Compound and composition for treating condition related to NLRP activity

Abstract

To provide a NLRP3 activity regulator.SOLUTION: An activity regulator is characterized by a compound of formula AA or a pharmaceutically acceptable salt thereof. The compound of formula AA is NLRP3 activity regulator, and therefore, can be used for the treatment of metabolic disorder (e.g., TYPE 2 diabetes mellitus, atherosclerosis, obesity or gout), disease of central nervous system (e.g., Alzheimer disease, multiple sclerosis, amyotrophic lateral sclerosis or Parkinson disease), lung disease (e.g., asthma, COPD or idiopathic pulmonary fibrosis), liver disease (e.g., NASH syndrome, viral hepatitis or cirrhosis), pancreatic disease (e.g., acute pancreatitis or chronic pancreatitis), kidney disease (e.g., acute nephropathy or chronic nephropathy), intestinal disease (e.g., Crohn's disease or ulcerative colitis), dermatosis, musculoskeletal disease (e.g., scleroderma), vascular disease, bone disease, eye disease (e.g., glaucoma or macular degeneration), disease originated from virus infection, autoimmune disease, cancer or aging.SELECTED DRAWING: None

Description

Technical Field

[0001] Priority Claim This application claims the benefit of U.S. Provisional Patent Application No. 62 / 536,271, filed Jul. 24, 2017 ; and U.S. Provisional Patent Application No. 62 / 573,894, filed Oct. 18, 2017 ; and these provisional patent applications are hereby incorporated by reference in their entirety into this specification.

[0002] The present disclosure features, for example, a chemical substance (e.g., a compound that modulates (e.g., antagonizes ) NLRP3, or a pharmaceutically acceptable salt, and / or hydrate, and / or co-crystal, and / or combination drug of this compound) useful for treating a condition, disease, or disorder in which a decrease or increase in NLRP3 activity (e.g., an increase, e.g., a condition, disease, or disorder associated with NLRP3 signaling) is a factor in the lesion and / or symptoms and / or progression of the condition, disease, or disorder in a subject (e.g., a human). The present disclosure also features compositions and other methods of using and making the same.

Background Art

[0003] The NLRP3 inflammasome is a component of the inflammatory process, and its abnormal activation causes genetic diseases 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 reported to be associated with gain-of-function mutations in NLRP3.

[0004] NLRP3 can form a complex and is associated with, but not limited to, type 2 diabetes, atherosclerotic arteries Metabolic disorders such as sclerosis, obesity and gout, and central nervous system diseases such as Alzheimer's disease, multiple sclerosis and amyotrophic lateral sclerosis, Parkinson's disease, asthma, COPD and idiopathic pulmonary fibrosis and other lung diseases, NASH syndrome, viral hepatitis and liver cirrhosis and other liver diseases, acute and chronic pancreatitis and other pancreatic diseases, acute and chronic kidney disorders and other kidney diseases, Crohn's disease and ulcerative colitis and other intestinal diseases, skin diseases such as psoriasis, rheumatic diseases such as scleroderma, giant cell arteritis and other vascular diseases, osteoarthritis, osteoporosis and marble bone disease disorders and other bone disorders, glaucoma and macular degeneration and other eye diseases, diseases caused by viral infections such as HIV and AIDS, rheumatoid arthritis, systemic lupus erythematosus, autoimmune diseases such as autoimmune thyroiditis, Addison's disease, pernicious anemia, cancer and aging are involved in the development of many complex diseases.

Summary of the Invention

Problems to be Solved by the Invention

[0005] In view of the above, it would be desirable to provide a compound that modulates (e.g., antagonizes) NLRP3.

Means for Solving the Problems

[0006] The present disclosure relates to, for example, a pathological condition, disease or disorder in which NLRP3 activity is decreased or increased (e.g., increased, e.g., a pathological condition, disease or disorder associated with NLRP3 signaling) for treating useful chemical substances (e.g., compounds that modulate (e.g., antagonize) NLRP3, or pharmaceutically acceptable salts of this compound, and / or hydrates, and / or co-crystals, and / or combination drugs).

[0007] In one embodiment, formula AA [Chemical formula] compounds or pharmaceutically acceptable salts thereof are provided herein, wherein the variables in formula AA can be as defined anywhere in this specification.

[0008] The present disclosure also features compositions and other methods of using and making the same.

[0009] An "antagonist" of NLRP3 inhibits 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, or otherwise acting on NLRP3. LRP3 through inactivation, destabilization, alteration of distribution, or other means. / or IL-18, and includes compounds that inhibit the ability of NLRP3 to induce the production of IL-1β and / or IL-18.

[0010] In one aspect, a pharmaceutical composition is provided that includes a chemical substance (e.g., a compound generally or specifically described herein, or a pharmaceutically acceptable salt thereof, or a composition containing the same) and one or more pharmaceutically acceptable excipients. In one aspect, a method for modulating (e.g., stimulating, partially stimulating, antagonizing) NLRP3 activity is provided, the method including contacting NLRP3 with a chemical substance (e.g., a compound generally or specifically described herein, or a pharmaceutically acceptable salt thereof, or a composition containing the same) described herein. The method includes in vitro methods, e.g., contacting a sample containing one or more cells including NLRP3, and in vivo methods.

[0011] In one aspect, a method for modulating (e.g., stimulating, partially stimulating, antagonizing) NLRP3 activity is provided, the method including contacting NLRP3 with a chemical substance (e.g., a compound generally or specifically described herein, or a pharmaceutically acceptable salt thereof, or a composition containing the same) described herein. The method includes in vitro methods, e.g., contacting a sample containing one or more cells including NLRP3, and in vivo methods. substance (e.g., a compound generally or specifically described herein, or a pharmaceutically acceptable salt thereof, or a composition containing the same) substance (e.g., a compound generally or specifically described herein, or a pharmaceutically acceptable salt thereof, or a composition containing the same) permissible salt or a composition containing the same) and contacting the NLRP3 with the chemical substance. The method includes in vitro methods, e.g., contacting a sample containing one or more cells including NLRP3, and in vivo methods. method includes contacting a sample containing one or more cells including NLRP3, and in vivo methods. The method includes in vitro methods, e.g., contacting a sample containing one or more cells including NLRP3, and in vivo methods.

[0012] In a further aspect, a method of treating a disease in which NLRP3 signaling contributes to the lesions and / or symptoms and / or progression of the disease, the method comprising administering to a subject in need of such treatment an effective amount of a chemical substance described herein (e.g., a compound generally or specifically described herein or a pharmaceutically acceptable salt thereof or a composition containing the same). In a further aspect, a method of treating a disease in which NLRP3 signaling contributes to the lesions and / or symptoms and / or progression of the disease, the method comprising administering to a subject in need of such treatment an effective amount of a chemical substance described herein (e.g., a compound generally or specifically described herein or a pharmaceutically acceptable salt thereof or a composition containing the same). In a further aspect, a method of treating a disease in which NLRP3 signaling contributes to the lesions and / or symptoms and / or progression of the disease, the method comprising administering to a subject in need of such treatment an effective amount of a chemical substance described herein (e.g., a compound generally or specifically described herein or a pharmaceutically acceptable salt thereof or a composition containing the same). In a further aspect, a method of treating a disease in which NLRP3 signaling contributes to the lesions and / or symptoms and / or progression of the disease, the method comprising administering to a subject in need of such treatment an effective amount of a chemical substance described herein (e.g., a compound generally or specifically described herein or a pharmaceutically acceptable salt thereof or a composition containing the same). In a further aspect, a method of treating a disease in which NLRP3 signaling contributes to the lesions and / or symptoms and / or progression of the disease, the method comprising administering to a subject in need of such treatment an effective amount of a chemical substance described herein (e.g., a compound generally or specifically described herein or a pharmaceutically acceptable salt thereof or a composition containing the same).

[0013] In a further aspect, a method of treating a disease in which NLRP3 signaling contributes to the lesions and / or symptoms and / or progression of the disease, the method comprising administering to a subject in need of such treatment an effective amount of a chemical substance described herein (e.g., a compound generally or specifically described herein or a pharmaceutically acceptable salt thereof or a composition containing the same). In a further aspect, a method of treating a disease in which NLRP3 signaling contributes to the lesions and / or symptoms and / or progression of the disease, the method comprising administering to a subject in need of such treatment an effective amount of a chemical substance described herein (e.g., a compound generally or specifically described herein or a pharmaceutically acceptable salt thereof or a composition containing the same). In a further aspect, a method of treating a disease in which NLRP3 signaling contributes to the lesions and / or symptoms and / or progression of the disease, the method comprising administering to a subject in need of such treatment an effective amount of a chemical substance described herein (e.g., a compound generally or specifically described herein or a pharmaceutically acceptable salt thereof or a composition containing the same). In a further aspect, a method of treating a disease in which NLRP3 signaling contributes to the lesions and / or symptoms and / or progression of the disease, the method comprising administering to a subject in need of such treatment an effective amount of a chemical substance described herein (e.g., a compound generally or specifically described herein or a pharmaceutically acceptable salt thereof or a composition containing the same). In a further aspect, a method of treating a disease in which NLRP3 signaling contributes to the lesions and / or symptoms and / or progression of the disease, the method comprising administering to a subject in need of such treatment an effective amount of a chemical substance described herein (e.g., a compound generally or specifically described herein or a pharmaceutically acceptable salt thereof or a composition containing the same).

[0014] Embodiments may include one or more of the following features.

[0015] The chemical substance may be administered in combination with one or more additional treatments with one or more agents suitable for the treatment of the condition, disease or disorder. The chemical substance may be administered in combination with one or more additional treatments with one or more agents suitable for the treatment of the condition, disease or disorder.

[0016] Examples of indications that may be treated with the compounds disclosed herein include, but are 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, NASH syndrome, viral hepatitis and cirrhosis of the liver, pancreatic diseases such as acute and chronic pancreatitis, acute and chronic kidney disorders. Examples of indications that may be treated with the compounds disclosed herein include, but are 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, NASH syndrome, viral hepatitis and cirrhosis of the liver, pancreatic diseases such as acute and chronic pancreatitis, acute and chronic kidney disorders. Examples of indications that may be treated with the compounds disclosed herein include, but are 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, NASH syndrome, viral hepatitis and cirrhosis of the liver, pancreatic diseases such as acute and chronic pancreatitis, acute and chronic kidney disorders. Examples of indications that may be treated with the compounds disclosed herein include, but are 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, NASH syndrome, viral hepatitis and cirrhosis of the liver, pancreatic diseases such as acute and chronic pancreatitis, acute and chronic kidney disorders. Examples of indications that may be treated with the compounds disclosed herein include, but are 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, NASH syndrome, viral hepatitis and cirrhosis of the liver, pancreatic diseases such as acute and chronic pancreatitis, acute and chronic kidney disorders. Renal diseases such as harm, intestinal diseases such as Crohn's disease and ulcerative colitis, skin diseases such as psoriasis, scleroderma Skeletal diseases such as polymyositis, vascular diseases such as giant cell arteritis, osteoarthritis, osteoporosis and marble Bone disorders such as osteopetrosis, eye diseases such as glaucoma and macular degeneration, diseases caused by viral infections such as HIV and AIDS Rheumatoid arthritis, systemic lupus erythematosus, autoimmune diseases such as autoimmune thyroiditis; Addison's disease, pernicious anemia, cancer and aging are mentioned.

[0017] This method may further include the step of identifying a subject.

[0018] Other embodiments include those described in the detailed description and / or the claims.

[0019] Further Definitions To facilitate understanding of the disclosure described herein, several additional terms are defined below Generally, the nomenclature used herein, as well as the experimental procedures in organic chemistry, pharmaceutical chemistry, and pharmacology described herein Are well-known and commonly used in the art. Unless otherwise defined, all technical and scientific terms used herein Have the same meaning as generally understood by one of ordinary skill in the art to which this disclosure pertains By. Each patent, application, published application, and other publications and appendices referred to throughout this specification Are hereby incorporated by reference in their entirety. When used herein, the term "NLRP3" refers to, but is not limited to, nucleic acids, polynucleotides, oligonucleotides, sense and antisense polynucleotides

[0020] When used herein, the term "NLRP3" refers to, without limitation, nucleic acids, polynucleotides, oligonucleotides, sense and antisense polynucleotides ​​​Lock, complementary sequence, peptide, polypeptide, protein, homologous and / or ortholog NLR P3 molecule, isoform, precursor, mutant, variant, derivative, splice variant, pair Allele, different species, and is intended to include active fragments thereof.

[0021] As used herein, the term "acceptable" with respect to a formulation, composition or ingredient is intended to mean having no continuing adverse effect on the overall health of the subject being treated.

[0022] "API" refers to the active pharmaceutical ingredient.

[0023] As used herein, the term "effective amount" or "therapeutically effective amount" refers to a sufficient amount of a chemical substance (e.g., a compound exhibiting activity as a regulator of NLRP3, or a pharmaceutically acceptable salt and / or hydrate and / or co-crystal thereof) administered to alleviate to some extent one or more symptoms of a disease or disorder being treated. The result includes a decrease and / or alleviation of the signs, symptoms, or causes of the disease, or any other desired modification of the biological system. For example, an "effective amount" for therapeutic use is an amount of a composition comprising a compound disclosed herein necessary to provide a clinically significant decrease in disease symptoms. The appropriate "effective" amount in any individual case is determined using any suitable technique, such as a dose escalation study.

[0024] 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 compatible with the other components of the pharmaceutical formulation ​​​​​​​​​, suitable for use in contact with human and animal tissues or organs without excessive toxicity, irritation, allergic reactions, immunogenicity, or other problems or complications, and is "pharmaceutically acceptable" in the sense that it has a reasonable benefit / risk ratio. For example, see 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. and is suitable for use in contact with human and animal tissues or organs without excessive toxicity, irritation, allergic reactions, immunogenicity, or other problems or complications, and is "pharmaceutically acceptable" in the sense that it has a reasonable benefit / risk ratio. ton: The Science and Practice of Pharmacy , 21st ed.; Lippincott Williams & Wilkins: Philadelphia, PA, 2005; Handbook of Pharmac eutical Excipients, 6th ed.; Rowe et al., E ds.; The Pharmaceutical Press and the Ame rican Pharmaceutical Association: 2009; Ha ndbook of Pharmaceutical Additives, 3rd e d.; Ash and Ash Eds.; Gower Publishing Com pany: 2007; Pharmaceutical Preformulation and Formulation, 2nd ed.; Gibson Ed.; CRC P ress LLC: Boca Raton, FL, 2009. See 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.

[0025] The term "pharmaceutically acceptable salt" can refer to pharmaceutically acceptable addition salts prepared from pharmaceutically acceptable non-toxic acids, including inorganic and organic acids. In certain cases, pharmaceutically acceptable salts are prepared by reacting the compounds 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. and can refer to pharmaceutically acceptable addition salts prepared from pharmaceutically acceptable non-toxic acids, including inorganic and organic acids. In certain cases, pharmaceutically acceptable salts are prepared by reacting the compounds 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. ton: 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. and can refer to pharmaceutically acceptable addition salts prepared from pharmaceutically acceptable non-toxic acids, including inorganic and organic acids. In certain cases, pharmaceutically acceptable salts are prepared by reacting the compounds 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. It is obtained by reacting with an acid. The term "pharmaceutically acceptable salt" refers to a compound having an acidic group reacted with a base such as an ammonium salt, a sodium salt or a potassium salt of an alkali metal such as a calcium salt or a magnesium salt of an alkaline earth metal, dicyclohexyl amine, N-methyl-D-glucamine, tris(hydroxymethyl)methylamine, etc. to form salts such as salts of organic bases and salts with amino acids such as arginine and lysine and may also refer to pharmaceutically acceptable addition salts prepared by reacting with a base or by other methods already established. Pharmaceutically acceptable salts are not particularly limited as long as they can be used in drugs. Examples of salts formed by the compounds described herein with bases include: its salts with inorganic bases such as sodium, potassium, magnesium, calcium, and aluminum; its salts with organic bases such as methylamine, ethylamine, and ethanolamine; its salts with basic amino acids such as lysine and ornithine; and ammonium salts. The salts are acid addition salts specifically exemplified by: mineral 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 acid addition salts with acidic amino acids such as aspartic acid and glutamic acid. The term "pharmaceutical composition" refers to a compound described herein and other chemical components such as a carrier, a stabilizer, a diluent a dispersant, a suspending agent, and / or a thickening agent (collectively referred to herein as other chemical components)

[0026] and / or a thickening agent, etc. (collectively referred to herein as refers to a mixture with what is called an "excipient". The pharmaceutical composition facilitates the administration of the compound to a living being. There are, without limitation: rectal, oral, intravenous, aerosol, parenteral, intraocular, intralung, and a plurality of techniques for administering the compound, including topical administration, which exist in the art.

[0027] The term "subject" refers to an animal including, without limitation, primates (e.g., humans), monkeys, cows, pigs, sheep, goats, horses, dogs, cats, rabbits, rats, or mice. The terms "subject" and "patient" are used interchangeably herein with respect to mammalian subjects such as, for example, humans.

[0028] The terms "treat", "treating", and "treatment" in the context of treating a disease or disorder are intended to include reducing or arresting one or more of the disorder, disease, or condition, or symptoms of the disorder, disease, or condition; or slowing the progression, metastasis, or worsening of a disease, disorder or condition or one or more of its symptoms.

[0029] The terms "hydrogen" and "H" are used interchangeably herein.

[0030] The term "halo" refers to fluoro (F), chloro (Cl), bromo (Br), or iodo (I).

[0031] The term "alkyl" refers to a straight-chain or branched-chain, saturated or unsaturated hydrocarbon chain containing the indicated number of carbon atoms. For example, C indicates that the group can have from 1 to 10 or fewer carbon atoms therein. Non-limiting examples include methyl, ethyl 1~10 , including isopropyl, tert-butyl, and n-hexyl.

[0032] The term "haloalkyl" refers to an alkyl substituted with a halo where one or more hydrogen atoms are independently selected.

[0033] The term "alkoxy" refers to an -O-alkyl group (e.g., -OCH3).

[0034] As used herein, the term "carbocyclic" includes optionally substituted aromatic or non-aromatic cyclic hydrocarbon groups having 3 to 10 carbons, such as 3 to 8 carbons, such as 3 to 7 carbons. Examples of carbocycles include 5-membered, 6-membered, and 7-membered carbocycles.

[0035] The term "heterocyclic" refers to aromatic or non-aromatic 5- to 8-membered monocyclic, 8- to 12-membered bicyclic, or 11- to 14-membered tricyclic ring systems having 1 to 3 heteroatoms in the monocyclic case, 1 to 6 heteroatoms in the bicyclic case, or 1 to 9 heteroatoms in the tricyclic case, wherein the heteroatoms are selected from O, N, or S (e.g., 1 to 3, 1 to 6, or 1 to 9 N, O, or S heteroatoms in the monocyclic, bicyclic, or tricyclic cases respectively), and 0, 1, 2, or 3 atoms of each ring may be substituted with substituents. Examples of heterocycles include 5-membered, 6-membered, and 7-membered heterocycles.

[0036] As used herein, the term "cycloalkyl" includes non-aromatic cyclic, bicyclic, fused, or spiro hydrocarbon groups having 3 to 10 carbons, such as 3 to 8 carbons, such as 3 to 7 carbons, and the cycloalkyl group may be optionally substituted. ​​​​​​​Examples of cycloalkyl include 5-membered, 6-membered, and 7-membered rings. Examples include cyclo propyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclo hexenyl, cycloheptyl, and cyclooctyl.

[0037] The term "heterocycloalkyl" refers to a non-aromatic 5- to 8-membered monocyclic, 8- to 12-membered bicyclic, or 11- to 14-membered tricyclic ring, fused, or spiro system having 1 to 3 heteroatoms in the monocyclic case, 1 to 6 heteroatoms in the bicyclic case, or 1 to 9 heteroatoms in the tricyclic case, where the heteroatoms are selected from O, N, or S (e.g., 1 to 3, 1 to 6, or 1 to 9 N, O, or S heteroatoms in the monocyclic, bicyclic, or tricyclic cases, respectively), and 0, 1, 2, or 3 atoms of each ring may be substituted with substituents. Examples of heterocycloalkyl include 5-membered, 6-membered, and 7-membered heterocycles such as piperazinyl, pyrrolidinyl, dioxanyl, morpholinyl, tetrahydro furanyl, etc.

[0038]

[0039] The term "aryl" is intended to mean an aromatic ring group containing 6 to 10 ring carbons. Examples include phenyl and naphthyl.

[0039] The term "heteroaryl" is intended to mean an aromatic ring system that can be monocyclic, two fused rings or three fused rings, containing 5 to 14 aromatic ring atoms, where at least one aromatic ring atom is a heteroatom selected from the group consisting of, but not limited to, O, S, and N. Examples include furanyl, thienyl, pyrrolyl, imidazolyl, oxazol Ril, thiazolyl, isoxazolyl, pyrazolyl, isothiazolyl, oxadiazolyl , triazolyl, thiadiazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazin yl, triazinyl, etc. Examples include carbazolyl, quinolidinyl, quinoli nyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, triazinyl, indolyl, isoindolyl, indazolyl, indolizinyl, purinyl , naphthyridinyl, pteridinyl, carbazolyl, acridinyl. phenazinyl, pheno thiazinyl, phenoxazinyl, benzoxazolyl, benzothiazolyl, 1H-benz imidazolyl, imidazopyridinyl, benzothienyl, benzofuranyl, isobenzofura nyl, etc. are also included.

[0040] The term "hydroxy" refers to the OH group.

[0041] The term "amino" refers to the NH2 group.

[0042] The term "oxo" refers to O. For example, substitution of the CH2 group by oxo gives the C=O group.

[0043] When used in this specification, the terms "ring A" or "A" are used synonymously to

Chemical formula

Chemical formula

[0044] As used herein, the term "ring B" or "B" is used synonymously to denote

Chem.

Chem.

[0045] As used herein, the term "optionally substituted ring A" is used to denote

Chem.

Chem.

[0046] As used herein, the term "substituted ring B" is used to denote

Chem.

Chem.

[0047] As used herein, the notation "S(O2)" refers to the group either alone or as part of a larger

Chem.

[0048] Furthermore, the atoms that make up the compounds of this embodiment are intended to include all isotopic forms of such atoms. Isotopes as used herein include atoms that have the same number of atoms but different mass numbers. By way of general example and without limitation, isotopes of hydrogen include tritium and deuterium, and isotopes of carbon include 13C and 13 14C 14 and so on.

[0049] The scope of the compounds disclosed herein includes the tautomeric forms of the compounds. Thus, by way of example, a compound represented as containing the moiety

Chem.

Chem.

Chem.

Chem.

[0050] Non-limiting exemplary compounds of the formulas described herein contain a stereogenic sulfur atom and optionally one or more stereogenic carbon atoms. The present disclosure provides examples of mixtures of stereoisomers (e.g., racemic mixtures of enantiomers; mixtures of diastereomers). The present disclosure also describes and illustrates methods for separating the individual components of such mixtures of stereoisomers (e.g., resolving the enantiomers of a racemic mixture). In the case of compounds containing only a stereogenic sulfur atom, the resolved enantiomers are depicted using one of two following formats: Formula A / B (a dashed and solid wedge-shaped three-dimensional representation); and Formula C (a flat structure with the stereogenic sulfur atom shown). In reaction schemes showing the resolution of racemic mixtures, Formulas A / B and C are depicted only to indicate that the constituent enantiomers have been resolved in enantiopure form (≥ about 98% ee). Schemes showing the resolution products using the Formula A / B format are not intended to disclose or suggest a correlation between absolute configuration and elution order. Some of the compounds shown in the following table are depicted using the Formula A / B format. However, with the exception of Compounds 181a and 181b, the depicted stereochemistry shown for each of the compounds listed in the Formula A / B format is a provisional assignment and is based on the absolute stereochemistry assigned to Compound 181b (see, e.g., FIGS. 1 and 2) by analogy. For compounds containing only a stereogenic sulfur atom, the resolved enantiomers are depicted using one of two following formats: Formula A / B (a dashed and solid wedge-shaped three-dimensional representation); and Formula C (a flat structure with the stereogenic sulfur atom shown). In reaction schemes showing the resolution of racemic mixtures, Formulas A / B and C are depicted only to indicate that the constituent enantiomers have been resolved in enantiopure form (≥ about 98% ee). Schemes showing the resolution products using the Formula A / B format are not intended to disclose or suggest a correlation between absolute configuration and elution order. Some of the compounds shown in the following table are depicted using the Formula A / B format. However, with the exception of Compounds 181a and 181b, the depicted stereochemistry shown for each of the compounds listed in the Formula A / B format is a provisional assignment and is based on the absolute stereochemistry assigned to Compound 181b (see, e.g., FIGS. 1 and 2) by analogy. In reaction schemes showing the resolution of racemic mixtures, Formulas A / B and C are depicted only to indicate that the constituent enantiomers have been resolved in enantiopure form (≥ about 98% ee). Schemes showing the resolution products using the Formula A / B format are not intended to disclose or suggest a correlation between absolute configuration and elution order. Some of the compounds shown in the following table are depicted using the Formula A / B format. However, with the exception of Compounds 181a and 181b, the depicted stereochemistry shown for each of the compounds listed in the Formula A / B format is a provisional assignment and is based on the absolute stereochemistry assigned to Compound 181b (see, e.g., FIGS. 1 and 2) by analogy. For compounds containing only a stereogenic sulfur atom, the resolved enantiomers are depicted using one of two following formats: Formula A / B (a dashed and solid wedge-shaped three-dimensional representation); and Formula C (a flat structure with the stereogenic sulfur atom shown). * For compounds containing only a stereogenic sulfur atom, the resolved enantiomers are depicted using one of two following formats: Formula A / B (a dashed and solid wedge-shaped three-dimensional representation); and Formula C (a flat structure with the stereogenic sulfur atom shown). In reaction schemes showing the resolution of racemic mixtures, Formulas A / B and C are depicted only to indicate that the constituent enantiomers have been resolved in enantiopure form (≥ about 98% ee). Schemes showing the resolution products using the Formula A / B format are not intended to disclose or suggest a correlation between absolute configuration and elution order. Some of the compounds shown in the following table are depicted using the Formula A / B format. However, with the exception of Compounds 181a and 181b, the depicted stereochemistry shown for each of the compounds listed in the Formula A / B format is a provisional assignment and is based on the absolute stereochemistry assigned to Compound 181b (see, e.g., FIGS. 1 and 2) by analogy.

