1,3-Dihydro-2H-pyrrolo[3,4-c]quinoline derivatives are used as cGAS inhibitors to treat inflammatory and / or autoimmune diseases.

Abstract

This invention relates to novel compounds and their use as pharmaceuticals, more specifically for the prevention or treatment of diseases mediated by cGAS activity, particularly for the prevention or treatment of inflammatory conditions or cancer. The invention also relates to methods for preventing or treating said diseases, the methods comprising using the novel compounds. The invention further relates to pharmaceutical compositions or formulations of the novel compounds and their use as pharmaceuticals, more preferably for the prevention or treatment of diseases mediated by cGAS activity, particularly for the prevention or treatment of inflammatory conditions or cancer. The invention also relates to methods for preparing the compounds.

Description

Technical Field

[0001] This invention relates to novel compounds. The invention also relates to the use of said compounds as medicines, more specifically for the prevention or treatment of diseases mediated by cyclic GMP-AMP synthase (cGAS) activity, particularly for the prevention or treatment of inflammatory and / or autoimmune diseases. The invention further relates to methods for the prevention or treatment of said diseases, the methods comprising using said novel compounds.

[0002] This invention also relates to pharmaceutical compositions or formulations of the novel compounds, and to the use of the compositions or formulations as medicines, more preferably for the prevention or treatment of diseases mediated by cGAS activity, particularly for the prevention or treatment of inflammatory and / or autoimmune diseases. This invention also relates to methods for preparing the compounds. This invention further relates to the combination of the novel compounds with other therapeutic agents. Background Technology

[0003] Innate immunity is considered the first line of defense in cellular stress responses, protecting host cells from pathogen invasion and initiating signals to the adaptive immune system. These processes are triggered by conserved pathogen-associated molecular patterns (PAMPs), which are sensed by multiple pattern recognition receptors (PRRs), thereby activating the expression of cytokine and type I interferon genes. Major antigen-presenting cells, such as monocytes, macrophages, and dendritic cells, produce type I interferons, which are crucial for triggering adaptive T-cell and B-cell immune system responses. Major pattern recognition receptors detect abnormal (i.e., misplaced, immature, or unmodified) nucleic acids on the cell surface, inside the lysosomal membrane, or in other cellular compartments (Barbalat et al., Annu. Rev. Immunol. 29, 185-214 (2011)).

[0004] Circular GMP-AMP (cGAMP) synthase (cGAS) is a key sensor for cytoplasmic double-stranded DNA. When this DNA originates from microorganisms or the host (which can be mitochondrial, extracellular (myeloid cells phagocytose damaged DNA), or nuclear (reverse transcription by reverse elements, nuclear damage)), it functions as a ubiquitous danger-related molecule. Upon binding to double-stranded DNA, cGAS uses one ATP and one GTP to catalyze the synthesis of a cyclic nucleotide (and second messenger), cGAMP. cGAMP binds to the endoplasmic reticulum-resident dimeric transmembrane receptor interferon gene stimulating factor (STING), leading to its activation and release from the endoplasmic reticulum. STING translocates to the Golgi apparatus, where it recruits and activates TANK-binding kinase 1 (TBK1), resulting in the phosphorylation and activation of interferon-regulated transcription factor 3 (IRF3). Subsequently, IRF3 forms a dimer and translocates to the nucleus, where it promotes the expression of type I interferon (IFN-I). In addition, STING also activates the classical NFκβ pathway through the kinase Iκβ, leading to the production of pro-inflammatory cytokines.

[0005] The cGAS-STING signaling pathway has become a key mediator of inflammatory responses in various disease indications, including infection, cellular stress, and tissue damage. Rare genetic diseases, such as type I interferonopathies, are driven by loss-of-function mutations in cytoplasmic nucleases (TREX1, SAMHD1, DNASE2), leading to the accumulation of cytoplasmic double-stranded DNA, thereby amplifying the cGAS-STING signaling pathway and type I interferon responses. The following are some of the most prominent autoimmune diseases that benefit from cGAS inhibition, such as Aicardi Goutieres syndrome (AGS), TREX1 subtypes of lupus, and heterozygous TREX1 mutations in familial frostbite-like lupus. Mitochondrial leakage or defects leading to the accumulation of mtDNA in the cytoplasm are increasingly considered a potential pathological inflammatory response in neurodegenerative diseases such as subtypes of Parkinson's disease (TDP43, PINK1-Perkin), subtypes of amyotrophic lateral sclerosis (α-synuclein, SOD1), and frontotemporal dementia (FTD). Several other inflammatory diseases are also associated with the accumulation of cytoplasmic mtDNA, including nonalcoholic steatohepatitis (NASH), chronic obstructive pulmonary disease (COPD), inflammatory bowel disease (IBD), antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), and autoimmune diseases (several subtypes of systemic lupus erythematosus). Furthermore, the reverse transcription of Alu repeat elements into cytoplasmic Alu cDNA has been shown to activate cGAS and is causally associated with the late form of dry age-related macular degeneration (AMD), namely geographic atrophy (GA). Additionally, chromosomal instability can also lead to increased cytoplasmic DNA. Recent studies have shown that certain subtypes of various cancer types exhibit TREX deficiency, which is associated with enhanced type I interferon responses and disease progression, suggesting that the cGAS-STING pathway has pro-tumorigenic properties. Therefore, small molecule inhibitors of cGAS could be used to treat or prevent various diseases caused by abnormal cGAS-STING activity.

[0006] In 2017, Pfizer published research results on compound PF-06928215 as a cGAS inhibitor (Hall et al., PLoS ONE 12(9): e0184843). Nitropyrazoles and pyridoindole compounds have been published as cGAS inhibitors (Lama et al., Nat Com 10, 2261 (2019)). Patent applications WO / 2022066851, WO / 2023081441, WO / 2022238327, WO / 2022238335, WO / 2022051634 and WO / 2022137082 also describe cGAS inhibitors.

[0007] However, for the prevention or treatment of inflammatory and / or autoimmune diseases mediated by cGAS activation, and for the indications for these diseases, there remains a pressing need for novel, alternative, or superior therapeutic agents. Therapeutic agents with superior target binding affinity, (cellular) potency, fewer side effects, higher activity, lower toxicity, better pharmacokinetic or pharmacodynamic properties, better (oral) bioavailability, higher (hepatocyte) metabolic stability, diverse volumes of distribution, effective doses, or combinations thereof, are highly anticipated.

[0008] This invention provides a novel class of compounds that can be used as cGAS inhibitors or cGAS activity modulators for indications of cGAS-mediated diseases. Summary of the Invention

[0009] The present invention is based on the following unexpected discovery: at least one of the above problems can be solved by the following compounds.

[0010] This invention provides novel compounds, particularly compounds of formula (I) as defined in the claims and / or embodiments described herein, their stereoisomers, tautomers, salts (especially pharmaceutically acceptable salts), solvates, polymorphs, and / or prodrugs. (I).

[0011] This invention provides novel compounds that have been shown to have regulatory activity against cGAS, and more specifically, inhibitory activity. This invention also demonstrates that these compounds effectively inhibit cGAS activity. Therefore, these compounds constitute a useful new class of potent compounds for the treatment and / or prevention of cGAS-mediated diseases in animals, mammals, and humans, and more specifically for the treatment and / or prevention of inflammatory conditions, particularly those related to cGAS activity or activation, and more specifically including inflammatory diseases, autoimmune diseases, allergic diseases, fibrotic diseases, and cancer.

[0012] The present invention also relates to the use of the compounds of the invention as medicines, the use of such compounds as medicines and their use in the preparation of medicines, and more specifically for the treatment and / or prevention of cGAS-mediated diseases, particularly inflammatory conditions, such as (i) inflammatory diseases, (ii) autoimmune diseases, (iii) allergic diseases, (iv) fibrotic diseases, and cancers in animals or mammals (especially humans).

[0013] The present invention also relates to pharmaceutical compositions comprising an effective amount of the compounds of the present invention, the use of said pharmaceutical compositions as medicines (more specifically as medicines for the prevention or treatment of cGAS-mediated diseases), and methods for preparing said pharmaceutical compositions.

[0014] This invention also relates to a method for treating or preventing cGAS-mediated diseases in humans by administering one or more such compounds to a patient in need, optionally in combination with one or more other drugs. This document also discloses a method for treating inflammatory conditions (inflammatory diseases, autoimmune diseases, allergic diseases, fibrotic diseases) and cancer in a patient in need, comprising administering to the patient an effective amount of a combination of the disclosed compounds with other therapeutic agents. In some embodiments, the other drugs or therapeutic agents are anti-inflammatory agents, anti-fibrotic agents, or anti-allergic agents.

[0015] When referring to the treatment or prevention of cGAS-mediated diseases in animals or mammals (especially humans), in the specific implementation plan, it specifically refers to (i) inflammatory conditions, more specifically inflammatory diseases, autoimmune diseases, allergic diseases, inflammatory conditions of any tissue or organ, diseases with inflammatory components, or any other inflammatory condition, more specifically conditions that respond to treatment with cGAS inhibitors or modulators, especially conditions in which cGAS activity or activation drives, promotes, maintains, empowers, or similarly acts on such diseases; and (ii) cancer. In specific implementation plans, cGAS-mediated diseases are selected from inflammatory, allergic, or autoimmune diseases, such as systemic lupus erythematosus (SLE), cutaneous lupus erythematosus (CLE), lupus nephritis (LN), interferon disease, psoriasis, insulin-dependent diabetes mellitus (IDDM), vasculitis, scleroderma, Aicardi Goutieres syndrome, dermatomyositis, sepsis, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, Sjögren's syndrome (SS), age-related macular degeneration (AMD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer's disease, Huntington's disease, and Parkinson's disease.

[0016] More specifically, relating to the treatment or prevention of inflammatory conditions, the present invention includes administering an effective amount of the compounds disclosed herein to a patient, possibly in combination with other therapeutic agents. In some embodiments, the other therapeutic agents are anti-inflammatory agents, anti-fibrotic agents, or anti-allergic agents. Specifically, relating to the treatment or prevention of inflammatory conditions, including the treatment or prevention of systemic lupus erythematosus (SLE), interferon disease, or Aicardi Goutieres syndrome in patients in need, comprising administering an effective amount of the compounds disclosed herein to the patient; or comprising the treatment and / or control of neuroinflammation in patients in need, comprising administering an effective amount of the compounds disclosed herein to the patient. The present invention also relates to methods for preparing the compounds of the present invention, comprising the compound synthesis steps described herein. Attached Figure Description

[0017] Figure 1In vivo activity of CPD 058. Anti-inflammatory activity of CPD 058 in a mouse model of UVB-induced injury and inflammation according to Example 65. Detailed Implementation

[0018] The invention will be further described below, and in some cases in conjunction with specific embodiments, but the invention is not limited to the embodiments described.

[0019] The term "cGAS-mediated disease" or "cGAS-mediated condition" refers to a disease, disorder, or condition in which the cGAS signaling pathway is active or activated, and where cGAS activity or activation promotes, drives, maintains, or empowers such disease. cGAS-mediated diseases include inflammatory diseases, autoimmune diseases, and allergic diseases, as well as cancer, fibrotic diseases, and neurodegenerative diseases, and any other disease with an inflammatory component or any other disease, disorder, or condition that responds well to treatment with cGAS inhibitors or modulators. In the specific implementation plan, the term "cGAS-mediated disease" or "cGAS-mediated condition" refers to a disease, disorder, or condition in which cGAS is active or activated, more specifically due to, or where cGAS activity is considered to be associated with: (i) a genetic abnormality or hereditary disease, such as type I interferon disease, driven by loss-of-function mutations in cytoplasmic nucleases (TREX1, SAMHD1, DNASE2), such as those seen in Aicardi Goutieres syndrome (AGS), TREX1 subtypes of lupus, and heterozygous TREX1 mutations in familial frostbite-like lupus; and / or (ii) accumulation of mtDNA in the cytoplasm, such as that caused by mitochondrial leakage or defects, resulting in a potential pathological inflammatory response, such as Seen in neurodegenerative diseases (e.g., subtypes of Parkinson's disease (TDP43, PINK1-Perkin), subtypes of amyotrophic lateral sclerosis (α-synuclein, SOD1), and frontotemporal dementia (FTD)) or a variety of other diseases with inflammatory components (e.g., nonalcoholic steatohepatitis (NASH), chronic obstructive pulmonary disease (COPD), inflammatory bowel disease (IBD), antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), and systemic lupus erythematosus (SLE) subtypes); and / or (iii) cytoplasmic AlucDNA (e.g., reverse transcription via Alu repeat elements) can induce inflammation by activating cGAS, as seen in dry age-related macular degeneration (AMD) (a late form) or geographic atrophy (GA).

[0020] The term "autoimmune disease" or "autoimmune syndrome" refers to a disease caused by the body's inability to recognize its own components (down to the submolecular level) as "self," resulting in an abnormal immune response against its own cells and / or tissues. Autoimmune diseases are classified into "systemic autoimmune diseases" (e.g., lupus erythematosus, psoriasis, vasculitis, polymyositis, scleroderma, multiple sclerosis, ankylosing spondylitis, rheumatoid arthritis, and Sjögren's syndrome), "autoimmune endocrine diseases" (e.g., thyroiditis), and "organ-specific autoimmune diseases" (e.g., Addison's disease, hemolytic anemia or pernicious anemia, Goodpasser syndrome, Graves' disease, idiopathic thrombocytopenic purpura, insulin-dependent diabetes mellitus, juvenile diabetes mellitus, uveitis, Crohn's disease, ulcerative colitis, pemphigus, atopic dermatitis, autoimmune hepatitis, primary biliary cirrhosis, autoimmune pneumonia, autoimmune carditis, myasthenia gravis, glomerulonephritis, and spontaneous infertility). Therefore, autoimmune diseases target the body's own cells or tissues, including responses to "self-antigens," which are antigens (e.g., protein antigens) that are components of a specific mammalian organism. In this mechanism, self-antigens are recognized by B cells and / or T cells, thereby triggering an immune response against said self-antigen.

[0021] Therefore, the non-restrictive list of diseases covered by the term "autoimmune disease" or "autoimmune syndrome" includes: acute disseminated encephalomyelitis (ADEM), Addison's disease, alopecia areata, antiphospholipid antibody syndrome (APS), autoimmune hemolytic anemia, autoimmune hepatitis, bullous pemphigoid, Behçet's disease, celiac disease, inflammatory bowel disease (IBD) (e.g., Crohn's disease and ulcerative colitis), dermatomyositis, type 1 diabetes, Goodpass syndrome, Graves' disease, Guillain-Barré syndrome (GBS), Hashimoto's disease, idiopathic thrombocytopenic purpura, lupus erythematosus, mixed connective tissue disease, multiple sclerosis (MS), myasthenia gravis, narcolepsy, pemphigus vulgaris, pernicious anemia, psoriasis, psoriatic arthritis, polymyositis, primary biliary cirrhosis, rheumatoid arthritis (RA), Sjögren's syndrome, temporal arteritis, vasculitis, Wegener's granulomatosis, and atopic dermatitis. The following diseases are also suspected to be autoimmune diseases: ankylosing spondylitis, autoimmune inner ear disease, Chagas disease, chronic obstructive pulmonary disease (COPD), endometriosis, hidradenitis suppurativa, Kawasaki disease, IgA nephropathy, interstitial cystitis, morphine scleroderma, neuromuscular myotonia, schizophrenia, scleroderma, stiff-person syndrome, and vitiligo. Autoimmune diseases are classified into "systemic autoimmune diseases" (such as lupus erythematosus, psoriasis, vasculitis, polymyositis, scleroderma, multiple sclerosis, ankylosing spondylitis, rheumatoid arthritis, and Sjögren's syndrome), "autoimmune endocrine diseases" (such as thyroiditis), and "organ-specific autoimmune diseases" (such as Addison's disease, hemolytic anemia or pernicious anemia, Goodpasser syndrome, Graves' disease, idiopathic thrombocytopenic purpura, insulin-dependent diabetes mellitus, juvenile diabetes mellitus, uveitis, Crohn's disease, ulcerative colitis, pemphigus, atopic dermatitis, autoimmune hepatitis, primary biliary cirrhosis, autoimmune pneumonia, autoimmune carditis, myasthenia gravis, glomerulonephritis, and spontaneous infertility).

[0022] The term "inflammatory disease" or "inflammatory condition" refers to, but is not limited to, the following diseases: rheumatoid arthritis, conjunctivitis, rheumatoid spondylitis, osteoarthritis, gouty arthritis, bronchitis, tuberculosis, chronic cholecystitis, inflammatory bowel disease, acute pancreatitis, sepsis, asthma, chronic obstructive pulmonary disease, inflammatory skin diseases (e.g., psoriasis and atopic dermatitis), systemic inflammatory response syndrome (SIRS), acute respiratory distress syndrome (ARDS), cancer-related inflammation, tumor-related angiogenesis reduction, diabetes, treatment of graft-versus-host disease and related tissue rejection inflammation, Crohn's disease, delayed-type hypersensitivity reactions, and immune-mediated and inflammatory components of central nervous system diseases, such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis.

[0023] The term "allergic disease" or "allergic condition" refers to, but is not limited to, the following conditions: asthma, allergic rhinitis, allergic sinusitis, allergic syndrome, urticaria, angioedema, atopic dermatitis, allergic contact dermatitis, erythema nodosum, erythema multiforme, necrotizing phlebitis of the skin, skin inflammation caused by insect bites, and blood-sucking parasite infections.

[0024] The term "fibrotic disease" as used in this article refers to pulmonary fibrosis (e.g., asbestosis, COVID-19-associated pulmonary fibrosis, drug-induced pulmonary fibrosis, hypersensitivity pneumonitis (HP), idiopathic pulmonary fibrosis (IPF), idiopathic nonspecific interstitial pneumonia, pneumoconiosis, rheumatoid arthritis-associated interstitial lung disease (RA-ILD)), liver fibrosis, cardiac fibrosis, mediastinal fibrosis, retroperitoneal fibrosis (including renal fibrosis), myelofibrosis, skin fibrosis, scleroderma or systemic sclerosis, and other types of pathological fibrosis.

[0025] As used herein, the term "cancer" refers to all types of cancer, growths, or (malignant) tumors in animals (more specifically, humans), including carcinomas, sarcomas, lymphomas, leukemias, germ cell tumors, and germ cell tumors, thus encompassing solid cancers and lymphomas. Exemplary cancers that can be treated with the compounds, pharmaceutical compositions, or methods provided herein include lymphomas, sarcomas, bladder cancer, bone cancer, brain tumors, cervical cancer, colon cancer, esophageal cancer, gastric cancer, head and neck cancer, kidney cancer, myeloma, thyroid cancer, leukemia, prostate cancer, breast cancer (e.g., ER-positive, ER-negative, chemotherapy-resistant, resistant to Herceptin, HER2-positive, resistant to doxorubicin, resistant to tamoxifen, ductal carcinoma, lobular carcinoma, primary, metastatic), ovarian cancer, pancreatic cancer, liver cancer (e.g., hepatocellular carcinoma), lung cancer (e.g., non-small cell lung cancer, squamous cell lung cancer, adenocarcinoma, large cell lung cancer, small cell lung cancer, carcinoid, sarcoma), glioblastoma multiforme, glioma, or melanoma. Other examples include thyroid cancer, endocrine system cancers, brain cancer, breast cancer, cervical cancer, colon cancer, head and neck cancer, liver cancer, kidney cancer, lung cancer, non-small cell lung cancer, melanoma, mesothelioma, ovarian cancer, sarcoma, stomach cancer, uterine cancer or medulloblastoma, Hodgkin lymphoma, non-Hodgkin lymphoma, multiple myeloma, neuroblastoma, glioma, glioblastoma multiforme, ovarian cancer, rhabdomyosarcoma, essential thrombocytosis, essential macroglobulinemia, primary brain tumors, and cancer. Malignant insulinoma, malignant carcinoid tumor, bladder cancer, precancerous skin lesions, testicular cancer, lymphoma, thyroid cancer, neuroblastoma, esophageal cancer, urogenital tract cancer, malignant hypercalcemia, endometrial cancer, adrenocortical carcinoma, endocrine or exocrine pancreatic tumors, medullary thyroid carcinoma, medullary thyroid carcinoma, melanoma, colorectal cancer, papillary thyroid carcinoma, hepatocellular carcinoma, papillary Paget's disease, phyllodes tumor, lobular carcinoma, ductal carcinoma, pancreatic stellate cell carcinoma, hepatic stellate cell carcinoma, or prostate cancer. In some implementations, the term cancer refers to bladder cancer, bone cancer, brain cancer, breast cancer, gastric cardia cancer, cervical cancer, colon cancer, colorectal cancer, esophageal cancer, fibrosarcoma, gastric cancer, gastrointestinal cancer, head and neck cancer, Kaposi's sarcoma, kidney cancer, pancreatic cancer, penile cancer, testicular germ cell carcinoma, thymoma, thymic carcinoma, lung cancer, ovarian cancer, or prostate cancer.

[0026] In the specific implementation plan, the term "inflammatory condition" as used herein refers to inflammatory diseases, autoimmune diseases, allergic diseases, inflammatory conditions of any tissue or organ, diseases with inflammatory components, or any other inflammatory condition, more specifically to conditions that respond to treatment with cGAS inhibitors or modulators, and especially to conditions in which cGAS activity or activation drives, promotes, maintains, empowers, or similarly acts on such diseases.

[0027] Therefore, the term "inflammatory disease" as used in this article includes inflammatory, allergic, or autoimmune diseases or diseases with inflammatory components, such as systemic lupus erythematosus (SLE), cutaneous lupus erythematosus (CLE), lupus nephritis (LN), interferon disease, psoriasis, insulin-dependent diabetes mellitus (IDDM), vasculitis, scleroderma, Aicardi Goutieres syndrome, dermatomyositis, sepsis, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, Sjögren's syndrome (SS), age-related macular degeneration (AMD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer's disease, Huntington's disease, and Parkinson's disease.

[0028] The term "inflammatory condition" also includes conditions involving inflammation of any tissue or organ in the body, including musculoskeletal inflammation, vascular inflammation, neurological inflammation, digestive system inflammation, eye inflammation, reproductive system inflammation, and other inflammations (such as cardiovascular system inflammation). Musculoskeletal inflammation refers to any inflammatory condition of the musculoskeletal system, particularly those affecting the joints of the bones, including the joints of the hands, wrists, elbows, shoulders, jaws, spine, neck, hips, knees, ankles, and feet, as well as conditions affecting the tissues that connect muscles to bones (such as tendons). Examples of musculoskeletal inflammation include arthritis (including, for example, osteoarthritis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, acute and chronic infectious arthritis, arthritis associated with gout and pseudogout, and juvenile idiopathic arthritis), tendinitis, synovitis, tenosynovitis, bursitis, fibrositis (fibromyalgia), epicondylitis, myositis, and osteitis (such as Paget's disease, pubic osteitis, and cystic fibrosis). Neuroinflammatory diseases or inflammation of the nervous system include encephalitis, Guillain-Barré syndrome, meningitis, neuromuscular rigidity, narcolepsy, multiple sclerosis, myelitis, schizophrenia, and inflammation of the central nervous system, including neurodegenerative diseases such as Parkinson's disease, amyotrophic lateral sclerosis (ALS), and Alzheimer's disease. Ocular inflammation refers to inflammation of any structure of the eye, including the eyelids. Examples of ocular inflammation that can be treated with the compounds disclosed herein include blepharitis, blepharochalasis, conjunctivitis, dacryoadenitis, keratitis, keratoconjunctivitis sicca (dry eye syndrome), scleritis, trichiasis, and uveitis. Inflammation of the vascular or lymphatic system includes atherosclerosis, arthritis, phlebitis, vasculitis, and lymphangitis. Inflammatory conditions of the digestive system include cholangitis, cholecystitis, enteritis, enterocolitis, gastritis, gastroenteritis, inflammatory bowel diseases (e.g., Crohn's disease and ulcerative colitis), ileitis, and proctitis. Inflammatory conditions of the reproductive system include cervicitis, chorioamnionitis, endometritis, epididymitis, omphalitis, oophoritis, orchitis, salpingitis, tubo-ovarian abscess, urethritis, vaginitis, vulvitis, and vulvar pain.

[0029] Autoimmune diseases with inflammatory components are also included in the term "inflammatory diseases." These include systemic lupus erythematosus, cutaneous lupus erythematosus, acute disseminated alopecia areata, Behçet's disease, Chagas disease, chronic fatigue syndrome, autonomic dysfunction, encephalomyelitis, ankylosing spondylitis, aplastic anemia, hidradenitis suppurativa, autoimmune hepatitis, autoimmune oophoritis, celiac disease, Crohn's disease, type 1 diabetes, giant cell arteritis, Goodpasser syndrome, Graves' disease, Guillain-Barré syndrome, Hashimoto's disease, Hennech-Schönlein purpura, Kawasaki disease, microscopic colitis, microscopic polyarteritis, mixed connective tissue disease, multiple sclerosis, myasthenia gravis, nystagmus-myoclonus syndrome, optic neuritis, Oddi's thyroiditis, pemphigus, polyarteritis nodosa, polymyalgia, rheumatoid arthritis, Reiter's syndrome, Sjögren's syndrome, and Aicardiosis. Goutieres syndrome, temporal arteritis, Wegener's granulomatosis, warm antibody-type autoimmune hemolytic anemia, interstitial cystitis, Lyme disease, scleroderma, psoriasis, sarcoidosis, scleroderma, ulcerative colitis, and vitiligo.

[0030] The term "inflammatory condition" also refers to allergic diseases or T-cell-mediated allergic diseases with inflammatory components, such as contact hypersensitivity, contact dermatitis, urticaria, skin allergies, respiratory allergies (e.g., hay fever, allergic rhinitis), and gluten-sensitive enteropathy (celiac disease).

[0031] Generally, the term "inflammatory condition" encompasses any disease with inflammatory components, and therefore also includes appendicitis, dermatitis, dermatomyositis, endocarditis, fibrositis, gingivitis, glossitis, hepatitis, hidradenitis suppurativa, iritis, laryngitis, mastitis, myocarditis, nephritis, otitis, pancreatitis, mumps, pericarditis, peritonitis, pharyngitis, pleurisy, pneumonia, prostatitis, pyelonephritis, stomatitis, transplant rejection (involving the kidney, liver, heart, lung, pancreas (e.g., islet cells), bone marrow, cornea, small intestine, skin allografts, skin allografts, heart valve xenografts, serum sickness, and graft-versus-host disease), acute pancreatitis, chronic pancreatitis, acute respiratory distress syndrome, Cezari syndrome, congenital adrenal hyperplasia, and non-suppurative diseases. Hypothyroidism, cancer-related hypercalcemia, pemphigus, bullous herpetic dermatitis, severe erythema multiforme, exfoliative dermatitis, seborrheic dermatitis, seasonal or perennial allergic rhinitis, bronchial asthma, contact dermatitis, atopic dermatitis, drug allergy, allergic conjunctivitis, keratitis, ocular herpes zoster, iritis and iridocyclitis, chorioretinitis, optic neuritis, symptomatic sarcoidosis, fulminant or disseminated pulmonary tuberculosis, chemotherapy, adult idiopathic thrombocytopenic purpura, adult secondary thrombocytopenia, acquired (autoimmune) hemolytic anemia, adult leukemia and lymphoma, childhood acute leukemia, regional enteritis, autoimmune vasculitis, multiple sclerosis, chronic obstructive pulmonary disease, solid organ transplant rejection, and sepsis.

[0032] Furthermore, fibrotic diseases also fall under the category of cGAS-mediated conditions or diseases. Fibrosis, also known as fibrotic scarring, is a pathological wound healing process in which connective tissue replaces normal parenchymal tissue, and this process is uncontrolled, leading to significant tissue remodeling and the formation of permanent scar tissue. Fibrosis is the end result of a chronic inflammatory response triggered by a variety of stimuli, including persistent infection, autoimmune reactions, allergic reactions, chemical damage, radiation, and tissue injury. Fibrotic diseases, especially those with active inflammatory components, are also included in the term "inflammatory conditions," which include systemic sclerosis (SSc), interferon disease, non-alcoholic steatohepatitis (NASH), interstitial lung disease (ILD), especially progressive fibrotic interstitial lung disease (PF-ILD), and particularly idiopathic pulmonary fibrosis (IPF).

[0033] As used herein, the term "treatment" is intended to refer to the administration of the compounds or compositions of the present invention to a subject to achieve a therapeutic or preventive benefit, specifically achieved by inhibiting cGAS. Treatment includes reversing, improving, alleviating, inhibiting the progression of a disease, disorder, or condition, or one or more symptoms, complications, or biochemical indicators of such disease, disorder, or condition, reducing its severity, or preventing said disease, disorder, or condition, or one or more symptoms thereof, specifically disease, disorder, or condition mediated by cGAS. "Therapeutic benefit" means eradicating, improving, reversing, alleviating, inhibiting the progression of the treated underlying disease, or reducing its severity. Furthermore, a therapeutic benefit is achieved by eradicating or improving one or more physiological symptoms associated with an underlying disease, thereby observing improvement in the patient's condition, although in some embodiments the patient is still troubled by the underlying disease. Regarding preventive benefits, in some embodiments, the composition is administered to a patient at risk of developing a specific disease, or to a patient who reports one or more physiological symptoms of a disease but has not yet been diagnosed with the disease. For example, some methods described herein treat cancer by reducing or preventing the occurrence, growth, metastasis, or progression of cancer, or by alleviating the symptoms of cancer.

[0034] As used herein, the term “prevention” is intended to refer to the administration of the compounds or compositions of the present invention to a subject to achieve a therapeutic or preventive benefit, specifically by inhibiting cGAS, thereby at least delaying the onset or progression of a disease, disorder, or condition, or delaying the onset or progression of one or more symptoms, complications, or biochemical indicators of such a disease, disorder, or condition.

[0035] The term “subject” as used in this article refers to an animal, preferably a mammal, and most preferably a human, i.e., a patient, that has become the subject of treatment, observation or experimentation, or is in need of such treatment.

[0036] As used in this article, “therapeutic effective amount” refers to the amount of an active compound or agent that elicits a biological or pharmacological response in a tissue system, animal, or human that is expected by the investigator, veterinarian, physician, or other clinician, including the relief or partial relief of symptoms of the disease or condition being treated.

[0037] The term “composition” as used herein is intended to cover products containing a therapeutically effective amount of a specified ingredient, and any product derived directly or indirectly from a specified amount of a specified ingredient.

[0038] The terms “antagonist” or “inhibitor” used in this article refer to inhibitors of cGAS activity or activation, which are compounds that can functionally antagonize or inhibit cGAS activity or activation, depending on the specific circumstances.

[0039] It should be noted that the term "comprising" as used in the claims should not be construed as limited to the components listed thereafter; it does not exclude other elements or steps.

[0040] Throughout this specification, references to "an embodiment" or "a particular embodiment" mean that a specific feature, structure, or characteristic described in connection with that embodiment is included in at least one embodiment of the invention. Therefore, the phrases "in an embodiment" or "in a particular embodiment" appearing throughout this specification do not necessarily all refer to the same embodiment, but may refer to the same embodiment. Furthermore, in one or more embodiments, a particular feature, structure, or characteristic may be combined in any suitable manner, as will be apparent to those skilled in the art based on this disclosure. When referring to a singular noun, the use of an indefinite or definite article (e.g., "an," "a," or "the") includes the plural form of that noun, unless otherwise expressly stated.

[0041] Similarly, it should be understood that in the description of exemplary embodiments of the invention, various features of the invention are sometimes summarized in a single embodiment, drawing or description thereof in order to simplify the disclosure and facilitate understanding of one or more different aspects of the invention.

[0042] In the following definitions, the number of carbon atoms represents the upper limit of the optimal number of carbon atoms normally present in the substituent or linker; it should be understood that, unless otherwise stated in this application, the number of carbon atoms represents the upper limit of the optimal number of carbon atoms for that particular substituent or linker.

[0043] As used herein, the term "leaving group" or "LG" refers to a chemical group that is readily substituted, cleaved, or hydrolyzed by a nucleophile under alkaline or acidic conditions. In specific embodiments, the leaving group is selected from halogen atoms (e.g., Cl, Br, I) or sulfonate groups (e.g., methanesulfonate, p-toluenesulfonate, trifluoromethanesulfonate).

[0044] The term "protecting group" refers to a portion of a compound that masks or alters the properties of functional groups or the overall properties of the compound. The chemical substructures of protecting groups vary considerably. One function of protecting groups is as intermediates in the synthesis of parent drug substances. Chemical protecting groups and protecting / deprotecting strategies are well known in the art. See: "Protective Groups in Organic Chemistry", Theodora W. Greene (John Wiley & Sons, Inc., New York, 1991). Protecting groups are commonly used to mask the reactivity of certain functional groups to facilitate the efficiency of desired chemical reactions, such as the orderly and planned formation and breaking of chemical bonds. In addition to the reactivity of the protected functional groups, protection of compound functional groups can alter other physical properties, such as polarity, lipophilicity (hydrophobicity), and other properties that can be determined using common analytical tools. Chemically protected intermediates may be biologically active or inactive. In some embodiments, the protecting group is selected from urethane groups (e.g., Boc), benzyl, p-methoxybenzyl, or acetyl.

[0045] Protected compounds can also exhibit altered, and in some cases optimized, in vitro and in vivo properties, such as the ability to penetrate cell membranes and resistance to enzymatic degradation or sequestration. In this role, the protected compound with the intended therapeutic effect can be referred to as a prodrug. Another function of the protecting group is to convert the parent drug into a prodrug, thereby releasing the parent drug during prodrug conversion in vivo. Because the active prodrug can be absorbed more efficiently than the parent drug, the in vivo potency of the prodrug can be greater than that of the parent drug. The protecting group can be removed in vitro (for chemical intermediates) or in vivo (for prodrugs). For chemical intermediates, the physiological acceptability of the product (e.g., alcohols) resulting from deprotection is not particularly important, although pharmacologically harmless products are generally preferred.

[0046] As used herein, the prefix C is used for the terms alkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl as defined herein. x-y Or C x -C y This indicates that the alkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group consists of x to y carbon atoms or heteroatoms constituting the alkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group. This excludes carbon atoms and / or heteroatoms in (optionally) substituents, as well as carbon atoms and / or heteroatoms in the groups / molecules they substituted.

[0047] The term "alkyl" or "C" as used in this article 1-18 "Alkyl" refers to a C1-C group that does not have an unsaturated site. 18Primary, secondary, or tertiary, linear, branched, or straight-chain hydrocarbons. Examples include methyl, ethyl, 1-propyl (n-propyl), 2-propyl (isopropyl), 1-butyl, 2-methyl-1-propyl (isobutyl), 2-butyl (sec-butyl), 2-dimethyl-2-propyl (tert-butyl), 1-pentyl (n-pentyl), 2-pentyl, 3-pentyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 3-methyl-1-butyl, 2-methyl-1-butyl, 1-hexyl, 2-hexyl, 3-hexyl, 2... -Methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 3-methyl-3-pentyl, 2-methyl-3-pentyl, 2,3-dimethyl-2-butyl, 3,3-dimethyl-2-butyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl, n-tridecyl, n-tetradecyl, n-pentadecanyl, n-hexadecyl, n-heptadecyl, n-octadecyl, n-nonadecanyl, and n-eicosyl. In specific embodiments, the term "alkyl" refers to C14. 1-12 Alkyl (C 1-12 Hydrocarbons), more specifically C 1-9 Alkyl (C 1-9 Hydrocarbons), and more specifically C 1-6 Alkyl (C 1-6 hydrocarbons or C 1-4 Alkyl (C 1-4 Hydrocarbons), as further defined herein. Such embodiments may be applied independently to terms comprising multiple alkyl moieties; for example, embodiments of alkoxyalkyl groups include, but are not limited to, C14-12 ... 1-4 Alkoxy-C 1-6 Alkyl, C 1-6 Alkoxy-C 1-6 Alkyl or C 1-6 Alkoxy-C 1-4 Alkyl. The term “haloalkyl” as a group or part of a group refers to an alkyl group having the meaning as defined above, wherein one, two, or three hydrogen atoms are each substituted with a halogen as defined herein. Non-limiting examples of such haloalkyl groups include chloromethyl, 1-bromoethyl, fluoromethyl, difluoromethyl, trifluoromethyl, 1,1,1-trifluoroethyl, etc.

[0048] The term "hydroxyalkyl" as a group or part of a group refers to an alkyl group having the meaning as defined above, wherein one, two, or three hydrogen atoms are each substituted with a hydroxyl group as defined herein, i.e., monohydroxyalkyl, dihydroxyalkyl, and trihydroxyalkyl, respectively. Non-limiting examples of such hydroxyalkyl groups include hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 1,2-dihydroxyethyl, etc.

[0049] The term "alkoxy" or "alkyloxy" as a group or part of a group refers to a group having the formula -OR b The group, wherein Rb C as defined above 1-6 Alkyl group. Suitable C 1-6 Non-limiting examples of alkoxy groups include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentoxy, and hexoxy.

[0050] The term "hydroxyalkoxy" as a group or part of a group refers to an alkoxy group having the meaning as defined above, wherein one, two, or three hydrogen atoms are each substituted with a hydroxyl group as defined herein, namely monohydroxyalkoxy, dihydroxyalkoxy, and trihydroxyalkoxy, respectively. Non-limiting examples of such hydroxyalkoxy groups include hydroxymethoxy, 1-hydroxyethoxy, 2-hydroxyethoxy, 1,2-dihydroxyethoxy, etc.

[0051] The term "aminoalkoxy" as a group or part of a group refers to an alkoxy group having the meaning as defined above, wherein one, two, or three hydrogen atoms are each substituted with an amino group (-NH2) as defined herein, namely monoaminoalkoxy, diaminoalkoxy, and triaminoalkoxy, respectively. Non-limiting examples of such aminoalkoxy groups include aminomethoxy, 1-aminoethoxy, 2-aminoethoxy, 1,2-diaminoethoxy, etc.

[0052] The term "hydroxycarbonylalkyl" as a group or part of a group refers to the formula -R a The -COOH group, where R a alkylene compounds as defined in this article.

[0053] The term "haloalkoxy" as a group or part of a group refers to the formula -OR c The group, wherein R c "Haloalkyl" is defined herein. Non-limiting examples of suitable haloalkoxy groups include fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2,2-difluoroethoxy, 2,2,2-trichloroethoxy, trichloromethoxy, 2-bromoethoxy, pentafluoroethyl, 3,3,3-trichloropropoxy, and 4,4,4-trichlorobutoxy.

[0054] As used herein and unless otherwise stated, the term "cycloalkyl" or "C" refers to the cycloalkyl group or cycloalkyl group. 3-18 "Cycloalkyl" refers to a monovalent group of a saturated hydrocarbon having 3 to 18 carbon atoms, which is composed of C... 3-10 Single ring or C 7-18The saturated hydrocarbon comprises or includes the polycyclic saturated hydrocarbon, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclopropylethylene, methylcyclopropene, cyclohexyl, cycloheptyl, cyclooctyl, cyclooctylmethylene, norbornyl, flavyl, trimethyltricycloheptyl, decahydronaphthyl, adamantyl, etc. In a specific embodiment, the term "cycloalkyl" refers to C14-C ... 3-12 cycloalkyl (saturated cyclic C 3-12 Hydrocarbons), more specifically C 3-9 cycloalkyl (saturated cyclic C 3-9 Hydrocarbons), and more specifically C 3-6 cycloalkyl (saturated cyclic C 3-6 Hydrocarbons), as further defined above. For the avoidance of ambiguity, fused systems of cycloalkyl rings and heterocyclic rings are considered heterocyclic, regardless of the ring bonded to the core structure. Fused systems of cycloalkyl rings and aromatic rings are considered aryl, regardless of the ring bonded to the core structure. Fused systems of cycloalkyl rings and heteroaryl rings are considered heteroaryl, regardless of the ring bonded to the core structure.

[0055] The term "alkenyl" or "C2-C" is used in this article. 18 "Alkenyl" refers to a C2-C group having at least one (usually 1 to 3, preferably 1) unsaturated site (i.e., carbon-carbon sp2 double bond). 18 Primary, secondary, or tertiary, linear, branched, or straight-chain hydrocarbons. Examples include, but are not limited to, vinyl (-CH=CH2), allyl (-CH2CH=CH2), and 5-hexenyl (-CH2CH2CH2CH2CH=CH2). The double bond may be in cis or trans configuration. In a specific embodiment, the term "alkenyl" refers to C... 2-12 alkenyl (C 2-12 Hydrocarbons), more specifically C 2-9 alkenyl (C 2-9 Hydrocarbons), and more specifically C 2-6 alkenyl (C 2-6 Hydrocarbons, as further defined above, have at least one (usually 1 to 3, preferably 1) unsaturated site (i.e. carbon-carbon sp2 double bond).

[0056] The term "olefin" as a group or part of a group refers to a group having the formula -OR d The group, wherein R d It is an alkenyl group as defined above.

[0057] As used herein, the term "cycloalkenyl" refers to a non-aromatic hydrocarbon group having 5 to 18 carbon atoms and at least one (usually 1 to 3, preferably 1) unsaturated site (i.e., a carbon-carbon sp2 double bond), which is composed of C 5-10 Single ring or C 7-18The hydrocarbon comprises or includes a polycyclic hydrocarbon. Examples include, but are not limited to, cyclopentenyl (-C5H7), cyclopentenylpropene, methylcyclohexeneyl, and cyclohexenyl (-C6H9). The double bond may be in either cis or trans configuration. In a specific embodiment, the term "cycloalkenyl" refers to C... 5-12 Cycloalkenyl (cyclic C) 5-12 Hydrocarbons), more specifically C 5-9 Cycloalkenyl (cyclic C) 5-9 Hydrocarbons), and more specifically C 5-6 Cycloalkenyl (cyclic C) 5-6 Hydrocarbons, as further defined above, possess at least one unsaturated site (i.e., a carbon-carbon sp2 double bond). To avoid ambiguity, fused systems of cycloalkenyl rings with heterocycles are considered heterocycles, independent of the ring bonded to the core structure. Fused systems of cycloalkenyl rings with aromatic rings are considered aryl rings, independent of the ring bonded to the core structure. Fused systems of cycloalkenyl rings with heteroaryl rings are considered heteroaryl rings, independent of the ring bonded to the core structure.

