6-alkoxypyrazolopyrimidine compound and pharmaceutical use thereof

Abstract

To provide a 6-alkoxypyrazolopyrimidine compound or a pharmaceutically acceptable salt thereof that has an inhibitory activity on NLRP3 inflammasomes, a pharmaceutical composition containing the same, and a pharmaceutical use thereof.SOLUTION: Provided is a compound of formula [I] or a pharmaceutically acceptable salt thereof.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a 6-alkoxypyrazolopyrimidine compound or a pharmaceutically acceptable salt thereof having NLRP3 inflammasome inhibitory activity, a pharmaceutical composition containing the same, and medical uses thereof. [Background technology]

[0002] NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) is a pattern recognition receptor belonging to the NLR (NOD-like receptors) family, and is expressed not only in phagocytic cells such as macrophages and microglia but also in non-immune cells such as glomerular epithelial cells and renal tubular epithelial cells.

[0003] NLRP3 recognizes DAMPs (Danger Associated Molecular Patterns), which are molecular patterns specific to cytotoxic factors (ATP, HMGB1, S100, uric acid crystals, silica, etc.), and PAMPs (Pathogen Associated Molecular Patterns), which are molecular patterns specific to pathogenic microorganisms (viruses, bacteria, fungi, etc.), and is activated by binding to these molecules.

[0004] Activated NLRP3 associates with the adaptor protein ASC (Apoptosis-associated speck-like protein containing a caspase recruitment domain) and the cysteine ​​protease caspase-1 through protein-protein interactions to form the intracellular protein complex NLRP3 inflammasome. Upon NLRP3 inflammasome formation, caspase-1 within the complex is converted to its active form, which converts proIL-1β, the precursor of the proinflammatory cytokine IL-1β, to active IL-1β, and proIL-18, the precursor of IL-18, to active IL-18. The extracellularly secreted active IL-1β induces inflammatory responses by inducing the production of inflammatory cytokines and chemokines by surrounding cells and activating immune cells such as T cells.

[0005] Increased levels of DAMPs were observed in the brains and cerebrospinal fluid of multiple sclerosis patients (Non-Patent Document 1), as well as increased caspase 1 expression in lesions and increased IL-1β levels in cerebrospinal fluid (Non-Patent Document 2). Furthermore, activated microglia are present in lesions during the chronic progression stage of this disease (Non-Patent Document 3), and activated microglia stimulated by DAMPs produce inflammatory cytokines such as IL-1β, inducing neuroinflammation and neurological disorders (Non-Patent Document 4). Therefore, the NLRP3 inflammasome is thought to be involved in the pathogenesis of multiple sclerosis.

[0006] Myelin Oligodendrocyte Glycoprotein (MOG) produced by sensitizing mice to MOG 35-55 EAE model mice exhibit motor dysfunction similar to that seen in multiple sclerosis. However, NLRP3 knockout mice exhibited no significant motor deficits. 35-55In EAE models, the onset of motor dysfunction is suppressed (Non-Patent Document 5). Furthermore, in cuprizone model mice created by administering the copper chelating compound cuprizone to mice, central nervous system demyelination similar to multiple sclerosis develops, but the progression of demyelination is delayed in NLRP3 knockout mice (Non-Patent Document 6). JC-171, an NLPR3 inflammasome inhibitor, inhibits MOG 35-55 In an EAE model, administration after the onset of symptoms suppressed motor dysfunction (Non-Patent Document 7). Therefore, NLRP3 inflammasome inhibitors are considered to be therapeutic agents for multiple sclerosis.

[0007] Increased expression of NLRP3 inflammasome-related genes has been reported in the kidneys of patients with chronic kidney disease (Non-Patent Documents 8 and 9). Furthermore, in a 5 / 6 nephrectomy model, a preclinical chronic kidney disease model, it has been reported that NLRP3 knockout suppresses proteinuria and tubulointerstitial fibrosis (Non-Patent Document 10). Based on these results, NLRP3 inflammasome inhibitors are considered to be potential therapeutic agents for chronic kidney disease.

[0008] Increased expression of NLRP3 inflammasome-related genes has been reported in the intestines of patients with inflammatory bowel diseases (e.g., ulcerative colitis and Crohn's disease) (Non-Patent Document 11). IL-1β, produced by activation of NLRP3, is elevated in the intestinal mucosa of IBD patients, and increased IL-1β secretion from the colon has been reported to be positively correlated with worsening pathology (Non-Patent Document 11). It has also been reported that dysfunction of CARD8, which negatively regulates inflammasome activity, increases susceptibility to Crohn's disease and activates the NLRP3 inflammasome, enhancing IL-1β production from monocytes (Non-Patent Document 12). It has been reported that NLRP3 deficiency suppresses intestinal pathology in a TNBS-induced colitis model (Non-Patent Document 13). Based on these results, NLRP3 inflammasome inhibitors are considered to be potential therapeutic agents for inflammatory bowel disease.

[0009] Increased expression of NLRP3 inflammasome-related genes has been reported in atherosclerotic areas of the coronary arteries of patients with myocardial infarction (Non-Patent Document 14). Furthermore, it has been reported that NLRP3 knockout suppresses lesion formation in high-fat diet-fed low-density lipoprotein receptor (LDL) receptor-deficient mice, a model of atherosclerosis (Non-Patent Document 15). Based on these results, NLRP3 inflammasome inhibitors are considered to be therapeutic agents for atherosclerosis.

[0010] Cryopyrin-associated periodic syndrome (CAPS) is a collective term for autoinflammatory diseases caused by activating mutations in the NLRP3 gene. It is classified into three disease types: mild familial cold autoinflammatory syndrome (FCAS), moderate Muckle-Wells syndrome (MWS), and severe chronic infantile neurologic cutaneous and articular syndrome (CINCA) or neonatal onset multisystem inflammatory disease (NOMID) (Non-Patent Document 16). More than 200 mutations in the NLRP3 gene have been reported in CAPS (Non-Patent Document 17). These NLRP3 gene mutations result in the formation and activation of the NLRP3 inflammasome even in the absence of activating signals. Mice expressing CAPS-associated NLRP3 mutations exhibit systemic, lethal inflammation dependent on the NLRP3 inflammasome and downstream signaling molecules IL-1β and IL-18 (Non-Patent Document 18). In mice expressing CAPS-associated NLRP3 mutations, the NLRP3 inflammasome inhibitor CY-09 suppressed systemic, lethal inflammation and improved survival (Non-Patent Document 19). Based on these results, NLRP3 inflammasome inhibitors are considered to be potential therapeutic agents for CAPS.

[0011] Increased expression of NLRP3 inflammasome-related genes has been reported in the liver tissue of patients with nonalcoholic steatohepatitis (NASH) (Non-Patent Document 20). Furthermore, it has been reported that NLRP3 knockout suppresses liver fibrosis in a choline-deficient, amino acid-substituted diet model of NASH (Non-Patent Document 20). Based on these results, NLRP3 inflammasome inhibitors are considered to be potential therapeutic agents for NASH.

[0012] In gout and gouty arthritis, uric acid crystals deposited in joints and periarticular tissues induce inflammation (Non-Patent Document 21). Uric acid crystals activate NLRP3 in macrophages, leading to the production of IL-1β and IL-18 (Non-Patent Document 22). In an arthritis model induced by intra-articular uric acid injection, the NLRP3 inflammasome inhibitor OLT1177 suppressed arthritis (Non-Patent Document 23). Based on these results, NLRP3 inflammasome inhibitors are considered to be potential therapeutic agents for gout and gouty arthritis.

[0013] Increased expression of NLRP3 inflammasome-related genes has been reported in the synovial membranes and peripheral blood mononuclear cells of patients with rheumatoid arthritis (Non-Patent Document 24). Increased expression of NLRP3 inflammasome-related genes has also been reported in the synovial membranes of collagen-induced arthritis, a model of rheumatoid arthritis (Non-Patent Document 25). Based on these results, NLRP3 inflammasome inhibitors are considered to be therapeutic agents for rheumatoid arthritis.

[0014] Trinitrochlorobenzene, which induces contact dermatitis, increases IL-1β production from human skin keratinocytes via NLRP3 activation, and it has been reported that NLRP3 knockout suppresses the onset of dermatitis in a trinitrochlorobenzene-induced contact dermatitis model (Non-Patent Document 26). Based on these results, NLRP3 inflammasome inhibitors are considered to be potential therapeutic agents for contact dermatitis.

[0015] Increased expression of NLRP3 inflammasome-related genes has been reported in the tears and ocular surface of dry eye patients (Non-Patent Documents 27, 28). Furthermore, when cultured human corneal epithelial cells are subjected to hyperosmotic stress to induce dry eye, increased expression of NLRP3 inflammasome-related genes and increased IL-1β production have been observed, and knockdown of the NLRP3 gene has been reported to suppress IL-1β production (Non-Patent Document 28). Based on these results, NLRP3 inflammasome inhibitors are considered to be potential therapeutic agents for dry eye.

[0016] It has been reported that the expression of the ASC domain of the NLRP3 inflammasome is elevated in macrophages and neutrophils infiltrating the myocardial tissue of patients with acute myocardial infarction (Non-Patent Document 29). Furthermore, in an ischemia-reperfusion model of myocardial infarction, it has been reported that the expression of NLRP3 inflammasome-related genes is elevated in the infarcted area, and that knockdown of the NLRP3 gene reduces the infarct size and myocardial contractility (Non-Patent Document 30). Based on these results, it is believed that NLRP3 inflammasome inhibitors could be used as therapeutic agents for ischemic heart disease, such as acute myocardial infarction.

[0017] It has been reported that the expression of IL-1β or IL-18 is increased in the serum and glomeruli of patients with systemic lupus erythematosus (SLE) (Non-Patent Documents 31, 32), and that NLRP3 gene expression and IL-1β production are increased in macrophages (Non-Patent Document 33). Furthermore, in Nlrp3-R258W mice, which have an activating mutation in the NLRP3 gene, administration of pristane exacerbates lupus nephritis-like symptoms (Non-Patent Document 34). Based on these results, NLRP3 inflammasome inhibitors are considered to be potential therapeutic agents for SLE.

[0018] In addition to the above diseases, diseases for which NLRP3 inflammasome inhibitors are expected to be effective include systemic juvenile idiopathic arthritis (Non-Patent Document 35), recurrent pericarditis (Non-Patent Document 36), adult-onset Still's disease (e.g., hemophagocytic lymphohistiocytosis and macrophage activation syndrome) (Non-Patent Document 37), Schnitzler syndrome (Non-Patent Document 38), IL-1 receptor antagonist molecule deficiency (Non-Patent Document 39), familial Mediterranean fever (Non-Patent Document 40), mevalonate kinase deficiency (Non-Patent Document 40), hyper-IgD syndrome (Non-Patent Document 40), TNF receptor-associated periodic syndrome (Non-Patent Document 40), Behçet's disease (Non-Patent Document 41), and lung cancer (Non-Patent Document 42). The therapeutic effects of anti-IL-1β antibodies such as canakinumab and IL-1 inhibitors such as rilonacept have been reported for these diseases. Since the NLRP3 inflammasome is involved in the production of inflammatory cytokines such as IL-1β, NLRP3 inflammasome inhibitors are thought to be a potential treatment for these diseases.

[0019] It has been reported that the NLRP3 rs10733113 genotype is significantly elevated in psoriasis patients, increasing their susceptibility to psoriasis (Non-Patent Document 43). It has also been reported that NLRP3 deficiency suppresses psoriasis symptoms in an IL-23-induced psoriasis model (Non-Patent Document 44). Based on these results, NLRP3 inflammasome inhibitors are considered to be potential therapeutic agents for psoriasis.