Chemical Structure

[0051] In reaction schemes showing the resolution of racemic mixtures, Formulas A / B and C are depicted only to indicate that the constituent enantiomers have been resolved in enantiopure form (≥ about 98% ee). Schemes showing the resolution products using the Formula A / B format are not intended to disclose or suggest a correlation between absolute configuration and elution order. Some of the compounds shown in the following table are depicted using the Formula A / B format. However, with the exception of Compounds 181a and 181b, the depicted stereochemistry shown for each of the compounds listed in the Formula A / B format is a provisional assignment and is based on the absolute stereochemistry assigned to Compound 181b (see, e.g., FIGS. 1 and 2) by analogy. For compounds containing only a stereogenic sulfur atom, the resolved enantiomers are depicted using one of two following formats: Formula A / B (a dashed and solid wedge-shaped three-dimensional representation); and Formula C (a flat structure with the stereogenic sulfur atom shown). In reaction schemes showing the resolution of racemic mixtures, Formulas A / B and C are depicted only to indicate that the constituent enantiomers have been resolved in enantiopure form (≥ about 98% ee). Schemes showing the resolution products using the Formula A / B format are not intended to disclose or suggest a correlation between absolute configuration and elution order. Some of the compounds shown in the following table are depicted using the Formula A / B format. However, with the exception of Compounds 181a and 181b, the depicted stereochemistry shown for each of the compounds listed in the Formula A / B format is a provisional assignment and is based on the absolute stereochemistry assigned to Compound 181b (see, e.g., FIGS. 1 and 2) by analogy. In reaction schemes showing the resolution of racemic mixtures, Formulas A / B and C are depicted only to indicate that the constituent enantiomers have been resolved in enantiopure form (≥ about 98% ee). Schemes showing the resolution products using the Formula A / B format are not intended to disclose or suggest a correlation between absolute configuration and elution order. Some of the compounds shown in the following table are depicted using the Formula A / B format. However, with the exception of Compounds 181a and 181b, the depicted stereochemistry shown for each of the compounds listed in the Formula A / B format is a provisional assignment and is based on the absolute stereochemistry assigned to Compound 181b (see, e.g., FIGS. 1 and 2) by analogy. In reaction schemes showing the resolution of racemic mixtures, Formulas A / B and C are depicted only to indicate that the constituent enantiomers have been resolved in enantiopure form (≥ about 98% ee). Schemes showing the resolution products using the Formula A / B format are not intended to disclose or suggest a correlation between absolute configuration and elution order. Some of the compounds shown in the following table are depicted using the Formula A / B format. However, with the exception of Compounds 181a and 181b, the depicted stereochemistry shown for each of the compounds listed in the Formula A / B format is a provisional assignment and is based on the absolute stereochemistry assigned to Compound 181b (see, e.g., FIGS. 1 and 2) by analogy. In reaction schemes showing the resolution of racemic mixtures, Formulas A / B and C are depicted only to indicate that the constituent enantiomers have been resolved in enantiopure form (≥ about 98% ee). Schemes showing the resolution products using the Formula A / B format are not intended to disclose or suggest a correlation between absolute configuration and elution order. Some of the compounds shown in the following table are depicted using the Formula A / B format. However, with the exception of Compounds 181a and 181b, the depicted stereochemistry shown for each of the compounds listed in the Formula A / B format is a provisional assignment and is based on the absolute stereochemistry assigned to Compound 181b (see, e.g., FIGS. 1 and 2) by analogy. In reaction schemes showing the resolution of racemic mixtures, Formulas A / B and C are depicted only to indicate that the constituent enantiomers have been resolved in enantiopure form (≥ about 98% ee). Schemes showing the resolution products using the Formula A / B format are not intended to disclose or suggest a correlation between absolute configuration and elution order. Some of the compounds shown in the following table are depicted using the Formula A / B format. However, with the exception of Compounds 181a and 181b, the depicted stereochemistry shown for each of the compounds listed in the Formula A / B format is a provisional assignment and is based on the absolute stereochemistry assigned to Compound 181b (see, e.g., FIGS. 1 and 2) by analogy. In reaction schemes showing the resolution of racemic mixtures, Formulas A / B and C are depicted only to indicate that the constituent enantiomers have been resolved in enantiopure form (≥ about 98% ee). Schemes showing the resolution products using the Formula A / B format are not intended to disclose or suggest a correlation between absolute configuration and elution order. Some of the compounds shown in the following table are depicted using the Formula A / B format. However, with the exception of Compounds 181a and 181b, the depicted stereochemistry shown for each of the compounds listed in the Formula A / B format is a provisional assignment and is based on the absolute stereochemistry assigned to Compound 181b (see, e.g., FIGS. 1 and 2) by analogy.

[0052] Details of one or more embodiments of the invention are set forth in the accompanying drawings and the following description. will be. Other features and advantages of the present invention will be apparent from this specification, the drawings, and the claims. BRIEF DESCRIPTION OF THE DRAWINGS

[0053]

Figure 1

Figure 2

Figure 3

[0054] In one embodiment, formula AA CHEM. (wherein m = 0, 1, or 2; n = 0, 1, or 2; o = 1 or 2; p = 0, 1, 2, or 3; here, A is a 5- to 10-membered heteroaryl or C6-C 10 aryl; B is a 5- to 10-membered heteroaryl or C6-C 10 aryl; here, at least one R 6 is ortho to the bond connecting the B ring of formula AA to the NR 3 (CO) group; R 1 and R 2 are each independently C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, NO2, COC1-C ​​6-alkyl, CO-C6-C 10 aryl, CO-(5- to 10-membered heteroaryl), C O2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl , OCOC6-C 10 aryl, OCO(5- to 10-membered heteroaryl), OCO(3-membered -7-membered heterocycloalkyl), C6-C 10 aryl, 5- to 10-membered heteroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, NHCOC1-C6 al kyl, NHCOC6-C 10 aryl, NHCO(5- to 10-membered heteroaryl), N HCO(3- to 7-membered heterocycloalkyl), NHCOC2-C6 alkynyl, NHCO OC1-C6 alkyl, NH-(C=NR 13 )NR 11 R 12 , CONR 8 R 9 , SF 5, 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 heterocyclo alkyl selected from, wherein C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, and 3- to 7-membered heterocycloalkyl are hydroxy, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, COOC1-C6 alkyl, NR 8 R 9 , 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 (member heteroaryl), and OCO (3-member to 7-member heterocycloalkyl), NHCOC1~ C6 alkyl, NHCOC6~C 10 aryl, NHCO (5-member to 10-member heteroaryl ), NHCO (3-member to 7-member heterocycloalkyl), and NHCOC2~C6 alkynyl optionally substituted with one or more substituents independently selected from; wherein, R 1 or R 2 C3~C7 cycloalkyl or R 1 or R 2 3-member~ each C1~C6 alkyl substituent and each C1~C6 alkoxy substituent of 7-member heterocycloalkyl are further optionally independently substituted with 1 to 3 hydroxy, halo, or oxo; ; wherein, R 1 or R 2 C1~C6 alkyl, R 1 or R 2 C1~C6 halo alkyl, R 1 or R 2 C3~C7 cycloalkyl, or R 1 or R 2 3-member ~7-member heterocycloalkyl of 3-member to 7-member heterocycloalkyl, C6~C 10 aryl , or 5-member to 10-member heteroaryl is optionally substituted with one or more substituents independently selected from halo, C1~C6 alkyl, oxo, and OC1 ~C6 alkyl; or at least one pair of R 1 and R 2 on adjacent atoms, together with the atoms connecting them form at least one C4~C8 carbocyclic ring or at least one 5-member to 8-member heterocyclic ring containing 1 or 2 heteroatoms independently selected from O, N, and S ; ​formed here, wherein the carbocyclic or heterocyclic ring is hydroxy, halo, oxo, C1-C6 alkyl yl, C1-C6 alkoxy, NR 8 R 9 、=NR 10 、COOC1-C6 alkyl, C6 -C 10 aryl, and CONR 8 R 9 optionally substituted with one or more substituents independently selected from herein, C1-C6 alkyl and C1-C6 alkoxy are optionally substituted with hydroxy, halo, oxo, COOC1-C6 alkyl, C6-C aryl, and C 10 ONR R 8 R 9 ; R 6 and R 7 are each independently C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, NO2, COC1-C 6 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 he teroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, CON R 8 R 9 、SF5、SC1-C6 alkyl, S(O2)C1-C6 alkyl, C3-C1 0 cycloalkyl, 3- to 10-membered heterocycloalkyl, and C2-C6 alkenyl, selected from herein, R 6 and R 7 are each independently hydroxy, halo, CN, oxo, C1-C6 al Kill, C1-C6 alkoxy, NR 8 R 9 , =NR 10 , COOC1-C6 alkyl, C ONR 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), NHCOC 1-C6 alkyl, NHCOC6-C 10 aryl, NHCO(5- to 10-membered heteroary -l), NHCO(3- to 7-membered heterocycloalkyl), NHCOC2-C6 alkynyl , C6-C 10 aryloxy, and S(O2)C1-C6 alkyl, and is optionally substituted with one or more substituents independently selected from ; wherein R 6 or R 7 substituted C1 -C6 alkyl or C1-C6 alkoxy is optionally substituted with one or more hydroxyl, halo, C6-C 10 aryl or NR 8 R 9 , or R 6 or R 7 is a 5- to 7-membered carbocyclic ring or is optionally fused to a heterocyclic ring containing one or two heteroatoms independently selected from oxygen, sulfur and nitrogen ; wherein, 3- to 7-membered heterocycloalkyl, C6-C 10 aryl, 5- to 10-membered hete roaryl, NHCOC6-C 10 aryl, NHCO(5- to 10-membered heteroaryl) and NHCO(3- to 7-membered heterocycloalkyl) are halo, C1-C6 alkyl, and Optionally substituted with one or more substituents independently selected from C1-C6 alkyl ; or R on adjacent atoms 6 and R 7 at least one pair of which, together with the atoms connecting them form, independently, at least one C4-C8 carbocyclic ring or at least one 4- to 8-membered heterocyclic ring containing one or two heteroatoms independently selected from O, N, NR 20 , and S, where the carbocyclic or heterocyclic ring is optionally independently substituted with one or more substituents independently selected from hydroxy, hydroxymethyl, halo , oxo, C1-C6 alkyl, C1-C6 alkoxy, NR R , CH2NR 8 R 9 , =NR 8 R 9 , COOC1-C6 alkyl, C6-C 10 aryl, and CONR 10 R 8 R 9 ; each of R and R 4 is independently selected from hydrogen and C1-C6 alkyl; 5 R is C1-C6 alkyl; 10 each of R and R 8 is, each time it occurs, independently selected from hydrogen, C1-C6 alkyl, 9 C2-C6 alkenyl, C2-C6 alkynyl, (C=NR )NR 13 R 11 R 12 , S( O2)C1-C6 alkyl, S(O2)NR 11 R 12 , COR 13 , CO2R 13 and CONR 11 R 12 ; where C1-C6 alkyl, C2-C6 alkenyl 、 or C2-C6 alkynyl is optionally substituted with one or more hydroxy, halo, oxo, C1-C6 alk oxy, C2-C6 alkynyl, CO2R 13 、 C6-C 10 aryl, 5- to 10-membered he teroaryl, C3-C7 cycloalkyl, or 3- to 7-membered heterocycloalkyl; or R and R 8 together with the nitrogen to which they are attached optionally contain one or more heteroatoms in addition to the nitrogen to which they are attached to form a 3- to 7-membered ring 9 ; formed; R 13 is C1-C6 alkyl, C6-C 10 aryl, or 5- to 10-membered heteroaryl ; Each of R 11 and R 12 is independently selected from hydrogen and C1-C6 alk yl each time it appears; Each R 3 is independently hydrogen, cyano, hydroxy, C1-C6 alkoxy, C1-C6 alkyl, CO2C1-C6 alkyl, and

Chemical formula

[0055] In certain embodiments, formula AA

Chemical formula

Chemical formula

[0056] In certain embodiments, formula AA

Chemical formula

Chemical formula

[0057] In one embodiment, formula AA

Chemical formula

Chem.

[0058]

Chem.

Chem.

Chemical formula

Chemical formula

[0059] In certain embodiments, formula AA [Chemical formula] (wherein, m = 0, 1, or 2; n = 0, 1, or 2; o = 1 or 2; p = 0, 1, 2, or 3, wherein, A is a 5- to 10-membered monocyclic or bicyclic heteroaryl or C6-C 10 monocyclic or bicyclic aryl; B is a 5-membered heteroaryl, 7- to 10-membered monocyclic or bicyclic heteroaryl, or C 6-C 10 monocyclic or bicyclic aryl; wherein, at least one R 6 is ortho to the bond connecting the B ring of formula AA to the NH(CO) group; is ortho; R 1 and R 2 are each independently C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, NO2, COC1-C 6 alkyl, CO-C6-C 10 aryl; CO(5- to 10-membered heteroaryl); CO 2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C 10 aryl, OCO(5- to 10-membered heteroaryl), OCO(3-membered to 7-membered heterocycloalkyl), C6-C 10 aryl, 5- to 10-membered heteroaryl, N H2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, NHCOC1-C6 al kyl, NHCOC6-C 10 aryl, NHCO(5- to 10-membered heteroaryl), NH CO(3- to 7-membered heterocycloalkyl), NHCOC2-C6 alkynyl, NHCOO CC1-C6 alkyl, NH-(C=NR 13 )NR 11 R 12 , CONR 8 R 9 , SF 5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, S(O)C1-C6 alk yl, S(O2)NR 11 R 12 , C3-C7 cycloalkyl and 3- to 7-membered heterocyclo alkyl selected from, wherein C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl and 3- to 7-membered heterocycloalkyl are each independently selected from hydroxy, halo, CN, oxo, C1-C6 al kyl, 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), NHCO C1-C6 alkyl, NHCOC6-C 10 aryl, NHCO(5- to 10-membered hetero aryl), NHCO(3- to 7-membered heterocycloalkyl), and NHCOC2-C6 alk ynyl, each optionally substituted with one or more substituents independently selected therefrom; Here, R 1 or R 2 C3-C7 cycloalkyl or R 1 or R 2 3-membered to each C1-C6 alkyl substituent and each C1-C6 alkoxy substituent of 7-membered heterocycloalkyl are optionally independently substituted with 1-3 hydroxy, halo, NR R 8 R 9 or oxo; Here, 3-membered to 7-membered heterocycloalkyl, C6-C aryl, 5-membered to 10-membered hete 10 roaryl, NHCOC6-C aryl, NHCO(5-membered to 10-membered heteroaryl) 10 and NHCO(3-membered to 7-membered heterocycloalkyl) are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl; ; or at least one pair of R 1 and R 2 on adjacent atoms together form at least one C4-C8 carbocyclic ring or at least one 5-membered to 8-membered heterocyclic ring containing one or two heteroatoms independently selected from O, N, and S, where the carbocyclic ring or heterocyclic ring is optionally independently substituted with one or more substituents independently selected from hydroxy, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR R R , =NR , COOC1-C6 alkyl, C6 8 R 9 R 10 R -C 10 aryl, and CONR 8 R 9 R ; here, C1-C6 alkyl and C1-C6 alkoxy are optionally independently substituted with hydroxy, halo, oxo, NR R 8 R 9 ​, =NR 10 , COOC1-C6 alkyl, C6 -C 10 aryl, and CONR 8 R 9 optionally substituted; R 6 and R 7 are each, independently, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, NO2, COC1-C 6 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 he teroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, CON R 8 R 9 , SF5, S(O2)C1-C6 alkyl, C3-C 10 cycloalkyl and 3 - to 10-membered heterocycloalkyl, and C2-C6 alkenyl, selected from, wherein, R 6 and R 7 are each, hydroxy, halo, CN, oxo, C1-C6 al kyl, C1-C6 alkoxy, NR 8 R 9 , =NR 10 , COOC1-C6 alkyl, C ONR 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), NHCOC 1 to C6 alkyl, NHCOC6 - C 10 aryl, NHCO(5 - to 10 - membered heteroaryl ), NHCO(3 - to 7 - membered heterocycloalkyl), NHCOC2 - C6 alkynyl , C6 - C 10 aryloxy, and S(O2)C1 - C6 alkyl, independently selected from one or more substituents, optionally substituted; wherein R 6 or R 7 substituted C1 - C6 alkyl or C1 - C6 alkoxy is optionally substituted with one or more hydroxyl, C6 - C 10 ar yl or NR 8 R 9 , or R 6 or R 7 is optionally condensed with a 5 - to 7 - membered carbocyclic ring or a heterocyclic ring containing one or two heteroatoms independently selected from oxygen, sulfur, and nitrogen; wherein 3 - to 7 - membered heterocycloalkyl, C6 - C 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 10 OC1 - C6 alkyl; or at least one pair of R and R on adjacent atoms together with the atoms connecting them form at least one C4 - C8 carbocyclic ring or at least one 5 - to 8 - membered heterocyclic ring containing one or two heteroatoms independently selected from O, N, and S, wherein the carbocyclic or heterocyclic ring is hydroxy, hydroxymethyl, halo, oxo 6 and R 7 ; wherein the carbocyclic or heterocyclic ring is hydroxy, hydroxymethyl, halo, oxo and S(O2)C1 - C6 alkyl, independently selected from one or more substituents, optionally substituted; wherein R , 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 independently substituted with one or more substituents independently selected from; R 4 and R 5 each independently is selected from hydrogen and C1-C6 alkyl; R 10 is C1-C6 alkyl; R 8 and R 9 each time they occur, independently is hydrogen, C1-C6 alkyl, (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 selected from; wherein C1 -C6 alkyl is optionally substituted with one or more hydroxy, halo, C1-C6 alkoxy, C6-C 10 aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl or 3- to 7-membered hete rocycloalkyl; or R 8 and R 9 together with the nitrogen to which they are attached, form a 3- to 7-membered ring optionally containing one or more heteroatoms in addition to the nitrogen to which they are attached; ; R 13 is C1-C6 alkyl, C6-C 10 aryl, or 5- to 10-membered heteroaryl -yl;​ R 11 and R 12 each, upon occurrence, is independently selected from hydrogen and C1-C6 al kyl; R 3 is hydrogen, cyano, hydroxy, C1-C6 alkoxy, C1-C6 alkyl, and and

Chemical formula

[0060] In certain embodiments, m = 0, 1, or 2.

[0061] The variables m and n In certain embodiments, m = 0 or 1.

[0062] In certain embodiments, m = 1 or 2.

[0063] In certain embodiments, m = 0 or 2.

[0064] In certain embodiments, m = 0.

[0065] In certain embodiments, m = 0.

[0066] In one embodiment, m = 1.

[0067] In one embodiment, m = 2.

[0068] In one embodiment, n = 0, 1, or 2.

[0069] In one embodiment, n = 0 or 1.

[0070] In one embodiment, n = 1 or 2.

[0071] In one embodiment, n = 0 or 2.

[0072] In one embodiment, n = 0.

[0073] In one embodiment, n = 1.

[0074] In one embodiment, n = 2.

[0075] In one embodiment, m = 0 and n = 0.

[0076] In one embodiment, m = 1 and n = 0.

[0077] In one embodiment, m = 1 and n = 1.

[0078] Ring A and substitutions on ring A In one embodiment, A is a 5- to 10-membered (e.g., 5- to 6-membered) monocyclic or bicyclic heteroaryl or a C6-C 10 (e.g., C6) monocyclic or bicyclic aryl, for example, phenyl.

[0079] In one embodiment, A is a 5- to 10-membered (e.g., 5- to 6-membered) monocyclic or bicyclic heteroaryl.

[0080] In one embodiment, A is a 5-membered heteroaryl containing sulfur and optionally one or more nitrogens. is a teroaryl.

[0081] In one embodiment, A is a C6-C 10 is a monocyclic or bicyclic aryl.

[0082] In one embodiment, A is optionally substituted with one or two Rs 1 and is optionally substituted with one or two Rs 2 is a phenyl optionally substituted with.

[0083] In one embodiment, A is optionally substituted with one or two Rs 1 and is optionally substituted with one or two Rs 2 is a naphthyl optionally substituted with.

[0084] In one embodiment, A is optionally substituted with one or two Rs 1 and is optionally substituted with one of R 2 is a furanyl optionally substituted with.

[0085] In one embodiment, A is optionally substituted with one R 1 and is optionally substituted with one or two of R 2 is a furanyl optionally substituted with.

[0086] In one embodiment, A is optionally substituted with one or two Rs 1 and is optionally substituted with one or two Rs 2 is a thiophenyl optionally substituted with.

[0087] In one embodiment, A is optionally substituted with one or two Rs 1 and is optionally substituted with one or two Rs 2It is oxazolyl optionally substituted with

[0088] In certain embodiments, A is one or two R 1 optionally substituted with, and one or two R 2 is thiazolyl optionally substituted with.

[0089] In certain embodiments, A is two R 1 optionally substituted with, or two R 2 with is oxazolyl optionally substituted with.

[0090] In certain embodiments, A is two R 1 optionally substituted with, or two R 2 with is thiazolyl optionally substituted with.

[0091] In certain embodiments, A is one or two R 1 optionally substituted with, and one or two R 2 is pyrazolyl optionally substituted with.

[0092] In certain embodiments, A is one R 1 optionally substituted with, and one or two of R 2 is pyrazolyl optionally substituted with.

[0093] In certain embodiments, A is one or two R 1 optionally substituted with, and one of R 2 is pyrazolyl optionally substituted with.

[0094] In certain embodiments, A is one or two R 1 optionally substituted with, and one or two R 2 is pyridyl optionally substituted with.

[0095] In one embodiment, A is one or two Rs 1 optionally substituted with and one or two Rs 2 and is indazolyl optionally substituted with.

[0096] In one embodiment, A is one R 1 substituted with and one R 2 optionally substituted phenyl.

[0097] In one embodiment, A is one R 1 substituted with and one R 2 optionally substituted naphthyl.

[0098] In one embodiment, A is one R 1 substituted with and one R 2 optionally substituted furanyl.

[0099] In one embodiment, A is one R 1 substituted with and one R 2 optionally substituted thiophenyl.

[0100] In one embodiment, A is one R 1 substituted with and one R 2 optionally substituted oxazolyl.

[0101] In one embodiment, A is one R 1 substituted with and one R 2 optionally substituted thiazolyl.

[0102] In one embodiment, A is one R 1 substituted with and one R2 is optionally substituted with pyrazolyl.

[0103] In certain embodiments, A is one R 1 substituted with and one R 2 is optionally substituted with pyridyl.

[0104] In certain embodiments, A is one R 1 optionally substituted with and one R 2 with is optionally substituted with indazolyl.

[0105] In certain embodiments, A is one R 1 substituted with and one R 2 substituted with ph enyl.

[0106] In certain embodiments, A is one R 1 substituted with and one R 2 substituted with ph ranil.

[0107] In certain embodiments, A is one R 1 substituted with and one R 2 substituted with th ophenyl.

[0108] In certain embodiments, A is one R 1 substituted with and one R 2 substituted with ox azole.

[0109] In certain embodiments, A is one R 1 substituted with and one R 2 substituted with th azole.

[0110] In certain embodiments, A is one R 1is replaced, and one R 2 is replaced by a pi razolyl.

[0111] In certain embodiments, A is one R 1 is replaced, and one R 2 is replaced by a pi ridyl.

[0112] In certain embodiments, A is phenyl, m is 0 or 1, and n is 0, 1, or 2.

[0113] In certain embodiments, A is furanyl, m is 0 or 1, and n is 0, 1, or 2.

[0114] In certain embodiments, A is thiophenyl, m is 0 or 1, and n is 0, 1, or 2.

[0115] In certain embodiments, A is oxazolyl, m is 0 or 1, and n is 0, 1, or 2.

[0116] In certain embodiments, A is thiazolyl, m is 0 or 1, and n is 0, 1 , or 2.

[0117] In certain embodiments, A is pyrazolyl, m is 0 or 1, and n is 0, 1 , or 2.

[0118] In certain embodiments, A is pyridyl, m is 0 or 1, and n is 0, 1, or 2.

[0119] In certain embodiments, A is indazolyl, m is 0 or 1, and n is 0, 1, or 2.

[0120] In one embodiment, A is phenyl, m is 0, and n is 0 or 1.

[0121] In one embodiment, A is furanyl, m is 0, and n is 0 or 1.

[0122] In one embodiment, A is thiophenyl, m is 0, and n is 0 or 1.

[0123] In one embodiment, A is oxazolyl, m is 0, and n is 0 or 1.

[0124] In one embodiment, A is thiazolyl, m is 0, and n is 0 or 1.

[0125] In one embodiment, A is pyrazolyl, m is 0, and n is 0 or 1.

[0126] In one embodiment, A is pyridyl, m is 0, and n is 0 or 1.

[0127] In one embodiment, A is one of the rings optionally substituted as disclosed hereinbelow, and in each case, the bond shown as broken by the wavy line is linked to the A of formula AA to the S(O)(NR

Chemical Structure

[0128] In one embodiment, the optionally substituted ring A(

Chemical Structure

[0129] In certain embodiments, optionally substituted ring A is [Chem.] as follows.

[0130] In certain embodiments, optionally substituted ring A is [Chem.] as follows.

[0131] In certain embodiments, optionally substituted ring A is [Chem.] as follows.

[0132] In certain embodiments, optionally substituted ring A is [Chem.] as follows.

[0133] In certain embodiments, optionally substituted ring A is [Chem.] as follows.

[0134] In certain embodiments, optionally substituted ring A is [Chem.] is as follows.

[0135] In certain embodiments, the optionally substituted ring A is

Chemical Structure

[0136] In certain embodiments, the optionally substituted ring A is

Chemical Structure

[0137] In certain embodiments, the optionally substituted ring A is

Chemical Structure

[0138] In certain embodiments, the optionally substituted ring A is

Chemical Structure

[0139] In certain embodiments, the optionally substituted ring A is

Chemical Structure

[0140] In certain embodiments, the optionally substituted ring A is

Chemical Structure

[0141] In certain embodiments, the optionally substituted ring A is [Chemical formula] is as follows.

[0142] In certain embodiments, optionally substituted ring A is [Chemical formula] is as follows.

[0143] In certain embodiments, optionally substituted ring A is [Chemical formula] is as follows.

[0144] In certain embodiments, optionally substituted ring A is [Chemical formula] is as follows.

[0145] In certain embodiments, optionally substituted ring A is [Chemical formula] is as follows.

[0146] In certain embodiments, optionally substituted ring A is [Chemical formula] is as follows.

[0147] In certain embodiments, optionally substituted ring A is [Chemical formula] is as follows.

[0148] In one embodiment, the optionally substituted ring A is

Chemical formula

[0149] In one embodiment, the optionally substituted ring A is

Chemical formula

[0150] In one embodiment, the optionally substituted ring A is

Chemical formula

[0151] In one embodiment, the optionally substituted ring A is

Chemical formula

[0152] In one embodiment, the optionally substituted ring A is

Chemical formula

[0153] In one embodiment, the optionally substituted ring A is

Chemical formula

[0154] In one embodiment, the optionally substituted ring A is

Chemical formula

[0155] In certain embodiments, the optionally substituted ring A is

Chemical formula

[0156] In certain embodiments, the optionally substituted ring A is

Chemical formula

[0157] In certain embodiments, the optionally substituted ring A is

Chemical formula

[0158] In certain embodiments, the optionally substituted ring A is

Chemical formula

[0159] In certain embodiments, the optionally substituted ring A is

Chemical formula

[0160] In certain embodiments, the optionally substituted ring A is

Chemical formula

[0161] In certain embodiments, the optionally substituted ring A is

Chem.

[0162] In certain embodiments, the optionally substituted ring A is

Chem.

[0163] In certain embodiments, the optionally substituted ring A is

Chem.