[0058] The term "alkynyl" or "C2-C" is used in this article. 18 "Alkyne group" refers to a C2-C group having at least one (usually 1 to 3, preferably 1) unsaturated site (i.e., carbon-carbon sp triple bond). 18 Primary, secondary, or tertiary, linear, branched, or straight-chain hydrocarbons. Examples include, but are not limited to: ethynyl (-C≡CH), 3-ethyl-cycloheptane-1-ynyneyl, and 1-propynyl (propynyl, -CH2C≡CH). In specific embodiments, the term "ynyneyl" refers to C... 2-12 alkynyl (C 2-12 Hydrocarbons), more specifically C 2-9 alkynyl (C 2-9 Hydrocarbons), and more specifically C 2-6 alkynyl (C 2-6 Hydrocarbons, as further defined above, have at least one (usually one to three, preferably one) unsaturated site (i.e., carbon-carbon sp triple bond).

[0059] The term "alkynyloxy group" as a group or part of a group refers to a group having the formula -OR e The group, wherein R e It is an alkynyl group as defined above.

[0060] As used herein, the term "cycloalkynyl" refers to a non-aromatic hydrocarbon group having 5 to 18 carbon atoms and at least one (usually 1 to 3, preferably 1) unsaturated site (i.e., a carbon-carbon sp triple bond), which is composed of C 5-10 Single ring or C 7-18The hydrocarbon comprises or includes a polycyclic hydrocarbon. Examples include, but are not limited to, cyclohepta-1-yne, 3-ethyl-cyclohepta-1-ynyne, 4-cyclohepta-1-yne-methylene, and ethylene-cyclohepta-1-yne. In a specific embodiment, the term "cycloynyne" refers to C14-cyclohepta-1-yne. 5-10 Cycloalkynyl (cyclic C) 5-10 Hydrocarbons), more specifically C 5-9 Cycloalkynyl (cyclic C) 5-9 Hydrocarbons), and more specifically C 5-6 Cycloalkynyl (cyclic C) 5-6 Hydrocarbons, as further defined above, have at least one (usually 1 to 3, preferably 1) unsaturated site (i.e., carbon-carbon sp triple bond). For the avoidance of ambiguity, fused systems of cycloalkynyl rings with heterocycles are considered heterocycles, independent of the ring bonded to the core structure. Fused systems of cycloalkynyl rings with aromatic rings are considered aryl, independent of the ring bonded to the core structure. Fused systems of cycloalkynyl rings with heteroaryl rings are considered heteroaryl, independent of the ring bonded to the core structure.

[0061] As used in this article, the term "alkylene" refers to a group having 1 to 18 carbon atoms (more specifically, C16-C16-C16). 1-12 C 1-9 Or C 1-6 A saturated, branched, or straight-chain hydrocarbon group (containing a carbon atom) and having two monovalent group centers derived by removing two hydrogen atoms from the same carbon atom or two different carbon atoms of the parent alkane. Typical alkylene groups include, but are not limited to: methylene (-CH2-), 1,2-ethyl (-CH2CH2-), 1,3-propyl (-CH2CH2CH2-), 1,4-butyl (-CH2CH2CH2CH2-), etc.

[0062] The term "alkenyl" as used in this article refers to a group having 2 to 18 carbon atoms (more specifically, C24-18 ... 2-12 C 2-9 Or C 2-6 A branched or straight-chain hydrocarbon group consisting of a carbon atom and at least one (usually 1 to 3, preferably 1) unsaturated site (i.e., carbon-carbon sp2 double bond), and having two monovalent centers derived by removing two hydrogen atoms from the same carbon atom or two different carbon atoms of the parent alkene.

[0063] The term "hypoynyl" as used in this article refers to a group having 2 to 18 carbon atoms (more specifically, C24-18 ... 2-12 C 2-9 Or C 2-6 A branched or straight-chain hydrocarbon group consisting of a carbon atom and at least one (usually 1 to 3, preferably 1) unsaturated site (i.e., carbon-carbon sp triple bond), and having two monovalent centers derived by removing two hydrogen atoms from the same carbon atom or two different carbon atoms of the parent alkyne.

[0064] As used herein, the term "heteroalkyl" refers to an alkyl group in which one or more carbon atoms are substituted by one or more atoms selected from oxygen, nitrogen, or sulfur atoms. Therefore, the term "heteroalkyl" includes -OR b -NR o -R b -R a -OR b and -SR b , where R a It is an alkylene group, R b It is an alkyl group, and R o It is hydrogen or alkyl, as defined herein. In specific embodiments, the term refers to C 1-12 Heteroalkyl, C 1-9 Heteroalkyl or C 1-6 Heteroalkyl. In some embodiments, the heteroalkyl is selected from alkoxy, alkoxyalkyl, (mono or di)alkylamino, (mono or di)alkylaminoalkyl, alkylthio, and alkylthioalkyl.

[0065] As used herein, the term "heteroalkenyl" refers to a noncyclic alkenyl group in which one or more carbon atoms are replaced by one or more atoms selected from oxygen, nitrogen, or sulfur. Therefore, the term "heteroalkenyl" includes -OR d -NH-(R d ), -N(R d )2、-N(R b (R) d ) and -SR d , where R b It is an alkyl group and R d It is an alkenyl group, as defined herein. In specific embodiments, this term refers to C... 2-12 Heterene, C 2-9 Heterene or C 2-6 Heteroalkenyl. In some embodiments, the heteroalkenyl is selected from alkenoxyl, alkenyloxyalkenyl, (mono or di)alkenylamino, (mono or di)alkenylaminoalkenyl, alkenylthiol, and alkenylthioalkenyl.

[0066] As used herein, the term "heterynyl" refers to a noncyclic ynyl group in which one or more carbon atoms are replaced by oxygen, nitrogen, or sulfur atoms. Therefore, the term "heterynyl" includes, but is not limited to, -OR d -N(R) d 2. NHR d -N(R) b (R) e ), -N(R d (R) e ) and -SR d , where R b It is an alkyl group, Re It is an alkynyl group, and R d It is an alkenyl group, as defined herein. In specific embodiments, this term refers to C... 2-12 Neyne group, C 2-9 pyrynyl or C 2-6 Xyrynyl. In some embodiments, the xyrynyl group is selected from alkynoxy, alkynyloxyalkynyl, (mono or di)alkynylamino, (mono or di)alkynylaminoalkynyl, alkynylthio, and alkynylthioalkynyl.

[0067] As used in this article, "heteroalkylene" refers to an alkylene group in which one or more carbon atoms are replaced by one or more oxygen, nitrogen, or sulfur atoms.

[0068] As used in this article, "hesenoyl" refers to an alkylene group in which one or more carbon atoms are replaced by one or more oxygen, nitrogen, or sulfur atoms.

[0069] As used in this article, "hypo-ynyl" refers to a ynyl group in which one or more carbon atoms are replaced by one or more oxygen, nitrogen, or sulfur atoms.

[0070] As used herein, the term "aryl" refers to an aromatic hydrocarbon of 6 to 20 carbon atoms derived by removing hydrogen atoms from the carbon atoms of a parent aromatic ring system. Typical aryl groups include, but are not limited to, one ring or two or three rings fused together derived from benzene, naphthalene, anthracene, biphenyl, etc. In specific embodiments, the term "aryl" refers to an aromatic ring of 6 to 14 carbon atoms, more specifically, an aromatic ring of 6 to 10 carbon atoms. Fused systems of aromatic rings with cycloalkyl, cycloalkenyl, or cycloalkynyl rings are considered aryl, regardless of the ring bonded to the core structure. Fused systems of aromatic rings with heterocyclic rings are considered heterocyclic, regardless of the ring bonded to the core structure. Therefore, indoline, dihydrobenzofuran, dihydrobenzothiophene, etc., are considered heterocyclic according to the present invention. Fused systems of aromatic rings with heteroaromatic rings are considered heteroaryl, regardless of the ring bonded to the core structure.

[0071] The term "aryloxy group," as a group or part of a group, refers to a group having the formula -OR g The group, wherein R g It is an aryl group as defined above.

[0072] As used herein, the term "arylalkyl" or "arylalkyl-" refers to an alkyl group in which one hydrogen atom bonded to a carbon atom (usually the terminal carbon atom or sp3 carbon atom) is replaced by an aryl group. Typical arylalkyl groups include, but are not limited to, benzyl, 2-phenylethyl-1-yl, 2-phenylvinyl-1-yl, naphthylmethyl, 2-naphthylethyl, etc. Arylalkyl groups contain 6 to 20 carbon atoms; for example, an arylalkyl group may have an alkyl portion of 1 to 6 carbon atoms and an aryl portion of 6 to 14 carbon atoms.

[0073] The term "arylalkoxy" as a group or part of a group refers to a group having the formula -OR a -R g The group, wherein R g It is aryl and R a It is an alkylene group, as defined above.

[0074] As used herein, the term "aryl-alkenyl" or "aryl-alkenyl-" refers to an alkenyl group in which one hydrogen atom bonded to a carbon atom is replaced by an aryl group. Aryl-alkenyl groups contain 6 to 20 carbon atoms; for example, the alkenyl portion of an aryl-alkenyl group has 1 to 6 carbon atoms and the aryl portion has 6 to 14 carbon atoms.

[0075] As used herein, the term "arylynyl" or "arylynyl-" refers to an ynyl group in which one hydrogen atom bonded to a carbon atom is replaced by an aryl group. Arylynyl groups contain 6 to 20 carbon atoms; for example, the ynyl portion of an arylynyl group has 1 to 6 carbon atoms and the aryl portion has 6 to 14 carbon atoms.

[0076] As used herein, the term "arylhexaalkyl" or "arylhexaalkyl-" refers to a heteroalkyl group in which one hydrogen atom bonded to a carbon atom (typically a terminal carbon atom or sp3 carbon atom) is replaced by an aryl group. Arylhexaalkyl groups contain 6 to 20 carbon atoms; for example, the heteroalkyl portion of an arylhexaalkyl group has 1 to 6 carbon atoms and the aryl portion has 6 to 14 carbon atoms. In some embodiments, the arylhexaalkyl group is selected from aryl-O-alkyl, arylalkyl-O-alkyl, aryl-NH-alkyl, aryl-N(alkyl)2, arylalkyl-NH-alkyl, arylalkyl-N-(alkyl)2, aryl-S-alkyl, and arylalkyl-S-alkyl.

[0077] As used herein, the term "arylhexeneyl" or "arylhexeneyl-" refers to a heteroalkenyl group in which one hydrogen atom bonded to a carbon atom is replaced by an aryl group. Arylhexeneyl groups contain 6 to 20 carbon atoms; for example, the heteroalkenyl portion of an arylhexeneyl group has 1 to 6 carbon atoms and the aryl portion has 6 to 14 carbon atoms. In some embodiments, the arylhexeneyl group is selected from aryl-O-alkenyl, aryl-alkenyl-O-alkenyl, aryl-NH-alkenyl, aryl-N(alkenyl)2, aryl-alkenyl-NH-alkenyl, aryl-alkenyl-N-(alkenyl)2, aryl-S-alkenyl, and aryl-alkenyl-S-alkenyl.

[0078] As used herein, the term "aryl-pyrynyl" or "aryl-pyrynyl-" refers to a pyrynyl group in which one hydrogen atom bonded to a carbon atom is replaced by an aryl group. Aryl-pyrynyl groups contain 6 to 20 carbon atoms; for example, the pyrynyl portion of an aryl-pyrynyl group has 1 to 6 carbon atoms and the aryl portion has 6 to 14 carbon atoms. In some embodiments, the aryl-pyrynyl group is selected from aryl-O-pyrynyl, aryl-pyrynyl-O-pyrynyl, aryl-NH-pyrynyl, aryl-N(pyrynyl)2, aryl-pyrynyl-NH-pyrynyl, aryl-pyrynyl-N-(pyrynyl)2, aryl-S-pyrynyl, and aryl-pyrynyl-S-pyrynyl.

[0079] As used herein, the term "heterocyclic" or "heterocyclic group" refers to a non-aromatic, fully saturated, or partially unsaturated ring system (i.e., C164-C ... 3-18 For example, 3 to 7 cyclic rings (C 3-7 ), 7 to 11 yuan for double ring (C) 3-11 ) or contains a total of 3 to 10 ring atoms (C 3-10 Each ring of the heterocyclic group or heterocyclic group may have 1, 2, 3, or 4 heteroatoms selected from N, O, and / or S, wherein the N and S heteroatoms may optionally be oxidized, and the N heteroatoms may optionally be quaternized; and wherein at least one carbon atom of the heterocyclic group may be oxidized to form at least one C=O. Heterocyclic groups may be linked by any heteroatom or carbon atom of the ring or ring system, provided that the valence allows. The rings of a polycyclic heterocyclic group or heterocyclic group may be fused, bridged, and / or linked by one or more spiro atoms. A fused system of a heterocyclic group or heterocyclic group with an aromatic ring is considered a heterocyclic group or heterocyclic group, regardless of the ring bonded to the core structure. A fused system of a heterocyclic group or heterocyclic group with a heteroaromatic ring is considered a heteroaryl group, regardless of the ring bonded to the core structure.

[0080] Non-limiting examples of heterocyclic or heterocyclic groups include piperidinyl, piperazinyl, homopiperazinyl, morpholinyl, tetrahydropyranyl, tetrahydrofuranyl, pyrrolidinyl, aziridinepropyl, ethylene oxide, thioheteropropyl, aziridinebutyl, oxacyclobutyl, thioheterobutyl, 2-imidazolinyl, pyrazolyl, imidazolinyl, isoxazolinyl, oxazolyl, isoxazolyl, thiazolinyl, isothiazolyl, succinimide, 3 H -Indoleyl, indololinyl, isoindolinyl, chromanyl (also known as 3,4-dihydrobenzo[] b ]pyranyl), 2 H -pyrroloyl, 1-pyrrololinoyl, 2-pyrrololinoyl, 3-pyrrololinoyl, 4 H -quinazolinyl, 2-oxopiperazinyl, 2-pyrazolinyl, 3-pyrazolinyl, tetrahydro-2 H -pyranyl, 2 H -pyranyl, 4 H -pyranyl, 3,4-dihydro-2 H-pyranyl, 3-dioxolane, 1,4-dioxane, 2,5-dioxoimidazolyl, 2-oxopiridyl, 2-oxopirolyl, indololinyl, tetrahydrothiophene, tetrahydroquinolinyl, tetrahydroisoquinolin-1-yl, tetrahydroisoquinolin-2-yl, tetrahydroisoquinolin-3-yl, tetrahydroisoquinolin-4-yl, thiomorpholin-4-yl, thiomorpholin-4-yl sulfoxide, thiomorpholin-4-yl sulfone, 1,3-dioxolane, 1,4-oxothionylhexyl, 1,4-dithiaalkyl, 1,3,5-trioxane, 1 H -pyrrolizinyl, tetrahydro-1,1-dioxothiopheneyl, N -Formylpiperazinyl and morpholin-4-yl. The term "azacyclopropyl" as used herein includes azacyclopropyl-1-yl and azacyclopropyl-2-yl. The term "ethylene oxide" as used herein includes ethylene oxide-2-yl. The term "thiocyclopropyl" as used herein includes thiocyclopropyl-2-yl. The term "azacyclobutyl" as used herein includes azacyclobutyl-1-yl, azacyclobutyl-2-yl, and azacyclobutyl-3-yl. The term "oxacyclobutyl" as used herein includes oxacyclobutyl-2-yl and oxacyclobutyl-3-yl. The term "thiocyclobutyl" as used herein includes thiocyclobutyl-2-yl and thiocyclobutyl-3-yl. The term "pyrrolyl" as used herein includes pyrrolidine-1-yl, pyrrolidine-2-yl, and pyrrolidine-3-yl. The term "tetrahydrofuranyl" as used herein includes tetrahydrofuran-2-yl and tetrahydrofuran-3-yl. The term "tetrahydrothiophenyl" as used herein includes tetrahydrothiophene-2-yl and tetrahydrothiophene-3-yl. The term "succinimide" as used herein includes succinimide-1-yl and succinimide-3-yl. The term "dihydropyrroleyl" as used herein includes 2,3-dihydropyrrole-1-yl, 2,3-dihydro-1... H -pyrrolo-2-yl, 2,3-dihydro-1 H -pyrrolo-3-yl, 2,5-dihydropyrrolo-1-yl, 2,5-dihydro-1H-pyrrolo-3-yl, and 2,5-dihydropyrrolo-5-yl. The term "2" as used herein... H "-pyrrole" includes 2 H -pyrrole-2-yl, 2 H -pyrrole-3-yl, 2 H -pyrrole-4-yl and 2 H -pyrrole-5-yl. The term "3" is used in this document. H "-pyrrole" includes 3 H -pyrrole-2-yl, 3 H -pyrrole-3-yl, 3 H -pyrrole-4-yl and 3 H-pyrrolo-5-yl. The term "dihydrofuranyl" as used herein includes 2,3-dihydrofuran-2-yl, 2,3-dihydrofuran-3-yl, 2,3-dihydrofuran-4-yl, 2,3-dihydrofuran-5-yl, 2,5-dihydrofuran-2-yl, 2,5-dihydrofuran-3-yl, 2,5-dihydrofuran-4-yl, and 2,5-dihydrofuran-5-yl. The term "dihydrothiophenyl" as used herein includes 2,3-dihydrothiophenyl-2-yl, 2,3-dihydrothiophenyl-3-yl, 2,3-dihydrothiophenyl-4-yl, 2,3-dihydrothiophenyl-5-yl, 2,5-dihydrothiophenyl-2-yl, 2,5-dihydrothiophenyl-3-yl, 2,5-dihydrothiophenyl-4-yl, and 2,5-dihydrothiophenyl-5-yl. The term "imidazolinyl" as used herein includes imidazolin-1-yl, imidazolin-2-yl, and imidazolin-4-yl. The term "pyrazolyl" as used herein includes pyrazolyl-1-yl, pyrazolyl-3-yl, and pyrazolyl-4-yl. The term "imidazolinyl" as used herein includes imidazolin-1-yl, imidazolin-2-yl, imidazolin-4-yl, and imidazolin-5-yl. The term "pyrazolyl" as used herein includes 1-pyrazolyl-3-yl, 1-pyrazolyl-4-yl, 2-pyrazolyl-1-yl, 2-pyrazolyl-3-yl, 2-pyrazolyl-4-yl, 2-pyrazolyl-5-yl, 3-pyrazolyl-1-yl, 3-pyrazolyl-2-yl, 3-pyrazolyl-3-yl, 3-pyrazolyl-4-yl, and 3-pyrazolyl-5-yl. The term "dioxolane" as used herein, also known as "1,3-dioxolane," includes dioxolane-2-yl, dioxolane-4-yl, and dioxolane-5-yl. The term "dioxacyclopentenyl" as used herein, also known as "1,3-dioxacyclopentenyl," includes dioxacyclopenten-2-yl, dioxacyclopenten-4-yl, and dioxacyclopenten-5-yl. The term "oxazolidinyl" as used herein includes oxazolidin-2-yl, oxazolidin-3-yl, oxazolidin-4-yl, and oxazolidin-5-yl. The term "isooxazolidinyl" as used herein includes isoxazolidin-3-yl, isoxazolidin-4-yl, and isoxazolidin-5-yl. The term "oxazoline" as used herein includes 2-oxazoline-2-yl, 2-oxazoline-4-yl, 2-oxazoline-5-yl, 3-oxazoline-2-yl, 3-oxazoline-4-yl, 3-oxazoline-5-yl, 4-oxazoline-2-yl, 4-oxazoline-3-yl, 4-oxazoline-4-yl, and 4-oxazoline-5-yl. The term "isoxazoline" as used herein includes 2-isoxazoline-3-yl, 2-isoxazoline-4-yl, 2-isoxazoline-5-yl, 3-isoxazoline-3-yl, 3-isoxazoline-4-yl, 3-isoxazoline-5-yl, 4-isoxazoline-2-yl, 4-isoxazoline-3-yl, 4-isoxazoline-4-yl, and 4-isoxazoline-5-yl. The term “thiazolyl” as used in this article includes thiazolyl-2-yl, thiazolyl-3-yl, thiazolyl-4-yl, and thiazolyl-5-yl.The term "isothiazolinyl" as used herein includes isothiazolidine-3-yl, isothiazolidine-4-yl, and isothiazolidine-5-yl. The term "thiazolinyl" as used herein includes 2-thiazolin-2-yl, 2-thiazolin-4-yl, 2-thiazolin-5-yl, 3-thiazolin-2-yl, 3-thiazolin-4-yl, 3-thiazolin-5-yl, 4-thiazolin-2-yl, 4-thiazolin-3-yl, 4-thiazolin-4-yl, and 4-thiazolin-5-yl. The term "isothiazolinyl" as used herein includes 2-isothiazolin-3-yl, 2-isothiazolin-4-yl, 2-isothiazolin-5-yl, 3-isothiazolin-3-yl, 3-isothiazolin-4-yl, 3-isothiazolin-5-yl, 4-isothiazolin-2-yl, 4-isothiazolin-3-yl, 4-isothiazolin-4-yl, and 4-isothiazolin-5-yl. The term "piperidyl" as used herein includes piperidin-1-yl, piperidin-2-yl, piperidin-3-yl, and piperidin-4-yl. The term "dihydropyridyl" as used herein includes 1,2-dihydropyridin-1-yl, 1,2-dihydropyridin-2-yl, 1,2-dihydropyridin-3-yl, 1,2-dihydropyridin-4-yl, 1,2-dihydropyridin-5-yl, 1,2-dihydropyridin-6-yl, 1,4-dihydropyridin-1-yl, 1,4-dihydropyridin-2-yl, 1,4-dihydropyridin-3-yl, 1,4-dihydropyridin-4-yl, 2,3-dihydropyridin-2-yl, and 2,3-dihydropyridin-3-yl. 2,3-Dihydropyridin-4-yl, 2,3-Dihydropyridin-5-yl, 2,3-Dihydropyridin-6-yl, 2,5-Dihydropyridin-2-yl, 2,5-Dihydropyridin-3-yl, 2,5-Dihydropyridin-4-yl, 2,5-Dihydropyridin-5-yl, 2,5-Dihydropyridin-6-yl, 3,4-Dihydropyridin-2-yl, 3,4-Dihydropyridin-3-yl, 3,4-Dihydropyridin-4-yl, 3,4-Dihydropyridin-5-yl and 3,4-Dihydropyridin-6-yl.The term "tetrahydropyridyl" as used herein includes 1,2,3,4-tetrahydropyridin-1-yl, 1,2,3,4-tetrahydropyridin-2-yl, 1,2,3,4-tetrahydropyridin-3-yl, 1,2,3,4-tetrahydropyridin-4-yl, 1,2,3,4-tetrahydropyridin-5-yl, 1,2,3,4-tetrahydropyridin-6-yl, 1,2,3,6-tetrahydropyridin-1-yl, 1,2,3,6-tetrahydropyridin-2-yl, 1,2,3,6-tetrahydropyridin-6-yl, 1,2,3,6-tetrahydropyridin-1-yl, 1,2,3,6-tetrahydropyridin-2-yl, 1,2,3,6-tetrahydropyridinyl ...1-yl, 1,2,3,6-tetrahydropyridinyl-1-yl, 1,2,3,6-tetrahydropyridinyl-1-yl, 1,2,3,4-tetrahydropyridinyl-1-yl, 1,2,3,4-tetrahydropyridinyl-1-yl, 1,2,3,4-tetrahydropyridinyl-1-yl, 1,2, Tetrahydropyridin-3-yl, 1,2,3,6-tetrahydropyridin-4-yl, 1,2,3,6-tetrahydropyridin-5-yl, 1,2,3,6-tetrahydropyridin-6-yl, 2,3,4,5-tetrahydropyridin-2-yl, 2,3,4,5-tetrahydropyridin-3-yl, 2,3,4,5-tetrahydropyridin-3-yl, 2,3,4,5-tetrahydropyridin-4-yl, 2,3,4,5-tetrahydropyridin-5-yl, and 2,3,4,5-tetrahydropyridin-6-yl. The term "tetrahydropyranyl" as used herein is also referred to as "oxalyl" or "tetrahydro-2". H "-pyranyl" includes tetrahydropyran-2-yl, tetrahydropyran-3-yl, and tetrahydropyran-4-yl. The term "2" as used herein... H "-pyranyl" includes 2 H -pyran-2-yl, 2 H -pyran-3-yl, 2 H -pyran-4-yl, 2 H -pyran-5-yl and 2 H -Pyran-6-yl. The term "4" is used in this article. H "-pyranyl" includes 4 H -pyran-2-yl, 4 H -pyran-3-yl and 4-yl H -pyran-4-yl. The term "3,4-dihydro-2-yl" is used herein. H "-pyranyl" includes 3,4-dihydro-2 H -pyran-2-yl, 3,4-dihydro-2 H -pyran-3-yl, 3,4-dihydro-2 H -pyran-4-yl, 3,4-dihydro-2 H -pyran-5-yl and 3,4-dihydro-2 H -pyran-6-yl. The term "3,6-dihydro-2-yl" is used herein. H "-pyranyl" includes 3,6-dihydro-2 H -pyran-2-yl, 3,6-dihydro-2 H -pyran-3-yl, 3,6-dihydro-2 H -pyran-4-yl, 3,6-dihydro-2 H -pyran-5-yl and 3,6-dihydro-2 H-pyran-6-yl. The term "tetrahydrothiopheneyl" as used herein includes tetrahydrothiophene-2-yl, tetrahydrothiophene-3-yl, and tetrahydrothiophene-4-yl. The term "2-pyran-6-yl" as used herein... H "-Thiaranyl" includes 2 H -Thiaran-2-yl, 2 H -Thiaran-3-yl, 2 H -Thiaran-4-yl, 2 H -Thiaran-5-yl and 2 H -Thiaran-6-yl. The term "4" is used in this article. H "-Thiaranyl" includes 4 H -Thiaran-2-yl, 4 H -Thiaran-3-yl and 4-yl H -Thiaran-4-yl. The term "3,4-dihydro-2-yl" is used herein. H "-Thiamyl" includes 3,4-dihydro-2 H -thiaran-2-yl, 3,4-dihydro-2 H -Thiaran-3-yl, 3,4-dihydro-2 H -thiaran-4-yl, 3,4-dihydro-2 H -thiaran-5-yl and 3,4-dihydro-2 H -Thiaran-6-yl. The term "3,6-dihydro-2-yl" is used herein. H "-Thiamyl" includes 3,6-dihydro-2 H -thiaran-2-yl, 3,6-dihydro-2 H -Thiaran-3-yl, 3,6-dihydro-2 H -thiaran-4-yl, 3,6-dihydro-2 H -thiaran-5-yl and 3,6-dihydro-2 H-Thiaran-6-yl. The term "piperazinyl" as used herein includes piperazin-1-yl and piperazin-2-yl. The term "morpholinyl" as used herein includes morpholin-2-yl, morpholin-3-yl, and morpholin-4-yl. The term "thiomorpholinyl" as used herein includes thiomorpholin-2-yl, thiomorpholin-3-yl, and thiomorpholin-4-yl. The term "dioxane" as used herein includes 1,2-dioxane-3-yl, 1,2-dioxane-4-yl, 1,3-dioxane-2-yl, 1,3-dioxane-4-yl, 1,3-dioxane-5-yl, and 1,4-dioxane-2-yl. As used herein, the term "dithiaalkyl" includes 1,2-dithiaalkyl-3-yl, 1,2-dithiaalkyl-4-yl, 1,3-dithiaalkyl-2-yl, 1,3-dithiaalkyl-4-yl, 1,3-dithiaalkyl-5-yl, and 1,4-dithiaalkyl-2-yl. The term "oxothiacyclohexyl" as used herein includes oxothiacyclohexyl-2-yl and oxothiacyclohexyl-3-yl. The term "trioxyl" as used herein includes 1,2,3-trioxane-4-yl, 1,2,3-trioxane-5-yl, 1,2,4-trioxane-3-yl, 1,2,4-trioxane-5-yl, 1,2,4-trioxane-6-yl, and 1,3,4-trioxane-2-yl. The term "azheptacyclic heptyl" as used herein includes azheptacyclic hept-1-yl, azheptacyclic hept-2-yl, azheptacyclic hept-3-yl, and azheptacyclic hept-4-yl. The term "homoperazinyl" as used herein includes holopiperazin-1-yl, holopiperazin-2-yl, holopiperazin-3-yl, and holopiperazin-4-yl. The term "indolineyl" as used herein includes indoline-1-yl, indoline-2-yl, indoline-3-yl, indoline-4-yl, indoline-5-yl, indoline-6-yl, and indoline-7-yl. The term "quinazinyl" as used herein includes quinazinyl-1-yl, quinazinyl-2-yl, quinazinyl-3-yl, and quinazinyl-4-yl. The term "isoindoline" as used in this document includes isoindoline-1-yl, isoindoline-2-yl, isoindoline-3-yl, isoindoline-4-yl, isoindoline-5-yl, isoindoline-6-yl, and isoindoline-7-yl. H "-indolyl" includes 3 H -Indole-2-yl, 3 H -Indole-3-yl, 3 H -Indole-4-yl, 3 H -Indole-5-yl, 3 H -Indole-6-yl and 3 H-Indole-7-yl. The term "quinazolinyl" as used herein includes quinazolin-1-yl, quinazolin-2-yl, quinazolin-3-yl, and quinazolin-4-yl. The term "tetrahydroquinazolinyl" as used herein includes tetrahydroquinazolin-1-yl, tetrahydroquinazolin-2-yl, tetrahydroquinazolin-3-yl, tetrahydroquinazolin-4-yl, tetrahydroquinazolin-5-yl, tetrahydroquinazolin-6-yl, tetrahydroquinazolin-7-yl, and tetrahydroquinazolin-8-yl. The term "tetrahydroisoquinolinyl" as used herein includes tetrahydroisoquinolin-1-yl, tetrahydroisoquinolin-2-yl, tetrahydroisoquinolin-3-yl, tetrahydroisoquinolin-4-yl, tetrahydroisoquinolin-5-yl, tetrahydroisoquinolin-6-yl, tetrahydroisoquinolin-7-yl, and tetrahydroisoquinolin-8-yl. The term "chromanyl" as used herein includes chroman-2-yl, chroman-3-yl, chroman-4-yl, chroman-5-yl, chroman-6-yl, chroman-7-yl, and chroman-8-yl. H "-pyrrolizine" includes 1 H -pyrrolizin-1-yl, 1 H -pyrrolizin-2-yl, 1 H -pyrrolizin-3-yl, 1 H -pyrrolizin-5-yl, 1 H -pyrrolizine-6-yl and 1 H -pyrrolizin-7-yl. The term "3" is used in this document. H "-pyrrolizine" includes 3 H -pyrrolizin-1-yl, 3 H -pyrrolizin-2-yl, 3 H -pyrrolizin-3-yl, 3 H -pyrrolizin-5-yl, 3 H -pyrrolizine-6-yl and 3 H -pyrrolizin-7-yl.

[0081] The term "heteroaryl" refers to an aromatic ring system (i.e., C14-C14) containing 5 to 18 (cyclic) atoms with at least one N, O, S, or P atom. 5-18This compound contains one or two rings that can be fused together or covalently linked, each ring typically containing 5 to 6 atoms; at least one of the rings is an aromatic ring, wherein the N and S heteroatoms may optionally be oxidized, the N heteroatomole may optionally be quaternized, and at least one carbon atom of the heteroaryl group may be oxidized to form at least one C=O. Fused systems of heteroaryl rings with cycloalkyl, cycloalkenyl, or cycloalkynyl rings are considered heteroaryl groups, regardless of the ring bonded to the core structure. Fused systems of heteroaryl rings with heterocycles are considered heteroaryl groups, regardless of the ring bonded to the core structure. Fused systems of heteroaryl rings with aromatic rings are considered heteroaryl groups, regardless of the ring bonded to the core structure. Non-limiting examples of such heteroaryl groups include: triazol-2-yl, pyridinyl, 1... H -pyrazol-5-yl, pyrroloyl, furanyl, thiopheneyl, pyrazolyl, imidazoleyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiazolyl, tetrazolyl, oxtriazolyl, thiazolyl, pyrimidinyl, pyrazinyl, pyrazinyl, dioxazinyl, thiazolyl, triazinyl, imidazole[2,1-] b [1,3]thiazolyl, thiophene[3,2-] b Furanyl, thiophene[3,2- b Thiophene group, thiophene[2,3- d [1,3]thiazolyl, thiophene[2,3- d Imidazolyl, tetrazol[1,5-] a Pyridyl, indolyl, indazinyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzothiophenyl, isobenzothiophenyl, indazoleyl, benzimidazolyl, 1,3-benzoxazolyl, 1,2-benzoisoxazolyl, 2,1-benzoisoxazolyl, 1,3-benzothiazolyl, 1,2-benzoisothiazolyl, 2,1-benzoisothiazolyl, benzotriazolyl, 1,2,3-benzoxadiazolyl, 2,1,3-benzoxadiazolyl, 1,2,3-benzothiadiazolyl, 2,1,3-benzothiadiazolyl, benzo[d]oxazole-2(3 H )-ketone, 2,3-dihydro-benzofuranyl, thienopyridyl, purine, imidazo[1,2- a ]Pyridyl, 6-oxopyridazine-1(6 H )-yl, 2-oxopyridine-1(2 H )-yl, 6-oxopyridazine-1(6 H )-yl, 2-oxopyridine-1(2 HThe heteroaryl group is selected from pyridyl, pyrazinyl, pyrimidinyl, pyrazolyl, pyrroleyl, isoxazolyl, thiophenyl, imidazolyl, indolyl, benzimidazolyl, triazinyl, oxazolyl, isothiazolyl, furanyl, thiophenyl, triazolyl, and thiazolyl; more preferably, the heteroaryl group is selected from pyridyl, pyrazinyl, pyrimidinyl, indolyl, and benzimidazolyl.

[0082] The term "pyrroleyl" (also known as pyrazole) as used herein includes pyrrole-1-yl, pyrrole-2-yl, and pyrrole-3-yl. The term "furanyl" (also known as furanyl / furyl) as used herein includes furan-2-yl and furan-3-yl. The term "thiophenyl" (also known as thienyl) as used herein includes thiophene-2-yl and thiophene-3-yl. The term "pyrazolyl" (also known as pyrroleyl / furyl) as used herein... H -pyrazolyl and 1,2-diazolyl) including pyrazol-1-yl, pyrazol-3-yl or 1 H -Pyrazol-5-yl, pyrazol-4-yl, and pyrazol-5-yl. The term "imidazolyl" as used herein includes imidazolyl-1-yl, imidazolyl-2-yl, imidazolyl-4-yl, and imidazolyl-5-yl. The term "oxazolyl" (also known as 1,3-oxazolyl) as used herein includes oxazol-2-yl, oxazol-4-yl, and oxazol-5-yl. The term "isooxazolyl" (also known as 1,2-oxazolyl) as used herein includes isoxazol-3-yl, isoxazol-4-yl, and isoxazol-5-yl. The term "thiazolyl" (also known as 1,3-thiazolyl) as used herein includes thiazolyl-2-yl, thiazolyl-4-yl, and thiazolyl-5-yl (also known as 2-thiazolyl, 4-thiazolyl, and 5-thiazolyl). The term "isothiazolyl" (also known as 1,2-thiazolyl) as used herein includes isothiazol-3-yl, isothiazol-4-yl, and isothiazol-5-yl. The term "triazolyl" as used herein includes triazol-2-yl, 1 H -triazolyl and 4 H -1,2,4-triazolyl. "1 H "-triazolyl" includes 1 H -1,2,3-triazol-1-yl, 1 H -1,2,3-triazol-4-yl, 1 H -1,2,3-triazol-5-yl, 1 H -1,2,4-triazol-1-yl, 1 H -1,2,4-triazol-3-yl and 1 H -1,2,4-triazol-5-yl. "4 H "-1,2,4-triazolyl" includes 4 H -1,2,4-triazol-4-yl and 4 H-1,2,4-Triazol-3-yl. The term "oxadiazolyl" as used herein includes 1,2,3-oxadiazol-4-yl, 1,2,3-oxadiazol-5-yl, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, 1,2,5-oxadiazol-3-yl, and 1,3,4-oxadiazol-2-yl. The term "thiadiazolyl" as used herein includes 1,2,3-thiadiazol-4-yl, 1,2,3-thiadiazol-5-yl, 1,2,4-thiadiazol-3-yl, 1,2,4-thiadiazol-5-yl, 1,2,5-thiadiazol-3-yl (also known as furazon-3-yl), and 1,3,4-thiadiazol-2-yl. The term "tetraazolyl" as used herein includes 1... H -Tetrazole-1-yl, 1 H -Tetrazole-5-yl, 2 H -Tetrazole-2-yl and 2 H -Tetrazol-5-yl. The term "oxatriazolyl" as used herein includes 1,2,3,4-oxatriazolyl-5-yl and 1,2,3,5-oxatriazolyl-4-yl. The term "thiatriazolyl" as used herein includes 1,2,3,4-thiatriazolyl-5-yl and 1,2,3,5-thiatriazolyl-4-yl. The term "pyridinyl" as used herein includes pyridin-2-yl, pyridin-3-yl, and pyridin-4-yl (also known as 2-pyridinyl, 3-pyridinyl, and 4-pyridinyl). The term "pyrimidinyl" as used herein includes pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, and pyrimidin-6-yl. The term "pyrazinyl" as used herein includes pyrazin-2-yl and pyrazin-3-yl. The term "pyridazinyl" as used herein includes pyridazin-3-yl and pyridazin-4-yl. The term "oxazinyl" (also known as 1,4-oxazinyl) as used herein includes 1,4-oxazin-4-yl and 1,4-oxazin-5-yl. The term "dioxacyclohexenyl" (also known as "1,4-dioxacyclohexenyl") as used herein includes 1,4-dioxacyclohexen-2-yl and 1,4-dioxacyclohexen-3-yl. The term "thiazinyl" (also known as "1,4-thiazinyl") as used herein includes 1,4-thiazin-2-yl, 1,4-thiazin-3-yl, 1,4-thiazin-4-yl, 1,4-thiazin-5-yl, and 1,4-thiazin-6-yl. The term "triazinyl" as used herein includes 1,3,5-triazin-2-yl, 1,2,4-triazin-3-yl, 1,2,4-triazin-5-yl, 1,2,4-triazin-6-yl, 1,2,3-triazin-4-yl, and 1,2,3-triazin-5-yl. The term "imidazo[2,1-" as used herein... b [1,3]thiazolyl" includes imidazo[2,1- b [1,3]thiazolyl-2-yl, imidazo[2,1-] b [1,3]thiazolyl-3-yl, imidazo[2,1-] b[1,3]thiazolyl-5-yl and imidazo[2,1-] b [1,3]thiazolyl-6-yl. The term "thiopheno[3,2-]" is used herein. b "Furanyl" includes thiophene[3,2- b Furan-2-yl, thiophene[3,2-] b Furan-3-yl, thiophene[3,2-] b Furan-4-yl and thiophene[3,2-] b ]furan-5-yl. The term "thiophene[3,2-" is used in this article. b "Thiophene group" includes thiophene[3,2- b Thiophene-2-yl, thiophene[3,2-] b Thiophene-3-yl, thiophene[3,2-] b ]Thiophene-5-yl and thiophene[3,2- b Thiophene-6-yl. The term "thiopheno[2,3-]" is used herein. d [1,3]thiazolyl" includes thiophene[2,3- d [1,3]thiazolyl-2-yl, thiophene[2,3-] d [1,3]thiazolyl-5-yl and thiophene[2,3-] d [1,3]thiazolyl-6-yl. The term "thiopheno[2,3-yl]" is used herein. d "Imidazolyl" includes thiophene[2,3- d Imidazol-2-yl, thiophene[2,3-] d Imidazol-4-yl and thiophene[2,3-] d Imidazol-5-yl. The term "tetrazo[1,5-]" as used herein. a "Pyridyl" includes tetrazolo[1,5- a ]pyridin-5-yl, tetrazolo[1,5- a ]pyridin-6-yl, tetrazolo[1,5- a ]pyridin-7-yl and tetrazolo[1,5- a ]pyridin-8-yl. The term "indolyl" as used herein includes indol-1-yl, indol-2-yl, indol-3-yl, indol-4-yl, indol-5-yl, indol-6-yl, and indol-7-yl. The term "inzazyl" as used herein includes inzazyl-1-yl, inzazyl-2-yl, inzazyl-3-yl, inzazyl-5-yl, inzazyl-6-yl, inzazyl-7-yl, and inzazyl-8-yl. The term "isoindolyl" as used herein includes isoindol-1-yl, isoindol-2-yl, isoindol-3-yl, isoindol-4-yl, isoindol-5-yl, isoindol-6-yl, and isoindol-7-yl. The term "benzofuranyl" as used herein (also known as benzo[ b[Furfuranyl] includes benzofuran-2-yl, benzofuran-3-yl, benzofuran-4-yl, benzofuran-5-yl, benzofuran-6-yl, and benzofuran-7-yl. The term "isobenzofuranyl" (also known as benzo[]) is used herein. c [Furfuranyl] includes isobenzofuran-1-yl, isobenzofuran-3-yl, isobenzofuran-4-yl, isobenzofuran-5-yl, isobenzofuran-6-yl, and isobenzofuran-7-yl. The term "benzothiophenyl" (also known as benzo[]) is used herein. b ]Thienyl) including 2-benzo[ b ]Thienyl, 3-benzo[ b ]Thienyl, 4-benzo[ b ]Thienyl, 5-benzo[ b ]Thienyl, 6-benzo[ b ]Thienyl and 7-benzo[ b Thiophene group (also known as benzothiophene-2-yl, benzothiophene-3-yl, benzothiophene-4-yl, benzothiophene-5-yl, benzothiophene-6-yl, and benzothiophene-7-yl). The term "isobenzothiophene group" (also known as benzo[…]) is used herein. c [Thiophene] includes isobenzothiophene-1-yl, isobenzothiophene-3-yl, isobenzothiophene-4-yl, isobenzothiophene-5-yl, isobenzothiophene-6-yl, and isobenzothiophene-7-yl. The term "indazole" (also known as 1) is used herein. H -Indazole or 2-azaindolyl) including 1 H -Indazole-1-yl, 1 H -Indazole-3-yl, 1 H -Indazole-4-yl, 1 H -Indazole-5-yl, 1 H -Indazole-6-yl, 1 H -Indazole-7-yl, 2 H -Indazole-2-yl, 2 H -Indazole-3-yl, 2 H -Indazole-4-yl, 2 H -Indazole-5-yl, 2 H -Indazole-6-yl and 2 H-Indazole-7-yl. The term "benzimidazole" as used herein includes benzimidazole-1-yl, benzimidazole-2-yl, benzimidazole-4-yl, benzimidazole-5-yl, benzimidazole-6-yl, and benzimidazole-7-yl. The term "1,3-benzoxazole" as used herein includes 1,3-benzoxazole-2-yl, 1,3-benzoxazole-4-yl, 1,3-benzoxazole-5-yl, 1,3-benzoxazole-6-yl, and 1,3-benzoxazole-7-yl. The term "1,2-benzoisoxazole" as used herein includes 1,2-benzoisoxazole-3-yl, 1,2-benzoisoxazole-4-yl, 1,2-benzoisoxazole-5-yl, 1,2-benzoisoxazole-6-yl, and 1,2-benzoisoxazole-7-yl. The term "2,1-benzisoxazolyl" as used herein includes 2,1-benzisoxazol-3-yl, 2,1-benzisoxazol-4-yl, 2,1-benzisoxazol-5-yl, 2,1-benzisoxazol-6-yl, and 2,1-benzisoxazol-7-yl. The term "1,3-benzothiazolyl" as used herein includes 1,3-benzothiazol-2-yl, 1,3-benzothiazol-4-yl, 1,3-benzothiazol-5-yl, 1,3-benzothiazol-6-yl, and 1,3-benzothiazol-7-yl. The term "1,2-benzisothiazolyl" as used herein includes 1,2-benzisothiazol-3-yl, 1,2-benzisothiazol-4-yl, 1,2-benzisothiazol-5-yl, 1,2-benzisothiazol-6-yl, and 1,2-benzisothiazol-7-yl. The term "2,1-benzisothiazolyl" as used herein includes 2,1-benzisothiazol-3-yl, 2,1-benzisothiazol-4-yl, 2,1-benzisothiazol-5-yl, 2,1-benzisothiazol-6-yl, and 2,1-benzisothiazol-7-yl. The term "benzotriazolyl" as used herein includes benzotriazol-1-yl, benzotriazol-4-yl, benzotriazol-5-yl, benzotriazol-6-yl, and benzotriazol-7-yl. The term "1,2,3-benzoxadiazole" as used herein includes 1,2,3-benzoxadiazole-4-yl, 1,2,3-benzoxadiazole-5-yl, 1,2,3-benzoxadiazole-6-yl, and 1,2,3-benzoxadiazole-7-yl. The term "2,1,3-benzoxadiazole" as used herein includes 2,1,3-benzoxadiazole-4-yl, 2,1,3-benzoxadiazole-5-yl, 2,1,3-benzoxadiazole-6-yl, and 2,1,3-benzoxadiazole-7-yl. The term “1,2,3-benzothiadiazole” as used herein includes 1,2,3-benzothiadiazole-4-yl, 1,2,3-benzothiadiazole-5-yl, 1,2,3-benzothiadiazole-6-yl and 1,2,3-benzothiadiazole-7-yl.The term "2,1,3-benzothiadiazole" as used herein includes 2,1,3-benzothiadiazole-4-yl, 2,1,3-benzothiadiazole-5-yl, 2,1,3-benzothiadiazole-6-yl, and 2,1,3-benzothiadiazole-7-yl. The term "thienopyridyl" as used herein includes thieno[2,3-] b ]pyridyl, thiophene[2,3- c ]pyridyl, thiophene[3,2- c ]pyridyl and thiophene[3,2- b ]pyridyl. The term "purinyl" as used herein includes purin-2-yl, purin-6-yl, purin-7-yl, and purin-8-yl. The term "imidazo[1,2-]pyridyl" as used herein... a "Pyridyl" includes imidazo[1,2- a ]pyridin-2-yl, imidazo[1,2- a ]pyridin-3-yl, imidazo[1,2- a ]pyridin-4-yl, imidazo[1,2- a ]pyridin-5-yl, imidazo[1,2- a ]pyridin-6-yl and imidazo[1,2- a ]Pyridin-7-yl. The term "1,3-benzodioxacyclopentenyl" as used herein includes 1,3-benzodioxacyclopenten-4-yl, 1,3-benzodioxacyclopenten-5-yl, 1,3-benzodioxacyclopenten-6-yl, and 1,3-benzodioxacyclopenten-7-yl. The term "quinolinyl" as used herein includes quinolin-2-yl, quinolin-3-yl, quinolin-4-yl, quinolin-5-yl, quinolin-6-yl, quinolin-7-yl, and quinolin-8-yl. The term "isoquinolinyl" as used herein includes isoquinolin-1-yl, isoquinolin-3-yl, isoquinolin-4-yl, isoquinolin-5-yl, isoquinolin-6-yl, isoquinolin-7-yl, and isoquinolin-8-yl. The term "cenolinyl" as used herein includes cenolin-3-yl, cenolin-4-yl, cenolin-5-yl, cenolin-6-yl, cenolin-7-yl, and cenolin-8-yl. The term "quinazolinyl" as used herein includes quinazolin-2-yl, quinazolin-4-yl, quinazolin-5-yl, quinazolin-6-yl, quinazolin-7-yl, and quinazolin-8-yl. The term "quinoxalinyl" as used herein includes quinoxalin-2-yl, quinoxalin-5-yl, and quinoxalin-6-yl.