[0020] Gout, atherosclerosis, and chronic kidney disease, which are associated with NLRP3 inflammasome activation, are accompanied by hypertension. NLRP3 deficiency has been reported to suppress hypertension in a mouse left renal artery stenosis model (Non-Patent Document 45). Furthermore, the NLRP3 inflammasome inhibitor MCC950 has been reported to suppress hypertension in a deoxycorticosterone acetate-treated mouse model (Non-Patent Document 46). Based on these results, NLRP3 inflammasome inhibitors are considered to be potential therapeutic agents for hypertension.

[0021] It has been reported that NLRP3 expression is elevated in the proliferative membranes of patients with diabetic retinopathy (Non-Patent Document 47). Furthermore, NLRP3 expression is elevated in the STZ-induced diabetic retinopathy model (Non-Patent Document 48). In this model, it has been reported that reduction of NLRP3 expression by NLRP3 shRNA results in decreased IL-1β and VEGF secretion, increased ganglion cell mass, and recovery from retinal damage (Non-Patent Document 49). Based on these results, NLRP3 inflammasome inhibitors are considered to be potential therapeutic agents for diabetic retinopathy.

[0022] NLRP3 inflammasome activation occurs in the brains of patients with Alzheimer's disease, mild cognitive impairment (MCI), and APP / PS1 mice, a mouse model of Alzheimer's disease. NLRP3 deficiency in APP / PS1 mice suppresses the development of spatial memory impairment (Non-Patent Document 50). The NLRP3 inhibitor MCC950 suppresses NLRP3 activation in microglia and improves cognitive dysfunction in APP / PS1 mice (Non-Patent Document 51). Therefore, NLRP3 inflammasome inhibitors are considered to be potential therapeutic agents for Alzheimer's disease and MCI.

[0023] In the substantia nigra of Parkinson's disease patients and mice injected with α-synuclein preformed fibrils (PFFs), a pathological model of Parkinson's disease, increased expression of NLRP3 inflammasome-related molecules in microglia and activation of the NLRP3 inflammasome occur (Non-Patent Document 52). The NLRP3 inhibitor MCC950 suppresses NLRP3 activation in the substantia nigra and inhibits the neuronal death of dopamine neurons in the substantia nigra in mice injected with α-synuclein PFFs (Non-Patent Document 52). Therefore, NLRP3 inflammasome inhibitors are considered to be potential therapeutic agents for Parkinson's disease.

[0024] In patients with Huntington's disease, the cerebrospinal fluid concentration of IL-1β, an NLRP3 inflammasome-associated cytokine, is increased (Non-Patent Document 53). In R6 / 2 mice, a pathological model of Huntington's disease, NLRP3 inflammasome expression levels in the striatum are increased (Non-Patent Document 54). The NLRP3 inhibitor MCC950 suppresses NLRP3 inflammasome activation in the striatum of R6 / 2 mice, suppressing neuronal cell death in the striatum and symptom progression (Non-Patent Document 55). Therefore, NLRP3 inflammasome inhibitors are considered to be therapeutic agents for Huntington's disease.

[0025] In the spinal cords of patients with amyotrophic lateral sclerosis (ALS), expression of the NLRP3 inflammasome, IL-18, and activated caspase 1 is increased (Non-Patent Document 56). In the spinal cords of ALS model mice, SOD1G93A mice and TDP-43Q331K mice, mRNA expression of IL-1β, Nlrp3, Pycard, and Casp1 is increased (Non-Patent Document 57). The NLRP3 inhibitor MCC950 suppresses NLRP3 activation in microglia induced by SOD1G93A and TDP-43 proteins, reducing IL-1β production (Non-Patent Document 57). In SOD1G93A mice, deficiency of IL-1β or caspase 1 extends survival, and administration of an IL-1β receptor antibody suppresses disease progression and extends survival (Non-Patent Document 58). Therefore, NLRP3 inflammasome inhibitors are considered to be potential treatments for ALS.

[0026] The expression level of the NLRP3 inflammasome is increased in the brain tissue and cerebrospinal fluid of patients with traumatic brain injury (TBI) (Non-Patent Documents 59, 60). In the brain tissue of TBI model rats, the expression level of the NLRP3 inflammasome is increased, along with the expression levels of IL-1β and IL-18 (Non-Patent Document 61). The NLRP3 inhibitor MCC950 suppresses IL-1β production in TBI model mice and suppresses the onset of neurological symptoms after brain trauma (Non-Patent Document 62). Therefore, NLRP3 inflammasome inhibitors are considered to be potential therapeutic agents for TBI.

[0027] Expression of the NLRP3 inflammasome, IL-1β, and IL-18 is increased in the brain tissue of patients with cerebral infarction, mice with middle cerebral artery occlusion (MCAO), a model of cerebral infarction, and rats with intracerebral hemorrhage (Non-Patent Documents 63, 64). Furthermore, the NLRP3 inhibitor MCC950 exhibited neuroprotective effects in MCAO and rats with intracerebral hemorrhage. Therefore, NLRP3 inflammasome inhibitors are considered to be potential therapeutic agents for cerebral infarction and cerebral hemorrhage.

[0028] Expression of the NLRP3 inflammasome is increased in the brain tissue of patients with temporal lobe epilepsy and in pilocarpine-induced epilepsy model mice (Non-Patent Documents 65, 66). Furthermore, in pilocarpine-induced epilepsy model mice, NLRP3 inflammasome deficiency and administration of the NLRP3 inhibitor MCC950 suppressed hippocampal neuronal apoptosis, which is the cause of epilepsy (Non-Patent Document 66). Therefore, NLRP3 inflammasome inhibitors are considered to be potential therapeutic agents for epilepsy.

[0029] In the peripheral blood of patients with depression, NLRP3 inflammasome expression levels, IL-1β levels, and IL-18 levels are increased, and IL-1β levels correlate with depression symptom scores (Non-Patent Document 67). In pathological models of depression, such as LPS-induced models, chronic stress-induced models, and social defeat models, increased expression of NLRP3 inflammasome, IL-1β, or IL-18 in brain tissue and NLRP3 inflammasome activation occur (Non-Patent Documents 68, 69, 70). Furthermore, in pathological models, administration of the NLRP3 inhibitor MCC950 or NLRP3 deficiency has been shown to improve depressive symptoms (Non-Patent Documents 69, 70). Therefore, NLRP3 inflammasome inhibitors are considered to be potential therapeutic agents for depression.

[0030] In the peripheral blood of patients with autism spectrum disorder (ASD), NLRP3 inflammasome expression levels and IL-1β and IL-18 concentrations are increased (Non-Patent Document 71). In the maternal immune activation (MIA) model, administration of PolyIC to pregnant animals causes ASD symptoms in offspring. In this model, IL-1β expression is increased in the fetal brain, and administration of the NLRP3 inhibitor MCC950 to the mother suppresses the onset of ASD symptoms in offspring (Non-Patent Document 72). Therefore, NLRP3 inflammasome inhibitors are considered to be potential therapeutic agents for ASD.

[0031] In the spinal cord of mice with spinal cord injury, NLRP3 inflammasome or IL-1β expression is increased, and NLRP3 activation is observed (Non-Patent Documents 73, 74). Furthermore, administration of the NLRP3 inhibitor MCC950 to mice after spinal cord injury suppresses NLRP3 activation and IL-1β expression in the spinal cord and promotes recovery of motor function (Non-Patent Document 73). Therefore, NLRP3 inflammasome inhibitors are considered to be therapeutic agents for spinal cord injury.

[0032] In an intestinal perforation model, an animal model of sepsis, increased expression and activation of the NLRP3 inflammasome or IL-1β occurs in the brain, resulting in hippocampal neuronal damage and memory impairment, a symptom of septic encephalopathy (Non-Patent Documents 75, 76). Administration of the NLRP3 inhibitor MCC950 to an intestinal perforation model suppresses NLRP3 inflammasome activation and improves memory impairment (Non-Patent Document 76). Therefore, NLRP3 inflammasome inhibitors are considered to be therapeutic agents for septic encephalopathy.

[0033] In the chronic constriction injury (CCI) model, an animal model of neuropathic pain, the expression levels of IL-1β and NLRP3 inflammasome-related molecules are increased in glial cells and neurons in the spinal cord (Non-Patent Document 77). Furthermore, in the paclitaxel-induced pain model, a neuropathic pain model in anticancer drug-induced neuropathy, the expression levels of NLRP3 inflammasome-related molecules are increased in the dorsal root ganglion and sciatic nerve (Non-Patent Document 78). Furthermore, in an animal model of trigeminal neuralgia, the expression level of NLRP3 inflammasome is increased in the dorsal horn of the spinal cord, and deletion of NLRP3 in the spinal cord suppresses spinal NLRP3 inflammasome activation and allodynia in response to mechanical stimulation (Non-Patent Document 79). Therefore, NLRP3 inflammasome inhibitors are considered to be therapeutic agents for neuropathic pain.

[0034] Mice infected with SARS-CoV-2 exhibit increased expression of IL-1β and NLRP3 inflammasome-related molecules in lung tissue. In contrast, NLRP3 knockout mice exhibit no increase in these expression levels, and severe respiratory inflammation caused by SARS-CoV-2 is suppressed. Furthermore, administration of the NLRP3 inhibitor MCC950 to SARS-CoV-2-infected mice suppresses NLRP3 inflammasome activation and excessive immune responses in the lungs (Non-Patent Document 80). Therefore, NLRP3 inflammasome inhibitors are considered to be a potential treatment for COVID-19 caused by SARS-CoV-2.

[0035] Increased levels of the ASC domain of the NLRP3 inflammasome and mature IL-1β protein have been reported in the cerebral cortex of patients with frontotemporal dementia with tau protein mutations (Non-Patent Document 81). Increased levels of the ASC domain of the NLRP3 inflammasome and post-cleavage caspase 1 have also been reported in the cerebral cortex of Tau22 mice (mice expressing human mutant tau protein), a model of frontotemporal dementia. NLRP3 knockout has also been reported to suppress tau pathology formation and cognitive decline (Non-Patent Document 81). Based on these results, NLRP3 inflammasome inhibitors are considered to be potential therapeutic agents for frontotemporal dementia.

[0036] Patients with NLRP3-associated autoinflammatory disease (NLRP3-AID), caused by activating mutations in the NLRP3 gene, exhibited drusen formation, which is thought to be the causative agent of age-related macular degeneration (AMD) (Non-Patent Document 82). Furthermore, in an Alu RNA-induced retinal pigment epithelial cell degeneration model, a model of age-related macular degeneration, NLRP3 inhibitors suppressed retinal pigment epithelial cell degeneration (Non-Patent Document 83). In a laser-induced choroidal neovascularization model, another model of age-related macular degeneration, NLRP3 inhibitors suppressed angiogenesis (Non-Patent Document 83). Based on these results, NLRP3 inflammasome inhibitors are considered to be potential therapeutic agents for age-related macular degeneration.

[0037] In patients with diabetic macular edema, diabetes increases retinal vascular permeability, causing leakage of blood components into the retina (Non-Patent Document 84). The NLRP3 inhibitor MCC950 improved the increased retinal vascular permeability in STZ-induced diabetic mice (Non-Patent Document 85). Therefore, NLRP3 inflammasome inhibitors are considered to be a therapeutic agent for diabetic macular edema.

