymethyl; 1-hydroxyethyl; 2-hydroxyethyl; 1-hydroxy-2-propyl; 1-hydroxy-1-cyclopropyl; 1-hydroxy-1-cyclobutyl; 1-hydroxy-1-cyclopentyl; 1-hydroxy-1-cyclohexyl; morpholinyl; 1,3-dioxolanecyclo-2-yl; COCH3; COCH2CH3; 2-methoxy-2-propyl; (dimethylamino)methyl; (methylamino)methyl; 1-(dimethylamino)ethyl; fluorine; chlorine; phenyl; pyridyl; pyrazolyl; S(O2)CH3; and S(O2)NR 11 R 12 .

[1097] In some embodiments, R 1 When present, select from the group consisting of: 1-hydroxy-2-methylpropyl-2-yl; methyl; difluoromethyl; isopropyl; 2-hydroxy-2-propyl; hydroxymethyl; 1-hydroxyethyl; 2-hydroxyethyl; 1-hydroxy-2-propyl; 1-hydroxy-1-cyclopropyl; 1-hydroxy-1-cyclobutyl; 1-hydroxy-1-cyclopentyl; 1-hydroxy-1-cyclohexyl; morpholinyl; 1,3-dioxolanecyclo-2-yl; COCH3; COCH2CH3; 2-methoxy-2-propyl; (dimethylamino)methyl; 1-(dimethylamino)ethyl; fluorine; chlorine; phenyl; pyridyl; pyrazolyl; S(O2)CH3; and S(O2)NR 11 R 12 .

[1098] In some embodiments, R 1 When present, it is selected from the group consisting of: methyl; ethyl; difluoromethyl; 2-hydroxy-2-propyl; 1,2-dihydroxy-2-propyl; hydroxymethyl; (dimethylamino)methyl; (methylamino)methyl; and fluorine. For example, R 1 It is 2-hydroxy-2-propyl or 1,2-dihydroxy-2-propyl (e.g., R 1 It is 2-hydroxy-2-propyl; or R 1 It is 1,2-dihydroxy-2-propyl).

[1099] In some embodiments, R 1 When present, it is selected from the group consisting of: methyl; difluoromethyl; 2-hydroxy-2-propyl; hydroxymethyl; (dimethylamino)methyl; and fluorine. For example, R 1 It is 2-hydroxy-2-propyl. For example, R 1 It's fluorine.

[1100] In some embodiments, R 2When present, it is independently selected from the group consisting of: C1-C6 alkyl groups optionally substituted with one or more hydroxyl groups, optionally substituted with one or more halogenated, oxo-, C1-C6 alkoxy, or NR groups. 8 R 9 Substituted C1-C6 alkyl; optionally with one or more hydroxyl, halogenated, oxo-, C1-C6 alkoxy, C1-C6 alkyl, or NR 8 R 9 Substituted C3-C7 cycloalkyl groups, wherein the C1-C6 alkoxy or C1-C6 alkyl group is further optionally substituted with one to three hydroxyl groups, halogenated, or NR-substituted. 8 R 9 , or oxo-substituted; a 3- to 7-membered heterocyclic alkyl group optionally substituted with one or more hydroxyl, halogen, oxo, C1-C6 alkyl, or NR8R9, wherein the C1-C6 alkoxy or C1-C6 alkyl group is further optionally substituted with one to three hydroxyl, halogen, NR8R9, or oxo-substituted; C1-C6 haloalkyl; C1-C6 alkoxy; C1-C6 haloalkoxy; halogen; CN; CO-C1-C6 alkyl; CO-C6-C 10 Aryl; CO (5- to 10-membered heteroaryl); CO2C1-C6 alkyl; CO2C3-C8 cycloalkyl; OCOC1-C6 alkyl; OCOC6-C 10 Aryl; OCO (5- to 10-membered heteroaryl); OCO (3- to 7-membered heterocycloalkyl); C6-C 10 Aryl; 5- to 10-membered heteroaryl; NH2; NHC1-C6 alkyl; N(C1-C6 alkyl)2; CONR 8 R 9 ;SF5;S(O2)NR 11 R 12 ;S(O)C1-C6 alkyl; and S(O2)C1-C6 alkyl.

[1101] In some embodiments, R 2 When present, it is independently selected from the group consisting of: optionally substituted with one or more hydroxyl groups, halogenated, or NR. 8 R 9 Substituted C1-C6 alkyl groups.

[1102] In some embodiments, R 2When present, select from the group consisting of: 1-hydroxy-2-methylpropyl-2-yl; 1,2-dihydroxy-2-propyl; methyl; ethyl; difluoromethyl; isopropyl; 2-hydroxy-2-propyl; hydroxymethyl; 1-hydroxyethyl; 2-hydroxyethyl; 1-hydroxy-2-propyl; 1-hydroxy-1-cyclopropyl; 1-hydroxy-1-cyclobutyl; 1-hydroxy-1-cyclopentyl; 1-hydroxy-1-cyclohexyl; morpholinyl; 1,3-dioxolanecyclo-2-yl; COCH3; COCH2CH3; 2-methoxy-2-propyl; (dimethylamino)methyl; (methylamino)methyl; 1-(dimethylamino)ethyl; fluorine; chlorine; phenyl; pyridyl; pyrazolyl; S(O2)CH3; and S(O2)NR 11 R 12 .

[1103] In some embodiments, R 2 When present, select from the group consisting of: 1-hydroxy-2-methylpropyl-2-yl; methyl; difluoromethyl; isopropyl; 2-hydroxy-2-propyl; hydroxymethyl; 1-hydroxyethyl; 2-hydroxyethyl; 1-hydroxy-2-propyl; 1-hydroxy-1-cyclopropyl; 1-hydroxy-1-cyclobutyl; 1-hydroxy-1-cyclopentyl; 1-hydroxy-1-cyclohexyl; morpholinyl; 1,3-dioxolanecyclo-2-yl; COCH3; COCH2CH3; 2-methoxy-2-propyl; (dimethylamino)methyl; 1-(dimethylamino)ethyl; fluorine; chlorine; phenyl; pyridyl; pyrazolyl; S(O2)CH3; and S(O2)NR 11 R 12 .

[1104] In some embodiments, R 2 When present, the following groups are selected: methyl; ethyl; difluoromethyl; 2-hydroxy-2-propyl; hydroxymethyl; 1,2-dihydroxy-2-propyl; (dimethylamino)methyl; (methylamino)methyl; and fluorine.

[1105] In some embodiments of compounds of Formula AA-1, R 2 When present, the following groups are selected: methyl; difluoromethyl; 2-hydroxy-2-propyl; hydroxymethyl; (dimethylamino)methyl; and fluorine.

[1106] In some embodiments, one or more R 1 When present, it is independently a C1-C6 alkyl group substituted with one or more hydroxyl groups.

[1107] In some of these embodiments, one or more R 1Independently selected from 1-hydroxy-2-methylpropan-2-yl; 2-hydroxy-2-propyl; hydroxymethyl; 1-hydroxyethyl; 2-hydroxyethyl; 1-hydroxy-2-propyl; 1,2-dihydroxy-2-propyl; and 1,2,3-trihydroxy-2-propyl.

[1108] In some embodiments, one or more R 1 When present, it is independently substituted by one or more hydroxyl groups and further substituted by one or more (e.g., one) NR 8 R 9 Substituted C1-C6 alkyl groups.

[1109] In some of these embodiments, one or more R 1 Independently selected from 1-amino-2-hydroxy-propan-2-yl; 1-acetamido-2-hydroxy-propan-2-yl; and 1-(tert-butoxycarbonyl)amino-2-hydroxy-propan-2-yl.

[1110] In some embodiments, one or more R 1 When present, it is independently substituted by one or more hydroxyl groups and further by one or more (e.g., one) R 15 Substituted C1-C6 alkyl groups.

[1111] In some of these embodiments (e.g., a2 = 1 or 2), one or more R 1 It is independently selected from 1-(2-hydroxyethoxy)-2-hydroxy-2-propyl; 1-(2-benzyloxyethoxy)-2-hydroxy-2-propyl; and 1-(2-methoxyethoxy)-2-hydroxy-2-propyl.

[1112] In some of these embodiments (e.g., a2 = 1), one or more R 1 It is independently selected from 1-(2-hydroxyethoxy)-2-hydroxy-2-propyl and 1-(2-methoxyethyl)-2-hydroxy-2-propyl.

[1113] In some embodiments (e.g., a2 = 1), one or more R 1 Independently selected from:

[1114] as well as

[1115] In some embodiments (e.g., a2>1), one or more R 1 yes

[1116] In some embodiments, one or more R 1 Independently is controlled by one or more (e.g., one) NR 8 R 9C1-C6 alkyl substituted and further optionally substituted with one or more halo.

[1117] In some of these embodiments, one or more R 1 Independently selected from: (methylamino)methyl; (2,2-difluoroethyl-1-yl)(methyl)aminomethyl; (2,2,2-trifluoroethyl-1-yl)(methyl)aminomethyl; (dimethylamino)methyl; 1-(dimethylamino)ethyl; 2-((methyl)aminomethyl)-propyl-2-yl; 2-((methyl)amino)-propyl-2-yl; (methyl)(cyclopropylmethyl)aminomethyl; (methyl)(2-(dimethylamino)ethyl-1-yl)aminomethyl; (cyclobutyl)(methyl)aminomethyl; 1-(cyclobutyl)amino-ethyl-1-yl; isopropylaminomethyl; (cyclobutyl)aminomethyl ; cycloheptylaminomethyl; tetrahydropyranylaminomethyl; sec-butylaminomethyl; ethylaminomethyl; allylaminomethyl; (2,2-difluoroeth-1-yl)aminomethyl; (2-methoxy-eth-1-yl)aminomethyl; (2-methoxy-eth-1-yl)(methyl)aminomethyl; 2-fluoro-1-dimethylamino-eth-1-yl; 1-dimethylamino-2,2-difluoroeth-1-yl; 1-dimethylamino-2,2,2-trifluoroeth-1-yl; 1-dimethylamino-2,2,2-trimethyleth-1-yl; and dimethylamino(cyclopropyl)methyl (e.g., one or more R 1 is dimethylaminomethyl or methylaminomethyl).

[1118] In some embodiments, one or more R 1 is C1-C6 alkyl optionally substituted by one or more halo. In certain of these embodiments, one or more R 1 is a C2-C6 alkyl group optionally substituted with one or more halogen groups. As a non-limiting example, R 1 It is ethyl or difluoromethyl.

[1119] In some embodiments, one or more R 1 When present, it is a 3 to 7 membered heterocycloalkyl group optionally substituted with one or more oxo groups and further optionally substituted with one or more C1-C6 alkyl groups. For example, R 1 It is 5-methyl-oxazolidin-2-one-5-yl.

[1120] In R 1 Any of the foregoing embodiments wherein one or more R 2 Independently selected from C1-C6 alkyl, C1-C6 alkyl optionally substituted with one or more hydroxyl groups, C1-C6 alkyl optionally substituted with one or more C1-C6 alkoxy groups, and halo.

[1121] In some embodiments of compounds of Formula AA-1, R 1 and R 2 Located on adjacent atoms, and together with the atoms connecting them, independently forming a monocyclic or bicyclic C4-C ring. 12 A carbon ring (e.g., a C5 or C6 carbon ring) or a monocyclic or bicyclic 5- to 12-membered heterocycle, wherein a) when each of the adjacent atoms is a carbon atom, the heterocycle comprises 1 to 3 heteroatoms and / or heteroatom groups independently selected from: O, NH, NR 13 S, S(O), and S(O)2; and b) when one or both of the adjacent atoms are nitrogen atoms, the heterocycle comprises 0-2 heteroatoms and / or heteroatom groups independently selected from: O, NH, NR 13 S, S(O), and S(O)2 (except for the aforementioned connection to R) 1 and / or R 2 (excluding one or more nitrogen atoms), and wherein the carbocyclic or heterocyclic ring is optionally independently substituted by one or more substituents each independently selected from: hydroxyl, halogen, oxo, C1-C6 alkyl (e.g., methyl), C2-C6 alkenyl, C2-C6 alkoxy (e.g., isopropoxy), C1-C6 alkoxy (e.g., isopropoxy), OC3-C 10 Cycloalkyl, NR 8 R 9 、=NR 10 CN, COOC1-C6 alkyl, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, 3- to 10-membered heterocycloalkyl (eg, azetidinyl or oxetanyl), and CONR 8 R 9 The C1-C6 alkyl, C1-C6 alkoxy, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 The cycloalkyl and 3- to 10-membered heterocycloalkyl groups are optionally substituted by one or more substituents, each independently selected from the following: hydroxyl, halogen (e.g., fluorine), C1-C6 alkyl, C2-C6 alkenyl, C2-C6 ynyl, C3-C 10 Cycloalkyl, C1-C6 alkoxy, oxo, NR 8 R 9 (e.g., amino, methylamino, or dimethylamino), =NR 10 COOC1-C6 alkyl, C6-C 10 Aryl and CONR 8 R9 .

[1122] In some embodiments of compounds of Formula AA-1, R 1 and R 2 Located on adjacent atoms and together with the atoms connecting them, independently forming a monocyclic or bicyclic C5-C6 carbon ring, said carbon ring optionally and independently being substituted by one or more substituents each independently selected from the following: hydroxyl, halogen, oxo, methyl, isopropoxy, aziridine, oxetidine, wherein said methyl, isopropoxy, aziridine, and oxetidine are optionally substituted by one or more substituents each independently selected from the following: hydroxyl, fluorine, amino, methylamino, and dimethylamino; or

[1123] R 1 and R 2 Located on adjacent atoms, and formed together independently. Each of these substituents is optionally substituted by one or more substituents independently selected from the following: hydroxyl, halogen, oxo, methyl, isopropoxy, aziridine, oxetidine, wherein the methyl, isopropoxy, aziridine, and oxetidine are optionally substituted by one or more substituents independently selected from the following: hydroxyl, fluorine, amino, methylamino, and dimethylamino; wherein the asterisk indicates a connection point with a carbon atom; and the Indicates the connection point with a carbon or nitrogen atom.

[1124] In some embodiments of compounds of Formula AA-1, R 1 and R 2 Located on adjacent atoms, and taken together with the atoms connecting them, independently form at least one bicyclic spiro C4-C 12 A carbon ring, wherein the carbon ring is optionally substituted by one or more substituents each independently selected from the following: hydroxyl, halogen, oxo, methyl, isopropoxy, aziridine, oxetidine, wherein the methyl, isopropoxy, aziridine, and oxetidine are optionally substituted by one or more substituents each independently selected from the following: hydroxyl, fluorine, amino, methylamino, and dimethylamino.

[1125] In some embodiments of compounds of Formula AA-1, R 1 and R 2 Located on adjacent atoms, and taken together with the atoms connecting them, independently form at least one bicyclic spirocyclic 5- to 12-membered heterocycle, wherein a) when each of the adjacent atoms is a carbon atom, the heterocycle contains from 1 to 3 heteroatoms and / or heteroatom groups independently selected from the following: O, NH, NR 13S, S(O), and S(O)2; and b) when one or both of the adjacent atoms are nitrogen atoms, the heterocycle comprises 0-2 heteroatoms and / or heteroatom groups independently selected from: O, NH, NR 13 S, S(O), and S(O)2 (except for the aforementioned connection to R) 1 and / or R 2 wherein the carbocyclic or heterocyclic ring is optionally substituted with one or more substituents each independently selected from the group consisting of hydroxy, halo, oxo, methyl, isopropoxy, azetidinyl, oxetanyl, wherein the methyl, isopropoxy, azetidinyl, and oxetanyl are optionally substituted with one or more substituents each independently selected from the group consisting of hydroxy, fluoro, amino, methylamino, and dimethylamino.