[0083] The heteroaryl and heterocyclic or heterocyclic groups used in this article include, for example, but not limited to, groups described in the following literature: Paquette, Leo A. “Principles of Modern Heterocyclic Chemistry” (WABenjamin, New York, 1968), especially Chapters 1, 3, 4, 6, 7 and 9; “The Chemistry of Heterocyclic Compounds, A series of Monographs” (John Wiley & Sons, New York, 1950 to present), especially Volumes 13, 14, 16, 19 and 28; Katritzky, Alan R., Rees, CW and Scriven, E. “Comprehensive Heterocyclic Chemistry” (Pergamon Press, 1996); and J. Am. Chem. Soc. (1960) 82: 5566.

[0084] The term "heterocyclic oxy group" or "heterocyclic oxy group" as a group or part of a group refers to a group having the formula -OR i The group, wherein R i It is a heterocyclic group as defined above.

[0085] The term "heterocyclic alkoxy" as a group or part of a group refers to a group having the formula -OR a -R i The group, wherein R i It is a heterocyclic group and R a It is an alkyl group, as defined above.

[0086] The term "heteroaryloxy" as a group or part of a group refers to a group having the formula -OR k The group, wherein R k It is a heteroaryl group as defined above.

[0087] The term "heteroarylalkoxy" as a group or part of a group refers to a group having the formula -OR a -R i The group, wherein R i It is a heteroaryl group and R a It is an alkyl group, as defined above.

[0088] The term "heterocyclic alkyl" or "heterocyclic alkyl" as a group or part of a group refers to an alkyl group in which one hydrogen atom bonded to a carbon atom (usually a terminal carbon atom or sp3 carbon atom) is replaced by a heterocyclic group. A non-limiting example of a heterocyclic alkyl or heterocyclic alkyl group is 2-piperidinylmethylene. A heterocyclic alkyl or heterocyclic alkyl group may contain 6 to 20 atoms, for example, the alkyl portion may have 1 to 6 carbon atoms and the heterocyclic group portion may have 3 to 14 atoms.

[0089] The term "heterocyclic alkenyl" or "heterocyclic alkenyl," as a group or part of a group, refers to an alkenyl group in which one hydrogen atom bonded to a carbon atom is replaced by a heterocyclic group. Heterocyclic alkenyl or heterocyclic alkenyl groups can contain 6 to 20 atoms, for example, the alkenyl portion has 2 to 6 carbon atoms and the heterocyclic portion has 3 to 14 atoms.

[0090] The term "heterocyclic ynylene" or "heterocyclic ynylene," as a group or part of a group, refers to an ynylene group in which one hydrogen atom bonded to a carbon atom is replaced by a heterocyclic group. Heterocyclic ynylene or heterocyclic ynylene can contain 6 to 20 atoms; for example, the ynylene moiety can contain 2 to 6 carbon atoms and the heterocyclic moiety can contain 3 to 14 atoms.

[0091] The term "heterocyclic heteroalkyl" or "heterocyclic heteroalkyl" as a group or part of a group refers to a heteroalkyl group in which one hydrogen atom bonded to a carbon atom (usually a terminal carbon atom or sp3 carbon atom) is replaced by a heterocyclic group. Heterocyclic heteroalkyl or heterocyclic heteroalkyl can contain 6 to 20 atoms (i.e., C6-C6). 20 For example, the heteroalkyl moiety can be C1-C6 and the heterocyclic moiety can contain 3 to 14 atoms (i.e., C3-C6). 14 In some embodiments, the heterocyclic heteroalkyl or heterocyclic heteroalkyl is selected from heterocyclic-O-alkyl, heterocyclic alkyl-O-alkyl, heterocyclic-NH-alkyl, heterocyclic-N(alkyl)2, heterocyclic alkyl-NH-alkyl, heterocyclic alkyl-N-(alkyl)2, heterocyclic-S-alkyl and heterocyclic alkyl-S-alkyl.

[0092] The term "heterocyclic heteroene" or "heterocyclic heteroene," as a group or part of a group, refers to a heteroene group in which one hydrogen atom bonded to a carbon atom is replaced by a heterocyclic group. Heterocyclic heteroenes or heterocyclic heteroenes can contain 6 to 20 atoms (i.e., C6-C6). 20 For example, the heteroene moiety can be C2-C6 and the heterocyclic moiety can contain 3 to 14 atoms (i.e., C3-C6). 14In some embodiments, the heterocyclic heteroalkenyl or heterocyclic heteroalkenyl is selected from heterocyclic-O-alkenyl, heterocyclic alkyl-O-alkenyl, heterocyclic-NH-alkenyl, heterocyclic-N(alkenyl)2, heterocyclic alkyl-NH-alkenyl, heterocyclic alkyl-N-(alkenyl)2, heterocyclic-S-alkenyl and heterocyclic alkenyl-S-alkenyl.

[0093] The term "heterocyclic pyrynyl" or "heterocyclic pyrynyl," as a group or part of a group, refers to a pyrynyl group in which one hydrogen atom bonded to a carbon atom is replaced by a heterocyclic group. Heterocyclic pyrynyl or heterocyclic pyrynyl can contain 6 to 20 atoms (i.e., C6-C). 20 For example, the heteroyne moiety can be C2-C6 and the heterocyclic moiety can contain 3 to 14 atoms (i.e., C3-C6). 14 In some embodiments, the heterocyclic kyneylyl group or heterocyclic kyneylyl group is selected from heterocyclic -O-kyneyl, heterocyclic kyneyl-O-kyneyl, heterocyclic -NH-kyneyl, heterocyclic -N(kyneyl)2, heterocyclic kyneyl-NH-kyneyl, heterocyclic kyneyl-N-(kyneyl)2, heterocyclic -S-kyneyl and heterocyclic kyneyl-S-kyneyl.

[0094] The term "heteroarylalkyl," as a group or part of a group, refers to an alkyl group in which one hydrogen atom bonded to a carbon atom (usually the terminal carbon atom or sp3 carbon atom) is replaced by a heteroaryl group. An example of a heteroarylalkyl group is 2-pyridylmethylene. Heteroarylalkyl groups can contain 6 to 20 atoms (i.e., C6-C6). 20 For example, the alkyl portion of a heteroarylalkyl group may contain 1 to 6 carbon atoms (i.e., C1-C6) and the heteroaryl portion may contain 5 to 14 atoms (i.e., C5-C6). 14 ).

[0095] The term "heteroaryl" as a group or part of a group refers to an alkenyl group in which one hydrogen atom bonded to a carbon atom is replaced by a heteroaryl group. Heteroaryl groups can contain 6 to 20 atoms (i.e., C6-C5). 20 For example, the alkenyl portion of a heteroaryl group may contain 2 to 6 carbon atoms and the heteroaryl portion may contain 5 to 14 atoms.

[0096] As used herein, the term "heteroarylynyl" refers to an ynyl group, or part thereof, in which one hydrogen atom bonded to a carbon atom is replaced by a heteroaryl group. Heteroarylynyl groups contain 6 to 20 atoms (i.e., C6-C6). 20 For example, the alkynyl moiety of a heteroaryl alkynyl group has 2 to 6 carbon atoms (i.e., C2-C6) and the heteroaryl moiety has 5 to 14 atoms (i.e., C5-C6). 14 ).

[0097] As used herein, the term "heteroarylheteroalkyl" as a group or part of a group refers to a heteroalkyl group in which one hydrogen atom bonded to a carbon atom (usually the terminal carbon atom or sp3 carbon atom) is replaced by a heteroaryl group. Heteroarylheteroalkyl groups contain 7 to 20 atoms (i.e., C7-C1). 20 For example, in heteroaryl-heteroalkyl groups, the heteroalkyl moiety has 2 to 6 carbon atoms (i.e., C2-C6) and the heteroaryl moiety has 5 to 14 atoms (i.e., C5-C6). 14 In some embodiments, the heteroaryl-heteroalkyl group is selected from heteroaryl-O-alkyl, heteroarylalkyl-O-alkyl, heteroaryl-NH-alkyl, heteroaryl-N(alkyl)2, heteroarylalkyl-NH-alkyl, heteroarylalkyl-N-(alkyl)2, heteroaryl-S-alkyl, and heteroarylalkyl-S-alkyl.

[0098] As used herein, the term "heteroarylheterenyl" as a group or part of a group refers to a heteroalkenyl group in which one hydrogen atom bonded to a carbon atom is replaced by a heteroaryl group. Heteroarylheterenyl groups contain 8 to 20 atoms (i.e., C8-C1). 20 For example, the heteroalkenyl moiety of heteroaryl-heterenyl groups has 3 to 6 carbon atoms (i.e., C3-C6) and the heteroaryl moiety has 5 to 14 atoms (i.e., C5-C6). 14 In some embodiments, the heteroaryl-heterenyl group is selected from heteroaryl-O-enyl, heteroaryl-O-enyl, heteroaryl-NH-enyl, heteroaryl-N(enyl)2, heteroaryl-NH-enyl, heteroaryl-N-(enyl)2, heteroaryl-S-enyl, and heteroaryl-S-enyl.

[0099] As used herein, the term "heteroaryl-heterynyl" as a group or part of a group refers to a heterynyl group in which one hydrogen atom bonded to a carbon atom is replaced by a heteroaryl group. Heteroaryl-heterynyl groups contain 8 to 20 atoms (i.e., C8-C1). 20 For example, the heteroynyl moiety of heteroaryl-heterynyl groups has 2 to 6 carbon atoms (i.e., C2-C6) and the heteroaryl moiety has 5 to 14 atoms (i.e., C5-C6). 14 In some embodiments, the heteroaryl-heterynyl group is selected from heteroaryl-O-ynyl, heteroarylynyl-O-ynyl, heteroaryl-NH-ynyl, heteroaryl-N(ynyl)2, heteroarylynyl-NH-ynyl, heteroarylynyl-N-(ynyl)2, heteroaryl-S-ynyl and heteroarylynyl-S-ynyl.

[0100] For example, carbon-bonded heteroaryl or heterocyclic groups may be bonded to the 2, 3, 4, 5, or 6 positions of pyridine, the 3, 4, 5, or 6 positions of pyridazine, the 2, 4, 5, or 6 positions of pyrimidine, the 2, 3, 5, or 6 positions of pyrazine, the 2, 3, 4, or 5 positions of furan, tetrahydrofuran, thiophene, pyrrole, or tetrahydropyrrole, the 2, 4, or 5 positions of oxazole, imidazole, or thiazole, the 3, 4, or 5 positions of isoxazole, pyrazole, or isothiazole, the 2 or 3 positions of azircyclopropane, the 2, 3, or 4 positions of azircyclobutane, the 2, 3, 4, 5, 6, 7, or 8 positions of quinoline, or the 1, 3, 4, 5, 6, 7, or 8 positions of isoquinoline. More typically, carbon-bonded heteroaryl and heterocyclic groups include 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, 5-pyridinyl, 6-pyridinyl, 3-pyridazinyl, 4-pyridazinyl, 5-pyridazinyl, 6-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 6-pyrimidinyl, 2-pyrazinyl, 3-pyrazinyl, 5-pyrazinyl, 6-pyrazinyl, 2-thiazolyl, 4-thiazolyl, or 5-thiazolyl. For example, nitrogen-bonded heterocycles may be bonded to aziridine, aziridine, butane, pyrrole, pyrrolidine, 2-pyrrololine, 3-pyrroleoline, imidazole, imidazolidine, 2-imidazoline, 3-imidazoline, pyrazole, pyrazoline, 2-pyrazoline, 3-pyrazoline, piperidine, piperazine, indole, indoline, 1 H At the 1-position of -indazole, at the 2-position of isoindole or isoindoline, at the 4-position of morpholine, and at the 9-position of carbazole or β-carbline. More typically, nitrogen-bonded heteroaryl or heterocyclic groups include 1-azacyclopropyl, 1-azacyclobutyl, 1-pyrrole, 1-imidazolyl, 1-pyrazolyl, and 1-piperidinyl.

[0101] As used herein and unless otherwise stated, the terms "alkoxy," "cycloalkoxy," "aryloxy," "arylalkoxy," "heteroaryloxy," "heterocyclicoxy," "alkathio," "cycloalkylthio," "arylthio," "arylalkylthio," "heteroarylthio," and "heterocyclicthio" refer to a substituent in which an alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, or heterocyclic group (each as defined herein) is respectively connected by a single bond to an oxygen or sulfur atom, such as, but not limited to, methoxy, ethoxy, propoxy, butoxy, ethylthio, methylthio, phenoxy, benzyloxy, mercaptobenzyl, etc. The same definitions apply to alkenyl and alkynyl groups in place of alkyl.

[0102] The term "alkathio" as a group or part of a group refers to a group having the formula -SR b The group, wherein R b Alkyl groups are defined as above. Non-limiting examples of alkylthio groups include methylthio (-SCH3), ethylthio (-SCH2CH3), n-propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio, tert-butylthio, etc.

[0103] The term "enethio" as a group or part of a group refers to a group having the formula -SR d The group, wherein R d It is an alkenyl group as defined above.

[0104] The term "acetylenyl thio" as a group or part of a group refers to a group having the formula -SR e The group, wherein R e It is an alkynyl group as defined above.

[0105] The term "arylthio" as a group or part of a group refers to a group having the formula -SR g The group, wherein R g It is an aryl group as defined above.

[0106] The term "arylalkylthio" as a group or part of a group refers to a group having the formula -SR a -R g The group, wherein R a It is an alkylene group and R g It is an aryl group, as defined above.

[0107] The term "heterocyclic thio" as a group or part of a group refers to a group having the formula -SR i The group, wherein R i It is a heterocyclic group as defined above.

[0108] The term "heteroarylthio" as a group or part of a group refers to a group having the formula -SR k The group, wherein R k It is a heteroaryl group as defined above.

[0109] The term "heterocyclic alkylthio" as a group or part of a group refers to a group having the formula -SR a -R i The group, wherein R a It is an alkylene group and R i It is a heterocyclic group, as defined above.

[0110] The term "heteroarylalkylthio" as a group or part of a group refers to a group having the formula -SR a -R k The group, wherein R a It is an alkylene group and R k It is a heteroaryl group, as defined above.

[0111] The term "aminoalkyl" as a group or part of a group refers to an alkyl group having the meaning as defined above, wherein one, two, or three hydrogen atoms are each substituted with an amino group (-NH2) as defined herein, i.e., monoaminoalkyl, diaminoalkyl, and triaminoalkyl, respectively. Non-limiting examples of such aminoalkyl groups include aminomethyl, 1-aminoethyl, 2-aminoethyl, 1,2-diaminoethyl, etc.

[0112] The term "monoalkylamino or dialkylamino" as a group or part of a group refers to the formula -N(R o (R) b ) groups, wherein R o R is hydrogen or alkyl. b The alkyl group is alkyl. Therefore, alkylamino groups include monoalkylamino groups (e.g., monoalkylamino and ethylamino groups) and dialkylamino groups (e.g., dialkylamino and diethylamino groups). Non-limiting examples of suitable monoalkylamino or dialkylamino groups include n-propylamino, isopropylamino, n-butylamino, isobutylamino, sec-butylamino, tert-butylamino, pentylamino, n-hexylamino, di-n-propylamino, diisopropylamino, ethylmethylamino, methyl-n-propylamino, methyl isopropylamino, n-butylmethylamino, isobutylmethylamino, tert-butylmethylamino, ethyl-n-propylamino, ethyl isopropylamino, n-butylethylamino, isobutylethylamino, tert-butylethylamino, di-n-butylamino, diisobutylamino, methylpentylamino, methylhexylamino, ethylpentylamino, ethylhexylamino, propylpentylamino, propylhexylamino, etc.

[0113] The term "monoarylamino or diarylamino" as a group or part of a group refers to the formula -N(R q (R) r ) groups, wherein R q and R r Each is independently selected from hydrogen, aryl, or alkyl, and wherein R q or R r At least one of them is aryl.

[0114] The term "monoarylene or diarylene" as a group or part of a group refers to the formula -N(R u (R) v ) groups, wherein R u and R v Each is independently selected from hydrogen, heteroaryl, or alkyl, and wherein R u or R v At least one of them is a heteroaryl group as defined in this paper.

[0115] The term "mono-heterocyclic amino or di-heterocyclic amino" as a group or part of a group refers to the formula -N(R w (R) x ) groups, wherein Rw and R x Each is independently selected from hydrogen, heterocyclic or alkyl, and wherein R w or R x At least one of them is a heterocyclic group as defined in this paper.

[0116] As used herein and unless otherwise stated, the term "halogen" means any atom selected from fluorine (F), chlorine (Cl), bromine (Br), and iodine (I).

[0117] As used herein, the term "optionally containing one or more heteroatoms selected from O, S, and N atoms" refers to a group in which one or more carbon atoms are substituted by oxygen, nitrogen, or sulfur atoms. Therefore, depending on the group referred to, this term includes heteroalkyl, heteroalkenyl, heteroynyl, heteroalkyl, heteroalkenyl, heteroynyl, cyclohexaalkyl, cyclohexakenyl, cyclohexaynyl, heteroaryl, arylhexaalkyl, heteroarylalkyl, heteroarylhexaalkyl, arylhexakenyl, heteroarylalkenyl, heteroarylhexakenyl, heteroarylhexaynyl, arylhexaynyl, heteroarylhexaynyl, etc. Therefore, depending on the group referred to, this term includes, for example, alkoxy, alkenyloxy, alkynoxy, alkyl-O-alkylene, alkenyl-O-alkylene, arylalkoxy, benzyloxy, heteroarylhexaalkyl, heterocyclic heteroalkyl, heteroarylalkoxy, heterocyclic alkoxy, etc. Therefore, as an example, the term "alkyl group optionally comprising one or more heteroatoms selected from O, S, and N atoms" refers to a heteroalkyl group, i.e., an alkyl group containing one or more heteroatoms in a hydrocarbon chain, which may be located at the beginning, inside, or end of the hydrocarbon chain. Examples of heteroalkyl groups include methoxy, methylthio, ethoxy, propoxy, CH3-O-CH2-, CH3-S-CH2-, CH3-CH2-O-CH2-, CH3-NH-, (CH3)2-N-, (CH3)2-CH2-NH-CH2-CH2-, etc. Therefore, as an example, the term "arylalkylene group optionally comprising one or more heteroatoms selected from O, S, and N atoms in an alkylene chain" refers to an arylheteroalkylene group, i.e., an arylalkylene group containing one or more heteroatoms in a hydrocarbon chain, which may be located at the beginning, inside, or end of the hydrocarbon chain. Therefore, "arylheteroalkylene" includes aryloxy, arylalkoxy, aryl-alkyl-NH-, etc., examples of which include phenoxy, benzyloxy, aryl-CH2-S-CH2-, aryl-CH2-O-CH2-, aryl-NH-CH2-, etc. When referring to "optionally containing one or more heteroatoms selected from O, S, and N atoms," the terms "heteroalkenyl," "heteroynyl," and other terms used herein are equally applicable to this definition.

[0118] As used herein, the term "wherein two or more hydrogen atoms on the carbon atom or heteroatom of the group optionally form =O or =S" means that two or more hydrogen atoms on the carbon atom or heteroatom of the group optionally form =O or =S. As an example, the term refers to "alkyl group, wherein two or more hydrogen atoms on the carbon atom or heteroatom of the alkyl group optionally form =O or =S", including but not limited to the following examples: CH3-C(O)-CH2-, CH3-C(O)-, CH3-C(S)-CH2-, and (CH3)2-CH2-C(O)-CH2-CH2-.

[0119] For the combination of the group “optionally comprising one or more heteroatoms selected from O, S and N atoms” and “wherein two or more hydrogen atoms on the carbon atom or heteroatom of the group can together form =O or =S”, the two aspects described above can be combined. If the group referred to is an alkyl group, it includes, but is not limited to, the following examples: CH3-C(O)O-, CH3-C(O)O-CH2-, CH3-NH-C(O)-, CH3-C(O)-NH-, CH3-NH-C(O)-CH2-, CH3-NH-C(S)-CH2-, CH3-NH-C(S)-NH-CH2-, CH3-NH-S(O)2- and CH3-NH-S(O)2-NH-CH2-.

[0120] The term “single bond” used in this article for linking groups (i.e., in this article, some linking groups are selected from single bonds, etc.) refers to a molecule in which there is no linking group, and therefore specifically refers to a compound in which two parts connected by a linking group are directly linked by a single bond.

[0121] As used herein with respect to substituents, unless otherwise stated, the term "substituted" in the likes of "substituted alkyl", "substituted alkenyl", "substituted alkynyl", "substituted aryl", "substituted heteroaryl", "substituted heterocyclic", "substituted arylalkyl", "substituted heteroarylalkyl", "substituted heterocyclic alkyl", etc., means a chemical structure as defined herein, and wherein the alkyl, alkenyl, alkynyl and / or the aryl, heteroaryl or heterocyclic group may optionally be substituted by one or more (preferably 1, 2, 3, 4, 5 or 6) substituents, meaning that one or more hydrogen atoms are each independently substituted by at least one substituent. Typical substituents include, but are not limited to, in specific embodiments, halogens, amino, hydroxyl, mercapto, alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, alkynyloxy, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocyclic, arylalkyl, arylalkenyl, arylalkynyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, heteroarylalkyl, heterocyclic alkyl, heteroarylalkenyl, heterocyclic alkenyl, heteroarylalkynyl, heterocyclic alkynyl, heterocyclic alkynyl, -X, -Z, -O - -OZ, =O, -SZ, -S - =S, -NZ2, -N + Z3, =NZ, =N-OZ, -CX3 (e.g., trifluoromethyl), -CN, -OCN, -SCN, -N=C=O, -N=C=S, -NO, -NO2, =N2, -N3, -NZC(O)Z, -NZC(S)Z, -NZC(O)O - , -NZC(O)OZ, -NZC(S)OZ, -NZC(O)NZZ, NZC(NZ)Z, NZC(NZ)NZZ, -C(O)NZZ, -C(NZ)Z, -S(O)2O - , -S(O)2OZ, -S(O)2Z, -OS(O)2OZ, -OS(O)2Z, -OS(O)2O - , -S(O)2NZZ, -S(O)(NZ)Z, -S(O)Z, -OP(O)(OZ)2, -P(O)(OZ)2, -P(O)(O - )2、-P(O)(OZ)(O - ), -P(O)(OH)2, -C(O)Z, -C(O)X, -C(S)Z, -C(O)OZ, -C(O)O - , -C(S)OZ, -C(O)SZ, -C(S)SZ, -C(O)NZZ, -C(S)NZZ, -C(NZ)NZZ, -OC(O)Z, -OC(S)Z, -OC(O)O --OC(O)OZ and -OC(S)OZ, wherein each X is independently a halogen selected from F, Cl, Br or I; each Z is independently -H, alkyl, alkenyl, ynyl, heteroalkyl, heteroalkenyl, heteroynyl, aryl, heteroaryl, heterocyclic, cycloalkyl, protecting group or prodrug moiety, and the two Zs bonded to the nitrogen atom may together with the nitrogen atom to which they are bonded to form a heteroaryl or heterocyclic group. Alkyl (alkylene), alkenyl (alkenylene), and ynyl (ynynylene) groups may also undergo similar substitutions.

[0122] Any substituents appearing at multiple sites in the compounds of this invention should be independently selected for labeling.

[0123] Substituents may or may not be marked with a bond symbol. Regardless of the bond symbol, if a substituent is multivalent (based on its position in the referred structure), it means any and all possible orientations of the substituent.

[0124] As used herein and unless otherwise stated, the term "solvent" includes any combination that can be formed from derivatives of the present invention with suitable inorganic solvents (e.g., hydrates) or organic solvents (e.g., but not limited to alcohols, ketones, esters, ethers, nitriles, etc.).

[0125] The term “heteroatom” as used in this article refers to an atom selected from nitrogen (which can be quaternized), oxygen, and sulfur (including sulfoxide and sulfone).

[0126] The term "hydroxyl group" as used in this article refers to -OH.

[0127] The term "carbonyl" as used in this article refers to a carbon atom bonded to an oxygen atom via a double bond, i.e., C=O.

[0128] The term "amino" as used in this article refers to the -NH2 group.

[0129] This invention provides novel compounds that have been shown to possess cGAS inhibitory activity. Therefore, these compounds constitute a useful new class of potent compounds for the treatment and / or prevention of cGAS-mediated diseases in subjects, and more specifically for the treatment and / or prevention of inflammatory conditions and cancer.

[0130] This invention also relates to the use of the said compounds as pharmaceuticals and their use in the preparation of pharmaceuticals for the treatment and / or prevention of inflammatory conditions and cancer. This invention relates to the use of the said compounds as pharmaceuticals for the treatment and / or prevention of cGAS-mediated diseases (e.g., inflammatory conditions and cancer) in animals, mammals (especially humans). This invention also relates to methods for the preparation of all such compounds, and pharmaceutical compositions comprising an effective amount of said compounds. This invention also relates to a method for treating or preventing inflammatory conditions and cancer in humans by administering one or more of these compounds, optionally in combination with one or more other pharmaceuticals, to a patient in need. This invention also relates to compounds for use in the veterinary field and their use as pharmaceuticals for the prevention or treatment of diseases in non-human mammals (e.g., inflammatory conditions or cancer in non-human mammals).