[0164] In certain embodiments, the optionally substituted ring A is

Chem.

[0165] In certain embodiments, the optionally substituted ring A is

Chem.

[0166] In certain embodiments, the optionally substituted ring A is

Chem.

[0167] In certain embodiments, the optionally substituted ring A is

Chem.

[0168] In certain embodiments, the optionally substituted ring A is

Chemical formula

[0169] In certain embodiments, the optionally substituted ring A is

Chemical formula

[0170] In certain embodiments, the optionally substituted ring A is

Chemical formula

[0171] In certain embodiments, the optionally substituted ring A is

Chemical formula

[0172] In certain embodiments, the optionally substituted ring A is

Chemical formula

[0173] In certain embodiments, the optionally substituted ring A is

Chemical formula

[0174] In certain embodiments, the optionally substituted ring A is

Chemical formula

[0175] In certain embodiments, optionally substituted ring A is

Chemical formula

[0176] In certain embodiments, optionally substituted ring A is

Chemical formula

[0177] In certain embodiments, optionally substituted ring A is

Chemical formula

[0178] In certain embodiments, optionally substituted ring A is

Chemical formula

[0179] In certain embodiments, optionally substituted ring A is

Chemical formula

[0180] In certain embodiments, optionally substituted ring A is

Chemical formula

[0181] In certain embodiments, the optionally substituted ring A is

Chemical formula

[0182] In certain embodiments, the optionally substituted ring A is

Chemical formula

[0183] In certain embodiments, the optionally substituted ring A is

Chemical formula

[0184] In certain embodiments, the optionally substituted ring A is

Chemical formula

[0185] In certain embodiments, the optionally substituted ring A is

Chemical formula

[0186] In certain embodiments, the optionally substituted ring A is

Chemical formula

[0187] In certain embodiments, the optionally substituted ring A is

Chemical formula

[0188] In certain embodiments, optionally substituted ring A is

Chemical formula

[0189] In certain embodiments, optionally substituted ring A is

Chemical formula

[0190] In certain embodiments, optionally substituted ring A is

Chemical formula

[0191] In certain embodiments, optionally substituted ring A is

Chemical formula

[0192] In certain embodiments, optionally substituted ring A is

Chemical formula

[0193] In certain embodiments, optionally substituted ring A is

Chemical formula

[0194] In certain embodiments, optionally substituted ring A is [Chemical formula] is as follows.

[0195] In certain embodiments, optionally substituted ring A is [Chemical formula] is as follows.

[0196] In certain embodiments, optionally substituted ring A is [Chemical formula] is as follows.

[0197] In certain embodiments, optionally substituted ring A is [Chemical formula] is as follows.

[0198] In certain embodiments, optionally substituted ring A is [Chemical formula] is as follows.

[0199] In certain embodiments, optionally substituted ring A is [Chemical formula] is as follows.

[0200] In certain embodiments, optionally substituted ring A is [Chemical formula] is as follows.

[0201] In certain embodiments, the optionally substituted ring A is

Chemical formula

[0202] In certain embodiments, the optionally substituted ring A is

Chemical formula

[0203] In certain embodiments, the optionally substituted ring A is

Chemical formula

[0204] In certain embodiments, the optionally substituted ring A is

Chemical formula

[0205] In certain embodiments, the optionally substituted ring A is

Chemical formula

[0206] In certain embodiments, the optionally substituted ring A is

Chemical formula

[0207] In certain embodiments, the optionally substituted ring A is

Chemical formula

[0208] In certain embodiments, ring A which is optionally substituted is

Chemical formula

[0209] Group R 1 and R 2 In certain embodiments, R 1 and R 2 are each independently C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, NO2, COC1-C 6 alkyl, CO-C6-C 10 aryl, CO(5- to 10-membered heteroaryl), CO 2C1-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, N H2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, 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 heterocyclo alkyl selected from, C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl and 3- to 7-membered heterocycloalkyl are 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 hetero aryl, OCOC1-C6 alkyl, OCOC6-C 10 aryl, OCO(5- to 1 0-membered heteroaryl), and OCO(3- to 7-membered heterocycloalkyl) are each independently optionally substituted with one or more substituents selected independently therefrom; wherein, R 1 or R 2 C3-C7 cycloalkyl or R 1 or R 2 3- to 7-membered heterocycloalkyl each C1-C6 alkyl substituent and each C1-C6 alkoxy substit uent are each independently further optionally substituted with 1 to 3 hydroxy, halo, NR 8 R 9 、or oxo; wherein, 3- to 7-membered heterocycloalkyl, C6-C aryl, and 5- to 10-membered 10 heteroaryl are each independently optionally substituted with one or more substituents selected from halo, C1-C6 alkyl, and OC1-C6 alkyl; or at least one pair of R and R on adjacent atoms together with the atom connecting them form at least one C4-C8 carbocyclic ring or at least one 5- to 8-membered heterocyclic ring containing 1 or 2 heteroatoms selected independently from O, N, and S, wherein the carbocyclic ring or heterocyclic ring is hydroxy, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR or R on adjacent atoms together with the atom connecting them form at least one C4-C8 carbocyclic ring or at least one 5- to 8-membered heterocyclic ring containing 1 or 2 heteroatoms selected independently from O, N, and S, wherein the carbocyclic ring or heterocyclic ring is hydroxy, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR 1 and R 2 of at least one pair thereof together with the atom connecting them form at least one C4-C8 carbocyclic ring or at least one 5- to 8-membered heterocyclic ring containing 1 or 2 heteroatoms selected independently from O, N, and S, wherein the carbocyclic ring or heterocyclic ring is hydroxy, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR together with the atom connecting them form at least one C4-C8 carbocyclic ring or at least one 5- to 8-membered heterocyclic ring containing 1 or 2 heteroatoms selected independently from O, N, and S, wherein the carbocyclic ring or heterocyclic ring is hydroxy, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR independently form at least one 5- to 8-membered heterocyclic ring containing 1 or 2 heteroatoms selected independently from O, N, and S, wherein the carbocyclic ring or heterocyclic ring is hydroxy, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR alkyl, C1-C6 alkoxy, NR alkyl, C1-C6 alkoxy, NR 8 R9 、 =NR 10 、 COOC1-C6 alkyl, C6 ~C 10 aryl, and CONR 8 R 9 is optionally substituted with one or more substituents independently selected from and is optionally independently substituted; In certain embodiments, R 1 and R 2 are each independently C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, NO2, COC1-C 6 alkyl, CO-C6-C 10 aryl; CO(5- to 10-membered heteroaryl); CO 2C1-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, N H2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, 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 heterocyclo alkyl selected from, wherein C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl and and 3- to 7-membered heterocycloalkyl are hydroxy, halo, CN, oxo, C1-C6 a lkyl, C1-C6 alkoxy, NR 8 R 9 、 =NR 10 、 COOC1-C6 alkyl, CONR8 R 9 、 a 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), NHCO C1-C6 alkyl, NHCOC6-C 10 aryl, NHCO(5- to 10-membered hetero aryl), NHCO(3- to 7-membered heterocycloalkyl), and NHCOC2-C6 al kenyl, each independently optionally substituted with one or more substituents selected therefrom; wherein R 1 or R 2 C3-C7 cycloalkyl or R 1 or R 2 3- to each C1-C6 alkyl substituent and each C1-C6 alkoxy substituent of a 7-membered heterocycloalkyl is further optionally independently substituted with 1 to 3 hydroxy, halo, NR R 8 R 9 、 or oxo; wherein the 3- to 7-membered heterocycloalkyl, C6-C aryl, 5- to 10-membered hete 10 roaryl, NHCOC6-C aryl, NHCO(5- to 10-membered heteroaryl) 10 and NHCO(3- to 7-membered heterocycloalkyl) are each optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl; or at least one pair of R and R on adjacent atoms together with the atom connecting them forms at least one C4-C8 carbocyclic ring or is independently selected from O, N, and S 1 and R 2 forms, together with the atom connecting them, at least one C4-C8 carbocyclic ring or is independently selected from O, N, and S and together form at least one C4-C8 carbocyclic ring or is independently selected from O, N, and S to independently form at least one 5- to 8-membered heterocyclic ring containing one or two heteroatoms wherein the carbocyclic or heterocyclic ring is optionally independently substituted with one or more substituents selected independently from hydroxy, halo, oxo, C1-C6 alkyl , C1-C6 alkoxy, NR 8 R 9 , =NR 10 , COOC1-C6 alkyl, C6 -C 10 aryl, and CONR 8 R 9 ; optionally independently substituted; In certain embodiments, R and R 1 are each independently C1-C6 haloalkyl, C1-C6 alkoxy 2 , C1-C6 haloalkoxy, halo, CN, NO2, COC1-C6 alkyl, CO-C 6-C aryl, CO(5- to 10-membered heteroaryl), CO2C1-C6 alkyl 10 , CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C aryl, OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered heterocycloalkyl 10 yl), C6-C aryl, 5- to 10-membered heteroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, CONR 10 R R 8 , SF5, SC1-C6 alkyl 9 , S(O2)C1-C6 alkyl, S(O2)NR R 11 , S(O)C1-C6 a 12 lkyl, C3-C7 cycloalkyl and 3- to 7-membered heterocycloalkyl, and wherein C3-C7 cycloalkyl, C1-C6 haloalkyl, and 3- to 7-membered hetero cycloalkyl, and Cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR 8 R 9 , =NR 10 , COOC1-C6 alkyl, CONR 8 R 9 , 3 membered-7-membered heterocycloalkyl, C6-C 10 aryl, 5-membered-10-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 aryl, OCO(5-membered-10-membered hetero aryl), OCO(3-membered-7-membered heterocycloalkyl), NHCOC1-C6 alkyl , NHCOC6-C 10 aryl, NHCO(5-membered-10-membered heteroaryl), NHCO (3-membered-7-membered heterocycloalkyl), and NHCOC2-C6 alkynyl; wherein each C1-C6 alkyl substituent and each C1-C6 alkoxy substituent of the 3-membered-7-membered heterocycloalkyl is optionally further independently substituted with 1-3 hydroxy, halo, NR here, R 1 or R 2 C3-C7 cycloalkyl or R 1 or R 2 3-membered- 7-membered heterocycloalkyl; and each C1-C6 alkyl substituent and each C1-C6 alkoxy substituent of the 3-membered-7-membered heterocycloalkyl is optionally further independently substituted with 1-3 hydroxy, halo, NR R 8 R 9 , or oxo; wherein the 3-membered-7-membered heterocycloalkyl, C6-C aryl, 5-membered-10-membered hete 10 roaryl, NHCOC6-C aryl, NHCO(5-membered-10-membered heteroaryl) 10 and NHCO(3-membered-7-membered heterocycloalkyl) are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl; ; ; or R on an adjacent atom 1 and R 2 at least one pair of which, together with the atom connecting them forms, independently, at least one C4-C8 carbocyclic ring or at least one 5- to 8-membered heterocyclic ring containing one or two heteroatoms independently selected from O, N, and S wherein the carbocyclic or heterocyclic ring is optionally independently substituted with one or more substituents independently selected from hydroxy, halo, oxo, C1-C6 alkyl C1-C6 alkoxy, NR R 8 R 9 =NR 10 COOC1-C6 alkyl, C6 -C 10 aryl, and CONR 8 R 9 and is optionally independently substituted with one or more substituents independently selected from In certain embodiments

[0210] R and R 1 each independently is C1-C6 alkyl, halo, CN, NO2, CO 2 C1-C6 alkyl, CO-C6-C aryl, CO(5- to 10-membered heteroaryl 10 ), CO2C1-C6 alkyl, OCOC1-C6 alkyl, OCOC6-C aryl 10 OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered heterocycloalkyl ), C6-C aryl, 5- to 10-membered heteroaryl, NH2, NHC1-C6 alkyl 10 N(C1-C6 alkyl)2, CONR R 8 R 9 SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, S(O2)NR 11 R 12 S(O)C1-C6 alkyl cycloalkyl and 3- to 7-membered heterocycloalkyl and is selected from C3-C7 Here, C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl and 3- to 7-membered heterocycloalkyl are each optionally substituted with one or more substituents independently selected from 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), NHCO C1-C6 alkyl, NHCOC6-C 10 aryl, NHCO(5- to 10-membered hetero aryl), NHCO(3- to 7-membered heterocycloalkyl), and NHCOC2-C6 alk ynyl; and are each optionally substituted with one or more substituents independently selected therefrom; Here, R 1 or R 2 C3-C7 cycloalkyl or R 1 or R 2 3- to each C1-C6 alkyl substituent and each C1-C6 alkoxy substituent of 7-membered heterocycloalkyl are each further optionally and independently substituted with 1 to 3 hydroxy, halo, NR R 8 R 9 、or oxo; and are each optionally substituted with one or more substituents independently selected therefrom; Here, 3- to 7-membered heterocycloalkyl, C6-C 10 aryl, 5- to 10-membered hetero aryl, NHCOC6-C 10 aryl, NHCO(5- to 10-membered heteroaryl) and NHCO(3- to 7-membered heterocycloalkyl) are each halo, C1-C6 alkyl, and optionally substituted with one or more substituents independently selected from C1-C6 alkyl ; or R on adjacent atoms 1 and R 2 at least one pair of which, together with the atom connecting them form, independently, at least one C4-C8 carbocyclic ring or at least one 5- to 8-membered heterocyclic ring containing one or two heteroatoms independently selected from O, N, and S wherein the carbocyclic or heterocyclic ring is optionally independently substituted with one or more substituents independently selected from hydroxy, halo, oxo, C1-C6 alkyl C1-C6 alkoxy, NR R 8 R 9 =NR 10 COOC1-C6 alkyl, C6 -C 10 aryl, and CONR 8 R 9 optionally independently substituted with one or more substituents independently selected from .

[0211] In certain embodiments R 1 and R 2 are each, independently, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, NO2, COC1-C 6 alkyl, CO-C6-C 10 aryl, CO(5- to 10-membered heteroaryl), CO 2C1-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, N H2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, 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 selected from, wherein C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl and 3- to 7-membered heterocycloalkyl are each independently optionally substituted with one or more substituents selected from hydroxy, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR R 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), NHCO C1-C6 alkyl, NHCOC6-C 10 aryl, NHCO(5- to 10-membered heteroaryl), NHCO(3- to 7-membered heterocycloalkyl), and NHCOC2-C6 alk ynyl, each independently optionally substituted with one or more substituents selected therefrom; wherein each C1-C6 alkyl substituent and each C1-C6 alkoxy substituent of 3- to 7-membered heterocycloalkyl, C3-C7 cycloalkyl or R wherein R 1 or R 2 C3-C7 cycloalkyl or R 1 or R 2 3- to 7-membered heterocycloalkyl is further optionally independently substituted with 1 to 3 hydroxy, halo, or oxo; wherein 3- to 7-membered heterocycloalkyl, C6-C ; wherein 3- to 7-membered heterocycloalkyl, C6-C 10Aryl, 5- to 10-membered hetero Lower aryl, 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 ; Or R on adjacent atoms 1 And R 2 At least one pair of which, together with the atoms connecting them Forms at least one C4-C8 carbocyclic ring or at least one 5- to 8-membered heterocyclic ring containing one or two heteroatoms independently selected from O, N, and S Independently, where the carbocyclic ring or heterocyclic ring is hydroxy, halo, oxo, C1-C6 alkyl C1-C6 alkoxy, NR R 8 R 9 =NR 10 COOC1-C6 alkyl, C6 -C 10 Aryl, and CONR 8 R 9 Optionally independently substituted with one or more substituents independently selected from Optionally independently substituted.

[0212] In certain embodiments R 1 And R 2 Are each independently C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, NO2, COC1-C 6 alkyl, CO-C6-C 10 Aryl, CO(5- to 10-membered heteroaryl), CO 2C1-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-membered to 10-membered heteroaryl, N H2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, 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-membered to 7-membered heterocyclo alkyl selected from, wherein C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl and 3-membered to 7-membered heterocycloalkyl are hydroxy, halo, CN, oxo, C1-C6 a lkyl, C1-C6 alkoxy, NR 8 R 9 , =NR 10 , COOC1-C6 alkyl, CONR 8 R 9 , 3-membered to 7-membered heterocycloalkyl, C6-C 10 aryl, 5-membered to 10 membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 aryl, OCO( 5-membered to 10-membered heteroaryl), OCO(3-membered to 7-membered heterocycloalkyl), NHCO C1-C6 alkyl, NHCOC6-C 10 aryl, NHCO(5-membered to 10-membered hetero aryl), NHCO(3-membered to 7-membered heterocycloalkyl), and NHCOC2-C6 al kenyl are each independently optionally substituted with one or more substituents selected therefrom; wherein 3-membered to 7-membered heterocycloalkyl, C6-C 10 aryl, 5-membered to 10-membered hete roaryl, NHCOC6-C 10 aryl, NHCO(5-membered 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.

[0213] In certain embodiments, R 1 and R 2 are each independently C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, NO2, COC1-C 6 alkyl, CO-C6-C 10 aryl, CO(5- to 10-membered heteroaryl), CO 2C1-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, N H2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, 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 selected from, wherein C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl and 3- to 7-membered heterocycloalkyl are each unsubstituted; or at least one pair of R 1 and R 2 on adjacent atoms, together with the atoms connecting them, form at least one C4-C8 carbocyclic ring or are independently selected from O, N, and S ​to independently form at least one 5- to 8-membered heterocyclic ring containing one or two heteroatoms wherein the carbocyclic or heterocyclic ring is optionally independently substituted with one or more substituents independently selected from hydroxy, halo, oxo, C1-C6 alkyl , C1-C6 alkoxy, NR 8 R 9 , =NR 10 , COOC1-C6 alkyl, C6 -C 10 aryl, and CONR 8 R 9 ; In certain embodiments R and R 1 are each independently selected from C1-C6 alkyl, halo, CN, COC1-C 2 6 alkyl, CO2C1-C6 alkyl, C6-C aryl, S(O)C1-C6 al 10 kyl, 5- to 10-membered heteroaryl, and 3- to 7-membered heterocycloalkyl wherein the C1-C6 alkyl and 3- to 7-membered heterocycloalkyl are each optionally substituted with one or more substituents independently selected from hydroxy and oxo. In certain embodiments, m = 1 and n = 0; R

[0214] is C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1 -C6 haloalkoxy, halo, CN, NO2, COC1-C6 alkyl, CO-C6-C 1 aryl , CO(5- to 10-membered heteroaryl), CO2C1-C6 alkyl, CO 10 2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C aryl 10 , 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 group, N(C1 - C6 alkyl)2, CONR 8 R 9 , SF5, SC1 - C6 alkyl, S (O2)C1 - C6 alkyl, S(O2)NR 11 R 12 , S(O)C1 - C6 alkyl , selected from C3 - C7 cycloalkyl and 3 - to 7 - membered heterocycloalkyl, wherein C1 - C6 alkyl, C1 - C6 haloalkyl, C3 - C7 cycloalkyl and 3 - to 7 - membered heterocycloalkyl are each independently optionally substituted with one or more substituents selected from hydroxy, halo, CN, oxo, C1 - C6 alkyl, C1 - C6 alkoxy, NR R 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), NHCO C1 - C6 alkyl, NHCOC6 - C 10 aryl, NHCO(5 - to 10 - membered heteroaryl yl), NHCO(3 - to 7 - membered heterocycloalkyl), and NHCOC2 - C6 alk ynyl, each independently optionally substituted with one or more substituents selected therefrom; wherein 3 - to 7 - membered heterocycloalkyl, C6 - C 10 aryl, 5 - to 10 - membered hete roaryl, NHCOC6 - C 10 aryl, NHCO(5 - to 10 - membered heteroaryl) and NHCO(3- to 7-membered hetero cycloalkyl) is optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl.

[0215] In certain embodiments, m = 1; n = 0; R 1 is selected from C1-C6 alkyl, halo, CN, COC1-C6 alkyl, CO2C1-C 6 alkyl, C6-C 10 aryl, 5- to 10-membered heteroaryl, S(O)C1-C6 alkyl, and 3- to 7-membered hetero cycloalkyl, where C1-C6 alkyl and 3- to 7-membered hetero cycloalkyl are optionally substituted with one or more substituents independently selected from hydroxy and oxo.

[0216] In certain embodiments, m = 1; n = 1; R 1 and R 2 are each independently C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, NO2, COC1-C 6 alkyl, CO-C6-C 10 aryl, CO(5- to 10-membered heteroaryl), CO 2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6-C 10 aryl, OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered hetero cycloalkyl), C6-C 10 aryl, 5- to 10-membered heteroaryl, N H2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, 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 selected from, wherein C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl and 3- to 7-membered heterocycloalkyl are each independently optionally substituted with one or more substituents selected from hydroxy, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR R 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), NHCO C1-C6 alkyl, NHCOC6-C 10 aryl, NHCO(5- to 10-membered heteroaryl yl), NHCO(3- to 7-membered heterocycloalkyl), and NHCOC2-C6 alk ynyl are each independently optionally substituted with one or more substituents selected therefrom; wherein 3- to 7-membered heterocycloalkyl, C6-C 10 aryl, 5- to 10-membered hete roaryl, NHCOC6-C 10 aryl, NHCO(5- to 10-membered heteroaryl) and NHCO(3- to 7-membered heterocycloalkyl) are each independently optionally substituted with one or more substituents selected from halo, C1-C6 alkyl, and OC1-C6 alkyl; ; In certain embodiments, m = 1; n = 1; R 1 and R 2 are each, independently, C1-C6 alkyl, halo, CN, COC1-C 6 alkyl, CO2C1-C6 alkyl, C6-C 10 aryl, 5- to 10-membered heteroar yl, S(O)C1-C6 alkyl, and 3- to 7-membered heterocycloalkyl, selected from among them, wherein C1-C6 alkyl and 3- to 7-membered heterocycloalkyl are each optionally substituted with one or more substituents independently selected from hydroxy and oxo.

[0217] In certain embodiments, m = 1; n = 1; R 1 and R 2 are on adjacent atoms and together with the atom connecting them form a C4- C8 carbocyclic ring or a 5- to 8-membered heterocyclic ring containing one or two heteroatoms independently selected from O, N, and S, wherein the carbocyclic or heterocyclic ring is optionally independently substituted with one or more substituents selected from hydroxy, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR R 8 R 9 =NR 10 =, COOC1 -C6 alkyl, C6-C 10 aryl, and CONR 8 R 9 from among 1 or more substituents.

[0218] In certain embodiments, m = 1; n = 1; R 1 and R 2 are on adjacent atoms and together with the atom connecting them form a C6 carbo cyclic ring or a 5-membered heterocyclic ring containing one or two heteroatoms independently selected from O, N, and S, Form a 5- to 6-membered carbocyclic or heterocyclic ring, where the carbocyclic or heterocyclic ring is hydroxy, halo, oxo, C 1-C6 alkyl, C1-C6 alkoxy, NR 8 R 9 , =NR 10 , COOC1-C6 alkyl, C6-C 10 aryl, and CONR 8 R 9 is optionally independently substituted with one or more substituents independently selected from.

[0219] In certain embodiments, m = 1; n = 1; R 1 and R 2 are on adjacent atoms and together with the atom connecting them form a C5 carb ocyclic or 5-membered to 6-membered heterocyclic ring containing one or two heteroatoms independently selected from O, N, and S, where the carbocyclic or heterocyclic ring is hydroxy, halo, oxo, C 1-C6 alkyl, C1-C6 alkoxy, COOC1-C6 alkyl, C6-C aryl, and CONR 10 A ryl, and CONR 8 R 9 is optionally independently substituted with one or more substituents independently selected from.

[0220] In certain embodiments, m = 1; n = 1; R 1 and R 2 are on adjacent atoms and together with the atom connecting them form a C4- C8 carbocyclic or 5-membered to 8-membered heterocyclic ring containing one or two heteroatoms independently selected from O, N, and S, where the carbocyclic or heterocyclic ring is unsubstituted.

[0221] Specific embodiments where m = 1 and n = 0: In certain embodiments, R 1 ​​is C1 optionally substituted with one or more hydroxy groups ~C6 alkyl.

[0222] In certain embodiments, R 1 is 1-hydroxy-2-methylpropan-2-yl .

[0223] In certain embodiments, R 1 is 2-hydroxyethyl.

[0224] In certain embodiments, R 1 is C1~C6 alkyl.

[0225] In certain embodiments, R 1 is methyl.

[0226] In certain embodiments, R 1 is isopropyl.

[0227] In certain embodiments, R 1 is isopropyl.

[0228] In certain embodiments, R 1 is C1~C6 alkyl substituted with hydroxy at the carbon directly linked to ring A ~C6 alkyl.

[0229] In certain embodiments, R 1 is 2-hydroxy-2-propyl.

[0230] In certain embodiments, R 1 is hydroxymethyl.

[0231] In certain embodiments, R 1 is 1-hydroxyethyl.

[0232] In certain embodiments, R 1 is 1-hydroxy-2-propyl.

[0233] In one embodiment, R 1 is a C1-C6 alkyl substituted with two or more hydroxy groups.

[0234] In one embodiment, R 1 is a C1-C6 alkyl substituted with two or more hydroxy groups, where one of the two or more hydroxy groups is bonded to the carbon directly linked to ring A.

[0235] In one embodiment, R 1 is 1,2-dihydroxy-prop-2-yl.

[0236] In one embodiment, R 1 is a C3-C7 cycloalkyl optionally substituted with one or more hydroxy groups.

[0237] In one embodiment, R 1 is a C3-C7 cycloalkyl.

[0238] In one embodiment, R 1 is a C3-C7 cycloalkyl substituted with hydroxy at the carbon directly linked to ring A.

[0239] In one embodiment, R 1 is 1-hydroxy-1-cyclopropyl.

[0240] In one embodiment, R 1 is 1-hydroxy-1-cyclobutyl.

[0241] In one embodiment, R 1 is 1-hydroxy-1-cyclopentyl.

[0242] In one embodiment, R 1 is 1-hydroxy-1-cyclohexyl.​​​​​

[0243] In certain embodiments, R 1 is a 3- to 7-membered heterocycloalkyl optionally substituted with one or more hydroxy groups.

[0244] In certain embodiments, R 1 is a 3- to 7-membered heterocycloalkyl.

[0245] In certain embodiments, R 1 is morpholinyl (e.g., 1-morpholinyl).

[0246] In certain embodiments, R 1 is 1,3-dioxolan-2-yl.

[0247] In certain embodiments, R 1 is a 3- to 7-membered heterocycloalkyl optionally substituted with one or more C1-C6 alkyl groups.

[0248] In certain embodiments, R 1 is 1-methylpyrrolidin-2-yl.

[0249] In certain embodiments, R 1 is a 3- to 7-membered heterocycloalkyl substituted with hydroxy at the carbon directly linked to ring A.

[0250] In certain embodiments, R 1 is a C1-C6 alkyl optionally substituted with one or more oxo groups.

[0251] In certain embodiments, R 1 is COCH3.

[0252] In certain embodiments, R 1 is COCH2CH3.

[0253] ​​​​ In one embodiment, R 1 is C3-C 7 cycloalkyl optionally substituted with one or more oxo groups.