[1126] When the formula AA is the group R of the formula AA-2 1 and R 2

[1127] In some embodiments, R 1 When present, it is independently selected from the group consisting of: C1-C6 alkyl groups optionally substituted with one or more hydroxyl groups, optionally substituted with one or more halogenated, oxo-, C1-C6 alkoxy, or NR groups. 8 R 9 Substituted C1-C6 alkyl; optionally with one or more hydroxyl, halogenated, oxo-, C1-C6 alkoxy, C1-C6 alkyl, or NR 8 R 9 Substituted C3-C7 cycloalkyl groups, wherein the C1-C6 alkoxy or C1-C6 alkyl group is further optionally substituted with one to three hydroxyl groups, halogenated, or NR-substituted. 8 R 9 , or oxo-substituted; a 3- to 7-membered heterocyclic alkyl group optionally substituted with one or more hydroxyl, halogen, oxo, C1-C6 alkyl, or NR8R9, wherein the C1-C6 alkoxy or C1-C6 alkyl group is further optionally substituted with one to three hydroxyl, halogen, NR8R9, or oxo-substituted; C1-C6 haloalkyl; C1-C6 alkoxy; C1-C6 haloalkoxy; halogen; CN; CO-C1-C6 alkyl; CO-C6-C 10 Aryl; CO (5- to 10-membered heteroaryl); CO2C1-C6 alkyl; CO2C3-C8 cycloalkyl; OCOC1-C6 alkyl; OCOC6-C 10 Aryl; OCO (5- to 10-membered heteroaryl); OCO (3- to 7-membered heterocycloalkyl); C6-C 10 Aryl; 5- to 10-membered heteroaryl; NH2; NHC1-C6 alkyl; N(C1-C6 alkyl)2; CONR 8 R9 ;SF5;S(O2)NR 11 R 12 ;S(O)C1-C6 alkyl; and S(O2)C1-C6 alkyl.

[1128] In some embodiments, R 1 When present, it is independently selected from the group consisting of: optionally substituted with one or more hydroxyl groups, halogenated, or NR. 8 R 9 Substituted C1-C6 alkyl groups.

[1129] In some embodiments, R 1 When present, select from the group consisting of: 1-hydroxy-2-methylpropyl-2-yl; 1,2-dihydroxy-2-propyl; methyl; ethyl; difluoromethyl; isopropyl; 2-hydroxy-2-propyl; hydroxymethyl; 1-hydroxyethyl; 2-hydroxyethyl; 1-hydroxy-2-propyl; 1-hydroxy-1-cyclopropyl; 1-hydroxy-1-cyclobutyl; 1-hydroxy-1-cyclopentyl; 1-hydroxy-1-cyclohexyl; morpholinyl; 1,3-dioxolanecyclo-2-yl; COCH3; COCH2CH3; 2-methoxy-2-propyl; (dimethylamino)methyl; (methylamino)methyl; 1-(dimethylamino)ethyl; fluorine; chlorine; phenyl; pyridyl; pyrazolyl; S(O2)CH3; and S(O2)NR 11 R 12 .

[1130] In some embodiments, R 1 When present, select from the group consisting of: 1-hydroxy-2-methylpropyl-2-yl; methyl; difluoromethyl; isopropyl; 2-hydroxy-2-propyl; hydroxymethyl; 1-hydroxyethyl; 2-hydroxyethyl; 1-hydroxy-2-propyl; 1-hydroxy-1-cyclopropyl; 1-hydroxy-1-cyclobutyl; 1-hydroxy-1-cyclopentyl; 1-hydroxy-1-cyclohexyl; morpholinyl; 1,3-dioxolanecyclo-2-yl; COCH3; COCH2CH3; 2-methoxy-2-propyl; (dimethylamino)methyl; 1-(dimethylamino)ethyl; fluorine; chlorine; phenyl; pyridyl; pyrazolyl; S(O2)CH3; and S(O2)NR 11 R 12 .

[1131] In some embodiments, R 1 When present, it is selected from the group consisting of: methyl; difluoromethyl; 2-hydroxy-2-propyl; hydroxymethyl; (dimethylamino)methyl; and fluorine. For example, R 1 It is 2-hydroxy-2-propyl. For example, R 1 It's fluorine.

[1132] In some embodiments, R1 When present, it is selected from the group consisting of: methyl; ethyl; difluoromethyl; 2-hydroxy-2-propyl; 1,2-dihydroxy-2-propyl; hydroxymethyl; (dimethylamino)methyl; (methylamino)methyl; and fluorine. For example, R 1 When present, it is 2-hydroxy-2-propyl or 1,2-dihydroxy-2-propyl (e.g., R...). 1 It is 2-hydroxy-2-propyl; or R 1 It is 1,2-dihydroxy-2-propyl).

[1133] In some embodiments, R 2 When present, it is independently selected from the group consisting of: C1-C6 alkyl groups optionally substituted with one or more hydroxyl groups, optionally substituted with one or more halogenated, oxo-, C1-C6 alkoxy, or NR groups. 8 R 9 Substituted C1-C6 alkyl; optionally with one or more hydroxyl, halogenated, oxo-, C1-C6 alkoxy, C1-C6 alkyl, or NR 8 R 9 Substituted C3-C7 cycloalkyl groups, wherein the C1-C6 alkoxy or C1-C6 alkyl group is further optionally substituted with one to three hydroxyl groups, halogenated, or NR-substituted. 8 R 9 , or oxo-substituted; a 3- to 7-membered heterocyclic alkyl group optionally substituted with one or more hydroxyl, halogen, oxo, C1-C6 alkyl, or NR8R9, wherein the C1-C6 alkoxy or C1-C6 alkyl group is further optionally substituted with one to three hydroxyl, halogen, NR8R9, or oxo-substituted; C1-C6 haloalkyl; C1-C6 alkoxy; C1-C6 haloalkoxy; halogen; CN; CO-C1-C6 alkyl; CO-C6-C 10 Aryl; CO (5- to 10-membered heteroaryl); CO2C1-C6 alkyl; CO2C3-C8 cycloalkyl; OCOC1-C6 alkyl; OCOC6-C 10 Aryl; OCO (5- to 10-membered heteroaryl); OCO (3- to 7-membered heterocycloalkyl); C6-C 10 Aryl; 5- to 10-membered heteroaryl; NH2; NHC1-C6 alkyl; N(C1-C6 alkyl)2; CONR 8 R 9 ;SF5;S(O2)NR 11 R 12 ;S(O)C1-C6 alkyl; and S(O2)C1-C6 alkyl.

[1134] In some embodiments, R 2 When present, it is independently selected from the group consisting of: optionally substituted with one or more hydroxyl groups, halogenated, or NR. 8 R9 Substituted C1-C6 alkyl groups.

[1135] In some embodiments, R 2 When present, select from the group consisting of: 1-hydroxy-2-methylpropyl-2-yl; 1,2-dihydroxy-2-propyl; methyl; ethyl; difluoromethyl; isopropyl; 2-hydroxy-2-propyl; hydroxymethyl; 1-hydroxyethyl; 2-hydroxyethyl; 1-hydroxy-2-propyl; 1-hydroxy-1-cyclopropyl; 1-hydroxy-1-cyclobutyl; 1-hydroxy-1-cyclopentyl; 1-hydroxy-1-cyclohexyl; morpholinyl; 1,3-dioxolanecyclo-2-yl; COCH3; COCH2CH3; 2-methoxy-2-propyl; (dimethylamino)methyl; (methylamino)methyl; 1-(dimethylamino)ethyl; fluorine; chlorine; phenyl; pyridyl; pyrazolyl; S(O2)CH3; and S(O2)NR 11 R 12 .

[1136] In some embodiments, R 2 When present, select from the group consisting of: 1-hydroxy-2-methylpropyl-2-yl; methyl; difluoromethyl; isopropyl; 2-hydroxy-2-propyl; hydroxymethyl; 1-hydroxyethyl; 2-hydroxyethyl; 1-hydroxy-2-propyl; 1-hydroxy-1-cyclopropyl; 1-hydroxy-1-cyclobutyl; 1-hydroxy-1-cyclopentyl; 1-hydroxy-1-cyclohexyl; morpholinyl; 1,3-dioxolanecyclo-2-yl; COCH3; COCH2CH3; 2-methoxy-2-propyl; (dimethylamino)methyl; 1-(dimethylamino)ethyl; fluorine; chlorine; phenyl; pyridyl; pyrazolyl; S(O2)CH3; and S(O2)NR 11 R 12 .

[1137] In some embodiments, R 2 When present, the following groups are selected: methyl; ethyl; difluoromethyl; 2-hydroxy-2-propyl; 1,2-dihydroxy-2-propyl; hydroxymethyl; (dimethylamino)methyl; (methylamino)methyl; and fluorine.

[1138] In some embodiments, R 2 When present, the following groups are selected: methyl; difluoromethyl; 2-hydroxy-2-propyl; hydroxymethyl; (dimethylamino)methyl; and fluorine.

[1139] In some embodiments, one or more R 1 When present, it is independently a C1-C6 alkyl group substituted with one or more hydroxyl groups.

[1140] In some of these embodiments, one or more R 1Independently selected from 1-hydroxy-2-methylpropan-2-yl; 2-hydroxy-2-propyl; hydroxymethyl; 1-hydroxyethyl; 2-hydroxyethyl; 1-hydroxy-2-propyl; 1,2-dihydroxy-2-propyl; and 1,2,3-trihydroxy-2-propyl.

[1141] In some embodiments, one or more R 1 When present, it is independently substituted by one or more hydroxyl groups and further substituted by one or more (e.g., one) NR 8 R 9 Substituted C1-C6 alkyl groups.

[1142] In some of these embodiments, one or more R 1 Independently selected from 1-amino-2-hydroxy-propan-2-yl; 1-acetamido-2-hydroxy-propan-2-yl; and 1-(tert-butoxycarbonyl)amino-2-hydroxy-propan-2-yl.

[1143] In some embodiments, one or more R 1 When present, it is independently substituted by one or more hydroxyl groups and further by one or more (e.g., one) R 15 Substituted C1-C6 alkyl groups.

[1144] In some of these embodiments (e.g., a2 = 1 or 2), one or more R 1 It is independently selected from 1-(2-hydroxyethoxy)-2-hydroxy-2-propyl; 1-(2-benzyloxyethoxy)-2-hydroxy-2-propyl; and 1-(2-methoxyethoxy)-2-hydroxy-2-propyl.

[1145] In some of these embodiments (e.g., a2 = 1), one or more R 1 It is independently selected from 1-(2-hydroxyethoxy)-2-hydroxy-2-propyl and 1-(2-methoxyethyl)-2-hydroxy-2-propyl.

[1146] In some embodiments (e.g., a2 = 1), one or more R 1 Independently selected from:

[1147] as well as

[1148] In some embodiments (e.g., a2>1), one or more R 1 yes

[1149] In some embodiments, one or more R 1 Independently is controlled by one or more (e.g., one) NR 8 R 9C1-C6 alkyl substituted and further optionally substituted with one or more halo.

[1150] In some of these embodiments, one or more R 1 Independently selected from: (methylamino)methyl; (2,2-difluoroethyl-1-yl)(methyl)aminomethyl; (2,2,2-trifluoroethyl-1-yl)(methyl)aminomethyl; (dimethylamino)methyl; 1-(dimethylamino)ethyl; 2-((methyl)aminomethyl)-propyl-2-yl; 2-((methyl)amino)-propyl-2-yl; (methyl)(cyclopropylmethyl)aminomethyl; (methyl)(2-(dimethylamino)ethyl-1-yl)aminomethyl; (cyclobutyl)(methyl)aminomethyl; 1-(cyclobutyl)amino-ethyl-1-yl; isopropylaminomethyl; (cyclobutyl)aminomethyl ; cycloheptylaminomethyl; tetrahydropyranylaminomethyl; sec-butylaminomethyl; ethylaminomethyl; allylaminomethyl; (2,2-difluoroeth-1-yl)aminomethyl; (2-methoxy-eth-1-yl)aminomethyl; (2-methoxy-eth-1-yl)(methyl)aminomethyl; 2-fluoro-1-dimethylamino-eth-1-yl; 1-dimethylamino-2,2-difluoroeth-1-yl; 1-dimethylamino-2,2,2-trifluoroeth-1-yl; 1-dimethylamino-2,2,2-trimethyleth-1-yl; and dimethylamino(cyclopropyl)methyl (e.g., one or more R 1 is dimethylaminomethyl or methylaminomethyl).

[1151] In some embodiments, one or more R 1 is C1-C6 alkyl optionally substituted by one or more halo. In certain of these embodiments, one or more R 1 is a C2-C6 alkyl group optionally substituted with one or more halogen groups. As a non-limiting example, R 1 It is ethyl or difluoromethyl.

[1152] In some embodiments, one or more R 1 When present, it is a 3 to 7 membered heterocycloalkyl group optionally substituted with one or more oxo groups and further optionally substituted with one or more C1-C6 alkyl groups. For example, R 1 It is 5-methyl-oxazolidin-2-one-5-yl.

[1153] In R 1 Any of the foregoing embodiments wherein one or more R 2 Independently selected from C1-C6 alkyl, C1-C6 alkyl optionally substituted with one or more hydroxyl groups, C1-C6 alkyl optionally substituted with one or more C1-C6 alkoxy groups, and halo.

[1154] In some embodiments, when the compound having formula AA is a compound having formula AA-2, a pair of R atoms located on adjacent atoms 1 and R 2 Together with the atoms that connect them, they independently form a monocyclic or bicyclic C4-C ring. 12 A carbon ring or a monocyclic or bicyclic 5- to 12-membered heterocycle, said heterocycle comprising 1 to 3 heteroatoms and / or heteroatom groups independently selected from the following: O, NH, NR. 13 S, S(O), and S(O)2, wherein the carbocyclic or heterocyclic ring is optionally and independently substituted by one or more substituents independently selected from the following: hydroxyl, halogenated, oxo-substituted, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, OC3-C 10 Cycloalkyl, NR 8 R 9 、=NR 10 、CN、COOC1-C6 alkyl、OS(O2)C6-C 10 Aryl, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, 3- to 10-membered heterocycloalkyl, and CONR 8 R 9 The C1-C6 alkyl, C1-C6 alkoxy, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, and 3 to 10 membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from the group consisting of hydroxy, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 alkyl, C4-C6 alkyl, C6-C6 alkyl, C7-C6 alkyl, C8-C6 alkyl, C9-C6 alkyl, C10-C6 alkyl, C11-C6 alkyl, C12-C6 alkyl, C13-C6 alkyl, C14-C6 alkyl, C15-C6 alkyl, C16-C6 alkyl, C17-C6 alkyl, C18-C6 alkyl, C19-C6 alkyl, C21-C6 alkyl, C22-C6 alkyl, C23-C6 alkyl, C24-C6 alkyl, C25-C6 alkyl, C2 10 Cycloalkyl, C1-C6 alkoxy, oxo, NR 8 R 9 、=NR 10 COOC1-C6 alkyl, C6-C 10 Aryl and CONR 8 R 9 .