[0131] The compounds of this invention are compounds of formula (I) as described herein and any subclass thereof, their stereoisomers, tautomers, salts (especially pharmaceutically acceptable salts), solvates, polymorphs and / or prodrugs. (I) in: - Each dashed line (---) represents an optional double bond, and two adjacent dashed lines cannot form a double bond at the same time; - R 1 Selected from hydrogen, halogen, =O, alkyl, alkenyl, alkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, cycloalkenyl, and cycloalkynyl; preferably, R 1 Selected from hydrogen, halogens, O, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, hydroxyl group C 1-6 Alkyl, hydroxyl C 2-6 alkenyl, hydroxyl C 2-6 alkynyl, amino C 1-6 Alkyl, amino C 2-6 alkenyl, amino C 2-6 alkynyl, halogenated C 1-6 Alkyl, Halogenated C 2-6 alkenyl, halogenated C 2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl and C 5-12 Cycloacetic group; The alkyl, alkenyl, alkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, cycloalkenyl, and cycloalkynyl groups are each unsubstituted or substituted by one or more substituents, each substituent being independently selected from halogens, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cycloalkyl, cycloalkenyl, cycloalkynyl, -C(O)OH, -NH2, -NHalkyl, and -N(alkyl)2; preferably, the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, hydroxyl group C 1-6 Alkyl, hydroxyl C 2-6 alkenyl, hydroxyl C 2-6 alkynyl, amino C 1-6 Alkyl, amino C 2-6 alkenyl, amino C 2-6 alkynyl, halogenated C 1-6 Alkyl, Halogenated C 2-6 alkenyl, halogenated C 2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl and C 5-12 Each of the cycloalkyne groups is either unsubstituted or substituted with one or more substituents, each substituent being independently selected from halogens, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalkynyl, -C(O)OH, -NH2, -NHC 1-6 Alkyl and -N(C) 1-6 Alkyl)2; - R 2 Selected from hydrogen, halogen, =O, hydroxyl, alkyl, alkenyl, alkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, alkoxyalkyl, mono- or dialkylaminoalkyl, cycloalkyl, cycloalkenyl, cycloalkynyl, haloalkyl, haloalkenyl, haloalkynyl, alkoxy, haloalkoxy, -CONR 2a R 2band -CO2R 2c Preferably, R 2 Selected from hydrogen, halogen, =O, hydroxyl, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, hydroxyl group C 1-6 Alkyl, hydroxyl C 2-6 alkenyl, hydroxyl C 2-6 alkynyl, amino C 1-6 Alkyl, amino C 2-6 alkenyl, amino C 2-6 alkynyl group, C 1-6 Alkoxy C 1-6 Alkyl, mono-C 1-6 Alkylamino C 1-6 Alkyl, diC 1-6 Alkylamino C 1-6 Alkyl, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalynyl, Halogenated C 1-6 Alkyl, Halogenated C 2-6 alkenyl, halogenated C 2-6 alkynyl group, C 1-6 Alkoxy, halogenated C 1-6 Alkyl group, -CONR 2a R 2b and -CO2R 2c ; The alkyl, alkenyl, alkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, alkoxyalkyl, mono- or dialkylaminoalkyl, cycloalkyl, cycloalkenyl, cycloalkynyl, haloalkyl, haloalkenyl, haloalkynyl, alkoxy, and haloalkoxy groups are each unsubstituted or substituted by one or more substituents, each of which is independently selected from halogen, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, -N3, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cycloalkyl, cycloalkenyl, cycloalkynyl, -C(O)OH, -C(O)OR 2c -NH2, -NHalkyl and -N(alkyl)2; -COR 2d -NR 2a R 2b -NR 2a COR 2d -CONR 2a R 2b and -OR 2c Preferably, the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6alkynyl group, hydroxyl group C 1-6 Alkyl, hydroxyl C 2-6 alkenyl, hydroxyl C 2-6 alkynyl, amino C 1-6 Alkyl, amino C 2-6 alkenyl, amino C 2-6 alkynyl group, C 1-6 Alkoxy C 1-6 Alkyl, mono-C 1-6 Alkylamino C 1-6 Alkyl, diC 1-6 Alkylamino C 1-6 Alkyl, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalynyl, Halogenated C 1-6 Alkyl, Halogenated C 2-6 alkenyl, halogenated C 2-6 alkynyl group, C 1-6 Alkoxy and halogenated C 1-6 Each alkoxy group is either unsubstituted or substituted with one or more substituents, each substituent being independently selected from halogens, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, -N3, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalkynyl, -C(O)OH, -C(O)OR 2c -NH2, -NHalkyl and -N(alkyl)2; -COR 2d -NR 2a R 2b -NR 2a COR 2d -CONR 2a R 2b and -OR 2c ; - R 2a Selected from hydrogen, alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, and cycloynyl; preferably, R 2a Selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl and C 5-12Cycloacetic group; - R 2b Selected from hydrogen, alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, and cycloynyl; preferably, R 2b Selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl and C 5-12 Cycloacetic group; - R 2c Selected from hydrogen, alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, and cycloynyl; preferably, R 2c Selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl and C 5-12 Cycloacetic group; - R 2d Selected from hydroxyalkyl, alkoxyalkyl, hydroxy, hydrogen, alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, and cycloynyl; preferably, R 2d Selected from hydroxyl, hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl and C 5-12 Cycloacetic group; - Or, R 1 and R 2 Together with the carbon atom it is attached to, it can form a heterocyclic group (such as pyrrolidinyl). The heterocyclic group is either unsubstituted or substituted with one or more substituents, each substituent being independently selected from halogens, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cycloalkyl, cycloalkenyl, cycloalkynyl, -C(O)OH, -NH2, -NHalkyl, and -N(alkyl)2; preferably, the heterocyclic group is either unsubstituted or substituted with one or more substituents, each substituent being independently selected from halogens, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalkynyl, -C(O)OH, -NH2, -NHC 1-6 Alkyl and -N(C) 1-6 Alkyl)2; - Or, R 2 X, together with the atoms to which it is attached, can form a heterocyclic group, wherein the heterocyclic group is unsubstituted or substituted by one or more substituents, each of which is independently selected from halogens, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, -C(O)OH, -NH2, -NHalkyl, and -N(alkyl)2; preferably, R 2 X, together with the atoms it is attached to, can form a heterocyclic group, wherein the heterocyclic group is unsubstituted or substituted by one or more substituents, each of which is independently selected from halogens, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, -C(O)OH, -NH2, -NHC 1-6 Alkyl and -N(C) 1-6 Alkyl)2; - R 3 Selected from hydrogen, halogen, nitro, -CN, -NR 3a R 3b 、-(CR 3f R 3g ) q -NR 3a R 3b -NR 3a -(CR 3f R 3g ) q -C(O)NR 3a R 3b -NR 3a -(CR 3f R 3g ) q -CO2R 3c -NR 3a-(CR 3f R 3g ) q -OR 3c 、-NR 3a -(CR 3f R 3g ) q -PO(OR 3i )2、-NR 3a -(CR 3f R 3g ) q -NR 3a C(O)R 3d 、-SR 3c 、-S(O)R 3d 、-S(O)2R 3c 、-S(O)2-NR 3a R 3b 、-OR 3c 、-(CR 3f R 3g ) q -OR 3c 、 、 、oxo, -NR 3a S(O)2R 3d 、-(CR 3f R 3g ) q -NR 3a S(O)2R 3d 、-NR 3a C(O)R 3d 、-(CR 3f R 3g ) q -NR 3a C(O)R 3d 、-(CR 3f R 3g ) q -CO2R 3c 、-(CR 3f R 3g ) q -C(O)R 3c 、-(CR 3f R 3g ) q -C(O)NR 3a R 3bhydroxyl, mercapto, alkyl, alkenyl, alkynyl, alkoxy, alkylamino, dialkylamino, alkylaminoalkyl, dialkylaminoalkyl, thioalkyl, alkoxyalkyl, alkylthioalkyl, alkoxyalkylamino, cycloalkyl, cycloalkenyl, cycloalkynyl, haloalkyl, haloalkenyl, haloalkynyl, aryl, heteroaryl, heterocyclic, arylalkyl, arylalkenyl, arylalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heterocyclic alkyl, heterocyclic alkenyl, and heterocyclic alkynyl; preferably, R 3 Selected from hydrogen, halogen, nitro, -CN, -NR 3a R 3b 、-(CR 3f R 3g ) q -NR 3a R 3b -NR 3a -(CR 3f R 3g ) q -C(O)NR 3a R 3b -NR 3a -(CR 3f R 3g ) q -CO2R 3c -NR 3a -(CR 3f R 3g ) q -OR 3c -NR 3a -(CR 3f R 3g ) q -PO(OR 3i )2、-NR 3a -(CR 3f R 3g ) q -NR 3a C(O)R 3d -SR 3c -S(O)R 3d -S(O)2R 3c -S(O)2-NR 3a R 3b -OR 3c 、-(CR 3f R 3g ) q -OR 3c , , Oxygenation, -NR 3a S(O)2R 3d 、-(CR 3f R3g ) q -NR 3a S(O)2R 3d -NR 3a C(O)R 3d 、-(CR 3f R 3g ) q -NR 3a C(O)R 3d 、-(CR 3f R 3g ) q -CO2R 3c 、-(CR 3f R 3g ) q -C(O)R 3c 、-(CR 3f R 3g ) q -C(O)NR 3a R 3b hydroxyl, thiol, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylamino, diC 1-6 Alkylamino, C 1-6 Alkylamino C 1-6 Alkyl, diC 1-6 Alkylamino C 1-6 Alkyl, Thio C 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl, C 1-6 Alkyl thioC 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkylamino, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalynyl, Halogenated C 1-6 Alkyl, Halogenated C 2-6 alkenyl, halogenated C 2-6 alkynyl, aryl, heteroaryl, heterocyclic, aryl C 1-6 Alkyl, aryl C 2-6 alkenyl, aryl C 2-6 alkynyl, heteroaryl C 1-6 Alkyl, heteroaryl C 2-6 alkenyl, heteroaryl C 2-6 alkynyl, heterocyclic C 1-6 Alkyl, heterocyclic C 2-6 alkenyl and heterocyclic C 2-6 alkynyl group, The alkyl, alkenyl, alkynyl, alkoxy, alkylamino, dialkylamino, alkylaminoalkyl, dialkylaminoalkyl, thioalkyl, alkoxyalkyl, alkylthioalkyl, alkoxyalkylamino, cycloalkyl, cycloalkenyl, cycloalkynyl, haloalkyl, haloalkenyl, haloalkynyl, aryl, heteroaryl, heterocyclic, arylalkyl, arylalkenyl, arylalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heterocyclic alkyl, heterocyclic alkenyl, and heterocyclic alkynyl Each group is either unsubstituted or substituted with one or more substituents, each substituent being independently selected from halogens, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, alkoxy, alkylthio, cycloalkyl, cycloalkenyl, cycloalkynyl, heterocyclic, -C(O)OH, -C(O)R 3i -C(O)-O-CH2-O-CO-R 3i -PO-(OR) 3i )2, -SO2F, -NH2, -NHalkyl and -N(alkyl)2; preferably, the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylamino, diC 1-6 Alkylamino, C 1-6 Alkylamino C 1-6 Alkyl, diC 1-6 Alkylamino C 1-6 Alkyl, Thio C 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl, C 1-6 Alkyl thioC 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkylamino, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalynyl, Halogenated C 1-6 Alkyl, Halogenated C 2-6 alkenyl, halogenated C 2-6 alkynyl, aryl, heteroaryl, heterocyclic, aryl C 1-6 Alkyl, aryl C 2-6 alkenyl, aryl C 2-6 alkynyl, heteroaryl C 1-6 Alkyl, heteroaryl C 2-6 alkenyl, heteroaryl C 2-6 alkynyl, heterocyclic C 1-6 Alkyl, heterocyclic C 2-6alkenyl and heterocyclic C 2-6 Each alkynyl group is either unsubstituted or substituted with one or more substituents, each substituent being independently selected from halogens, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 1-6 Alkylthio, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalkynyl, heterocyclic, -C(O)OH, -C(O)R 3i -C(O)-O-CH2-O-CO-R 3i -PO-(OR) 3i )2、-SO2F、-NH2、-NHC 1-6 Alkyl and -N(C) 1-6 Alkyl)2; - Ring A is selected from aryl, cycloalkyl, cycloalkenyl, cycloynyl, heterocyclic, and heteroaryl groups; ring A is selected from aryl, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalkynyl, heterocyclic and heteroaryl; - Y is NR 3h Or O; preferably, Y is NH or NC. 1-6 Alkyl or O; - Each R 6 Independently selected from hydrogen, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, alkoxy, (mono or di)alkylamino, alkylthio, alkylthioalkyl, alkoxyalkyl, (mono or di)alkylaminoalkyl, -(CR 3f R 3g ) q -O-(CR 3f R 3g ) v -CO2R 3c , hydroxyalkyl, -(CR 3f R 3g ) q -NR 3a SO2R 3d -CO2R 3c 、-(CR 3f R 3g ) q -O-(CR3f R 3g ) v -Aryl, -(CR 3f R 3g ) q -O-(CR 3f R 3g ) v -Heteroaryl, -CONR 3a S(O)2R 3d -S(O)2R 3d 、-(CR 3f R 3g ) q -O-(CR 3f R 3g ) v -CN、-C(O)R 3d aryl, heteroaryl, heterocyclic, -C(O)NR 3a R 3b , Oxygenated, -S(O)2NR 3a R 3b -OR 3c and -(CR 3f R 3g ) q -O-(CR 3f R 3g ) v -O-aryl; preferably, each R 6 Independently selected from hydrogen, halogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalkynyl, C 1-6 Alkoxy, single C 1-6 Alkylamino, diC 1-6 Alkylamino, C 1-6 Alkylthio, C 1-6 Alkyl thioc 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl, mono-C 1-6 Alkylamino C 1-6 Alkyl, diC 1-6 Alkylamino C 1-6 Alkyl, -(CR) 3f R 3g ) q -O-(CR 3f R 3g ) v -CO2R 3c hydroxyl C 1-6 Alkyl, -(CR)3f R 3g ) q -NR 3a SO2R 3d -CO2R 3c 、-(CR 3f R 3g ) q -O-(CR 3f R 3g ) v -Aryl, -(CR 3f R 3g ) q -O-(CR 3f R 3g ) v -Heteroaryl, -CONR 3a S(O)2R 3d -S(O)2R 3d 、-(CR 3f R 3g ) q -O-(CR 3f R 3g ) v -CN、-C(O)R 3d aryl, heteroaryl, heterocyclic, -C(O)NR 3a R 3b , Oxygenated, -S(O)2NR 3a R 3b -OR 3c and -(CR 3f R 3g ) q -O-(CR 3f R 3g ) v -O-aryl, The alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, alkoxy, (mono- or di)alkylamino, alkylthio, alkylthioalkyl, alkoxyalkyl, (mono- or di)alkylaminoalkyl, aryl, heteroaryl, and heterocyclic groups are each unsubstituted or substituted by one or more substituents, each substituent being independently selected from halogens, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cycloalkyl, cycloalkenyl, cycloalkynyl, -C(O)OH, -NH2, -NHalkyl, and -N(alkyl)2; preferably, the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C5-12 Cycloalkynyl, C 1-6 Alkoxy, single C 1-6 Alkylamino, diC 1-6 Alkylamino, C 1-6 Alkylthio, C 1-6 Alkyl thioc 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl, mono-C 1-6 Alkylamino C 1-6 Alkyl, diC 1-6 Alkylamino C 1-6 The alkyl, aryl, heteroaryl, and heterocyclic groups are each unsubstituted or substituted by one or more substituents, each independently selected from halogens, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalkynyl, -C(O)OH, -NH2, -NHC 1-6 Alkyl and -N(C) 1-6 Alkyl)2; Or, two Rs 6 Together with the carbon atom to which it is attached, it can form cycloalkyl, cycloalkenyl, cycloynyl, heterocyclic, or heteroaryl groups; wherein each of the cycloalkyl, cycloalkenyl, cycloynyl, heterocyclic, and heteroaryl groups is unsubstituted or substituted by one or more substituents, each of which is independently selected from -OH, halogen, -NR. 3a R 3b aryl, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cycloalkyl, cycloalkenyl, and cycloalkynyl; preferably, two R 6 Together with the carbon atom it is attached to, it can form C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalkynyl, heterocyclic or heteroaryl; wherein the C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12The cycloalkynyl, heterocyclic, and heteroaryl groups are each unsubstituted or substituted by one or more substituents, each independently selected from -OH, halogen, and -NR. 3a R 3b Aryl, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, Cyano, Nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl and C 5-12 Cycloacetic group; - R 3a Selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, alkoxy, (mono or di)alkylamino, alkoxyalkyl, alkylthioalkyl, (mono or di)alkylaminoalkyl, haloalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, -SO2-alkyl, aryl, heteroaryl, and heterocyclic; preferably, R 3a Selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalkynyl, C 1-6 Alkoxy, single C 1-6 Alkylamino, diC 1-6 Alkylamino, C 1-6 Alkoxy C 1-6 Alkyl, C 1-6 Alkyl thioc 1-6 Alkyl, mono-C 1-6 Alkylamino C 1-6 Alkyl, diC 1-6 Alkylamino C 1-6 Alkyl, Halogenated C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, hydroxyl C 2-6 alkenyl, hydroxyl C 2-6 alkynyl, amino C 1-6 Alkyl, amino C 2-6 alkenyl, amino C 2-6 alkynyl group, -SO2-C 1-6 Alkyl, aryl, heteroaryl, and heterocyclic groups; - R 3bSelected from hydrogen, alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, and cycloynyl; preferably, R 3b Selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl and C 5-12 Cycloacetic group; - R 3c Selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, alkoxyalkyl, alkylthioalkyl, (mono- or di)alkylaminoalkyl, haloalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, hydroxycarbonylalkyl, aminoalkyl, aminoalkenyl, aminoalkynyl, aryl, heteroaryl, and heterocyclic; preferably, R 3c Selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalkynyl, C 1-6 Alkoxy C 1-6 Alkyl, C 1-6 Alkyl thioc 1-6 Alkyl, mono-C 1-6 Alkylamino C 1-6 Alkyl, diC 1-6 Alkylamino C 1-6 Alkyl, Halogenated C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, hydroxyl C 2-6 alkenyl, hydroxyl C 2-6 alkynyl group, hydroxycarbonyl group C 1-6 Alkyl, amino C 1-6 Alkyl, amino C 2-6 alkenyl, amino C 2-6 Alkynyl, aryl, heteroaryl, and heterocyclic groups; - R 3d Selected from alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, alkoxyalkyl, alkoxy, (mono or di)alkylamino, (mono or di)alkylaminoalkyl, alkylthio, alkylthioalkyl, haloalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, aryl, heteroaryl, and heterocyclic; preferably, R 3d Selected from C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalkynyl, C 1-6 Alkoxy C1-6 Alkyl, C 1-6 Alkoxy, single C 1-6 Alkylamino, diC 1-6 Alkylamino, mono-C 1-6 Alkylamino C 1-6 Alkyl, diC 1-6 Alkylamino C 1-6 Alkyl, C 1-6 Alkylthio, C 1-6 Alkyl thioc 1-6 Alkyl, Halogenated C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, hydroxyl C 2-6 alkenyl, hydroxyl C 2-6 alkynyl, amino C 1-6 Alkyl, amino C 2-6 alkenyl, amino C 2-6 Alkynyl, aryl, heteroaryl, and heterocyclic groups; - R 3f and R 3g Each is independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, haloalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, -NH2, aminoalkyl, aminoalkenyl, aminoalkynyl, aryl, heteroaryl, and heterocyclic; preferably, R 3f and R 3g Each is independently selected from hydrogen and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalynyl, Halogenated C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, hydroxyl C 2-6 alkenyl, hydroxyl C 2-6 Alkyne group, -NH2 group, amino group C 1-6 Alkyl, amino C 2-6 alkenyl, amino C 2-6 Alkynyl, aryl, heteroaryl, and heterocyclic groups; - R 3h Selected from hydrogen, alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, and cycloynyl; preferably, R 3h Selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl and C 5-12 Cycloacetic group; - R 3iSelected from hydrogen, alkyl, cycloalkyl, and aryl, wherein each alkyl, cycloalkyl, and aryl group is optionally further substituted with one or more halogens; preferably, R 3i Selected from hydrogen, C 1-6 Alkyl, C 3-12 cycloalkyl and aryl, wherein each C 1-6 Alkyl, C 3-12 The cycloalkyl and aryl groups may optionally be further substituted with one or more halogens; - m is an integer selected from 0, 1, 2, 3, 4 or 5; preferably, m is selected from 0, 1, 2 and 3; - p is an integer selected from 0, 1, 2, 3, 4 or 5; preferably, p is selected from 0, 1, 2 and 3; - q is an integer selected from 0, 1, 2, 3, 4 or 5; preferably, q is selected from 0, 1, 2 and 3; - v is an integer selected from 0, 1, 2, 3, 4 or 5; preferably, v is selected from 0, 1, 2 and 3; - W is selected from -CO-, -SO2-, and -SO(=NH)-; - L is selected from -CR Lg R Lh -、-NR Lb - or a single key; - R Lg Selected from hydrogen, halogen, alkyl, alkenyl, alkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, -NR La R Lb , aminoalkyl, aminoalkenyl, aminoynyl, haloalkyl, -C(O)NR La R Lb Alkoxy, alkylamino, dialkylamino, alkylaminoalkyl, dialkylaminoalkyl, thioalkyl, alkoxyalkyl, alkylthioalkyl, deuterium, cycloalkyl, cycloalkenyl, and cycloynyl; preferably, R Lg Selected from hydrogen, halogens, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, hydroxyl group C 1-6 Alkyl, hydroxyl C 2-6 alkenyl, hydroxyl C 2-6 alkynyl, -NR La R Lb amino C 1-6 Alkyl, amino C 2-6 alkenyl, amino C 2-6 alkynyl, halogenated C 1-6 Alkyl, -C(O)NR La R Lb C 1-6 Alkoxy, C 1-6 Alkylamino, diC 1-6Alkylamino, C 1-6 Alkylamino C 1-6 Alkyl, diC 1-6 Alkylamino C 1-6 Alkyl, Thio C 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl, C 1-6 Alkyl thioC 1-6 Alkyl, deuterium, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl and C 5-12 Cycloacetic group; - R Lh Selected from hydrogen, halogen, alkyl, alkenyl, alkynyl, deuterium, cycloalkyl, cycloalkenyl, and cycloalkynyl; preferably, R Lh Selected from hydrogen, halogens, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, deuterium, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl and C 5-12 Cycloacetic group; - R La Selected from hydrogen, alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, and cycloynyl; preferably, R La Selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl and C 5-12 Cycloacetic group; - R Lb Selected from hydrogen, alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, and cycloynyl; preferably, R Lb Selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl and C 5-12 Cycloacetic group; - Or, R Lg and R Lh Together with the carbon atom it is attached to, it can form cycloalkyl, cycloalkenyl, cycloynyl, and heterocyclic groups; preferably, R Lg and R Lh Together with the carbon atom it is attached to, it can form C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalynyl and heterocyclic groups; - X is selected from -OR Xc -NRXa R Xb aryl, heteroaryl, heterocyclic, aminoalkyl, aminoalkenyl, aminoynyl, -S(O)2R Xd -NR Xb S(O)2R Xd -NR Xb C(O)OR Xc -OC(O)R Xd -C(O)NR Xa R Xb -C(O)OR Xc , hydroxyalkyl, hydroxyalkenyl, hydroxyynyl, alkyl, alkenyl, ynyl, (mono- or di)alkylaminoalkyl, thioalkyl, alkoxyalkyl, alkylthioalkyl, cycloalkyl, cycloalkenyl, cycloynyl and -N3; ​​preferably, X is selected from -OR Xc -NR Xa R Xb aryl, heteroaryl, heterocyclic, amino C 1-6 Alkyl, amino C 2-6 alkenyl, amino C 2-6 alkynyl group, -S(O)2R Xd -NR Xb S(O)2R Xd -NR Xb C(O)OR Xc -OC(O)R Xd -C(O)NR Xa R Xb -C(O)OR Xc hydroxyl C 1-6 Alkyl, hydroxyl C 2-6 alkenyl, hydroxyl C 2-6 alkynyl group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, single C 1-6 Alkylamino C 1-6 Alkyl, diC 1-6 Alkylamino C 1-6 Alkyl, Thio C 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl, C 1-6 Alkyl thioC 1-6 Alkyl, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalynyl group and -N3; The heteroaryl, heterocyclic, aryl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, hydroxyalkyl, hydroxyalkenyl, and hydroxyalkynyl groups are each unsubstituted or substituted by one or more substituents, each of which is independently selected from hydroxyalkyl, -C(O)NR Xa R Xb Heteroaryl, heterocyclic, alkyl-substituted heterocyclic, alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, cycloynyl, -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, -C(O)OH, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, hydroxyalkoxy, aminoalkoxy, (mono- or di)alkylaminoalkoxy, -NH2, -NHalkyl and -N(alkyl)2; preferably, the aryl, heteroaryl, heterocyclic, aminoC 1-6 Alkyl, amino C 2-6 alkenyl, amino C 2-6 alkynyl group, hydroxyl group C 1-6 Alkyl, hydroxyl C 2-6 alkenyl, hydroxyl C 2-6 alkynyl group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, single C 1-6 Alkylamino C 1-6 Alkyl, diC 1-6 Alkylamino C 1-6 Alkyl, Thio C 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl, C 1-6 Alkyl thioC 1-6 Alkyl, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl and C 5-12 Each of the cycloalkynyl groups is either unsubstituted or substituted with one or more substituents, each of which is independently selected from hydroxyalkyl, -C(O)NR Xa R Xb Heteroaryl, heterocyclic, alkyl-substituted heterocyclic, alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, cycloynyl, -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, -C(O)OH, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, hydroxyl C 1-6 Alkoxy, amino C 1-6 Alkoxy, single C1-6 Alkylamino C 1-6 Alkoxy, diC 1-6 Alkylamino C 1-6 Alkoxy, -C(O)OH, -NH2, -NHC 1-6 Alkyl and -N(C) 1-6 Alkyl)2; - R Xa Selected from hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, alkoxyalkyl, aminoalkyl, aminoalkenyl, aminoalkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroaryl, heterocyclic, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heterocyclic alkyl, heterocyclic alkenyl, and heterocyclic alkynyl; preferably, R Xa Selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl, amino C 1-6 Alkyl, amino C 2-6 alkenyl, amino C 2-6 alkynyl group, hydroxyl group C 1-6 Alkyl, hydroxyl C 2-6 alkenyl, hydroxyl C 2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalkynyl, heteroaryl, heterocyclic, heteroaryl C 1-6 Alkyl, heteroaryl C 2-6 alkenyl, heteroaryl C 2-6 alkynyl, heterocyclic C 1-6 Alkyl, heterocyclic C 2-6 alkenyl and heterocyclic C 2-6 alkynyl group; The alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, alkoxyalkyl, aminoalkyl, aminoalkenyl, aminoalkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, heteroaryl, heterocyclic, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heterocyclic alkyl, heterocyclic alkenyl, and heterocyclic alkynyl are each unsubstituted or substituted by one or more substituents, each of which is independently selected from -CONR. Xe R Xf, hydroxyalkyl, heteroaryl, heterocyclic, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, -C(O)OH, O-alkyl, haloalkyl, alkoxy, haloalkoxy, -NH2, -NHalkyl and -N(alkyl)2; preferably, the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl, amino C 1-6 Alkyl, amino C 2-6 alkenyl, amino C 2-6 alkynyl group, hydroxyl group C 1-6 Alkyl, hydroxyl C 2-6 alkenyl, hydroxyl C 2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalkynyl, heteroaryl, heterocyclic, heteroaryl C 1-6 Alkyl, heteroaryl C 2-6 alkenyl, heteroaryl C 2-6 alkynyl, heterocyclic C 1-6 Alkyl, heterocyclic C 2-6 alkenyl and heterocyclic C 2-6 Each alkynyl group is either unsubstituted or substituted by one or more substituents, each of which is independently selected from -CONR. Xe R Xf hydroxyl C 1-6 Alkyl, heteroaryl, heterocyclic, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalkynyl, -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, -C(O)OH, OC 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl and -N(C) 1-6 Alkyl)2; - R XbSelected from hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, aminoalkyl, aminoalkenyl, aminoalkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, cycloalkyl, cycloalkenyl, and cycloalkynyl; preferably, R Xb Selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogenated C 1-6 Alkyl, amino C 1-6 Alkyl, amino C 2-6 alkenyl, amino C 2-6 alkynyl group, hydroxyl group C 1-6 Alkyl, hydroxyl C 2-6 alkenyl, hydroxyl C 2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl and C 5-12 Cycloacetic group; The alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, hydroxyalkyl, hydroxyalkenyl, and hydroxyalkynyl groups are each unsubstituted or substituted by one or more substituents, each of which is independently selected from -CONR. Xe R Xf , hydroxyalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, C(O)OH, O-alkyl, haloalkyl, alkoxy, haloalkoxy, -NH2, -NHalkyl, and -N(alkyl)2; preferably, the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogenated C 1-6 Alkyl, amino C 1-6 Alkyl, amino C 2-6 alkenyl, amino C 2-6 alkynyl group, hydroxyl group C 1-6 Alkyl, hydroxyl C 2-6 alkenyl, hydroxyl C 2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl and C 5-12 Each of the cycloalkyne groups is either unsubstituted or substituted with one or more substituents, each of which is independently selected from -CONR. Xe R Xf hydroxyl C 1-6 Alkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C5-12 Cycloalkynyl, -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, C(O)OH, OC 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl and -N(C) 1-6 Alkyl)2; - Each R Xc Selected from hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, alkoxyalkyl, aminoalkyl, aminoalkenyl, aminoalkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroaryl, heterocyclic, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heterocyclic alkyl, heterocyclic alkenyl, and heterocyclic alkynyl; preferably, each R Xc Selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl, amino C 1-6 Alkyl, amino C 2-6 alkenyl, amino C 2-6 alkynyl group, hydroxyl group C 1-6 Alkyl, hydroxyl C 2-6 alkenyl, hydroxyl C 2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalkynyl, heteroaryl, heterocyclic, heteroaryl C 1-6 Alkyl, heteroaryl C 2-6 alkenyl, heteroaryl C 2-6 alkynyl, heterocyclic C 1-6 Alkyl, heterocyclic C 2-6 alkenyl and heterocyclic C 2-6 alkynyl group; The alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, alkoxyalkyl, aminoalkyl, aminoalkenyl, aminoalkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, heteroaryl, heterocyclic, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heterocyclic alkyl, heterocyclic alkenyl, and heterocyclic alkynyl are each unsubstituted or substituted by one or more substituents, each of which is independently selected from -CONR. Xa R Xb, hydroxyalkyl, heteroaryl, heterocyclic, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, -C(O)OH, haloalkyl, alkoxy, haloalkoxy, -NH2, -NHalkyl and -N(alkyl)2; preferably, the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl, amino C 1-6 Alkyl, amino C 2-6 alkenyl, amino C 2-6 alkynyl group, hydroxyl group C 1-6 Alkyl, hydroxyl C 2-6 alkenyl, hydroxyl C 2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalkynyl, heteroaryl, heterocyclic, heteroaryl C 1-6 Alkyl, heteroaryl C 2-6 alkenyl, heteroaryl C 2-6 alkynyl, heterocyclic C 1-6 Alkyl, heterocyclic C 2-6 alkenyl and heterocyclic C 2-6 Each alkynyl group is either unsubstituted or substituted by one or more substituents, each of which is independently selected from -CONR. Xa R Xb hydroxyl C 1-6 Alkyl, heteroaryl, heterocyclic, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalkyne, -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, -C(O)OH, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl and -N(C) 1-6 Alkyl)2; - R XdSelected from alkyl, alkenyl, alkynyl, haloalkyl, aminoalkyl, aminoalkenyl, aminoalkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroaryl, heterocyclic, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heterocyclic alkyl, heterocyclic alkenyl, and heterocyclic alkynyl; preferably, R Xd Selected from C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl, amino C 1-6 Alkyl, amino C 2-6 alkenyl, amino C 2-6 alkynyl group, hydroxyl group C 1-6 Alkyl, hydroxyl C 2-6 alkenyl, hydroxyl C 2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalkynyl, heteroaryl, heterocyclic, heteroaryl C 1-6 Alkyl, heteroaryl C 2-6 alkenyl, heteroaryl C 2-6 alkynyl, heterocyclic C 1-6 Alkyl, heterocyclic C 2-6 alkenyl and heterocyclic C 2-6 alkynyl group; The alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, cycloynyl, aminoalkyl, aminoalkenyl, aminoynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyynyl, heteroaryl, heterocyclic, heteroarylalkyl, heteroarylalkenyl, heteroarylynyl, heterocyclic alkyl, heterocyclic alkenyl, and heterocyclic ynynyl are each unsubstituted or substituted by one or more substituents, each of which is independently selected from -CONR. Xa R Xb hydroxyalkyl, heteroaryl, heterocyclic, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, mercapto, -SCF3, -SF5, cyano, nitro, oxo, amino, -C(O)OH, halogen, hydroxyl, haloalkyl, alkoxy, and haloalkoxy; preferably, the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl, amino C 1-6 Alkyl, amino C 2-6 alkenyl, amino C 2-6 alkynyl group, hydroxyl group C 1-6 Alkyl, hydroxyl C 2-6 alkenyl, hydroxyl C2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalkynyl, heteroaryl, heterocyclic, heteroaryl C 1-6 Alkyl, heteroaryl C 2-6 alkenyl, heteroaryl C 2-6 alkynyl, heterocyclic C 1-6 Alkyl, heterocyclic C 2-6 alkenyl and heterocyclic C 2-6 Each alkynyl group is either unsubstituted or substituted by one or more substituents, each of which is independently selected from -CONR. Xa R Xb hydroxyl C 1-6 Alkyl, heteroaryl, heterocyclic, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalkynyl, mercapto, -SCF3, -SF5, cyano, nitro, oxo, amino, -C(O)OH, halogen, hydroxyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy and halogenated C 1-6 Alkoxy; - R Xe and R Xf Each is independently selected from alkyl, alkenyl, alkynyl, haloalkyl, aminoalkyl, aminoalkenyl, aminoalkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroaryl, heterocyclic, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heterocyclic alkyl, heterocyclic alkenyl, and heterocyclic alkynyl; preferably, R Xe and R Xf Each is independently selected from C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogenated C 1-6 Alkyl, amino C 1-6 Alkyl, amino C 2-6 alkenyl, amino C 2-6 alkynyl group, hydroxyl group C 1-6 Alkyl, hydroxyl C 2-6 alkenyl, hydroxyl C 2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalkynyl, heteroaryl, heterocyclic, heteroaryl C 1-6 Alkyl, heteroaryl C 2-6 alkenyl, heteroaryl C 2-6 alkynyl, heterocyclic C 1-6Alkyl, heterocyclic C 2-6 alkenyl and heterocyclic C 2-6 alkynyl group; The alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, heteroaryl, heterocyclic, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heterocyclic alkyl, heterocyclic alkenyl, and heterocyclic alkynyl are each unsubstituted or substituted by one or more substituents, each of which is independently selected from hydroxyalkyl, heteroaryl, heterocyclic, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, mercapto, -SCF3, -SF5, cyano, nitro, oxo, amino, -C(O)OH, halogen, hydroxyl, haloalkyl, alkoxy, and haloalkoxy; preferably, the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogenated C 1-6 Alkyl, amino C 1-6 Alkyl, amino C 2-6 alkenyl, amino C 2-6 alkynyl group, hydroxyl group C 1-6 Alkyl, hydroxyl C 2-6 alkenyl, hydroxyl C 2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalkynyl, heteroaryl, heterocyclic, heteroaryl C 1-6 Alkyl, heteroaryl C 2-6 alkenyl, heteroaryl C 2-6 alkynyl, heterocyclic C 1-6 Alkyl, heterocyclic C 2-6 alkenyl and heterocyclic C 2-6 Each alkynyl group is either unsubstituted or substituted by one or more substituents, each of which is independently selected from hydroxyl C. 1-6 Alkyl, heteroaryl, heterocyclic, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalkynyl, mercapto, -SCF3, -SF5, cyano, nitro, oxo, amino, -C(O)OH, halogen, hydroxyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy; - n is an integer selected from 1, 2, 3 or 4; preferably, n is 1, 2 or 3; - Each R 4Independently selected from halogens, -SCF3, -SF5, -CF3, -OCF3, -CHF2, -OCHF2, -B(OH)2, -O-SO2-F, -SO2-F, cyano, nitro, -OR 4c -NR 4a R 4b -NR 4a S(O)2R 4d -NR 4a SO2NR 4a R 4b -NR 4a C(O)R 4c -NR 4a C(O)OR 4c -NR 4a C(O)NR 4a R 4b SR 4c -S(O)R 4d -S(O)2R 4c -S(O)2NR 4a R 4b -S(O)(NR) 4a )R 4c -S(NR) 4a (NR) 4a )R 4c -C(O)OR 4c -C(O)R 4c -C(O)NR 3a R 3b -P(O)R 4a R 4b Alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, heteroaryl, heterocyclic, cycloalkyl, cycloalkenyl, and cycloalkynyl; preferably, each R 4 Independently selected from halogens, -SCF3, -SF5, -CF3, -OCF3, -CHF2, -OCHF2, -B(OH)2, -O-SO2-F, -SO2-F, cyano, nitro, -OR 4c -NR 4a R 4b -NR 4a S(O)2R 4d -NR 4a SO2NR 4a R 4b -NR 4a C(O)R 4c -NR 4a C(O)OR 4c -NR 4a C(O)NR4a R 4b SR 4c -S(O)R 4d -S(O)2R 4c -S(O)2NR 4a R 4b -S(O)(NR) 4a )R 4c -S(NR) 4a (NR) 4a )R 4c -C(O)OR 4c -C(O)R 4c -C(O)NR 3a R 3b -P(O)R 4a R 4b C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogenated C 1-6 Alkyl, Halogenated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, hydroxyl C 2-6 alkenyl, hydroxyl C 2-6 alkynyl, heteroaryl, heterocyclic, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl and C 5-12 Cycloacetic group; The alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxy, heteroaryl, heterocyclic, cycloalkyl, cycloalkenyl, and cycloalkynyl groups are each unsubstituted or substituted by one or more substituents, each substituent being independently selected from -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, -B(OH)2, cyano, nitro, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, hydroxyalkyl, haloalkyl, alkoxy, haloalkoxy, -C(O)OH, -C(O)Oalkyl, -C(O)NH2, -C(O)NHalkyl, -C(O)N(alkyl)2, -NH2, -NHalkyl, and -N(alkyl)2; preferably, the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogenated C 1-6 Alkyl, Halogenated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, hydroxyl C 2-6 alkenyl, hydroxyl C 2-6 alkynyl, heteroaryl, heterocyclic, C 3-12 cycloalkyl, C 5-12Cycloalkenyl and C 5-12 Each of the cycloalkyne groups is either unsubstituted or substituted with one or more substituents, each substituent being independently selected from -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, -B(OH)2, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalkynyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy group, -C(O)OH, -C(O)OC 1-6 Alkyl group, -C(O)NH2, -C(O)NHC 1-6 Alkyl, -C(O)N(C) 1-6 Alkyl group 2, -NH2, -NHC 1-6 Alkyl and -N(C) 1-6 Alkyl)2; - Or, two Rs 4 Together with the carbon atom to which it is attached, it can form cycloalkyl, cycloalkenyl, cycloynyl, or heterocyclic groups. Preferably, the two R groups... 4 Together with the carbon atom it is attached to, it can form C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalkynyl or heterocyclic group. The cycloalkyl, cycloalkenyl, cycloynyl, and heterocyclic groups are each unsubstituted or substituted by one or more substituents, each substituent being independently selected from -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, alkyl, alkenyl, ynyl, cycloalkyl, aryl, cycloalkenyl, cycloynyl, hydroxyalkyl, haloalkyl, alkoxy, haloalkoxy, alkoxyalkyl, haloalkoxyalkyl, hydroxyalkoxyalkyl, -C(O)OH, -C(O)Oalkyl, -C(O)NH2, -C(O)NHalkyl, -C(O)N(alkyl)2, -NH2, -NHalkyl, and -N(alkyl)2; preferably, the C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 The cycloalkynyl or heterocyclic group is either unsubstituted or substituted with one or more substituents, each independently selected from -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, C1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 cycloalkyl, aryl, C 5-12 Cycloalkenyl, C 5-12 Cycloalkynyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 1-6 Alkoxy C 1-6 Alkyl, Halogenated C 1-6 Alkoxy C 1-6 Alkyl, hydroxyl C 1-6 Alkoxy C 1-6 Alkyl, -C(O)OH, -C(O)OC 1-6 Alkyl group, -C(O)NH2, -C(O)NHC 1-6 Alkyl, -C(O)N(C) 1-6 Alkyl group 2, -NH2, -NHC 1-6 Alkyl and -N(C) 1-6 Alkyl)2; - R 4a Selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, haloalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, aminoalkyl, aminoalkenyl, and aminoalkynyl; preferably, R 4a Selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalynyl, Halogenated C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, hydroxyl C 2-6 alkenyl, hydroxyl C 2-6 alkynyl, amino C 1-6 Alkyl, amino C 2-6 alkenyl and amino C 2-6 alkynyl group; - R 4b Selected from hydrogen, alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, and cycloynyl; preferably, R 4b Selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl and C 5-12 Cycloacetic group; - R 4cSelected from hydrogen, alkyl, deuterated alkyl, alkenyl, alkynyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, alkoxyalkyl, and (mono- or di)alkylaminoalkyl; preferably, R 4c Selected from hydrogen, C 1-6 Alkyl, deuterated C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, hydroxyl C 2-6 alkenyl, hydroxyl C 2-6 alkynyl, amino C 1-6 Alkyl, amino C 2-6 alkenyl, amino C 2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalkynyl, mono-C 1-6 Alkylamino C 1-6 Alkyl and diC 1-6 Alkylamino C 1-6 alkyl; - R 4d Selected from alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, and cycloynyl; preferably, R 4d Selected from C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl and C 5-12 Cycloacetic group; - R 5 Selected from hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, alkoxyalkyl, mono- or dialkylaminoalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, heterocyclic alkyl, heterocyclic alkenyl, and heterocyclic alkynyl; preferably, R 5 Selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl, mono-C 1-6 Alkylamino C 1-6 Alkyl, diC 1-6 Alkylamino C 1-6 Alkyl, hydroxyl C1-6 Alkyl, hydroxyl C 2-6 alkenyl, hydroxyl C 2-6 alkynyl, amino C 1-6 Alkyl, amino C 2-6 alkenyl, amino C 2-6 alkynyl group, C 3-10 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalkynyl, C 3-10 cycloalkyl C 1-6 Alkyl, C 3-10 cycloalkyl C 2-6 alkenyl, C 3-10 cycloalkyl C 2-6 alkynyl, heterocyclic C 1-6 Alkyl, heterocyclic C 2-6 alkenyl and heterocyclic C 2-6 alkynyl group; The alkyl, alkenyl, alkynyl, haloalkyl, alkoxyalkyl, mono- or dialkylaminoalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, heterocyclic alkyl, heterocyclic alkenyl, and heterocyclic alkynyl are each unsubstituted or substituted by one or more substituents, each of which is independently selected from -OH, =O, halogen, -SH, = S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, hydroxyalkyl, haloalkyl, alkoxy, haloalkoxy, -C(O)OH, C(O)Oalkyl, -C(O)NH2, -C(O)NHalkyl, -C(O)N(alkyl)2, -NH2, -NHalkyl and -N(alkyl)2; preferably, the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl, mono-C 1-6 Alkylamino C 1-6 Alkyl, diC 1-6 Alkylamino C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, hydroxyl C 2-6 alkenyl, hydroxyl C 2-6 alkynyl, amino C 1-6 Alkyl, amino C 2-6 alkenyl, amino C 2-6 alkynyl group, C 3-10 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalkynyl, C3-10 cycloalkyl C 1-6 Alkyl, C 3-10 cycloalkyl C 2-6 alkenyl, C 3-10 cycloalkyl C 2-6 alkynyl, heterocyclic C 1-6 Alkyl, heterocyclic C 2-6 alkenyl and heterocyclic C 2-6 Each alkynyl group is either unsubstituted or substituted with one or more substituents, each substituent being independently selected from -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 cycloalkyl, C 5-12 Cycloalkenyl, C 5-12 Cycloalkynyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy group, -C(O)OH, C(O)OC 1-6 Alkyl group, -C(O)NH2, -C(O)NHC 1-6 Alkyl, -C(O)N(C) 1-6 Alkyl group 2, -NH2, -NHC 1-6 Alkyl and -N(C) 1-6 Alkyl)2; - Or, R 3 and R 5 Together with the atoms to which it is attached, it forms a heteroaryl or heterocyclic group, wherein the heteroaryl or heterocyclic group is optionally substituted by one or more substituents, the substituents being independently selected from -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, alkyl, alkenyl, alkynyl, phenyl, hydroxyalkyl, haloalkyl, alkoxy, haloalkoxy, -NH2, -NHalkyl, and -N(alkyl)2; preferably, R 3 and R 5 Together with the atoms to which it is attached, it forms a heteroaryl or heterocyclic group, wherein the heteroaryl or heterocyclic group is optionally substituted by one or more substituents, the substituents being independently selected from -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, hydroxyl C 1-6 Alkyl, Halogenated C1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl and -N(C) 1-6 Alkyl)2; - Wherein, when a portion of -WLX is -C(O)O-tert-butyl, R 3 Not oxygenated or hydrogenated; The condition is that the compound is not: 1,3-Dihydro-6,8-dimethoxy-4-methyl-N-(1-methylethyl)-2H-pyrrolo[3,4-c]quinoline-2-carboxamide, N-Butyl-1,3-dihydro-6,8-dimethoxy-4-methyl-2H-pyrrolo[3,4-c]quinoline-2-carboxamide, 1,3-Dihydro-6,8-Dimethoxy-4-methyl-N-phenyl-2H-pyrrolo[3,4-c]quinoline-2-carboxamide, 1-(1,3-dihydro-6,8-dimethoxy-4-methyl-2H-pyrrolo[3,4-c]quinolin-2-yl)ketene, N-(2-ethoxyphenyl)-1,3-dihydro-6,8-dimethoxy-4-methyl-2H-pyrrolo[3,4-c]quinoline-2-carboxamide, N-(3,4-dichlorophenyl)-1,3-dihydro-6,8-dimethoxy-4-methyl-2H-pyrrolo[3,4-c]quinoline-2-carboxamide, 6-(1-((tert-butyloxycarbonyl)amino)propyl-2-yl)-1-oxo-1,3-dihydro-2H-pyrrolo[3,4-c]quinoline-2-carboxylic acid tert-butyl ester 1,3-Dihydro-6,8-Dimethoxy-4-methyl-N-[3-(trifluoromethyl)phenyl]-2H-pyrrolo[3,4-c]quinoline-2-carboxamide, 2-(2-Chloroacetyl)-4-methyl-8-[(2-nitro-1-pyrrolidinyl)sulfonyl]-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione 1,3-Dihydro-4-methyl-8-[(2-nitro-1-pyrrolidinyl)sulfonyl]-α,1,3-trioxo-2H-pyrrolo[3,4-c]quinoline-2-acetyl chloride, 2,3-Dihydro-8-methyl-2-[(4-methylphenyl)sulfonyl]-4-phenyl-1H-pyrrolo[3,4-c]quinoline-1-one, 7-Chloro-2,3-dihydro-2-[(4-methylphenyl)sulfonyl]-4-phenyl-1H-pyrrolo[3,4-c]quinoline-1-one, 8-Bromo-2,3-dihydro-2-[(4-methylphenyl)sulfonyl]-4-phenyl-1H-pyrrolo[3,4-c]quinoline-1-one, 8-Chloro-2,3-dihydro-2-[(4-methylphenyl)sulfonyl]-4-phenyl-1H-pyrrolo[3,4-c]quinoline-1-one, 8-Fluoro-2,3-dihydro-2-[(4-methylphenyl)sulfonyl]-4-phenyl-1H-pyrrolo[3,4-c]quinoline-1-one, 2,3-Dihydro-8-methoxy-4-(6-methyl-1H-indol-3-yl)-2-[(4-methylphenyl)sulfonyl]-1H-pyrrolo[3,4-c]quinoline, 8-(1,1-Dimethylethyl)-2,3-dihydro-4-(1H-indol-3-yl)-2-[(4-methylphenyl)sulfonyl]-1H-pyrrolo[3,4-c]quinoline, 2,3-Dihydro-2-[(4-methylphenyl)sulfonyl]-8-(4-morpholinylsulfonyl)-4-phenyl-1H-pyrrolo[3,4-c]quinoline-1-one, (3aS,9bS)-2-(benzo[d][1,3]dioxacyclopenten-5-ylsulfonyl)-8-hydroxy-5-methyl-1,2,3,3a,5,9b-hexahydro-4H-pyrrolo[3,4-c]quinoline-4-one (3aS,9bS)-2-(benzo[d][1,3]dioxacyclopenten-5-ylsulfonyl)-5-methyl-4-oxo-2,3,3a,4,5,9b-hexahydro-1H-pyrrolo[3,4-c]quinoline-8-carboxynitrile, (3aS,9bS)-2-(benzo[d][1,3]dioxacyclopenten-5-ylsulfonyl)-8-fluoro-5-methyl-1,2,3,3a,5,9b-hexahydro-4H-pyrrolo[3,4-c]quinoline-4-one (3aR,9bR)-1,3,3a,4,5,9b-hexahydro-2H-pyrrolo[3,4-c]quinoline-2-carboxylic acid tert-butyl ester (3aS,9bR)-8-(2-(trifluoromethyl)phenyl)-1,3,3a,4,5,9b-hexahydro-2H-pyrrolo[3,4-c]quinoline-2-carboxylic acid tert-butyl ester , , , .