[0254] In one embodiment, R 1 is 3- to 7-membered heterocycloalkyl optionally substituted with one or more oxo groups.

[0255] In one embodiment, R 1 is C1-C6 alkyl optionally substituted with one or more C1-C6 alkoxy groups.

[0256] In one embodiment, R 1 is 2-methoxy-2-propyl.

[0257] In one embodiment, R 1 is methoxymethyl.

[0258] In one embodiment, R 1 is C3-C7 cycloalkyl optionally substituted with one or more C1-C6 alkoxy groups.

[0259] In one embodiment, R 1 is 3- to 7-membered heterocycloalkyl optionally substituted with one or more C1-C6 alkoxy groups.

[0260] In one embodiment, R 1 is C1 8 R 9 -C6 alkyl optionally substituted with one or more NR R.

[0261] In one embodiment, R 1 is substituted with NR 8 R 9 at the carbon directly linked to ring A. It is C1-C6 alkyl.

[0262] In certain embodiments, R 1 is (methylamino)methyl.

[0263] In certain embodiments, R 1 is (dimethylamino)methyl.

[0264] In certain embodiments, R 1 is aminomethyl.

[0265] In certain embodiments, R 1 is N-methylacetamidomethyl.

[0266] In certain embodiments, R 1 is 1-(dimethylamino)ethan-1-yl.

[0267] In certain embodiments, R 1 is 2-(dimethylamino)propan-2-yl.

[0268] In certain embodiments, R 1 is (2-methoxy-ethan-1-yl)(methyl)aminometh yl.

[0269] In certain embodiments, R 1 is (methyl)(acetyl)aminomethyl.

[0270] In certain embodiments, R 1 is (methyl)(cyclopropylmethyl)aminomethyl is.

[0271] In certain embodiments, R 1 is (methyl)(2,2-difluoroethan-1-yl)ami nomethyl.

[0272] In certain embodiments, R 1 is one or more NR8 R 9 is optionally replaced with C3 ~C7 cycloalkyl.

[0273] In certain embodiments, R 1 is a 3-membered 8 R 9 ~7-membered heterocycloalkyl optionally substituted with one or more NR R.

[0274] In certain embodiments, R 1 is C1 ~C6 haloalkyl optionally substituted with one or more hydroxy.

[0275] In certain embodiments, R 1 is C1~C6 alkoxy.

[0276] In certain embodiments, R 1 is C1~C6 haloalkoxy.

[0277] In certain embodiments, R 1 is C1~C6 alkyl optionally substituted with 3-membered~7-membered heterocycloalkyl, where the 3-membered~7-membered heterocycloalkyl is further optionally substituted as defined elsewhere in this specification.

[0278] In certain embodiments, R 1 is pyrrolidinylmethyl (e.g., pyrrolidin-1-ylmethyl).

[0279] In certain embodiments, R 1 is optionally substituted pyrrolidinylmethyl (e.g., 3,3-difluoropyrrolidin-1-ylmethyl).

[0280] In certain embodiments, R 1 ​​​is azetidinylmethyl (e.g., azetidin-1-ylmethyl).

[0281] In certain embodiments, R 1 is optionally substituted azetidinylmethyl (e.g., 3-methoxyazetidin-1-ylmethyl).

[0282] In certain embodiments, R 1 is morpholinylmethyl (e.g., morpholin-4-ylmethyl).

[0283] In certain embodiments, R 1 is halo.

[0284] In certain embodiments, R 1 is fluoro.

[0285] In certain embodiments, R 1 is chloro.

[0286] In certain embodiments, R 1 is CN.

[0287] In certain embodiments, R 1 is NO2.

[0288] In certain embodiments, R 1 is COC1-C6 alkyl.

[0289] In certain embodiments, R 1 is CO-C6-C 10 aryl.

[0290] In certain embodiments, R 1 is CO(5-membered to 10-membered heteroaryl).

[0291] In certain embodiments, R 1 is CO2C1-C6 alkyl. ​​

[0292] In one embodiment, R 1 is CO2C3-C8 cycloalkyl.

[0293] In one embodiment, R 1 is OCOC1-C6 alkyl.

[0294] In one embodiment, R 1 is OCOC6-C 10 aryl.

[0295] In one embodiment, R 1 is OCO(5- to 10-membered heteroaryl).

[0296] In one embodiment, R 1 is OCO(3- to 7-membered heterocycloalkyl).

[0297] In one embodiment, R 1 is C6-C 10 aryl.

[0298] In one embodiment, R 1 is phenyl.

[0299] In one embodiment, R 1 is 5- to 10-membered heteroaryl.

[0300] In one embodiment, R 1 is pyridyl (e.g., 4-pyridyl).

[0301] In one embodiment, R 1 is pyrazolyl (e.g., 1-pyrazolyl).

[0302] In one embodiment, R 1 is NH2.

[0303] In one embodiment, R 1 is NHC1-C6 alkyl.

[0304] In one embodiment, R 1 is N(C1-C6 alkyl)2.

[0305] In one embodiment, R 1 is CONR 8 R 9 wherein.

[0306] In one embodiment, R 1 is SF5.

[0307] In one embodiment, R 1 is SC1-C6 alkyl, In one embodiment, R 1 is S(O2)C1-C6 alkyl.

[0308] In one embodiment, R 1 is S(O2)CH3.

[0309] In one embodiment, R 1 is S(O2)NR 11 R 12 wherein.

[0310] In one embodiment, R 1 is S(O2)N(CH3)2.

[0311] In one embodiment, R 1 is S(O)C1-C6 alkyl.

[0312] In one embodiment, R 1 is S(O)CH3.

[0313] In one embodiment, R 1 is attached to the carbon of aryl ring A.

[0314] In one embodiment, R 1 is attached to the carbon of heteroaryl ring A.

[0315] In one embodiment, R 1 is attached to the nitrogen of heteroaryl ring A.

[0316] A specific embodiment where m = 1 and n = 1: In one embodiment, R 1 is C1-C6 alkyl optionally substituted with one or more hydroxy, and R is C1-C6 alkyl optionally substituted with one or more hydroxy. 2 is C1-C6 alkyl optionally substituted with one or more hydroxy. is C1-C6 alkyl optionally substituted with one or more hydroxy.

[0317] In one embodiment, R 1 is 1-hydroxy-2-methylpropan-2-yl and R 2 is methyl.

[0318] In one embodiment, R 1 is 2-hydroxy-2-propyl and R 2 is methyl is.

[0319] In one embodiment, R 1 is 2-hydroxy-2-propyl and R 2 is isopro pyl.

[0320] In one embodiment, R 1 is 2-hydroxy-2-propyl and R 2 is 2-hydro xy-2-propyl.

[0321] In one embodiment, R 1 is 2-hydroxy-2-propyl and R 2 is 1-hydro xyethyl.

[0322] In one embodiment, R 1 is hydroxymethyl and R 2 is methyl.

[0323] In one embodiment, R 1 is 1-hydroxyethyl, and R 2 is methyl.

[0324] In one embodiment, R 1 is 2-hydroxyethyl, and R 2 is methyl.

[0325] In one embodiment, R 1 is 1-hydroxy-2-propyl, and R 2 is methyl is.

[0326] In one embodiment, R 1 is C1 to C6 alkyl optionally substituted with one or more hydroxy groups, and R 2 is C6 to C 10 aryl.

[0327] In one embodiment, R 1 is 2-hydroxy-2-propyl, and R 2 is phenyl is.

[0328] In one embodiment, R 1 is C1 to C6 alkyl optionally substituted with one or more hydroxy groups, and R 2 is 5- to 10-membered heteroaryl.

[0329] In one embodiment, R 1 is 2-hydroxy-2-propyl, and R 2 is pyridyl is.

[0330] In one embodiment, R 1 is 2-hydroxy-2-propyl, and R 2 is pyrazol yl.

[0331] In one embodiment, R1 is C1 ~C6 alkyl optionally substituted with one or more hydroxy groups, and R 2 is SF5.

[0332] In certain embodiments, R 1 is C1 ~C6 alkyl optionally substituted with one or more hydroxy groups, and R 2 is SC1~C6 alkyl, In certain embodiments, R 1 is C1 ~C6 alkyl optionally substituted with one or more hydroxy groups, and R 2 is S(O2)C1~C6 alkyl.

[0333] In certain embodiments, R 1 is C1 ~C6 alkyl optionally substituted with one or more hydroxy groups, and R 2 is S(O2)CH3.

[0334] In certain embodiments, R 1 is C1 ~C6 alkyl optionally substituted with one or more hydroxy groups, and R 2 is halo.

[0335] In certain embodiments, R 1 is 2-hydroxy-2-propyl, and R 2 is chloro there is.

[0336] In certain embodiments, R 1 is 2-hydroxy-2-propyl, and R 2 is fluoro there is.

[0337] In certain embodiments, R 1 is C3 ~C7 cycloalkyl optionally substituted with one or more hydroxy groups, and R 2is C1-C6 alkyl.

[0338] In certain embodiments, R 1 is 1-hydroxy-1-cyclopropyl and R 2 is me thyl.

[0339] In certain embodiments, R 1 is 1-hydroxy-1-cyclobutyl and R 2 is methyl yl.

[0340] In certain embodiments, R 1 is 1-hydroxy-1-cyclopentyl and R 2 is me thyl.

[0341] In certain embodiments, R 1 is 1-hydroxy-1-cyclohexyl and R 2 is me thyl.

[0342] In certain embodiments, R 1 is a 3- to 7-membered heterocycloalkyl optionally substituted with one or more hydroxy groups, and R 2 is C1-C6 alkyl.

[0343] In certain embodiments, R 1 is morpholinyl and R 2 is methyl.

[0344] In certain embodiments, R 1 is 1,3-dioxolan-2-yl and R 2 is methyl yl.

[0345] In certain embodiments, R 1 is a 3- to 7-membered heterocycloalkyl optionally substituted with one or more hydroxy groups, and R 2 is halo.

[0346] In one embodiment, R 1 is 1,3-dioxolan-2-yl and R 2 is fluoro .

[0347] In one embodiment, R 1 is 1,3-dioxolan-2-yl and R 2 is chloro .

[0348] In one embodiment, R 1 is C1-C 6 alkyl optionally substituted with one or more oxo and R 2 is methyl.

[0349] In one embodiment, R 1 is COCH3 and R 2 is methyl.

[0350] In one embodiment, R 1 is C1-C6 alkyl optionally substituted with one or more C1-C6 alkoxy and R 2 is C1-C6 alkyl.

[0351] In one embodiment, R 1 is 2-methoxy-2-propyl and R 2 is methyl .

[0352] In one embodiment, R 1 is C1 8 -C6 alkyl optionally substituted with one or more NR 9 R and R 2 is C1-C6 alkyl.

[0353] In one embodiment, R 1 is (dimethylamino)methyl and R 2 is methyl .

[0354] In one embodiment, R 1 is C1 8 R 9 to C6 alkyl optionally substituted with one or more NR and R 2 is halo.

[0355] In one embodiment, R 1 is (dimethylamino)methyl and R 2 is fluoro .

[0356] In one embodiment, R 1 is (dimethylamino)methyl and R 2 is fluoro .

[0357] In one embodiment, R 1 is (methylamino)methyl and R 2 is fluoro .

[0358] In one embodiment, R 1 is aminomethyl and R 2 is fluoro

[0359] In one embodiment, R 1 is C1 to C6 alkyl and R 2 is C1 to C6 alkyl .

[0360] In one embodiment, R 1 is methyl and R 2 is methyl

[0361] In one embodiment, R 2 is 1-hydroxy-2-methylpropan-2-yl and R 1 is methyl

[0362] In one embodiment, R 2 is 2-hydroxy-2-propyl, and R 1 is methyl there is.

[0363] In one embodiment, R 2 is 2-hydroxy-2-propyl, and R 1 is isopro pyl.

[0364] In one embodiment, R 2 is 2-hydroxy-2-propyl, and R 1 is 1-hyd roxyethyl.

[0365] In one embodiment, R 2 is hydroxymethyl, and R 1 is methyl.

[0366] In one embodiment, R 2 is 1-hydroxyethyl, and R 1 is methyl.

[0367] In one embodiment, R 2 is 2-hydroxyethyl, and R 1 is methyl.

[0368] In one embodiment, R 2 is 1-hydroxy-2-propyl, and R 1 is methyl there is.

[0369] In one embodiment, R 2 is C1 optionally substituted with one or more hydroxy groups and is C6 1 alkyl, and R 10 is C6~C

[0370] In one embodiment, R 2 is 2-hydroxy-2-propyl, and R 1 is phenyl It is.

[0371] In certain embodiments, R 2 is C1 -C6 alkyl optionally substituted with one or more hydroxy groups, and R 1 is a 5- to 10-membered heteroaryl.

[0372] In certain embodiments, R 2 is 2-hydroxy-2-propyl, and R 1 is pyridyl It is.

[0373] In certain embodiments, R 2 is 2-hydroxy-2-propyl, and R 1 is pyrazol It is.

[0374] In certain embodiments, R 2 is C1 -C6 alkyl optionally substituted with one or more hydroxy groups, and R 1 is SF5.

[0375] In certain embodiments, R 2 is C1 -C6 alkyl optionally substituted with one or more hydroxy groups, and R 1 is SC1-C6 alkyl.

[0376] In certain embodiments, R 2 is C1 -C6 alkyl optionally substituted with one or more hydroxy groups, and R 1 is S(O2)C1-C6 alkyl.

[0377] In certain embodiments, R 2 is C1 -C6 alkyl optionally substituted with one or more hydroxy groups, and R 1 is S(O2)CH3.

[0378] In one embodiment, R 2 is C1 ~C6 alkyl optionally substituted with one or more hydroxy groups, and R 1 is halo.

[0379] In one embodiment, R 2 is 2-hydroxy-2-propyl, and R 1 is chloro thereby.

[0380] In one embodiment, R 2 is 2-hydroxy-2-propyl, and R 1 is fluoro thereby.

[0381] In one embodiment, R 2 is C3 ~C7 cycloalkyl optionally substituted with one or more hydroxy groups, and R 1 is C1~C6 alkyl.

[0382] In one embodiment, R 2 is 1-hydroxy-1-cyclopropyl, and R 1 is me thyl.

[0383] In one embodiment, R 2 is 1-hydroxy-1-cyclobutyl, and R 1 is meth yl.

[0384] In one embodiment, R 2 is 1-hydroxy-1-cyclopentyl, and R 1 is me thyl.

[0385] In one embodiment, R 2 is 1-hydroxy-1-cyclohexyl, and R 1 is me thyl.

[0386] In one embodiment, R 2 is a 3-membered to 7-membered heterocycloalkyl optionally substituted with one or more hydroxy groups, and R 1 is C1-C6 alkyl.

[0387] In one embodiment, R 2 is morpholinyl, and R 1 is methyl.

[0388] In one embodiment, R 2 is 1,3-dioxolan-2-yl, and R 1 is methyl is.

[0389] In one embodiment, R 2 is a 3-membered to 7-membered heterocycloalkyl optionally substituted with one or more hydroxy groups, and R 1 is halo.

[0390] In one embodiment, R 2 is 1,3-dioxolan-2-yl, and R 1 is fluoro is.

[0391] In one embodiment, R 2 is 1,3-dioxolan-2-yl, and R 1 is chloro is.

[0392] In one embodiment, R 2 is C1-C 6 alkyl optionally substituted with one or more oxo groups, and R 1 is methyl.

[0393] In one embodiment, R 2 is COCH3, and R 1 is methyl.

[0394] In one embodiment, R2 is C1-C6 alkyl optionally substituted with one or more C1-C6 alkoxy and R 1 is C1-C6 alkyl.

[0395] In one embodiment, R 2 is 2-methoxy-2-propyl and R 1 is methyl .

[0396] In one embodiment, R 2 is C1-C6 alkyl optionally substituted with one or more NR 8 R 9 and R is C1-C6 alkyl. 1 is C1-C6 alkyl.

[0397] In one embodiment, R 2 is (dimethylamino)methyl and R 1 is methyl .

[0398] In one embodiment, R 2 is C1-C6 alkyl optionally substituted with one or more NR 8 R 9 and R is halo. 1 is halo.

[0399] In one embodiment, R 2 is (dimethylamino)methyl and R 1 is fluoro .

[0400] In one embodiment, R 2 is (methylamino)methyl and R 1 is fluoro .

[0401] In one embodiment, R 2 is aminomethyl and R 1 is fluoro.

[0402] In one embodiment, R 2 is C1-C6 alkoxy, and R 1 is C1-C6 alkyl optionally substituted with one or more NR 8 R 9 .

[0403] In one embodiment, R 2 is methoxy and R 1 is (dimethylamino)methyl .

[0404] In one embodiment, R 1 and R 2 are each attached to a carbon of aryl ring A.

[0405] In one embodiment, R 1 and R 2 are each attached to a carbon of heteroaryl ring A .

[0406] In one embodiment, R 1 is attached to carbon and R 2 is attached to nitrogen of heteroaryl ring A .

[0407] In one embodiment, R 2 is attached to carbon and R 1 is attached to nitrogen of heteroaryl ring A .

[0408] In one embodiment, R 1 and R 2 are on adjacent atoms and together with the atom connecting them form hydroxy, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy , NR 8 R 9 , =NR 10 , COOC1-C6 alkyl, C6-C 10 aryl, and CONR 8 R 9 optionally substituted with one or more substituents independently selected from to form a C5 carbocyclic ring.

[0409] In certain embodiments, R 1 and R 2 are on adjacent atoms and together with the atom connecting them form a C5 aliphatic carbocyclic ring.

[0410] In certain embodiments, R 1 and R 2 are on adjacent atoms and together with the atom connecting them form a C6 carbocyclic ring optionally substituted with one or more substituents independently selected from hydroxy, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR 8 R 9 =NR 10 COOC1-C6 alkyl, C6-C 10 aryl, and CONR 8 R 9 to form a C6 carbocyclic ring optionally substituted with one or more substituents independently selected from to form a C6 carbocyclic ring.

[0411] In certain embodiments, R 1 and R 2 are on adjacent atoms and together with the atom connecting them form a C6 aliphatic carbocyclic ring.

[0412] In certain embodiments, R 1 and R 2 are on adjacent atoms and together with the atom connecting them form a C6 aromatic carbocyclic ring.

[0413] In certain embodiments, R 1 and R 2 are on adjacent atoms and together with the atom together with, containing one or two heteroatoms independently selected from O, N, and S having, hydroxy, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR 8 R 9 、=NR 10 、COOC1-C6 alkyl, C6-C 10 aryl, and CONR 8 R 9 optionally substituted with one or more substituents independently selected from to form a 5-membered heterocyclic ring

[0414] In certain embodiments, R 1 and R 2 are on adjacent atoms and together with the atom connecting them, contain one or two heteroatoms independently selected from O, N, and S to form a 5-membered aliphatic heterocyclic ring

[0415] In certain embodiments, R 1 and R 2 are on adjacent atoms and together with the atom connecting them, contain one or two heteroatoms independently selected from O, N, and S to form a 5-membered heteroaromatic ring

[0416] In certain embodiments, R 1 and R 2 are on adjacent atoms and together with the atom connecting them, contain one or two heteroatoms independently selected from O, N, and S having, hydroxy, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR 8 R 9 、=NR 10 、COOC1-C6 alkyl, C6-C 10 aryl, and CONR 8 R 9forms a 6-membered heterocyclic ring optionally substituted with one or more substituents independently selected therefrom. Formed.

[0417] In certain embodiments, R 1 and R 2 are on adjacent atoms and together with the atom connecting them form a 6-membered aliphatic heterocyclic ring containing one or two heteroatoms independently selected from O, N, and S. Containing.

[0418] In certain embodiments, R 1 and R 2 are on adjacent atoms and together with the atom connecting them form a 6-membered heteroaromatic ring containing one or two heteroatoms independently selected from O, N, and S. Containing.

[0419] In certain embodiments, R 1 and R 2 are different.

[0420] In certain embodiments, R 1 and R 2 are different, and R 2 contains a carbonyl group.

[0421] In certain embodiments, R 1 and R 2 are different, and R 2 contains one or two (e.g., one ) nitrogen atoms.

[0422] In certain embodiments, R 1 and R 2 are different, and R 2 contains one or two (e.g., one ) oxygen atoms.

[0423] In certain embodiments, R 1 and R 2 are different, and R 2contains a sulfur atom.

[0424] In certain embodiments, R 2 and R 1 are different, and R 2 contains a carbonyl group.

[0425] In certain embodiments, R 2 and R 1 are different, and R 2 contains one or two (e.g., one ) nitrogen atoms.

[0426] In certain embodiments, R 2 and R 1 are different, and R 2 contains one or two (e.g., one ) oxygen atoms.

[0427] In certain embodiments, R 2 and R 1 are different, and R 2 contains a sulfur atom.

[0428] In certain embodiments, R 1 and R 2 are the same.

[0429] In certain embodiments, R 1 is para or meta to R 2 .

[0430] In certain embodiments, R 1 is para or ortho to R 2 .

[0431] In certain embodiments, R 1 is ortho or meta to R 2 . In certain embodiments wherein, R 1 is para to R 2 .

[0432] In certain embodiments, R 1is meta with respect to R 2 In certain embodiments, R

[0433] is ortho with respect to R 1 is ortho with respect to R 2 In certain embodiments, o = 1 or 2

[0434] Variables o and p In certain embodiments, o = 1

[0435] In certain embodiments, o = 2

[0436] In certain embodiments, p = 0, 1, 2, or 3

[0437] In certain embodiments, p = 0

[0438] In certain embodiments, p = 1

[0439] In certain embodiments, p = 2

[0440] In certain embodiments, p = 3

[0441] In certain embodiments, o = 1 and p = 0

[0442] In certain embodiments, o = 2 and p = 0

[0443] In certain embodiments, o = 1 and p = 1

[0444] In certain embodiments, o = 1 and p = 2

[0445] In certain embodiments, o = 2 and p = 1

[0446] In certain embodiments, o = 2 and p = 2

[0447] In certain embodiments, o = 2 and p = 3

[0448] Ring B and substitutions on ring B In certain embodiments, B is a 5- to 10-membered monocyclic or bicyclic heteroaryl or C6-C 10 monocyclic or bicyclic aryl, such as phenyl.

[0449] In certain embodiments, B is a 5- to 6-membered monocyclic heteroaryl or C6 monocyclic aryl group.

[0450] In certain embodiments, B is a 5- to 10-membered monocyclic or bicyclic heteroaryl.

[0451] In certain embodiments, B is a C6-C 10 monocyclic or bicyclic aryl.

[0452] In certain embodiments, B is a 5-membered heteroaryl.

[0453] In certain embodiments, B is a 7- to 10-membered monocyclic or bicyclic heteroaryl.

[0454] In certain embodiments, B is phenyl substituted with one or two Rs 6 and optionally substituted with one, two, or three Rs of 7

[0455] In certain embodiments, B is pyridyl substituted with one or two Rs 6 and optionally substituted with one, two, or three Rs of 7

[0456] In certain embodiments, B is indazolyl substituted with one or two Rs 6 and optionally substituted with one, two, or three Rs of 7

[0457] ​​​In one embodiment, B is a pyrazolyl which is substituted with one or two Rs 6 and optionally substituted with one or two Rs 7 .

[0458] In one embodiment, B is phenyl, o is 1 or 2, and p is 0, 1, 2, or 3.

[0459] In one embodiment, B is phenyl, o is 1, and p is 0, 1, 2, or 3.

[0460] In one embodiment, B is phenyl, o is 2, and p is 0, 1, 2, or 3.

[0461] In one embodiment, it is one of the rings disclosed below in this specification and substituted as disclosed below in this specification, and in any case, the bond indicated as broken by the wavy line connects B of formula AA to the NH(CO) group.

Chemical formula

[0462] In one embodiment, the substituted ring B

Chemical formula

Chemical formula

[0463] In one embodiment, the substituted ring B

Chemical formula

[0464] In certain embodiments, the ring B to be substituted is [Chem.] .

[0465] In certain embodiments, the ring B to be substituted is [Chem.] .

[0466] In certain embodiments, the ring B to be substituted is [Chem.] .

[0467] In certain embodiments, the ring B to be substituted is [Chem.] .

[0468] In certain embodiments, the ring B to be substituted is [Chem.] .

[0469] In certain embodiments, the ring B to be substituted is [Chem.] .

[0470] In certain embodiments, the ring B to be substituted is

Chemical formula

[0471] In certain embodiments, the ring B to be substituted is

Chemical formula

[0472] In certain embodiments, the ring B to be substituted is

Chemical formula

[0473] In certain embodiments, the ring B to be substituted is

Chemical formula

[0474] In certain embodiments, the ring B to be substituted is

Chemical formula

[0475] In certain embodiments, the ring B to be substituted is

Chemical formula

[0476] In certain embodiments, the ring B to be substituted is

Chemical formula

[0477] In certain embodiments, the ring B to be substituted is [Chemical formula] as follows.

[0478] In certain embodiments, the ring B to be substituted is [Chemical formula] as follows.

[0479] In certain embodiments, the ring B to be substituted is [Chemical formula] as follows.

[0480] In certain embodiments, the ring B to be substituted is [Chemical formula] as follows.

[0481] In certain embodiments, the ring B to be substituted is [Chemical formula] as follows.

[0482] In certain embodiments, the ring B to be substituted is [Chemical formula] as follows.

[0483] In certain embodiments, the ring B to be substituted is [Chemical formula] as follows.

[0484] In certain embodiments, the ring B to be substituted is

Chemical formula

[0485] In certain embodiments, the ring B to be substituted is

Chemical formula

[0486] In certain embodiments, the ring B to be substituted is

Chemical formula

[0487] In certain embodiments, the ring B to be substituted is

Chemical formula

[0488] In certain embodiments, the ring B to be substituted is

Chemical formula

[0489] In certain embodiments, the ring B to be substituted is

Chemical formula

[0490] In certain embodiments, the ring B to be substituted is

Chemical formula

[0491] In one embodiment, the ring B to be substituted is [Chemical formula] as follows.

[0492] In one embodiment, the ring B to be substituted is [Chemical formula] as follows.

[0493] In one embodiment, the ring B to be substituted is [Chemical formula] as follows.

[0494] In one embodiment, the ring B to be substituted is [Chemical formula] as follows.

[0495] In one embodiment, the ring B to be substituted is [Chemical formula] as follows.

[0496] In one embodiment, the ring B to be substituted is [Chemical formula] as follows.

[0497] In one embodiment, the ring B to be substituted is [Chemical formula] It is.