[1155] When formula AA is the same as formula AA-3, the group R 1’ and R 2’

[1156] In some embodiments, R 1’ When present, it is independently selected from the group consisting of: C2-C6 alkyl groups optionally substituted with one or more hydroxyl groups, optionally substituted with one or more halogenated, oxo-, C1-C6 alkoxy, or NR groups.8 R 9 Substituted C2-C6 alkyl; optionally substituted by one or more hydroxyl, halo, oxo, C1-C6 alkoxy, C1-C6 alkyl, or NR 8 R 9 Substituted C3-C7 cycloalkyl groups, wherein the C1-C6 alkoxy or C1-C6 alkyl group is further optionally substituted with one to three hydroxyl groups, halogenated, or NR-substituted. 8 R 9 , or oxo-substituted; a 3- to 7-membered heterocyclic alkyl group optionally substituted with one or more hydroxyl, halogen, oxo, C1-C6 alkyl, or NR8R9, wherein the C1-C6 alkoxy or C1-C6 alkyl group is further optionally substituted with one to three hydroxyl, halogen, NR8R9, or oxo-substituted; C1-C6 haloalkyl; C1-C6 alkoxy; C1-C6 haloalkoxy; Cl; Br; I; CN; CO-C1-C6 alkyl; CO-C6-C 10 Aryl; CO (5- to 10-membered heteroaryl); CO2C1-C6 alkyl; CO2C3-C8 cycloalkyl; OCOC1-C6 alkyl; OCOC6-C 10 Aryl; OCO (5- to 10-membered heteroaryl); OCO (3- to 7-membered heterocycloalkyl); C6-C 10 Aryl; 5- to 10-membered heteroaryl; NH2; NHC1-C6 alkyl; N(C1-C6 alkyl)2; CONR 8 R 9 ;SF5;S(O2)NR 11 R 12 ;S(O)C1-C6 alkyl; and S(O2)C1-C6 alkyl.

[1157] In some embodiments, R 1’ When present, independently selected from the group consisting of: optionally replaced by one or more hydroxyl groups, or NR 8 R 9 Substituted C2-C6 alkyl.

[1158] In some embodiments, R 1’ When present, select from the group consisting of: 1-hydroxy-2-methylpropyl-2-yl; 1,2-dihydroxy-2-propyl; isopropyl; ethyl; 2-hydroxy-2-propyl; 1-hydroxyethyl; 2-hydroxyethyl; 1-hydroxy-2-propyl; 1-hydroxy-1-cyclopropyl; 1-hydroxy-1-cyclobutyl; 1-hydroxy-1-cyclopentyl; 1-hydroxy-1-cyclohexyl; morpholinyl; 1,3-dioxolanecyclo-2-yl; COCH3; COCH2CH3; 2-methoxy-2-propyl; 1-(dimethylamino)ethyl; chloro; phenyl; pyridyl; pyrazolyl; S(O2)CH3; and S(O2)NR 11 R12 In some of these embodiments, R 1’ It is 2-hydroxy-2-propyl or 1,2-dihydroxy-2-propyl. For example, R 1’ It is 2-hydroxy-2-propyl. For example, R... 1’ It is 1,2-dihydroxy-2-propyl.

[1159] In some embodiments, R 1’ When present, selected from the group consisting of: 1-hydroxy-2-methylpropan-2-yl; isopropyl; 2-hydroxy-2-propyl; 1-hydroxyethyl; 2-hydroxyethyl; 1-hydroxy-2-propyl; 1-hydroxy-1-cyclopropyl; 1-hydroxy-1-cyclobutyl; 1-hydroxy-1-cyclopentyl; 1-hydroxy-1-cyclohexyl; morpholinyl; 1,3-dioxolan-2-yl; COCH3; COCH2CH3; 2-methoxy-2-propyl; 1-(dimethylamino)ethyl; chloro; phenyl; pyridyl; pyrazolyl; S(O2)CH3; and S(O2)NR 11 R 12 For example, R 1’ It is 2-hydroxy-2-propyl.

[1160] In some embodiments, R 2’ When present, it is independently selected from the group consisting of: C2-C6 alkyl groups optionally substituted with one or more hydroxyl groups, optionally substituted with one or more halogenated, oxo-, C1-C6 alkoxy, or NR groups. 8 R 9 Substituted C2-C6 alkyl; optionally substituted by one or more hydroxyl, halo, oxo, C1-C6 alkoxy, C1-C6 alkyl, or NR 8 R 9 Substituted C3-C7 cycloalkyl groups, wherein the C1-C6 alkoxy or C1-C6 alkyl group is further optionally substituted with one to three hydroxyl groups, halogenated, or NR-substituted. 8 R 9 , or oxo-substituted; a 3- to 7-membered heterocyclic alkyl group optionally substituted with one or more hydroxyl, halogen, oxo, C1-C6 alkyl, or NR8R9, wherein the C1-C6 alkoxy or C1-C6 alkyl group is further optionally substituted with one to three hydroxyl, halogen, NR8R9, or oxo-substituted; C1-C6 haloalkyl; C1-C6 alkoxy; C1-C6 haloalkoxy; Cl; Br; I; CN; CO-C1-C6 alkyl; CO-C6-C 10 Aryl; CO (5- to 10-membered heteroaryl); CO2C1-C6 alkyl; CO2C3-C8 cycloalkyl; OCOC1-C6 alkyl; OCOC6-C 10 Aryl; OCO (5- to 10-membered heteroaryl); OCO (3- to 7-membered heterocycloalkyl); C6-C 10Aryl; 5- to 10-membered heteroaryl; NH2; NHC1-C6 alkyl; N(C1-C6 alkyl)2; CONR 8 R 9 ;SF5;S(O2)NR 11 R 12 ;S(O)C1-C6 alkyl; and S(O2)C1-C6 alkyl.

[1161] In some embodiments, R 2’ When present, it is independently selected from the group consisting of: optionally substituted with one or more hydroxyl groups, halogenated, or NR. 8 R 9 Substituted C2-C6 alkyl.

[1162] In some embodiments, R 2’ When present, select from the group consisting of: 1-hydroxy-2-methylpropyl-2-yl; 1,2-dihydroxy-2-propyl; isopropyl; ethyl; 2-hydroxy-2-propyl; 1-hydroxyethyl; 2-hydroxyethyl; 1-hydroxy-2-propyl; 1-hydroxy-1-cyclopropyl; 1-hydroxy-1-cyclobutyl; 1-hydroxy-1-cyclopentyl; 1-hydroxy-1-cyclohexyl; morpholinyl; 1,3-dioxolanecyclo-2-yl; COCH3; COCH2CH3; 2-methoxy-2-propyl; 1-(dimethylamino)ethyl; chloro; phenyl; pyridyl; pyrazolyl; S(O2)CH3; and S(O2)NR 11 R 12 For example, R 2’ It is 2-hydroxy-2-propyl or 1,2-dihydroxy-2-propyl (e.g., R 2’ It is 2-hydroxy-2-propyl; or R 2’ It is 1,2-dihydroxy-2-propyl).

[1163] In some embodiments, R 2’ When present, selected from the group consisting of: 1-hydroxy-2-methylpropan-2-yl; isopropyl; 2-hydroxy-2-propyl; 1-hydroxyethyl; 2-hydroxyethyl; 1-hydroxy-2-propyl; 1-hydroxy-1-cyclopropyl; 1-hydroxy-1-cyclobutyl; 1-hydroxy-1-cyclopentyl; 1-hydroxy-1-cyclohexyl; morpholinyl; 1,3-dioxolan-2-yl; COCH3; COCH2CH3; 2-methoxy-2-propyl; 1-(dimethylamino)ethyl; chloro; phenyl; pyridyl; pyrazolyl; S(O2)CH3; and S(O2)NR 11 R 12 For example, R 2’ It is 2-hydroxy-2-propyl.

[1164] In some embodiments, one or more R 1’When present is independently C2-C6 alkyl substituted with one or more hydroxy groups.

[1165] In some of these embodiments, one or more R 1’ Independently selected from 1-hydroxy-2-methylpropan-2-yl; 2-hydroxy-2-propyl; 1-hydroxyethyl; 2-hydroxyethyl; 1-hydroxy-2-propyl; 1,2-dihydroxy-2-propyl; and 1,2,3-trihydroxy-2-propyl.

[1166] In some embodiments, one or more R 1’ When present, it is independently substituted by one or more hydroxyl groups and further substituted by one or more (e.g., one) NR 8 R 9 Substituted C2-C6 alkyl.

[1167] In some of these embodiments, one or more R 1’ Independently selected from 1-amino-2-hydroxy-propan-2-yl; 1-acetamido-2-hydroxy-propan-2-yl; and 1-(tert-butoxycarbonyl)amino-2-hydroxy-propan-2-yl.

[1168] In some embodiments, one or more R 1’ When present, it is independently substituted by one or more hydroxyl groups and further by one or more (e.g., one) R 15 Substituted C2-C6 alkyl.

[1169] In some of these embodiments (e.g., a2 = 1 or 2), one or more R 1’ It is independently selected from 1-(2-hydroxyethoxy)-2-hydroxy-2-propyl; 1-(2-benzyloxyethoxy)-2-hydroxy-2-propyl; and 1-(2-methoxyethoxy)-2-hydroxy-2-propyl.

[1170] In some of these embodiments (e.g., a2 = 1), one or more R 1’ It is independently selected from 1-(2-hydroxyethoxy)-2-hydroxy-2-propyl and 1-(2-methoxyethyl)-2-hydroxy-2-propyl.

[1171] In some embodiments (e.g., a2 = 1), one or more R 1’ Independently selected from:

[1172]

[1173] In some embodiments (e.g., a2>1), one or more R 1’ yes

[1174] In some embodiments, one or more R 1’ Independently is controlled by one or more (e.g., one) NR 8 R 9 The C2-C6 alkyl group is substituted and may be further optionally substituted by one or more halogenations.

[1175] In some of these embodiments, one or more R 1’ Independently selected from: 1-(dimethylamino)ethyl; 2-((methyl)aminomethyl)-propan-2-yl; 2-((methyl)amino)-propan-2-yl; (1-(cyclobutyl)amino-eth-1-yl; 2-fluoro-1-dimethylamino-eth-1-yl; 1-dimethylamino-2,2-difluoroeth-1-yl; 1-dimethylamino-2,2,2-trifluoroeth-1-yl; and 1-dimethylamino-2,2,2-trimethyleth-1-yl.

[1176] In some embodiments, one or more R 1’ It is a C2-C6 alkyl group optionally substituted with one or more halogens. In some of these embodiments, one or more R 1’ is a C2-C6 alkyl group optionally substituted with one or more halogen groups. As a non-limiting example, R 1’ It is ethyl or difluoroethyl.

[1177] In some embodiments, one or more R 1’ When present, it is a 3 to 7 membered heterocycloalkyl group optionally substituted with one or more oxo groups and further optionally substituted with one or more C1-C6 alkyl groups. For example, R 1’ It is 5-methyl-oxazolidin-2-one-5-yl.

[1178] In R 1’ Any of the foregoing embodiments wherein one or more R 2’ The components are independently selected from C2-C6 alkyl groups, C2-C6 alkyl groups optionally substituted with one or more hydroxyl groups, C2-C6 alkyl groups optionally substituted with one or more C1-C6 alkoxy groups, Br, Cl, and I.

[1179] In some embodiments, a pair of R atoms located on adjacent atoms 1’ and R 2’ Together with the atoms that connect them, they independently form a monocyclic or bicyclic C4-C ring. 12 A carbon ring or a monocyclic or bicyclic 5- to 12-membered heterocycle, said heterocycle comprising 1 to 3 heteroatoms and / or heteroatom groups independently selected from the following: O, NH, NR. 13S, S(O), and S(O)2, wherein the carbocyclic or heterocyclic ring is optionally and independently substituted by one or more substituents independently selected from the following: hydroxyl, halogenated, oxo-substituted, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, OC3-C 10 Cycloalkyl, NR 8 R 9 、=NR 10 、CN、COOC1-C6 alkyl、OS(O2)C6-C 10 Aryl, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, 3- to 10-membered heterocycloalkyl, and CONR 8 R 9 The C1-C6 alkyl, C1-C6 alkoxy, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, and 3 to 10 membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from the group consisting of hydroxy, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 alkyl, C4-C6 alkyl, C6-C6 alkyl, C7-C6 alkyl, C8-C6 alkyl, C9-C6 alkyl, C10-C6 alkyl, C11-C6 alkyl, C12-C6 alkyl, C13-C6 alkyl, C14-C6 alkyl, C15-C6 alkyl, C16-C6 alkyl, C17-C6 alkyl, C18-C6 alkyl, C19-C6 alkyl, C21-C6 alkyl, C22-C6 alkyl, C23-C6 alkyl, C24-C6 alkyl, C25-C6 alkyl, C2 10 Cycloalkyl, C1-C6 alkoxy, oxo, NR 8 R 9 、=NR 10 COOC1-C6 alkyl, C6-C 10 Aryl and CONR 8 R 9 .

[1180] In some embodiments, R 1’ and R 2’ They are the same.

[1181] In some embodiments, R 1’ and R 2’ are different.

[1182] In some embodiments, R 1’ Located in R 2’ The position of the interval.

[1183] In some embodiments, R 1’ Located in R 2’ The adjacent position.

[1184] When formula AA is the same as formula AA-4, the group R 1 and R 2”

[1185] In some embodiments, R 1 Independently selected from the group consisting of: C1-C6 alkyl groups optionally substituted with one or more hydroxyl groups, optionally substituted with one or more halogenated, oxo-, C1-C6 alkoxy, or NR groups. 8 R 9 Substituted C1-C6 alkyl; optionally with one or more hydroxyl, halogenated, oxo-, C1-C6 alkoxy, C1-C6 alkyl, or NR 8 R 9 Substituted C3-C7 cycloalkyl groups, wherein the C1-C6 alkoxy or C1-C6 alkyl group is further optionally substituted with one to three hydroxyl groups, halogenated, or NR-substituted. 8 R 9 , or oxo-substituted; a 3- to 7-membered heterocyclic alkyl group optionally substituted with one or more hydroxyl, halogen, oxo, C1-C6 alkyl, or NR8R9, wherein the C1-C6 alkoxy or C1-C6 alkyl group is further optionally substituted with one to three hydroxyl, halogen, NR8R9, or oxo-substituted; C1-C6 haloalkyl; C1-C6 alkoxy; C1-C6 haloalkoxy; halogen; CN; CO-C1-C6 alkyl; CO-C6-C 10 Aryl; CO (5- to 10-membered heteroaryl); CO2C1-C6 alkyl; CO2C3-C8 cycloalkyl; OCOC1-C6 alkyl; OCOC6-C 10 Aryl; OCO (5- to 10-membered heteroaryl); OCO (3- to 7-membered heterocycloalkyl); C6-C 10 Aryl; 5- to 10-membered heteroaryl; NH2; NHC1-C6 alkyl; N(C1-C6 alkyl)2; CONR 8 R 9 ;SF5;S(O2)NR 11 R 12 ;S(O)C1-C6 alkyl; and S(O2)C1-C6 alkyl.

[1186] In some embodiments, R 1 Independently selected from the group consisting of: optionally coated with one or more hydroxyl groups, halogenated, or NR. 8 R 9 Substituted C1-C6 alkyl groups.

[1187] In some embodiments, R 1Selected from the group consisting of: 1-hydroxy-2-methylpropan-2-yl; 1,2-dihydroxy-2-propyl; methyl; ethyl; difluoromethyl; isopropyl; 2-hydroxy-2-propyl; hydroxymethyl; 1-hydroxyethyl; 2-hydroxyethyl; 1-hydroxy-2-propyl; 1-hydroxy-1-cyclopropyl; 1-hydroxy-1-cyclobutyl; 1-hydroxy-1-cyclopentyl; 1-hydroxy-1-cyclohexyl; morpholinyl; 1,3-dioxolan-2-yl; COCH3; COCH2CH3; 2-methoxy-2-propyl; (dimethylamino)methyl; (methylamino)methyl; 1-(dimethylamino)ethyl; fluoro; chloro; phenyl; pyridyl; pyrazolyl; S(O2)CH3; and S(O2)NR 11 R 12 .