[0132] In one embodiment, a compound of formula (I) is provided, wherein: - Each dashed line (---) represents an optional double bond, and two adjacent dashed lines cannot form a double bond at the same time; - R 1 Selected from hydrogen, halogen, =O, alkyl, alkenyl, alkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, haloalkyl, haloalkenyl, haloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, and cycloalkynyl; The alkyl, alkenyl, alkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, haloalkyl, haloalkenyl, haloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, and cycloalkynyl groups are each unsubstituted or substituted by one or more substituents, each of which is independently selected from halogen, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, -C(O)OH, -NH2, -NHalkyl, and -N(alkyl)2; - R 2 Selected from hydrogen, halogen, =O, hydroxyl, alkyl, alkenyl, alkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, heteroalkyl (e.g., alkoxyalkyl, mono- or dialkylaminoalkyl), heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, haloalkyl, haloalkenyl, haloalkynyl, alkoxy, haloalkoxy, -CONR 2a R 2b and -CO2R 2c ; The alkyl, alkenyl, alkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, haloalkyl, haloalkenyl, haloalkynyl, alkoxy, and haloalkoxy groups are each unsubstituted or substituted by one or more substituents, each of which is independently selected from halogen, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, -C(O)OH, -NH2, -NHalkyl, -N(alkyl)2; -COR 2d -NR 2a R 2b -NR 2a COR 2d -CONR 2a R2b and -OR 2c ; - R 2a Selected from hydrogen, alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, and cycloynyl; - R 2b Selected from hydrogen, alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, and cycloynyl; - R 2c Selected from hydrogen, alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, and cycloynyl; - R 2d Selected from hydroxyalkyl, heteroalkyl (e.g., alkoxyalkyl), hydroxy, hydrogen, alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, and cycloynyl; - Or, R 1 and R 2 Together with the carbon atom to which it is attached, it can form cycloalkyl, cycloalkenyl, or heterocyclic groups (such as pyrrolidinyl). The cycloalkyl, cycloalkenyl, or heterocyclic groups are each unsubstituted or substituted by one or more substituents, each of which is independently selected from halogens, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, heteroalkyl, heteroalkenyl, heteroynyl, cycloalkyl, cycloalkenyl, cycloynyl, -C(O)OH, -NH2, -NHalkyl, and -N(alkyl)2; - R 3 Selected from hydrogen, halogen, nitro, -CN, -NR 3a R 3b 、-(CR 3f R 3g ) q -NR 3a R 3b -NR 3a -(CR 3f R 3g ) q -C(O)NR 3a R 3b -NR 3a -(CR 3f R 3g ) q -NR 3a C(O)R 3d -SR 3c -S(O)R 3d -S(O)2R 3c -S(O)2-NR 3a R 3b -OR 3c、-(CR 3f R 3g ) q -OR 3c , , Oxygenation, -NR 3a S(O)2R 3d 、-(CR 3f R 3g ) q -NR 3a S(O)2R 3d -NR 3a C(O)R 3d 、-(CR 3f R 3g ) q -NR 3a C(O)R 3d 、-(CR 3f R 3g ) q -CO2R 3c 、-(CR 3f R 3g ) q -C(O)R 3c 、-(CR 3f R 3g ) q -C(O)NR 3a R 3b , hydroxyl, mercapto, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroynyl, cycloalkyl, cycloalkenyl, cycloynyl, haloalkyl, haloalkenyl, haloynyl, aryl, heteroaryl, heterocyclic, arylalkyl, arylalkenyl, arylynyl, arylhexaneyl, arylhexaneyl, arylhexaneyl, heteroarylalkyl, heteroarylalkenyl, heteroarylhexaneyl, heteroarylhexaneyl, heteroarylhexaneyl, heterocyclic alkyl, heterocyclic alkenyl, heterocyclic alkynyl, heterocyclic alkynyl, heterocyclic alkynyl, heterocyclic alkynyl, heterocyclic heteroalkyl, heterocyclic alkenyl, heterocyclic alkynyl, heterocyclic heteroalkyl, heterocyclic heteroalkenyl and heterocyclic heteroynyl; The alkyl, alkenyl, ynyl, heteroalkyl, heteroalkenyl, heteroynyl, cycloalkyl, cycloalkenyl, cycloynyl, haloalkyl, haloalkenyl, haloynyl, aryl, heteroaryl, heterocyclic, arylalkyl, arylalkenyl, arylynyl, arylheteroalkyl, arylheteroalkenyl, arylheteryneyl, heteroarylalkyl, heteroarylalkenyl, heteroarylynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteryneyl, heterocyclic alkyl, heterocyclic alkenyl, heterocyclic ynyneyl, heterocyclic heteroalkyl, heterocyclic heteroalkenyl, heterocyclic heteroalkyl, heterocyclic heteroalkenyl, and heterocyclic heterocyclic heteroalkyl Each alkynyl group is either unsubstituted or substituted with one or more substituents, each of which is independently selected from halogens, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, -C(O)OH, -NH2, -NHalkyl and -N(alkyl)2; - Cycle A is selected from aryl (phenyl), cycloalkyl, cycloalkenyl, cycloynyl, heterocyclic and heteroaryl; - Y is NR 3h Or O; - Each R 6 Independently selected from hydrogen, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl (e.g., alkoxyalkyl), heteroalkenyl, heteroalkynyl, -(CR 3f R 3g ) q -O-(CR 3f R 3g ) v -CO2R 3c , hydroxyalkyl, -(CR 3f R 3g ) q -NR 3a SO2R 3d -CO2R 3c 、-(CR 3f R 3g ) q -O-(CR 3f R 3g ) v -Aryl, -(CR 3f R 3g ) q -O-(CR 3f R 3g ) v -Heteroaryl, -CONR 3a S(O)2R 3d -S(O)2R 3d 、-(CR 3f R 3g) q -O-(CR 3f R 3g ) v -CN、-C(O)R 3d aryl, heteroaryl, heterocyclic, -C(O)NR 3a R 3b , Oxygenated, -S(O)2NR 3a R 3b -OR 3c and -(CR 3f R 3g ) q -O-(CR 3f R 3g ) v -O-aryl; The alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, and heterocyclic groups are each unsubstituted or substituted by one or more substituents, each of which is independently selected from halogens, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, -C(O)OH, -NH2, -NHalkyl, and -N(alkyl)2; Or, two Rs 6 Together with the carbon atom to which it is attached, it can form cycloalkyl, cycloalkenyl, cycloynyl, or heterocyclic groups; wherein each of the cycloalkyl, cycloalkenyl, cycloynyl, and heterocyclic groups is unsubstituted or substituted by one or more substituents, each of which is independently selected from -OH, halogen, -NR. 3a R 3b , aryl, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, heteroalkyl, heteroalkenyl, heteroynyl, cycloalkyl, cycloalkenyl, and cycloynyl; - R 3a Selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, haloalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, aryl, heteroaryl, and heterocyclic groups; - R 3b Selected from hydrogen, alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, and cycloynyl; - R 3cSelected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl (alkoxyalkyl), heteroalkenyl, heteroalkynyl, haloalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, aryl, heteroaryl, and heterocyclic groups; - R 3d Selected from alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl (alkoxyalkyl), heteroalkenyl, heteroalkynyl, haloalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, aryl, heteroaryl, and heterocyclic groups; - R 3f and R 3g Each is independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkenyl, heteroalkynyl, haloalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, aryl, heteroaryl, and heterocyclic groups; - R 3h Selected from hydrogen, alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, and cycloynyl; - m is an integer selected from 0, 1, 2, 3, 4 or 5; - p is an integer selected from 0, 1, 2, 3, 4 or 5; - q is an integer selected from 0, 1, 2, 3, 4 or 5; - v is an integer selected from 0, 1, 2, 3, 4 or 5; - W is selected from -CO-, -SO2-, -SO(=NH)- (sulfinimide group); - L is selected from -CR Lg R Lh -、-NR Lb - or a single key; - R Lg Selected from hydrogen, halogen, alkyl, alkenyl, alkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, -NR La R Lb , aminoalkyl, aminoalkenyl, aminoynyl, haloalkyl, -C(O)NR La R Lb heteroalkyl, heteroalkenyl, heteroynyl, cycloalkyl, cycloalkenyl, and cycloynyl; - R Lh Selected from hydrogen, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, and cycloalkynyl; - R La Selected from hydrogen, alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, and cycloynyl; - R Lb Selected from hydrogen, alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, and cycloynyl; - Or, RLg and R Lh Together with the carbon atom to which it is attached, it can form cycloalkyl, cycloalkenyl, cycloynyl, or heterocyclic groups; - X is selected from -OR Xc -NR Xa R Xb heteroaryl, heterocyclic, aminoalkyl, aminoalkenyl, aminoynyl, -S(O)2R Xd -NR Xb S(O)2R Xd -NR Xb C(O)2R Xc -OC(O)R Xd -C(O)NR Xa R Xb -CO2R Xc , hydroxyalkyl, hydroxyalkenyl, hydroxyynyl, alkyl, alkenyl, ynyl, heteroalkyl, heteroalkenyl, heteroynyl, cycloalkyl, cycloalkenyl, cycloynyl and -N3; The heteroaryl, heterocyclic, aryl, alkyl, alkenyl, ynyl, heteroalkyl, heteroalkenyl, heteroynyl, cycloalkyl, cycloalkenyl, cycloynyl, aminoalkyl, aminoalkenyl, aminoynyl, hydroxyalkyl, hydroxyalkenyl, and hydroxyynyl are each unsubstituted or substituted by one or more substituents, each of which is independently selected from hydroxyalkyl, -C(O)NR Xa R Xb Heteroaryl, heterocyclic, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, -C(O)OH, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, -NH2, -NHalkyl and -N(alkyl)2; - R Xa Selected from hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl (alkoxyalkyl), heteroalkenyl, heteroynyl, aminoalkyl, aminoalkenyl, aminoynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyynyl, cycloalkyl, cycloalkenyl, cycloynyl, heteroaryl, heterocyclic, heteroarylalkyl, heteroarylalkenyl, heteroarylynyl, heterocyclic alkyl, heterocyclic alkenyl, and heterocyclic alkynyl; The alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, cycloynyl, heteroalkyl, heteroalkenyl, heteroynyl, aminoalkyl, aminoalkenyl, aminoynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyynyl, heteroaryl, heterocyclic, heteroarylalkyl, heteroarylalkenyl, heteroarylynyl, heterocyclic alkyl, heterocyclic alkenyl, and heterocyclic ynynyl are each unsubstituted or substituted by one or more substituents, each of which is independently selected from -CONR. Xa RXb Hydroxylalkyl, heteroaryl, heterocyclic, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, -C(O)OH, O-alkyl, haloalkyl, alkoxy, haloalkoxy, -NH2, -NHalkyl and -N(alkyl)2; - R Xb Selected from hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, cycloalkyl, cycloalkenyl, and cycloalkynyl; The alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, cycloynyl, heteroalkyl, heteroalkenyl, heteroynyl, aminoalkyl, aminoalkenyl, aminoynyl, hydroxyalkyl, hydroxyalkenyl, and hydroxyynyl groups are each unsubstituted or substituted by one or more substituents, each of which is independently selected from -CONR. Xa R Xb Hydroxylalkyl, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, -C(O)OH, O-alkyl, haloalkyl, alkoxy, haloalkoxy, -NH2, -NHalkyl and -N(alkyl)2; - Each R Xc Selected from hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl (alkoxyalkyl), heteroalkenyl, heteroynyl, aminoalkyl, aminoalkenyl, aminoynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyynyl, cycloalkyl, cycloalkenyl, cycloynyl, heteroaryl, heterocyclic, heteroarylalkyl, heteroarylalkenyl, heteroarylynyl, heterocyclic alkyl, heterocyclic alkenyl, and heterocyclic alkynyl; The alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, cycloynyl, heteroalkyl, heteroalkenyl, heteroynyl, aminoalkyl, aminoalkenyl, aminoynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyynyl, heteroaryl, heterocyclic, heteroarylalkyl, heteroarylalkenyl, heteroarylynyl, heterocyclic alkyl, heterocyclic alkenyl, and heterocyclic ynynyl are each unsubstituted or substituted by one or more substituents, each of which is independently selected from -CONR. Xa R XbHydroxylalkyl, heteroaryl, heterocyclic, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, -C(O)OH, O-alkyl, haloalkyl, alkoxy, haloalkoxy, -NH2, -NHalkyl and -N(alkyl)2; - R Xd Selected from alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroaryl, heterocyclic, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heterocyclic alkyl, heterocyclic alkenyl, and heterocyclic alkynyl; The alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, cycloynyl, heteroalkyl, heteroalkenyl, heteroynyl, aminoalkyl, aminoalkenyl, aminoynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyynyl, heteroaryl, heterocyclic, heteroarylalkyl, heteroarylalkenyl, heteroarylynyl, heterocyclic alkyl, heterocyclic alkenyl, and heterocyclic ynynyl are each unsubstituted or substituted by one or more substituents, each of which is independently selected from -CONR. Xa R Xb , hydroxyalkyl, heteroaryl, heterocyclic, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, mercapto, -SCF3, -SF5, cyano, nitro, oxo, amino, -C(O)OH, halogen, hydroxyl, haloalkyl, alkoxy and haloalkoxy; - n is an integer selected from 1, 2, 3 or 4; - Each R 4 Independently selected from halogen, -SCF3, -SF5, -CF3, -OCF3, -CHF2, -OCHF2, cyano, nitro, -OR 4c -NR 4a R 4b -NR 4a S(O)2R 4d -NR 4a SO2NR 4a R 4b -NR 4a C(O)R 4d -NR 4a C(O)OR 4c -NR 4a C(O)NR 4a R 4b SR 4c -S(O)R 4d -S(O)2R 4c-S(O)2NR 4a R 4b -S(O)(NR) 4a )R 4c -S(NR) 4a (NR) 4a )R 4c -C(O)OR 4c -C(O)R 4c -C(O)NR 3a R 3b -P(O)R 4a R 4b Alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, and cycloalkynyl; The alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, and cycloalkynyl groups are each unsubstituted or substituted by one or more substituents, each of which is independently selected from -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, hydroxyalkyl, haloalkyl, alkoxy, haloalkoxy, -C(O)OH, -C(O)Oalkyl, -C(O)NH2, -C(O)NHalkyl, C(O)N(alkyl)2, -NH2, -NHalkyl, and -N(alkyl)2; - Or, two Rs 4 Together with the carbon atom to which it is attached, it can form cycloalkyl, cycloalkenyl, cycloynyl, or heterocyclic groups; The cycloalkyl, cycloalkenyl, cycloynyl, and heterocyclic groups are each unsubstituted or substituted by one or more substituents, each of which is independently selected from -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, cycloynyl, heteroalkyl, heteroalkenyl, heteroynyl, hydroxyalkyl, haloalkyl, alkoxy, haloalkoxy, -C(O)OH, C(O)Oalkyl, -C(O)NH2, -C(O)NHalkyl, C(O)N(alkyl)2, -NH2, -NHalkyl, and -N(alkyl)2; - R 4a Selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, haloalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, aminoalkyl, aminoalkenyl, and aminoalkynyl; - R4b Selected from hydrogen, alkyl, alkenyl, ynyl, heteroalkyl, heteroalkenyl, heteroynyl, cycloalkyl, cycloalkenyl, and cycloynyl; - R 4c Selected from hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl and heteroalkynyl; - R 4d Selected from alkyl, alkenyl, ynyl, heteroalkyl, heteroalkenyl, heteroynyl, cycloalkyl, cycloalkenyl, and cycloynyl; - R 5 Selected from hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl (e.g., alkoxyalkyl, mono- or dialkylaminoalkyl), heteroalkenyl, heteroynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyynyl, aminoalkyl, aminoalkenyl, aminoynyl, cycloalkyl, cycloalkenyl, cycloynyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylynyl, heterocyclic alkyl, heterocyclic alkenyl and heterocyclic ynynyl; The alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, heteroalkenyl, heteroalkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, heterocyclic alkyl, heterocyclic alkenyl, and heterocyclic alkynyl are each unsubstituted or substituted by one or more substituents, each of which is independently selected from -OH, =O, halogen, -SH, =S, and -C. F3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, cycloynyl, heteroalkyl, heteroalkenyl, heteroynyl, hydroxyalkyl, haloalkyl, alkoxy, haloalkoxy, -C(O)OH, -C(O)Oalkyl, -C(O)NH2, -C(O)NHalkyl, C(O)N(alkyl)2, -NH2, -NHalkyl and -N(alkyl)2; The condition is that the compound is not: 1,3-Dihydro-6,8-dimethoxy-4-methyl-N-(1-methylethyl)-2H-pyrrolo[3,4-c]quinoline-2-carboxamide, N-Butyl-1,3-dihydro-6,8-dimethoxy-4-methyl-2H-pyrrolo[3,4-c]quinoline-2-carboxamide, 1,3-Dihydro-6,8-Dimethoxy-4-methyl-N-phenyl-2H-pyrrolo[3,4-c]quinoline-2-carboxamide, 1-(1,3-dihydro-6,8-dimethoxy-4-methyl-2H-pyrrolo[3,4-c]quinolin-2-yl)ketene, N-(2-ethoxyphenyl)-1,3-dihydro-6,8-dimethoxy-4-methyl-2H-pyrrolo[3,4-c]quinoline-2-carboxamide, N-(3,4-dichlorophenyl)-1,3-dihydro-6,8-dimethoxy-4-methyl-2H-pyrrolo[3,4-c]quinoline-2-carboxamide, 6-(1-((tert-butyloxycarbonyl)amino)propyl-2-yl)-1-oxo-1,3-dihydro-2H-pyrrolo[3,4-c]quinoline-2-carboxylic acid tert-butyl ester 1,3-Dihydro-6,8-Dimethoxy-4-methyl-N-[3-(trifluoromethyl)phenyl]-2H-pyrrolo[3,4-c]quinoline-2-carboxamide, 2-(2-Chloroacetyl)-4-methyl-8-[(2-nitro-1-pyrrolidinyl)sulfonyl]-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione 1,3-Dihydro-4-methyl-8-[(2-nitro-1-pyrrolidinyl)sulfonyl]-α,1,3-trioxo-2H-pyrrolo[3,4-c]quinoline-2-acetyl chloride, 2,3-Dihydro-8-methyl-2-[(4-methylphenyl)sulfonyl]-4-phenyl-1H-pyrrolo[3,4-c]quinoline-1-one, 7-Chloro-2,3-dihydro-2-[(4-methylphenyl)sulfonyl]-4-phenyl-1H-pyrrolo[3,4-c]quinoline-1-one, 8-Bromo-2,3-dihydro-2-[(4-methylphenyl)sulfonyl]-4-phenyl-1H-pyrrolo[3,4-c]quinoline-1-one, 8-Chloro-2,3-dihydro-2-[(4-methylphenyl)sulfonyl]-4-phenyl-1H-pyrrolo[3,4-c]quinoline-1-one, 8-Fluoro-2,3-dihydro-2-[(4-methylphenyl)sulfonyl]-4-phenyl-1H-pyrrolo[3,4-c]quinoline-1-one, 2,3-Dihydro-8-methoxy-4-(6-methyl-1H-indol-3-yl)-2-[(4-methylphenyl)sulfonyl]-1H-pyrrolo[3,4-c]quinoline, 8-(1,1-Dimethylethyl)-2,3-dihydro-4-(1H-indol-3-yl)-2-[(4-methylphenyl)sulfonyl]-1H-pyrrolo[3,4-c]quinoline, 2,3-Dihydro-2-[(4-methylphenyl)sulfonyl]-8-(4-morpholinylsulfonyl)-4-phenyl-1H-pyrrolo[3,4-c]quinoline-1-one.

[0133] Preferred or specific statements (features), aspects, and embodiments of the compounds of this invention are set forth below. Unless expressly indicated otherwise, each statement, aspect, and embodiment so defined in this invention may be combined with any other statement, aspect, and / or embodiment. Specifically, any feature indicated as preferred, specific, or advantageous may be combined with any other feature or statement indicated as preferred, specific, or advantageous. Accordingly, this invention particularly covers any of the following statements and embodiments, or any combination of one or more of them, and combinations with any other statement, aspect, and / or embodiment.

[0134] The compound according to any one of the formula, statement, embodiment or claim, wherein R 1 Selected from hydrogen, alkyl, or hydroxyalkyl; preferably, R 1 Selected from hydrogen, C 1-6 Alkyl or hydroxyl C 1-6 alkyl.

[0135] In one implementation, R 1 Selected from hydrogen, alkyl, and hydroxyalkyl, such as C 1-4 Alkyl and hydroxy C 1-4 Alkyl. In another embodiment, R 1 Selected from hydrogen, methyl, hydroxymethyl, ethyl, and (iso- or n-)propyl. In another embodiment, R 1 C 1-4 Alkyl groups, such as methyl groups, are stereochemically defined as having an S configuration.

[0136] The compound according to any one of the formula, statement, embodiment or claim, wherein

[0137] - R 2 Selected from hydrogen, -CONR 2a R 2b , aminoalkyl, alkyl, hydroxyalkyl and heteroalkyl; preferably, R 2 Selected from hydrogen, -CONR 2a R 2b amino C 1-6 Alkyl, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl, mono-C 1-6 Alkylamino C 1-6 Alkyl and diC 1-6 Alkylamino C 1-6 alkyl; - R 2a Selected from hydrogen or alkyl; preferably, R 2a Selected from hydrogen or C 1-6 Alkyl; and - R 2b Selected from hydrogen or alkyl; preferably, R 2b Selected from hydrogen or C 1-6 alkyl.

[0138] In some implementation schemes, R 2 Selected from hydrogen, -CONR 2a R 2b , aminoalkyl, alkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, (mono- or dialkyl)amino, (mono- or dialkyl)aminoalkyl, alkylthio and alkylthioalkyl; R 2a Selected from hydrogen or alkyl; and R 2b Selected from hydrogen or alkyl; preferably, R 2 Selected from hydrogen, -CONR 2a R 2b amino C 1-6 Alkyl, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkoxy C 1-6 Alkyl, mono-C 1-6 Alkylamino, diC 1-6 Alkylamino, mono-C 1-6 Alkylamino C 1-6 Alkyl, diC 1-6 Alkylamino C 1-6 Alkyl, C 1-6 alkylthio and C 1-6 Alkyl thioc 1-6 Alkyl; R 2a Selected from hydrogen or C 1-6 Alkyl; and R 2b Selected from hydrogen or C 1-6 alkyl.

[0139] In some implementation schemes, R 2 C 1-4 Alkyl groups, such as methyl groups.

[0140] In a further implementation scheme, R 2 In stereochemistry, it is defined as the S configuration.

[0141] The compound according to any one of the formula, statement, embodiment or claim, wherein

[0142] - R 3 Selected from hydrogen, -NR 3a R 3b -NR 3a -(CR 3f R 3g ) q -CONR 3a-NR 3a -(CR 3f R 3g ) q -NR 3a COR 3d -SR 3c OR 3c ,alkyl, , Oxygenation, -NR 3a SO2R 3d Halogen, -NR 3a COR 3d and heteroalkyl groups (e.g., alkoxy, alkoxyalkyl, (mono- or dialkyl)amino, (mono- or dialkyl)aminoalkyl, alkylthio, and alkylthioalkyl); preferably, R 3 Selected from hydrogen, -NR 3a R 3b -NR 3a -(CR 3f R 3g ) q -CONR 3a -NR 3a -(CR 3f R 3g ) q -NR 3a COR 3d -SR 3c OR 3c C 1-6 alkyl, , Oxygenation, -NR 3a SO2R 3d Halogen, -NR 3a COR 3d C 1-6 Alkoxy, C 1-6 Alkoxy C 1-6 Alkyl, mono-C 1-6 Alkylamino, diC 1-6 Alkylamino, mono-C 1-6 Alkylamino C 1-6 Alkyl, diC 1-6 Alkylamino C 1-6 Alkyl, C 1-6 alkylthio and C 1-6 Alkyl thioc 1-6 Alkyl group; ring A is selected from aryl (phenyl), 3- to 7-membered cycloalkyl, 4- to 12-membered heterocyclic and 5- to 12-membered heteroaryl; - Y is NR 3h Or O; - Each R 6 Independently selected from hydrogen, -(CR 3fR 3g ) q -O-(CR 3f R 3g ) v -CO2R 3c , hydroxyalkyl, -(CR 3f R 3g ) q -NR 3a SO2R 3d -CO2R 3c 、-(CR 3f R 3g ) q -O-(CR 3f R 3g ) v -Heteroaryl, -CONR 3a SO2R 3d -SO2R 3d 、-(CR 3f R 3g ) q -O-(CR 3f R 3g ) v -CN、-COR 3d Heteroaryl, heteroalkyl (e.g., alkoxy, alkoxyalkyl, (mono or dialkyl)amino, (mono or dialkyl)aminoalkyl, alkylthio and alkylthioalkyl), aryl (phenyl), halogen, alkyl, -CONR 3a R 3b Oxygenation, -SO2NR 3a R 3b -OR 3c and -(CR 3f R 3g ) q -O-(CR 3f R 3g ) v -O-aryl; wherein the alkyl, aryl, heteroalkyl, or heteroaryl group is unsubstituted or substituted by one or more substituents, each substituent being independently selected from halogens, hydroxyl groups, alkoxy groups, haloalkyl groups, and haloalkoxy groups; preferably, each R 6 Independently selected from hydrogen, -(CR 3f R 3g ) q -O-(CR 3f R 3g ) v -CO2R 3c hydroxyl C 1-6 Alkyl, -(CR) 3f R 3g ) q -NR 3aSO2R 3d -CO2R 3c 、-(CR 3f R 3g ) q -O-(CR 3f R 3g ) v -Heteroaryl, -CONR 3a SO2R 3d -SO2R 3d 、-(CR 3f R 3g ) q -O-(CR 3f R 3g ) v -CN、-COR 3d , heteroaryl, C 1-6 Alkoxy, C 1-6 Alkoxy C 1-6 Alkyl, mono-C 1-6 Alkylamino, diC 1-6 Alkylamino, mono-C 1-6 Alkylamino C 1-6 Alkyl, diC 1-6 Alkylamino C 1-6 Alkyl, C 1-6 alkylthio and C 1-6 Alkyl thioc 1-6 Alkyl; aryl, halogen, C 1-6 Alkyl, -CONR 3a R 3b Oxygenation, -SO2NR 3a R 3b -OR 3c and -(CR 3f R 3g ) q -O-(CR 3f R 3g ) v -O-aryl; wherein the C 1-6 Alkyl, aryl, C 1-6 Alkoxy, C 1-6 Alkoxy C 1-6 Alkyl, mono-C 1-6 Alkylamino, diC 1-6 Alkylamino, mono-C 1-6 Alkylamino C 1-6 Alkyl, diC 1-6 Alkylamino C 1-6 Alkyl, C 1-6 Alkylthio, C 1-6 Alkyl thioc 1-6The alkyl or heteroaryl groups are either unsubstituted or substituted with one or more substituents, each independently selected from halogens, hydroxyl groups, C... 1-6 Alkoxy, halogenated C 1-6 Alkyl and Halogenated C 1-6 Alkoxy; Or, two Rs 6 Together with the carbon atom to which it is attached, it can form a heterocyclic group or a cycloalkyl group; wherein each of the heterocyclic group or cycloalkyl group is unsubstituted or substituted by one or more substituents, each of which is independently selected from -OH, halogen, -NR. 3a R 3b Heteroalkyl groups (e.g., alkoxy, alkoxyalkyl, (mono or dialkyl)amino, (mono or dialkyl)aminoalkyl, alkathio and alkathioalkyl), alkoxy, haloalkyl and haloalkoxy; preferably, two R 6 Together with the carbon atom to which it is attached, it can form a heterocyclic group or a cycloalkyl group; wherein each of the heterocyclic group or cycloalkyl group is unsubstituted or substituted by one or more substituents, each of which is independently selected from -OH, halogen, -NR. 3a R 3b C 1-6 Alkoxy, C 1-6 Alkoxy C 1-6 Alkyl, mono-C 1-6 Alkylamino, diC 1-6 Alkylamino, mono-C 1-6 Alkylamino C 1-6 Alkyl, diC 1-6 Alkylamino C 1-6 Alkyl, C 1-6 Alkylthio, C 1-6 Alkyl thioc 1-6 Alkyl, Halogenated C 1-6 Alkyl and Halogenated C 1-6 Alkoxy; - R 3a Selected from hydrogen, alkyl, cycloalkyl, or hydroxyalkyl; preferably, R 3a Selected from hydrogen, C 1-6 Alkyl, C 3-10 cycloalkyl or hydroxy C 1-6 alkyl; - R 3b Selected from hydrogen or alkyl; preferably, R 3b Selected from hydrogen or C 1-6 alkyl; - R 3c Selected from alkyl, heteroalkyl (alkoxyalkyl), haloalkyl, hydroxyalkyl, and hydrogen; preferably, R 3c Selected from C 1-6 Alkyl, C 1-6 Alkoxy C 1-6Alkyl, Halogenated C 1-6 Alkyl, hydroxyl C 1-6 Alkyl and hydrogen; - R 3d Selected from alkyl, heteroalkyl, cycloalkyl, or aryl; preferably, R 3d Selected from hydrogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkoxy C 1-6 Alkyl, mono-C 1-6 Alkylamino, diC 1-6 Alkylamino, mono-C 1-6 Alkylamino C 1-6 Alkyl, diC 1-6 Alkylamino C 1-6 Alkyl, C 1-6 Alkylthio, C 1-6 Alkyl thioc 1-6 Alkyl, C 3-10 cycloalkyl or aryl; - R 3f and R 3g Each is independently selected from hydrogen or alkyl; preferably, R 3f and R 3g Each is independently selected from hydrogen or C. 1-6 alkyl; - R 3h It is hydrogen or alkyl; preferably, R 3h It is hydrogen or C 1-6 alkyl; - m is an integer selected from 0, 1, 2, 3 or 4; - p is an integer selected from 0, 1, or 2; - q is an integer selected from 0, 1, or 2; and - v is an integer selected from 0, 1, or 2.

[0143] The compound according to any one of the formula, statement, embodiment or claim, wherein R 3 Selected from hydrogen, -NR 3a R 3b 、-(CR 3f R 3g ) q -NR 3a R 3b -NR 3a -(CR 3f R 3g ) q -C(O)NR 3a R 3b -NR 3a -(CR 3f R 3g )q -CO2R 3c -NR 3a -(CR 3f R 3g ) q -OR 3c -NR 3a -(CR 3f R 3g ) q -PO(OR 3i )2、-NR 3a -(CR 3f R 3g ) q -NR 3a C(O)R 3d -SR 3c -OR 3c 、-(CR 3f R 3g ) q -OR 3c , , Oxygenation, -NR 3a S(O)2R 3d 、-(CR 3f R 3g ) q -NR 3a S(O)2R 3d -NR 3a C(O)R 3d 、-(CR 3f R 3g ) q -NR 3a C(O)R 3d 、-(CR 3f R 3g ) q -CO2R 3c 、-(CR 3f R 3g ) q -C(O)R 3c 、-(CR 3f R 3g ) q -C(O)NR 3a R 3b , hydroxyl, alkyl, alkenyl, alkynyl, alkoxy, alkylamino, dialkylamino, alkylaminoalkyl, dialkylaminoalkyl, thioalkyl, alkoxyalkyl, alkylthioalkyl, alkoxyalkylamino, and cycloalkyl; preferably, R 3 Selected from hydrogen, -NR 3a R 3b 、-(CR 3f R3g ) q -NR 3a R 3b 、 -NR 3a -(CR 3f R 3g ) q -C(O)NR 3a R 3b 、 -NR 3a -(CR 3f R 3g ) q -CO2R 3c 、 -NR 3a -(CR 3f R 3g ) q -OR 3c 、 -NR 3a -(CR 3f R 3g ) q -PO(OR 3i )2、 -NR 3a -(CR 3f R 3g ) q -NR 3a C(O)R 3d 、 -SR 3c 、 -OR 3c 、 -(CR 3f R 3g ) q -OR 3c 、 、 、 oxo, -NR 3a S(O)2R 3d 、 -(CR 3f R 3g ) q -NR 3a S(O)2R 3d 、 -NR 3a C(O)R 3d 、 -(CR 3f R 3g ) q -NR 3a C(O)R 3d 、 -(CR 3f R 3g ) q -CO2R 3c 、 -(CR 3f R 3g ) q -C(O)R 3c 、 -(CR 3f R3g ) q -C(O)NR 3a R 3b hydroxyl group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylamino, diC 1-6 Alkylamino, C 1-6 Alkylamino C 1-6 Alkyl, diC 1-6 Alkylamino C 1-6 Alkyl, Thio C 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl, C 1-6 Alkyl thioc 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkylamino and C 3-10 cycloalkyl, The alkyl, alkenyl, alkynyl, alkoxy, alkylamino, dialkylamino, alkylaminoalkyl, dialkylaminoalkyl, thioalkyl, alkoxyalkyl, alkylthioalkyl, alkoxyalkylamino, and cycloalkyl groups are each unsubstituted or substituted by one or more substituents, each substituent being independently selected from halogens, -OH, =O, -SH, =S, alkyl, alkoxy, haloalkoxy, hydroxyalkyl, alkoxy, alkylthio, cycloalkyl, -C(O)OH, -C(O)R 3i -C(O)-O-CH2-O-CO-R 3i -PO-(OR) 3i )2, -NH2, -NHalkyl and -N(alkyl)2; preferably, wherein the C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylamino, diC 1-6 Alkylamino, C 1-6 Alkylamino C 1-6 Alkyl, diC 1-6 Alkylamino C 1-6 Alkyl, Thio C 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl, C 1-6 Alkyl thioc 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkylamino and C 3-10Each cycloalkyl group is either unsubstituted or substituted with one or more substituents, each substituent being independently selected from halogens, -OH, =O, -SH, =S, and C. 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 3-10 Cycloalkyl, -C(O)OH, -C(O)R 3i -C(O)-O-CH2-O-CO-R 3i -PO-(OR) 3i )2、-NH2、-NHC 1-6 Alkyl and -N(C) 1-6 Alkyl)2; - Cyclone A is selected from aryl, C 3-7 cycloalkyl, C 4-12 Heterocyclic groups and C 5-12 Mixed aromatics; - Y is NR 3h Or O; - Each R 6 Independently selected from hydrogen, halogen, alkyl, cycloalkyl, alkoxy, (mono or di)alkylamino, alkylthio, alkylthioalkyl, alkoxyalkyl, (mono or di)alkylaminoalkyl, -(CR 3f R 3g ) q -O-(CR 3f R 3g ) v -CO2R 3c , hydroxyalkyl, -(CR 3f R 3g ) q -NR 3a SO2R 3d -C(O)OR 3c 、-(CR 3f R 3g ) q -O-(CR 3f R 3g ) v -Aryl, -(CR 3f R 3g ) q -O-(CR 3f R 3g ) v -Heteroaryl, -CONR 3a S(O)2R 3d -S(O)2R 3d 、-(CR 3f R3g ) q -O-(CR 3f R 3g ) v -CN、-C(O)R 3d aryl, heteroaryl, heterocyclic, -C(O)NR 3a R 3b , Oxygenated, -S(O)2NR 3a R 3b -OR 3c and -(CR 3f R 3g ) q -O-(CR 3f R 3g ) v -O-aryl; preferably, each R 6 Independently selected from hydrogen, halogen, C 1-6 Alkyl, C 3-10 cycloalkyl, C 1-6 Alkoxy, single C 1-6 Alkylamino, diC 1-6 Alkylamino, C 1-6 Alkylthio, C 1-6 Alkyl thioc 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl, mono-C 1-6 Alkylamino C 1-6 Alkyl, diC 1-6 Alkylamino C 1-6 Alkyl, -(CR) 3f R 3g ) q -O-(CR 3f R 3g ) v -CO2R 3c hydroxyl C 1-6 Alkylamino C 1-6 Alkyl, -(CR) 3f R 3g ) q -NR 3a SO2R 3d -C(O)OR 3c 、-(CR 3f R 3g ) q -O-(CR 3f R 3g ) v -Aryl, -(CR 3f R 3g ) q -O-(CR 3f R 3g )v -Heteroaryl, -CONR 3a S(O)2R 3d -S(O)2R 3d 、-(CR 3f R 3g ) q -O-(CR 3f R 3g ) v -CN、-C(O)R 3d aryl, heteroaryl, heterocyclic, -C(O)NR 3a R 3b , Oxygenated, -S(O)2NR 3a R 3b -OR 3c and -(CR 3f R 3g ) q -O-(CR 3f R 3g ) v -O-aryl, The alkyl, cycloalkyl, alkoxy, (mono- or di-)alkylamino, alkylthio, alkylthioalkyl, alkoxyalkyl, (mono- or di-)alkylaminoalkyl, aryl, heteroaryl, and heterocyclic groups are each unsubstituted or substituted by one or more substituents, each substituent being independently selected from halogens, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cycloalkyl, cycloalkenyl, cycloalkynyl, -C(O)OH, -NH2, -NHalkyl, and -N(alkyl)2; preferably, the C 1-6 Alkyl, C 3-10 cycloalkyl, C 1-6 Alkoxy, single C 1-6 Alkylamino, diC 1-6 Alkylamino, C 1-6 Alkylthio, C 1-6 Alkyl thioc 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl, mono-C 1-6 Alkylamino C 1-6 Alkyl, diC 1-6 Alkylamino C 1-6 The alkyl, aryl, heteroaryl, and heterocyclic groups are each unsubstituted or substituted with one or more substituents, each independently selected from halogens, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 3-10 cycloalkyl, C 5-10 Cycloalkenyl, C 4-10 Cycloalkynyl, -C(O)OH, -NH2, -NHC 1-6 Alkyl and -N(C) 1-6 Alkyl)2; - R 3a Selected from hydrogen, alkyl, cycloalkyl, alkoxy, (mono or di)alkylamino, alkoxyalkyl, alkylthioalkyl, (mono or di)alkylaminoalkyl, hydroxyalkyl, and aminoalkyl; preferably, R 3a Selected from hydrogen, C 1-6 Alkyl, C 3-10 cycloalkyl, C 1-6 Alkoxy, single C 1-6 Alkylamino, diC 1-6 Alkylamino, C 1-6 Alkoxy C 1-6 Alkyl, C 1-6 Alkyl thioc 1-6 Alkyl, mono-C 1-6 Alkylamino C 1-6 Alkyl, diC 1-6 Alkylamino C 1-6 Alkyl, hydroxyl C 1-6 Alkyl and amino C 1-6 alkyl; - R 3b Selected from hydrogen and alkyl; preferably, R 3b Selected from hydrogen and C 1-6 alkyl; - R 3c Selected from hydrogen, alkyl, alkoxyalkyl, alkylthioalkyl, (mono- or di)alkylaminoalkyl, hydroxyalkyl, hydroxycarbonylalkyl, and aminoalkyl; preferably, R 3c Selected from hydrogen, C 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl, C 1-6 Alkyl thioc 1-6 Alkyl, mono-C 1-6 Alkylamino C 1-6 Alkyl, diC 1-6 Alkylamino C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, hydroxycarbonyl C 1-6 Alkyl and amino C 1-6 alkyl; - R 3dSelected from alkyl, cycloalkyl, alkoxyalkyl, alkoxy, (mono or di)alkylamino, (mono or di)alkylaminoalkyl, alkylthio, alkylthioalkyl, hydroxyalkyl, and aminoalkyl; preferably, R 3d Selected from C 1-6 Alkyl, C 3-10 cycloalkyl, C 1-6 Alkoxy C 1-6 Alkyl, C 1-6 Alkoxy, single C 1-6 Alkylamino, diC 1-6 Alkylamino, mono-C 1-6 Alkylamino C 1-6 Alkyl, diC 1-6 Alkylamino C 1-6 Alkyl, C 1-6 Alkylthio, C 1-6 Alkyl thioc 1-6 Alkyl, hydroxyl C 1-6 Alkyl and amino C 1-6 alkyl; - R 3f and R 3g Each is independently selected from hydrogen, alkyl, cycloalkyl, hydroxyalkyl, -NH2, and aminoalkyl; preferably, R 3f and R 3g Each is independently selected from hydrogen and C. 1-6 Alkyl, C 3-10 Cycloalkyl, hydroxy C 1-6 Alkyl, -NH2 and amino C 1-6 alkyl; - R 3h Selected from hydrogen and alkyl; preferably, R 3h Selected from hydrogen and C 1-6 alkyl; - R 3i Selected from hydrogen, alkyl, cycloalkyl, and aryl, wherein each alkyl, cycloalkyl, and aryl group is optionally further substituted with one or more halogens; preferably, R 3i Selected from hydrogen, C 1-6 Alkyl, C 3-10 cycloalkyl and aryl, wherein each C 1-6 Alkyl, C 3-10 The cycloalkyl and aryl groups may optionally be further substituted with one or more halogens; - m is an integer selected from 0, 1, 2, 3 or 4; - p is an integer selected from 0, 1, or 2; - q is an integer selected from 0, 1, or 2; or - v is an integer selected from 0, 1, or 2.

[0144] The compound according to any one of the formula, statement, embodiment or claim, wherein R 3 Selected from hydrogen, alkyl, -NR 3x R 3y and -OR 3z Preferably, R 3 Selected from hydrogen, C 1-6 Alkyl, -NR 3x R 3y and -OR 3z ,in: - The alkyl group is optionally substituted by one, two, or three substituents, each of which is independently selected from halogens, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, alkylthio, cycloalkyl, cycloalkenyl, cycloalkynyl, -C(O)OH, -C(O)R 3i -C(O)-O-CH2-O-CO-R 3i -PO-(OR) 3i )2, -NH2, -NHalkyl and -N(alkyl)2; preferably, C 1-6 The alkyl group is optionally substituted with one, two, or three substituents, each of which is independently selected from halogens, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 1-6 Alkylthio, C 3-10 cycloalkyl, C 5-10 Cycloalkenyl, -C(O)OH, -C(O)R 3i -C(O)-O-CH2-O-CO-R 3i -PO-(OR) 3i )2、-NH2、-NHC 1-6 Alkyl and -N(C) 1-6 Alkyl)2; - R 3x R 3y and R 3z Each is independently selected from hydrogen, alkyl, alkenyl, ynyl, cycloalkyl, and heterocyclic groups; preferably, R 3x R 3y and R 3zEach is independently selected from hydrogen and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 cycloalkyl and heterocyclic groups; Each of the alkyl, alkenyl, alkynyl, cycloalkyl, and heterocyclic groups is optionally further substituted by one, two, or three substituents, said substituents being independently selected from halogens, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, alkoxy, alkylthio, cycloalkyl, cycloalkenyl, cycloalkynyl, -C(O)OH, -C(O)R 3i -C(O)-O-CH2-O-CO-R 3i -PO-(OR) 3i )2, -NH2, -NHalkyl and -N(alkyl)2; preferably, each C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 The cycloalkyl and heterocyclic groups are optionally further substituted by one, two, or three substituents, said substituents being independently selected from halogens, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 3-10 cycloalkyl, C 5-10 Cycloalkenyl, -C(O)OH, -C(O)R 3i -C(O)-O-CH2-O-CO-R 3i -PO-(OR) 3i )2、-NH2、-NHC 1-6 Alkyl and -N(C) 1-6 Alkyl)2; - Or, R 3x and R 3yTogether they form a heterocycle optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cycloalkyl, cycloalkenyl, cycloalkynyl, -C(O)OH, -NH2, -NHalkyl, and -N(alkyl)2; preferably, R 3x and R 3y Together they form a heterocycle optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 3-10 cycloalkyl, C 5-10 Cycloalkenyl, C 5-10 Cycloalkynyl, -C(O)OH, -NH2, -NHC 1-6 Alkyl and -N(C) 1-6 Alkyl)2.