[0498] In certain embodiments, the ring B to be substituted is

Chemical formula

[0499] In certain embodiments, the ring B to be substituted is

Chemical formula

[0500] In certain embodiments, the ring B to be substituted is

Chemical formula

[0501] In certain embodiments, the ring B to be substituted is

Chemical formula

[0502] In certain embodiments, the ring B to be substituted is

Chemical formula

[0503] In certain embodiments, the ring B to be substituted is

Chemical formula

[0504] In certain embodiments, the ring B to be substituted is

Chemical formula

[0505] In certain embodiments, the ring B to be substituted is

Chemical formula

[0506] In certain embodiments, the ring B to be substituted is

Chemical formula

[0507] In certain embodiments, the ring B to be substituted is

Chemical formula

[0508] In certain embodiments, the ring B to be substituted is

Chemical formula

[0509] In certain embodiments, the ring B to be substituted is

Chemical formula

[0510] In certain embodiments, the ring B to be substituted is

Chemical formula

[0511] In certain embodiments, the ring B to be substituted is

Chemical formula

[0512] group R 6 and R 7 In one embodiment, R 6 and R 7 are each, independently, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, NO2, COC1-C 6 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 he teroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, CON R 8 R 9 , SF5, S(O2)C1-C6 alkyl, C3-C 10 cycloalkyl and 3 - to 10-membered heterocycloalkyl, and C2-C6 alkenyl, and are selected from wherein, R 6 and R 7 are each, independently, hydroxy, halo, CN, oxo, C1-C6 al kyl, C1-C6 alkoxy, NR 8 R 9 , =NR 10 , COOC1-C6 alkyl, C ONR 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), NHCOC 1-C6 alkyl, NHCOC6-C 10 aryl, NHCO(5- to 10-membered heteroaryl -), NHCO(3- to 7-membered heterocycloalkyl), NHCOC2-C6 alkynyl , C6-C 10 aryloxy, and S(O2)C1-C6 alkyl, independently selected from one or more substituents optionally substituted; wherein R or R 6 or R 7 substituted C1 -C6 alkyl or C1-C6 alkoxy is optionally substituted with one or more hydroxyls, C6-C 10 a ryl or NR 8 R 9 optionally substituted, or R 6 or R 7 is a 5- to 7-membered carbocyclic or optionally condensed with a complex containing one or two heteroatoms independently selected from oxygen, sulfur and nitrogen ; wherein 3- to 7-membered heterocycloalkyl, C6-C 10 aryl, 5- to 10-membered hete roaryl, 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 ; or at least one pair of R 6 and R 7 on adjacent atoms together with the atoms connecting them form at least one C4-C8 carbocyclic or at least one 5- to 8-membered heterocyclic containing one or two heteroatoms independently selected from O, N, and S wherein the carbocyclic or heterocyclic ring is hydroxy, hydroxymethyl, halo, oxo ​, 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 independently optionally and independently substituted with one or more substituents selected from

[0513] In certain embodiments, R 6 and R 7 are each independently C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, NO2, COC1-C 6 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 he teroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, CON R 8 R 9 , SF5, S(O2)C1-C6 alkyl, C3-C 10 cycloalkyl and 3 - to 10-membered heterocycloalkyl, and C2-C6 alkenyl, and wherein R 6 and R 7 are each hydroxy, halo, CN, oxo, C1-C6 al kyl, C1-C6 alkoxy, NR 8 R 9 , =NR 10 , COOC1-C6 alkyl, C ONR 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), NHCOC 1-C6 alkyl, NHCOC6-C 10 aryl, NHCO(5- to 10-membered heteroaryl -yl), NHCO(3- to 7-membered heterocycloalkyl), NHCOC2-C6 alkynyl , C6-C 10 aryloxy, and S(O2)C1-C6 alkyl, independently selected from one or more substituents optionally substituted therewith; wherein R or R 6 or R 7 substituted C1 -C6 alkyl or C1-C6 alkoxy is optionally substituted with one or more hydroxyls, C6-C 10 ar yl or NR 8 R 9 optionally substituted with, or R 6 or R 7 is optionally condensed with a 5- to 7-membered carbocyclic or a heterocyclic ring containing one or two heteroatoms independently selected from oxygen, sulfur and nitrogen ; wherein 3- to 7-membered heterocycloalkyl, C6-C 10 aryl, 5- to 10-membered hete roaryl, 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 ; or at least one pair of R 6 and R 7 on adjacent atoms, together with the atoms connecting them Together, form at least one C4-C6 aliphatic carbocyclic ring or at least one 5- to 6-membered heterocyclic ring containing one or two heteroatoms independently selected from O, N, and S, wherein the carbocyclic ring or heterocyclic ring is independently optionally substituted with one or more substituents independently selected from hydroxy, hydroxymethyl, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR R 8 R 9 、CH2NR 8 R 9 、 =NR 10 、COOC1-C6 alkyl, C6-C 10 aryl, and CONR 8 R 9 where in is optionally independently substituted with one or more substituents independently selected from.

[0514] In certain embodiments, R 6 and R 7 are each independently C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, NO2, COC1-C 6 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 he teroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, CON R 8 R 9 、SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, C3-C7 cycloalkyl and 3- to 7-membered heterocycloalkyl, and wherein C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl and 3- to 7-membered heterocycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR R 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), NHCO C1-C6 alkyl, NHCOC6-C 10 aryl, NHCO(5- to 10-membered hetero aryl), NHCO(3- to 7-membered heterocycloalkyl), and NHCOC2-C6 alk ynyl, each optionally substituted with one or more substituents independently selected therefrom; wherein 3- to 7-membered heterocycloalkyl, C6-C 10 aryl, 5- to 10-membered hete roaryl, NHCOC6-C 10 aryl, NHCO(5- to 10-membered heteroaryl) and NHCO(3- to 7-membered heterocycloalkyl) are each optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl; ; or at least one pair of R 6 and R 7 on adjacent atoms together with the atom connecting them forms at least one 5- to 8-membered carbocyclic ring or at least one 5- to 8-membered heterocyclic ring containing one or two heteroatoms independently selected from O, N, and S, wherein the carbocyclic or heterocyclic ring is hydroxy, hydroxymethyl, halo, oxo , 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 independently substituted, optionally and independently, with one or more substituents selected from

[0515] In certain embodiments, R 6 and R 7 are each, independently, C1-C6 haloalkyl, C1-C6 alkoxy , C1-C6 haloalkoxy, halo, CN, NO2, COC1-C6 alkyl, CO2C 1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OC OC6-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 C1-C6 alkyl, S(O2)C1-C6 alkyl, C3-C7 cycloalkyl and 3 membered to 7-membered heterocycloalkyl, selected from wherein C3-C7 cycloalkyl, C1-C6 haloalkyl, and 3-membered to 7-membered hetero cycloalkyl are hydroxy, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR 8 R 9 , =NR 10 , COOC1-C6 alkyl, CONR 8 R 9 , 3 from 1-member to 7-member heterocycloalkyl, C6-C 10 aryl, 5-member to 10-member heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 aryl, OCO(5-member to 10-member hetero aryl), OCO(3-member to 7-member heterocycloalkyl), NHCOC1-C6 alkyl , NHCOC6-C 10 aryl, NHCO(5-member to 10-member heteroaryl), NHCO (3-member to 7-member heterocycloalkyl), and NHCOC2-C6 alkynyl, each optionally substituted with one or more substituents independently selected from; herein, 3-member to 7-member heterocycloalkyl, C6-C 10 aryl, 5-member to 10-member hete roaryl, NHCOC6-C 10 aryl, NHCO(5-member to 10-member heteroaryl) and NHCO(3-member to 7-member heterocycloalkyl) are optionally substituted with one or more substituents independently selected from halo, C1-C6 alkyl, and OC1-C6 alkyl; ; or at least one pair of R 6 and R 7 on adjacent atoms together with the atoms connecting them form at least one C4-C8 carbocyclic ring or at least one 5-member to 8-member heterocyclic ring containing one or two heteroatoms independently selected from O, N, and S, wherein the carbocyclic or heterocyclic ring is hydroxy, hydroxymethyl, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR R , CH2NR 8 R 9 , =NR 8 R 9 , COOC1-C6 alkyl, C6-C 10 aryl, and CONR 10 R 8 R9 independent from optionally and independently substituted with one or more substituents selected from

[0516] In certain embodiments, R 6 and R 7 are each independently C1-C6 alkyl, halo, CN, NO2, CO C1-C6 alkyl, CO2C1-C6 alkyl, OCOC1-C6 alkyl, OCOC 6-C 10 aryl, OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered hetero cycloalkyl), C6-C 10 aryl, 5- to 10-membered heteroaryl, NH2, N HC1-C6 alkyl, N(C1-C6 alkyl)2, CONR 8 R 9 、SF5、SC1 -C6 alkyl, S(O2)C1-C6 alkyl, C3-C7 cycloalkyl and 3- to 7-membered heterocycloalkyl, selected from wherein C1-C6 alkyl, C3-C7 cycloalkyl and 3- to 7-membered heterocyclo alkyl are hydroxy, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy xy, 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, OCO C1-C6 alkyl, OCOC6-C 10 aryl, OCO(5- to 10-membered heteroaryl yl), OCO(3- to 7-membered heterocycloalkyl), NHCOC1-C6 alkyl, NH COC6-C 10 aryl, NHCO(5- to 10-membered heteroaryl), NHCO(3-member ~7-membered heterocycloalkyl), and NHCOC2-C6 alkynyl, each independently selected and optionally substituted with one or more substituents selected from; wherein, 3-membered to 7-membered heterocycloalkyl, C6-C 10 aryl, 5-membered to 10-membered hete roaryl, NHCOC6-C 10 aryl, NHCO(5-membered to 10-membered heteroaryl) and NHCO(3-membered to 7-membered heterocycloalkyl) are each independently optionally substituted with one or more substituents selected from halo, C1-C6 alkyl, and OC1-C6 alkyl; ; or at least one pair of R 6 and R 7 on adjacent atoms, together with the atoms connecting them form at least one C4-C8 carbocyclic ring or at least one 5-membered to 8-membered heterocyclic ring containing one or two heteroatoms independently selected from O, N, and S, wherein the carbocyclic or heterocyclic ring is hydroxy, hydroxymethyl, halo, oxo , C1-C6 alkyl, C1-C6 alkoxy, NR R , CH2NR 8 R 9 , =NR 8 R 9 , =NR 10 , COOC1-C6 alkyl, C6-C 10 aryl, and CONR 8 R 9 independently selected and optionally independently substituted with one or more substituents selected from.

[0517] In certain embodiments, R 6 and R 7 are each independently C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, NO2, COC1-C 6-alkyl, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1 -C6 alkyl, OCOC6-C 10 aryl, OCO(5-membered to 10-membered heteroaryl) , OCO(3-membered to 7-membered heterocycloalkyl), C6-C 10 aryl, 5-membered to 10-membered he teroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, CON R 8 R 9 , SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, C3-C7 cycloalkyl and 3-membered to 7-membered heterocycloalkyl are selected from, wherein C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, and 3-membered to 7-membered heterocycloalkyl are hydroxy, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR 8 R 9 , =NR 10 , COOC1-C6 alkyl , CONR 8 R 9 , 3-membered to 7-membered heterocycloalkyl, C6-C 10 aryl, 5-membered to 1 0-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 aryl, OCO (5-membered to 10-membered heteroaryl), OCO(3-membered to 7-membered heterocycloalkyl), NHC OC1-C6 alkyl, NHCOC6-C 10 aryl, NHCO(5-membered to 10-membered hete roaryl), NHCO(3-membered to 7-membered heterocycloalkyl), and NHCOC2-C6 a lkynyl are each independently selected from one or more substituents and are optionally substituted; wherein 3-membered to 7-membered heterocycloalkyl, C6-C 10 aryl, 5-membered to 10-membered he Lower real, NHCOC6~C 10 Aryl, NHCO(5-membered to 10-membered heteroaryl) And NHCO(3-membered to 7-membered heterocycloalkyl) are unsubstituted; Or R on adjacent atoms 6 And R 7 At least one pair of which, together with the atoms connecting them Form, independently, at least one C4-C8 carbocyclic ring or at least one 5-membered to 8-membered heterocyclic ring containing one or two heteroatoms independently selected from O, N, and S Wherein the carbocyclic ring or heterocyclic ring is hydroxy, hydroxymethyl, halo, oxo C1-C6 alkyl, C1-C6 alkoxy, NR R 8 R 9 CH2NR 8 R 9 =NR 10 COOC1-C6 alkyl, C6-C 10 Aryl, and CONR 8 R 9 Independently Optionally independently substituted with one or more substituents selected from

[0518] In certain embodiments, R 6 And R 7 Are each, independently, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, NO2, COC1-C 6 alkyl, CO2C1-C6 alkyl, CO2C3-C8 cycloalkyl, OCOC1 -C6 alkyl, OCOC6-C 10 Aryl, OCO(5-membered to 10-membered heteroaryl) OCO(3-membered to 7-membered heterocycloalkyl), C6-C 10 Aryl, 5-membered to 10-membered he teroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, CON R 8 R 9 、 SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, C3-C7 cycloalkyl and 3- to 7-membered heterocycloalkyl, selected from wherein C1-C6 alkyl, C3-C7 cycloalkyl and 3- to 7-membered heterocyclo alkyl are each unsubstituted; or R on adjacent atoms 6 and R 7 at least one pair of which, together with the atom connecting them forms at least one C4-C8 carbocyclic ring or at least one 5- to 8-membered heterocyclic ring containing one or two heteroatoms independently selected from O, N, and S independently, wherein the carbocyclic or heterocyclic ring is hydroxy, hydroxymethyl, halo, oxo , C1-C6 alkyl, C1-C6 alkoxy, NR R 8 R 9 , CH2NR 8 R 9 , =NR 10 , COOC1-C6 alkyl, C6-C 10 aryl, and CONR 8 R 9 independently selected and optionally independently substituted with one or more substituents selected from

[0519] In certain embodiments, R 6 is independently selected from C1-C6 alkyl, C3-C7 cycloalkyl, C1-C6 halo alkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, C6-C1 0 aryl, 5- to 10-membered heteroaryl, CO-C1-C6 alkyl; CONR 8 R 9 and 4- to 6-membered heterocycloalkyl, selected from Here, C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl and 4- to 6-membered heterocycloalkyl are each independently optionally substituted with one or more substituents selected from hydroxy, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR R 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 heterocycloalkyl), NHCO C1-C6 alkyl, NHCOC6-C 10 aryl, NHCO(5- to 10-membered hetero aryl), NHCO(4- to 6-membered heterocycloalkyl), and NHCOC2-C6 alk ynyl; and R 7 is independently C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, COC1-C6 alkyl, CO2C1- C6 alkyl, CO2C3-C6 cycloalkyl, OCOC1-C6 alkyl, OCOC 6-C aryl, OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered hete 10 rocycloalkyl), C6-C aryl, 5- to 10-membered heteroaryl, CONR 10 R 8 R 9 、SF5, S(O2)C1-C6 alkyl, C3-C7 cycloalkyl and 4- to 6 membered heterocycloalkyl, where C1-C6 alkyl is optionally substituted with 1 to 2 C1 optionally substituted with C6 alkoxy; or R 6 and R 7 together with the atoms connecting them form at least one C4-C7 carbocyclic ring or O containing one or two heteroatoms independently selected from N and S and forming at least one 5- to 7-membered heterocyclic ring independently, where the carbocyclic or heterocyclic ring is hydroxy, halo oxo, C1-C6 alkyl, C1-C6 alkoxy, NR 8 R 9 =NR 10 C OOC1-C6 alkyl, C6-C 10 aryl, and CONR 8 R 9 optionally independently substituted with one or more substituents selected from the following.

[0520] In certain embodiments, R 6 and R 7 are each independently selected from C1-C6 alkyl, C1-C6 alkoxy, halo CN, NO2, COC1-C6 alkyl, CO2C1-C6 alkyl, C6-C 10 aryl, 5- to 10-membered heteroaryl, CONR 8 R 9 and 3- to 7-membered heterocyclo alkyl, where C1-C6 alkyl and 3- to 7-membered heterocycloalkyl are each optionally substituted with one or more substituents independently selected from hydroxy or oxo, or at least one pair of R and R on adjacent atoms together with the atoms connecting them form at least one C4-C8 carbocyclic ring independently, where the carbocyclic ring is 6 optionally independently substituted with one or more hydroxy or oxo. 7 optionally independently substituted with one or more hydroxy or oxo.

[0521] In one embodiment, R 6 and R 7 are each independently selected from C1-C6 alkyl, C1-C6 alkoxy, halo, CN, NO2, COC1-C6 alkyl, CO2C1-C6 alkyl, C6-C 10 aryl, 5- to 10-membered heteroaryl, CONR 8 R 9 , and 3- to 7-membered heterocyclo alkyl, where C1-C6 alkyl and 3- to 7-membered heterocycloalkyl are each optionally substituted with one or more substituents independently selected from hydroxy or oxo, or at least one pair of R and R on adjacent atoms together independently forms at least one C4-C6 aliphatic carbocycle, where the carbocycle is optionally independently substituted with one or more hydroxy or oxo. 6 and R 7 is connected to the atom connecting them to form at least one C4-C6 aliphatic carbocycle, where the carbocycle is optionally independently substituted with one or more hydroxy or oxo. In one embodiment,

[0522] R and R 6 are each independently selected from C1-C6 alkyl, C1-C6 alkoxy, halo, 7 CN, NO2, COC1-C6 alkyl, CO2C1-C6 alkyl, C6-C aryl, 5- to 10-membered heteroaryl, CONR 10 R 8 and R 9 are each independently selected from C1-C6 alkyl, C1-C6 alkoxy, halo, CN, NO2, COC1-C6 alkyl, CO2C1-C6 alkyl, C6-C aryl, 5- to 10-membered heteroaryl, CONR R and R 6 on adjacent atoms together independently forms at least one C4-C6 aliphatic carbocycle, where the carbocycle is optionally independently substituted with one or more hydroxy or oxo.7 At least one pair of them, together with the atom connecting them, independently forms at least one 5- to 8-membered heterocyclic ring containing one or two heteroatoms independently selected from O, N, and S, where the heterocyclic ring is optionally independently substituted with one or more hydroxy or oxo.

[0523] In certain embodiments, R 6 and R 7 are each independently selected from C1-C6 alkyl, C1-C6 alkoxy, halo, CN, NO2, COC1-C6 alkyl, CO2C1-C6 alkyl, C6-C 10 aryl, 5- to 10-membered heteroaryl, CONR 8 R 9 and 3- to 7-membered heterocycloalkyl, wherein C1-C6 alkyl and 3- to 7-membered heterocycloalkyl are each optionally substituted with one or more substituents independently selected from hydroxy or oxo, or at least one pair of R and R on adjacent atoms, together with the atom connecting them, 6 and R 7 independently forms at least one C4-C8 carbocyclic ring, where the carbocyclic ring is optionally independently substituted with one or more hydroxy or oxo.

[0524] In certain embodiments, at least one pair of R 6 and R 7 on adjacent atoms, together with the atom connecting them, independently forms at least one C4-C6 aliphatic carbocyclic ring, where the carbocyclic ring is optionally independently substituted with one or more hydroxy or oxo.

[0525] In one embodiment, at least one pair of R on adjacent atoms 6 and R 7 together with the atom connecting them independently form at least one C4 aliphatic carbocyclic ring, where the carbocyclic ring is optionally and independently substituted with one or more hydroxy or oxo.

[0526] In one embodiment, at least one pair of R on adjacent atoms 6 and R 7 together with the atom connecting them independently form at least one C5 aliphatic carbocyclic ring, where the carbocyclic ring is optionally and independently substituted with one or more hydroxy or oxo.

[0527] In one embodiment, at least one pair of R on adjacent atoms 6 and R 7 together with the atom connecting them independently form at least one C6 aliphatic carbocyclic ring, where the carbocyclic ring is optionally and independently substituted with one or more hydroxy or oxo.

[0528] In one embodiment, at least one pair of R on adjacent atoms 6 and R 7 together with the atom connecting them independently form at least one 5- to 6-membered heterocyclic ring containing one heteroatom selected independently from O, N, and S, where the heterocyclic ring is optionally and independently substituted with one or more hydroxy or oxo.

[0529] In one embodiment, at least one pair of R on adjacent atoms 6 and R7 At least one pair of them, together with the atom connecting them independently forms at least one 5-membered heterocyclic ring containing one heteroatom selected independently from O, N, and S, where the heterocyclic ring is optionally and independently substituted with one or more hydroxy or oxo.

[0530] In certain embodiments, R on adjacent atoms 6 and R 7 At least one pair of them, together with the atom connecting them independently forms at least one 6-membered heterocyclic ring containing one heteroatom selected independently from O, N, and S, where the heterocyclic ring is optionally and independently substituted with one or more hydroxy or oxo.

[0531] In certain embodiments, R on adjacent atoms 6 and R 7 At least one pair of them, together with the atom connecting them independently forms at least one C4 aliphatic carbocyclic ring, where the carbocyclic ring is optionally and independently substituted with one or more C1-C6 alkyls.

[0532] In certain embodiments, R on adjacent atoms 6 and R 7 At least one pair of them, together with the atom connecting them independently forms at least one C5 aliphatic carbocyclic ring, where the carbocyclic ring is optionally and independently substituted with one or more C1-C6 alkyls.

[0533] In certain embodiments, R on adjacent atoms 6 and R 7At least one pair of them, together with the atom connecting them forms, independently, at least one C6 aliphatic carbocyclic ring, where the carbocyclic ring is optionally and independently substituted with one or more C1-C6 alkyls. In certain embodiments,

[0534] At least one pair of R on adjacent atoms and R 6 forms, together with the atom connecting them, at least one 5- to 6-membered heterocyclic ring containing one heteroatom independently selected from O, N, and S, where the heterocyclic ring is optionally and independently substituted with one or more C1-C6 7 alkyls. In certain embodiments, At least one pair of R on adjacent atoms and R

[0535] forms, together with the atom connecting them, at least one 5-membered heterocyclic ring containing one heteroatom independently selected from O, N, and S, where the heterocyclic ring is optionally and independently substituted with one or more C1-C6 alkyls. 6 In certain embodiments, 7 At least one pair of R on adjacent atoms and R forms, together with the atom connecting them, at least one 6-membered heterocyclic ring containing one heteroatom independently selected from O, N, and S, where the heterocyclic ring is optionally and independently substituted with one or more C1-C6 alkyls.

[0536] In certain embodiments, At least one pair of R on adjacent atoms 6 and R 7 forms, together with the atom connecting them, at least one 6-membered heterocyclic ring containing one heteroatom independently selected from O, N, and S, where the heterocyclic ring is optionally and independently substituted with one or more C1-C6 alkyls. In certain embodiments, o = 1; p = 0; R

[0537] In certain embodiments, o = 1; p = 0; R6 is C1-C6 alkyl, C1-C6 haloalkyl, C1 -C6 haloalkoxy, halo, CN, NO2, COC1-C6 alkyl, CO2C1-C 6 alkyl, CO2C3-C8 cycloalkyl, OCOC1-C6 alkyl, OCOC6 -C 10 aryl, OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered hetero cycloalkyl), C6-C 10 aryl, 5- to 10-membered heteroaryl, NH2, NH C1-C6 alkyl, N(C1-C6 alkyl)2, CONR 8 R 9 、SF5、SC1- C6 alkyl, S(O2)C1-C6 alkyl, C3-C7 cycloalkyl and 3- to 7 membered heterocycloalkyl selected from, wherein C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl and 3- to 7-membered heterocycloalkyl are hydroxy, halo, CN, oxo, C1-C6 a lkyl, 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), NHCO C1-C6 alkyl, NHCOC6-C 10 aryl, NHCO(5- to 10-membered hetero aryl), NHCO(3- to 7-membered heterocycloalkyl), and NHCOC2-C6 al Optionally substituted with one or more substituents independently selected from kinyl; wherein 3- to 7-membered heterocycloalkyl, C6-C 10 aryl, 5- to 10-membered hete roaryl, 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; is.

[0538] In certain embodiments, o = 1; p = 1; R 6 and R 7 are each independently C1-C6 alkyl, C1-C6 alkoxy, ha lo, CN, NO2, COC1-C6 alkyl, CO2C1-C6 alkyl, C6-C 10 aryl, 5- to 10-membered heteroaryl, CONR 8 R 9 and 3- to 7-membered heterocyclo alkyl, selected from; wherein C1-C6 alkyl and 3- to 7-membered heterocycloalkyl are optionally substituted with one or more substituents independently selected from hydroxy or oxo; or at least one pair of R 6 and R 7 on adjacent atoms together form at least one independent C4-C8 carbocyclic ring, where the carbocyclic ring is optionally independently substituted with one or more hydroxy or oxo. ;

[0539] In certain embodiments, o = 1 or 2; p = 1, 2, or 3; R 6 and R 7Each is independently C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, NO2, COC1-C 6 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 he teroaryl, NH2, NHC1-C6 alkyl, N(C1-C6 alkyl)2, CON R 8 R 9 , SF5, SC1-C6 alkyl, S(O2)C1-C6 alkyl, C3-C7 cycloalkyl and 3- to 7-membered heterocycloalkyl, selected from wherein C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, and 3- to 7-membered heterocycloalkyl are 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 1 0-membered heteroaryl, OCOC1-C6 alkyl, OCOC6-C 10 aryl, OCO (5- to 10-membered heteroaryl), OCO(3- to 7-membered heterocycloalkyl), NHC OC1-C6 alkyl, NHCOC6-C 10 aryl, NHCO(5- to 10-membered hetero aryl), NHCO(3- to 7-membered heterocycloalkyl), and NHCOC2-C6 a Optionally substituted with one or more substituents independently selected from luquinyl; wherein 3- to 7-membered heterocycloalkyl, C6-C 10 aryl, 5- to 10-membered hete roaryl, 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 .

[0540] In certain embodiments, o = 2; p = 1; each R 6 is independently C1-C6 alkyl, C3-C7 cycloalkyl, C1-C6 ha loalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, C6-C 10 aryl, 5- to 10-membered heteroaryl, CO-C1-C6 alkyl; CONR 8 R 9 and 4- to 6-membered heterocycloalkyl, selected from wherein C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl and 4- to 6-membered heterocycloalkyl are hydroxy, halo, CN, oxo, C1-C6 a lkyl, 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 heterocycloalkyl), NHCO C1-C6 alkyl, NHCOC6-C 10 aryl, NHCO(5- to 10-membered heteroaryl), NHCO(4- to 6-membered heterocycloalkyl), and NHCOC2-C6 alk ynyl, each independently optionally substituted with one or more substituents selected therefrom; R 7 is independently C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alk oxy, C1-C6 haloalkoxy, halo, CN, COC1-C6 alkyl, CO2C1- C6 alkyl, CO2C3-C6 cycloalkyl, OCOC1-C6 alkyl, OCOC 6-C 10 aryl, OCO(5- to 10-membered heteroaryl), OCO(3- to 7-membered hete rocycloalkyl), C6-C 10 aryl, 5- to 10-membered heteroaryl, CONR 8 R 9 、SF5, S(O2)C1-C6 alkyl, C3-C7 cycloalkyl and 4- to 6 membered heterocycloalkyl, where C1-C6 alkyl is optionally substituted with 1-2 C1 -C6 alkoxy; or R 6 and R 7 together with the atoms connecting them form at least one 5- to 7-membered carbocyclic ring or O 、N, and S, independently containing one or two heteroatoms selected therefrom, at least one 5- to 7-membered heterocyclic ring is independently formed, where the carbocyclic or heterocyclic ring is hydroxy, ha lo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR 8 R 9 、=NR 10 、C OOC1-C6 alkyl, C6-C 10 aryl, and CONR 8 R 9 independently selected from ​Optionally and independently substituted with one or more substituents.