[1188] In some embodiments, R 1 Selected from the group consisting of: 1-hydroxy-2-methylpropan-2-yl; methyl; difluoromethyl; isopropyl; 2-hydroxy-2-propyl; hydroxymethyl; 1-hydroxyethyl; 2-hydroxyethyl; 1-hydroxy-2-propyl; 1-hydroxy-1-cyclopropyl; 1-hydroxy-1-cyclobutyl; 1-hydroxy-1-cyclopentyl; 1-hydroxy-1-cyclohexyl; morpholinyl; 1,3-dioxolan-2-yl; COCH3; COCH2CH3; 2-methoxy-2-propyl; (dimethylamino)methyl; 1-(dimethylamino)ethyl; fluoro; chloro; phenyl; pyridyl; pyrazolyl; S(O2)CH3; and S(O2)NR 11 R 12 .

[1189] In some embodiments, R 1 is selected from the group consisting of: methyl; ethyl; difluoromethyl; 2-hydroxy-2-propyl; 1,2-dihydroxy-2-propyl; hydroxymethyl; (methylamino)methyl; (dimethylamino)methyl; and fluorine. As non-limiting examples of the foregoing embodiments, for example, R 1 It is 2-hydroxy-2-propyl or 1,2-dihydroxy-2-propyl (e.g., R 1 It is 2-hydroxy-2-propyl; or R 1 It is 1,2-dihydroxy-2-propyl).

[1190] In some embodiments, R 1 is selected from the group consisting of: methyl; difluoromethyl; 2-hydroxy-2-propyl; hydroxymethyl; (dimethylamino)methyl; and fluorine. In some embodiments of compounds of formula AA-4, R 1 is 2-hydroxy-2-propyl. In some embodiments of compounds of formula AA-4, R 1 It's fluorine.

[1191] In some embodiments, R2” It's fluorine.

[1192] In some embodiments, R 2” It is a methyl group.

[1193] In some embodiments, one or more R 1 When present, it is independently a C1-C6 alkyl group substituted with one or more hydroxyl groups.

[1194] In some of these embodiments, one or more R 1 Independently selected from 1-hydroxy-2-methylpropan-2-yl; 2-hydroxy-2-propyl; hydroxymethyl; 1-hydroxyethyl; 2-hydroxyethyl; 1-hydroxy-2-propyl; 1,2-dihydroxy-2-propyl; and 1,2,3-trihydroxy-2-propyl.

[1195] In some embodiments, one or more R 1 When present, it is independently substituted by one or more hydroxyl groups and further substituted by one or more (e.g., one) NR 8 R 9 Substituted C1-C6 alkyl groups.

[1196] In some of these embodiments, one or more R 1 Independently selected from 1-amino-2-hydroxy-propan-2-yl; 1-acetamido-2-hydroxy-propan-2-yl; and 1-(tert-butoxycarbonyl)amino-2-hydroxy-propan-2-yl.

[1197] In some embodiments, one or more R 1 When present, it is independently substituted by one or more hydroxyl groups and further by one or more (e.g., one) R 15 Substituted C1-C6 alkyl groups.

[1198] In some of these embodiments (e.g., a2 = 1 or 2), one or more R 1 It is independently selected from 1-(2-hydroxyethoxy)-2-hydroxy-2-propyl; 1-(2-benzyloxyethoxy)-2-hydroxy-2-propyl; and 1-(2-methoxyethoxy)-2-hydroxy-2-propyl.

[1199] In some of these embodiments (e.g., a2 = 1), one or more R 1 It is independently selected from 1-(2-hydroxyethoxy)-2-hydroxy-2-propyl and 1-(2-methoxyethyl)-2-hydroxy-2-propyl.

[1200] In some embodiments (e.g., a2 = 1), one or more R 1 Independently selected from:

[1201]

[1202] In some embodiments (e.g., a2>1), one or more R 1 yes

[1203] In some embodiments, one or more R 1 Independently is controlled by one or more (e.g., one) NR 8 R 9 C1-C6 alkyl substituted and further optionally substituted with one or more halo.

[1204] In some of these embodiments, one or more R 1 Independently selected from: (methylamino)methyl; (2,2-difluoroethyl-1-yl)(methyl)aminomethyl; (2,2,2-trifluoroethyl-1-yl)(methyl)aminomethyl; (dimethylamino)methyl; 1-(dimethylamino)ethyl; 2-((methyl)aminomethyl)-propyl-2-yl; 2-((methyl)amino)-propyl-2-yl; (methyl)(cyclopropylmethyl)aminomethyl; (methyl)(2-(dimethylamino)ethyl-1-yl)aminomethyl; (cyclobutyl)(methyl)aminomethyl; 1-(cyclobutyl)amino-ethyl-1-yl; isopropylaminomethyl; (cyclobutyl)aminomethyl ; cycloheptylaminomethyl; tetrahydropyranylaminomethyl; sec-butylaminomethyl; ethylaminomethyl; allylaminomethyl; (2,2-difluoroeth-1-yl)aminomethyl; (2-methoxy-eth-1-yl)aminomethyl; (2-methoxy-eth-1-yl)(methyl)aminomethyl; 2-fluoro-1-dimethylamino-eth-1-yl; 1-dimethylamino-2,2-difluoroeth-1-yl; 1-dimethylamino-2,2,2-trifluoroeth-1-yl; 1-dimethylamino-2,2,2-trimethyleth-1-yl; and dimethylamino(cyclopropyl)methyl (e.g., one or more R 1 is dimethylaminomethyl or methylaminomethyl).

[1205] In some embodiments, one or more R 1 is C1-C6 alkyl optionally substituted by one or more halo. In certain of these embodiments, one or more R 1 is a C2-C6 alkyl group optionally substituted with one or more halogen groups. As a non-limiting example, R 1 It is ethyl or difluoromethyl.

[1206] In some embodiments, one or more R 1 When present, it is a 3 to 7 membered heterocycloalkyl group optionally substituted with one or more oxo groups and further optionally substituted with one or more C1-C6 alkyl groups. For example, R 1It is 5-methyl-oxazolidin-2-one-5-yl.

[1207] In some embodiments, a pair of R atoms located on adjacent atoms 1 and R 2” Together with the atoms that connect them, they independently form a monocyclic or bicyclic C4-C ring. 12 A carbon ring or a monocyclic or bicyclic 5- to 12-membered heterocycle, said heterocycle comprising 1 to 3 heteroatoms and / or heteroatom groups independently selected from the following: O, NH, NR. 13 , S, S(O), and S(O)2, wherein the carbocyclic or heterocyclic ring is optionally substituted independently by one or more substituents independently selected from the group consisting of hydroxy, halo, oxo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, OC3-C 10 Cycloalkyl, NR 8 R 9 、=NR 10 、CN、COOC1-C6 alkyl、OS(O2)C6-C 10 Aryl, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, 3- to 10-membered heterocycloalkyl, and CONR 8 R 9 The C1-C6 alkyl, C1-C6 alkoxy, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, and 3 to 10 membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from the group consisting of hydroxy, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 alkyl, C4-C6 alkyl, C6-C6 alkyl, C7-C6 alkyl, C8-C6 alkyl, C9-C6 alkyl, C10-C6 alkyl, C11-C6 alkyl, C12-C6 alkyl, C13-C6 alkyl, C14-C6 alkyl, C15-C6 alkyl, C16-C6 alkyl, C17-C6 alkyl, C18-C6 alkyl, C19-C6 alkyl, C21-C6 alkyl, C22-C6 alkyl, C23-C6 alkyl, C24-C6 alkyl, C25-C6 alkyl, C2 10 Cycloalkyl, C1-C6 alkoxy, oxo, NR 8 R 9 、=NR 10 COOC1-C6 alkyl, C6-C 10 Aryl and CONR 8 R 9 .

[1208] In some embodiments, R 1 and R 2” They are the same.

[1209] In some embodiments, R 1 and R 2” are different.

[1210] In some embodiments, R1 Located in R 2” The position of the interval.

[1211] In some embodiments, R 1 Located in R 2” The adjacent position.

[1212] When the formula AA is the formula AA-5, the group R 1 and R 2”

[1213] In some embodiments, R 1 Independently selected from the group consisting of: C1-C6 alkyl groups optionally substituted with one or more hydroxyl groups, optionally substituted with one or more halogenated, oxo-, C1-C6 alkoxy, or NR groups. 8 R 9 Substituted C1-C6 alkyl; optionally with one or more hydroxyl, halogenated, oxo-, C1-C6 alkoxy, C1-C6 alkyl, or NR 8 R 9 Substituted C3-C7 cycloalkyl groups, wherein the C1-C6 alkoxy or C1-C6 alkyl group is further optionally substituted with one to three hydroxyl groups, halogenated, or NR-substituted. 8 R 9 , or oxo-substituted; a 3- to 7-membered heterocyclic alkyl group optionally substituted with one or more hydroxyl, halogen, oxo, C1-C6 alkyl, or NR8R9, wherein the C1-C6 alkoxy or C1-C6 alkyl group is further optionally substituted with one to three hydroxyl, halogen, NR8R9, or oxo-substituted; C1-C6 haloalkyl; C1-C6 alkoxy; C1-C6 haloalkoxy; halogen; CN; CO-C1-C6 alkyl; CO-C6-C 10 Aryl; CO (5- to 10-membered heteroaryl); CO2C1-C6 alkyl; CO2C3-C8 cycloalkyl; OCOC1-C6 alkyl; OCOC6-C 10 Aryl; OCO (5- to 10-membered heteroaryl); OCO (3- to 7-membered heterocycloalkyl); C6-C 10 Aryl; 5- to 10-membered heteroaryl; NH2; NHC1-C6 alkyl; N(C1-C6 alkyl)2; CONR 8 R 9 ;SF5;S(O2)NR 11 R 12 ;S(O)C1-C6 alkyl; and S(O2)C1-C6 alkyl.

[1214] In some embodiments, R 1 Independently selected from the group consisting of: optionally coated with one or more hydroxyl groups, halogenated, or NR. 8 R 9 Substituted C1-C6 alkyl groups.

[1215] In some embodiments, R 1 Selected from the group consisting of: 1-hydroxy-2-methylpropan-2-yl; 1,2-dihydroxy-2-propyl; methyl; ethyl; difluoromethyl; isopropyl; 2-hydroxy-2-propyl; hydroxymethyl; 1-hydroxyethyl; 2-hydroxyethyl; 1-hydroxy-2-propyl; 1-hydroxy-1-cyclopropyl; 1-hydroxy-1-cyclobutyl; 1-hydroxy-1-cyclopentyl; 1-hydroxy-1-cyclohexyl; morpholinyl; 1,3-dioxolan-2-yl; COCH3; COCH2CH3; 2-methoxy-2-propyl; (dimethylamino)methyl; (methylamino)methyl; 1-(dimethylamino)ethyl; fluoro; chloro; phenyl; pyridyl; pyrazolyl; S(O2)CH3; and S(O2)NR 11 R 12 .

[1216] In some embodiments, R 1 Selected from the group consisting of: 1-hydroxy-2-methylpropan-2-yl; methyl; difluoromethyl; isopropyl; 2-hydroxy-2-propyl; hydroxymethyl; 1-hydroxyethyl; 2-hydroxyethyl; 1-hydroxy-2-propyl; 1-hydroxy-1-cyclopropyl; 1-hydroxy-1-cyclobutyl; 1-hydroxy-1-cyclopentyl; 1-hydroxy-1-cyclohexyl; morpholinyl; 1,3-dioxolan-2-yl; COCH3; COCH2CH3; 2-methoxy-2-propyl; (dimethylamino)methyl; 1-(dimethylamino)ethyl; fluoro; chloro; phenyl; pyridyl; pyrazolyl; S(O2)CH3; and S(O2)NR 11 R 12 .

[1217] In some embodiments, R 1 Choose from the group consisting of: methyl; ethyl; difluoromethyl; 2-hydroxy-2-propyl; hydroxymethyl; 1,2-dihydroxy-2-propyl; (dimethylamino)methyl; (methylamino)methyl; and fluorine. For example, R 1 It is 2-hydroxy-2-propyl or 1,2-dihydroxy-2-propyl (e.g., R 1 It is 2-hydroxy-2-propyl; or R 1 It is 1,2-dihydroxy-2-propyl).

[1218] In some embodiments, R 1 Choose from the group consisting of: methyl; difluoromethyl; 2-hydroxy-2-propyl; hydroxymethyl; (dimethylamino)methyl; and fluorine. For example, R 1 It is 2-hydroxy-2-propyl. For example, R 1 It's fluorine.

[1219] In some embodiments, one or more R1 When present, it is independently a C1-C6 alkyl group substituted with one or more hydroxyl groups.

[1220] In some of these embodiments, one or more R 1 Independently selected from 1-hydroxy-2-methylpropan-2-yl; 2-hydroxy-2-propyl; hydroxymethyl; 1-hydroxyethyl; 2-hydroxyethyl; 1-hydroxy-2-propyl; 1,2-dihydroxy-2-propyl; and 1,2,3-trihydroxy-2-propyl.

[1221] In some embodiments, one or more R 1 When present, it is independently substituted by one or more hydroxyl groups and further substituted by one or more (e.g., one) NR 8 R 9 Substituted C1-C6 alkyl groups.

[1222] In some of these embodiments, one or more R 1 Independently selected from 1-amino-2-hydroxy-propan-2-yl; 1-acetamido-2-hydroxy-propan-2-yl; and 1-(tert-butoxycarbonyl)amino-2-hydroxy-propan-2-yl.

[1223] In some embodiments, one or more R 1 When present, it is independently substituted by one or more hydroxyl groups and further by one or more (e.g., one) R 15 Substituted C1-C6 alkyl groups.

[1224] In some of these embodiments (e.g., a2 = 1 or 2), one or more R 1 It is independently selected from 1-(2-hydroxyethoxy)-2-hydroxy-2-propyl; 1-(2-benzyloxyethoxy)-2-hydroxy-2-propyl; and 1-(2-methoxyethoxy)-2-hydroxy-2-propyl.

[1225] In some of these embodiments (e.g., a2 = 1), one or more R 1 It is independently selected from 1-(2-hydroxyethoxy)-2-hydroxy-2-propyl and 1-(2-methoxyethyl)-2-hydroxy-2-propyl.

[1226] In some embodiments (e.g., a2 = 1), one or more R 1 Independently selected from:

[1227]

[1228] In some embodiments (e.g., a2>1), one or more R 1 yes

[1229] In some embodiments, one or more R 1 Independently is controlled by one or more (e.g., one) NR 8 R 9 C1-C6 alkyl substituted and further optionally substituted with one or more halo.