[0145] The compound according to any one of the formula, statement, embodiment or claim, wherein R 3 Selected from hydrogen, alkyl, -NR 3x R 3y and -OR 3z Preferably, R 3 Selected from hydrogen, C 1-6 Alkyl, -NR 3x R 3y and -OR 3z ,in: - The alkyl group is optionally substituted by one, two, or three substituents, each of which is independently selected from halogens, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, alkylthio, cycloalkyl, cycloalkenyl, cycloalkynyl, -C(O)OH, -C(O)R 3i -C(O)-O-CH2-O-CO-R 3i -PO-(OR) 3i )2, -NH2, -NHalkyl and -N(alkyl)2; preferably, C1-6 The alkyl group is optionally substituted with one, two, or three substituents, each of which is independently selected from halogens, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 1-6 Alkylthio, C 3-10 cycloalkyl, C 5-10 Cycloalkenyl, -C(O)OH, -C(O)R 3i -C(O)-O-CH2-O-CO-R 3i -PO-(OR) 3i )2、-NH2、-NHC 1-6 Alkyl and -N(C) 1-6 Alkyl)2; - R 3x R 3y and R 3z Each is independently selected from hydrogen, alkyl, alkenyl, ynyl, cycloalkyl, and heterocyclic groups; preferably, R 3x R 3y and R 3z Each is independently selected from hydrogen and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 cycloalkyl and heterocyclic groups; Each of the alkyl, alkenyl, alkynyl, cycloalkyl, and heterocyclic groups is optionally further substituted by one, two, or three substituents, said substituents being independently selected from halogens, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, alkoxy, alkylthio, cycloalkyl, cycloalkenyl, cycloalkynyl, -C(O)OH, -C(O)R 3i -C(O)-O-CH2-O-CO-R 3i -PO-(OR) 3i )2, -NH2, -NHalkyl and -N(alkyl)2; preferably, each C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10The cycloalkyl and heterocyclic groups are optionally further substituted by one, two, or three substituents, said substituents being independently selected from halogens, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 3-10 cycloalkyl, C 5-10 Cycloalkenyl, -C(O)OH, -C(O)R 3i -C(O)-O-CH2-O-CO-R 3i -PO-(OR) 3i )2、-NH2、-NHC 1-6 Alkyl and -N(C) 1-6 Alkyl)2; - Or, R 3x and R 3y Together they form a heterocycle optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cycloalkyl, cycloalkenyl, cycloalkynyl, -C(O)OH, -NH2, -NHalkyl, and -N(alkyl)2; preferably, R 3x and R 3y Together they form a heterocycle optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 3-10 cycloalkyl, C 5-10 Cycloalkenyl, C 5-10 Cycloalkynyl, -C(O)OH, -NH2, -NHC 1-6 Alkyl and -N(C) 1-6 Alkyl)2.

[0146] The compound according to any one of the formula, statement, embodiment or claim, wherein R 3 Selected from hydrogen, amino, -NHC 1-6 Alkyl, -N(C) 1-6 Alkyl)2, -NR 3a -(CR 3f R 3g ) q -C(O)NR 3a R 3b -NR 3a -(CR 3f R 3g ) q -CO2R 3c -NR 3a -(CR 3f R 3g ) q -OR 3c -NR 3a -(CR 3f R 3g ) q -PO(OR 3i )2、-NR 3a -(CR 3f R 3g ) q -NR 3a C(O)R 3d -OR 3c 、-(CR 3f R 3g ) q -OR 3c , , Oxygenation, -NR 3a S(O)2R 3d -NR 3a C(O)R 3d hydroxyl group, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylamino, diC 1-6 Alkylamino and C 3-12 cycloalkyl; Wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 1-6 Alkylamino, diC 1-6 Alkylamino or C 3-12Each cycloalkyl group is either unsubstituted or substituted with one or more substituents, each substituent being independently selected from halogens, -OH, =O, -CF3, -CHF2, -OCF3, -OCHF2, cyano, nitro, C 1-4 Alkyl, Halogenated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, hydroxy C 1-4 Alkyl, C 3-10 Cycloalkyl, heterocyclic, -C(O)OH, -PO-(OH)2, -PO-(OC) 1-4 Alkyl group 2, -NH2, -NHC 1-4 Alkyl and -N(C) 1-4 Alkyl)2; Cyclone A is selected from aryl, C 3-12 Cycloalkyl, heterocyclic, and heteroaryl; preferably, ring A is selected from: aryl, C 3-10 cycloalkyl, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ; Y represents NH and NC. 1-6 Alkyl or O; Each R 6 Independently selected from hydrogen, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkoxy C 1-6 Alkyl, -(CR) 3f R3g ) q -O-(CR 3f R 3g ) v -CO2R 3c hydroxyl C 1-6 Alkyl, -CO2R 3c 、-(CR 3f R 3g ) q -O-(CR 3f R 3g ) v -Heteroaryl, -CONR 3a S(O)2R 3d -C(O)R 3d -C(O)NR 3a R 3b Oxygenation and -OR 3c , Wherein C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkoxy C 1-6 Alkyl, hydroxyl C 1-6 Each alkyl group is either unsubstituted or substituted with one or more substituents, each substituent being independently selected from halogens, -OH, =O, -CF3, -CHF2, -OCF3, -OCHF2, cyano, C 1-4 Alkyl, Halogenated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, hydroxy C 1-4 Alkyl, -C(O)OH, -NH2, -NHalkyl and -N(alkyl)2; R 3a Selected from hydrogen, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, amino C 1-6 Alkyl group, -SO2-C 1-6 alkyl; R 3b Selected from hydrogen, C 1-6 alkyl; R 3c Selected from hydrogen, C 1-6 Alkyl, Halogenated C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, hydroxycarbonyl C 1-6 Alkyl, amino C 1-6 alkyl; R 3d Selected from C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, amino C 1-6 alkyl; R 3f and R 3g Each is independently selected from hydrogen and C. 1-6 Alkyl, hydroxyl C 1-6 Alkyl group, -NH2; R 3h It is hydrogen; R 3i It is hydrogen or C 1-6 alkyl; m is an integer selected from 0, 1, 2 or 3; p is an integer selected from 0 or 1; q is an integer selected from 0, 1, or 2; v is an integer selected from 0, 1, or 2.

[0147] The compound according to any one of the formula, statement, embodiment or claim, wherein R 3 Selected from -NH2, -NHMe, and -N(Me)2. A compound according to any one of the formulas, statements, embodiments, or claims, wherein R... 3 Not oxidized. A compound according to any one of the formulas, statements, embodiments, or claims, wherein R... 3 It is not hydrogen.

[0148] The compound according to any one of the formula, statement, embodiment or claim, wherein W is -CO-.

[0149] The compound according to any one of the formula, statement, embodiment or claim, wherein

[0150] - L is -CR Lg R Lh -or-NR Lb -; - R Lg Selected from hydrogen, alkyl, hydroxyalkyl, -NR La R Lb Aminoalkyl, heteroalkyl, haloalkyl and -C(O)NR La R Lb ; - R Lh Selected from hydrogen or alkyl; - R La Selected from hydrogen or alkyl; and - R Lb Selected from hydrogen or alkyl groups.

[0151] The compound according to any one of the formula, statement, embodiment or claim, wherein

[0152] - R Lg Selected from hydrogen, alkyl, hydroxyalkyl, -NRLa R Lb Aminoalkyl, alkoxy, alkylamino, dialkylamino, alkylaminoalkyl, dialkylaminoalkyl, thioalkyl, alkoxyalkyl, alkylthioalkyl, haloalkyl, -C(O)NR La R Lb And deuterium; preferably, R Lg Selected from hydrogen, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, -NR La R Lb amino C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylamino, diC 1-6 Alkylamino, C 1-6 Alkylamino C 1-6 Alkyl, diC 1-6 Alkylamino C 1-6 Alkyl, Thio C 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl, C 1-6 Alkyl thioc 1-6 Alkyl, Halogenated C 1-6 Alkyl, -C(O)NR La R Lb and deuterium; - R Lh Selected from hydrogen, deuterium, or alkyl; preferably, R Lh Selected from hydrogen, deuterium, or C 1-6 alkyl; - R La Selected from hydrogen or alkyl; preferably, R La Selected from hydrogen or C 1-6 Alkyl; and - R Lb Selected from hydrogen or alkyl; preferably, R Lb Selected from hydrogen or C 1-6 alkyl.

[0153] The compound according to any one of the formula, statement, embodiment or claim, wherein L is -CR Lg R Lh -, R Lg It is hydrogen, deuterium or C 1-4 Alkyl (e.g., methyl), and R Lh It is hydrogen or deuterium. In another embodiment, L is methylene or deuterated methylene (-CD2-).

[0154] In some implementations, for example when L is -CR Lg R Lh -When, X is selected from -OR Xcand -NR Xa R Xb In some implementations (e.g., but not limited to, when L is -CR) Lg R Lh -, and / or X is selected from -OR Xc and -NR Xa R Xb Or, when the compound has structural formula (VI) or (VII)). - R Xa Selected from hydrogen, alkyl, alkoxyalkyl, aminoalkyl, hydroxyalkyl, cycloalkyl, and heterocyclic groups. The alkyl, alkoxyalkyl, aminoalkyl, hydroxyalkyl, cycloalkyl and heterocyclic groups are each unsubstituted or substituted by one or more substituents, each of which is independently selected from hydroxyalkyl, heteroaryl, heterocyclic, alkyl, cycloalkyl, -OH, =O, halogen, -SH, =S, -C(O)OH, O-alkyl, alkoxy, -NH2, -NHalkyl and -N(alkyl)2; - R Xb Selected from hydrogen, alkyl, aminoalkyl, hydroxyalkyl, and cycloalkyl. The alkyl, aminoalkyl, hydroxyalkyl, and cycloalkyl groups are each unsubstituted or substituted by one or more substituents, each of which is independently selected from hydroxyalkyl, alkyl, cycloalkyl, -OH, =O, halogen, -SH, =S, -C(O)OH, alkoxy, -NH2, -NHalkyl, and -N(alkyl)2; - Each R Xc Selected from hydrogen, alkyl, alkoxyalkyl, aminoalkyl, hydroxyalkyl, cycloalkyl, and heterocyclic groups. The alkyl, alkoxyalkyl, aminoalkyl, hydroxyalkyl, cycloalkyl, and heterocyclic groups are each unsubstituted or substituted by one or more substituents, each of which is independently selected from -CONR. Xa R Xb Hydroxyalkyl, heteroaryl, heterocyclic, alkyl, deuterium, cycloalkyl, -OH, =O, halogen, -SH, =S, -C(O)OH, O-alkyl, alkoxy, -NH2, -NHalkyl and -N(alkyl)2.

[0155] The compound according to any one of the formula, statement, embodiment or claim, wherein X is selected from -OR Xc -NH2, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , amino C 1-6 Alkyl, -C(O)ONH2 and hydroxyl C 1-6 Alkyl; wherein each of the groups is unsubstituted or substituted by one or more substituents, each substituent being independently selected from hydroxyl C 1-6 Alkyl, -C(O)NR Xa R Xb heteroaryl, heterocyclic, C 1-6 Alkyl-substituted heterocyclic groups, C 1-6 Alkyl, C 3-10 Cycloalkyl, -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, -C(O)OH, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, hydroxyl C 1-6 Alkoxy, amino C 1-6 Alkoxy, (mono or di)C 1-6 Alkylamino C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl and -N(C) 1-6 Alkyl)2.

[0156] The compound according to any one of the formula, statement, embodiment or claim, wherein L is a single bond and X is a heterocyclic or heteroaryl group, wherein the heterocyclic and heteroaryl groups are optionally substituted by one or more substituents, the substituents being independently selected from hydroxyl C 1-6 Alkyl, -C(O)NR Xa R Xb heteroaryl, heterocyclic, C 1-6 Alkyl-substituted heterocyclic groups, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Cycloalkyl, -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, -C(O)OH, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, hydroxy C 1-6 Alkoxy, amino C 1-6 Alkoxy, monoamino C 1-6 Alkoxy, diamino C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl and -N(C) 1-6 Alkyl)2; and wherein R Xa and R Xb As defined in any of the embodiments, statements or claims described herein.

[0157] In some embodiments, L is a single bond and X is a heterocyclic or heteroaryl group, wherein the heterocyclic or heteroaryl group is optionally composed of one or more substituents R. 7 Replace, where each R 7 Independently selected from hydroxyl C 1-6 Alkyl, -C(O)NR Xa R Xb heteroaryl, heterocyclic, C 1-6 Alkyl-substituted heterocyclic groups, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Cycloalkyl, -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, -C(O)OH, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, hydroxy C 1-6 Alkoxy, amino C 1-6 Alkoxy, monoamino C 1-6 Alkoxy, diamino C1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl and -N(C) 1-6 Alkyl)2; and wherein R Xa and R Xb As defined in any of the embodiments, statements or claims described herein.

[0158] In some implementation schemes, - Partial LX conforms ; - Z is either N or O; - Ring B is a heterocyclic group or a heteroaryl group; - u is 0, 1, 2, or 3; and - Each R 7 Independently selected from hydroxyalkyl, -C(O)NR Xa R Xb Heteroaryl, heterocyclic, heterocyclic substituted with one or more alkyl groups, alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, cycloynyl, -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, -C(O)OH, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, hydroxyalkoxy, aminoalkoxy, (mono or di)alkylaminoalkoxy, -NH2, -NHalkyl and -N(alkyl)2; preferably, each R 7 Independently selected from hydroxyl C 1-6 Alkyl, -C(O)NR Xa R Xb heteroaryl, heterocyclic, via one or more C 1-6 Alkyl-substituted heterocyclic groups, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 cycloalkyl, C 5-10 Cycloalkenyl, C 5-10 Cycloalkyne, -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, -C(O)OH, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, hydroxyl C 1-6 Alkoxy, amino C 1-6 Alkoxy, single C 1-6 Alkylamino C 1-6 Alkoxy, diC 1-6 Alkylamino C 1-6Alkoxy, -NH2, -NHC 1-6 Alkyl and -N(C) 1-6 Alkyl)2.

[0159] In some implementations, for example when W is -CO- and / or L is a single bond, X is optionally composed of one or more R bonds. 7 Substituted heteroaryl groups.

[0160] In some implementations, part-LX conforms to Ring B is selected from , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and .

[0161] In some implementations, u is 0, 1, or 2.

[0162] In some implementations, each R 7 It is independently selected from hydroxyalkyl, alkyl, -OH, halogen, -SH, =S, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, hydroxyalkoxy, aminoalkoxy, (mono- or di)alkylaminoalkoxy, -NH2, -NHalkyl and -N(alkyl)2.

[0163] In some implementations, each R 7 Selected independently from C 1-4 Alkyl (methyl), halogen, C 1-4 Alkoxy (methoxy), halogenated C 1-4 Alkoxy, hydroxy C 1-4 Alkyl, hydroxyl C 1-4 Alkoxy, C 1-4 Aminoalkoxy, (mono or di)C 1-4 Alkylamino C 1-4 Alkoxy, -NH2, -NH(C) 1-4 alkyl) and -N(C) 1-4 Alkyl)2.

[0164] The compound according to any one of the formula, statement, embodiment or claim, wherein

[0165] - X is selected from -OR Xc -NR Xa R Xb heteroaryl, heterocyclic, aminoalkyl, -SO2R Xd -CONR Xa R Xb -C(O)OR Xc , hydroxyalkyl and alkyl; wherein the heterocyclic group, heteroaryl group and alkyl group are each unsubstituted or substituted by one or more substituents, each substituent being independently selected from halogen, -OH, =O, alkoxy, hydroxyalkyl, alkyl, haloalkyl, amino, mono- or dialkylamino, -CONR Xa R Xb X is a heteroaryl and a carboxyl group; preferably, X is selected from -OR Xc -NR Xa R Xb heteroaryl, heterocyclic, amino C 1-6 Alkyl, -SO2R Xd -CONR Xa R Xb -C(O)OR Xc hydroxyl C 1-6 Alkyl and C 1-6 Alkyl groups; wherein the heterocyclic group, heteroaryl group, and C14 group are present. 1-6 Each alkyl group is either unsubstituted or substituted with one or more substituents, each substituent being independently selected from halogens, -OH, =O, C. 1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 1-6 Alkyl, Halogenated C 1-6 Alkyl, amino, mono-C 1-6 Alkylamino, diC 1-6Alkylamino, -CONR Xa R Xb heteroaryl and carboxyl groups; - R Xa Selected from hydrogen, hydroxyalkyl, alkyl, or heteroalkyl (alkoxyalkyl); preferably, R Xa Selected from hydrogen, hydroxyl C 1-6 Alkyl, C 1-6 Alkyl or C 1-6 Alkoxy C 1-6 alkyl; - R Xb Selected from hydrogen or alkyl; preferably, R Xb Selected from hydrogen or C 1-6 alkyl; - Each R Xc Selected from hydrogen, alkyl, aminoalkyl, hydroxyalkyl, cycloalkyl, heteroalkyl (alkoxyalkyl, mono- or dialkylaminoalkyl) and heteroarylalkyl, wherein the alkyl and cycloalkyl groups are each unsubstituted or substituted by one or more substituents, each of which is independently selected from -CONR. Xa R Xb -NH2 or hydroxyalkyl; preferably, each R Xc Selected from hydrogen, C 1-6 Alkyl, amino C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, C 3-10 cycloalkyl, C 1-6 Alkoxy C 1-6 Alkyl, mono-C 1-6 Alkylamino C 1-6 Alkyl, diC 1-6 Alkylamino C 1-6 Alkyl and heteroaryl C 1-6 Alkyl, wherein the C 1-6 Alkyl and C 3-10 The cycloalkyl groups are either unsubstituted or substituted with one or more substituents, each of which is independently selected from -CONR. Xa R Xb -NH2 or hydroxyl C 1-6 Alkyl; and - R Xd Selected from alkyl, cycloalkyl, and heteroaryl groups; preferably, R Xd Selected from C 1-6 Alkyl, C 3-10 Cycloalkyl and heteroaryl groups.

[0166] The compound according to any one of the formula, statement, embodiment or claim, wherein

[0167] - W stands for -CO-; - L is either -CH2- or -NH-; and - X is selected from -OR Xc -NR Xa R Xb heteroaryl, heterocyclic, aminoalkyl, -SO2R Xd -CONR Xa R Xb -C(O)OR Xc , hydroxyalkyl and alkyl; wherein the heterocyclic group, heteroaryl group and alkyl group are each unsubstituted or substituted by one or more substituents, each substituent being independently selected from halogen, -OH, =O, alkoxy, hydroxyalkyl, alkyl, haloalkyl, amino, mono- or dialkylamino, -CONR Xa R Xb heteroaryl and carboxyl groups; - R Xa and R Xc Each of the following groups is independently selected from hydrogen, alkyl, hydroxyalkyl, aminoalkyl, heteroalkyl, cycloalkyl, heteroaryl, heterocyclic, heteroarylalkyl, and heterocyclic alkyl; wherein the alkyl, hydroxyalkyl, aminoalkyl, heteroalkyl, cycloalkyl, heteroaryl, heterocyclic, heteroarylalkyl, and heterocyclic alkyl groups are either unsubstituted or substituted by one or more substituents, and each substituent is independently selected from -CONR. Xa R Xb Hydroxylalkyl, heteroaryl, heterocyclic, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, -C(O)OH, O-alkyl, haloalkyl, alkoxy, haloalkoxy, -NH2, -NHalkyl and -N(alkyl)2; - R Xb Selected from hydrogen or alkyl; and - R Xd Selected from alkyl, hydroxyalkyl, aminoalkyl, heteroalkyl, cycloalkyl, heteroaryl, heterocyclic, heteroarylalkyl, and heterocyclicalkyl; The alkyl, hydroxyalkyl, aminoalkyl, heteroalkyl, cycloalkyl, heteroaryl, heterocyclic, heteroarylalkyl, and heterocyclic alkyl groups are each unsubstituted or substituted by one or more substituents, each of which is independently selected from -CONR. Xa R XbHydroxylalkyl, heteroaryl, heterocyclic, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, -C(O)OH, O-alkyl, haloalkyl, alkoxy, haloalkoxy, -NH2, -NHalkyl and -N(alkyl)2.

[0168] The compound according to any one of the formula, statement, embodiment or claim, wherein

[0169] - Each R 4 Independently selected from halogens, -CF3, -OCF3, -CHF2, -OCHF2, alkyl groups, -OR 4c , haloalkyl, -CN, haloalkoxy, hydroxyalkyl, heteroalkyl (alkoxyalkyl) and cycloalkyl, Or, two Rs 4 Together with the carbon atom it is attached to, it can form cycloalkyl or cycloalkenyl groups; - R 4c Selected from alkyl, alkoxy, hydroxyalkyl, and haloalkyl groups; and - n is an integer selected from 1, 2, 3 or 4.

[0170] The compound according to any one of the formula, statement, embodiment or claim, wherein

[0171] - Each R 4 Independently selected from -CF3, -OCF3, -CHF2, -B(OH)2, -O-SO2-F, -SO2-F, -OCHF2, alkyl, -OR 4c , haloalkyl, -CN, haloalkoxy, hydroxyalkyl, haloalkoxy, hydroxyalkyl, alkoxyC 1-6 Alkyl and cycloalkyl; preferably, each R 4 Independently selected from halogens, -CF3, -OCF3, -CHF2, -OCHF2, -B(OH)2, -O-SO2-F, -SO2-F, alkyl groups, -OR 4c -NR 4a C(O)R 4c Halogenated C 1-6 Alkyl, -CN, Halogenated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl and C 3-10 cycloalkyl; - Or, two Rs 4Together with the carbon atom to which it is attached, it can form a cycloalkyl, cycloalkenyl, or heterocyclic group; preferably, the two R groups... 4 Together with the carbon atom it is attached to, it can form C 3-10 cycloalkyl, C 5-10 Cycloalkenyl or heterocyclic groups; - R 4c Selected from alkyl, deuterated alkyl, alkoxyalkyl, hydroxyalkyl, and haloalkyl; preferably, R 4c Selected from C 1-6 Alkyl, -CD3, C 1-6 Alkoxy C 1-6 Alkyl, hydroxyl C 1-6 Alkyl and Halogenated C 1-6 Alkyl; and - n is an integer selected from 1, 2, 3 or 4.

[0172] The compound according to any one of the formula, statement, embodiment or claim, wherein R 5 Selected from hydrogen, alkyl, haloalkyl, heteroalkyl (e.g., alkoxyalkyl), hydroxyalkyl, aminoalkyl, cycloalkylalkyl, and heterocyclic alkyl; preferably, R 5 Selected from hydrogen, C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl, monoamino C 1-6 Alkyl, diamino C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, amino C 1-6 Alkyl, C 3-10 Cycloalkylalkyl and heterocyclic alkyl.

[0173] In some implementation schemes, R 5 Selected from hydrogen, alkyl, alkoxyalkyl, hydroxyalkyl, aminoalkyl; preferably, R 5 Selected from hydrogen, C 1-4 Alkyl, C 1-4 Alkoxy C 1-4 Alkyl, hydroxyl C 1-4 Alkyl, amino C 1-4 alkyl.

[0174] The compound according to any one of the formulas, statements, embodiments or claims has a structural formula (II), (III) or (IV). (II) (III) (IV) Where R 1 R 2 R 3 R4 R 5 , n, L and X each have the same meaning as defined in any formula, statement, embodiment or claim herein.

[0175] The compound according to any one of the formulas, statements, embodiments or claims has the structural formula (IIa), (IIIa), (IVa), (IIb), (IIIb), (IVb), (IIc), (IIIc), (IVc), (IId), (IIId), (IVd), (IIe), (IIIe) or (IVe). (IIa) (IIIa) (IVa) (IIb) (IIIb) (IVb) (IIc) (IIIc) (IVc) (IId) (IIId) (IVd) (IIe) (IIIe) (IVe) in - r is an integer selected from 0, 1, 2 or 3; s is an integer selected from 0, 1 or 2; t is an integer selected from 0 or 1; - R 4.1 R 4.2 R 4.3 R 4.4 Each has its own independent R 4 The meaning; and - where R 1 R 2 R 3 R 4 R 5 L and X each have the same meaning as defined in any of the formulas, statements, embodiments or claims herein.

[0176] In some implementation schemes, R 4.1 It is a halogen, such as chlorine. In some embodiments, R 4.3 C 1-4Alkyl groups, such as methoxy groups. In a further embodiment, the compound conforms to formula (IIc), (IId), (IVc), or (IVd), wherein R 4.1 For halogen (chlorine), R 4.3 C 1-4 Alkoxy (methoxy), R 4.2 (If it exists) is a halogen, s is 0 and t is 0.

[0177] The compound according to any one of the formulas, statements, embodiments or claims has a structural formula (V), (VI) or (VII). (V) (VI) (VII) Where R 1 R 3 R 4 n, R Xa R Xb R Xc R Lg X and X each have the same meaning as defined in any of the formulas, statements, embodiments or claims herein.

[0178] The compound according to any one of the formulas, statements, embodiments or claims has the structural formula (Va), (VIa), (VIIa), (Vb), (VIb), (VIIb), (Vc), (VIc), (VIIc), (Vd), (VId), (VIId), (Ve), (VIe) or (VIIe). (Va) (VIa) (VIIa) (Vb) (VIb) (VIIb) (Vc) (VIc) (VIIc) (Vd) (VId) (VIId) (VIIe) (Ve) (VIe) in - r is an integer selected from 0, 1, 2 or 3; preferably, r is an integer selected from 1 or 2; - s is an integer selected from 0, 1 or 2; preferably, s is an integer selected from 0 or 1; - t is an integer selected from 0 or 1; - R 4.1 R 4.2 R 4.3 R 4.4 Each has its own independent R 4 The meaning; and - where R 1 R 3 R 4 R Xa R Xb R Xc R Lg X and each have the same meaning as defined in any formula, statement, embodiment or claim.

[0179] In some embodiments, the compound conforms to the formula (Vc), (VIc), (Vd), or (VId), wherein R 4.1 For halogen (chlorine), R 4.3 C 1-4 Alkoxy (methoxy), R 4.2 (If it exists) is a halogen, s is 0 and t is 0, and R is a halogen. Xa R Xb R Xc R Lg X has the same meaning as defined in any formula, statement, embodiment, or claim.

[0180] The compound according to any one of the formulas, statements, embodiments or claims has the structural formulas (VIII), (IX), (X), (XI) and (XII). (VIII) (IX) (X) (XI) (XII) Where R 1 R 3 R 4 , n and R Lg Each has the same meaning as defined in any of the formulas, statements, embodiments or claims herein.

[0181] The compound according to any one of the formulas, statements, embodiments or claims has the structural formula (VIIIa), (IXa), (Xa), (VIIIb), (IXb), (Xb), (VIIIc), (IXc), (Xc), (VIIId), (IXd), (Xd), (VIIIe), (IXe) or (Xe). (VIIIa) (IXa) (Xa) (VIIIb) (IXb) (Xb) (VIIIc) (IXc) (Xc) (VIIId) (IXd) (Xd) (VIIIe) (IXe) (Xe) in - r is an integer selected from 0, 1, 2 or 3; s is an integer selected from 0, 1 or 2; t is an integer selected from 0 or 1; - R 4.1 R 4.2 R 4.3 R 4.4 Each has its own independent R 4 The meaning; and - where R 1 R 3 R 4 and R Lg Each has the same meaning as defined in any of the formulas, statements, embodiments or claims herein.

[0182] A compound having the structures shown in (VIIIa), (IXa), (VIIIb), (IXb), (VIIIc), (IXc), (VIIId), and (IXd) is also provided, wherein...

[0183] - r is an integer selected from 1, 2, or 3; s is an integer selected from 0, 1, or 2; t is an integer selected from 0 or 1; - R4.1 R 4.2 R 4.3 Each has its own independent R 4 The meaning; and - where R 1 R 3 R 4 and R Lg Each has the same meaning as defined in any of the formulas, statements, embodiments or claims herein.

[0184] The compound according to any one of the formulas, statements, embodiments or claims has the structural formula (XIII), (XIIIa), (XIV), (XIVa), (XV), (XVa) or (XVI). (XIII) (XIIIa) (XIV) (XIVa) (XV) (XVa) (XVI) Among them, W, part R 1 R 2 R 3 R 3a R 3b R 4 n, R 7 "u" and "u" each have the same meaning as defined in any of the formulas, statements, embodiments or claims herein.

[0185] The compound according to any one of the formulas, statements, embodiments or claims has the structural formula (XIIIb), (XIIIc), (XIIId), (XIIIe) or (XIIIf). (XIIIb) (XIIIc) (XIIId) (XIIIe) (XIIIf) in - r is an integer selected from 0, 1, 2 or 3; s is an integer selected from 0, 1 or 2; t is an integer selected from 0 or 1; - R 4.1 R 4.2 R 4.3 R4.4 Each has its own independent R 4 The meaning; and - some of them R 1 R 2 R 3 R 3a R 3b R 4 n, R 7 "u" and "u" each have the same meaning as defined in any of the formulas, statements, embodiments or claims herein.

[0186] In specific embodiments, the compounds of the present invention are selected from the compounds listed in Table 1 or the compounds described by their chemical names as shown in Table 1 or the examples.

[0187] A pharmaceutical composition comprising a compound according to any one of the formulas, statements, embodiments or claims herein, and a pharmaceutically acceptable carrier, solvent, adjuvant or diluent.

[0188] The compound according to any one of the formulas, statements, embodiments or claims herein, or the pharmaceutical composition according to any one of the statements, embodiments or claims herein, is used as a medicine.

[0189] The compounds used in this invention may also exist in their stereochemical isomers, defined as all possible compounds consisting of identical atoms linked by the same bond sequence but having different three-dimensional structures, and these structures are not interchangeable. Unless otherwise stated or indicated, the chemical name of a compound covers a mixture of all possible stereochemical isomers that the compound may have. Such mixtures may contain all diastereomers and / or enantiomers of the basic molecular structure of the compound. All stereochemical isomers of the compounds used in this invention, whether in pure form or in mixtures thereof, are intended to be covered within the scope of this invention, including any racemic mixture or racemate.

[0190] More generally, this invention relates to compounds of the formulas described herein, and embodiments, statements, and aspects thereof, which can be used as biologically active pharmaceutical or diagnostic agents. Any use mentioned in this invention may be limited to non-medical, non-therapeutic, non-diagnostic, or exclusive in vitro uses, or uses related to in vitro animal cells.

[0191] The disclosed compounds are small molecule cGAS inhibitors or modulators. Small molecule cGAS inhibitors can be used, for example, to treat inflammatory conditions, including but not limited to inflammatory diseases, autoimmune diseases, allergic diseases, inflammation of specific tissues or organs, fibrotic diseases, and any other conditions involving inflammation, particularly those related to cGAS activity or activation. In specific embodiments, the compounds of the present invention can be used to prevent or treat inflammatory, allergic, or autoimmune diseases or diseases with inflammatory components, such as systemic lupus erythematosus (SLE), cutaneous lupus erythematosus (CLE), lupus nephritis (LN), interferon disease, psoriasis, insulin-dependent diabetes mellitus (IDDM), vasculitis, scleroderma, Aicardi Goutieres syndrome, dermatomyositis, sepsis, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, Sjögren's syndrome (SS), age-related macular degeneration (AMD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer's disease, Huntington's disease, and Parkinson's disease. In other implementations, cGAS inhibitors can be used to treat cancers selected from, for example, bladder cancer, bone cancer, brain cancer, breast cancer, gastric cardia cancer, cervical cancer, colon cancer, colorectal cancer, esophageal cancer, fibrosarcoma, gastric cancer, gastrointestinal cancer, head and neck cancer, Kaposi's sarcoma, kidney cancer, pancreatic cancer, penile cancer, testicular germ cell cancer, thymoma, thymic carcinoma, lung cancer, ovarian cancer, or prostate cancer. In some implementations, solid tumors are characterized by cGAS overexpression, gene activation, etc. cGAS inhibitors can also be used to treat cancers that have developed resistance to prior treatments. For example, this may include treating cancers resistant to chemotherapy, targeted therapy, or immunotherapy. Small molecule cGAS inhibitors can also be used to treat metastatic cancers. In some cases, metastatic cancers are selected from metastatic uveal melanoma, esophageal cancer, liver cancer, breast cancer, hepatocellular carcinoma, lung adenocarcinoma, glioma, colon cancer, gastric cancer, medulloblastoma, ovarian cancer, esophageal squamous cell carcinoma, sarcoma, Ewing's sarcoma, head and neck cancer, prostate cancer, and meningioma.

[0192] The compounds of the present invention according to any one of the formulas, statements, embodiments, or claims herein, or the pharmaceutical compositions according to any one of the statements, embodiments, or claims herein, are used to treat or prevent cGAS-mediated diseases, particularly diseases in which the cGAS-STING pathway or type I interferon (IFN) response is abnormally activated. In a specific embodiment, the compounds of the present invention according to any one of the formulas, statements, embodiments, or claims herein, or the pharmaceutical compositions according to any one of the statements, embodiments, or claims herein, are used to treat inflammatory conditions or diseases selected from inflammatory diseases, autoimmune diseases, allergic diseases, fibrotic diseases, or cancer. More specifically, the compound or pharmaceutical composition according to any one of the formulas, statements, embodiments or claims herein, wherein the disease is selected from systemic lupus erythematosus (SLE), cutaneous lupus erythematosus (CLE), lupus nephritis (LN), interferon disease, psoriasis, insulin-dependent diabetes mellitus (IDDM), vasculitis, scleroderma, Aicardi Goutieres syndrome, dermatomyositis, sepsis, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, Sjögren's syndrome (SS), age-related macular degeneration (AMD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer's disease, Huntington's disease and Parkinson's disease.

[0193] The present invention also relates to a method for treating or preventing cGAS-mediated diseases in a subject in need, the method comprising administering to the subject in need of such treatment an effective amount of one or more compounds according to any one of the present invention, statements, embodiments, or claims, or a pharmaceutical composition according to any one of the present invention, embodiments, or claims. In a specific embodiment, the method relates to inhibiting the cGAS / STING pathway or abnormal type I interferon (IFN) response in a subject, the method comprising administering to the subject in need of such treatment an effective amount of one or more compounds according to any one of the present invention, statements, embodiments, or claims, or a pharmaceutical composition according to any one of the present invention, embodiments, or claims. In a specific embodiment, the present invention provides a method for treating an inflammatory condition, the method comprising administering to the subject in need of such treatment an effective amount of one or more compounds according to any one of the present invention, statements, embodiments, or claims, or a pharmaceutical composition according to any one of the present invention, embodiments, or claims. A method for treating or preventing a disease according to any one of the statements, embodiments, or claims herein is also provided, wherein the disease is selected from systemic lupus erythematosus (SLE), cutaneous lupus erythematosus (CLE), lupus nephritis (LN), interferon disease, psoriasis, insulin-dependent diabetes mellitus (IDDM), vasculitis, scleroderma, Aicardi Goutieres syndrome, dermatomyositis, sepsis, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, Sjögren's syndrome (SS), age-related macular degeneration (AMD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer's disease, Huntington's disease, and Parkinson's disease.

[0194] Small molecule cGAS inhibitors and pharmaceutical compositions comprising them may also be used in combination (simultaneous or subsequent) with other agents for the treatment of diseases such as inflammatory diseases, autoimmune diseases, allergic diseases, fibrotic diseases, neurodegenerative diseases, and cancer. Combined administration includes simultaneous administration, substantially simultaneous administration (e.g., at intervals of approximately 1, 5, 10, 15, 20, or 30 minutes), or sequential administration of the two active agents in any order. In some embodiments, combined administration may be achieved through co-formulation, i.e., preparing a single pharmaceutical composition comprising the two active agents. In other embodiments, the active agents may be formulated individually. In yet another embodiment, the active agents and / or adjuvants may be linked or conjugated together.

[0195] In some embodiments, the other drugs or therapeutic agents are anti-inflammatory agents, anti-fibrotic agents, or anti-allergic agents, or more generally selected from agents used to treat or prevent inflammatory conditions, such as anti-inflammatory agents, anti-fibrotic agents, anti-allergic agents / antihistamines, bronchodilators, β2 agonists / β receptor agonists, adrenergic agonists, anticholinergic agents, methotrexate, mycophenolate mofetil, leukotriene modulators, JAK inhibitors, anti-interleukin antibodies, cytokine / chemokine receptor modulators (i.e., cytokine receptor antagonists), anti-TNF antibodies (e.g., adalimumab (Humira™)), and anti-BAFF agents (e.g., belimumab and etanercept).

[0196] Examples of anti-inflammatory agents include nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids. Examples of NSAIDs include ibuprofen, naproxen, diclofenac, meloxicam, celecoxib, acetylsalicylic acid (aspirin™), indomethacin, mefenamic acid, and etoricoxib. Examples of corticosteroids include flunisolone, beclomethasone, triamcinolone, budesonide, fluticasone, mometasone, ciclesonide, roflureponide, and dexamethasone.

[0197] Antihistamines / anti-allergy agents may be selected, for example, from epinastine, cetirizine, azelastine, fexofenadine, levocabastine, loratadine, ebastine, desloratidine, and mizolastine. Antifibrotic agents may be selected, for example, from pirfenidone and tyrosine kinase inhibitors (e.g., nintedanib). β2 agonists / β-receptor agonists may be long-acting β2 agonists (LABA) or short-acting β agonists (SABA). Examples of anticholinergic agents include Bambuterol, Bitolterol, Carbuterol, Clenbuterol, Fenoterol, Formoterol, Flukloprin, Ibuterol, Pirbuterol, Procaterol, Reproterol, Salmeterol, Sulfonterol, Terbutalin, Tolubuterol, Olodaterol, and Salbutamol, with Olodaterol being particularly preferred. Anticholinergic agents include ipratropium bromide, tiotropium bromide, glycopyrronium bromide, and theophylline, with tiotropium bromide being especially preferred. Leukotriene modifiers may be selected, for example, from Montelukast, Pranlukast, Zafirlukast, Ibudilast, and Zileuton. JAK inhibitors may be selected, for example, from Baricitinib, Cerdulatinib, Fedratinib, Filgotinib, Gandotinib, Lestaurtinib, Momelotinib, Pacritinib, Peffitinib, Ruxolitinib, Tofacitinib, and Upadacitinib.Examples of anti-interleukin antibodies include anti-IL-23 antibodies (such as Risankizumab), anti-IL-17 antibodies, anti-IL-1 antibodies, anti-IL-4 antibodies, anti-IL-13 antibodies, anti-IL-5 antibodies, anti-IL-6 antibodies (such as Actemra™), anti-IL-12 antibodies, and anti-IL-15 antibodies.

[0198] In some embodiments, the second agent is an anticancer agent. In some embodiments, the second agent is a chemotherapeutic agent. "Anticancer agent" refers to a composition (e.g., compound, drug, antagonist, inhibitor, modulator, vaccine, cell) that has antitumor properties or is capable of inhibiting cell growth or proliferation, or generally refers to an agent useful in the treatment or prevention of cancer, including chemotherapeutic agents, immunotherapeutic agents, radiotherapy agents, cancer vaccines, etc. In some embodiments, an anticancer agent refers to an agent approved by the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), or a similar regulatory agency in a country outside the U.S. or Europe for the treatment of cancer. Examples of anticancer agents include, but are not limited to: MEK inhibitors, EGFR inhibitors, RAS inhibitors, β-RAF inhibitors, alkylating agents, nitrogen mustards, ethyleneimine and methylmelamine derivatives, alkyl sulfonates, nitrosoureas, triazine derivatives, antimetabolites, pyrimidine analogs, purine analogs, plant alkaloids, topoisomerase inhibitors, antitumor antibiotics, platinum compounds, anthraquinones, substituted ureas, methylhydrazine derivatives, adrenocortical inhibitors, epipodophyllotoxins, mitogen-activated protein kinase signaling inhibitors, mTOR inhibitors, agents that arrest cells in the G2-M phase and / or regulate microtubule formation or stability, anti-estrogens, anti-androgens, monoclonal antibodies (e.g., anti-CD20, anti-HER2, anti-CD52, anti-HLA-DR, and anti-VEGF monoclonal antibodies, such as alemtuzumab, bevacizumab, and bretuximab). vedotin), cetuximab, gemtuzumab / ozomicin, tiuxetan, ipilimumab, offatumumab, panitumumab, rituximab, tositumomab, trastuzumab, nivolumab, pembrolizumab, avelumab, durvalumab, and pitilizumab), immunotoxins (e.g., anti-CD33 monoclonal antibody-calichiomycin conjugate, anti-CD22 monoclonal antibody-pseudomonas exotoxin conjugate, etc.), radioimmunotherapy (e.g., with... U1 In、 90 Y or 131(e.g., anti-CD20 monoclonal antibodies conjugated with type I). In the category of anticancer agents, "chemotherapeutic agents" or "chemotherapeutic drugs" refer to chemical compositions or compounds that have antitumor properties or can inhibit cell growth or proliferation. In another embodiment, the compounds described herein may be administered in combination with conventional radiotherapy agents, including but not limited to radionuclides, such as... 47 Sc、 64 Cu、 67 Cu、 9 Sr、 86 Y、 87 Y、 90 Y、 105 Rh、 m Ag、 m In、 117m Sn、 149 Pm, 153 Sm、 166 Ho、 177 Lu、 86 Re、 188 Re、 211 At and 212 Bi, optionally conjugated with an antibody against a tumor antigen.

[0199] The compounds of this invention can inhibit cGAS activity. Studies have shown that these compounds can inhibit cGAS activity in both cell and animal models.

[0200] The compounds of the present invention can optionally be covalently bound to an insoluble matrix and used for affinity chromatography (separation, depending on the nature of the compound's functional groups; for example, compounds with side-chain aryl groups can be used for hydrophobic affinity separation).

[0201] When using one or more derivatives as defined herein: - The active ingredient of the compound may be administered to the animal or mammal (including humans) to be treated by any means known in the art (i.e., oral, intranasal, subcutaneous, intramuscular, intradermal, intravenous, intra-arterial, parenteral, or via catheter insertion).