[0038] Hereditary transient keratoephtheria is a cryopyrin-associated periodic fever syndrome caused by activating mutations in the NLRP3 gene (Non-patent Document 86). Therefore, NLRP3 inflammasome inhibitors are thought to be a potential therapeutic agent for hereditary transient keratoephtheria. [Prior art documents]

Non-licensed literature

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[0040] The present invention provides a 6-alkoxypyrazolopyrimidine compound or a pharmaceutically acceptable salt thereof having NLRP3 inflammasome inhibitory activity, a pharmaceutical composition containing the same, and a pharmaceutical use thereof, etc. That is, the present invention includes the following exemplary embodiments.

[0041] [Section 1] A compound of formula [I] or a pharmaceutically acceptable salt thereof (hereinafter, in this specification, "a compound of formula [I] or a pharmaceutically acceptable salt thereof" may also be referred to as "compound [I]"). [ka] {In the formula, The ring group Cy is (1) Formula: [ka] (In the formula, R 4 and R 5 are each independently (a) hydrogen, (b) cyano, (c)C 1-6 alkyl {wherein the alkyl is (1) Hydroxy, (2) C 1-4 Alkoxy, and (3) C 3-6 cycloalkyl; (d)C 1-4 Alkoxy, (e) halogens, (f)C 1-4 haloalkyl, (g)-OC 1-4 haloalkyl, (h)-O-CD3, or (I C 3-6 cycloalkyl, R 6 and R 7 are each independently (a) hydrogen, (b)C 1-4 Alkyl, (c)C 1-4 alkoxy, or (d) a halogen; R 8 teeth, (a) hydrogen, (b)C 1-6 alkyl (wherein the alkyl is hydroxy or C 1-4 optionally substituted with alkoxy; (c)C 1-4 Alkoxy, (d) halogens, (e)C 1-6 haloalkyl, (f)-OC 1-4 haloalkyl, or (g)C 3-6 cycloalkyl, wherein the cycloalkyl is optionally substituted with one or two hydroxy or halogen groups; or R 8 is R 6 or R 7 and together with the carbon atom to which they are attached may form a 5- to 7-membered heterocycloalkene containing 1 or 2 oxygen atoms. or a group represented by (2) Formula: [ka] (In the formula, R 9 and R 10 are each independently, C 1-4 Alkyl or C 1-4 is haloalkyl, R 11 is C 1-6 alkyl) is a group represented by R 1 teeth, (1) Hydrogen, (2) Cyano, (3) C 1-4 Alkyl, (4) Halogen, or (5) C 3-6 cycloalkyl, R 2 is hydrogen or C 1-4 is alkyl, R 3 teeth, (1)C 1-6 alkyl {wherein the alkyl is (a) hydroxy, (b) cyano, (c)C 1-4 Alkoxy, (d)-NR 12 R 13 (where R 12 and R 13 are each independently, C 1-4 alkyl), (e)-SO2-C 1-6 Alkyl, (f)C 3-6 Cycloalkyl (wherein the cycloalkyl is cyano, or C 1-4 C optionally substituted with alkoxy 1-4 optionally substituted with alkyl, (g) 4- to 6-membered heterocycloalkyl containing one oxygen or sulfur atom, wherein the heterocycloalkyl is optionally substituted with one or two oxo; and (h) phenyl, optionally substituted with 1 or 2 substituents independently selected from the group consisting of: (2) C 1-6 haloalkyl (wherein the haloalkyl is optionally substituted with hydroxy); (3)-CD3, (4) C 3-6 Cycloalkyl (wherein the cycloalkyl is -SO2-C 1-4 optionally substituted with alkyl, or (5) a 4- to 6-membered heterocycloalkyl containing one oxygen or sulfur atom, wherein the heterocycloalkyl is optionally substituted with one or two oxo groups. [Section 2] R 1 Item 2. The compound according to Item 1, or a pharmaceutically acceptable salt thereof, wherein is hydrogen. [Section 3] R 2Item 3. The compound or pharmaceutically acceptable salt thereof according to Item 1 or 2, wherein is hydrogen. [Section 4] The ring group Cy is (1) Formula: [ka] (In the formula, R 4 , R 5 , R 6 , R 7 and R 8 is equivalent to term 1) Item 4. The compound according to any one of Items 1 to 3, wherein the compound is a group represented by the formula: or a pharmaceutically acceptable salt thereof. [Section 5] R 6 and R 7 Item 5. The compound or a pharmaceutically acceptable salt thereof according to any one of Items 1 to 4, wherein is hydrogen. [Section 6] Item 6. The compound according to any one of items 1 to 5, which is represented by formula [II] or a pharmaceutically acceptable salt thereof. [ka] (In the formula, R 3 , R 4 , R 5 and R 8 is equivalent to term 1) [Section 7] R 4 and R 5 At least one of (1) Cyano, (2) C 1-6 alkyl {wherein the alkyl is (a) hydroxy, (b)C 1-4 Alkoxy, and (c)C 3-6 cycloalkyl; (3) C 1-4 Alkoxy, (4) halogens, (5) C 1-4 haloalkyl, (6)-OC1-4 haloalkyl, (7)-O-CD3, or (8) C 3-6 Item 7. The compound according to any one of Items 1 to 6, wherein R is cycloalkyl, or a pharmaceutically acceptable salt thereof. [Section 8] R 3 but (1)C 1-6 alkyl {wherein the alkyl is (a) hydroxy, (b) cyano, (c)C 1-4 Alkoxy, (d)-NR 12 R 13 (where R 12 and R 13 are each independently, C 1-4 alkyl), (e)-SO2-C 1-6 Alkyl, (f)C 3-6 Cycloalkyl (wherein the cycloalkyl is cyano, or C 1-4 C optionally substituted with alkoxy 1-4 optionally substituted with alkyl, (g) 4- to 6-membered heterocycloalkyl containing one oxygen or sulfur atom, wherein the heterocycloalkyl is optionally substituted with one or two oxo; and (h) phenyl, optionally substituted with 1 or 2 substituents independently selected from the group consisting of; (2) The compound according to any one of items 1 to 7, which is a 4- to 6-membered heterocycloalkyl containing one oxygen or sulfur atom (wherein the heterocycloalkyl is optionally substituted with one or two oxo groups), or a pharmaceutically acceptable salt thereof. [Section 9] The following structural formula: [ka] Item 1. The compound according to item 1, or a pharmaceutically acceptable salt thereof, selected from the group consisting of: [Section 10] A pharmaceutical composition comprising the compound according to any one of items 1 to 9 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. [Section 11] Item 10. An NLRP3 inflammasome inhibitor comprising the compound according to any one of items 1 to 9 or a pharmaceutically acceptable salt thereof. [Section 12] Item 10. A composition for treating multiple sclerosis, chronic kidney disease, inflammatory bowel disease (e.g., ulcerative colitis and Crohn's disease), arteriosclerosis, cryopyrin-associated periodic fever syndrome (e.g., familial cold autoinflammatory syndrome, Muckle-Wells syndrome, chronic infantile neurological cutaneous and articular syndrome, and neonatal-onset multi-organ inflammatory disease), non-alcoholic steatohepatitis, gout, gouty arthritis, rheumatoid arthritis, contact dermatitis, dry eye, ischemic heart disease (e.g., acute myocardial infarction), systemic lupus erythematosus, systemic juvenile idiopathic arthritis, recurrent pericarditis, adult-onset Still's disease (e.g., rheumatoid arthritis), rheumatoid arthritis, ... For example, a therapeutic or preventive agent for a disease selected from the group consisting of hemophagocytic lymphohistiocytosis and macrophage activation syndrome, Schnitzler syndrome, IL-1 receptor antagonist molecule deficiency, familial Mediterranean fever, mevalonate kinase deficiency, hyper IgD syndrome, Behcet's disease, lung cancer, psoriasis, hypertension, diabetic retinopathy, Alzheimer's disease, mild cognitive impairment, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, cerebral infarction, cerebral hemorrhage, epilepsy, depression, autism spectrum disorder, spinal cord injury, septic encephalopathy, neuropathic pain, COVID-19, and TNF receptor-associated periodic syndrome. [Section 13] Item 13. The therapeutic or preventive agent according to Item 12, wherein the inflammatory bowel disease is ulcerative colitis or Crohn's disease. [Section 14] Item 13. The therapeutic or preventive agent according to Item 12, wherein the cryopyrin-associated periodic fever syndrome is familial cold autoinflammatory syndrome, Muckle-Wells syndrome, chronic infantile neurological cutaneous and articular syndrome, or neonatal-onset multiorgan inflammatory disease. [Section 15] A method for inhibiting NLRP3 inflammasome, comprising administering a therapeutically effective amount of the compound according to any one of items 1 to 9 or a pharmaceutically acceptable salt thereof to a mammal. [Section 16] Item 10. A method for treating multiple sclerosis, chronic kidney disease, inflammatory bowel disease (e.g., ulcerative colitis and Crohn's disease), arteriosclerosis, cryopyrin-associated periodic fever syndrome (e.g., familial cold autoinflammatory syndrome, Muckle-Wells syndrome, chronic infantile neurological cutaneous and articular syndrome, and neonatal-onset multi-organ inflammatory disease), non-alcoholic steatohepatitis, gout, gouty arthritis, rheumatoid arthritis, contact dermatitis, dry eye, ischemic heart disease (e.g., acute myocardial infarction), systemic lupus erythematosus, systemic juvenile idiopathic arthritis, recurrent pericarditis, A method for treating or preventing a disease selected from the group consisting of adult-onset Still's disease (e.g., hemophagocytic lymphohistiocytosis and macrophage activation syndrome), Schnitzler syndrome, IL-1 receptor antagonist molecule deficiency, familial Mediterranean fever, mevalonate kinase deficiency, hyper-IgD syndrome, Behcet's disease, lung cancer, psoriasis, hypertension, diabetic retinopathy, Alzheimer's disease, mild cognitive impairment, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, cerebral infarction, cerebral hemorrhage, epilepsy, depression, autism spectrum disorder, spinal cord injury, septic encephalopathy, neuropathic pain, COVID-19, and TNF receptor-associated periodic syndrome. [Section 17] Item 17. The method according to Item 16, wherein the inflammatory bowel disease is ulcerative colitis or Crohn's disease. [Section 18] Item 17. The method according to Item 16, wherein the cryopyrin-associated periodic fever syndrome is familial cold autoinflammatory syndrome, Muckle-Wells syndrome, chronic infantile neurological cutaneous and articular syndrome, or neonatal-onset multisystem inflammatory disease. [Section 19] Use of the compound or a pharmaceutically acceptable salt thereof according to any one of items 1 to 9 for the manufacture of an NLRP3 inflammasome inhibitor. [Section 20] Multiple sclerosis, chronic kidney disease, inflammatory bowel disease (e.g., ulcerative colitis and Crohn's disease), arteriosclerosis, cryopyrin-associated periodic fever syndromes (e.g., familial cold autoinflammatory syndrome, Muckle-Wells syndrome, chronic infantile neurological cutaneous and articular syndrome, and neonatal-onset multisystem inflammatory disease), non-alcoholic steatohepatitis, gout, gouty arthritis, rheumatoid arthritis, contact dermatitis, dry eye, ischemic heart disease (e.g., acute myocardial infarction), systemic lupus erythematosus, systemic juvenile idiopathic arthritis, relapsing pericarditis, adult-onset Still's disease (e.g., hemophagocytic lymphohistiocytosis and macrophage activation syndrome), Schnitzler's disease Item 10. Use of the compound or a pharmaceutically acceptable salt thereof according to any one of Items 1 to 9 for the manufacture of an agent for the treatment or prevention of a disease selected from the group consisting of idiopathic pulmonary fibrosis (IPF) syndrome, IL-1 receptor antagonist molecule deficiency, familial Mediterranean fever, mevalonate kinase deficiency, hyper IgD syndrome, Behcet's disease, lung cancer, psoriasis, hypertension, diabetic retinopathy, Alzheimer's disease, mild cognitive impairment, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, cerebral infarction, cerebral hemorrhage, epilepsy, depression, autism spectrum disorder, spinal cord injury, septic encephalopathy, neuropathic pain, COVID-19, and TNF receptor-associated periodic syndrome. [Section 21] Item 21. The use according to Item 20, wherein the inflammatory bowel disease is ulcerative colitis or Crohn's disease. [Section 22] Item 21. The use according to Item 20, wherein the cryopyrin-associated periodic fever syndrome is familial cold autoinflammatory syndrome, Muckle-Wells syndrome, chronic infantile neurological cutaneous and articular syndrome, or neonatal-onset multisystem inflammatory disease. [Section 23] Item 10. The compound or a pharmaceutically acceptable salt thereof according to any one of items 1 to 9, for use in inhibiting NLRP3 inflammasome. [Section 24] Multiple sclerosis, chronic kidney disease, inflammatory bowel disease (e.g., ulcerative colitis and Crohn's disease), arteriosclerosis, cryopyrin-associated periodic fever syndromes (e.g., familial cold autoinflammatory syndrome, Muckle-Wells syndrome, chronic infantile neurological cutaneous and articular syndrome, and neonatal-onset multisystem inflammatory disease), non-alcoholic steatohepatitis, gout, gouty arthritis, rheumatoid arthritis, contact dermatitis, dry eye, ischemic heart disease (e.g., acute myocardial infarction), systemic lupus erythematosus, systemic juvenile idiopathic arthritis, relapsing pericarditis, adult-onset Still's disease (e.g., hemophagocytic lymphohistiocytosis and macrophage activation syndrome), Schnitz syndrome Item 10. The compound or a pharmaceutically acceptable salt thereof according to any one of Items 1 to 9 for use in the treatment or prevention of a disease selected from the group consisting of Lehr syndrome, IL-1 receptor antagonist molecule deficiency, familial Mediterranean fever, mevalonate kinase deficiency, hyper IgD syndrome, Behcet's disease, lung cancer, psoriasis, hypertension, diabetic retinopathy, Alzheimer's disease, mild cognitive impairment, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, cerebral infarction, cerebral hemorrhage, epilepsy, depression, autism spectrum disorder, spinal cord injury, septic encephalopathy, neuropathic pain, COVID-19, and TNF receptor-associated periodic syndrome. [Section 25] Item 25. The compound or a pharmaceutically acceptable salt thereof according to Item 24, wherein the inflammatory bowel disease is ulcerative colitis or Crohn's disease. [Section 26] Item 25. The compound or a pharmaceutically acceptable salt thereof according to Item 24, wherein the cryopyrin-associated periodic fever syndrome is familial cold autoinflammatory syndrome, Muckle-Wells syndrome, chronic infantile neurological cutaneous and articular syndrome, or neonatal-onset multisystem inflammatory disease. [Section 27] Item 10. A pharmaceutical composition according to Item 10, and administration of the pharmaceutical composition to a patient suffering from multiple sclerosis, chronic kidney disease, inflammatory bowel disease (e.g., ulcerative colitis and Crohn's disease), arteriosclerosis, cryopyrin-associated periodic fever syndrome (e.g., familial cold autoinflammatory syndrome, Muckle-Wells syndrome, chronic infantile neurological cutaneous and articular syndrome, and neonatal-onset multi-organ inflammatory disease), non-alcoholic steatohepatitis, gout, gouty arthritis, rheumatoid arthritis, contact dermatitis, dry eye, ischemic heart disease (e.g., acute myocardial infarction), systemic lupus erythematosus, systemic juvenile idiopathic arthritis, recurrent pericarditis, adult-onset Still's disease (e.g., hemophagocytic lymphohistiocytosis and macrophage activation