[0541] In certain embodiments, o = 2; p = 2 or 3; Each R 6 is independently selected from C1-C6 alkyl, C3-C7 cycloalkyl, C1-C6 halo alkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, C6-C 10 aryl, 5- to 10-membered heteroaryl, CO-C1-C6 alkyl; CONR 8 R 9 and 4- to 6-membered heterocycloalkyl, and is optionally substituted with one or more substituents independently selected from hydroxy, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR R R, =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 heterocycloalkyl), NHCO C1-C6 alkyl, NHCOC6-C 10 aryl, NHCO(5- to 10-membered heteroaryl ), NHCO(4- to 6-membered heterocycloalkyl), and NHCOC2-C6 alk ynyl, each optionally substituted with one or more substituents independently selected therefrom; wherein each R 7 is independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C1- C6 alkoxy, C1-C6 haloalkoxy, halo, CN, COC1-C6 alkyl, C O2C1-C6 alkyl, CO2C3-C6 cycloalkyl, OCOC1-C6 alkyl 、OCOC6-C 10 aryl, OCO(5- to 10-membered heteroaryl), OCO(3-membered -7-membered heterocycloalkyl), C6-C 10 aryl, 5- to 10-membered heteroaryl, CONR 8 R 9 、SF5, S(O2)C1-C6 alkyl, C3-C7 cycloalkyl and 4- to 6-membered heterocycloalkyl, wherein C1-C6 alkyl is optionally substituted with 1- 2 C1-C6 alkoxy groups; or at least one pair of R 6 and R 7 on adjacent atoms together form at least one C4-C7 (e.g., C4-C6) carbocyclic ring (e.g., aliphatic carbocyclic ring) or at least one 5- to 7-membered (e.g., 5- to 6-membered) heterocyclic ring containing 1 or 2 heteroatoms independently selected from O, N, and S, wherein the carbocyclic or heterocyclic ring is optionally independently substituted with one or more substituents independently selected from hydroxy, hydroxymethyl, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR R 、CH2NR 8 R 9 、=NR 8 、COO 9 C1-C6 alkyl, C6-C 10 aryl, and CONR R 10 、aryl, and CONR 8 R 9 。 In certain embodiments, o = 1 or 2; p = 1, 2, or 3;

[0542] R 6 and R 7 are each, independently, C1-C6 alkyl, C1-C6 alkoxy, halo, CN, NO2, COC1-C6 alkyl, CO2C1-C6 alkyl, C6-C 10 aryl, 5- to 10-membered heteroaryl, CONR 8 R 9 , and 3- to 7-membered heterocyclo alkyl, selected from, wherein C1-C6 alkyl and 3- to 7-membered heterocycloalkyl are each optionally substituted with one or more substituents independently selected from hydroxy or oxo, or at least one pair of R 6 and R 7 are joined together with the atom connecting them to independently form at least one C4-C8 carbocyclic ring, wherein the carbocyclic ring is optionally independently substituted with one or more hydroxy or oxo.

[0543] In certain embodiments, o = 1 or 2; p = 1, 2, or 3; R 6 and R 7 are each, independently, C1-C6 alkyl, C1-C6 alkoxy, halo, CN, NO2, COC1-C6 alkyl, CO2C1-C6 alkyl, C6-C 10 aryl, 5- to 10-membered heteroaryl, CONR 8 R 9 , and 3- to 7-membered heterocyclo alkyl, selected from, wherein C1-C6 alkyl and 3- to 7-membered heterocycloalkyl are each optionally substituted with one or more substituents independently selected from hydroxy or oxo.

[0544] In certain embodiments, o = 1 or 2; p = 1, 2, or 3;​ One R 6 and one R 7 are on adjacent atoms and together with the atom connecting them form a C4-C8 carbocyclic ring or a 5- to 8-membered heterocyclic ring containing one or two heteroatoms independently selected from O, N, and S, where the carbocyclic or heterocyclic ring is optionally independently substituted with one or more substituents selected from hydroxy , halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR R 8 R 9 , =NR 10 , COOC1-C6 alkyl, C6-C 10 aryl, and CONR 8 R 9 independently substituted.

[0545] In certain embodiments, o = 1 or 2; p = 1, 2, or 3; One R 6 and one R 7 are on adjacent atoms and together with the atom connecting them form a C6 carbocyclic ring or a 5- to 6-membered heterocyclic ring containing one or two heteroatoms independently selected from O, N, and S, where the carbocyclic or heterocyclic ring is optionally independently substituted with one or more substituents selected from hydroxy, halo , oxo, C1-C6 alkyl, C1-C6 alkoxy, NR R 8 R 9 , =NR 10 , CO OC1-C6 alkyl, C6-C 10 aryl, and CONR 8 R 9 independently selected and optionally independently substituted with one or more substituents.

[0546] In certain embodiments, o = 1 or 2; p = 1, 2, or 3; One R 6 and one R 7is on adjacent atoms and together with the atoms connecting them form a C4-C8 carbocyclic ring or a 5- to 8-membered heterocyclic ring containing one or two hetero atoms independently selected from O, N, and S, wherein the carbocyclic or heterocyclic ring is unsubstituted .

[0547] In certain embodiments, o = 2; p = 2 or 3; One R 6 and one R 7 Each of the two pairs is on adjacent atoms, and one R 6 and one R 7 Each pair, together with the atoms connecting them, forms independently a C4-C8 carbocyclic ring or a 5- to 8-membered heterocyclic ring containing one or two heteroatoms independently selected from O, N, and S, where each carbocyclic or heterocyclic ring is hydroxy, halo, oxo , C1-C6 alkyl, C1-C6 alkoxy, NR R 8 R 9 , =NR 10 , COOC1- C6 alkyl, C6-C 10 aryl, and CONR 8 R 9 Optionally independently substituted with one or more substituents independently selected from.

[0548] In certain embodiments, o = 2; p = 2 or 3; One R 6 and one R 7 Each of the two pairs is on adjacent atoms, and one R 6 and one R 7 Each pair, together with the atoms connecting them, forms a C6 carbocyclic ring or a 5- to 6-membered heterocyclic ring containing one or two heteroatoms independently selected from O, N, and S, Form the rings independently, where the carbocyclic or heterocyclic ring is hydroxy, halo, oxo, C1~ C6 alkyl, C1~C6 alkoxy, NR 8 R 9 、=NR 10 、COOC1~C6 alk yl, C6~C 10 aryl, and CONR 8 R 9 and is optionally independently substituted with one or more substituents selected independently from .

[0549] In certain embodiments, o = 2; p = 2 or 3; One R 6 and one R 7 each of the two pairs is on adjacent atoms, and one R 6 and one R 7 each pair, together with the atom connecting them, forms a C5 carbocyclic ring independently where the carbocyclic ring is hydroxy, halo, oxo, C1~C6 alkyl, C1~ C6 alkoxy, NR 8 R 9 、=NR 10 、COOC1~C6 alkyl, C6~C 10 ar yl, and CONR 8 R 9 and is optionally independently substituted with one or more substituents selected independently from .

[0550] In certain embodiments, o = 2; p = 2 or 3; One R 6 and one R 7 each of the two pairs is on adjacent atoms, and one R 6 and one R 7 each pair, together with the atom connecting them, forms a C4 carbocyclic ring independently where the carbocyclic ring is hydroxy, halo, oxo, C1~C6 alkyl, C1~ C6 alkoxy, NR 8 R 9 , =NR 10 , COOC1-C6 alkyl, C6-C 10 aryl reel, and CONR 8 R 9 optionally independently substituted with one or more substituents independently selected from them.

[0551] In certain embodiments, o = 2; p = 2 or 3; One R 6 and one R 7 of each of the two pairs are on adjacent atoms, and one R 6 and one R 7 of one pair together with the atom connecting them independently form a C4 carbocyclic ring, and one R and one R 6 and one R 7 of the other pair together with the atom connecting them independently form a C5 carbocyclic ring, where each of the C4 and C5 carbocyclic rings is optionally independently substituted with one or more substituents independently selected from hydroxy, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR R 8 R 9 , =N R 10 , COOC1-C6 alkyl, C6-C 10 aryl, and CONR 8 R 9 from them.

[0552] In certain embodiments, o = 2; p = 2 or 3; One R 6 and one R 7 of each of the two pairs are on adjacent atoms, and one R 6 and one R 7 of one pair together with the atom connecting them independently form a C5 carbocyclic ring, and one R formed upright, one R 6 and one R 7 the other pair, together with the atom connecting them forms a 5- to 8-membered heterocyclic ring containing one or two heteroatoms independently selected from O, N, and S (e.g., a 5-membered heterocyclic ring, e.g., a 5-membered heterocyclic ring containing one heteroatom ), and each of the carbocyclic and heterocyclic rings is independently optionally substituted with one or more substituents independently selected from hydroxy, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR R 8 R 9 , =NR 10 , COOC1 -C6 alkyl, C6-C 10 aryl, and CONR 8 R 9 and is optionally independently substituted with one or more substituents.

[0553] In certain embodiments, o = 2; p = 2 or 3; one R 6 and one R 7 each of the two pairs is on adjacent atoms, and one R 6 and one R 7 each pair, together with the atom connecting them, forms a C4-C8 carbocyclic ring or a 5- to 8-membered heterocyclic ring containing one or two heteroatoms independently selected from O, N, and S, wherein the carbocyclic or heterocyclic ring is unsubstituted.

[0554] A specific embodiment where o = 1; p = 0: In certain embodiments, R 6 is C1-C6 alkyl.

[0555] In certain embodiments, R 6 is isopropyl.

[0556] In certain embodiments, R6 is ethyl.

[0557] In certain embodiments, R 6 is methyl.

[0558] In certain embodiments, R 6 is C1-C6 alkyl substituted with one or more halos.

[0559] In certain embodiments, R 6 is trifluoromethyl.

[0560] In certain embodiments, R 6 is trifluoromethoxy.

[0561] In certain embodiments, R 6 is C3-C7 cycloalkyl.

[0562] In certain embodiments, R 6 is cyclopropyl.

[0563] In certain embodiments, R 6 is halo.

[0564] In certain embodiments, R 6 is chloro.

[0565] In certain embodiments, R 6 is fluoro.

[0566] In certain embodiments, R 6 is cyano.

[0567] In certain embodiments, R 6 is attached to a carbon of aryl ring B.

[0568] In certain embodiments, R 6 is attached to a carbon of heteroaryl ring B.

[0569] ​ In one embodiment, R 6 is bonded to the nitrogen of heteroaryl ring B.

[0570] A specific embodiment where o = 1 or 2; p = 1, 2, or 3: In one embodiment, at least one R 6 is C1-C6 alkyl, and at least one R 7 is C1-C6 alkyl optionally substituted with one or more halos.

[0571] In one embodiment, at least one R 6 is C1-C6 alkyl, and at least one R 7 is C1-C6 alkyl.

[0572] In one embodiment, at least one R 6 is isopropyl, and at least one of the R 7 is methyl.

[0573] In one embodiment, at least one R 6 is isopropyl, and at least one of the R 7 is isopropyl.

[0574] In one embodiment, o = 1; p = 1; R 6 is isopropyl; R 7 is isopropyl.

[0575] In one embodiment, at least one R 6 is C1-C6 alkyl, and at least one R 7 is C1-C6 alkyl substituted with one or more halos.

[0576] In one embodiment, at least one R 6is isopropyl and at least one of R 7 is trifluoromethyl.

[0577] In certain embodiments, at least one R 6 is C1-C6 alkyl and at least one R 7 is C3-C7 cycloalkyl.

[0578] In certain embodiments, at least one R 6 is isopropyl and at least one of R 7 is cyclopropyl.

[0579] In certain embodiments, o = 1; p = 1; R 6 is isopropyl; R 7 is cyclopropyl.

[0580] In certain embodiments, at least one R 6 is C1-C6 alkyl and at least one R 7 is halo.

[0581] In certain embodiments, at least one R 6 is isopropyl and at least one of R 7 is halo.

[0582] In certain embodiments, at least one R 6 is isopropyl and at least one of R 7 is chloro.

[0583] In certain embodiments, at least one R 6 is isopropyl and at least one of R 7 is fluoro.

[0584] In one embodiment, o = 1; p = 1; R 6 is isopropyl; R 7 is chloro.

[0585] In one embodiment, o = 2; p = 1; at least one R 6 is isop ropyl; R 7 is chloro.

[0586] In one embodiment, o = 1; p = 1; R 6 is isopropyl; R 7 is fluoro.

[0587] In one embodiment, o = 2; p = 1; at least one R 6 is isop ropyl; R 7 is fluoro.

[0588] In one embodiment, o = 2; p = 2; at least one R 6 is isop ropyl; at least one R 7 is fluoro.

[0589] In one embodiment, o = 2; p = 2; at least one R 6 is isop ropyl; one R 7 is fluoro; the other R 7 is cyano.

[0590] In one embodiment, o = 2; p = 3; at least one R 6 is isop ropyl; two Rs 7 are fluoro; one R 7 is chloro.

[0591] In one embodiment, o = 2; p = 1; and at least one R 6 is ethyl ; R 7 is fluoro.

[0592] In one embodiment, o = 2; p = 1; and one R 6 is isopropyl ; the other R 6 is trifluoromethyl; and R 7 is chloro.

[0593] In one embodiment, at least one R 6 is C1-C6 alkyl, and at least one R 7 is cyano.

[0594] In one embodiment, at least one R 6 is isopropyl, and at least one of R 7 is cyano.

[0595] In one embodiment, o = 1; p = 1; and R 6 is isopropyl; and R 7 is cyano.

[0596] In one embodiment, o = 2; p = 1; and at least one R 6 is isop ropyl; and R 7 is cyano.

[0597] In one embodiment, at least one R 6 is C3-C7 cycloalkyl, and at least one R 7 is C3-C7 cycloalkyl.

[0598] In one embodiment, at least one R 6 is cyclopropyl, and at least one One R 7 is cyclopropyl.

[0599] In certain embodiments, at least one R 6 is C3-C7 cycloalkyl, and at least one R 7 is halo.

[0600] In certain embodiments, at least one R 6 is cyclopropyl, and at least one R 7 is halo.

[0601] In certain embodiments, at least one R 6 is cyclopropyl, and at least one R 7 is chloro.

[0602] In certain embodiments, at least one R 6 is cyclopropyl, and at least one R 7 is fluoro.

[0603] In certain embodiments, o = 1; p = 1; R 6 is cyclopropyl; R 7 is chloro.

[0604] In certain embodiments, o = 1; p = 1; R 6 is cyclopropyl; R 7 is fluoro.

[0605] In certain embodiments, at least one R 6 is C1-C6 alkyl, and at least one R 7 is C1-C6 alkoxy optionally substituted with one or more halo .

[0606] In one embodiment, at least one R 6 is isopropyl, and at least one of R 7 is C1-C6 alkoxy.

[0607] In one embodiment, at least one R 6 is isopropyl, and at least one of R 7 is methoxy.

[0608] In one embodiment, o = 1; p = 1; R 6 is isopropyl, and R 7 is methoxy.

[0609] In one embodiment, o = 2; p = 1; at least one R 6 is isop ropyl, and R 7 is methoxy.

[0610] In one embodiment, at least one R 6 is C1-C6 alkyl, and at least one of R 7 is C1-C6 alkoxy substituted with one or more halos.

[0611] In one embodiment, at least one R 6 is isopropyl, and at least one of R 7 is trifluoromethoxy.

[0612] In one embodiment, at least one R 6 is isopropyl, and at least one of R 7 is difluoromethoxy.

[0613] In one embodiment, at least one R 6 is halo, and at least one R7 is a C1-C6 haloalkyl optionally substituted with hydroxy.

[0614] In certain embodiments, o = 1; p = 1; R 6 is chloro, and R 7 is trifluoromethyl.

[0615] In certain embodiments, at least one R 6 is halo, and at least one R 7 is a C1-C6 haloalkoxy.

[0616] In certain embodiments, at least one R 6 is chloro, and at least one R 7 is trifluoromethoxy.

[0617] In certain embodiments, o = 1; p = 1; R 6 is chloro, and R 7 is trifluoromethoxy.

[0618] In certain embodiments, at least one R 6 is a C1-C6 alkoxy; at least one R 7 is halo.

[0619] In certain embodiments, o = 1; p = 2; R 6 is a C1-C6 alkoxy and at least one R 7 is chloro.

[0620] In certain embodiments, at least one R 7 is a C1-C6 alkyl, and at least one R 6 is a C1-C6 alkyl optionally substituted with one or more halos.

[0621] In one embodiment, at least one R 7 is isopropyl and at least one of the R 6 is methyl.

[0622] In one embodiment, at least one R 7 is C1-C6 alkyl and at least one of the R 6 is C1-C6 alkyl substituted with one or more halos.

[0623] In one embodiment, at least one R 7 is isopropyl and at least one of the R 6 is trifluoromethyl.

[0624] In one embodiment, at least one R 7 is C1-C6 alkyl and at least one of the R 6 is C3-C7 cycloalkyl.

[0625] In one embodiment, at least one R 7 is isopropyl and at least one of the R 6 is cyclopropyl.

[0626] In one embodiment, o = 1; p = 1; R 7 is isopropyl; R 6 is cyclopropyl.

[0627] In one embodiment, at least one R 7 is C1-C6 alkyl and at least one of the R 6 is halo.

[0628] In one embodiment, at least one R 7is isopropyl and at least one of R 6 is halo.

[0629] In certain embodiments, at least one R 7 is isopropyl and at least one of R 6 is chloro.

[0630] In certain embodiments, at least one R 7 is isopropyl and at least one of R 6 is fluoro.

[0631] In certain embodiments, o = 1; p = 1; R 7 is isopropyl; R 6 is chloro.

[0632] In certain embodiments, o = 2; p = 1; R 7 is isopropyl; at least one of R 6 is chloro.

[0633] In certain embodiments, o = 1; p = 1; R 7 is isopropyl; R 6 is fluoro.

[0634] In certain embodiments, o = 2; p = 1; R 7 is isopropyl; at least one of R 6 is fluoro.

[0635] In certain embodiments, o = 2; p = 2; R 7 is isopropyl; at least one of R 6 is fluoro.

[0636] In one embodiment, o = 2; p = 2; and at least one R 7 is isopropyl ; one R 6 is fluoro; and the other R 6 is cyano.

[0637] In one embodiment, o = 2; p = 1; R 7 is ethyl; and at least one R 6 is fluoro.

[0638] In one embodiment, o = 1; p = 2; one R 7 is isopropyl ; the other R 7 is trifluoromethyl; and R 6 is chloro.

[0639] In one embodiment, at least one R 7 is C1-C6 alkyl, and at least one R 6 is cyano.

[0640] In one embodiment, at least one R 7 is isopropyl, and at least one of the R 6 is cyano.

[0641] In one embodiment, o = 1; p = 1; R 7 is isopropyl; and R 6 is cyano.

[0642] In one embodiment, o = 2; p = 1; R 7 is isopropyl; and at least one R 6 is cyano.

[0643] In one embodiment, at least one R 7is C3-C7 cycloalkyl, at least one R 6 is C3-C7 cycloalkyl.

[0644] In certain embodiments, at least one R 7 is cyclopropyl, and at least one R 6 is cyclopropyl.

[0645] In certain embodiments, at least one R 7 is C3-C7 cycloalkyl, and at least one R 6 is halo.

[0646] In certain embodiments, at least one R 7 is cyclopropyl, and at least one R 6 is halo.

[0647] In certain embodiments, at least one R 7 is cyclopropyl, and at least one R 6 is chloro.

[0648] In certain embodiments, at least one R 7 is cyclopropyl, and at least one R 6 is fluoro.

[0649] In certain embodiments, o = 1; p = 1; R 7 is cyclopropyl; R 6 is chloro.

[0650] In certain embodiments, o = 1; p = 1; R 7 is cyclopropyl; R 6 is fluoro.

[0651] In one embodiment, at least one R 7 is C1-C6 alkyl, and at least one R 6 is C1-C6 alkoxy optionally substituted with one or more halos. .

[0652] In one embodiment, at least one R 7 is isopropyl, and at least one of R 6 is C1-C6 alkoxy.

[0653] In one embodiment, at least one R 7 is isopropyl, and at least one of R 6 is methoxy.

[0654] In one embodiment, o = 1; p = 1; R 7 is isopropyl, and R 6 is methoxy.

[0655] In one embodiment, o = 2; p = 1; R 7 is isopropyl, and at least one of R 6 is methoxy.

[0656] In one embodiment, at least one R 7 is C1-C6 alkyl, and at least one of R 6 is C1-C6 alkoxy substituted with one or more halos.

[0657] In one embodiment, at least one R 7 is isopropyl, and at least one of R 6 is trifluoromethoxy.

[0658] In one embodiment, at least one R 7is halo and at least one R 6 is , a C1-C6 haloalkyl optionally substituted with one or more hydroxy groups.

[0659] In certain embodiments, o = 1; p = 1; R 7 is chloro and R 6 is trifluoromethyl.

[0660] In certain embodiments, at least one R 7 is halo and at least one R 6 is C1-C6 haloalkoxy.

[0661] In certain embodiments, at least one R 7 is chloro and at least one R 6 is trifluoromethoxy.

[0662] In certain embodiments, o = 1; p = 1; R 7 is chloro and R 6 is trifluoromethoxy.

[0663] In certain embodiments, at least one R 7 is C1-C6 alkoxy; at least one R 6 is halo.

[0664] In certain embodiments, o = 1; p = 2; at least one R 7 is C1- C6 alkoxy; R 6 is chloro.

[0665] In certain embodiments, R 6 and R 7 are each attached to a carbon of aryl ring B.

[0666] In certain embodiments, R 6 and R 7 are each attached to a carbon of heteroaryl ring B .

[0667] In certain embodiments, R 6 is attached to a carbon and R 7 is attached to a nitrogen of heteroaryl ring B .

[0668] In certain embodiments, R 7 is attached to a carbon and R 6 is attached to a nitrogen of heteroaryl ring B .

[0669] In certain embodiments, one R 6 and one R 7 are on adjacent atoms and together with the atom connecting them form a C5 carbocyclic ring optionally substituted with one or more substituents independently selected from hydroxy, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR R R 8 R 9 , =NR 10 , COOC1-C6 alkyl, C6-C 10 aryl, and CONR R 8 R 9 .

[0670] In certain embodiments, R 6 and R 7 are on adjacent atoms and together with the atom connecting them form a C5 aliphatic carbocyclic ring .

[0671] In certain embodiments, R 6 and R 7 are on adjacent atoms and together with the atom connecting them form a ring having hydroxy, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy , NR ​​8 R 9 、 =NR 10 、 COOC1 - C6 alkyl, C6 - C 10 aryl, and CONR 8 R 9 optionally substituted with one or more substituents independently selected from C6 forms a carbocyclic ring.

[0672] In certain embodiments, R 6 and R 7 are on adjacent atoms and together with the atom connecting them form a C6 aliphatic carbocyclic ring.

[0673] In certain embodiments, R 6 and R 7 are on adjacent atoms and together with the atom connecting them form a C6 aromatic carbocyclic ring.

[0674] In certain embodiments, R 6 and R 7 are on adjacent atoms and together with the atom connecting them contain one or two heteroatoms independently selected from O, N, and S and are optionally substituted with one or more substituents independently selected from hydroxy, halo, oxo, C1 - C6 alkyl, C1 - C6 alkoxy, NR 8 R 9 、 =NR 10 、 COOC1 - C6 alkyl, C6 - C 10 aryl, and CONR 8 R 9 to form a 5 - membered heterocyclic ring optionally substituted with one or more substituents independently selected from form.

[0675] In certain embodiments, R 6 and R 7 are on adjacent atoms and together with the atom Combine to form a 5-membered aliphatic heterocyclic ring containing one or two heteroatoms independently selected from O, N, and S. Have.

[0676] In certain embodiments, R 6 And R 7 Are on adjacent atoms, and the atom connecting them Combine to form a 5-membered heteroaromatic ring containing one or two heteroatoms independently selected from O, N, and S. Have.

[0677] In certain embodiments, R 6 And R 7 Are on adjacent atoms, and the atom connecting them Combine to form a 6-membered heterocyclic ring containing one or two heteroatoms independently selected from O, N, and S, and optionally substituted with one or more substituents independently selected from hydroxy, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR R 8 R 9 =NR 10 COOC1-C6 alkyl, C6-C 10 Aryl, and CONR 8 R 9 Form. Have.

[0678] In certain embodiments, R 6 And R 7 Are on adjacent atoms, and the atom connecting them Combine to form a 6-membered aliphatic heterocyclic ring containing one or two heteroatoms independently selected from O, N, and S. Have.

[0679] In certain embodiments, R 6 And R 7 Are on adjacent atoms, and the atom connecting them Combine to form a 6-membered heterocyclic ring containing one or two heteroatoms independently selected from O, N, and S. forms a 6-membered heteroaromatic ring.

[0680] In certain embodiments, one R 6 and one R 7 are on adjacent atoms and together with the atoms connecting them form a 5- to 8-membered heterocyclic ring containing a C4-C8 carbocyclic ring or one or two heteroatoms independently selected from O, N, and S, wherein the ring is fused to the B ring at the 2- and 3-positions relative to the bond connecting the B ring to the NH(CO) group. In certain embodiments, o = 1; p = 2; one pair of one R

[0681] and one R is on adjacent atoms; one pair of one R 6 and one R 7 is on adjacent atoms; one pair of one R 6 and one of R 7 forms, together with the atoms connecting them, a 5- to 8-membered heterocyclic ring containing a C4-C8 carbocyclic ring or one or two heteroatoms independently selected from O, N, and S, wherein the ring is fused to the B ring at the 2- and 3-positions relative to the bond connecting the B ring to the NR (CO) group. 3 (CO) group.

[0682] In certain embodiments, o = 1; p = 2; one pair of one R 6 and one R 7 is on adjacent atoms; one pair of one R 6 and one of R 7 forms, together with the atoms connecting them, hydroxy, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR 8 R 9 , =NR 10 , COOC1-C ​​6-alkyl, C6-C 10 aryl, and CONR 8 R 9 independently selected from one or more substituents optionally independently substituted to form a C4-C8 carbocyclic ring.

[0683] In certain embodiments, o = 1; p = 2; one R 6 and one R 7 pair is on adjacent atoms; one R 6 and one R 7 pair, together with the atom connecting them, forms hydroxy, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR 8 R 9 , =NR 10 , COOC1-C 6 alkyl, C6-C 10 aryl, and CONR 8 R 9 independently selected from one or more substituents optionally independently substituted to form a C5 carbocyclic ring.

[0684] In certain embodiments, o = 1; p = 2; one R 6 and one R 7 pair is on adjacent atoms; one R 6 and one R 7 pair, together with the atom connecting them, forms a C5 aliphatic carbocyclic ring .