[1230] In some of these embodiments, one or more R 1 Independently selected from: (methylamino)methyl; (2,2-difluoroethyl-1-yl)(methyl)aminomethyl; (2,2,2-trifluoroethyl-1-yl)(methyl)aminomethyl; (dimethylamino)methyl; 1-(dimethylamino)ethyl; 2-((methyl)aminomethyl)-propyl-2-yl; 2-((methyl)amino)-propyl-2-yl; (methyl)(cyclopropylmethyl)aminomethyl; (methyl)(2-(dimethylamino)ethyl-1-yl)aminomethyl; (cyclobutyl)(methyl)aminomethyl; 1-(cyclobutyl)amino-ethyl-1-yl; isopropylaminomethyl; (cyclobutyl)aminomethyl ; cycloheptylaminomethyl; tetrahydropyranylaminomethyl; sec-butylaminomethyl; ethylaminomethyl; allylaminomethyl; (2,2-difluoroeth-1-yl)aminomethyl; (2-methoxy-eth-1-yl)aminomethyl; (2-methoxy-eth-1-yl)(methyl)aminomethyl; 2-fluoro-1-dimethylamino-eth-1-yl; 1-dimethylamino-2,2-difluoroeth-1-yl; 1-dimethylamino-2,2,2-trifluoroeth-1-yl; 1-dimethylamino-2,2,2-trimethyleth-1-yl; and dimethylamino(cyclopropyl)methyl (e.g., one or more R 1 is dimethylaminomethyl or methylaminomethyl).

[1231] In some embodiments, one or more R 1 is C1-C6 alkyl optionally substituted by one or more halo. In certain of these embodiments, one or more R 1 is a C2-C6 alkyl group optionally substituted with one or more halogen groups. As a non-limiting example, R 1 It is ethyl or difluoromethyl.

[1232] In some embodiments, one or more R 1 When present, it is a 3 to 7 membered heterocycloalkyl group optionally substituted with one or more oxo groups and further optionally substituted with one or more C1-C6 alkyl groups. For example, R 1 It is 5-methyl-oxazolidin-2-one-5-yl.

[1233] In R 1 Any of the foregoing embodiments wherein one or more R 2Independently selected from C1-C6 alkyl, C1-C6 alkyl optionally substituted with one or more hydroxyl groups, C1-C6 alkyl optionally substituted with one or more C1-C6 alkoxy groups, and halo.

[1234] In some embodiments, R 2” It's fluorine.

[1235] In some embodiments, R 2” It is a methyl group.

[1236] Variables o and p

[1237] In some embodiments, o=1 or 2.

[1238] In some embodiments, o = 1.

[1239] In some embodiments, o=2.

[1240] In some embodiments, p = 0, 1, 2 or 3.

[1241] In some embodiments, p=0.

[1242] In some embodiments, p=1.

[1243] In some embodiments, p=2.

[1244] In some embodiments, o=1 and p=0.

[1245] In some embodiments, o = 2 and p = 0.

[1246] In some embodiments, o = 1 and p = 1.

[1247] In some embodiments, o = 1 and p = 2.

[1248] In some embodiments, o = 2 and p = 1.

[1249] In some embodiments, o = 2 and p = 2.

[1250] In some embodiments, o=2 and p=3.

[1251] Ring B and substitution on ring B

[1252] In some embodiments, B is pyridyl or its N oxide (e.g., 2-pyridyl or its N oxide, 3-pyridyl or its N oxide, or 4-pyridyl or its N oxide).

[1253] In some embodiments, B is pyridyl (e.g., 2-pyridyl, 3-pyridyl, or 4-pyridyl).

[1254] In some embodiments, B is a pyridyl N-oxide (eg, a 2-pyridyl N-oxide, a 3-pyridyl N-oxide, or a 4-pyridyl N-oxide).

[1255] In some embodiments, B is pyrimidinyl or an N-oxide thereof (eg, 4-pyrimidinyl or an N-oxide thereof, or 5-pyrimidinyl or an N-oxide thereof).

[1256] In some embodiments, B is a pyridazinyl group.

[1257] In some embodiments, B is a pyrazinyl group.

[1258] In some embodiments, B is a triazine group.

[1259] In some embodiments, B is one of the rings disclosed below substituted as disclosed below, wherein in each case, the ring represented by the wavy line The bond shown as broken connects B to the NHC(O) group of formula AA.

[1260] In some embodiments, the replaced ring B is

[1261] In some embodiments, the replaced ring B is

[1262] In some embodiments, the replaced ring B is

[1263] In some embodiments, the replaced ring B is

[1264] In some embodiments, the replaced ring B is

[1265] In some embodiments, the replaced ring B is

[1266] In some embodiments, the replaced ring B is

[1267] In some embodiments, the replaced ring B is

[1268] In some embodiments, the replaced ring B is

[1269] In some embodiments, the replaced ring B is

[1270] In some embodiments, the replaced ring B is

[1271] In some embodiments, the replaced ring B is

[1272] In some embodiments, the replaced ring B is

[1273] In some embodiments, the replaced ring B is

[1274] In some embodiments, the replaced ring B is

[1275] In some embodiments, the replaced ring B is

[1276] In some embodiments, the replaced ring B is

[1277] In some embodiments, the replaced ring B is

[1278] In some embodiments, the replaced ring B is

[1279] In some embodiments, the replaced ring B is

[1280] In some embodiments, the replaced ring B is

[1281] In some embodiments, the replaced ring B is

[1282] In some embodiments, the replaced ring B is

[1283] In some embodiments, the replaced ring B is

[1284] In some embodiments, the replaced ring B is

[1285] In some embodiments, the replaced ring B is

[1286] In some embodiments, the replaced ring B is

[1287] In some embodiments, the replaced ring B is

[1288] In some embodiments, the replaced ring B is

[1289] In some embodiments, the replaced ring B is

[1290] In some embodiments, the replaced ring B is

[1291] In some embodiments, the replaced ring B is

[1292] In some embodiments, the replaced ring B is

[1293] In some embodiments, the replaced ring B is

[1294] In some embodiments, the replaced ring B is

[1295] In some embodiments, the replaced ring B is

[1296] In some embodiments, the replaced ring B is

[1297] In some embodiments, the replaced ring B is

[1298] In some embodiments, the replaced ring B is

[1299] In some embodiments, the replaced ring B is

[1300] In some embodiments, the replaced ring B is

[1301] In some embodiments, the replaced ring B is

[1302] In some embodiments, the replaced ring B is

[1303] In some embodiments, the replaced ring B is

[1304] In some embodiments, the replaced ring B is

[1305] In some embodiments, the replaced ring B is

[1306] In some embodiments, the replaced ring B is

[1307] In some embodiments, the replaced ring B is

[1308] In some embodiments, the replaced ring B is

[1309] In some embodiments, the replaced ring B is

[1310] In some embodiments, the replaced ring B is

[1311] In some embodiments, the replaced ring B is

[1312] In some embodiments, the replaced ring B is

[1313] In some embodiments, the replaced ring B is

[1314] In some embodiments, the replaced ring B is

[1315] In some embodiments, the replaced ring B is

[1316] In some embodiments, the replaced ring B is

[1317] In some embodiments, the replaced ring B is

[1318] In some embodiments, the replaced ring B is

[1319] In some embodiments, the replaced ring B is

[1320] In some embodiments, the replaced ring B is

[1321] In some embodiments, the replaced ring B is

[1322] In some embodiments, the replaced ring B is

[1323] In some embodiments, the replaced ring B is

[1324] In some embodiments, the replaced ring B is

[1325] In some embodiments, the replaced ring B is

[1326] In some embodiments, the replaced ring B is

[1327] In some embodiments, the replaced ring B is

[1328] In some embodiments, the replaced ring B is

[1329] In some embodiments, the replaced ring B is

[1330] In some embodiments, the replaced ring B is

[1331] In some embodiments, the replaced ring B is

[1332] In some embodiments, the replaced ring B is

[1333] In some embodiments, the replaced ring B is

[1334] In some embodiments, the replaced ring B is

[1335] In some embodiments, the replaced ring B is

[1336] In some embodiments, the replaced ring B is

[1337] In some embodiments, the substituted Ring B is selected from the group consisting of:

[1338]

[1339] In some embodiments, the substituted ring B is selected from the group consisting of: (For example, ).

[1340] In some embodiments, the substituted ring B is selected from the group consisting of:

[1341]

[1342] In some embodiments, the substituted ring B is selected from the group consisting of:

[1343]

[1344]

[1345] In some embodiments, the substituted Ring B is:

[1346] In certain of these embodiments, the substituted Ring B is:

[1347] In some embodiments, the replaced ring B is

[1348] In certain of these embodiments, the substituted Ring B is

[1349] In some embodiments, the replaced ring B is

[1350] In certain of these embodiments, the substituted Ring B is

[1351] When equation AA is equation AA-1, ring B

[1352] In some embodiments, B is pyridyl or its N oxide (e.g., 2-pyridyl or its N oxide, 3-pyridyl or its N oxide, or 4-pyridyl or its N oxide).

[1353] In some embodiments, B is pyridyl (e.g., 2-pyridyl, 3-pyridyl, or 4-pyridyl).

[1354] In some embodiments, B is a pyridyl N-oxide (eg, a 2-pyridyl N-oxide, a 3-pyridyl N-oxide, or a 4-pyridyl N-oxide).

[1355] In some embodiments, B is pyrimidinyl or an N-oxide thereof (eg, 4-pyrimidinyl or an N-oxide thereof, or 5-pyrimidinyl or an N-oxide thereof).

[1356] In some embodiments, B is a pyridazinyl group.

[1357] In some embodiments, B is a pyrazinyl group.

[1358] In some embodiments, B is a triazine group.

[1359] In some embodiments, the replaced ring B is

[1360] In some embodiments, the replaced ring B is

[1361] In some embodiments, the replaced ring B is

[1362] In some embodiments, the replaced ring B is

[1363] In some embodiments, the replaced ring B is

[1364] In some embodiments, the replaced ring B is

[1365] In some embodiments, the replaced ring B is

[1366] In some embodiments, the replaced ring B is

[1367] In some embodiments, the replaced ring B is

[1368] In some embodiments, the replaced ring B is

[1369] In some embodiments, the replaced ring B is

[1370] In some embodiments, the replaced ring B is

[1371] In some embodiments, the replaced ring B is

[1372] In some embodiments, the replaced ring B is

[1373] In some embodiments, the replaced ring B is

[1374] In some embodiments, the replaced ring B is

[1375] In some embodiments, the replaced ring B is

[1376] In some embodiments, the replaced ring B is

[1377] In some embodiments, the replaced ring B is

[1378] In some embodiments, the replaced ring B is

[1379] In some embodiments, the replaced ring B is

[1380] In some embodiments, the replaced ring B is

[1381] In some embodiments, the replaced ring B is

[1382] In some embodiments, the replaced ring B is

[1383] In some embodiments, the replaced ring B is

[1384] In some embodiments, the replaced ring B is

[1385] In some embodiments, the replaced ring B is

[1386] In some embodiments, the replaced ring B is

[1387] In some embodiments, the replaced ring B is

[1388] In some embodiments, the replaced ring B is

[1389] In some embodiments, the replaced ring B is

[1390] In some embodiments, the replaced ring B is

[1391] In some embodiments, the replaced ring B is

[1392] In some embodiments, the replaced ring B is

[1393] In some embodiments, the replaced ring B is

[1394] In some embodiments, the replaced ring B is

[1395] In some embodiments, the replaced ring B is

[1396] In some embodiments, the replaced ring B is

[1397] In some embodiments, the replaced ring B is

[1398] In some embodiments, the replaced ring B is

[1399] In some embodiments, the replaced ring B is

[1400] In some embodiments, the replaced ring B is

[1401] In some embodiments, the replaced ring B is

[1402] In some embodiments, the replaced ring B is

[1403] In some embodiments, the replaced ring B is

[1404] In some embodiments, the replaced ring B is

[1405] In some embodiments, the replaced ring B is

[1406] In some embodiments, the replaced ring B is

[1407] In some embodiments, the replaced ring B is

[1408] In some embodiments, the replaced ring B is

[1409] In some embodiments, the replaced ring B is

[1410] In some embodiments, the replaced ring B is

[1411] In some embodiments, the replaced ring B is

[1412] In some embodiments, the replaced ring B is

[1413] In some embodiments, the replaced ring B is

[1414] In some embodiments, the replaced ring B is

[1415] In some embodiments, the replaced ring B is

[1416] In some embodiments, the replaced ring B is

[1417] In some embodiments, the replaced ring B is

[1418] In some embodiments, the replaced ring B is

[1419] In some embodiments, the replaced ring B is

[1420] In some embodiments, the replaced ring B is

[1421] In some embodiments, the replaced ring B is

[1422] In some embodiments, the replaced ring B is

[1423] In some embodiments, the replaced ring B is

[1424] In some embodiments, the replaced ring B is

[1425] In some embodiments, the replaced ring B is

[1426] In some embodiments, the replaced ring B is

[1427] In some embodiments, the replaced ring B is

[1428] In some embodiments, the replaced ring B is

[1429] In some embodiments, the replaced ring B is

[1430] In some embodiments, the replaced ring B is

[1431] In some embodiments, the replaced ring B is

[1432] In some embodiments, the replaced ring B is

[1433] In some embodiments, the replaced ring B is

[1434] In some embodiments, the replaced ring B is

[1435] In some embodiments, the replaced ring B is

[1436] In some embodiments, the substituted ring B is selected from the group consisting of:

[1437]

[1438]

[1439] In some embodiments, the substituted ring B is selected from the group consisting of: (For example, ).

[1440] In some embodiments, the substituted ring B is selected from the group consisting of:

[1441]

[1442] In some embodiments, the substituted ring B is selected from the group consisting of:

[1443] In some embodiments, the substituted Ring B is:

[1444] In certain of these embodiments, the substituted Ring B is:

[1445] In some embodiments, the replaced ring B is

[1446] In certain of these embodiments, the substituted Ring B is

[1447] In some embodiments, the replaced ring B is

[1448] In certain of these embodiments, the substituted Ring B is

[1449] When equation AA is equation AA-2, ring B

[1450] In some embodiments, B is pyridyl or its N oxide (e.g., 2-pyridyl or its N oxide, 3-pyridyl or its N oxide, or 4-pyridyl or its N oxide).

[1451] In some embodiments, B is pyridyl (e.g., 2-pyridyl, 3-pyridyl, or 4-pyridyl).

[1452] In some embodiments, B is a pyridyl N-oxide (eg, a 2-pyridyl N-oxide, a 3-pyridyl N-oxide, or a 4-pyridyl N-oxide).

[1453] In some embodiments, B is pyrimidinyl or an N-oxide thereof (eg, 4-pyrimidinyl or an N-oxide thereof, or 5-pyrimidinyl or an N-oxide thereof).

[1454] In some embodiments, B is a pyridazinyl group.

[1455] In some embodiments, B is a pyrazinyl group.

[1456] In some embodiments, B is a triazine group.

[1457] In some embodiments, B is a 6-membered heteroaryl group comprising one to two optionally substituted nitrogen atoms.

[1458] In some embodiments, B is N-substituted pyridonyl (eg, N-substituted pyridin-2-on-4-yl).

[1459] In some embodiments, B is one of the rings disclosed below substituted as disclosed below, wherein in each case, the ring represented by the wavy line The bond shown as broken connects B to the NHC(O) group of formula AA.