syndrome), and and a commercial package containing a description of the pharmaceutical composition, which describes that the pharmaceutical composition can be used for the treatment or prevention of a disease selected from the group consisting of idiopathic pulmonary fibrosis (IPF) syndrome, Schnitzler syndrome, IL-1 receptor antagonist molecule deficiency, familial Mediterranean fever, mevalonate kinase deficiency, hyper IgD syndrome, Behcet's disease, lung cancer, psoriasis, hypertension, diabetic retinopathy, Alzheimer's disease, mild cognitive impairment, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, cerebral infarction, cerebral hemorrhage, epilepsy, depression, autism spectrum disorder, spinal cord injury, septic encephalopathy, neuropathic pain, COVID-19, and TNF receptor-associated periodic syndrome. [Section 28] Item 10. A pharmaceutical composition according to Item 10, and a method for administering the pharmaceutical composition to a patient suffering from multiple sclerosis, chronic kidney disease, inflammatory bowel disease (e.g., ulcerative colitis and Crohn's disease), arteriosclerosis, cryopyrin-associated periodic fever syndrome (e.g., familial cold autoinflammatory syndrome, Muckle-Wells syndrome, chronic infantile neurological cutaneous and articular syndrome, and neonatal-onset multi-organ inflammatory disease), non-alcoholic steatohepatitis, gout, gouty arthritis, rheumatoid arthritis, contact dermatitis, dry eye, ischemic heart disease (e.g., acute myocardial infarction), systemic lupus erythematosus, systemic juvenile idiopathic arthritis, recurrent pericarditis, adult-onset Still's disease (e.g., hemophagocytic lymphohistiocytosis and macrophage leukemia), and and a commercial kit comprising a description of the pharmaceutical composition, which is described as being usable for the treatment or prevention of a disease selected from the group consisting of inflammatory bowel disease (IL-1 receptor antagonist deficiency syndrome), Schnitzler syndrome, IL-1 receptor antagonist deficiency, familial Mediterranean fever, mevalonate kinase deficiency, hyper IgD syndrome, Behcet's disease, lung cancer, psoriasis, hypertension, diabetic retinopathy, Alzheimer's disease, mild cognitive impairment, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, cerebral infarction, cerebral hemorrhage, epilepsy, depression, autism spectrum disorder, spinal cord injury, septic encephalopathy, neuropathic pain, COVID-19, and TNF receptor-associated periodic syndrome. [Section 12A] Item 10. A compound according to any one of Items 1 to 9 or a pharmaceutically acceptable salt thereof, for use in treating multiple sclerosis, chronic kidney disease, inflammatory bowel disease (e.g., ulcerative colitis and Crohn's disease), arteriosclerosis, cryopyrin-associated periodic fever syndrome (e.g., familial cold autoinflammatory syndrome, Muckle-Wells syndrome, chronic infantile neurological cutaneous and articular syndrome, and neonatal-onset multi-organ inflammatory disease), non-alcoholic steatohepatitis, gout, gouty arthritis, rheumatoid arthritis, contact dermatitis, dry eye, ischemic heart disease (e.g., acute myocardial infarction), systemic lupus erythematosus, systemic juvenile idiopathic arthritis, recurrent pericarditis, adult-onset Still's disease (e.g., hemophagocytic lymphohistiocytosis and Muckle-Wells syndrome), and a therapeutic or preventive agent for a disease selected from the group consisting of inflammatory bowel disease (IGD), Schnitzler syndrome, IL-1 receptor antagonist deficiency, familial Mediterranean fever, mevalonate kinase deficiency, hyper IgD syndrome, Behcet's disease, lung cancer, psoriasis, hypertension, diabetic retinopathy, Alzheimer's disease, mild cognitive impairment, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, cerebral infarction, cerebral hemorrhage, epilepsy, depression, autism spectrum disorder, spinal cord injury, septic encephalopathy, neuropathic pain, COVID-19, frontotemporal dementia, age-related macular degeneration, diabetic macular edema, hereditary transient corneal endotheliitis, and TNF receptor-associated periodic syndrome. [Section 13A] The therapeutic or prophylactic agent according to Item 12A, wherein the inflammatory bowel disease is ulcerative colitis or Crohn's disease. [Section 14A] Item 12A. The therapeutic or preventive agent according to Item 12A, wherein the cryopyrin-associated periodic fever syndrome is familial cold autoinflammatory syndrome, Muckle-Wells syndrome, chronic infantile neurological cutaneous and articular syndrome, or neonatal-onset multisystem inflammatory disease. [Section 15A] Item 10. A method for treating multiple sclerosis, chronic kidney disease, inflammatory bowel disease (e.g., ulcerative colitis and Crohn's disease), arteriosclerosis, cryopyrin-associated periodic fever syndrome (e.g., familial cold autoinflammatory syndrome, Muckle-Wells syndrome, chronic infantile neurological cutaneous and articular syndrome, and neonatal-onset multi-organ inflammatory disease), non-alcoholic steatohepatitis, gout, gouty arthritis, rheumatoid arthritis, contact dermatitis, dry eye, ischemic heart disease (e.g., acute myocardial infarction), systemic lupus erythematosus, systemic juvenile idiopathic arthritis, recurrent pericarditis, adult-onset Still's disease (e.g., hemophagocytic phosphoinositide ... systemic lupus erythematosus, systemic lupus erythematosus, recurrent pericarditis, systemic lupus erythematosus, systemic lupus erythematosus, recurrent pericarditis, systemic lupus erythematosus, recurrent pericarditis, systemic lupus erythematosus, recurrent pericarditis, systemic lupus erythematosus, recurrent pericarditis, systemic lupus erythematosus, recurrent pericarditis, systemic lupus erythematosus, recurrent pericarditis, systemic lupus erythematosus, recurrent pericarditis, systemic lupus erythematos A method for treating or preventing a disease selected from the group consisting of inflammatory bowel disease (inflammatory disease, leukemia, and macrophage activation syndrome), Schnitzler syndrome, IL-1 receptor antagonist deficiency, familial Mediterranean fever, mevalonate kinase deficiency, hyper-IgD syndrome, Behcet's disease, lung cancer, psoriasis, hypertension, diabetic retinopathy, Alzheimer's disease, mild cognitive impairment, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, cerebral infarction, cerebral hemorrhage, epilepsy, depression, autism spectrum disorder, spinal cord injury, septic encephalopathy, neuropathic pain, COVID-19, frontotemporal dementia, age-related macular degeneration, diabetic macular edema, hereditary transient corneal endotheliitis, and TNF receptor-associated periodic syndrome. [Section 16A] The method according to paragraph 15A, wherein the inflammatory bowel disease is ulcerative colitis or Crohn's disease. [Section 17A] The method according to Item 15A, wherein the cryopyrin-associated periodic fever syndrome is familial cold autoinflammatory syndrome, Muckle-Wells syndrome, chronic infantile neurological cutaneous and articular syndrome, or neonatal-onset multisystem inflammatory disease. [Section 18A] Multiple sclerosis, chronic kidney disease, inflammatory bowel disease (e.g., ulcerative colitis and Crohn's disease), arteriosclerosis, cryopyrin-associated periodic fever syndromes (e.g., familial cold autoinflammatory syndrome, Muckle-Wells syndrome, chronic infantile neurological, cutaneous, and articular syndrome, and neonatal-onset multisystem inflammatory disease), non-alcoholic steatohepatitis, gout, gouty arthritis, rheumatoid arthritis, contact dermatitis, dry eye, ischemic heart disease (e.g., acute myocardial infarction), systemic lupus erythematosus, systemic juvenile idiopathic arthritis, relapsing pericarditis, adult-onset Still's disease (e.g., hemophagocytic lymphohistiocytosis and macrophage activation syndrome), Schnitzler syndrome, IL-1 receptor antagonist molecule deficiency, Item 10. Use of the compound or a pharmaceutically acceptable salt thereof according to any one of Items 1 to 9 for the manufacture of an agent for the treatment or prevention of a disease selected from the group consisting of familial Mediterranean fever, mevalonate kinase deficiency, hyper-IgD syndrome, Behcet's disease, lung cancer, psoriasis, hypertension, diabetic retinopathy, Alzheimer's disease, mild cognitive impairment, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, cerebral infarction, cerebral hemorrhage, epilepsy, depression, autism spectrum disorder, spinal cord injury, septic encephalopathy, neuropathic pain, COVID-19, frontotemporal dementia, age-related macular degeneration, diabetic macular edema, hereditary transient corneal endotheliitis, and TNF receptor-associated periodic syndrome. [Section 19A] The use according to paragraph 18A, wherein the inflammatory bowel disease is ulcerative colitis or Crohn's disease. [Section 20A] The use according to Item 18A, wherein the cryopyrin-associated periodic fever syndrome is familial cold autoinflammatory syndrome, Muckle-Wells syndrome, chronic infantile neurological cutaneous and articular syndrome, or neonatal-onset multisystem inflammatory disease. [Section 21A] Multiple sclerosis, chronic kidney disease, inflammatory bowel disease (e.g., ulcerative colitis and Crohn's disease), arteriosclerosis, cryopyrin-associated periodic fever syndromes (e.g., familial cold autoinflammatory syndrome, Muckle-Wells syndrome, chronic infantile neurological, cutaneous, and articular syndrome of the ulcerative colitis, and neonatal-onset multisystem inflammatory disease), non-alcoholic steatohepatitis, gout, gouty arthritis, rheumatoid arthritis, contact dermatitis, dry eye, ischemic heart disease (e.g., acute myocardial infarction), systemic lupus erythematosus, systemic juvenile idiopathic arthritis, relapsing pericarditis, adult-onset Still's disease (e.g., hemophagocytic lymphohistiocytosis and macrophage activation syndrome), Schnitzler syndrome, IL-1 receptor antagonist deficiency Item 10. The compound or a pharmaceutically acceptable salt thereof according to any one of Items 1 to 9 for use in the treatment or prevention of a disease selected from the group consisting of glaucoma, familial Mediterranean fever, mevalonate kinase deficiency, hyper-IgD syndrome, Behcet's disease, lung cancer, psoriasis, hypertension, diabetic retinopathy, Alzheimer's disease, mild cognitive impairment, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, cerebral infarction, cerebral hemorrhage, epilepsy, depression, autism spectrum disorder, spinal cord injury, septic encephalopathy, neuropathic pain, COVID-19, frontotemporal dementia, age-related macular degeneration, diabetic macular edema, hereditary transient corneal endotheliitis, and TNF receptor-associated periodic syndrome. [Section 22A] The compound or a pharmaceutically acceptable salt thereof according to Item 21A, wherein the inflammatory bowel disease is ulcerative colitis or Crohn's disease. [Section 23A] The compound or a pharmaceutically acceptable salt thereof according to Item 21A, wherein the cryopyrin-associated periodic fever syndrome is familial cold autoinflammatory syndrome, Muckle-Wells syndrome, chronic infantile neurological cutaneous and articular syndrome, or neonatal-onset multisystem inflammatory disease. [Section 24A] Item 10. A pharmaceutical composition according to Item 10, and a method for administering the pharmaceutical composition to a patient suffering from or having a disease, such as, multiple sclerosis, chronic kidney disease, inflammatory bowel disease (e.g., ulcerative colitis and Crohn's disease), arteriosclerosis, cryopyrin-associated periodic fever syndrome (e.g., familial cold autoinflammatory syndrome, Muckle-Wells syndrome, chronic infantile neurological cutaneous and articular syndrome, and neonatal-onset multi-organ inflammatory disease), non-alcoholic steatohepatitis, gout, gouty arthritis, rheumatoid arthritis, contact dermatitis, dry eye, ischemic heart disease (e.g., acute myocardial infarction), systemic lupus erythematosus, systemic juvenile idiopathic arthritis, recurrent pericarditis, adult-onset Still's disease (e.g., hemophagocytic lymphohistiocytosis and macrophage activation syndrome), Schnitzler's syndrome, I and a commercial package comprising a description of the pharmaceutical composition, which describes that the composition can be used for the treatment or prevention of a disease selected from the group consisting of L-1 receptor antagonist molecule deficiency, familial Mediterranean fever, mevalonate kinase deficiency, hyper-IgD syndrome, Behcet's disease, lung cancer, psoriasis, hypertension, diabetic retinopathy, Alzheimer's disease, mild cognitive impairment, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, cerebral infarction, cerebral hemorrhage, epilepsy, depression, autism spectrum disorder, spinal cord injury, septic encephalopathy, neuropathic pain, COVID-19, frontotemporal dementia, age-related macular degeneration, diabetic macular edema, hereditary transient corneal endotheliitis, and TNF receptor-associated periodic syndrome. [Section 25A] Item 10. A pharmaceutical composition according to Item 10, and a method for administering the pharmaceutical composition to a patient suffering from or having a complication of multiple sclerosis, chronic kidney disease, inflammatory bowel disease (e.g., ulcerative colitis and Crohn's disease), arteriosclerosis, cryopyrin-associated periodic fever syndrome (e.g., familial cold autoinflammatory syndrome, Muckle-Wells syndrome, chronic infantile neurological cutaneous and articular syndrome, and neonatal-onset multi-organ inflammatory disease), non-alcoholic steatohepatitis, gout, gouty arthritis, rheumatoid arthritis, contact dermatitis, dry eye, ischemic heart disease (e.g., acute myocardial infarction), systemic lupus erythematosus, systemic juvenile idiopathic arthritis, recurrent pericarditis, adult-onset Still's disease (e.g., hemophagocytic lymphohistiocytosis and macrophage activation syndrome), Schnitzler's syndrome, and a commercial kit comprising a description of the pharmaceutical composition, which is described as being usable for the treatment or prevention of a disease selected from the group consisting of IL-1 receptor antagonist molecule deficiency, familial Mediterranean fever, mevalonate kinase deficiency, hyper-IgD syndrome, Behcet's disease, lung cancer, psoriasis, hypertension, diabetic retinopathy, Alzheimer's disease, mild cognitive impairment, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, cerebral infarction, cerebral hemorrhage, epilepsy, depression, autism spectrum disorder, spinal cord injury, septic encephalopathy, neuropathic pain, COVID-19, frontotemporal dementia, age-related macular degeneration, diabetic macular edema, hereditary transient corneal endotheliitis, and TNF receptor-associated periodic syndrome. DETAILED DESCRIPTION OF THE INVENTION