[0685] In certain embodiments, o = 2; p = 2; one R 6 and one R 7 pair is on adjacent atoms; one R 6 and one R 7The pairs, together with the atoms connecting them, are hydroxy, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR 8 R 9 、=NR 10 、COOC1-C 6 alkyl, C6-C 10 aryl, and CONR 8 R 9 and are optionally independently substituted with one or more substituents independently selected from to form a C4-C8 carbocyclic ring.

[0686] In certain embodiments, o = 2; p = 2; One R 6 and one R 7 of one pair are on adjacent atoms; one R 6 and one of R 7 The pairs, together with the atoms connecting them, are hydroxy, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR 8 R 9 、=NR 10 、COOC1-C 6 alkyl, C6-C 10 aryl, and CONR 8 R 9 and are optionally independently substituted with one or more substituents independently selected from to form a C5 carbocyclic ring.

[0687] In certain embodiments, o = 1; p = 2; One R 6 and one R 7 of one pair are on adjacent atoms; one R 6 and one of R 7 The pairs, together with the atoms connecting them, form a C5 aliphatic carbocyclic ring .

[0688] In certain embodiments, o = 2; p = 2 or 3; One R 6 and one R 7 Each of the two pairs is on adjacent atoms; one R 6 and one R 7 One pair of and one R forms, together with the atom connecting them, a hydroxy, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR R 8 R 9 =NR 10 C OOC1-C6 alkyl, C6-C 10 aryl, and CONR 8 R 9 selected independently of each other from one or more substituents selected from form a C4 carbocyclic ring optionally independently substituted with one or more substituents; one R 6 and one R 7 The other pair of and one R forms, together with the atom connecting them, a hydroxy, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR 8 R 9 =NR 10 , COOC1-C6 alkyl, C6-C 10 aryl, and CONR 8 R 9 selected independently from one or more substituents selected from form a C5 carbocyclic ring optionally independently substituted with one or more substituents.

[0689] In certain embodiments, o = 2; p = 2 or 3; One R 6 and one R 7 Each of the two pairs is on adjacent atoms; one R 6 and one R 7 One pair of and one R forms, together with the atom connecting them, a C4 aliphatic carbocyclic ring, and one R 6 and one R 7 The other pair of and one R forms, together with the atom connecting them It forms a C5 aliphatic carbocyclic ring.

[0690] In certain embodiments, o = 2; p = 2 or 3; One R 6 and one R 7 Each of the two pairs of is on adjacent atoms, and one R 6 and one R 7 Each pair of forms, together with the atom connecting them, a C5 carbocyclic ring optionally independently substituted with one or more substituents independently selected from hydroxy, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR 8 R 9 =NR 10 COO C1-C6 alkyl, C6-C 10 aryl, and CONR 8 R 9 selected independently. It forms a C5 carbocyclic ring optionally independently substituted with one or more substituents independently selected from the above.

[0691] In certain embodiments, o = 2; p = 2 or 3; One R 6 and one R 7 Each of the two pairs of is on adjacent atoms, and one R 6 and one R 7 Each pair of forms, together with the atom connecting them, a C5 aliphatic carbocyclic ring. Form.

[0692] In certain embodiments, o = 2; p = 2 or 3; One R 6 and one R 7 Each of the two pairs of is on adjacent atoms, and one R 6 and one R 7 Each pair of forms, together with the atom connecting them, hydroxy, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR 8 R 9 =NR10 , COO C1-C6 alkyl, C6-C 10 aryl, and CONR 8 R 9 is independently selected from one or more substituents to form an optionally independently substituted C6 carbocyclic ring.

[0693] In certain embodiments, o = 2; p = 2 or 3; one R 6 and one R 7 each of the two pairs is on adjacent atoms, and one R 6 and one R 7 each pair, together with the atom connecting them, forms a C6 aliphatic carbocyclic ring forming.

[0694] In certain embodiments, o = 2; p = 2 or 3; one R 6 and one R 7 each of the two pairs is on adjacent atoms, and one R 6 and one R 7 each pair, together with the atom connecting them, forms a C6 aromatic carbocyclic ring forming.

[0695] In certain embodiments, o = 2; p = 2 or 3; one R 6 and one R 7 each of the two pairs is on adjacent atoms, and one R 6 and one R 7 each pair, together with the atom connecting them, contains one or two heteroatoms independently selected from O, N, and S, and is hydroxy, halo, oxo, C 1-C6 alkyl, C1-C6 alkoxy, NR R 8 R 9 , =NR 10 , COOC1-C6 Alkyl, C6 - C 10 Aryl, and CONR 8 R 9 One or more substituents independently selected from Optionally form a 5 - membered heterocyclic ring substituted with

[0696] In certain embodiments, o = 2; p = 2 or 3; One R 6 And one R 7 Each of the two pairs of 6 And one R 7 And one R Together with the atom connecting them, form a 5 - membered aliphatic heterocyclic ring containing one or two heteroatoms independently selected from O, N, and S.

[0697] In certain embodiments, o = 2; p = 2 or 3; One R 6 And one R 7 Each of the two pairs of 6 And one R 7 And one R Together with the atom connecting them, form a 5 - membered heteroaromatic ring containing one or two heteroatoms independently selected from O, N, and S.

[0698] In certain embodiments, o = 2; p = 2 or 3; One R 6 And one R 7 Each of the two pairs of 6 And one R 7 And one R Contain one or two heteroatoms independently selected from O, N, and S, and are hydroxy, halo, oxo, C 1 - C6 alkyl, C1 - C6 alkoxy, NR 8 R 9 , =NR10 、 COOC1 - C6 alkyl, C6 - C 10 aryl, and CONR 8 R 9 one or more selected independently from optionally substituted with substituents to form a 6 - membered heterocyclic ring.

[0699] In certain embodiments, o = 2; p = 2 or 3; one R 6 and one R 7 each of the two pairs of are on adjacent atoms, one R 6 and one R 7 each pair of together with the atom connecting them contains one or two heteroatoms independently selected from O, N, and S to form a 6 - membered aliphatic heterocyclic ring.

[0700] In certain embodiments, o = 2; p = 2 or 3; one R 6 and one R 7 each of the two pairs of are on adjacent atoms, one R 6 and one R 7 each pair of together with the atom connecting them contains one or two heteroatoms independently selected from O, N, and S to form a 6 - membered heteroaromatic ring.

[0701] In certain embodiments, o = 2; p = 2 or 3; one R 6 and one R 7 each of the two pairs of are on adjacent atoms; one R 6 and one R 7 one pair of together with the atom connecting them is hydroxy, halo, oxo, C1 - C6 alkyl, C1 - C6 alkoxy, NR R 8 R 9 =NR 10, C OOC1-C6 alkyl, C6-C 10 aryl, and CONR 8 R 9 independently selected from optionally independently substituted with one or more substituents selected from C 4~8 to form a carbocyclic ring; 1 one R 6 and one R 7 the other pair of which, together with the atoms connecting them, contains one or two heteroatoms independently selected from O, N, and S, and is optionally substituted with one or more substituents selected from hydroxy, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR 8 R 9 , =NR 10 , COO C1-C6 alkyl, C6-C 10 aryl, and CONR 8 R 9 independently selected from to form a 5- to 8-membered heterocyclic ring optionally substituted with one or more substituents selected from.

[0702] In certain embodiments, o = 2; p = 2 or 3; one R 6 and one R 7 each of the two pairs of which are on adjacent atoms; one R 6 and one R 7 one pair of which, together with the atoms connecting them, forms a C5 aliphatic carbon ring, and one R 6 and one R 7 the other pair of which, together with the atoms connecting them, contains one or two heteroatoms independently selected from O, N, and S and forms a 5-membered aliphatic heterocyclic ring.

[0703] In certain embodiments, o = 2; p = 2 or 3; one R 6 and one R 7Each of the two pairs is on adjacent atoms; one R 6 and one R 7 of one pair, together with the atom connecting them, form a C5 carbocyclic ring optionally independently substituted with one or more substituents selected independently from hydroxy, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR R 8 R 9 、=NR 10 、C OOC1-C6 alkyl, C6-C 10 aryl, and CONR 8 R 9 ; and the other pair of one R and one R R 6 and one R 7 contains one or two heteroatoms selected independently from O, N, and S and forms a 6-membered heterocyclic ring optionally substituted with one or more substituents selected independently from hydroxy, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR R 8 R 9 、=NR 10 、COOC1 -C6 alkyl, C6-C 10 aryl, and CONR 8 R 9 。 In certain embodiments, o = 2; p = 2 or 3;

[0704] each of the two pairs of one R and one R 6 and one R 7 is on adjacent atoms; one R 6 and one R 7 of one pair, together with the atom connecting them, form a C5 aliphatic carbocyclic ring, and the other pair of one R 6 and one R 7 together with the atom connecting them which forms a 5-membered aliphatic heterocyclic ring containing one or two heteroatoms independently selected from O, N, and S.

[0705] In certain embodiments, o = 2; p = 2 or 3; each two pairs of one R 6 and one R 7 are on adjacent atoms, and each pair of one R 6 and one R 7 together with the atom connecting them independently forms a C4-C8 carbocyclic ring or a 5- to 8-membered heterocyclic ring containing one or two heteroatoms independently selected from O, N, and S, wherein one of the two rings is fused to the B ring at the 2-position and 3-position with respect to the bond connecting the B ring to the NR 3 (CO) group, and the other of the two rings is fused to the B ring at the 5-position and 6-position with respect to the bond connecting the B ring to the NH(CO) group.

[0706] In certain embodiments, o = 2; p = 2 or 3; each two pairs of one R 6 and one R 7 are on adjacent atoms, and each pair of one R 6 and one R 7 together with the atom connecting them independently forms a C4-C8 carbocyclic ring or a 5- to 8-membered heterocyclic ring containing one or two heteroatoms independently selected from O, N, and S, wherein one of the two rings is fused to the B ring at the 2-position and 3-position with respect to the bond connecting the B ring to the NR 3 (CO) group, and the other of the two rings is fused to the B ring at the 4-position and 5-position with respect to the bond connecting the B ring to the NH(CO) group.

[0707] In one embodiment, o = 2; p = 2; One R 6 and one R 7 Each of the two pairs is on adjacent atoms, and one R 6 and one R 7 Each pair, together with the atom connecting them, forms a C5 aliphatic carbocyclic ring to form.

[0708] In one embodiment, o = 2; p = 2; One R 6 and one R 7 Each of the two pairs is on adjacent atoms, and one R 6 and one R 7 One pair, together with the atom connecting them, forms a C4 aliphatic carbon ring, and one R 6 and one R 7 The other pair, together with the atom connecting them forms a C5 aliphatic carbocyclic ring.

[0709] In one embodiment, o = 2; p = 2; One R 6 and one R 7 Each of the two pairs is on adjacent atoms, and one R 6 and one R 7 Each pair, together with the atom connecting them, forms a C4 aliphatic carbon ring to form.

[0710] In one embodiment, o = 2; p = 2; One R 6 and one R 7 Each of the two pairs is on adjacent atoms, and one R 6 and one R 7 One pair, together with the atom connecting them, forms a C5 aliphatic carbon Form a ring, with one R 6 and one R 7 The other pair, together with the atom connecting them, contains one or two heteroatoms independently selected from O, N, and S and forms a 5-membered heterocyclic ring.

[0711] In certain embodiments, o = 2; p = 3; One R 6 and one R 7 Each of the two pairs of which is on adjacent atoms, and one R 6 and one R 7 Each pair, together with the atom connecting them, forms a C5 aliphatic carbocyclic ring ; one R 7 is halo (e.g., Cl or F).

[0712] In certain embodiments, o = 2; p = 3; One R 6 and one R 7 Each of the two pairs of which is on adjacent atoms, and one R 6 and one R 7 Each pair, together with the atom connecting them, forms a C5 aliphatic carbocyclic ring ; one R 7 is CN.

[0713] In certain embodiments, one R 7 is pyrazolyl and is para to the bond connecting the B ring of formula AA to the NH(CO) group.

[0714] In certain embodiments, one R 7 is 3-pyrazolyl and is para to the bond connecting the B ring of formula AA to the NH(C O) group.

[0715] In certain embodiments, one R 7 is 4-pyrazolyl and the B ring of formula AA is para to the bond connecting it to the NH(C is para to the bond connecting to the (C═O) group.

[0716] In one embodiment, one R 7 is 5 - pyrazolyl and is para to the bond connecting the B ring of formula AA to the NH(C O) group.

[0717] In one embodiment, one R 7 is thiazolyl and is para to the bond connecting the B ring of formula AA to the NH(CO) group.

[0718] In one embodiment, one R 7 is 4 - thiazolyl and is para to the bond connecting the B ring of formula AA to the NH(C O) group.

[0719] In one embodiment, one R 7 is 5 - thiazolyl and is para to the bond connecting the B ring of formula AA to the NH(C O) group.

[0720] In one embodiment, one R 7 is furyl and is para to the bond connecting the B ring of formula AA to the NH(CO) group to which it is attached.

[0721] In one embodiment, one R 7 is 2 - furyl and is para to the bond connecting the B ring of formula AA to the NH(CO) group.

[0722] In one embodiment, one R 7 is thiophenyl and is para to the bond connecting the B ring of formula AA to the NH(CO ) group.

[0723] In one embodiment, one R 7 is 2 - thiophenyl and the B ring of formula AA is para to the bond connecting it to the NH( It is para to the bond connecting to the (CO) group.

[0724] In certain embodiments, one R 7 is phenyl and is para to the bond connecting the B ring of formula AA to the NH(CO) group

[0725] In certain embodiments, one R 7 is cycloalkenyl (e.g., cyclopentenyl, e.g., 1 - cyclopentenyl) and is para to the bond connecting the B ring of formula AA to the NR 3 (CO) group

[0726] In certain embodiments, one R 7 is one or more hydroxyls, NR 8 R 9 (e.g., , dimethylamino), or C6 - C 10 aryl (e.g., phenyl, naphthyl, or phenyl optionally substituted with one or more C1 - C6 alkyls ( e.g., methyl or propyl, e.g., 2 - propyl) optionally substituted with methylenedioxyphenyl) and is para to the bond connecting the B ring of formula AA to the NH(CO) group.

[0727] In certain embodiments, one R 7 is one or more hydroxyls, NR 8 R 9 (e.g., , dimethylamino), or C6 - C 10 aryl (e.g., phenyl, naphthyl, or phenyl optionally substituted with one or more C1 - C6 alkoxys ( (e.g., methoxy) optionally substituted with methylenedioxyphenyl) and is para to the bond connecting the B ring of formula AA to the NH( CO) group.

[0728] ​​ In one embodiment, one R 7 is phenyl optionally substituted with one or more C6-C 10 aryloxy (e.g., phenoxy), and is para to the bond connecting the B ring of formula AA to the NH(CO ) group.

[0729] In one embodiment, one R 7 is phenyl optionally substituted with one or more CN and is para to the bond connecting the B ring of formula AA to the NH(CO) group.

[0730] In one embodiment, one R 7 is phenyl optionally substituted with one or more halo (e.g., F, Cl) and is para to the bond connecting the B ring of formula AA to the NH(CO) group, and is para to the bond connecting the B ring of formula AA to the NH(CO) group.

[0731] In one embodiment, one R 7 is phenyl optionally substituted with one or more COOC1-C6 alkyl (e.g., CO2t-Bu) and is para to the bond connecting the B ring of formula AA to the NH(C O) group.

[0732] In one embodiment, one R 7 is phenyl optionally substituted with one or more S(O2)C1-C6 alkyl (e.g., S(O2)methyl) and is para to the bond connecting the B ring of formula AA to the N H(CO) group.

[0733] In one embodiment, one R 7 is phenyl optionally substituted with one or more 3- to 7-membered heterocycloalkyl ( e.g., morpholinyl) and is para to the bond connecting the B ring of formula AA to the NH ​It is para to the bond connecting to the (CO) group.

[0734] In certain embodiments, one R 7 is phenyl optionally substituted with one or more CONR 8 R 9 (e.g., unsubstituted amido) and is para to the bond connecting ring B of formula AA to the NH(CO) group. is phenyl optionally substituted with one or more CONR (e.g., unsubstituted amido) and is para to the bond connecting ring B of formula AA to the NH(CO) group.

[0735] In certain embodiments, one R 7 is phenyl optionally substituted with one or more C1-C6 alkyls (e.g., methyl or propyl, e.g., 2-propyl) and one or more halos (e.g., F, Cl) and is para to the bond connecting ring B of formula AA to the NH(CO) group. is phenyl optionally substituted with one or more C1-C6 alkyls (e.g., methyl or propyl, e.g., 2-propyl) and one or more halos (e.g., F, Cl) and is para to the bond connecting ring B of formula AA to the NH(CO) group.

[0736] In certain embodiments, R 6 and R 7 are each attached to a carbon of aryl ring B.

[0737] In certain embodiments, R 6 and R 7 are each attached to a carbon of heteroaryl ring B. are each attached to a carbon of heteroaryl ring B.

[0738] In certain embodiments, R 6 is attached to a carbon and R 7 is attached to a nitrogen of heteroaryl ring B. is attached to a nitrogen of heteroaryl ring B.

[0739] In certain embodiments, R 7 is attached to a carbon and R 6 is attached to a nitrogen of heteroaryl ring B. is attached to a nitrogen of heteroaryl ring B.

[0740] In certain embodiments of any of the formulas herein, R1 and R 2 each of which is independently optionally substituted with one or more hydroxy, halo, oxo, or C1-C6 alkoxy; C1-C6 alkyl optionally substituted with one or more hydroxy, halo, oxo, C1-C6 alkoxy, or C1-C6 alkyl; C3-C7 cycloalkyl optionally substituted with one or more hydroxy, halo, oxo, C1-C6 alkoxy, or C1-C6 alkyl (wherein C1-C6 alkoxy or C1-C6 alkyl is further optionally substituted with 1-3 hydroxy, halo, NR R, or oxo); 3- to 7-membered heterocycloalkyl optionally substituted with one or more hydroxy, halo, oxo, or C1-C6 alkyl (wherein C1-C6 alkoxy or C1-C6 alkyl is further optionally substituted with 1-3 hydroxy, halo, or oxo); C1-C6 haloalkyl; C1-C6 alkoxy; C1-C6 haloalkoxy; halo; CN; CO-C1-C6 alkyl; CO-C6-C aryl; CO(5- to 10-membered heteroaryl); CO2C1 8 R 9 R, or oxo); 3- to 7-membered heterocycloalkyl optionally substituted with one or more hydroxy, halo, oxo, or C1-C6 alkyl (wherein C1-C6 alkoxy or C1-C6 alkyl is further optionally substituted with 1-3 hydroxy, halo, or oxo); C1-C6 haloalkyl; 3- to 7-membered heterocycloalkyl optionally substituted with one or more hydroxy, halo, oxo, or C1-C6 alkyl (wherein C1-C6 alkoxy or C1-C6 alkyl is further optionally substituted with 1-3 hydroxy, halo, or oxo); C1-C6 haloalkyl; C1-C6 alkoxy; C1-C6 haloalkoxy; halo; CN; CO-C1-C6 alkyl; CO-C6-C aryl; CO(5- to 10-membered heteroaryl); CO2C1 -C6 alkyl; CO2C3-C8 cycloalkyl; OCOC1-C6 alkyl; OCO C6-C aryl; OCO(5- to 10-membered heteroaryl); OCO(3- to 7-membered he 10 terocycloalkyl); C6-C aryl; 5- to 10-membered heteroaryl; NH2; NHC1-C6 alkyl; N(C1-C6 alkyl)2; CONR 10 R R; SF5; S( 10 O2)NR R 8 R 9 ; S(O)C1-C6 alkyl; and S(O2)C1-C6 alkyl selected from the group consisting of. 11 R 12 ; S(O)C1-C6 alkyl; and S(O2)C1-C6 alkyl is selected from the group consisting of.

[0741] In certain embodiments of any of the formulas herein, R 1 is 1-hydroxy-2-methyl propan-2-yl; methyl; isopropyl; 2-hydroxy-2-propyl; hydro xymethyl; 1-hydroxyethyl; 2-hydroxyethyl; 1-hydroxy-2-pro pyl; 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; fluoro; chloro; phenyl; pyridyl; pyrazolyl; S(O2)CH3; and S(O2)NR 11 R 12 selected from the group consisting of.

[0742] In certain embodiments, R 2 is fluoro, chloro, cyano, methyl; methoxy; eth oxy; isopropyl; 1-hydroxy-2-methylpropan-2-yl; 2-hydroxy -2-propyl; hydroxymethyl; 1-hydroxyethyl; 2-hydroxyethyl; 1 -hydroxy-2-propyl; 1-hydroxy-1-cyclopropyl; COCH3; CO Ph; 2-methoxy-2-propyl; S(O2)CH3; and S(O2)NR 11 R 12 selected from the group consisting of.

[0743] In certain embodiments, the substituted ring B is

Chemical formula

[0744] In certain embodiments, the substituted ring B is

Chemical formula

[0745] In certain embodiments, the substituted ring B is [Chemical formula] wherein each R 6 is independently C1-C6 alkyl, C3-C7 cycloalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, C N, C6-C 10 aryl, 5- to 10-membered heteroaryl, CO-C1-C6 alkyl; CONR 8 R 9 and 4- to 6-membered heterocycloalkyl, and is selected from where C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl and 4- to 6-membered heterocycloalkyl are hydroxy, halo, CN, oxo, C1-C6 a lkyl, 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 heterocycloalkyl), NHCO C1-C6 alkyl, NHCOC6-C 10 aryl, NHCO(5- to 10-membered heteroaryl a reel), NHCO (4- to 6-membered heterocycloalkyl), and NHCOC2-C6 al optionally substituted with one or more substituents independently selected from herein, R 7 is independently C1-C6 alkyl, C1-C6 haloalkyl, C1-C 6 alkoxy, C1-C6 haloalkoxy, halo, CN, COC1-C6 alkyl, CO 2C1-C6 alkyl, CO2C3-C6 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, C ONR 8 R 9 , SF5, S(O2)C1-C6 alkyl, C3-C7 cycloalkyl and 4- to 6-membered heterocycloalkyl, wherein C1-C6 alkyl is optionally substituted with 1-2 C1-C6 alkoxy groups; or R 6 and R 7 together with the atoms connecting them form at least one 5- to 7-membered heterocycle containing 1 or 2 heteroatoms independently selected from O , N, and S, wherein the carbocycle or heterocycle is optionally independently substituted with one or more substituents selected from hydroxy, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR 8 R 9 , =NR 10 , C OOC1-C6 alkyl, C6-C 10 aryl, and CONR 8 R 9 and is optionally independently substituted.

[0746] In one embodiment, the ring B to be substituted is [Chemical formula] wherein each R 6 is independently C1-C6 alkyl, C3-C7 cycloalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, C N, C6-C 10 aryl, 5- to 10-membered heteroaryl, CO-C1-C6 alkyl; CONR 8 R 9 and 4- to 6-membered heterocycloalkyl, and is selected from wherein C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl and 4- to 6-membered heterocycloalkyl are each independently optionally substituted with one or more substituents selected from hydroxy, halo, CN, oxo, C1-C6 al kyl, 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 heterocycloalkyl), NHCO C1-C6 alkyl, NHCOC6-C 10 aryl, NHCO(5- to 10-membered heteroar yl), NHCO(4- to 6-membered heterocycloalkyl), and NHCOC2-C6 al kinyl; and wherein R 7 is independently C1-C6 alkyl, C1-C6 haloalkyl, C1-C 6 - alkoxy, C1 - C6 haloalkoxy, halo, CN, COC1 - C6 alkyl, CO 2C1 - C6 alkyl, CO2C3 - C6 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, C ONR 8 R 9 , SF5, S(O2)C1 - C6 alkyl, C3 - C7 cycloalkyl and 4 - to 6 - membered heterocycloalkyl, where C1 - C6 alkyl is optionally substituted with 1 - 2 C1 - C6 alkoxy groups; or R 6 and R 7 together with the atoms connecting them form at least one 5 - to 7 - membered heterocycle containing 1 or 2 heteroatoms independently selected from O, N, and S, where the carbocyclic or heterocyclic ring is optionally independently substituted with one or more substituents selected from hydroxy, halo, oxo, C1 - C6 alkyl, C1 - C6 alkoxy, NR 8 R 9 , =NR 10 , C OOC1 - C6 alkyl, C6 - C 10 aryl, and CONR 8 R 9 independently selected and optionally independently substituted with one or more such substituents.

[0747] In certain embodiments, the substituted ring B is

Chemical formula

[0748] In certain embodiments, the substituted ring B is

Chemical formula

[0749] In certain embodiments, the ring B to be substituted is

Chemical formula

[0750] In certain embodiments, the substituted ring B is [Chemical] wherein each R 6 is independently C1-C6 alkyl, C3-C7 cycloalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, C N, C6-C 10 aryl, 5- to 10-membered heteroaryl, CO-C1-C6 alkyl; CONR 8 R 9 and 4- to 6-membered heterocycloalkyl, and is selected from wherein C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl and 4- to 6-membered heterocycloalkyl are optionally substituted with one or more substituents independently selected from hydroxy, halo, CN, oxo, C1-C6 a lkyl, 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 heterocycloalkyl), NHCO C1-C6 alkyl, NHCOC6-C 10 aryl, NHCO(5- to 10-membered heteroar yl), NHCO(4- to 6-membered heterocycloalkyl), and NHCOC2-C6 al kinyl; and is optionally substituted with one or more substituents independently selected therefrom; wherein each R 7 is independently C1-C6 alkyl, C1-C6 haloalkyl, C1- C6 alkoxy, C1-C6 haloalkoxy, halo, CN, COC1-C6 alkyl, C O2C1-C6 alkyl, CO2C3-C6 cycloalkyl, OCOC1-C6 alkyl , OCOC6-C 10 aryl, OCO(5- to 10-membered heteroaryl), OCO(3-membered -7-membered heterocycloalkyl), C6-C 10 aryl, 5- to 10-membered heteroaryl, CONR 8 R 9 , SF5, S(O2)C1-C6 alkyl, C3-C7 cycloalkyl and 4- to 6-membered heterocycloalkyl, wherein C1-C6 alkyl is optionally substituted with 1 to 2 C1-C6 alkoxy groups; or at least one pair of R 6 and R 7 on adjacent atoms together with the atoms connecting them form at least one C4-C7 carbocyclic or at least one 5- to 7-membered heterocyclic ring containing 1 or 2 heteroatoms independently selected from O, N, and S, wherein the carbocyclic or heterocyclic ring is optionally independently substituted with one or more substituents independently selected from hydroxy, halo, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR R , =NR , COOC1-C6 alkyl, C6 -C 8 R 9 , =NR 10 , COOC1-C6 alkyl, C6 -C 10 aryl, and CONR 8 R 9 . Optionally and independently substituted.