[1460] In some embodiments, the replaced ring B is

[1461] In some embodiments, the replaced ring B is

[1462] In some embodiments, the replaced ring B is

[1463] In some embodiments, the replaced ring B is

[1464] In some embodiments, the replaced ring B is

[1465] In some embodiments, the replaced ring B is

[1466] In some embodiments, the replaced ring B is

[1467] In some embodiments, the replaced ring B is

[1468] In some embodiments, the replaced ring B is

[1469] In some embodiments, the replaced ring B is

[1470] In some embodiments, the replaced ring B is

[1471] In some embodiments, the replaced ring B is

[1472] In some embodiments, the replaced ring B is

[1473] In some embodiments, the replaced ring B is

[1474] In some embodiments, the replaced ring B is

[1475] In some embodiments, the replaced ring B is

[1476] In some embodiments, the replaced ring B is

[1477] In some embodiments, the replaced ring B is

[1478] In some embodiments, the replaced ring B is

[1479] In some embodiments, the replaced ring B is

[1480] In some embodiments, the replaced ring B is

[1481] In some embodiments, the replaced ring B is

[1482] In some embodiments, the replaced ring B is

[1483] In some embodiments, the replaced ring B is

[1484] In some embodiments, the replaced ring B is

[1485] In some embodiments, the replaced ring B is

[1486] In some embodiments, the replaced ring B is

[1487] In some embodiments, the replaced ring B is

[1488] In some embodiments, the replaced ring B is

[1489] In some embodiments, the replaced ring B is

[1490] In some embodiments, the replaced ring B is

[1491] In some embodiments, the replaced ring B is

[1492] In some embodiments, the replaced ring B is

[1493] In some embodiments, the replaced ring B is

[1494] In some embodiments, the replaced ring B is

[1495] In some embodiments, the replaced ring B is

[1496] In some embodiments, the replaced ring B is

[1497] In some embodiments, the replaced ring B is

[1498] In some embodiments, the replaced ring B is

[1499] In some embodiments, the replaced ring B is

[1500] In some embodiments, the replaced ring B is

[1501] In some embodiments, the replaced ring B is

[1502] In some embodiments, the replaced ring B is

[1503] In some embodiments, the replaced ring B is

[1504] In some embodiments, the replaced ring B is

[1505] In some embodiments, the replaced ring B is

[1506] In some embodiments, the replaced ring B is

[1507] In some embodiments, the replaced ring B is

[1508] In some embodiments, the replaced ring B is

[1509] In some embodiments, the replaced ring B is

[1510] In some embodiments, the replaced ring B is

[1511] In some embodiments, the replaced ring B is

[1512] In some embodiments, the replaced ring B is

[1513] In some embodiments, the replaced ring B is

[1514] In some embodiments, the replaced ring B is

[1515] In some embodiments, the replaced ring B is

[1516] In some embodiments, the replaced ring B is

[1517] In some embodiments, the replaced ring B is

[1518] In some embodiments, the replaced ring B is

[1519] In some embodiments, the replaced ring B is

[1520] In some embodiments, the replaced ring B is

[1521] In some embodiments, the replaced ring B is

[1522] In some embodiments, the replaced ring B is

[1523] In some embodiments, the replaced ring B is

[1524] In some embodiments, the replaced ring B is

[1525] In some embodiments, the replaced ring B is

[1526] In some embodiments, the replaced ring B is

[1527] In some embodiments, the replaced ring B is

[1528] In some embodiments, the replaced ring B is

[1529] In some embodiments, the replaced ring B is

[1530] In some embodiments, the replaced ring B is

[1531] In some embodiments, the replaced ring B is

[1532] In some embodiments, the replaced ring B is

[1533] In some embodiments, the replaced ring B is

[1534] In some embodiments, the replaced ring B is

[1535] In some embodiments, the replaced ring B is

[1536] In some embodiments, the replaced ring B is

[1537] In some embodiments, the substituted Ring B is:

[1538] In some embodiments, the substituted Ring B is:

[1539] In some embodiments, the substituted ring B is selected from the group consisting of:

[1540]

[1541] In some embodiments, the substituted ring B is selected from the group consisting of: (For example, ).

[1542] In some embodiments, the substituted ring B is selected from the group consisting of:

[1543]

[1544] In some embodiments, the substituted ring B is selected from the group consisting of:

[1545]

[1546] In some embodiments, the substituted Ring B is:

[1547] In certain of these embodiments, the substituted Ring B is:

[1548] In some embodiments, the replaced ring B is

[1549] In certain of these embodiments, the substituted Ring B is

[1550] In some embodiments, the replaced ring B is

[1551] In certain of these embodiments, the substituted Ring B is

[1552] When equation AA is equation AA-3, ring B

[1553] In some embodiments, B is pyridyl or its N oxide (e.g., 2-pyridyl or its N oxide, 3-pyridyl or its N oxide, or 4-pyridyl or its N oxide).

[1554] In some embodiments, B is pyridyl (e.g., 2-pyridyl, 3-pyridyl, or 4-pyridyl).

[1555] In some embodiments, B is a pyridyl N-oxide (eg, a 2-pyridyl N-oxide, a 3-pyridyl N-oxide, or a 4-pyridyl N-oxide).

[1556] In some embodiments, B is pyrimidinyl or an N-oxide thereof (eg, 4-pyrimidinyl or an N-oxide thereof, or 5-pyrimidinyl or an N-oxide thereof).

[1557] In some embodiments, B is a pyridazinyl group.

[1558] In some embodiments, B is a pyrazinyl group.

[1559] In some embodiments, B is a triazine group.

[1560] In some embodiments, B is one of the rings disclosed below substituted as disclosed below, wherein in each case, the ring represented by the wavy line The bond shown as broken connects B to the NHC(O) group of formula AA.

[1561] In some embodiments, the replaced ring B is

[1562] In some embodiments, the replaced ring B is

[1563] In some embodiments, the replaced ring B is

[1564] In some embodiments, the replaced ring B is

[1565] In some embodiments, the replaced ring B is

[1566] In some embodiments, the replaced ring B is

[1567] In some embodiments, the replaced ring B is

[1568] In some embodiments, the replaced ring B is

[1569] In some embodiments, the replaced ring B is

[1570] In some embodiments, the replaced ring B is

[1571] In some embodiments, the replaced ring B is

[1572] In some embodiments, the replaced ring B is

[1573] In some embodiments, the replaced ring B is

[1574] In some embodiments, the replaced ring B is

[1575] In some embodiments, the replaced ring B is

[1576] In some embodiments, the replaced ring B is

[1577] In some embodiments, the replaced ring B is

[1578] In some embodiments, the replaced ring B is

[1579] In some embodiments, the replaced ring B is

[1580] In some embodiments, the replaced ring B is

[1581] In some embodiments, the replaced ring B is

[1582] In some embodiments, the replaced ring B is

[1583] In some embodiments, the replaced ring B is

[1584] In some embodiments, the replaced ring B is

[1585] In some embodiments, the replaced ring B is

[1586] In some embodiments, the replaced ring B is

[1587] In some embodiments, the replaced ring B is

[1588] In some embodiments, the replaced ring B is

[1589] In some embodiments, the replaced ring B is

[1590] In some embodiments, the replaced ring B is

[1591] In some embodiments, the replaced ring B is

[1592] In some embodiments, the replaced ring B is

[1593] In some embodiments, the replaced ring B is

[1594] In some embodiments, the replaced ring B is

[1595] In some embodiments, the replaced ring B is

[1596] In some embodiments, the replaced ring B is

[1597] In some embodiments, the replaced ring B is

[1598] In some embodiments, the replaced ring B is

[1599] In some embodiments, the replaced ring B is

[1600] In some embodiments, the replaced ring B is

[1601] In some embodiments, the replaced ring B is

[1602] In some embodiments, the replaced ring B is

[1603] In some embodiments, the replaced ring B is

[1604] In some embodiments, the replaced ring B is

[1605] In some embodiments, the replaced ring B is

[1606] In some embodiments, the replaced ring B is

[1607] In some embodiments, the replaced ring B is

[1608] In some embodiments, the replaced ring B is

[1609] In some embodiments, the replaced ring B is

[1610] In some embodiments, the replaced ring B is

[1611] In some embodiments, the replaced ring B is

[1612] In some embodiments, the replaced ring B is

[1613] In some embodiments, the replaced ring B is

[1614] In some embodiments, the replaced ring B is

[1615] In some embodiments, the replaced ring B is

[1616] In some embodiments, the replaced ring B is

[1617] In some embodiments, the replaced ring B is

[1618] In some embodiments, the replaced ring B is

[1619] In some embodiments, the replaced ring B is

[1620] In some embodiments, the replaced ring B is

[1621] In some embodiments, the replaced ring B is

[1622] In some embodiments, the replaced ring B is

[1623] In some embodiments, the replaced ring B is

[1624] In some embodiments, the replaced ring B is

[1625] In some embodiments, the replaced ring B is

[1626] In some embodiments, the replaced ring B is

[1627] In some embodiments, the replaced ring B is

[1628] In some embodiments, the replaced ring B is

[1629] In some embodiments, the replaced ring B is

[1630] In some embodiments, the replaced ring B is

[1631] In some embodiments, the replaced ring B is

[1632] In some embodiments, the replaced ring B is

[1633] In some embodiments, the replaced ring B is

[1634] In some embodiments, the replaced ring B is

[1635] In some embodiments, the replaced ring B is

[1636] In some embodiments, the replaced ring B is

[1637] In some embodiments, the substituted ring B is selected from the group consisting of:

[1638]

[1639] In some embodiments, the substituted ring B is selected from the group consisting of: (For example, ).

[1640] In some embodiments, the substituted ring B is selected from the group consisting of:

[1641]

[1642] In some embodiments, the substituted ring B is selected from the group consisting of:

[1643]

[1644] When equation AA is equation AA-4, ring B'

[1645] In some embodiments, B' is 2-pyridyl or 3-pyridyl, or its N-oxide.

[1646] In some embodiments, B' is 2-pyridyl.

[1647] In some embodiments, B' is 3-pyridyl.

[1648] In some embodiments, B' is a 2-pyridyl N oxide.

[1649] In some embodiments, B' is a 3-pyridyl N oxide.

[1650] In some embodiments, B' is one of the rings that are replaced as disclosed below, wherein in each case, it is formed by the waveform line. The broken bond is shown to link B' to the NHC(O) group of formula AA.

[1651] In some embodiments, the replaced ring B' is

[1652] In some embodiments, the replaced ring B' is

[1653] In some embodiments, the replaced ring B' is

[1654] In some embodiments, the replaced ring B' is

[1655] In some embodiments, the replaced ring B' is

[1656] In some embodiments, the replaced ring B' is

[1657] In some embodiments, the replaced ring B' is

[1658] In some embodiments, the replaced ring B' is

[1659] In some embodiments, the replaced ring B' is

[1660] In some embodiments, the replaced ring B' is

[1661] In some embodiments, the replaced ring B' is

[1662] In some embodiments, the replaced ring B' is

[1663] In some embodiments, the replaced ring B' is

[1664] In some embodiments, the replaced ring B' is

[1665] In some embodiments, the replaced ring B' is

[1666] In some embodiments, the replaced ring B' is

[1667] In some embodiments, the replaced ring B' is

[1668] In some embodiments, the replaced ring B' is

[1669] In some embodiments, the replaced ring B' is

[1670] In some embodiments, the replaced ring B' is

[1671] In some embodiments, the replaced ring B' is

[1672] In some embodiments, the replaced ring B' is

[1673] In some embodiments, the replaced ring B' is

[1674] In some embodiments, the replaced ring B' is

[1675] In some embodiments, the replaced ring B' is

[1676] In some embodiments, the replaced ring B' is

[1677] In some embodiments, the replaced ring B' is

[1678] In some embodiments, the replaced ring B' is

[1679] In some embodiments, the replaced ring B' is

[1680] In some embodiments, the replaced ring B' is

[1681] In some embodiments, the replaced ring B' is

[1682] In some embodiments, the replaced ring B' is

[1683] In some embodiments, the replaced ring B' is

[1684] In some embodiments, the replaced ring B' is

[1685] In some embodiments, the replaced ring B' is

[1686] In some embodiments, the replaced ring B' is

[1687] In some embodiments, the replaced ring B' is

[1688] In some embodiments, the replaced ring B' is

[1689] In some embodiments, the replaced ring B' is

[1690] In some embodiments, the replaced ring B' is

[1691] In some embodiments, the replaced ring B' is

[1692] In some embodiments, the replaced ring B' is

[1693] In some embodiments, the replaced ring B' is:

[1694] In some embodiments, the replaced ring B' is:

[1695] In some embodiments, the replaced ring B' is

[1696] In some of these embodiments, the replaced ring B' is

[1697] In some embodiments, the replaced ring B' is

[1698] In some of these embodiments, the replaced ring B' is

[1699] Ring B"

[1700] In some embodiments, B" is 4-pyridyl.

[1701] In some embodiments, B" is 4-pyridyl N-oxide.

[1702] In some embodiments, B” is one of the loops that are replaced as disclosed below, wherein in each case, it is formed by the waveform line. The broken bond is shown to connect B” to the NHC(O) group of formula AA.

[1703] In some embodiments, the replaced ring B is

[1704] In some embodiments, the replaced ring B is

[1705] In some embodiments, the substituted ring B" is

[1706] In some embodiments, the replaced ring B is

[1707] In some embodiments, the substituted ring B" is

[1708] In some embodiments, the replaced ring B is

[1709] In some embodiments, the replaced ring B is

[1710] In some embodiments, the replaced ring B is

[1711] In some embodiments, the replaced ring B is

[1712] In some embodiments, the substituted ring B" is

[1713] In some embodiments, the substituted ring B" is

[1714] In some embodiments, the replaced ring B is

[1715] In some embodiments, the replaced ring B is

[1716] In some embodiments, the replaced ring B is

[1717] In some embodiments, the replaced ring B is

[1718] In some embodiments, the replaced ring B is

[1719] In some embodiments, the replaced ring B is

[1720] In some embodiments, the replaced ring B is

[1721] In some embodiments, the replaced ring B is

[1722] In some embodiments, the replaced ring B is

[1723] In some embodiments, the replaced ring B is

[1724] In some embodiments, the replaced ring B is

[1725] In some embodiments, the replaced ring B is

[1726] In some embodiments, the replaced ring B is

[1727] In some embodiments, the replaced ring B is

[1728] In some embodiments, the replaced ring B is

[1729] In some embodiments, the replaced ring B is

[1730] In some embodiments, the replaced ring B is

[1731] In some embodiments, the replaced ring B is

[1732] In some embodiments, the replaced ring B is

[1733] In some embodiments, the replaced ring B is

[1734] In some embodiments, the replaced ring B is

[1735] In some embodiments, the replaced ring B is

[1736] In some embodiments, the substituted ring B” is selected from the group consisting of:

[1737] In some embodiments, the substituted ring B” is selected from the group consisting of:

[1738]

[1739] In some embodiments, the substituted ring B” is selected from the group consisting of:

[1740]

[1741] In some embodiments, the substituted ring B” is selected from the group consisting of:

[1742] In some embodiments, the replaced ring B” is:

[1743] In some of these embodiments, the substituted ring B is:

[1744] Group R 6 、R 6’ 、R 6” 、R 7 and R 7’

[1745] Group R 6 and R 7

[1746] In some embodiments, R 6 and R 7 Each is independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halogen, NO2, COC1-C6 alkyl, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10Aryl, 5- to 10-membered heteroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, CONR 8 R 9 SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, C3-C 10 Cycloalkyl and 3 to 10-membered heterocyclic alkyl, and C2-C6 alkenyl.

[1747] In some embodiments, each R 6 Independently selected from the group consisting of: C1-C6 alkyl, C3-C7 cycloalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halogen, CN, C6-C 10 aryl, 5- to 10-membered heteroaryl, CO-C1-C6 alkyl; CONR 8 R 9 and 4- to 6-membered heterocyclic alkyl groups, wherein the C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl and 4- to 6-membered heterocyclic alkyl groups are optionally substituted by one or more substituents, each independently selected from: hydroxyl, halogen, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR 8 R 9 、=NR 10 、COOC1-C6 alkyl、CONR 8 R 9 , 4 to 6 membered heterocycloalkyl, C6-C 10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (4- to 6-membered heterocyclic alkyl), NHCOC1-C6 alkyl, NHCOC6-C 10 Aryl, NHCO (5- to 10-membered heteroaryl), NHCO (4- to 6-membered heterocyclic alkyl), and NHCOC2-C6 ynyl.