[0042] The definitions of terms used in this specification are as follows.

[0043] In the chemical formula: [ka] The wavy line indicates the bonding site of the structure or group shown in the chemical formula.

[0044] "C 1-4 "Alkyl" means a linear or branched saturated hydrocarbon group having 1 to 4 carbon atoms. 1-4"Alkyl" includes methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, and tert-butyl. Preferred are methyl and ethyl.

[0045] "C 1-6 "Alkyl" means a straight or branched chain saturated hydrocarbon group having 1 to 6 carbon atoms. 1-6 "Alkyl" includes, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, 2-methylbutyl, 1,1-dimethylpropyl, 1-ethylpropyl, n-hexyl, isohexyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, and 2-ethylbutyl. Preferred are methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, and isopentyl.

[0046] "C 1-4 "Alkoxy" refers to the above "C 1-4 "C" means a group in which "alkyl" is bonded to an oxygen atom. 1-4 "Alkoxy" includes methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, isobutoxy, and tert-butoxy. Preferred are methoxy and ethoxy.

[0047] "Halogen" includes, for example, fluorine, chlorine, bromine, and iodine.

[0048] "C 1-4 "Haloalkyl" refers to the above "C" substituted with 1 to 7 halogens independently selected from the above "halogen" group. 1-4 "C" means "alkyl". 1-4"Haloalkyl" includes, for example, monofluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 1,1-difluoroethyl, 2,2-difluoroethyl, 1-fluoro-1-methylethyl, 2,2,2-trifluoro-1-methylethyl, 2,2,2-trifluoroethyl, pentafluoroethyl, 3-fluoropropyl, 3-chloropropyl, 1,1-difluoropropyl, 3,3,3-trifluoropropyl, and 4,4,4-trifluorobutyl. Difluoromethyl and trifluoromethyl are preferred.

[0049] "C 1-6 "Haloalkyl" refers to the above "C" substituted with 1 to 9 halogens independently selected from the above "halogen" group. 1-6 "C" means "alkyl". 1-6 "Haloalkyl" includes, for example, monofluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 1,1-difluoroethyl, 2,2-difluoroethyl, 1-fluoro-1-methylethyl, 2,2,2-trifluoro-1-methylethyl, 2,2,2-trifluoroethyl, pentafluoroethyl, 3-fluoropropyl, 3-chloropropyl, 1,1-difluoropropyl, 2,2-difluoropropyl, 3,3,3-trifluoropropyl, 4,4,4-trifluorobutyl, 5,5,5-trifluoropentyl, and 6,6,6-trifluorohexyl. Preferred are difluoromethyl, trifluoromethyl, 1,1-difluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 1-fluoro-1-methylethyl, and 2,2-difluoropropyl.

[0050] "C 3-6 "Cycloalkyl" means a monocyclic saturated hydrocarbon ring group having 3 to 6 carbon atoms. 3-6"Cycloalkyl" includes, for example, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. Preferred are cyclopropyl, cyclobutyl, and cyclohexyl.

[0051] "4- to 6-membered heterocycloalkyl containing one oxygen or sulfur atom" refers to a 4- to 6-membered monocyclic saturated heterocyclic group containing one oxygen or sulfur atom in addition to carbon atoms as a ring-constituting atom. "4- to 6-membered heterocycloalkyl containing one oxygen or sulfur atom" includes, for example, oxetanyl, thietanyl, tetrahydrofuranyl, tetrahydrothiophenyl, tetrahydropyranyl, and tetrahydrothiopyranyl. Preferred are oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, and tetrahydrothiopyranyl.

[0052] "5- to 7-membered heterocycloalkene containing 1 or 2 oxygen atoms" means a 5- to 7-membered monocyclic partially unsaturated heterocycle containing 1 or 2 oxygen atoms as ring-constituting atoms other than carbon atoms and containing at least one double bond. "5- to 7-membered heterocycloalkene containing 1 or 2 oxygen atoms" includes, for example, dihydrofuran, dioxole, dihydropyran, dihydrodioxine, pyran, tetrahydrooxepin, dihydrodioxepin, dihydrooxepin, and dioxepin. Dihydrofuran and dihydropyran are preferred.

[0053] In some embodiments of the present invention, the moiety of formula [I]: [ka] is R 8 R 6 or R 7 and when these together with the carbon atoms to which they are attached form a ring structure, the whole is a 9- to 11-membered partially unsaturated fused ring group which may contain 1 or 2 oxygen atoms, and R 4 and R 5 and R 6 or R 7The fused ring group includes, for example, the following groups: [ka] Examples include:

[0054] The expression "α may be substituted" with β means that α is unsubstituted or any substitutable hydrogen of α is substituted with β. For example, "C optionally substituted with hydroxy" 1-6 "Alkyl" means C 1-6 The alkyl is unsubstituted or C 1-6 This means that any hydrogen in the alkyl is replaced with hydroxy.

[0055] Specific embodiments of each substituent of the compound of formula [I] are exemplified below, but each substituent of the compound of formula [I] is not limited to the specific embodiments, and the compound of formula [I] also includes embodiments in which any two or more of the specific embodiments of each substituent are combined.