[0751] In certain embodiments, the substituted ring B is

Chemical formula

[0752] In certain embodiments, the substituted ring B is [Chemical formula] wherein each R 6 is independently C1-C6 alkyl, C3-C7 cycloalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, C N, C6-C 10 aryl, 5-membered to 10-membered heteroaryl, CO-C1-C6 alkyl; CONR 8 R 9 , and 4-membered to 6-membered heterocycloalkyl, Here, C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl and 4- to 6-membered heterocycloalkyl are each independently optionally substituted with one or more substituents selected from hydroxy, halo, CN, oxo, C1-C6 alkyl, C1-C6 alkoxy, NR R 8 R 9 =NR 10 =NR, COOC1-C6 alkyl, CONR 8 R 9 =NR, 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 heterocycloalkyl), NHCO C1-C6 alkyl, NHCOC6-C 10 aryl, NHCO(5- to 10-membered hetero aryl), NHCO(4- to 6-membered heterocycloalkyl), and NHCOC2-C6 alk ynyl, respectively; and is optionally substituted with one or more substituents independently selected from each of them; here, each R 7 is independently C1-C6 alkyl, C1-C6 haloalkyl, C1- C6 alkoxy, C1-C6 haloalkoxy, halo, CN, COC1-C6 alkyl, C O2C1-C6 alkyl, CO2C3-C6 cycloalkyl, OCOC1-C6 alkyl OCOC6-C 10 aryl, OCO(5- to 10-membered heteroaryl), OCO(3-membered -7-membered heterocycloalkyl), C6-C 10 aryl, 5- to 10-membered heteroaryl, CONR 8 R 9 =NR, SF5, S(O2)C1-C6 alkyl, C3-C7 cycloalkyl and 4- to 6-membered heterocycloalkyl, where C1-C6 alkyl is 1- Optionally substituted with two C1-C6 alkoxys; or R on adjacent atoms 6 and R 7 at least one pair of which, together with the atom connecting them form, together, at least one C4-C7 carbocyclic ring or at least one 5- to 7-membered heterocyclic ring containing one or two heteroatoms independently selected from O, N, and S wherein the carbocyclic or heterocyclic ring is optionally independently substituted with one or more substituents independently selected from hydroxy, hydroxymethyl, halo, oxo , C1-C6 alkyl, C1-C6 alkoxy, NR R 8 R 9 , CH2NR 8 R 9 , =NR 10 , COOC1-C6 alkyl, C6-C 10 aryl, and CONR 8 R 9 independently and is optionally independently substituted with one or more substituents.

[0753] Group R 3 In certain embodiments, R 3 is hydrogen, C1-C6 alkyl, and [Chemical formula] selected from, wherein the C1-C2 alkylene group is optionally substituted with oxo.

[0754] In certain embodiments, R 3 is hydrogen.

[0755] In certain embodiments, R 3 is cyano.

[0756] In certain embodiments, R 3 is hydroxy.

[0757] In certain embodiments, R 3 is C1-C6 alkoxy. In certain embodiments, R 3 is C1-C6 alkyl.

[0758] In certain embodiments, R 3 is methyl.

[0759] In certain embodiments, R 3 is,

Chemical formula

[0760] In certain embodiments, R 3 is -CH2R 14 as defined above.

[0761] In certain embodiments, R 3 is -C(O)R 14 as defined above.

[0762] In certain embodiments, R 3 is -CH2CH2R 14 as defined above.

[0763] In certain embodiments, R 3 is -CHR 14 CH3.

[0764] In certain embodiments, R 3 is -CH2C(O)R 14 as defined above.

[0765] In certain embodiments, R 3 is -C(O)CH2R 14 as defined above.

[0766] In certain embodiments, R 3 is CO2C1-C6 alkyl.

[0767] Group R 14 In certain embodiments, R 14 is hydrogen, C1-C6 alkyl, a 5- to 10-membered monocyclic or bicyclic heteroaryl or C6-C 10 monocyclic or bicyclic aryl, where each C1-C6 alkyl, aryl or heteroaryl is optionally and independently substituted with one or two R s. 6 is optionally substituted.

[0768] In certain embodiments, R 14 is hydrogen or C1-C6 alkyl.

[0769] In certain embodiments, R 14 is hydrogen, a 5- to 10-membered monocyclic or bicyclic heteroaryl or C6-C monocyclic or bicyclic aryl, where each C1-C6 alkyl, aryl or heteroaryl is optionally and independently substituted with one or two R 10 s. is optionally and independently substituted with one or two R 6 s. substituted.

[0770] In certain embodiments, R 14 is hydrogen.

[0771] In certain embodiments, R 14 is C1-C6 alkyl.

[0772] In certain embodiments, R 14 is methyl.

[0773] In certain embodiments, R 14 is a 5- to 10-membered monocyclic or bicyclic heteroaryl optionally and independently substituted with one or two R 6 s. substituted.

[0774] In certain embodiments, R 14 is a 5- to 10-membered monocyclic or bicyclic heteroaryl optionally and independently substituted with one or two R 6optionally and independently replaced with a C6-C 10 monocyclic or bicyclic aryl.

[0775] moiety S(=O)(NHR 3 )=N- In certain embodiments, the sulfur in the moiety S(=O)(NHR 3 )=N- has (S) stereochemistry.

[0776] In certain embodiments, the sulfur in the moiety S(=O)(NHR 3 )=N- has (R) stereochemistry.

[0777] group R 10 In certain embodiments, R 10 is C1-C6 alkyl.

[0778] In certain embodiments, R 10 is methyl.

[0779] In certain embodiments, R 10 is ethyl.

[0780] group R 8 and R 9 In certain embodiments, each of R 8 and R 9 , each time it appears, is independently selected from hydrogen , C1-C6 alkyl, (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 C1-C6 alkyl is optionally substituted with one or more hydroxy, halo, C1-C6 alkoxy, C6-C yl​​​10 Aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl optionally substituted with a C3-C7 cycloalkyl or 3- to 7-membered heterocycloalkyl; or R 8 and R 9 together with the nitrogen to which they are attached form a 3- to 7-membered ring optionally containing one or more additional heteroatoms in addition to the nitrogen to which they are attached.

[0781] In certain embodiments, each R 8 and R 9 is, each occurrence, independently, hydrogen , C1-C6 alkyl, (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 selected from; where C1-C6 alkyl is optionally substituted with one or more hydroxy, halo, C1-C6 alkoxy, C6-C aryl, 5- to 10-membered heteroaryl, C3-C7 cycloalkyl or 3- to 7-membered heterocycloalkyl; or R 10 and R together with the nitrogen to which they are attached form a 3- to 7-membered ring optionally containing one or more additional 8 heteroatoms in addition to the nitrogen to which they are attached. 9

[0782] In certain embodiments, each R 8 and R 9 is, each occurrence, hydrogen, In certain embodiments, each R 8 is, each occurrence, hydrogen, and each R 9 is, each occurrence, ​​​​Each is C1-C6 alkyl.

[0783] In certain embodiments, each R 8 is, each time it appears, hydrogen, and each R 9 is, each time it appears each is methyl.

[0784] In certain embodiments, each R 8 is, each time it appears, hydrogen, and each R 9 is, each time it appears each is ethyl.

[0785] In certain embodiments, R 8 and R 9 each is, each time it appears, methyl.

[0786] In certain embodiments, R 8 and R 9 each is, each time it appears, ethyl.

[0787] In certain embodiments, R 8 and R 9 together with the nitrogen to which they are attached form a 3 membered ring.

[0788] In certain embodiments, R 8 and R 9 together with the nitrogen to which they are attached form a 4 membered ring.

[0789] In certain embodiments, R 8 and R 9 together with the nitrogen to which they are attached form a 5 membered ring.

[0790] In certain embodiments, R 8 and R 9 together with the nitrogen to which they are attached form a 6-membered ring optionally containing one or more oxygen atoms in addition to the nitrogen to which they are attached ​ Do.

[0791] In certain embodiments, R 8 and R 9 together with the nitrogen to which they are attached, optionally contain one or more nitrogen atoms in addition to the nitrogen to which they are attached to form a six-membered ring Do. Do.

[0792] In certain embodiments, R 8 and R 9 together with the nitrogen to which they are attached, form a seven-membered ring. Do.

[0793] Group R 13 In certain embodiments, R 13 is C1-C6 alkyl.

[0794] In certain embodiments, R 13 is methyl.

[0795] In certain embodiments, R 13 is ethyl.

[0796] In certain embodiments, R 13 is C6-C 10 aryl.

[0797] In certain embodiments, R 13 is phenyl.

[0798] In certain embodiments, R 13 is 5- to 10-membered heteroaryl.

[0799] Group R 11 and R 12 In certain embodiments, each of R 11 and R 12 is, each time it appears, independently selected from hydrogen and C1-C6 alkyl. Do.

[0800] In one embodiment, R 11 and R 12 each, each time it appears, is hydrogen , In one embodiment, each R 11 is, each time it appears, hydrogen, and each R 12 is, each time it appears C1-C6 alkyl optionally substituted with one or more hydroxy groups.

[0801] In one embodiment, each R 11 is, each time it appears, hydrogen, and each R 12 is, each time it appears methyl.

[0802] In one embodiment, each R 11 is, each time it appears, hydrogen, and each R 12 is, each time it appears ethyl.

[0803] In one embodiment, R 11 and R 12 each, each time it appears, is methyl .

[0804] In one embodiment, R 11 and R 12 each, each time it appears, is ethyl .

[0805] In one embodiment of the compound of formula AA, the ring A being substituted is [Chemical formula] ; R 1 is C1-C6 alkyl optionally substituted with one or more hydroxy groups; C3-C7 cycloalkyl optionally substituted with one or more hydroxy groups; optionally substituted with one or more hydroxy groups C3-C7 cycloalkyl optionally substituted with one or more hydroxy groups; optionally substituted with one or more hydroxy groups Optionally substituted 3- to 7-membered heterocycloalkyl; C substituted with one or more oxo 1-C6 alkyl; C3-C7 cycloalkyl substituted with one or more oxo; one or more C1-C6 alkyl substituted with C1-C6 alkoxy; C3-C7 cycloalkyl substituted with one or more C1-C6 alk oxy; C1-C6 haloalkyl; C1-C6 alk oxy; C1-C6 haloalkoxy; halo; CN; NO2; COC1-C6 alkyl; C O-C6-C 10 aryl; CO(5- to 10-membered heteroaryl); CO2C1-C6 al kyl; CO2C3-C8 cycloalkyl; OCOC1-C6 alkyl; OCOC6-C 10 aryl; OCO(5- to 10-membered heteroaryl); OCO(3- to 7-membered heterocycl oalkyl); C6-C 10 aryl; 5- to 10-membered heteroaryl; NH2; NHC1 -C6 alkyl; N(C1-C6 alkyl)2; CONR 8 R 9 ; SF5; and S(O2 )C1-C6 alkyl selected from.

[0806] In certain embodiments of the compound of formula AA, the substituted ring A is

Chemical formula

[0807] In certain embodiments of the compound of formula AA, the ring A that is substituted is

Chemical formula

[0808] In certain embodiments of the compound of formula AA, the substituted ring A is

Chemical formula

[0809] In certain embodiments of the compound of formula AA, the substituted ring A is

Chemical formula

[0810] In certain embodiments of the compound of formula AA, The substituted ring A is [Chemical formula] is; R 1 is 1-hydroxy-2-methylpropan-2-yl; methyl; 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-cycl ohexyl; morpholinyl; 1,3-dioxolan-2-yl; COCH3; COCH2 CH3; 2-methoxy-2-propyl; (dimethylamino)methyl; 1-(dimethylamino no)ethyl; fluoro; chloro; phenyl; pyridyl; pyrazolyl; and S(O2)CH selected from 3.

[0811] In certain embodiments of the compound of formula AA, the substituted ring A is [Chemical formula] is; R 1 is C1-C6 alkyl optionally substituted with one or more hydroxy; one or more hydro xy optionally substituted with one or more hydroxy; C3-C7 cycloalkyl optionally substituted with one or more hydroxy; 3- to 7-membered heterocycloalkyl optionally substituted with one or more oxo; C 1-C6 alkyl substituted with one or more oxo; C3-C7 cycloalkyl substituted with one or more C1-C6 alkoxy substituted C1-C6 alkyl; one or more C1-C6 alkoxyC3-C7 cycloalkyl substituted with xy; one or more NR 8 R 9 substituted C1- C6 alkyl; one or more NR 8 R 9 substituted 3- to 7-membered heterocycloalkyl; C 1-C6 haloalkyl; C1-C6 alkoxy; C1-C6 haloalkoxy; halo; CN ; NO2; COC1-C6 alkyl; CO-C6-C 10 aryl; CO(5- to 10-membered heteroaryl); CO2C1-C6 alkyl; CO2C3-C8 cycloalkyl; OC OC1-C6 alkyl; OCOC6-C 10 aryl; OCO(5- to 10-membered heteroaryl -yl); OCO(3- to 7-membered heterocycloalkyl); C6-C 10 aryl; 5- to 1 0-membered heteroaryl; NH2; NHC1-C6 alkyl; N(C1-C6 alkyl)2; CONR 8 R 9 ; SF5; and S(O2)C1-C6 alkyl.

[0812] In certain embodiments of the compound of formula AA, the substituted ring A is,

Chemical formula

[0813] In certain embodiments of the compound of formula AA, The substituted ring A is

Chemical formula

[0814] In certain embodiments of the compound of formula AA, the substituted ring A is

Chemical formula

[0815] In certain embodiments of the compound of formula AA, the substituted ring A is

Chemical formula

[0816] In certain embodiments of the compound of formula AA, Ring A which is substituted is

Chemical formula

[0817] In certain embodiments of the compound of formula AA, the substituted ring A is

Chemical formula

[0818] In certain embodiments of the compound of formula AA, the substituted ring A is,

Chemical formula

[0819] In certain embodiments of the compounds of formula AA, the ring A which is substituted is

Chemical formula

[0820] In certain embodiments of the compound of formula AA, the substituted ring A is

Chemical formula

[0821] In certain embodiments of the compound of formula AA, the substituted ring A is

Chemical formula

[0822] In certain embodiments of the compound of formula AA, the substituted ring A is

Chemical formula

[0823] In certain embodiments of the compound of formula AA, The substituted ring A is

Chemical formula

[0824] In certain embodiments of the compound of formula AA, the ring A which is substituted is

Chemical formula

[0825] In certain embodiments of the compound of formula AA, The substituted ring A is [ka] and; R 1 teeth, C1-C6 alkyl optionally substituted with one or more hydroxy; C3-C7 cycloalkyl optionally substituted with hydroxy; Optionally substituted 3- to 7-membered heterocycloalkyl; C substituted with one or more oxo 1-C6 alkyl; C3-C7 cycloalkyl substituted with one or more oxo; one or more C1-C6 alkyl substituted with one or more C1-C6 alkoxy; C3-C7 cycloalkyl substituted with oxy; one or more NR 8 R 9 C1~ substituted with C6 alkyl; one or more NR 8 R 9 3- to 7-membered heterocycloalkyl substituted with C 1-C6 haloalkyl;C1-C6 alkoxy;C1-C6 haloalkoxy;Halo;CN ;NO2;COC1~C6 alkyl;CO-C6~C 10 Aryl;CO(5-10 membered) Heteroaryl;CO2C1-C6 alkyl;CO2C3-C8 cycloalkyl;OC OC1~C6 alkyl;OCOC6~C 10 Aryl; OCO (5-10 membered heteroaryl OCO(3- to 7-membered heterocycloalkyl); C6-C 10 Aryl; 5-1 membered 0-membered heteroaryl;NH2;NHC1-C6 alkyl;N(C1-C6 alkyl)2; CONR 8 R 9 ;SF5; and S(O2)C1-C6 alkyl.

[0826] In certain embodiments of the compound of formula AA, the ring A to be substituted is

Chemical formula

[0827] In certain embodiments of the compound of formula AA, the ring A to be substituted is

Chemical formula

[0828] In certain embodiments of the compound of formula AA, the substituted ring A is

Chemical formula

[0829] In certain embodiments of the compound of formula AA, the substituted ring A is

Chemical formula

[0830] In certain embodiments of the compound of formula AA, the ring A being substituted is

Chemical formula

[0831] In certain embodiments of the compound of formula AA, the ring A being substituted is

Chemical formula

[0832] In certain embodiments of the compound of formula AA, The substituted ring A is [Chem.] is; R 1 is 1-hydroxy-2-methylpropan-2-yl; methyl; 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-cyclo hexyl; morpholinyl; 1,3-dioxolan-2-yl; COCH3; COCH2 CH3; 2-methoxy-2-propyl; (dimethylamino)methyl; 1-(dimethylamino )ethyl; fluoro; chloro; phenyl; pyridyl; pyrazolyl; and S(O2)CH selected from 3.

[0833] In certain embodiments of the compound of formula AA, the substituted ring A is [Chem.] is; R 1 is C1-C6 alkyl optionally substituted with one or more hydroxy; one or more hydroxy optionally substituted C3-C7 cycloalkyl substituted with; one or more hydroxy optionally substituted 3- to 7-membered heterocycloalkyl; C1 -C6 alkyl substituted with one or more oxo; C3-C7 cycloalkyl substituted with one or more oxo; one or more C1-C6 alkoxy substituted C1-C6 alkyl; one or more C1-C6 alkoxy C3-C7 cycloalkyl substituted with xy; one or more NR 8 R 9 substituted C1- C6 alkyl; one or more NR 8 R 9 substituted 3- to 7-membered heterocycloalkyl; C 1-C6 haloalkyl; C1-C6 alkoxy; C1-C6 haloalkoxy; halo; CN ; NO2; COC1-C6 alkyl; CO-C6-C 10 aryl; CO(5- to 10-membered heteroaryl); CO2C1-C6 alkyl; CO2C3-C8 cycloalkyl; OC OC1-C6 alkyl; OCOC6-C 10 aryl; OCO(5- to 10-membered heteroaryl -yl); OCO(3- to 7-membered heterocycloalkyl); C6-C 10 aryl; 5- to 1 0-membered heteroaryl; NH2; NHC1-C6 alkyl; N(C1-C6 alkyl)2; CONR 8 R 9 ; SF5; and selected from S(O2)C1-C6 alkyl.

[0834] In certain embodiments of the compound of formula AA, the substituted ring A is

Chemical formula

[0835] The substituted ring A is [Chemical formula] And R 1 Is C1-C6 alkyl optionally substituted with one or more hydroxy; one or more hydro C3-C7 cycloalkyl optionally substituted with xy; one or more hydroxy optionally Selected 3-membered to 7-membered heterocycloalkyl optionally substituted with one or more oxo; C 1-C6 alkyl substituted with one or more oxo; C3-C7 cycloalkyl substituted with one or more C1-C6 alkyl substituted with C1-C6 alkoxy; one or more C1-C6 alkoxy C3-C7 cycloalkyl substituted with xy; one or more NR 8 R 9 Substituted C1- C6 alkyl; one or more NR 8 R 9 3-membered to 7-membered heterocycloalkyl substituted with; C 1-C6 haloalkyl; C1-C6 alkoxy; C1-C6 haloalkoxy; halo; CN ; NO2; COC1-C6 alkyl; CO-C6-C 10 Aryl; CO(5-membered to 10-membered Heteroaryl); CO2C1-C6 alkyl; CO2C3-C8 cycloalkyl; OC OC1-C6 alkyl; OCOC6-C 10 Aryl; OCO(5-membered to 10-membered heteroaryl -yl); OCO (3- to 7-membered heterocycloalkyl); C6-C 10 aryl; 5- to 1 0-membered heteroaryl; NH2; NH(C1-C6 alkyl); N(C1-C6 alkyl)2; CONR 8 R 9 ; SF5; and S(O2)(C1-C6 alkyl) selected from.

[0836] In certain embodiments of the compound of formula AA, the ring A to be substituted is

Chemical formula

[0837] In certain embodiments of the compound of formula AA, the ring A to be substituted is

Chemical formula

[0838] In certain embodiments of the compound of formula AA, The substituted ring A is

Chemical formula

[0839] In certain embodiments of the compound of formula AA, The substituted ring A is

Chemical formula

[0840] In certain embodiments of the compound of formula AA, the substituted ring A is,

Chemical formula

[0841] In certain embodiments of the compound of formula AA, the ring A which is substituted

Chemical formula

[0842] The substituted ring A is [Chemical formula] and is R 1 is 1-hydroxy-2-methylpropan-2-yl; methyl; 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-cyclo hexyl; morpholinyl; (dimethylamino)methyl; 1,3-dioxolan-2-yl ; COCH3; COCH2CH3; 2-methoxy-2-propyl; fluoro; chloro; phenyl; pyridyl; pyrazolyl; and S(O2)CH3, selected therefrom

[0843] The substituted ring A is [Chemical formula] and is R 1 is C1-C6 alkyl optionally substituted with one or more hydroxy; one or more hydroxy C3-C7 cycloalkyl optionally substituted with; one or more hydroxy 3- to 7-membered heterocycloalkyl optionally substituted with; one or more oxo C1-C6 alkyl substituted with; one or more oxo; C3-C7 cycloalkyl substituted with one or more oxo C1-C6 alkyl substituted with C1-C6 alkoxy; one or more C1-C6 alk C3-C7 cycloalkyl substituted with C1-C6 alkoxy; C1-C6 haloalkyl; C1-C6 alk oxy; C1-C6 haloalkoxy; halo; CN; NO2; COC1-C6 alkyl; C O-C6-C 10 aryl; CO(5- to 10-membered heteroaryl); CO2C1-C6 al kyl; CO2C3-C8 cycloalkyl; OCOC1-C6 alkyl; OCOC6-C 10 aryl; OCO(5- to 10-membered heteroaryl); OCO(3- to 7-membered heterocycl oalkyl); C6-C 10 aryl; 5- to 10-membered heteroaryl; NH2; NHC1 -C6 alkyl; N(C1-C6 alkyl)2; CONR 8 R 9 ; SF5; one or more N R 8 R 9 C1-C6 alkyl substituted with; and S(O2)C1-C6 alkyl selected from is.

[0844] The substituted ring A is

Chemical formula

[0845] In certain embodiments of the compound of formula AA, the ring A to be substituted is

Chemical formula

[0846] R 2 is C1-C6 alkyl optionally substituted with one or more hydroxy groups, R 1 is S(O2)C1-C6 alkyl; R 2 is C1-C6 alkyl optionally substituted with one or more hydroxy groups, R 1 is halo; R 2 is C3-C7 cycloalkyl optionally substituted with one or more hydroxy groups, wherein R 1 is C1-C6 alkyl; R 2 is 3- to 7-membered heterocycloalkyl optionally substituted with one or more hydroxy groups, wherein R 1 is C1-C6 alkyl; R 2 is 3- to 7-membered heterocycloalkyl optionally substituted with one or more hydroxy groups, wherein R 1 is halo; R 2 is C1-C6 alkyl optionally substituted with one or more oxo groups, and R 1 is methyl; R 2 is C1-C6 alkyl optionally substituted with one or more C1-C6 alkoxy groups, wherein R 1 is C1-C6 alkyl; R 2 is C1-C6 alkyl optionally substituted with one or more NR 8 R 9 groups, R 1 is C1-C6 alkyl; R 2is C1-C6 alkyl optionally substituted by one or more NR 8 R 9 and is optionally substituted by R 1 which is halo. R 1 is halo.

[0847] In certain embodiments of the compound of formula AA, the ring A which is substituted is

Chemical formula

[0848] In certain embodiments of the compound of formula AA, the substituted ring A is

Chemical formula

[0849] R 2 is C1-C6 alkyl optionally substituted with one or more hydroxy; R 1 is S(O2)C1-C6 alkyl; R 2 is C1-C6 alkyl optionally substituted with one or more hydroxy; R 1 is halo; R 2 is C3-C7 cycloalkyl optionally substituted with one or more hydroxy and R is C1-C6 alkyl; 1 is C1-C6 alkyl; R 2 is 3- to 7-membered heterocycloalkyl optionally substituted with one or more hydroxy and R is C1-C6 alkyl; 1 is C1-C6 alkyl; R 2 is 3- to 7-membered heterocycloalkyl optionally substituted with one or more hydroxy and R is halo; 1 is halo; R 2 is C1-C6 alkyl optionally substituted with one or more oxo, and R 1 is methyl; or R 2 is C1-C6 alkyl optionally substituted with one or more C1-C6 alkoxy and R is C1-C6 alkyl; 1 is C1-C6 alkyl.

[0850] R 2 is one or more NR 8 R 9is C1-C6 alkyl optionally substituted with; R 1 is C1-C6 alkyl; or R 2 is C1-C6 alkyl optionally substituted with one or more NR 8 R 9 ; or R 1 is halo.

[0851] In certain embodiments of the compound of formula AA, the substituted ring A is

Chemical formula

[0852] R 2 is 1-hydroxy-2-methylpropan-2-yl, R 1 is methyl; R 2 is 2-hydroxy-2-propyl, R 1 is methyl; R 2 is 2-hydroxy-2-propyl, R 1 is isopropyl; R 2 is 2-hydroxy-2-propyl, R 1 is 1-hydroxyethyl; R 2 is hydroxymethyl, R 1 is methyl; R 2 is 1-hydroxyethyl, R 1 is methyl; R 2 is 2-hydroxyethyl, R 1 is methyl; R 2 is 1-hydroxy-2-propyl, R 1 is methyl; R 2 is 2-hydroxy-2-propyl, R 1 is phenyl; R 2 is C1-C6 alkyl optionally substituted with one or more hydroxy, R 1 is 5- to 10-membered heteroaryl; R2 is 2-hydroxy-2-propyl, and R 1 is pyridyl; R 2 is 2-hydroxy-2-propyl, and R 1 is pyrazolyl; R 2 is C1-C6 alkyl optionally substituted with one or more hydroxy groups, R 1 is S(O2)CH3; R 2 is 2-hydroxy-2-propyl, and R 1 is chloro; R 2 is 2-hydroxy-2-propyl, and R 1 is fluoro; R 2 is C3-C7 cycloalkyl optionally substituted with one or more hydroxy groups and R 1 is C1-C6 alkyl; R 2 is 1-hydroxy-1-cyclopropyl, and R 1 is methyl; R 2 is 1-hydroxy-1-cyclobutyl, and R 1 is methyl; R 2 is 1-hydroxy-1-cyclopentyl, and R 1 is methyl; R 2 is 1-hydroxy-1-cyclohexyl, and R 1 is methyl; R 2 is morpholinyl, and R 1 is methyl; R 2 is 1,3-dioxolan-2-yl, and R 1 is methyl; R 2 is 1,3-dioxolan-2-yl, and R 1 is fluoro; R 2is 1,3-dioxolan-2-yl, R 1 is chloro; R 2 is C1-C6 alkyl optionally substituted with one or more oxo, R 1 is methyl; R 2 is (dimethylamino)methyl, R 1 is methyl; R 2 is COCH3, R 1 is methyl; or R 2 is 2-methoxy-2-propyl, R 1 is methyl.

[0853] In certain embodiments of the compound of formula AA, the substituted ring A is

Chemical formula

Claims

1. A compound selected from the group consisting of: 【Chemical 1】 (wherein TBS represents tert-butyldimethylsilyl, and Boc represents tert-butyloxycarbonyl.)

2. 2. The compound of claim 1, wherein the compound is: or a pharmaceutically acceptable salt thereof. 【Chemistry 2】

3. 2. The compound of claim 1, wherein the compound is: or a pharmaceutically acceptable salt thereof. 【Chemistry 3】

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