[1748] In some embodiments, R 6 and R 7 Each is independently selected from C2-C6 alkyl, C2-C6 haloalkyl, C1-C6 haloalkoxy, I, CN, NO2, COC1-C6 alkyl, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10 Aryl, 5- to 10-membered heteroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, CONR 8 R 9SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, C3-C 10 Cycloalkyl and 3- to 10-membered heterocycloalkyl, and C2-C6 alkenyl,

[1749] Where R 6 and R 7 Each may optionally be substituted by one or more substituents independently selected from the following: hydroxyl, halogen, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR. 8 R 9 、=NR 10 、COOC1-C6 alkyl、CONR 8 R 9 3 to 7-membered heterocyclic alkyl groups, C6-C 10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocyclic alkyl), NHCOC1-C6 alkyl, NHCOC6-C 10 Aryl, NHCO (5- to 10-membered heteroaryl), NHCO (3- to 7-membered heterocycloalkyl), NHCOC2-C6 ynyl, C6-C 10 aryloxy, and S(O2)C1-C6 alkyl; and wherein substituted R 6 or R 7 The C1-C6 alkyl or C1-C6 alkoxy group is optionally surrounded by one or more hydroxyl groups, C6-C 10 Aryl or NR 8 R 9 Replace, or where R 6 or R 7 optionally fused to a five- to seven-membered carbocyclic or heterocyclic ring containing one or two heteroatoms independently selected from oxygen, sulfur, and nitrogen;

[1750] wherein the 3 to 7 membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, NHCOC6-C 10 Aryl, NHCO(5- to 10-membered heteroaryl), and NHCO(3- to 7-membered heterocycloalkyl) are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;

[1751] or a pair of R located on adjacent atoms 6 and R 7 Together with the atoms connecting them, they independently form at least one C4-C8 carbon ring or at least one 5- to 8-membered heterocycle, said heterocycle containing one or two heteroatoms and / or heteroatom groups independently selected from: O, NH, NR. 13S, S(O), and S(O)2, wherein the carbocyclic or heterocyclic ring is optionally and independently substituted by one or more substituents independently selected from the following: hydroxyl, hydroxymethyl, halogenated, oxo-substituted, C1-C6 alkyl, C1-C6 alkoxy, NR 8 R 9 CH2NR 8 R 9 、=NR 10 COOC1-C6 alkyl, C6-C 10 Aryl and CONR 8 R 9 .

[1752] In some embodiments, R 6 and R 7 Each is independently selected from C2-C6 alkyl, C2-C6 haloalkyl, C2-C6 alkoxy, C1-C6 haloalkoxy, I, CN, NO2, COC1-C6 alkyl, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10 Aryl, 5- to 10-membered heteroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, CONR 8 R 9 SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, C3-C 10 Cycloalkyl and 3- to 10-membered heterocycloalkyl, and C2-C6 alkenyl,

[1753] Where R 6 and R 7 Each may optionally be substituted by one or more substituents independently selected from the following: hydroxyl, halogen, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR. 8 R 9 、=NR 10 、COOC1-C6 alkyl、CONR 8 R 9 3 to 7-membered heterocyclic alkyl groups, C6-C 10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocyclic alkyl), NHCOC1-C6 alkyl, NHCOC6-C 10 Aryl, NHCO (5- to 10-membered heteroaryl), NHCO (3- to 7-membered heterocycloalkyl), NHCOC2-C6 ynyl, C6-C 10aryloxy, and S(O2)C1-C6 alkyl; and wherein substituted R 6 or R 7 The C1-C6 alkyl or C1-C6 alkoxy group is optionally surrounded by one or more hydroxyl groups, C6-C 10 Aryl or NR 8 R 9 Replace, or where R 6 or R 7 optionally fused to a five- to seven-membered carbocyclic or heterocyclic ring containing one or two heteroatoms independently selected from oxygen, sulfur, and nitrogen;

[1754] wherein the 3 to 7 membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, NHCOC6-C 10 Aryl, NHCO(5- to 10-membered heteroaryl), and NHCO(3- to 7-membered heterocycloalkyl) are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;

[1755] or a pair of R located on adjacent atoms 6 and R 7 Together with the atoms connecting them, they independently form at least one C4-C8 carbon ring or at least one 5- to 8-membered heterocycle, said heterocycle containing one or two heteroatoms and / or heteroatom groups independently selected from: O, NH, NR. 13 S, S(O), and S(O)2, wherein the carbocyclic or heterocyclic ring is optionally and independently substituted by one or more substituents independently selected from the following: hydroxyl, hydroxymethyl, halogenated, oxo-substituted, C1-C6 alkyl, C1-C6 alkoxy, NR 8 R 9 CH2NR 8 R 9 、=NR 10 COOC1-C6 alkyl, C6-C 10 Aryl and CONR 8 R 9 .

[1756] In some embodiments, R 6 and R 7 Each is independently selected from C2-C6 alkyl, C2-C6 haloalkyl, C1-C6 haloalkoxy, I, CN, NO2, COC1-C6 alkyl, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10Aryl, 5- to 10-membered heteroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, CONR 8 R 9 SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, C3-C 10 Cycloalkyl and 3- to 10-membered heterocycloalkyl, and C2-C6 alkenyl,

[1757] Where R 6 and R 7 Each may optionally be substituted by one or more substituents independently selected from the following: hydroxyl, halogen, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR. 8 R 9 、=NR 10 、COOC1-C6 alkyl、CONR 8 R 9 3 to 7-membered heterocyclic alkyl groups, C6-C 10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocyclic alkyl), NHCOC1-C6 alkyl, NHCOC6-C 10 Aryl, NHCO (5- to 10-membered heteroaryl), NHCO (3- to 7-membered heterocycloalkyl), NHCOC2-C6 ynyl, C6-C 10 aryloxy, and S(O2)C1-C6 alkyl; and wherein substituted R 6 or R 7 The C1-C6 alkyl or C1-C6 alkoxy group is optionally surrounded by one or more hydroxyl groups, C6-C 10 Aryl or NR 8 R 9 Replace, or where R 6 or R 7 optionally fused to a five- to seven-membered carbocyclic or heterocyclic ring containing one or two heteroatoms independently selected from oxygen, sulfur, and nitrogen;

[1758] wherein the 3 to 7 membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, NHCOC6-C 10 Aryl, NHCO(5- to 10-membered heteroaryl), and NHCO(3- to 7-membered heterocycloalkyl) are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;

[1759] or a pair of R located on adjacent atoms 6 and R 7Together with the atoms connecting them, they independently form at least one C4-C8 carbon ring or at least one 5- to 8-membered heterocycle, said heterocycle containing one or two heteroatoms and / or heteroatom groups independently selected from: O, NH, NR. 13 S, S(O), and S(O)2, wherein the carbocyclic or heterocyclic ring is optionally and independently substituted by one or more substituents independently selected from the following: hydroxyl, hydroxymethyl, halogenated, oxo-substituted, C1-C6 alkyl, C1-C6 alkoxy, NR 8 R 9 CH2NR 8 R 9 、=NR 10 COOC1-C6 alkyl, C6-C 10 Aryl and CONR 8 R 9 .

[1760] In some embodiments, R 6 and R 7 Each is independently selected from C2-C6 alkyl, C2-C6 haloalkyl, C2-C6 alkoxy, C1-C6 haloalkoxy, I, CN, NO2, COC1-C6 alkyl, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10 Aryl, 5- to 10-membered heteroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, CONR 8 R 9 SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, C3-C 10 Cycloalkyl and 3- to 10-membered heterocycloalkyl, and C2-C6 alkenyl,

[1761] Where R 6 and R 7 Each may optionally be substituted by one or more substituents independently selected from the following: hydroxyl, halogen, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR. 8 R 9 、=NR 10 、COOC1-C6 alkyl、CONR 8 R 9 3 to 7-membered heterocyclic alkyl groups, C6-C 10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocyclic alkyl), NHCOC1-C6 alkyl, NHCOC6-C10 Aryl, NHCO (5- to 10-membered heteroaryl), NHCO (3- to 7-membered heterocycloalkyl), NHCOC2-C6 ynyl, C6-C 10 aryloxy, and S(O2)C1-C6 alkyl; and wherein substituted R 6 or R 7 The C1-C6 alkyl or C1-C6 alkoxy group is optionally surrounded by one or more hydroxyl groups, C6-C 10 Aryl or NR 8 R 9 Replace, or where R 6 or R 7 optionally fused to a five- to seven-membered carbocyclic or heterocyclic ring containing one or two heteroatoms independently selected from oxygen, sulfur, and nitrogen;

[1762] wherein the 3 to 7 membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, NHCOC6-C 10 Aryl, NHCO(5- to 10-membered heteroaryl), and NHCO(3- to 7-membered heterocycloalkyl) are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl;

[1763] or a pair of R located on adjacent atoms 6 and R 7 Together with the atoms connecting them, they independently form at least one C4-C8 carbon ring or at least one 5- to 8-membered heterocycle, said heterocycle containing one or two heteroatoms and / or heteroatom groups independently selected from: O, NH, NR. 13 S, S(O), and S(O)2, wherein the carbocyclic or heterocyclic ring is optionally and independently substituted by one or more substituents independently selected from the following: hydroxyl, hydroxymethyl, halogenated, oxo-substituted, C1-C6 alkyl, C1-C6 alkoxy, NR 8 R 9 CH2NR 8 R 9 、=NR 10 COOC1-C6 alkyl, C6-C 10 Aryl and CONR 8 R 9 .

[1764] In some embodiments, each R 6 Independently selected from the group consisting of: C1-C6 alkyl, C3-C7 cycloalkyl, halogenated, and C6-C 10 Aryl.

[1765] In some embodiments, each R 6Independently selected from the group consisting of: C1-C6 alkyl, halogenated, C3-C7 cycloalkyl, and C6-C 10 Aryl.

[1766] In some embodiments, each R 6 It is independently selected from the group consisting of C1-C6 alkyl and C3-C7 cycloalkyl.

[1767] In some embodiments, each R 6 Independently selected from the group consisting of: methyl, isopropyl, cyclopropyl, fluorine, and phenyl. For example, each R 6 It is isopropyl.

[1768] In some embodiments, each R 7 When present, they are independently selected from the group consisting of: C1-C6 alkyl, C3-C7 cycloalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halogen, CN, C6-C 10 aryl, 5- to 10-membered heteroaryl, CO-C1-C6 alkyl; CONR 8 R 9 and 4- to 6-membered heterocyclic alkyl groups, wherein the C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl and 4- to 6-membered heterocyclic alkyl groups are optionally substituted by one or more substituents, each independently selected from: hydroxyl, halogen, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR 8 R 9 、=NR 10 、COOC1-C6 alkyl、CONR 8 R 9 , 4 to 6 membered heterocycloalkyl, C6-C 10 aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (4- to 6-membered heterocyclic alkyl), NHCOC1-C6 alkyl, NHCOC6-C 10 Aryl, NHCO (5- to 10-membered heteroaryl), NHCO (4- to 6-membered heterocyclic alkyl), and NHCOC2-C6 ynyl.

[1769] In some embodiments, each R 7 When present, they are independently selected from the group consisting of: C1-C6 alkyl, C3-C7 cycloalkyl, halogenated, and C6-C 10 Aryl.

[1770] In some embodiments, each R 7 When present, they are independently selected from the group consisting of: methyl, isopropyl, cyclopropyl, fluorine, and phenyl.

[1771] In some embodiments, a pair of R atoms located on adjacent atoms 6 and R 7 Together with the atoms connecting them, they independently form at least one C4-C8 carbon ring or at least one 5- to 8-membered heterocycle, said heterocycle containing one or two independently selected from and / or heteroatom groups: O, NH, NR. 13 S, S(O), and S(O)2, wherein the carbocyclic or heterocyclic ring is optionally and independently substituted by one or more substituents independently selected from the following: hydroxyl, hydroxymethyl, halogenated, oxo-substituted, C1-C6 alkyl, C1-C6 alkoxy, NR 8 R 9 CH2NR 8 R 9 、=NR 10 COOC1-C6 alkyl, C6-C 10 Aryl and CONR 8 R 9 .

[1772] In some embodiments, a pair of R atoms located on adjacent atoms 6 and R 7 Together with the atoms connecting them, they independently form at least one C4-C8 carbon ring, wherein the carbon ring is optionally and independently substituted by one or more substituents independently selected from: hydroxyl, hydroxymethyl, halogenated, oxo-substituted, C1-C6 alkyl, C1-C6 alkoxy, NR 8 R 9 CH2NR 8 R 9 、=NR 10 COOC1-C6 alkyl, C6-C 10 Aryl and CONR 8 R 9 .

[1773] In some embodiments (when a pair of R atoms are located on adjacent atoms) 6 and R 7 Together with the atoms connecting them, they independently form at least one C4-C8 carbon ring or at least one 5- to 8-membered heterocycle, said heterocycle containing one or two heteroatoms and / or heteroatom groups independently selected from: O, NH, NR. 13 S, S(O), and S(O)2, wherein the carbocyclic or heterocyclic ring is optionally and independently substituted by one or more substituents independently selected from the following: hydroxyl, hydroxymethyl, halogenated, oxo-substituted, C1-C6 alkyl, C1-C6 alkoxy, NR 8 R 9 CH2NR 8 R 9、=NR 10 COOC1-C6 alkyl, C6-C 10 Aryl and CONR 8 R 9 In the context of (the process), the C4-C8 carbon ring is a C5 carbon ring optionally substituted with one or more oxo, CH3, or hydroxyl groups. For example, the C5 carbon ring is substituted ...