[0056] The ring group Cy preferably has the formula: [ka] (wherein each symbol has the same meaning as defined above) It is a group represented by the formula:

[0057] R 4 and R 5 are preferably each independently (a) hydrogen, (b)C 1-6 alkyl {wherein the alkyl is (1) Hydroxy, (2) C 1-4 Alkoxy, and (3) C 3-6 cycloalkyl; (c)C 1-4 Alkoxy, (d) halogens, (e)C1-4 haloalkyl, (f)-OC 1-4 haloalkyl, or (g)C 3-6 Cycloalkyl.

[0058] R 6 and R 7 are preferably each independently hydrogen or C 1-4 Alkyl.

[0059] R 8 is preferably (a)C 1-6 alkyl (wherein the alkyl is hydroxy or C 1-4 optionally substituted with alkoxy; (b)C 1-4 Alkoxy, (c) halogens, (d)C 1-6 haloalkyl, (e)-OC 1-4 haloalkyl, or (f)C 3-6 cycloalkyl, wherein the cycloalkyl is optionally substituted with one or two hydroxy or halogen groups; or R 8 is R 6 or R 7 and together with the carbon atom to which they are attached form a 5- to 7-membered heterocycloalkene containing 1 or 2 oxygen atoms.

[0060] Substructure: [ka] is preferably R 4 and R 5 are each independently (a) hydrogen, (b)C 1-6 alkyl {wherein the alkyl is (1) Hydroxy, (2) C 1-4 Alkoxy, and (3) C 3-6 cycloalkyl; (c)C 1-4 Alkoxy, (d) halogens, (e)C 1-4 haloalkyl, (f)-OC 1-4 haloalkyl, or (g)C 3-6 cycloalkyl; R 6 and R 7 are each independently hydrogen or C 1-4 alkyl; R 8 teeth, (a)C 1-6 alkyl (wherein the alkyl is hydroxy or C 1-4 optionally substituted with alkoxy; (b)C 1-4 Alkoxy, (c) halogens, (d)C 1-6 haloalkyl, (e)-OC 1-4 haloalkyl, or (f)C 3-6 cycloalkyl, wherein the cycloalkyl is optionally substituted with one or two hydroxy or halogen groups; or R 8 is R 6 or R 7 and together with the carbon atom to which they are attached form a 5- to 7-membered heterocycloalkene containing 1 or 2 oxygen atoms.

[0061] R 1 is preferably hydrogen.

[0062] R 2 is preferably hydrogen.

[0063] R 3 is preferably (1)C1-6 alkyl {wherein the alkyl is (a) hydroxy, (b) cyano, (c)C 1-4 Alkoxy, (d)-NR 12 R 13 (where R 12 and R 13 are each independently, C 1-4 alkyl), (e)-SO2-C 1-6 Alkyl, (f)C 3-6 Cycloalkyl (wherein the cycloalkyl is cyano, or C 1-4 C optionally substituted with alkoxy 1-4 optionally substituted with alkyl, (g) 4- to 6-membered heterocycloalkyl containing one oxygen or sulfur atom, wherein the heterocycloalkyl is optionally substituted with one or two oxo; and (h) phenyl, optionally substituted with 1 or 2 substituents independently selected from the group consisting of: (2) C 1-6 haloalkyl, wherein the haloalkyl is optionally substituted with hydroxy; or (3) 4- to 6-membered heterocycloalkyl containing one oxygen or sulfur atom (wherein the heterocycloalkyl may be substituted with one or two oxo).

[0064] One preferred embodiment of the compound of formula [I] is The ring group Cy is of the formula: [ka] is a group represented by the formula: R 4 and R 5 However, each independently, (a) hydrogen, (b)C 1-6 alkyl {wherein the alkyl is (1) Hydroxy, (2) C 1-4Alkoxy, and (3) C 3-6 cycloalkyl; (c)C 1-4 Alkoxy, (d) halogens, (e)C 1-4 haloalkyl, (f)-OC 1-4 haloalkyl, or (g)C 3-6 cycloalkyl; R 6 and R 7 are each independently hydrogen or C 1-4 alkyl; R 8 but, (a)C 1-6 alkyl (wherein the alkyl is hydroxy or C 1-4 optionally substituted with alkoxy; (b)C 1-4 Alkoxy, (c) halogens, (d)C 1-6 haloalkyl, (e)-OC 1-4 haloalkyl, or (f)C 3-6 cycloalkyl, wherein the cycloalkyl is optionally substituted with one or two hydroxy or halogen groups; or R 8 is R 6 or R 7 together with the carbon atom to which they are attached to form a 5- to 7-membered heterocycloalkene containing 1 or 2 oxygen atoms; R 1 is hydrogen; R 2 is hydrogen; R 3 but, (1)C 1-6 alkyl {wherein the alkyl is (a) hydroxy, (b) cyano, (c)C1-4 Alkoxy, (d)-NR 12 R 13 (where R 12 and R 13 are each independently, C 1-4 alkyl), (e)-SO2-C 1-6 Alkyl, (f)C 3-6 Cycloalkyl (wherein the cycloalkyl is cyano, or C 1-4 C optionally substituted with alkoxy 1-4 optionally substituted with alkyl, (g) 4- to 6-membered heterocycloalkyl containing one oxygen or sulfur atom, wherein the heterocycloalkyl is optionally substituted with one or two oxo; and (h) phenyl, optionally substituted with 1 or 2 substituents independently selected from the group consisting of: (2) C 1-6 haloalkyl, wherein the haloalkyl is optionally substituted with hydroxy; or (3) A compound of formula [I] which is a 4- to 6-membered heterocycloalkyl containing one oxygen or sulfur atom (wherein the heterocycloalkyl may be substituted with one or two oxo).

[0065] As used herein, the term "pharmaceutically acceptable salt" refers to any salt known in the art that is not excessively toxic. Specific examples include salts with inorganic acids, salts with organic acids, salts with inorganic bases, and salts with organic bases. Various forms of pharmaceutically acceptable salts are well known in the art and are described, for example, in the following references: (a) Berge et al., J. Pharm. Sci., 66, pp. 1-19 (1977), (b) Stahl et al., "Handbook of Pharmaceutical Salt: Properties, Selection, and Use" (Wiley-VCH, Weinheim, Germany, 2002), (c) Paulekuhn et al., J. Med. Chem., 50, p6665-6672 (2007). According to a method known per se, the compound of formula [I] can be reacted with an inorganic acid, an organic acid, an inorganic base or an organic base to obtain a pharmaceutically acceptable salt thereof.

[0066] Examples of salts with inorganic acids include salts with hydrofluoric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, phosphoric acid, and sulfuric acid. Preferred examples include salts with hydrochloric acid, nitric acid, sulfuric acid, phosphoric acid, and hydrobromic acid. Salts with organic acids include acetic acid, adipic acid, alginic acid, 4-aminosalicylic acid, anhydromethylene citric acid, benzoic acid, benzenesulfonic acid, calcium edetate, camphoric acid, camphor-10-sulfonic acid, carbonic acid, citric acid, edetic acid, ethane-1,2-disulfonic acid, dodecylsulfuric acid, ethanesulfonic acid, fumaric acid, glucoheptonic acid, gluconic acid, glucuronic acid, glucoheptonic acid, glycolylarsanilic acid, hexylresorcylic acid, hydroxy-naphthoic acid, 2-hydroxy-1-ethanesulfonic acid, lactic acid, lactobionic acid, Examples include salts with malic acid, maleic acid, mandelic acid, methanesulfonic acid, methylsulfuric acid, methylnitric acid, methylenebis(salicylic acid), galactaric acid, naphthalene-2-sulfonic acid, 2-naphthoic acid, 1,5-naphthalenedisulfonic acid, oleic acid, oxalic acid, pamoic acid, pantothenic acid, pectinic acid, picric acid, propionic acid, polygalacturonic acid, salicylic acid, stearic acid, succinic acid, tannic acid, tartaric acid, teoclic acid, thiocyanic acid, trifluoroacetic acid, p-toluenesulfonic acid, undecanoic acid, aspartic acid, or glutamic acid. Preferred examples include salts with oxalic acid, maleic acid, citric acid, fumaric acid, lactic acid, malic acid, succinic acid, tartaric acid, acetic acid, trifluoroacetic acid, benzoic acid, glucuronic acid, oleic acid, pamoic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, or 2-hydroxy-1-ethanesulfonic acid.

[0067] Examples of salts with inorganic bases include salts with lithium, sodium, potassium, magnesium, calcium, barium, aluminum, zinc, bismuth, or ammonium, and preferably salts with sodium, potassium, calcium, magnesium, or zinc. Examples of salts with organic bases include salts with arecoline, betaine, choline, clemizole, ethylenediamine, N-methylglucamine, N-benzylphenethylamine, tris(hydroxymethyl)methylamine, arginine, or lysine. Preferably, salts with tris(hydroxymethyl)methylamine, N-methylglucamine, or lysine are used.

[0068] Compound [I] may exist as a solvate. A solvate is, for example, a compound [I] coordinated with solvent molecules. The solvate may be any pharmaceutically acceptable solvate, including a hydrate, acetate solvate, acetone solvate, ethanol solvate, and dimethyl sulfoxide solvate of compound [I]. Specific examples include the hemihydrate, monohydrate, dihydrate, monoacetate solvate, monoacetone solvate, and monoethanol solvate of the compound of formula [I], as well as the monohydrate, monoacetone solvate, and 2 / 3 ethanol solvate of the sodium salt of the compound of formula [I]. These solvates can be obtained according to known methods.

[0069] Compound [I] may exist as a tautomer. In that case, compound [I] may exist as an individual tautomer or a mixture of tautomers. For example, the compound [I] may exist as a tautomer of the following formula: [ka] Unless otherwise noted, the structure shown in (1) [ka] (2) [ka] (3) [ka] (4) [ka] , or (5) It means that these mixtures can exist and / or be expressed as such.

[0070] Compound [I] may have a carbon-carbon double bond, and in that case, compound [I] may exist as an E-isomer, a Z-isomer, or a mixture of E- and Z-isomers. Compound [I] may have stereoisomers that should be recognized as cis / trans isomers. In such cases, compound [I] may exist as a cis isomer, a trans isomer, or a mixture of cis and trans isomers. Compound [I] may have one or more asymmetric carbon atoms, and in that case, compound [I] may exist as a single enantiomer, a single diastereomer, a mixture of enantiomers, or a mixture of diastereomers. Compound [I] may exist as atropisomers, in which case compound [I] may exist as an individual atropisomer or a mixture of atropisomers. Compound [I] may simultaneously contain multiple structural features that give rise to the above isomers, and may contain the above isomers in any ratio.

[0071] In this specification, formulae, chemical structures or compound names expressed without specifying stereochemistry include all of the above-mentioned possible isomers unless otherwise noted.

[0072] Diastereomeric mixtures can be separated into individual diastereomers by conventional methods such as chromatography or crystallization, or the individual diastereomers can be prepared by synthetic methods using stereochemically pure starting materials or stereoselective reactions.

[0073] Separation of individual enantiomers from a mixture of enantiomers can be accomplished by methods well known in the art. For example, enriched or substantially pure single diastereomers can be separated from a diastereomeric mixture formed by reacting a mixture of enantiomers with a substantially pure enantiomer, known as a chiral auxiliary, by standard methods such as fractional crystallization or chromatography. The separated diastereomer can be converted to the desired enantiomer by cleavage and removal of the added chiral auxiliary. Alternatively, a mixture of enantiomers can be directly separated by chromatographic methods using chiral stationary phases, well known in the art. Alternatively, one enantiomer can be obtained by using substantially pure optically active starting materials or by stereoselective synthesis (asymmetric induction) of prochiral intermediates using chiral auxiliaries and asymmetric catalysts.