[0202] - The therapeutically effective amount of the compound formulation, particularly for treating diseases mediated by cGAS activity in humans and other mammals (e.g., cancer, metabolic diseases, and certain congenital diseases), is preferably the amount of cGAS inhibition of the compound as defined herein by formula, statement, aspect, and embodiment, and corresponds to an amount that ensures plasma levels can inhibit cGAS activity, in specific embodiments between 1 ng / mL and 100 mg / mL, more specifically between 1 ng / mL and 1 mg / mL, and even more specifically between 1 ng / mL and 1 µg / mL.

[0203] Appropriate doses of the compounds or compositions of the present invention are applied to treat or prevent a targeted disease in a subject. Depending on the pathological condition to be treated and the specific circumstances of the patient, the effective dose may be divided into several subunits per day, or may be administered at intervals exceeding one day.

[0204] According to specific embodiments of the present invention, the compounds of the present invention can be used in combination with other therapeutic agents to treat or prevent diseases mediated by cGAS activity in humans and other mammals. Therefore, the present invention relates to the use of compositions comprising: (a) one or more compounds as shown in this text, aspects, statements, and embodiments, and (b) One or more agents for the prevention or treatment of inflammatory diseases, autoimmune diseases, allergic diseases, fibrotic diseases and cancer, as well as other treatments or preventives commonly used for inflammatory conditions (including diabetes, metabolic diseases, cardiovascular diseases and neurodegenerative diseases), which are used as bioactive agents in combination formulations, either simultaneously, alone or sequentially.

[0205] The compounds or compositions described herein may be administered simultaneously, before, or after one or more other therapeutic agents, which are different from the compounds described herein and may be used, for example, in combination therapy. Examples of such other therapeutic agents for combination therapy include the anti-inflammatory agents, anti-autoimmune disease agents, anti-allergy agents, anti-fibrotic agents, anti-diabetic agents, agents for cardiovascular diseases, metabolic diseases, or neurodegenerative diseases, and anticancer agents described herein.

[0206] Pharmaceutical compositions or formulations according to the present invention may contain compounds of the present invention in a wide range of amounts, depending on the intended use and expected effect of the formulation. Typically, the content of derivatives of the present invention in the formulation is 0.1 to 99.9% by weight, preferably 1 to 99% by weight, more preferably 5 to 95% by weight.

[0207] Those skilled in the art will also recognize that the compounds of the present invention can exist in a variety of different protonated states, which depends in particular on the pH of their environment. Although the structural formulas provided herein depict only one of several possible protonated states of the compounds, it should be understood that these structures are illustrative only, and the invention is not limited to any particular protonated state; any and all protonated forms of the compounds are intended to fall within the scope of the invention.

[0208] As used herein, the term "pharmaceutically acceptable salt" refers to a non-toxic salt form of the compounds shown in this document that possesses therapeutic activity. Therefore, the compounds of the present invention optionally comprise salts of the compounds herein, particularly pharmaceutically acceptable non-toxic salts, which contain, for example, Na. + Li + K +Ca 2+ and Mg 2+ Such salts may comprise salts composed of a suitable cation (e.g., alkali metal and alkaline earth metal ions or ammonium and quaternary ammonium ions) combined with an acidic anionic moiety (typically a carboxylic acid). The compounds of this invention may carry multiple positive or negative charges. The net charge of the compounds of this invention may be positive or negative. Any associated counterion is typically determined by the synthetic and / or isolation method used to obtain the compound. Typical counterions include, but are not limited to, ammonium, sodium, potassium, lithium, halides, acetate, trifluoroacetate, and mixtures thereof. It should be understood that the properties of any associated counterion are not a key feature of this invention, and this invention covers compounds associated with any type of counterion. Furthermore, since compounds can exist in many different forms, this invention aims to cover not only forms associated with counterions (e.g., dry salts) but also forms not associated with counterions (e.g., aqueous or organic solutions). Metal salts are typically prepared by reacting a metal hydroxide with the compounds of this invention. Examples of metal salts prepared in this manner include those containing Li + Na + and K + Salts. By adding a suitable metal compound, a less soluble metal salt can be precipitated from a solution of a salt with higher solubility. Furthermore, salts can be formed by acid addition of certain organic and inorganic acids to a basic center (usually an amine) or an acidic group. Examples of such suitable acids include, for example, inorganic acids such as hydrohalic acids (e.g., hydrochloric acid or hydrobromic acid), sulfuric acid, nitric acid, phosphoric acid, etc.; or organic acids such as acetic acid, propionic acid, glycolic acid, 2-hydroxypropionic acid, 2-oxopropionic acid, lactic acid, pyruvic acid, oxalic acid (i.e., oxalic acid), malonic acid, succinic acid (i.e., succinic acid), maleic acid, fumaric acid, malic acid, tartaric acid, citric acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, cyclohexanesulfonic acid, salicylic acid (i.e., 2-hydroxybenzoic acid), p-aminosalicylic acid, etc. In addition, the term also includes solvates, such as hydrates, alcohols, etc., that can be formed from the compounds represented by the formulas described herein and their salts. Finally, it should be understood that the compositions herein comprise the nonionic and zwitterionic forms of the compounds of the present invention, as well as hydrates formed by stoichiometric combination with water.

[0209] Salts formed by the parent compound and one or more amino acids, particularly naturally occurring amino acids present as protein components, are also included within the scope of this invention. Amino acids are generally those with basic or acidic groups on their side chains, such as lysine, arginine, or glutamic acid, or those with neutral groups on their side chains, such as glycine, serine, threonine, alanine, isoleucine, or leucine.

[0210] The compounds of the present invention also include their physiologically acceptable salts. Examples of physiologically acceptable salts of the compounds of the present invention include those derived from suitable bases (e.g., alkali metals (e.g., sodium), alkaline earth metals (e.g., magnesium), ammonium, and NX4). + Salts of compounds containing a hydrogen atom or an amino group (where X is a C1-C4 alkyl group). Physiologically acceptable salts include salts of the following acids: organic carboxylic acids, such as acetic acid, benzoic acid, lactic acid, fumaric acid, tartaric acid, maleic acid, malonic acid, malic acid, hydroxyethanesulfonic acid, lactobionic acid, and succinic acid; organic sulfonic acids, such as methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid; and inorganic acids, such as hydrochloric acid, sulfuric acid, phosphoric acid, and aminosulfonic acid. Physiologically acceptable salts of compounds containing a hydroxyl group include the anion of said compound with a suitable cation (e.g., Na+). + and NX4 + (where X is typically selected independently from H or C1-C4 alkyl groups). However, salts of non-physiologically acceptable acids or bases may also be used, for example, to prepare or purify physiologically acceptable compounds. All salts, whether or not derived from physiologically acceptable acids or bases, are within the scope of this invention.

[0211] As used herein and unless otherwise stated, the term "enantiomer" refers to the optically active forms of the compounds of the present invention, having an optical purity or enantiomer excess (determined by standard methods in the art) of at least 80% (e.g., at least 90% of one enantiomer and at most 10% of another enantiomer), preferably at least 90%, more preferably at least 98%.

[0212] As used herein, the term "isomer" refers to all possible isomers that the compound represented by the formula described herein may have, including tautomers and stereochemical forms, but excluding positional isomers. Generally, the structures shown herein illustrate only one tautomer or resonance form of the compound, but corresponding alternative configurations are also considered. Unless otherwise stated, the chemical name of a compound represents a mixture of all possible stereochemical isomers, including all diastereomers and enantiomers of the basic molecular structure (since the compound represented by the formula described herein may have at least one chiral center), as well as stereochemically pure or enriched compounds. More specifically, the chiral center may have an R configuration or an S configuration, and the multiple bonds may have a cis configuration or a trans configuration.

[0213] The pure isomer of the compound is defined as an isomer that substantially does not contain other enantiomers or diastereomers with the same basic molecular structure. Specifically, the terms "stereoisomerically pure" or "chirally pure" refer to a compound in which the stereoisomer excess is at least about 80% (e.g., at least 90% of one isomer and at most 10% of other possible isomers), preferably at least 90%, more preferably at least 94%, and most preferably at least 97%. The terms "enantiomerically pure" and "diastereomerically pure" should be understood in a similar manner, taking into account either an enantiomer excess or a diastereomer excess of the mixture under discussion.

[0214] The separation of stereoisomers is achieved by standard methods well known to those skilled in the art. An enantiomer of a compound of the present invention can be substantially separated from its opposite enantiomer by, for example, the formation of a diastereomer using an optically active resolving agent (EL Eliel, Stereochemistry of Carbon Compounds (1962) McGraw Hill; Lochmuller, CH, (1975) J. Chromatogr., 113(3): 283-302). The separation of isomers in a mixture can be achieved by any suitable method comprising: (1) forming an ionic diastereoisomeric salt with a chiral compound and separating it by stepwise crystallization or other methods; (2) forming a diastereoisomeric compound with a chiral derivatizing agent, separating the diastereomer, and converting it to a pure enantiomer; or (3) directly separating the enantiomers under chiral conditions. In method (1), diastereomeric salts can be formed by reacting an enantiomerically pure chiral base (e.g., strychnine, quinine, ephedrine, bromelain, α-methyl-β-phenylethylamine (amphetamine) etc.) with an asymmetric compound having an acidic functional group (e.g., carboxylic acid and sulfonic acid). The diastereomeric salts can be separated by stepwise crystallization or ion chromatography. To separate the optical isomers of amino compounds, the addition of a chiral carboxylic acid or sulfonic acid (e.g., camphorsulfonic acid, tartaric acid, mandelic acid, or lactic acid) can form diastereomeric salts. Alternatively, by method (2), the substrate to be separated can be reacted with an enantiomer of a chiral compound to form a diastereomer pair (Eliel, E. & Wilen, S. (1994) Stereochemistry of Organic Compounds, John Wiley & Sons, Inc., p. 322). Diasteremeric compounds can be formed by reacting an asymmetric compound with an enantiomerically pure chiral derivatizing agent (e.g., a menthyl derivative), followed by separation of the diastereomers and hydrolysis, resulting in a free, enantiomer-enriched compound. Methods for determining optical purity involve preparing a chiral ester of the racemic mixture, such as menthyl ester or Mosher ester (α-methoxy-α-(trifluoromethyl)phenylacetic acid ester) (Jacob III. (1982) J. Org. Chem. 47: 4165), and detecting the presence of the two trans-restricted diastereomers by analyzing NMR spectra. Stable diastereomers can be separated and purified by normal-phase and reversed-phase chromatography according to the method for separating the trans-restricted isomer naphthyl-isoquinoline (Hoye, T., WO 96 / 15111). In method (3), the racemic mixture of the two asymmetric enantiomers can be separated by chromatography using a chiral stationary phase.Suitable chiral stationary phases are, for example, polysaccharides, particularly cellulose or amylose derivatives. Commercially available polysaccharide-based chiral stationary phases include ChiralCeI™ CA, OA, OB5, OC5, OD, OF, OG, OJ, and OK, as well as Chiralpak™ AD, AS, OP(+), and OT(+). Suitable eluents or mobile phases for use in combination with said polysaccharide chiral stationary phases are alcohol-modified hexane, etc. (“Chiral Liquid Chromatography” (1989) WJ Lough, Ed. Chapman and Hall, New York; Okamoto, (1990) “Optical resolution of dihydropyridineenantiomers by High-performance liquid chromatography using phenylcarbamates of polysaccharides as a chiral stationary phase”, J. of Chromatogr. 513: 375-378).

[0215] The terms “cis” and “trans” used herein follow Chemical Abstracts nomenclature and include reference to the position of substituents on the ring moiety. The absolute stereochemical configuration of the compounds shown in the formulas described herein can be readily determined by those skilled in the art using methods well known in the art, such as X-ray diffraction.

[0216] The present invention also includes isotopically labeled compounds, which are identical to those listed in the formulas described herein, except that one or more atoms are replaced by atoms with atomic masses or mass numbers different from those normally found in nature. Examples of isotopes that can be incorporated into the compounds of the present invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, and chlorine, for example, respectively. 2 H, 3 H, 13 C 11 C 14 C 15 N、 18 O、 17 O、 31 P, 32 P, 35 S, 18 F and 36 Cl. The compounds of this invention and their pharmaceutically acceptable salts, or other isotopes containing the aforementioned isotopes and / or other atoms, are all within the scope of this invention. Certain isotope-labeled compounds of this invention, for example, those doped with…3 H and 14 Compounds containing radioactive isotopes such as C can be used for the determination of drug and / or substrate tissue distribution. Tritium (i.e., 3 H) and carbon-14 (i.e. 14 C) Isotopes are particularly preferred due to their ease of preparation and detectability. Furthermore, heavier isotopes (e.g., deuterium, i.e., 2 H) Substitution may offer certain therapeutic advantages due to increased metabolic stability, such as prolonged in vivo half-life or reduced dosage requirements, and is therefore preferred in some cases. The isotopically labeled compounds of the present invention can generally be prepared by replacing non-isotopically labeled reagents with readily available isotopically labeled reagents by performing the procedures disclosed in the examples and preparation methods described herein.

[0217] Using PROTAC technology (Schapira M. et al., Nat. Rev. Drug Discov. Modifications to compounds or metabolites of formula (I) or other formulas, embodiments thereof, aspects thereof, or parts thereof, as described in (2019, 18(12), 949-963) are also covered within the scope of this invention. Specifically, PROTAC technology designs a bifunctional small molecule having one end a compound or metabolite of formula (I) or other formulas, embodiments thereof, aspects thereof, or parts thereof, and the other end linked to a ligand of an E3 ubiquitin ligase via a linker chain to form a targeted-induced protein degradation complex. Because this degradation has a catalytic effect, efficient degradation can be achieved at lower doses. Compounds or metabolites of formula (I) or other formulas, embodiments thereof, aspects thereof, or parts thereof, or parts thereof, can be linked to a ligand of an E3 ubiquitin ligase (e.g., a thalidomide analogue) via a linker arm (e.g., a long-chain ethylene glycol of length 2 to 10, a long-chain propylene glycol of length 2 to 10, or a long-chain aliphatic alkane of length 2 to 10).

[0218] The compounds of this invention can be formulated with conventional carriers and excipients, which will be selected according to conventional practice. Tablets will contain excipients, flow aids, fillers, binders, etc. Aqueous formulations are prepared aseptically and should generally be isotonic when intended for delivery by non-oral administration. Formulations optionally contain excipients, such as those described in "Handbook of Pharmaceutical Excipients" (1986), including ascorbic acid and other antioxidants, chelating agents (e.g., EDTA), carbohydrates (e.g., dextrin), hydroxyalkyl cellulose, hydroxyalkyl methyl cellulose, stearic acid, etc.

[0219] Therefore, as used herein, the term "pharmaceutically acceptable carrier" refers to any material or substance formulated with the active ingredient to facilitate its application or delivery to the site of treatment (e.g., by dissolving, dispersing, or diffusing the composition) and / or to facilitate its storage, transport, or handling without impairing its effectiveness. A pharmaceutically acceptable carrier may be a solid or liquid, or a gas compressed to form a liquid; for example, the compositions of the present invention may suitably be used as concentrates, emulsions, solutions, granules, powders, sprays, aerosols, suspensions, ointments, creams, tablets, pills, or powders.

[0220] Pharmaceutical carriers suitable for the pharmaceutical compositions and their formulations are well known to those skilled in the art, and their selection is not particularly limited in this invention. They may also include additives such as wetting agents, dispersants, adhesives, binders, emulsifiers, solvents, coating agents, antibacterial and antifungal agents (e.g., phenol, sorbic acid, chlorobutanol), isotonic agents (e.g., sugars or sodium chloride), provided that these additives conform to pharmaceutical practice, such as carriers and additives that will not cause permanent harm to mammals. The pharmaceutical compositions of this invention can be prepared by any known method, such as by a one-step or multi-step process of uniformly mixing, coating, and / or grinding the active ingredient with a selected carrier material and (where appropriate) other additives (e.g., surfactants), or by micronization, for example, to obtain compositions in the form of microspheres typically with a diameter of about 1 to 10 gm, i.e., microcapsules for the controlled or sustained release of the active ingredient.

[0221] The surfactants (also known as emulsifiers) suitable for the pharmaceutical compositions of the present invention are nonionic, cationic, and / or anionic materials with good emulsifying, dispersing, and / or wetting properties. Suitable anionic surfactants include water-soluble soaps and water-soluble synthetic surfactants. Suitable soaps are higher fatty acids (C... 10 -C 22Alkali metal or alkaline earth metal salts, unsubstituted or substituted ammonium salts, such as sodium or potassium salts of oleic acid or stearic acid, or sodium or potassium salts of mixtures of natural fatty acids obtainable from coconut oil or tallow. Synthetic surfactants include sodium or calcium salts of polyacrylic acid; fatty sulfonates and sulfates; sulfonated benzimidazole derivatives and alkyl aryl sulfonates. Fatty sulfonates or sulfates are generally in the following forms: alkali metal or alkaline earth metal salts, unsubstituted ammonium salts or ammonium salts substituted with alkyl or acyl groups having 8 to 22 carbon atoms, such as sodium or calcium salts of lignin sulfonate or dodecyl sulfonate, or alkali metal or alkaline earth metal salts of fatty alcohol sulfates, sulfate esters or sulfonates obtained from natural fatty acids (e.g., sodium lauryl sulfate), and mixtures of sulfonic acids of fatty alcohol / ethylene oxide adducts. Suitable sulfonated benzimidazole derivatives preferably contain 8 to 22 carbon atoms. Examples of alkylaryl sulfonates are sodium, calcium, or alkanolamine salts of dodecylbenzenesulfonic acid, dibutylnaphthalenesulfonic acid, or naphthalenesulfonic acid / formaldehyde condensation products. Corresponding phosphates are also suitable, such as salts of phosphate esters, salts of nonylphenol adducts with ethylene oxide and / or propylene oxide, or phospholipids. Phospholipids suitable for this purpose include natural (derived from animal or plant cells) or synthetic phospholipids of the cephalin or lecithin type, such as phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerol, lysophosphatidylcholine, cardiolipin, dioctylphosphatidylcholine, dipalmitoylphosphatidylcholine, and mixtures thereof.

[0222] Suitable nonionic surfactants include alkylphenols, fatty alcohols, fatty acids, aliphatic amines or amides containing at least 12 carbon atoms in their molecules, polyethoxylated and polypropoxylated derivatives of alkyl aryl sulfonates and dialkyl sulfosuccinates, such as aliphatic and cyclic aliphatic alcohols, polyethylene glycol ether derivatives of saturated and unsaturated fatty acids and alkylphenols, wherein the derivatives preferably contain 3 to 10 glycol ether groups, the (aliphatic) hydrocarbon moiety containing 8 to 20 carbon atoms, and the alkyl moiety of the alkylphenol containing 6 to 18 carbon atoms. Other suitable nonionic surfactants are water-soluble adducts of polyethylene oxide with polypropylene glycol, and ethylenediamine polypropylene glycol containing 1 to 10 carbon atoms in its alkyl chain, wherein the adducts contain 20 to 250 glycol ether groups and / or 10 to 100 propylene glycol ether groups. Such compounds typically contain 1 to 5 ethylene glycol units per propylene glycol unit. Representative examples of nonionic surfactants include nonylphenol ethoxyethanol, castor oil polyethylene glycol ether, polypropylene / polyethylene oxide adducts, tributylphenoxy ethoxyethanol, polyethylene glycol, and octylphenoxy ethoxyethanol. Fatty acid esters of polyethylene sorbitol (e.g., polyoxyethylene sorbitol trioleate), as well as fatty acid esters of glycerol, sorbitol, sucrose, and pentaerythritol, are also suitable nonionic surfactants.

[0223] Suitable cationic surfactants include quaternary ammonium salts, particularly halides, having four hydrocarbon groups optionally substituted with halogen, phenyl, substituted phenyl, or hydroxyl groups; for example, containing at least one C 8-22 Alkyl groups (e.g., cetyl, lauryl, palmityl, myristyl, oleyl, etc.) as N-substituents, and quaternary ammonium salts with unsubstituted or halogenated lower alkyl groups, benzyl and / or hydroxy-lower alkyl groups as other substituents.

[0224] More detailed descriptions of surfactants suitable for this purpose can be found in, for example, McCutcheon's Detergents and Emulsifiers Annual (MC Publishing Crop., Ridgewood, New Jersey, 1981), Tensid-Taschenbucw, 2nd edition (Hanser Verlag, Vienna, 1981), and Encyclopaedia of Surfactants (Chemical Publishing Co., New York, 1981).

[0225] The compounds of the present invention and their pharmaceutically acceptable salts (hereinafter collectively referred to as the active ingredients) may be administered via any route suitable for the condition to be treated, including oral, rectal, nasal, topical (including ocular, buccal, and sublingual), vaginal, and parenteral (including subcutaneous, intramuscular, intravenous, intradermal, intrathecal, and epidural). Preferred routes of administration may vary depending on, for example, the condition of the recipient.

[0226] Although the active ingredient can be administered alone, it is preferred to formulate it into a pharmaceutical preparation. The veterinary and human preparations of the present invention comprise at least one active ingredient as described above, and one or more pharmaceutically acceptable carriers, and optionally include other therapeutic ingredients. The carrier is preferably compatible with the other components of the preparation and harmless to the recipient in an "acceptable" sense. Preparations include those suitable for oral, rectal, nasal, topical (including buccal and sublingual), vaginal, or parenteral (including subcutaneous, intramuscular, intravenous, intradermal, intrathecal, and epidural) administration. Preparations can be conveniently presented in unit dosage forms and can be prepared by any method well known in the pharmaceutical field. Such methods include the step of associating the active ingredient with a carrier constituting one or more auxiliary ingredients. Typically, preparations are prepared by uniformly and sufficiently associating the active ingredient with a liquid carrier or a finely powdered solid carrier, or both, and then (if necessary) shaping the product.

[0227] The formulations of this invention suitable for oral administration may be presented as discrete units, such as capsules, pods, or tablets each containing a predetermined amount of the active ingredient; or as powders or granules; or as solutions or suspensions in aqueous or non-aqueous liquids; or as oil-in-water or water-in-oil liquid emulsions. The active ingredient may also be presented as pellets, saccharides, or pastes.

[0228] Tablets can be prepared by compression or molding, optionally using one or more excipients. Compressed tablets can be prepared by compressing an active ingredient in free-flowing form (e.g., powder or granules) in a suitable machine, optionally mixed with a binder, lubricant, inert diluent, preservative, surfactant, or dispersant. Molded tablets can be prepared by molding a mixture of powdered compounds wetted with an inert liquid diluent in a suitable machine. Tablets can optionally be coated or indented and can be formulated to provide sustained or controlled release of the active ingredient therein. For injection into the eye or other external tissues (e.g., the mouth and skin), the formulation is optionally applied as a topical ointment or cream, wherein the amount of active ingredient contained is, for example, 0.075% to 20% w / w (including active ingredient in increments of 0.1% w / w, such as 0.6% w / w, 0.7% w / w, etc.), preferably 0.2% to 15% w / w, and most preferably 0.5% to 10% w / w. When formulated as an ointment, the active ingredient may be used with a paraffin base or a water-soluble ointment base. Alternatively, the active ingredient may be formulated as a cream with an oil-in-water emulsion base. If desired, the aqueous phase of the cream base may contain, for example, at least 30% w / w of a polyol, such as an alcohol having two or more hydroxyl groups, such as propylene glycol, 1,3-butanediol, mannitol, sorbitol, glycerin, and polyethylene glycol (including PEG400) and mixtures thereof. Topical formulations may desiccately contain compounds that enhance the absorption or penetration of the active ingredient through the skin or other affected areas. Examples of such skin penetration enhancers include dimethyl sulfoxide and related analogues.

[0229] The oil phase of the emulsion of the present invention can be composed of known ingredients in a known manner. Although this phase may contain only emulsifiers, it is desirable to contain at least one emulsifier in a mixture of fats or oils, or in a mixture of both fats and oils. Optionally, a hydrophilic emulsifier is included together with a lipophilic emulsifier as a stabilizer. Preferably, both oils and fats are included. The emulsifier, with or without the stabilizer, constitutes a so-called emulsifying wax, which, together with the oils and fats, constitutes a so-called emulsifying ointment matrix, which forms the oily dispersed phase of the ointment formulation.

[0230] The choice of oil or fat for the formulation is based on achieving the desired cosmetic properties, as the active compound has very low solubility in most oils that may be used in pharmaceutical emulsion formulations. Therefore, the cream should optionally be a non-greasy, non-staining, and washable product with a suitable consistency to avoid leakage from tubes or other containers. Straight-chain or branched, mono- or dialkyl esters can be used, such as diisoadipate, isocetyl stearate, propylene glycol dicarboxylate, isopropyl myristate, decyl oleate, isopropyl palmitate, butyl stearate, 2-ethylhexyl palmitate, or branched ester blends known as Crodamol CAP, with the last three being preferred esters. These alkyl esters can be used alone or in combination, depending on the desired properties. Alternatively, high-melting-point lipids, such as white soft paraffin and / or liquid paraffin or other mineral oils, can be used.

[0231] Formulations suitable for topical ocular application also include eye drops, wherein the active ingredient is dissolved or suspended in a suitable carrier, particularly in an aqueous solvent of the active ingredient. The active ingredient is optionally present in such formulations at a concentration of 0.5% to 20% w / w, preferably 0.5% to 10% w / w, and particularly about 1.5% w / w. Formulations suitable for topical oral application include: lozenges containing the active ingredient in a flavoring matrix (typically sucrose and gum arabic or tragacanth); tablets containing the active ingredient in an inert matrix (e.g., gelatin and glycerin, or sucrose and gum arabic); and mouthwashes containing the active ingredient in a suitable liquid carrier.

[0232] Formulations for rectal administration may be in the form of suppositories with a suitable matrix, such as containing cocoa butter or salicylates. Formulations suitable for nasal administration (where the carrier is solid) include coarse powders with a particle size, for example, 20 to 500 micrometers (including particle sizes between 20 and 500 micrometers in 5-micrometer increments, such as 30 micrometers, 35 micrometers, etc.), administered by nasal inhalation, for example, by placing a container containing the powder tightly against the nose and rapidly inhaling through the nasal cavity. Formulations suitable for administration, such as nasal sprays or drops (where the carrier is liquid), include aqueous or oil solutions of the active ingredient. Formulations suitable for aerosol administration may be prepared according to conventional methods and may be delivered together with other therapeutic agents.

[0233] Preparations suitable for vaginal application may be in the form of vaginal suppositories, tampons, creams, gels, pastes, foams, or sprays, and in addition to the active ingredient, the preparation may contain a suitable carrier known in the art.

[0234] Formulations suitable for parenteral administration include aqueous and non-aqueous sterile injectable solutions that may contain antioxidants, buffers, antibacterial agents, and solutes that make the formulation isotonic with the blood of the intended recipient; and aqueous and non-aqueous sterile suspensions that may contain suspending agents and thickeners. Formulations may be presented in single-dose or multi-dose containers (e.g., sealed ampoules and vials) and may be stored under lyophilized (freeze-dried) conditions, requiring only the addition of a sterile liquid carrier (e.g., water for injection) just before use. Ready-to-use injectable solutions and suspensions may be prepared from sterile powders, granules, and tablets of the types described above.

[0235] Preferred unit-dose formulations are those containing the active ingredient at the daily dose or sub-daily dose or an appropriate fraction thereof as described above.

[0236] It should be understood that, in addition to the ingredients specifically mentioned above, the formulations of the present invention may also contain other pharmaceutical agents conventional in the art for the relevant formulation type, such as flavoring agents for oral administration.

[0237] The compounds of this invention can be used to provide controlled-release pharmaceutical formulations containing one or more of the compounds of this invention as active ingredients (“controlled-release formulations”), wherein the release of the active ingredient can be controlled and modulated to reduce dosing frequency or improve the pharmacokinetic or toxicological characteristics of a particular compound of this invention. Controlled-release formulations suitable for oral administration (where the discrete unit comprises one or more of the compounds of this invention) can be prepared according to conventional methods.

[0238] Additional components may be included to control the duration of action of the active ingredient in the composition. Therefore, controlled-release compositions can be achieved by selecting suitable polymer carriers (e.g., polyesters, polyamino acids, polyvinylpyrrolidone, ethylene-vinyl acetate copolymers, methylcellulose, carboxymethylcellulose, protamine sulfate, etc.). The drug release rate and duration of action can also be controlled by incorporating the active ingredient into particles (e.g., microcapsules) of polymeric substances (e.g., hydrogels, polylactic acid, hydroxymethylcellulose, polymethyl methacrylate, and other polymers mentioned above). Such methods include colloidal drug delivery systems such as liposomes, microspheres, microemulsions, nanoparticles, nanocapsules, etc. Depending on the route of administration, the drug composition may require protective coating. Suitable drug dosage forms for injection include sterile aqueous solutions or dispersions and sterile powders for their temporary formulation. Therefore, typical carriers for this purpose include biocompatible aqueous buffers, ethanol, glycerol, propylene glycol, polyethylene glycol, and mixtures thereof.

[0239] Given that when multiple active ingredients are used in combination, they may not simultaneously produce a combined therapeutic effect directly in the mammal to be treated, the corresponding composition can also be in the form of a medical kit or packaging, with the two components placed in adjacent but independent storage containers or compartments. Therefore, in the latter case, each active ingredient can be formulated for a different route of administration than the other ingredients; for example, one ingredient can be an oral or parenteral preparation, while the other can be an ampoule or aerosol for intravenous injection.

[0240] Another embodiment of the invention relates to various precursor or "prodrug" forms of the compounds of the invention. It may be necessary to formulate the compounds of the invention as a chemical substance that itself does not have significant biological activity, but when delivered to an animal, mammal, or human, it will undergo a chemical reaction catalyzed by enzymes present in the stomach or serum of the fish, resulting in the release of the compound as defined herein. Therefore, the term "prodrug" refers to a substance that is converted into an active pharmaceutical ingredient in vivo.

[0241] The prodrugs of the compounds of the present invention may have any form suitable to the formulation user; for example, esters are a common, non-limiting form of prodrug. However, in the case of the present invention, the prodrug may have to be present in a form in which the covalent bonds are cleaved by the action of an enzyme present at the target site. For example, the C-C covalent bonds may be selectively cleaved by one or more enzymes at the target site; therefore, prodrugs in forms other than readily hydrolyzable protons, especially esters, amides, etc., may be used. The corresponding portion of the active pharmaceutical ingredient in the prodrug may have different structures, such as amino acid or peptide structures, alkyl chains, sugar moieties, and other structures known in the art.

[0242] For the purposes of this invention, the term "therapeuticly applicable prodrug" is defined herein as "a modified compound which, upon contact with tissues of an animal, mammal, or human to which a prodrug has been administered, is converted in vivo into a therapeutically active form via one or more biotransformations without excessive toxicity, irritation, or allergic reactions, and achieves the desired therapeutic effect."

[0243] More specifically, the term "prodrug" as used herein refers to an inactive or significantly less active derivative of a compound (such as those shown in the structural formulas described herein) that releases the pharmacologically active form of the compound in vivo through spontaneous or enzymatic conversion. For a full review, see Rautio J. et al. ("Prodrugs: design and clinical applications," Nature Reviews Drug Discovery, 2008, doi: 10.1038 / nrd2468).

[0244] The compounds of the present invention can be prepared by a series of chemical reactions well known to those skilled in the art, which together constitute a method for preparing the compounds, and are further illustrated below. The methods described below are merely illustrative and are in no way intended to limit the scope of the invention.

[0245] This invention relates to a method for preparing the compound, comprising the following steps: - The pyrrolidine-containing compound shown in formula (A1) is coupled with the electrophilic reagent shown in formula LG-WLX-PG, and PG is further removed (if PG is different from Me) to obtain the compound shown in formula (A2), wherein R 1 R 2 R 3 R 4 W, L, X, and n have the meanings described in any formula or embodiment herein, wherein PG is a protecting group and LG is a leaving group; or

[0246] - Make the compound shown in formula (A3) and the preferred formula HR 3 The nucleophile reaction shown is followed by the removal of PG (if PG is different from Me) to obtain the compound shown in formula (A2), wherein R 1 R 2 R 3 R 4 W, L, X, and n have the meanings described in any formula or embodiment herein, wherein PG is a protecting group and LG is a leaving group; or

[0247] - The pyridone-containing compound shown in formula (A4) is combined with the preferred formula R 5 -LG is coupled with an electrophilic reagent and PG is further removed (if PG is different from Me) to obtain a compound of formula (A5) or (A6), wherein R 1 R 2 R 3 R 5 W, L, X, and n have the meanings described in any formula or embodiment herein, wherein PG is a protecting group, LG is a leaving group, and wherein the group -OR 5 The group corresponding to the -OR defined in any formula, statement or embodiment herein. 3c ;or

[0248] - The compound shown in formula (A7) is reacted with a nucleophile of preferred formula HX-PG, and PG is further removed to obtain the compound shown in formula (A2), wherein R1 R 2 R 3 R 4 W, L, X, and n have the meanings described in any formula or embodiment herein, wherein PG is a protecting group and LG is a leaving group; or

[0249] - The halogenated compound of formula (A8) is coupled with a suitable coupling agent (preferably a suitable R) by methods known to those skilled in the art (Suzuki coupling, Negishi coupling, Stille coupling, etc.). 4.4 The reagent (e.g., boric acid or borate ester, organozinc, tinane) reacts with the PG, and PG is further removed to obtain the compound shown in formula (A2a), wherein R 1 R 2 R 3 R 4 R 4.4 , W, L, X and n have the meanings described in any formula, statement or embodiment of this document, wherein PG is a protecting group and X1 is a halogen;

[0250] Representative compounds of the present invention can be synthesized according to the general synthetic methods described below and shown in the subsequent embodiments. Since the embodiments are merely examples, the invention should not be construed as being limited to the specific chemical reactions and conditions described in the embodiments and examples. Therefore, the above general embodiments should be considered as non-limiting examples. It should be understood that the compounds of the present invention can be obtained by other methods known to those skilled in the art. Various starting materials used in the embodiments are commercially available or can be prepared by methods well known to those skilled in the art. The definitions of variables are as described herein and fall within the conventional technical capabilities of those skilled in the art.

[0251] The abbreviations used in this specification, and especially in the schemes and embodiments, are as follows:

[0252] The compounds of the present invention can be prepared according to the general procedure outlined in Scheme 1.

[0253]

[0254] Option 1: All R 1 、R 2 、R 3 、R 4 W, L, X, and n are as described in the compounds of the present invention and their embodiments and formulas. PG = Protecting group, LG = Leaving group, X1 = Halogen.

[0255] The aniline compound represented by general formula 1 (commercially available or synthesized by methods known to those skilled in the art or by the methods described in the examples below) can be synthesized at temperatures from 0 to 25°C in a polar aprotic solvent (e.g., dichloromethane, tetrahydrofuran, etc.) using a suitable halogenating agent (e.g., bromine, etc.). N -bromosuccinimide, N -Chlorosuccinimide, N The intermediate shown in Formula 2 is obtained by halogenating an iodosuccinimide (e.g., iodosuccinimide) with a succinate (e.g., iodosuccinimide). The tricyclic compound shown in Formula 6 can be obtained by reacting the intermediate shown in Formula 2 with a borate ester derivative shown in Formula 3 (where PG is a protecting group (e.g., Boc, PMB, etc., which can be synthesized by methods known to those skilled in the art or by the methods described in the examples below) in the presence of a Pd catalyst (e.g., Pd(PPh3)4) and a base (e.g., K2CO3, KOAc, etc.) in a suitable solvent (e.g., dioxane, water, etc.). Alternatively, the intermediate shown in Formula 2 can be converted into a borate ester derivative shown in Formula 4 by reacting it with a pinacol diboronate in the presence of a corresponding Pd catalyst (e.g., Pd(dppf)Cl2, Pd2(dba)3, etc.), a ligand (e.g., PCy3), and a base (e.g., KOAc, etc.) in a polar aprotic solvent (e.g., dioxane). The borate ester derivative of general formula 4 can be further reacted with the ester derivative of general formula 5 (where LG is a leaving group (e.g., OTf, Br, etc.) and PG is a protecting group (e.g., Boc, etc.), which can be synthesized by methods known to those skilled in the art or by the methods described in the examples below) to obtain the tricyclic compound of general formula 6. The derivative of general formula 7 (where LG is a leaving group, e.g., OTf) can be obtained by reacting the tricyclic compound of general formula 6 by methods known to those skilled in the art or by the methods described in the examples below. The intermediate of general formula 7 can be reduced in the presence of a Pd catalyst (e.g., Pd(PPh3)4, Pd(OAc)2, Pd(dppf)Cl2, etc.) and a base (e.g., pyridine, Et3N, etc.) in a polar protic or aprotic solvent (e.g., THF, dioxane, DMF, MeOH, etc.) using a suitable reducing agent (e.g., Et3SiH, H2, HCOOH, etc.) to obtain the compound of general formula 8. The removal can be carried out by methods known to those skilled in the art. N- Protecting groups (e.g., if PG is Boc, then it is treated in the presence of an acid (e.g., HCl or TFA). For more information, see TW Greene and PGM Wuts (Protective Groups in Organic Chemistry, 3rd Edition, John Wiley and Sons, 1999). The target compound represented by Formula 11 can be obtained from the intermediate represented by Formula 9 via a two-step reaction: a coupling reaction with a suitable coupling agent represented by Formula 10 (where LG is a leaving group (e.g., Cl, Br, OR, etc.) and PG is a protecting group (e.g., Boc, Ac, etc., which is commercially available or synthesized by methods known to those skilled in the art or by the methods described in the examples below) at a temperature of -10 to 25°C in the presence of a base (e.g., DIEA, Et3N, etc.) in a polar aprotic solvent (e.g., DCM, DMF, etc.), followed by removal of the protecting group by methods known to those skilled in the art (e.g., treatment in the presence of an acid (e.g., HCl or TFA) if PG is Boc; treatment in the presence of a base (e.g., K2CO3, LiOH, etc.) if PG is Ac).

[0256] In another embodiment, the compound of the present invention may be prepared according to the general procedure outlined in Scheme 2.

[0257]

[0258] Option 2: All R 1 、R 2 、R 3 、R 4 、R 5 W, L, X and n are as described in the compounds of the present invention and their embodiments and formulas. PG = protecting group, LG = leaving group, X 1 = Halogen.

[0259] The intermediate shown in Formula 12 can be obtained from the intermediate shown in Formula 6 (synthesized according to the method described in Scheme 1) through a two-step reaction, including... N- Protecting group removal and coupling reaction, as described in Scheme 1. The intermediate shown in Formula 12 can be converted into the target compound shown in Formula 14 or 15 by reacting it with an alkylating agent shown in Formula 13 (commercially available or synthesized, wherein LG is a leaving group, such as Cl, Br, I, and OTs) at a temperature of 20 to 120°C in the presence of a base (e.g., Cs2CO3, etc.) in a polar aprotic solvent (e.g., DMF, etc.), followed by protecting group removal. Alternatively, the intermediate shown in Formula 12 can be converted into the derivative shown in Formula 16 by reacting it with a method known to those skilled in the art or the method described in the examples below, wherein LG is a leaving group (e.g., Cl, OTf, etc.). If LG is OTf, the intermediate of formula 17 can be synthesized from the derivative of formula 16 by reacting it with a suitable coupling agent (selected from, but not limited to, boric acid, borate esters, borooxanes, organotin reagents) in the presence of a Pd catalyst (e.g., Pd(PPh3)4, Pd(dppf)Cl2, etc.) and a base (e.g., pyridine or K2CO3, etc.) in a polar aprotic solvent (e.g., THF or dioxane) or a nonpolar aprotic solvent (e.g., toluene); or by replacing the leaving group with a suitable nucleophile (e.g., amine, etc.) using methods known to those skilled in the art or methods described in the examples below. If LG is Cl, the intermediate of formula 16 can be reacted with a suitable coupling agent (e.g., sulfonamide, amide, etc.) in the presence of a Pd catalyst (e.g., Pd2dba3), a ligand (e.g., Xantphos), and a base (e.g., K3PO4, etc.) in a suitable solvent (e.g., dioxane, etc.) to give the compound of formula 17. The target compound shown in general formula 11 can be obtained by removing the protecting group according to the method described in scheme 1.

[0260] In another embodiment, the compound of the present invention may be prepared according to the general procedure outlined in Scheme 3.

[0261]

[0262] Option 3: All R 1 、R 2 、R 3 、R 4 W, L, X, and n are as described in the compounds of the present invention and their embodiments and formulas. LG = Leaving group.

[0263] The intermediate shown in Formula 9 (synthesized according to the method described in Scheme 1) can be reacted with the electrophilic reagent shown in Formula 18 (commercially available or synthesized, wherein LG is a leaving group, such as Cl, etc.) by methods known to those skilled in the art or by methods described in the examples below, to obtain the compound shown in Formula 19. Substituting the leaving group with a suitable nucleophile (e.g., an amine, etc.) according to the method described in Scheme 2 yields the derivative shown in Formula 17. Removing the protecting group according to the method described in Scheme 1 yields the target compound shown in Formula 11.

[0264] The following examples are provided to illustrate the present invention and should not be construed as limiting the scope of the invention.

[0265] Table 1: Structures of example compounds of the present invention, their corresponding codes, and names generated using ChemBioDraw 20.0

[0266] If the absolute stereochemical configuration is known, draw and name the structure of the example compound containing the stereocenter. If the absolute stereochemical configuration is unknown, the compound may be a racemic mixture, a mixture of diastereomers, a pure diastereomer with an unknown stereochemical configuration, or a pure enantiomer with an unknown stereochemical configuration.

[0267] Example

[0268] Part A represents the preparation of compounds (intermediates and final products), while part B represents pharmacological examples.

[0269] Part A: Experimental Chemistry Procedures

[0270] All starting materials not explicitly described are commercially available products (details of suppliers such as Acros, Avocado, Aldrich, Fluka, FluoroChem, MatrixScientific, Maybridge, Merck, Sigma, etc. can be found in, for example, the SciFinder® database), or their synthesis methods have been precisely described in professional literature (experimental guidelines can be found in, for example, the Reaxys® database or the SciFinder® database), or can be prepared according to conventional methods known to those skilled in the art.