Claims

1. A compound having formula AA in m = 0, 1 or 2; n = 0, 1 or 2; o = 1 or 2; p=0, 1, 2 or 3; wherein the sum of o and p is from 1 to 4; in A is a 5- to 10-membered heteroaryl or a C6-C 10 Aryl; B is a 6-membered heteroaromatic ring containing 1-3 N atoms, or an N oxide thereof; At least one of the R 6 in the ortho position to the bond connecting the B ring to the NHC(O) group of formula AA; R 1 and R 2 Each is independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, NO2, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10 Aryl, 5- to 10-membered heteroaryl, NR 8 R 9 、C(O)R 13 ,CONR 8 R 9 、SF5、SC1-C6 alkyl、S(O2)C1-C6 alkyl、S(O2)NR 11 R 12 , S(O)C1-C6 alkyl, C3-C7 cycloalkyl and 3- to 7-membered heterocycloalkyl, wherein the C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl, 3- to 7-membered heterocycloalkyl are optionally substituted with one or more substituents each independently selected from the following: hydroxy, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, R 15 NR 8 R 9 , =NR 10 、COOC1-C6 alkyl、CONR 8 R 9 , 3 to 7 membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered heterocycloalkyl); Wherein R 1 or R 2 C3-C7 cycloalkyl or said R 1 or R 2 Each C1-C6 alkyl substituent and each C1-C6 alkoxy substituent of the 3- to 7-membered heterocycloalkyl is further optionally and independently substituted with one to three hydroxyl groups, -O(C0-C3 alkylene)C6-C 10 Aryl, halogenated, NR 8 R 9 , or oxo-substituted; or a pair of R located on adjacent atoms 1 and R 2 Together with the atoms connecting them, they independently form at least one monocyclic or bicyclic C4-C 12 carbocyclic ring or at least one monocyclic or bicyclic 5- to 12-membered heterocyclic ring, wherein: a) When each of the adjacent atoms is a carbon atom, the heterocyclic ring contains from 1 to 3 heteroatoms and / or heteroatom groups independently selected from the following: O, NH, NR 13 , S, S(O), S(O)2; and b) When one or two of the adjacent atoms are nitrogen atoms, the heterocyclic ring further comprises 0-2 heteroatoms and / or heteroatom groups independently selected from the following: O, NH, NR 13 , S, S(O), S(O)2, except for the aforementioned connections to R 1 and / or R 2 one or more nitrogen atoms, and wherein the carbocyclic or heterocyclic ring is optionally substituted independently by one or more substituents each independently selected from the following: hydroxy, halo, oxo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, OC3-C6 alkyl, C2-C6 alkynyl, C1-C6 alkoxy, C2-C6 alkynyl ...oxy, C2-C6 alkynyl, C2-C6 alkoxy, C2-C6 alkynyl, C2-C6 alkoxy, C2-C6 alkoxy, C2-C6 alkynyl, C2-C6 alkoxy, C2-C6 alkoxy, C2-C6 alkoxy, C2-C6 alkoxy, C2-C6 alkoxy, C 10 Cycloalkyl, NR 8 R 9 , =NR 10 、CN、COOC1-C6 alkyl、OS(O2)C6-C 10 Aryl, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, 3- to 10-membered heterocycloalkyl, CONR 8 R 9 , wherein the C1-C6 alkyl, C1-C6 alkoxy, S(O2)C6-C 10 Aryl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, C3-C 10 Cycloalkyl, 3 to 10 membered heterocycloalkyl are optionally substituted by one or more substituents each independently selected from the following: hydroxy, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C 10 Cycloalkyl, C1-C6 alkoxy, oxo, NR 8 R 9 , =NR 10 、COOC1-C6 alkyl、C6-C 10 Aryl, CONR 8 R 9 ; R 6 and R 7 Each independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, NO2, COC1-C6 alkyl, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10 Aryl, 5- to 10-membered heteroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, CONR 8 R 9 , SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, C3-C 10 Cycloalkyl and 3- to 10-membered heterocycloalkyl, C2-C6 alkenyl, Where R 6 and R 7 Each is optionally substituted by one or more substituents independently selected from the group consisting of hydroxy, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR 8 R 9 , =NR 10 、COOC1-C6 alkyl、CONR 8 R 9 , 3 to 7 membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 Aryl, OCO (5- to 10-membered heteroaryl), OCO (3- to 7-membered heterocycloalkyl), C6-C 10 Aryloxy, S(O2)C1-C6 alkyl; and wherein R is substituted 6 or R 7 The C1-C6 alkyl or C1-C6 alkoxy group is optionally substituted with one or more hydroxyl groups, C6-C 10 Aryl or NR 8 R 9 replace; wherein the 3- to 7-membered heterocycloalkyl, C6-C 10 Aryl, 5-membered to 10-membered heteroaryl are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, OC1-C6 alkyl; or at least one pair of R located on adjacent atoms 6 and R 7 Together with the atoms connecting them, they independently form at least one C4-C8 carbocyclic ring or at least one 5- to 8-membered heterocyclic ring containing 1 or 2 independently selected from O, NH, NR 13 , S heteroatom, wherein the carbocyclic or heterocyclic ring is optionally substituted independently by one or more substituents independently selected from the following: hydroxy, hydroxymethyl, halo, oxo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, NR 8 R 9 、CH2NR 8 R 9 , =NR 10 , COOH, COOC1-C6 alkyl, C6-C 10 Aryl, CONR 8 R 9 ; R 10 is a C1-C6 alkyl group; R 8 and R 9 Each of the above is independently selected at each occurrence from hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C3-C7 cycloalkyl, C1-C6 haloalkyl, (C=NR 13 )NR 11 R 12 、S(O2)C1-C6 alkyl、S(O2)NR 11 R 12 , COR 13 、CO2R 13 and CONR 11 R 12 wherein the C1-C6 alkyl group is optionally substituted by one or more hydroxyl groups, halo groups, C1-C6 alkoxy groups, C6-C 10 aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl, 3- to 7-membered heterocycloalkyl, or NR 11 R 12 ; or R 8 and R 9 Together with the nitrogen to which they are attached, they form a 3 to 10 membered monocyclic or bicyclic ring optionally containing one or more heteroatoms in addition to the nitrogen to which they are attached, wherein the ring is optionally substituted with one or more substituents independently selected from the group consisting of halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, oxo, N(C1-C6 alkyl)2, NH2, NH(C1-C6 alkyl), hydroxyl; R 13 is C1-C6 alkyl, C1-C6 haloalkyl, or -(Z 1 -Z 2 ) a1 -Z 3 ; R 11 and R 12 Each of the following is independently selected at each occurrence from hydrogen, C1-C6 alkyl and -(Z 1 -Z 2 ) a1 -Z 3 ; a1 is an integer selected from 0-10; Each Z 1 is independently a C1-C6 alkylene group optionally substituted by one or more substituents independently selected from oxo, halo, hydroxy; Each Z 2 are independently a bond, NH, N(C1-C6 alkyl), -O-, -S-, or a 5-10 membered heteroarylene; Z 3 Independently C6-C 10 Aryl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C 10 cycloalkyl, 5- to 10-membered heteroaryl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from the group consisting of halo, C1-C6 alkyl, C 1-6 Haloalkyl, C1-C6 alkoxy, oxo, N(C1-C6 alkyl)2, NH2, NH(C1-C6 alkyl), hydroxyl; R 3 Selected from hydrogen, cyano, hydroxyl, CO2C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkyl, wherein the C1-C2 alkylene group is optionally substituted with oxo; R 14 is hydrogen, C1-C6 alkyl, 5- to 10-membered monocyclic or bicyclic heteroaryl, or C6-C 10 A monocyclic or bicyclic aryl group, wherein each C1-C6 alkyl, aryl or heteroaryl group is optionally independently substituted by 1 or 2 R 6 replace; R 15 is -(Z 4 -Z 5 ) a2 -Z 6 ; a2 is an integer selected from 1-10; Each Z 4 Independently selected from -O-, -S-, -NH-, -N(C1-C3 alkyl)-; The prerequisite is to connect directly to R 1 or R 2 Z 4 The group is -O- or -S-; Each Z 5 is independently C1-C6 alkylene optionally substituted by one or more substituents independently selected from oxo, halo, hydroxy; and Z 6 is OH, OC1-C6 alkyl, NH2, NH(C1-C6 alkyl), N(C1-C6 alkyl)2, NHC(O)(C1-C6 alkyl), NHC(O)(C1-C6 alkoxy), or an optionally substituted group selected from the group consisting of: C6-C 10 Aryl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C 10 cycloalkyl, 5- to 10-membered heteroaryl, or 3- to 10-membered heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from the group consisting of halo, C1-C6 alkyl, C 1-6 Haloalkyl, C1-C6 alkoxy, oxo, N(C1-C6 alkyl)2, NH2, NH(C1-C6 alkyl), hydroxyl; Provided that the compound of formula AA is not a compound selected from the group consisting of: or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1, wherein a1 is an integer selected from 0-5, and a2 is an integer selected from 1-5.

3. The compound as claimed in claim 1, wherein R 3 It's hydrogen.

4. The compound of any one of claims 1 to 3, wherein A is a 5-membered heteroaryl, or A is a 6- to 10-membered heteroaryl, or A is a C6-C 10 Aryl.

5. The compound of any one of claims 1 to 4, wherein A is thienyl, or A is thiazolyl, or A is pyrazolyl, or A is phenyl.

6. A compound as described in any one of claims 1 to 5, wherein R 1 When present, independently selected from the group consisting of: C1-C6 alkyl optionally substituted with one or more hydroxyl groups, optionally substituted with one or more halo, oxo, C1-C6 alkoxy, or NR 8 R 9 Substituted C1-C6 alkyl; optionally substituted by one or more hydroxyl, halo, oxo, C1-C6 alkoxy, C1-C6 alkyl, or NR 8 R 9 Substituted C3-C7 cycloalkyl, wherein the C1-C6 alkoxy or C1-C6 alkyl is further optionally substituted with one to three hydroxyl, halo, NR 8 R 9 , or oxo-substituted; optionally substituted by one or more hydroxyl, halo, oxo, C1-C6 alkyl, or NR 8 R 9 substituted 3 to 7 membered heterocycloalkyl, wherein the C1-C6 alkoxy or C1-C6 alkyl is further optionally substituted with one to three hydroxyl, halo, NR 8 R 9 , or oxo-substituted; C1-C6 haloalkyl; C1-C6 alkoxy; C1-C6 haloalkoxy; halo; CN; CO-C1-C6 alkyl; CO-C6-C 10 Aryl; CO (5- to 10-membered heteroaryl); CO2C1-C6 alkyl; CO2C3-C8 cycloalkyl; OCOC1-C6 alkyl; OCOC6-C 10 Aryl; OCO(5- to 10-membered heteroaryl); OCO(3- to 7-membered heterocycloalkyl); C6-C 10 Aryl; 5- to 10-membered heteroaryl; NH2; NHC1-C6 alkyl; N(C1-C6 alkyl)2; CONR 8 R 9 ;SF5;S(O2)NR 11 R 12 ; S(O)C1-C6 alkyl; and S(O2)C1-C6 alkyl.

7. A compound as described in any one of claims 1 to 6, wherein R 1 Selected from the group consisting of: 1-hydroxy-2-methylpropan-2-yl; 1,2-dihydroxy-2-propyl; methyl; ethyl; difluoromethyl; isopropyl; 2-hydroxy-2-propyl; hydroxymethyl; 1-hydroxyethyl; 2-hydroxyethyl; 1-hydroxy-2-propyl; 1-hydroxy-1-cyclopropyl; 1-hydroxy-1-cyclobutyl; 1-hydroxy-1-cyclopentyl; 1-hydroxy-1-cyclohexyl; morpholinyl; 1,3-dioxolan-2-yl; COCH3; COCH2CH3; 2-methoxy-2-propyl; (dimethylamino)methyl; (methylamino)methyl; 1-(dimethylamino)ethyl; fluorine; chlorine; phenyl; pyridyl; pyrazolyl; S(O2)CH3; and S(O2)NR 11 R 12 .

8. The compound of any one of claims 1-7, wherein B is pyridyl, or an N-oxide thereof.

9. The compound of any one of claims 1 to 7, wherein the substituted ring B is q is 0, 1 or 2; r is 0, 1 or 2; wherein each of Y and Z is independently selected from C1-C6 alkyl and hydroxyl; or wherein when two Ys are attached to the same carbon, the two Ys are taken together with the carbons to which they are attached to form a cyclopropyl ring; or wherein when two Zs are attached to the same carbon, the two Zs are taken together with the carbons to which they are attached to form a cyclopropyl ring.

10. The compound of any one of claims 1 to 7, wherein the substituted ring B is R 7 Selected from C1-C6 alkyl, C6-C 10 Aryl, C3-C 10 cycloalkyl; p is 0, 1 or 2; q is 0, 1 or 2; wherein each Y is independently selected from C1-C6 alkyl and hydroxy; or when two Ys are attached to the same carbon, the two Ys are taken together with the carbon to which they are attached to form a cyclopropyl ring.

11. The compound of any one of claims 1 to 7, wherein the substituted ring B is Each R 6 Independently selected from C1-C6 alkyl; each R 7 independently selected from halo; p is 0 or 1.

12. The compound of any one of claims 1 to 7, wherein the substituted ring B is Each R 6 Independently selected from C1-C6 alkyl; each R 7 independently selected from halo; p is 0 or 1.

13. The compound of any one of claims 1 to 7, wherein the substituted ring B is R 6 Selected from C1-C6 alkyl and C3-C 10 Cycloalkyl; R 7 Selected from C1-C6 alkyl, C1-C6 haloalkyl and C3-C 10 Cycloalkyl; or R 6 and R 7 Together with the atoms to which they are attached, they independently form a C5 carbocycle optionally substituted with one or more C1-C6 alkyl groups; q is 0, 1 or 2; each Y is independently selected from C1-C6 alkyl groups; or when two Ys are attached to the same carbon, the two Ys are taken together with the carbons to which they are attached to form a cyclopropyl ring.

14. A compound selected from the group consisting of: or a pharmaceutically acceptable salt thereof.

15. A compound according to claim 1, which is of the formula: or a pharmaceutically acceptable salt thereof.

16. A compound according to claim 1, which is of the formula: or a pharmaceutically acceptable salt thereof.

17. The compound of any one of claims 1 to 13, wherein the moiety S(=O)(NHR 3 The sulfur in )=N- has a (S) stereochemistry.

18. The compound of any one of claims 1 to 13, wherein the moiety S(=O)(NHR 3 The sulfur in the )=N- has an (R) stereochemistry.

19. A pharmaceutical composition comprising a compound or salt according to any one of claims 1 to 18, and one or more pharmaceutically acceptable excipients.

20. A compound according to any one of claims 1-18 for use in treating a subject suffering from a disease in which NLRP3 signaling contributes to the pathology and / or symptoms and / or progression of the disease.

21. The compound of claim 20, wherein the use is for treating any of the following diseases, disorders or conditions: Metabolic disorders; Central nervous system diseases; Lung disease; Liver disease; Pancreatic disease; Kidney disease; Intestinal diseases; skin disease; musculoskeletal disorders; Vascular disorders; Bone disorders; Eye diseases; Diseases caused by viral infections; Autoimmune diseases.

22. The compound of claim 21, wherein the metabolic disorder is type 2 diabetes, atherosclerosis, obesity, or gout; the central nervous system disease is Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, or Parkinson's disease; the lung disease is asthma, COPD, or idiopathic pulmonary fibrosis; the liver disease is NASH syndrome, viral hepatitis, or cirrhosis; the pancreatic disease is acute pancreatitis or chronic pancreatitis; the kidney disease is acute kidney injury or chronic kidney injury; the intestinal disease is Crohn's disease or ulcerative colitis; the skin disease is psoriasis; the musculoskeletal disease is scleroderma; the vascular disorder is giant cell arteritis; the bone disorder is osteoarthritis, osteoporosis, or osteosclerotic disorder; the eye disease is glaucoma or macular degeneration; the disease caused by a viral infection is HIV or AIDS; the autoimmune disease is rheumatoid arthritis, systemic lupus erythematosus, autoimmune thyroiditis, cancer, and aging.

23. The compound of claim 22, wherein the disorder or condition of cancer is selected from: myelodysplastic syndrome (MDS); non-small cell lung cancer; acute lymphoblastic leukemia (ALL); Langerhans cell histiocytosis (LCH); multiple myeloma; promyelocytic leukemia; acute myeloid leukemia (AML); chronic myeloid leukemia (CML); gastric cancer; and lung cancer metastasis.

24. The compound according to claim 23, wherein the non-small cell lung cancer is non-small cell lung cancer in a patient carrying a NLRP3 mutation or overexpression, and the acute lymphoblastic leukemia (ALL) is ALL in a patient resistant to glucocorticoid treatment.

25. The compound of any one of claims 1-18 according to claim 20 or 21, further comprising administering to the subject a therapeutically effective amount of an anti-TNFa agent.

26. The compound of claim 25, wherein the NLRP3 antagonist is administered to the subject prior to administering the anti-TNFα agent to the subject; or wherein the anti-TNFα agent is administered to the subject prior to administering the NLRP3 antagonist to the subject; or wherein the NLRP3 antagonist and the anti-TNFαα agent are administered to the subject simultaneously.

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