[0074] Absolute configuration may be determined by X-ray crystallography of crystalline products or intermediates which are derivatized, if necessary, with a reagent containing an asymmetric center of known configuration.

[0075] Compound [I] is an isotope ( 2 H(D), 3 H, 11 C. 13 C. 14 C. 13 N, 15 N, 15 O. 18 O. 18 F, 35 S, 123The isotope-labeled compound [I] may be labeled with an isotope (e.g., -I). For example, if the compound of formula [I] has a methyl group, the methyl group may be replaced with a -CD3 group, and the compound obtained in this manner is also encompassed by the present invention. The isotope-labeled compound [I] may be useful in medicine, pharmacokinetic studies, in vitro and / or in vivo assays, and / or diagnostic agents (e.g., positron emission tomography (PET), single photon emission computed tomography (SPECT)). The isotope-labeled compound [I] can be prepared by known methods or the methods described herein, using an isotope-labeled compound instead of a non-isotopically labeled compound.

[0076] Compound [I] is preferably a substantially purified compound [I], more preferably a compound [I] purified to a purity of 80% or more.

[0077] The pharmaceutical composition of the present invention may be prepared by appropriately mixing compound [I] with at least one or more pharmaceutically acceptable carriers, etc. in appropriate amounts, according to a method known in the technical field of pharmaceutical formulation. The content of compound [I] in the pharmaceutical composition varies depending on the dosage form, dosage, etc., but is, for example, 0.1 to 100% by weight of the total composition.

[0078] Dosage forms of compound [I] include oral preparations such as tablets, capsules, granules, powders, troches, syrups, emulsions, and suspensions, and parenteral preparations such as topical preparations, suppositories, injections, eye drops, nasal preparations, and pulmonary preparations.

[0079] Examples of "pharmaceutically acceptable carriers" include various organic or inorganic carrier substances commonly used as formulation materials, such as excipients, disintegrants, binders, fluidizing agents, lubricants, etc. in solid preparations, solvents, solubilizing agents, suspending agents, isotonicity agents, buffers, soothing agents, etc. in liquid preparations, and bases, emulsifiers, wetting agents, stabilizers, dispersants, plasticizers, pH adjusters, absorption enhancers, gelling agents, preservatives, fillers, solubilizers, solubilizing agents, suspending agents, etc. in semi-solid preparations. Furthermore, additives such as preservatives, antioxidants, colorants, and sweeteners may be used as needed.

[0080] Examples of "excipients" include lactose, sucrose, D-mannitol, D-sorbitol, corn starch, dextrin, microcrystalline cellulose, crystalline cellulose, carmellose, carmellose calcium, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, and gum arabic. Examples of the "disintegrant" include carmellose, carmellose calcium, carmellose sodium, sodium carboxymethyl starch, croscarmellose sodium, crospovidone, low-substituted hydroxypropyl cellulose, hydroxypropylmethyl cellulose, and crystalline cellulose. Examples of "binders" include hydroxypropyl cellulose, hydroxypropylmethyl cellulose, povidone, crystalline cellulose, sucrose, dextrin, starch, gelatin, carmellose sodium, gum arabic, and the like. Examples of the "fluidizing agent" include light anhydrous silicic acid, magnesium stearate, and the like. "Lubricants" include magnesium stearate, calcium stearate, talc, and the like. Examples of "solvents" include purified water, ethanol, propylene glycol, macrogol, sesame oil, corn oil, olive oil, etc. Examples of "solubilizing agents" include propylene glycol, D-mannitol, benzyl benzoate, ethanol, triethanolamine, sodium carbonate, sodium citrate, and the like. Examples of the "suspending agent" include benzalkonium chloride, carmellose, hydroxypropyl cellulose, propylene glycol, povidone, methylcellulose, glycerin monostearate and the like. Examples of "isotonicity agents" include glucose, D-sorbitol, sodium chloride, D-mannitol, and the like. Examples of "buffers" include sodium hydrogen phosphate, sodium acetate, sodium carbonate, sodium citrate, and the like. "Soothing agents" include benzyl alcohol and the like. Examples of "bases" include water, animal and vegetable oils (olive oil, corn oil, peanut oil, sesame oil, castor oil, etc.), lower alcohols (ethanol, propanol, propylene glycol, 1,3-butylene glycol, phenol, etc.), higher fatty acids and their esters, waxes, higher alcohols, polyhydric alcohols, hydrocarbons (white petrolatum, liquid paraffin, paraffin, etc.), hydrophilic petrolatum, purified lanolin, absorbent ointment, hydrous lanolin, hydrophilic ointment, starch, pullulan, gum arabic, tragacanth gum, gelatin, dextran, cellulose derivatives (methylcellulose, carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, etc.), synthetic polymers (carboxyvinyl polymer, sodium polyacrylate, polyvinyl alcohol, polyvinylpyrrolidone, etc.), propylene glycol, macrogols (macrogol 200 to 600, etc.), and combinations of two or more thereof. Examples of the "preservative" include ethyl parahydroxybenzoate, chlorobutanol, benzyl alcohol, sodium dehydroacetate, sorbic acid, and the like. "Antioxidants" include sodium sulfite, ascorbic acid, and the like. Examples of "coloring agents" include food dyes (such as food red No. 2 or No. 3, food yellow No. 4 or No. 5, etc.), β-carotene, and the like. Examples of "sweetening agents" include sodium saccharin, dipotassium glycyrrhizinate, aspartame, etc.

[0081] The pharmaceutical composition of the present invention can be administered orally or parenterally (topically, rectally, intravenously, intramuscularly, subcutaneously, etc.) to mammals other than humans (mice, rats, hamsters, guinea pigs, rabbits, cats, dogs, pigs, cows, horses, sheep, monkeys, etc.) and humans. The dosage (also referred to herein as a "therapeutically effective amount") varies depending on the subject, disease, symptoms, dosage form, administration route, etc., but for example, the dosage when administered orally to an adult patient is usually in the range of about 0.01 mg to 1 g per day of the compound of formula [I] or a pharmaceutically acceptable salt thereof, which is the active ingredient. These amounts can be administered in one or several divided doses.

[0082] Compound [I] has an NLRP3 inflammasome inhibitory activity and is therefore useful for the treatment and / or prevention of various diseases or conditions that can be expected to be improved by modulating NLRP3 inflammasome activity. Examples of various diseases or conditions that can be expected to be improved by modulating NLRP3 inflammasome activity include multiple sclerosis, chronic kidney disease, inflammatory bowel disease (e.g., ulcerative colitis and Crohn's disease), arteriosclerosis, cryopyrin-associated periodic fever syndrome (e.g., familial cold autoinflammatory syndrome, Muckle-Wells syndrome, chronic infantile neurological cutaneous and articular syndrome, and neonatal-onset multisystem inflammatory disease), non-alcoholic steatohepatitis, gout, gouty arthritis, rheumatoid arthritis, contact dermatitis, dry eye, ischemic heart disease (e.g., acute myocardial infarction), systemic lupus erythematosus, systemic juvenile idiopathic arthritis, recurrent pericarditis, adult-onset Still's disease (e.g., hemophagocytic lymphoma), and other conditions. and macrophage activation syndrome), Schnitzler syndrome, IL-1 receptor antagonist molecule deficiency, familial Mediterranean fever, mevalonate kinase deficiency, hyper-IgD syndrome, Behcet's disease, lung cancer, psoriasis, hypertension, diabetic retinopathy, Alzheimer's disease, mild cognitive impairment, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, cerebral infarction, cerebral hemorrhage, epilepsy, depression, autism spectrum disorder, spinal cord injury, septic encephalopathy, neuropathic pain, COVID-19, frontotemporal dementia, age-related macular degeneration, diabetic macular edema, hereditary transient corneal endotheliitis, and TNF receptor-associated periodic syndrome.

[0083] "Inhibiting NLRP3 inflammasome" means inhibiting the function of NLRP3 inflammasome to eliminate or attenuate its activity, for example, inhibiting the function of NLRP3 inflammasome under the conditions of Test Example 1 described below. Inhibiting the function of NLRP3 inflammasome suppresses the production of IL-1β and / or IL-18, preferably suppressing the production of IL-1β and IL-18. "Inhibiting NLRP3 inflammasome" preferably means "inhibiting human NLRP3 inflammasome."

[0084] Since compound [I] has NLRP3 inflammasome inhibitory activity, compound [I] or a pharmaceutically acceptable salt thereof can be used as an NLRP3 inflammasome inhibitor either as is or after being appropriately formulated.

[0085] As used herein, "treatment" includes alleviation of symptoms, prevention of aggravation, maintenance of remission, prevention of recurrence, and even prevention of recurrence. As used herein, "prevention" includes suppressing and delaying the onset of symptoms.

[0086] Unless one embodiment disclosed in one place in this specification contradicts an embodiment disclosed in another place, any combination of two or more of these is also intended to be encompassed by the present invention.

[0087] [General manufacturing method] General methods for producing the compound of formula [I] or a pharmaceutically acceptable salt thereof are exemplified below: However, the method for producing the compound of formula [I] or a pharmaceutically acceptable salt thereof is not limited to these methods. The compounds obtained in each step can be isolated and / or purified by known methods such as distillation, recrystallization, column chromatography, etc., as necessary, but in some cases can be used to proceed to the next step without isolation and / or purification. In this specification, room temperature refers to a temperature in an uncontrolled state, and in one embodiment, it is 1°C to 40°C.

[0088] Production method A1: Production method for compound [IA] or a salt thereof Compound [IA] or a salt thereof can be prepared, for example, by the following Preparation Method A1. [ka] wherein Cy and R 3 is as defined above, R A11 are each independently, C 1-4 is alkyl, L A11 , L A12, and L A13 are each independently a leaving group (e.g., halogen, methanesulfonyloxy, and p-toluenesulfonyloxy). (Process A1-1) The compound [A1-3] or a salt thereof can be produced by reacting the compound [A1-1] or a salt thereof with the compound [A1-2] in a solvent in the presence of an acid. Examples of the acid include sulfuric acid, hydrochloric acid, formic acid, perchloric acid, methanesulfonic acid, and p-toluenesulfonic acid. Preferred acids are sulfuric acid and p-toluenesulfonic acid. Examples of the solvent include toluene, methanol, ethanol, isopropanol, tetrahydrofuran, 1,4-dioxane, and mixtures thereof. A preferred solvent is toluene. The reaction temperature is, for example, 0°C to 150°C, preferably 5°C to 40°C. The compound [A1-1] or a salt thereof is commercially available, or may be prepared from a commercially available product by a known method. The compound [A1-2] is a commercially available product, or may be prepared from a commercially available product by a known method.

[0089] (Process A1-2) The compound [A1-5] or a salt thereof can be produced by reacting the compound [A1-3] or a salt thereof with the compound [A1-4] or a salt thereof in a solvent in the presence of a base. Examples of the base include triethylamine, 1,8-diazabicyclo[5,4,0]-7-undecene, and N,N-diisopropylethylamine. Preferred bases are triethylamine and N,N-diisopropylethylamine. Examples of the solvent include toluene, methanol, ethanol, tetrahydrofuran, and mixtures thereof. Preferred solvents are toluene and methanol. The reaction temperature is, for example, from -78°C to 100°C, preferably from 0°C to 40°C. The compound [A1-4] or a salt thereof is commercially available, or may be prepared from a commercially available product by a known method.