[0271] If necessary, the reaction is carried out under an inert atmosphere (mainly argon and nitrogen). In different reactions carried out using similar methods, the equivalent number of reagents, the amount of solvent, and the reaction temperature and time may vary slightly. Post-treatment and purification methods are adjusted according to the characteristics of each compound and may vary slightly for similar methods. The yields of the prepared compounds have not been optimized.

[0272] The term "equivalent" ("eq." or "eq" or "equiv.") means molar equivalent, "RT" or "rt" means room temperature (T, 23 ± 7°C), "M" means concentration in mol / L, "sol." means solution, and "conc." means concentration. The mixing ratio of solvents is usually expressed as a volume / volume ratio.

[0273] Microwave irradiation reactions were performed using an Anton Paar Monowave 450 or a CEM Discover 2.0 microwave synthesizer.

[0274] pass 1 H-NMR spectroscopy and / or mass spectrometry (MS, m / z corresponding to [M+H)) + and / or [MH] -Key analytical characterization was performed on all exemplary compounds and selected intermediates. In some cases, such as if positional isomers and / or diastereomers may have formed or actually formed during the reaction, additional analyses were performed, for example... 13 C NMR and NOE (nuclear Overhouse effect) NMR experiments.

[0275] NMR data were acquired using a Bruker Avance III HD 400 MHz (TopSpin 3.6.5 software), a Bruker Avance Neo 400 MHz (TopSpin 4.1.4 software), a Bruker Avance III 400 MHz (TopSpin 3.6.2 software), or a Bruker Avance III HD 400 MHz Prodigy (TopSpin 3.2 software). 1 H data were calibrated using tetramethylsilane as an internal standard. δ values ​​are expressed in parts per million (ppm). The following abbreviations are used: s (singleton), d (doublet), t (triplet), q (quartet), quint (quintet), m (multiplet), br (broad peak).

[0276] If the absolute stereochemical configuration is known, draw and name the structure of the example compound containing the stereocenter. If the absolute stereochemical configuration is unknown, the compound may be a racemic mixture, a mixture of diastereomers, a pure diastereomer with an unknown stereochemical configuration, or a pure enantiomer with an unknown stereochemical configuration.

[0277] The LC-MS analyses mentioned in the experimental section were performed using the instruments, columns, and chromatographic conditions listed in the table below.

[0278]

[0279] Preparative HPLC purification was performed using the following systems: Waters 2545 (MassLynx 4.2 software, 2998 PDA detector, 3767 / 2767 autosampler, detection wavelengths from 200 to 400 nm), Ingos LCP5020 (Chromulanv0.91 software, LCD5000 detector, detection wavelength fixed at 260 nm), Gilson (GX-271) (Trilution software, DAD (171) detector, detection wavelengths fixed at 215 nm and 254 nm), Shimadzu (LC-20AP) (LC Solution software, UV / VIS (SPD-20AV) detector, detection wavelengths fixed at 215 nm and 254 nm) or Waters (Empower software, 2996 PDA detector, Max plot mode).

[0280]

[0281] Intermediate preparation examples

[0282] Synthesis of intermediate 01

[0283] Step 1 To an ice-bath-cooled solution of Boc-L-alanine methyl ester (50.0 g, 246.30 mmol) in anhydrous THF (1600 mL), LiHMDS (1.0 M THF solution, 246.3 mL) was added, and the mixture was stirred at 0°C for 30 min. Subsequently, methyl acrylate (26.5 mL, 295.57 mmol) was added, and the resulting reaction mixture was stirred at 0°C for 1 h, then heated to room temperature and stirred at that temperature for another 3 h. The reaction was then quenched with a saturated aqueous NH4Cl solution and diluted with EtOAc. The organic layer was separated, and the aqueous layer was extracted with EtOAc. The organic layers were combined, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by rapid column chromatography (0-20% EtOAc / hexane) to give 1-(tert-butyl)-3-methyl-(5-ethylhexane)-1-(tert-butyl)-3-methyl-3 ... S 5-Methyl-4-oxopyrrolidine-1,3-dicarboxylate (36.0 g, 57%) was a yellow oil. UPLC-MS (Method A): Rt = 2.38 min (95%); m / z 256 [MH] - .

[0284] Step 2 At -78°C, 1-(tert-butyl)-3-methyl-(5-ethylhexyl)-methylhexyl ... SA solution of 1-(tert-butyl)-3-methyl-( S )-5-methyl-4-(((trifluoromethyl)sulfonyl)oxy)-2,5-dihydro-1 H 1,3-pyrrole-1,3-dicarboxylate (16.2 g, 53%) was a yellow oil. UPLC-MS (Method A): Rt = 2.21 min (96%); m / z 375 [M+H-Me] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 4.66-4.61 (m, 1 H), 4.40-4.18 (m, 2 H), 3.75 (s, 3 H), 1.43-1.37 (m, 12 H).

[0285] The intermediates listed in the table below are prepared using similar steps as described above, with appropriate ester protection for the amino acids.

[0286]

[0287] Synthesis of intermediates 02 to 05

[0288] Step 1 : Add dropwise to a 400 mL solution of 2,3-dichloro-4-methoxyaniline (21.0 g, 110.53 mmol) (obtained according to the method described in WO2016042172) in DCM under a nitrogen atmosphere. NA solution of 19.7 g (110.53 mmol) of bromosuccinimide in 760 mL of DCM was added, and the resulting reaction mixture was stirred at room temperature for 10 min. The reaction was then quenched with water (1000 mL), and the organic layer was separated by filtration through a phase separator, dried over Na₂SO₄, filtered, and concentrated under reduced pressure. The residue was purified by rapid column chromatography (10–15% EtOAc / hexane) to give 16.0 g (55%) of 6-bromo-2,3-dichloro-4-methoxyaniline as a light brown solid. LC-MS (Method D): Rt = 1.69 min (86%); m / z 269.7 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 7.29 (s, 1 H), 5.20 (s, 2 H), 3.78 (s, 3 H).

[0289] Step 2 Pd2(dba)3 (1.70 g, 1.86 mmol) and tricyclohexylphosphine (1.05 g, 3.72 mmol) were added to an anhydrous 1,4-dioxane (100 mL) solution of degassed (argon-bubbling) 6-bromo-2,3-dichloro-4-methoxyaniline (10.00 g, 37.18 mmol), pinacol diboronate (14.16 g, 55.76 mmol), and potassium acetate (10.93 g, 111.52 mmol). The resulting reaction mixture was stirred at 110°C for 4 hours under an argon atmosphere. After cooling to room temperature, the mixture was filtered through a diatomaceous earth mat. The filtrate was concentrated under reduced pressure to give crude product 2,3-dichloro-4-methoxy-6-(4,4,5,5-tetramethyl-1,3,2-dioxoborhexacyclopentan-2-yl)aniline (7.6 g), which was used directly in the next reaction. UPLC-MS (Method A): Rt = 1.65 min; m / z 236 [M+H] + [m / z corresponding to boric acid].

[0290] Step 3 The crude product, 2,3-dichloro-4-methoxy-6-(4,4,5,5-tetramethyl-1,3,2-dioxoborhexacyclopentan-2-yl)aniline (7.6 g, 23.90 mmol), after degassing (argon bubbling), and 1-(tert-butyl)-3-methyl-( S )-5-methyl-4-(((trifluoromethyl)sulfonyl)oxy)-2,5-dihydro-1 HPd(PPh3)4 (1.4 g, 1.20 mmol) was added to a solution of pyrrole-1,3-dicarboxylate (11.2 g, 28.68 mmol) and K2CO3 (9.9 g, 71.70 mmol) in 1,4-dioxane / H2O (120 mL; 5:1 v / v). The resulting reaction mixture was stirred at 80°C for 3 hours under an argon atmosphere. After cooling to room temperature, the mixture was filtered through a diatomaceous earth mat and washed thoroughly with EtOAc (3 × 75 mL). The filtrates were combined, concentrated under reduced pressure, and the residue was purified by rapid column chromatography (40-60% EtOAc / hexane) to obtain ( S )-6,7-dichloro-8-methoxy-1-methyl-4-oxo-1,3,4,5-tetrahydro-2 H -pyrrolo[3,4- c Quinoline-2-carboxylic acid tert-butyl ester (5.0 g, 52% yield in two steps) was a light brown solid. UPLC-MS (Method A): Rt = 2.01 min (94%); m / z 399 [M+H] + . 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 11.19 (br s, 1 H), 7.31-7.24 (m, 1 H), 5.54-5.46 (m, 1 H), 4.54-4.41 (m, 2 H), 3.98-3.92 (m, 3 H), 1.52-1.47 (m, 12 H).

[0291] Step 4 : Cooled by an ice bath ( S )-6,7-dichloro-8-methoxy-1-methyl-4-oxo-1,3,4,5-tetrahydro-2 H -pyrrolo[3,4- c Hydrochloric acid (66.0 mL, 264.00 mmol; 4M 1,4-dioxane solution) was added dropwise to a solution of tert-butyl quinoline-2-carboxylate (7.0 g, 17.59 mmol) in 1,4-dioxane / MeOH (70 mL; 1:1 v / v). The resulting reaction mixture was stirred at room temperature for 4 hours. The mixture was concentrated under reduced pressure, and the residue was ground with n-pentane (2 × 50.0 mL) and further dried under reduced pressure to give the crude produ...

Claims

1. The compound represented by formula (I), its stereoisomers, tautomers, salts (especially pharmaceutically acceptable salts), solvates, hydrates, polymorphs, and / or prodrugs, (I) in: - Each dashed line (---) represents an optional double bond, and two adjacent dashed lines cannot form a double bond at the same time; - R 1 Selected from hydrogen, halogen, =O, alkyl, alkenyl, alkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, cycloalkenyl and cycloalkynyl; The alkyl, alkenyl, alkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, haloalkyl, haloalkenyl, haloalkynyl, cycloalkyl, cycloalkenyl, and cycloalkynyl groups are each unsubstituted or substituted by one or more substituents, each of which is independently selected from halogen, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cycloalkyl, cycloalkenyl, cycloalkynyl, -C(O)OH, -NH2, -NHalkyl, and -N(alkyl)2; - R 2 Selected from hydrogen, halogen, =O, hydroxyl, alkyl, alkenyl, alkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, alkoxyalkyl, mono- or dialkylaminoalkyl, cycloalkyl, cycloalkenyl, cycloalkynyl, haloalkyl, haloalkenyl, haloalkynyl, alkoxy, haloalkoxy, -CONR 2a R 2b and -CO2R 2c ; The alkyl, alkenyl, alkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, alkoxyalkyl, mono- or dialkylaminoalkyl, cycloalkyl, cycloalkenyl, cycloalkynyl, haloalkyl, haloalkenyl, haloalkynyl, alkoxy, and haloalkoxy groups are each unsubstituted or substituted by one or more substituents, each of which is independently selected from halogen, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, -N3, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cycloalkyl, cycloalkenyl, cycloalkynyl, -C(O)OH, -C(O)OR 2c -NH2, -NHalkyl and -N(alkyl)2; -COR 2d -NR 2a R 2b -NR 2a COR 2d -CONR 2a R 2b and -OR 2c ; - R 2a Selected from hydrogen, alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, and cycloynyl; - R 2b Selected from hydrogen, alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, and cycloynyl; - R 2c Selected from hydrogen, alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, and cycloynyl; - R 2d Selected from hydroxyalkyl, alkoxyalkyl, hydroxy, hydrogen, alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, and cycloynyl; - Or, R 1 and R 2 Together with the carbon atom it is attached to, it can form a heterocyclic group (such as pyrrolidinyl). The heterocyclic group is either unsubstituted or substituted by one or more substituents, each of which is independently selected from halogens, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cycloalkyl, cycloalkenyl, cycloalkynyl, -C(O)OH, -NH2, -NHalkyl and -N(alkyl)2; - Or, R 2 X and the atoms to which they are attached can form a heterocyclic group, wherein the heterocyclic group is unsubstituted or substituted by one or more substituents, each of which is independently selected from halogens, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, -C(O)OH, -NH2, -NHalkyl and -N(alkyl)2; - R 3 Selected from hydrogen, halogen, nitro, -CN, -NR 3a R 3b 、-(CR 3f R 3g ) q -NR 3a R 3b 、-NR 3a -(CR 3f R 3g ) q -C(O)NR 3a R 3b 、-NR 3a -(CR 3f R 3g ) q -CO2R 3c 、-NR 3a -(CR 3f R 3g ) q -OR 3c 、-NR 3a -(CR 3f R 3g ) q -PO(OR 3i )2、-NR 3a -(CR 3f R 3g ) q -NR 3a C(O)R 3d 、-SR 3c 、-S(O)R 3d 、-S(O)2R 3c 、-S(O)2-NR 3a R 3b 、-OR 3c 、-(CR 3f R 3g ) q -OR 3c 、 、 、oxo, -NR 3a S(O)2R 3d 、-(CR 3f R 3g ) q -NR 3a S(O)2R 3d 、-NR 3a C(O)R 3d 、-(CR 3f R 3g ) q -NR 3a C(O)R 3d 、-(CR 3f R 3g ) q -CO2R 3c 、-(CR 3f R 3g ) q -C(O)R 3c 、-(CR 3f R 3g ) q -C(O)NR 3a R 3b hydroxyl, mercapto, alkyl, alkenyl, alkoxy, alkylamino, dialkylamino, alkylaminoalkyl, dialkylaminoalkyl, thioalkyl, alkoxyalkyl, alkylthioalkyl, alkoxyalkylamino, cycloalkyl, cycloalkenyl, cycloalkynyl, haloalkyl, haloalkenyl, haloalkynyl, aryl, heteroaryl, heterocyclic, arylalkyl, arylalkenyl, arylalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heterocyclic alkyl, heterocyclic alkenyl, and heterocyclic alkynyl. The alkyl, alkenyl, alkynyl, alkoxy, alkylamino, dialkylamino, alkylaminoalkyl, dialkylaminoalkyl, thioalkyl, alkoxyalkyl, alkylthioalkyl, alkoxyalkylamino, cycloalkyl, cycloalkenyl, cycloalkynyl, haloalkyl, haloalkenyl, haloalkynyl, aryl, heteroaryl, heterocyclic, arylalkyl, arylalkenyl, arylalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heterocyclic alkyl, heterocyclic alkenyl, and heterocyclic alkynyl Each group is either unsubstituted or substituted with one or more substituents, each substituent being independently selected from halogens, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, alkoxy, alkylthio, cycloalkyl, cycloalkenyl, cycloalkynyl, heterocyclic, -C(O)OH, -C(O)R 3i -C(O)-O-CH2-O-CO-R 3i -PO-(OR) 3i )2, -SO2F, -NH2, -NHalkyl and -N(alkyl)2; - Cycle A is selected from aryl (e.g., phenyl), cycloalkyl, cycloalkenyl, cycloynyl, heterocyclic and heteroaryl; - Y is NR 3h Or O; - Each R 6 Independently selected from hydrogen, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, alkoxy, (mono or di)alkylamino, alkylthio, alkylthioalkyl, alkoxyalkyl, (mono or di)alkylaminoalkyl, -(CR 3f R 3g ) q -O-(CR 3f R 3g ) v -CO2R 3c , hydroxyalkyl, -(CR 3f R 3g ) q -NR 3a SO2R 3d -CO2R 3c 、-(CR 3f R 3g ) q -O-(CR 3f R 3g ) v -Aryl, -(CR 3f R 3g ) q -O-(CR 3f R 3g ) v -Heteroaryl, -CONR 3a S(O)2R 3d -S(O)2R 3d 、-(CR 3f R 3g ) q -O-(CR 3f R 3g ) v -CN、-C(O)R 3d aryl, heteroaryl, heterocyclic, -C(O)NR 3a R 3b , Oxygenated, -S(O)2NR 3a R 3b -OR 3c and -(CR 3f R 3g ) q -O-(CR 3f R 3g ) v -O-aryl, The alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, alkoxy, (mono- or di)alkylamino, alkylthio, alkylthioalkyl, alkoxyalkyl, (mono- or di)alkylaminoalkyl, aryl, heteroaryl, and heterocyclic groups are each unsubstituted or substituted by one or more substituents, each substituent being independently selected from halogens, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cycloalkyl, cycloalkenyl, cycloalkynyl, -C(O)OH, -NH2, -NHalkyl, and -N(alkyl)2; Or, two Rs 6 Together with the carbon atom to which it is attached, it can form cycloalkyl, cycloalkenyl, cycloynyl, heterocyclic, or heteroaryl groups; wherein each of the cycloalkyl, cycloalkenyl, cycloynyl, heterocyclic, and heteroaryl groups is unsubstituted or substituted by one or more substituents, each of which is independently selected from -OH, halogen, -NR. 3a R 3b , aryl, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cycloalkyl, cycloalkenyl, and cycloalkynyl; - R 3a Selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, alkoxy, (mono or di)alkylamino, alkoxyalkyl, alkylthioalkyl, (mono or di)alkylaminoalkyl, haloalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, -SO2-alkyl, aryl, heteroaryl and heterocyclic; - R 3b Selected from hydrogen, alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, and cycloynyl; - R 3c Selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, alkoxyalkyl, alkylthioalkyl, (mono- or di)alkylaminoalkyl, haloalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, hydroxycarbonylalkyl, aminoalkyl, aminoalkenyl, aminoalkynyl, aryl, heteroaryl, and heterocyclic groups; - R 3d Selected from alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, alkoxyalkyl, alkoxy, (mono or di)alkylamino, (mono or di)alkylaminoalkyl, alkylthio, alkylthioalkyl, haloalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, aryl, heteroaryl, and heterocyclic groups; - R 3f and R 3g Each is independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, haloalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, -NH2, aminoalkyl, aminoalkenyl, aminoalkynyl, aryl, heteroaryl, and heterocyclic groups; - R 3h Selected from hydrogen, alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, and cycloynyl; - R 3i Selected from hydrogen, alkyl, cycloalkyl and aryl, wherein each alkyl, cycloalkyl and aryl group is optionally further substituted by one or more halogens; - m is an integer selected from 0, 1, 2, 3, 4 or 5; - p is an integer selected from 0, 1, 2, 3, 4 or 5; - q is an integer selected from 0, 1, 2, 3, 4 or 5; - v is an integer selected from 0, 1, 2, 3, 4 or 5; - W is selected from -CO-, -SO2-, -SO(=NH)- (sulfinimide group); - L is selected from -CR Lg R Lh -、-NR Lb - or a single key; - R Lg Selected from hydrogen, halogen, alkyl, alkenyl, alkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, -NR La R Lb , aminoalkyl, aminoalkenyl, aminoynyl, haloalkyl, -C(O)NR La R Lb Alkoxy, alkylamino, dialkylamino, alkylaminoalkyl, dialkylaminoalkyl, thioalkyl, alkoxyalkyl, alkylthioalkyl, deuterium, cycloalkyl, cycloalkenyl, and cycloynyl; - R Lh Selected from hydrogen, halogen, alkyl, alkenyl, alkynyl, deuterium, cycloalkyl, cycloalkenyl, and cycloalkynyl; - R La Selected from hydrogen, alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, and cycloynyl; - R Lb Selected from hydrogen, alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, and cycloynyl; - Or, R Lg and R Lh Together with the carbon atom to which it is attached, it can form cycloalkyl, cycloalkenyl, cycloynyl, or heterocyclic groups; - X is selected from -OR Xc -NR Xa R Xb aryl, heteroaryl, heterocyclic, aminoalkyl, aminoalkenyl, aminoynyl, -S(O)2R Xd -NR Xb S(O)2R Xd -NR Xb C(O)OR Xc -OC(O)R Xd -C(O)NR Xa R Xb -C(O)OR Xc , hydroxyalkyl, hydroxyalkenyl, hydroxyynyl, alkyl, alkenyl, ynyl, (mono- or di)alkylaminoalkyl, thioalkyl, alkoxyalkyl, alkylthioalkyl, cycloalkyl, cycloalkenyl, cycloynyl and -N3, The heteroaryl, heterocyclic, aryl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, hydroxyalkyl, hydroxyalkenyl, and hydroxyalkynyl groups are each unsubstituted or substituted by one or more substituents, each of which is independently selected from hydroxyalkyl, -C(O)NR Xa R Xb Heteroaryl, heterocyclic, alkyl-substituted heterocyclic, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, -C(O)OH, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, hydroxyalkoxy, aminoalkoxy, (mono or di)alkylaminoalkoxy, -NH2, -NHalkyl and -N(alkyl)2; - R Xa Selected from hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, alkoxyalkyl, aminoalkyl, aminoalkenyl, aminoalkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroaryl, heterocyclic, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heterocyclic alkyl, heterocyclic alkenyl, and heterocyclic alkynyl. The alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, alkoxyalkyl, aminoalkyl, aminoalkenyl, aminoalkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, heteroaryl, heterocyclic, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heterocyclic alkyl, heterocyclic alkenyl, and heterocyclic alkynyl are each unsubstituted or substituted by one or more substituents, each of which is independently selected from -CONR. Xe R Xf Hydroxylalkyl, heteroaryl, heterocyclic, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, -C(O)OH, O-alkyl, haloalkyl, alkoxy, haloalkoxy, -NH2, -NHalkyl and -N(alkyl)2; - R Xb Selected from hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, aminoalkyl, aminoalkenyl, aminoalkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, cycloalkyl, cycloalkenyl, and cycloalkynyl. The alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, hydroxyalkyl, hydroxyalkenyl, and hydroxyalkynyl groups are each unsubstituted or substituted by one or more substituents, each of which is independently selected from -CONR. Xe R Xf , hydroxyalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, C(O)OH, O-alkyl, haloalkyl, alkoxy, haloalkoxy, -NH2, -NHalkyl and -N(alkyl)2; - Each R Xc Selected from hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, alkoxyalkyl, aminoalkyl, aminoalkenyl, aminoalkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroaryl, heterocyclic, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heterocyclic alkyl, heterocyclic alkenyl, and heterocyclic alkynyl. The alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, alkoxyalkyl, aminoalkyl, aminoalkenyl, aminoalkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, heteroaryl, heterocyclic, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heterocyclic alkyl, heterocyclic alkenyl, and heterocyclic alkynyl are each unsubstituted or substituted by one or more substituents, each of which is independently selected from -CONR. Xa R Xb Hydroxylalkyl, heteroaryl, heterocyclic, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, -C(O)OH, haloalkyl, alkoxy, haloalkoxy, -NH2, -NHalkyl and -N(alkyl)2; - R Xd Selected from alkyl, alkenyl, alkynyl, haloalkyl, aminoalkyl, aminoalkenyl, aminoalkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroaryl, heterocyclic, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heterocyclic alkyl, heterocyclic alkenyl, and heterocyclic alkynyl. The alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, cycloynyl, aminoalkyl, aminoalkenyl, aminoynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyynyl, heteroaryl, heterocyclic, heteroarylalkyl, heteroarylalkenyl, heteroarylynyl, heterocyclic alkyl, heterocyclic alkenyl, and heterocyclic ynynyl are each unsubstituted or substituted by one or more substituents, each of which is independently selected from -CONR. Xa R Xb , hydroxyalkyl, heteroaryl, heterocyclic, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, mercapto, -SCF3, -SF5, cyano, nitro, oxo, amino, -C(O)OH, halogen, hydroxyl, haloalkyl, alkoxy and haloalkoxy; - R Xe and R Xf Each is independently selected from alkyl, alkenyl, alkynyl, haloalkyl, aminoalkyl, aminoalkenyl, aminoalkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroaryl, heterocyclic, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heterocyclic alkyl, heterocyclic alkenyl, and heterocyclic alkynyl. The alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, heteroaryl, heterocyclic, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heterocyclic alkyl, heterocyclic alkenyl, and heterocyclic alkynyl are each unsubstituted or substituted by one or more substituents, each of which is independently selected from hydroxyalkyl, heteroaryl, heterocyclic, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, mercapto, -SCF3, -SF5, cyano, nitro, oxo, amino, -C(O)OH, halogen, hydroxyl, haloalkyl, alkoxy, and haloalkoxy; - n is an integer selected from 1, 2, 3 or 4; - Each R 4 Independently selected from halogens, -SCF3, -SF5, -CF3, -OCF3, -CHF2, -OCHF2, -B(OH)2, -O-SO2-F, -SO2-F, cyano, nitro, -OR 4c -NR 4a R 4b -NR 4a S(O)2R 4d -NR 4a SO2NR 4a R 4b -NR 4a C(O)R 4c -NR 4a C(O)OR 4c -NR 4a C(O)NR 4a R 4b SR 4c -S(O)R 4d -S(O)2R 4c -S(O)2NR 4a R 4b -S(O)(NR) 4a )R 4c -S(NR) 4a (NR) 4a )R 4c -C(O)OR 4c -C(O)R 4c -C(O)NR 3a R 3b -P(O)R 4a R 4b Alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, heteroaryl, heterocyclic, cycloalkyl, cycloalkenyl, and cycloalkynyl. The alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxy, heteroaryl, heterocyclic, cycloalkyl, cycloalkenyl, and cycloalkynyl groups are each unsubstituted or substituted by one or more substituents, each of which is independently selected from -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, -B(OH)2, cyano, nitro, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, hydroxyalkyl, haloalkyl, alkoxy, haloalkoxy, -C(O)OH, -C(O)Oalkyl, -C(O)NH2, -C(O)NHalkyl, -C(O)N(alkyl)2, -NH2, -NHalkyl, and -N(alkyl)2; - Or, two Rs 4 Together with the carbon atom it is attached to, it can form cycloalkyl, cycloalkenyl, cycloynyl, or heterocyclic groups. The cycloalkyl, cycloalkenyl, cycloalkynyl, and heterocyclic groups are each unsubstituted or substituted by one or more substituents, each of which is independently selected from -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, cycloalkenyl, cycloalkynyl, hydroxyalkyl, haloalkyl, alkoxy, haloalkoxy, alkoxyalkyl, haloalkoxyalkyl, hydroxyalkoxyalkyl, -C(O)OH, -C(O)Oalkyl, -C(O)NH2, -C(O)NHalkyl, -C(O)N(alkyl)2, -NH2, -NHalkyl, and -N(alkyl)2; - R 4a Selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, haloalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, aminoalkyl, aminoalkenyl, and aminoalkynyl; - R 4b Selected from hydrogen, alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, and cycloynyl; - R 4c Selected from hydrogen, alkyl, deuterated alkyl, alkenyl, alkynyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, alkoxyalkyl and (mono- or di)alkylaminoalkyl; - R 4d Selected from alkyl, alkenyl, ynyl, cycloalkyl, cycloalkenyl, and cycloynyl groups; - R 5 Selected from hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, alkoxyalkyl, mono- or dialkylaminoalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, heterocyclic alkyl, heterocyclic alkenyl and heterocyclic alkynyl; The alkyl, alkenyl, alkynyl, haloalkyl, alkoxyalkyl, mono- or dialkylaminoalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, heterocyclic alkyl, heterocyclic alkenyl, and heterocyclic alkynyl are each unsubstituted or substituted by one or more substituents, each of which is independently selected from -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, hydroxyalkyl, haloalkyl, alkoxy, haloalkoxy, -C(O)OH, C(O)Oalkyl, -C(O)NH2, -C(O)NHalkyl, -C(O)N(alkyl)2, -NH2, -NHalkyl, and -N(alkyl)2; - Or, R 3 and R 5 Together with the atoms to which it is attached, it forms a heteroaryl or heterocyclic group, wherein the heteroaryl or heterocyclic group is optionally substituted by one or more substituents, the substituents being independently selected from -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, alkyl, alkenyl, alkynyl, phenyl, hydroxyalkyl, haloalkyl, alkoxy, haloalkoxy, -NH2, -NHalkyl and -N(alkyl)2; - Wherein, when a portion of -WLX is -C(O)O-tert-butyl, R 3 Not oxygenated or hydrogenated; The condition is that the compound is not: 1,3-Dihydro-6,8-dimethoxy-4-methyl-N-(1-methylethyl)-2H-pyrrolo[3,4-c]quinoline-2-carboxamide, N-Butyl-1,3-dihydro-6,8-dimethoxy-4-methyl-2H-pyrrolo[3,4-c]quinoline-2-carboxamide, 1,3-Dihydro-6,8-Dimethoxy-4-methyl-N-phenyl-2H-pyrrolo[3,4-c]quinoline-2-carboxamide, 1-(1,3-dihydro-6,8-dimethoxy-4-methyl-2H-pyrrolo[3,4-c]quinolin-2-yl)ketene, N-(2-ethoxyphenyl)-1,3-dihydro-6,8-dimethoxy-4-methyl-2H-pyrrolo[3,4-c]quinoline-2-carboxamide, N-(3,4-dichlorophenyl)-1,3-dihydro-6,8-dimethoxy-4-methyl-2H-pyrrolo[3,4-c]quinoline-2-carboxamide, 6-(1-((tert-butyloxycarbonyl)amino)propyl-2-yl)-1-oxo-1,3-dihydro-2H-pyrrolo[3,4-c]quinoline-2-carboxylic acid tert-butyl ester 1,3-Dihydro-6,8-Dimethoxy-4-methyl-N-[3-(trifluoromethyl)phenyl]-2H-pyrrolo[3,4-c]quinoline-2-carboxamide, 2-(2-Chloroacetyl)-4-methyl-8-[(2-nitro-1-pyrrolidinyl)sulfonyl]-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione 1,3-Dihydro-4-methyl-8-[(2-nitro-1-pyrrolidinyl)sulfonyl]-α,1,3-trioxo-2H-pyrrolo[3,4-c]quinoline-2-acetyl chloride, 2,3-Dihydro-8-methyl-2-[(4-methylphenyl)sulfonyl]-4-phenyl-1H-pyrrolo[3,4-c]quinoline-1-one, 7-Chloro-2,3-dihydro-2-[(4-methylphenyl)sulfonyl]-4-phenyl-1H-pyrrolo[3,4-c]quinoline-1-one, 8-Bromo-2,3-dihydro-2-[(4-methylphenyl)sulfonyl]-4-phenyl-1H-pyrrolo[3,4-c]quinoline-1-one, 8-Chloro-2,3-dihydro-2-[(4-methylphenyl)sulfonyl]-4-phenyl-1H-pyrrolo[3,4-c]quinoline-1-one, 8-Fluoro-2,3-dihydro-2-[(4-methylphenyl)sulfonyl]-4-phenyl-1H-pyrrolo[3,4-c]quinoline-1-one, 2,3-Dihydro-8-methoxy-4-(6-methyl-1H-indol-3-yl)-2-[(4-methylphenyl)sulfonyl]-1H-pyrrolo[3,4-c]quinoline, 8-(1,1-Dimethylethyl)-2,3-dihydro-4-(1H-indol-3-yl)-2-[(4-methylphenyl)sulfonyl]-1H-pyrrolo[3,4-c]quinoline, 2,3-Dihydro-2-[(4-methylphenyl)sulfonyl]-8-(4-morpholinylsulfonyl)-4-phenyl-1H-pyrrolo[3,4-c]quinoline-1-one, (3aS,9bS)-2-(benzo[d][1,3]dioxacyclopenten-5-ylsulfonyl)-8-hydroxy-5-methyl-1,2,3,3a,5,9b-hexahydro-4H-pyrrolo[3,4-c]quinoline-4-one (3aS,9bS)-2-(benzo[d][1,3]dioxacyclopenten-5-ylsulfonyl)-5-methyl-4-oxo-2,3,3a,4,5,9b-hexahydro-1H-pyrrolo[3,4-c]quinoline-8-carboxynitrile, (3aS,9bS)-2-(benzo[d][1,3]dioxacyclopenten-5-ylsulfonyl)-8-fluoro-5-methyl-1,2,3,3a,5,9b-hexahydro-4H-pyrrolo[3,4-c]quinoline-4-one (3aR,9bR)-1,3,3a,4,5,9b-hexahydro-2H-pyrrolo[3,4-c]quinoline-2-carboxylic acid tert-butyl ester (3aS,9bR)-8-(2-(trifluoromethyl)phenyl)-1,3,3a,4,5,9b-hexahydro-2H-pyrrolo[3,4-c]quinoline-2-carboxylic acid tert-butyl ester 、 、 、 。 2. The compound according to claim 1, wherein R 1 Selected from alkyl or hydroxyalkyl, such as methyl, hydroxymethyl and (n- or iso)propyl.

3. The compound according to any one of claims 1 and 2, wherein - R 2 Selected from hydrogen, -CONR 2a R 2b , aminoalkyl, alkyl and hydroxyalkyl; - R 2a Selected from hydrogen or alkyl; and - R 2b Selected from hydrogen or alkyl groups.

4. The compound according to any one of claims 1 to 3, having structural formula (VI) or (VII). (VI) (VII) Where R 1 R 3 R 4 n, R Xa R Xb R Xc and R Lg Each has the same meaning as defined in claims 1 to 3.

5. The compound according to any one of claims 1 to 3, wherein - W is -C(O)-; - Partial LX conforms ； - Z is either N or O; - Ring B is a heterocyclic group or a heteroaryl group; - u is 0, 1, 2, or 3; and - Each R 7 Independently selected from hydroxyalkyl, -C(O)NR Xa R Xb Heteroaryl, heterocyclic, heterocyclic substituted with one or more alkyl groups, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, -C(O)OH, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, hydroxyalkoxy, aminoalkoxy, (mono- or di)alkylaminoalkoxy, -NH2, -NHalkyl and -N(alkyl)2.

6. The compound according to any one of claims 1 to 5, wherein R 3 Selected from hydrogen, alkyl, -NR 3x R 3y and -OR 3z ,in: - The alkyl group is optionally substituted by one, two, or three substituents, said substituents being independently selected from halogens, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, alkoxy, alkylthio, cycloalkyl, cycloalkenyl, cycloalkynyl, -C(O)OH, -C(O)R 3i -C(O)-O-CH2-O-CO-R 3i -PO-(OR) 3i )2, -NH2, -NHalkyl and -N(alkyl)2; - R 3x R 3y and R 3z Each group is independently selected from hydrogen, alkyl, alkenyl, ynyl, cycloalkyl, and heterocyclic groups, wherein each alkyl, alkenyl, ynyl, cycloalkyl, and heterocyclic group is optionally further substituted by one, two, or three substituents, said substituents being independently selected from halogen, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, alkyl, alkenyl, ynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, alkylthio, cycloalkyl, cycloalkenyl, cycloynyl, -C(O)OH, -C(O)R 3i -C(O)-O-CH2-O-CO-R 3i -PO-(OR) 3i )2, -NH2, -NHalkyl and -N(alkyl)2; - Or, R 3x and R 3y Together they form a heterocycle optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, =O, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cycloalkyl, cycloalkenyl, cycloalkynyl, -C(O)OH, -NH2, -NHalkyl, and -N(alkyl)2.

7. The compound according to any one of claims 1 to 6, wherein - Each R 4 Independently selected from halogens, -CF3, -OCF3, -CHF2, -B(OH)2, -O-SO2-F, -SO2-F, -OCHF2, alkyl groups, -OR 4c , haloalkyl, -CN, haloalkoxy, hydroxyalkyl, haloalkoxy, hydroxyalkyl, alkoxyC 1-6 Alkyl and cycloalkyl; - Or, two Rs 4 Together with the carbon atom it is attached to, it can form cycloalkyl, cycloalkenyl, or heterocyclic groups; - R 4c Selected from alkyl, deuterated alkyl, alkoxyalkyl, hydroxyalkyl, and haloalkyl; and - n is an integer selected from 1, 2, 3 or 4.

8. The compound according to any one of claims 1 to 5, wherein R 5 It is selected from hydrogen, alkyl, haloalkyl, alkoxyalkyl, (mono or di)aminoalkyl, hydroxyalkyl, aminoalkyl, cycloalkylalkyl and heterocyclic alkyl.

9. The compound according to any one of claims 1 to 3, having the structure shown in formula (IVc) or (IVd), (IVc) (IVd), of which - R 4.1 R 4.2 and R 4.3 With R 4 Same meaning; - s is 0, 1, or 2; - t is 0 or 1; - R 1 R 2 R 3 R 4 L and X each have the same meaning as defined in any one of claims 1 to 7.

10. The compound according to claim 9, wherein... - R 1 Selected from C 1-6 Alkyl or hydroxy C 1-6 Alkyl groups, such as methyl, hydroxymethyl, and (n- or iso)propyl; - R 2 It is hydrogen; - -LX is selected from -CH(R) Lg )-OR Xc -CD(R) Lg )-OR Xc -CH(R) Lg )-N(R Xa (R) Xb )or ; - u can be 0, 1, 2, or 3; - Ring B is a heterocyclic group or a heteroaryl group; - Each R 7 Independently selected from hydroxyl C 1-6 Alkyl, -C(O)NR Xa R Xb heteroaryl, heterocyclic, via one or more C 1-6 Alkyl-substituted heterocyclic groups, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 cycloalkyl, C 5-10 Cycloalkenyl, C 5-10 Cycloalkyne, -OH, =O, halogen, -SH, =S, -CF3, -CHF2, -OCF3, -OCHF2, -SCF3, -SF5, cyano, nitro, -C(O)OH, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, hydroxyl C 1-6 Alkoxy, amino C 1-6 Alkoxy, single C 1-6 Alkylamino C 1-6 Alkoxy, diC 1-6 Alkylamino C 1-6 Alkoxy, -NH2, -NHC 1-6 Alkyl and -N(C) 1-6 Alkyl)2; - R 4.1 and R 4.3 Independently selected from halogens, -CF3, -OCF3, -CHF2, -OCHF2, alkyl groups, -OR 4c Halogenated C 1-6 Alkyl, -CN, Halogenated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl and C 3-10 cycloalkyl; - R 4.2 Selected from hydrogen, halogens, -CF3, -OCF3, -CHF2, -OCHF2, C 1-6 Alkyl, -OR 4c Halogenated C 1-6 Alkyl, -CN, Halogenated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl and C 3-10 cycloalkyl; - s and t are 0; - Where Z and R 7 R 4c R Lg R Xa R Xb and R Xc It has the same meaning as defined in any one of claims 1 to 7.

11. A pharmaceutical composition comprising a compound according to any one of claims 1 to 10, and a pharmaceutically acceptable carrier, solvent, adjuvant, or diluent.

12. The compound according to any one of claims 1 to 10 or the pharmaceutical composition according to claim 11, used as a medicine.

13. The compound or pharmaceutical composition according to claim 12, used as a medicament for the treatment or prevention of cGAS-mediated diseases, more specifically diseases in which type I interferon (IFN) responses are abnormally activated.

14. The compound or pharmaceutical composition used as a medicament according to claim 13, wherein the cGAS-mediated disease is selected from systemic lupus erythematosus (SLE), cutaneous lupus erythematosus (CLE), lupus nephritis (LN), interferon disease, psoriasis, insulin-dependent diabetes mellitus (IDDM), vasculitis, scleroderma, Aicardi Goutieres syndrome, dermatomyositis, sepsis, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, Sjögren's syndrome (SS), age-related macular degeneration (AMD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer's disease, Huntington's disease, and Parkinson's disease.

15. A method for treating or preventing cGAS-mediated disease in a subject in need, the method comprising administering to the subject in need of such treatment an effective amount of one or more compounds according to any one of claims 1 to 10 or a pharmaceutical composition according to claim 11, wherein, in particular, the cGAS-mediated disease is an inflammatory condition, more particularly selected from systemic lupus erythematosus (SLE), cutaneous lupus erythematosus (CLE), lupus nephritis (LN), interferon disease, psoriasis, insulin-dependent diabetes mellitus (IDDM), vasculitis, scleroderma, Aicardi Goutieres syndrome, dermatomyositis, sepsis, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, Sjögren's syndrome (SS), age-related macular degeneration (AMD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer's disease, Huntington's disease, and Parkinson's disease.

16. A method for preparing a compound according to any one of claims 1 to 10, comprising the following steps: - The pyrrolidine-containing compound shown in formula (A1) is coupled with the electrophilic reagent shown in formula LG-WLX-PG, and PG is further removed (if PG is different from Me) to obtain the compound shown in formula (A2), wherein R 1 R 2 R 3 R 4 W, L, X, and n have the meaning according to any one of claims 1 to 10, wherein PG is a protecting group and LG is a leaving group; or - Make the compound shown in formula (A3) and formula HR 3 The nucleophile reaction shown is followed by the removal of PG (if PG is different from Me) to obtain the compound shown in formula (A2), wherein R 1 R 2 R 3 R 4 W, L, X, and n have the meaning according to any one of claims 1 to 10, wherein PG is a protecting group and LG is a leaving group; or - The pyridone-containing compound shown in formula (A4) is combined with formula R 5 -LG is coupled with an electrophilic reagent and PG is further removed (if PG is different from Me) to obtain a compound of formula (A5) or (A6), wherein R 1 R 2 R 3 R 5 W, L, X, and n have the meaning according to any one of claims 1 to 10, wherein PG is a protecting group, LG is a leaving group, and wherein the group -OR 5 Corresponding to the group -OR as defined in any one of claims 1 to 10 3c ;or - The compound shown in formula (A7) is reacted with the nucleophile shown in formula HX-PG, and PG is further removed to obtain the compound shown in formula (A2), wherein R 1 R 2 R 3 R 4 W, L, X, and n have the meaning according to any one of claims 1 to 10, wherein PG is a protecting group and LG is a leaving group; or - The halogen-containing compound of formula (A8) is coupled with a suitable R using methods known to those skilled in the art (Suzuki coupling, Negishi coupling, Stille coupling, etc.). 4.4 The reagent (e.g., boric acid or borate ester, organozinc, tinane) reacts with the product, and PG is further removed to obtain the compound shown in formula (A2a), wherein R 1 R 2 R 3 R 4 R 4.4 W, L, X and n have the meaning of any one of claims 1 to 10, wherein PG is a protecting group and X1 is a halogen; 。

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