[0090] (Process A1-3) The compound [A1-6] or a salt thereof can be produced by reacting the compound [A1-5] or a salt thereof in a solvent in the presence of an acid. Examples of acids include trifluoroacetic acid, sulfuric acid, hydrochloric acid, and triethylsilyl trifluoromethanesulfonate. A preferred acid is trifluoroacetic acid. Examples of the solvent include toluene, tetrahydrofuran, ethyl acetate, cyclopentyl methyl ether, dichloromethane, and mixtures thereof. A preferred solvent is toluene. The reaction temperature is, for example, from -78°C to 60°C, preferably from 0°C to 40°C.

[0091] (Process A1-4) The compound [A1-7] or a salt thereof can be produced by reacting the compound [A1-6] or a salt thereof in a solvent in the presence of a base. Examples of bases include sodium hydroxide and potassium hydroxide. A preferred base is sodium hydroxide. Examples of the solvent include tetrahydrofuran, 1,2-dimethoxyethane, 1,4-dioxane, chloroform, and mixtures thereof. The preferred solvent is tetrahydrofuran. The reaction temperature is, for example, 0°C to 150°C, preferably 50°C to 100°C.

[0092] (Process A1-5) The compound [IA] or a salt thereof can be prepared by reacting the compound [A1-7] or a salt thereof with the compound [A1-8] or a salt thereof in a solvent in the presence of a base. Examples of the base include sodium methoxide, sodium ethoxide, and sodium hydride. Preferred bases are sodium methoxide or sodium hydride. Examples of the solvent include N-methyl-2-pyrrolidone, N,N-dimethylformamide, methanol, ethanol, isopropanol, and mixtures thereof. The preferred solvent is methanol or N,N-dimethylformamide. The reaction temperature is, for example, 0°C to 120°C, preferably 60°C to 120°C. The compound [A1-8] or a salt thereof is commercially available, or may be prepared from a commercially available product by a known method.

[0093] In this production method, instead of compound [A1-4] or a salt thereof, a compound having a functional group or a protected substituent that can be converted to various substituents on the benzene ring by known reactions, or a salt thereof, may be used to carry out this production method, to obtain a compound corresponding to compound [IA] or a salt thereof, and then convert the functional group or the protected substituent to the various substituents to produce compound [IA] or a salt thereof. For example, instead of compound [A1-4] or a salt thereof, A2 or a salt thereof, to obtain a compound corresponding to compound [IA], i.e., compound [IB] or a salt thereof, and then, by Production Method A2, A2 Cy A2 Compound [IC] or a salt thereof may be prepared by converting the compound [IC] into the following compound.

[0094] Production method A2: Production method of compound [IC] or a salt thereof Compound [IC] or a salt thereof can be produced, for example, by the following Production Method A2. [ka] [In the formula, R 3 is as defined above, Cy A2 is C 3-6 cycloalkyl {wherein the cycloalkyl is optionally substituted with one or two hydroxy or halogen groups}; L A2is a leaving group (e.g., halogen, methanesulfonyloxy, and trifluoromethanesulfonyloxy), provided that the leaving group is attached at the ortho or para position of the benzene ring. (Process A2-1) Compound [IC] or a salt thereof can be produced by reacting compound [IB] or a salt thereof with compound [A2-1] or a derivative thereof (e.g., cyclopropylboronic acid pinacol ester and potassium cyclopropyltrifluoroborate) in a solvent in the presence of a catalyst and a base. Examples of the catalyst include [1,1'-bis(di-phenylphosphino)ferrocene]palladium(II) dichloride dichloromethane adduct, tetrakis(triphenylphosphine)palladium(0), and [1,1'-bis(di-tert-butylphosphino)ferrocene]palladium(II) dichloride. A preferred catalyst is [1,1'-bis(di-tert-butylphosphino)ferrocene]palladium(II) dichloride. Examples of bases include tripotassium phosphate, cesium carbonate, and potassium carbonate. A preferred base is tripotassium phosphate. Examples of the solvent include water, toluene, 1,2-dimethoxyethane, 1,4-dioxane, and mixtures thereof. A preferred solvent is a mixture of toluene and water. The reaction temperature is, for example, 10°C to 200°C, preferably 50°C to 150°C. Compound [IB] or a salt thereof may be prepared from a commercially available product by a known method. Compound [IB] or a salt thereof may be prepared, for example, by the above-mentioned preparation method. The compound [A2-1] or a derivative thereof is commercially available, or may be prepared from a commercially available product by a known method.

[0095] Production method A3: Production method of compound [ID] or a salt thereof Compound [ID] or a salt thereof can also be produced, for example, by Production Method A3 shown below. [ka] wherein Cy and R 3 is as defined above, R A3 is C 1-4 is alkyl, L A3 is a leaving group (e.g., halogen, methanesulfonyloxy, and p-toluenesulfonyloxy)} (Process A3-1) The compound [ID] or a salt thereof can be prepared by reacting the compound [IA] or a salt thereof with the compound [A3-1] in a solvent in the presence of a base. Examples of the base include cesium carbonate, sodium methoxide, sodium hydride, and potassium carbonate. A preferred base is sodium hydride. Examples of solvents include methanol, N,N-dimethylformamide, and tetrahydrofuran. A preferred solvent is N,N-dimethylformamide. The reaction temperature is, for example, 0°C to 100°C, preferably 10°C to 50°C. The compound [A3-1] is a commercially available product, or may be prepared from a commercially available product by a known method.

[0096] Production method A4: Production method for compound [IA] or a salt thereof Compound [IA] or a salt thereof can be produced, for example, by the following Production Method A4. [ka] wherein Cy and R 3 is as defined above, L A41 , and L A42 are each independently a leaving group (e.g., halogen, methanesulfonyloxy, and p-toluenesulfonyloxy). (Process A4-1) The compound [A4-3] or a salt thereof can be produced by reacting the compound [A4-1] or a salt thereof with the compound [A4-2] or a salt thereof in a solvent in the presence of a base. Examples of bases include triethylamine, N,N-diisopropylethylamine, and 1,8-diazabicyclo[5,4,0]-7-undecene. A preferred base is triethylamine. Examples of the solvent include methanol, ethanol, tetrahydrofuran, toluene, cyclopentyl methyl ether, acetonitrile, water, and mixtures thereof. A preferred solvent is a mixture of tetrahydrofuran and water. The reaction temperature is, for example, from −20° C. to 80° C., preferably from 0° C. to room temperature. The compound [A4-1] or a salt thereof is commercially available, or may be prepared from a commercially available product by a known method. The compound [A4-2] or a salt thereof is commercially available, or may be prepared from a commercially available product by a known method.

[0097] (Process A4-2) The compound [IA] or a salt thereof can be produced by reacting the compound [A4-3] or a salt thereof in a solvent in the presence of an acid. Acids include, for example, formic acid, trifluoroacetic acid, and hydrochloric acid. A preferred acid is trifluoroacetic acid. Examples of the solvent include toluene, water, acetonitrile, tetrahydrofuran, and mixtures thereof. A preferred solvent is toluene. The reaction temperature is, for example, 0° C. to 100° C., preferably 0° C. to room temperature.

[0098] In this production method, instead of compound [A4-2] or a salt thereof, a compound having a functional group or a protected substituent that can be converted to various substituents on the benzene ring by known reactions, or a salt thereof, may be used to carry out this production method, to obtain a compound corresponding to compound [IA] or a salt thereof, and then convert the functional group or the protected substituent to the various substituents to produce compound [IA] or a salt thereof. For example, instead of compound [A4-2] or a salt thereof, L A2or a salt thereof, to obtain a compound corresponding to compound [IA], i.e., compound [IB] or a salt thereof, and then, by Production Method A2, A2 Cy A2 Compound [IC] or a salt thereof may be prepared by converting the compound [IC] into the following compound. [Example]

[0099] Next, the method for producing the compound of formula [I] or a pharmaceutically acceptable salt thereof will be specifically explained by way of Preparation Examples, but the method for producing the compound of formula [I] or a pharmaceutically acceptable salt thereof is not limited to these Preparation Examples. Unless otherwise specified, % indicates % by weight. Ratios shown in mixed solvents indicate volume ratios unless otherwise specified. NMR was measured at 400 MHz.

[0100] [Production Example 1]: Synthesis of 2-(4-bromo-2,6-dimethylphenyl)-6-methoxy-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (Example 12) [ka] Step 1-1: 2-(4-bromo-2,6-dimethylphenyl)-6-methoxy-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one [ka] Under an argon atmosphere, a 5 M solution of sodium methoxide in methanol (0.56 mL) was added to a mixture of 2-(4-bromo-2,6-dimethylphenyl)-6-chloro-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (200 mg), synthesized in the same manner as in Step 2-4 of Preparation 2, and N-methyl-2-pyrrolidone (3.0 mL), and the mixture was stirred at 110°C for 1 hour. Acetic acid (0.5 mL) was added to the reaction mixture, and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (developing solvent: 20 vol% to 100 vol% ethyl acetate / hexane) and solidified using diisopropyl ether to give the title compound (190 mg). 1 H-NMR (DMSO-D6) δ: 11.85 (1H, br s), 8.60 (1H, s), 7.51 (2H, s), 3.91 (3H, s), 1.96 (6H, s). LC-MS (MH+): 349.

[0101] [Production Example 2]: Synthesis of 6-methoxy-2-(4-methoxy-2,6-dimethylphenyl)-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (Example 13) [ka] Step 2-1: 2,4,6-trichloro-5-(dimethoxymethyl)pyrimidine [ka] Under a nitrogen atmosphere, trimethyl orthoformate (230 mL) and sulfuric acid (0.48 mL) were added to a mixture of 2,4,6-trichloropyrimidine-5-carbaldehyde (76 g) and toluene (450 mL), and the mixture was stirred at room temperature for 1.5 hours. Basic silica gel (Fujisilica, 150 g) was added to the reaction mixture, and after stirring for 1 hour, the added silica gel was removed by filtration. The silica gel was washed with ethyl acetate (1.2 L), and the solvent was evaporated under reduced pressure to give the title compound (82 g). 1H-NMR (CDCl3) δ: 5.68 (1H, s), 3.49 (6H, s).

[0102] Step 2-2: 4-(2-(4-bromo-2,6-dimethylphenyl)hydrazinyl)-2,6-dichloro-5-(dimethoxymethyl)pyrimidine [ka] Under a nitrogen atmosphere, 2,4,6-trichloro-5-(dimethoxymethyl)pyrimidine (19 g) was added to a mixture of (4-bromo-2,6-dimethylphenyl)hydrazine hydrochloride (19 g) and methanol (130 mL), and the reaction mixture was cooled in an ice bath. Triethylamine (31 mL) was slowly added to the reaction mixture, and the mixture was stirred at the same temperature for 2 hours. The resulting solid was collected by filtration and washed successively with methanol (40 mL) and hexane (20 mL) to give the title compound (29 g). 1 H-NMR (CDCl3) δ: 8.28 (1H, d, J = 4.4 Hz), 7.10 (2H, s), 6.14 (1H, d, J = 4.9 Hz), 5.56 (1H, s), 3.45 (6H, s), 2.43 (6H, s). LC-MS (MH+): 436.

[0103] Step 2-3: 2-(4-bromo-2,6-dimethylphenyl)-4,6-dichloro-2H-pyrazolo[3,4-d]pyrimidine [ka] Under an argon atmosphere, trifluoroacetic acid (10 mL) was slowly added dropwise to a mixture of 4-(2-(4-bromo-2,6-dimethylphenyl)hydrazinyl)-2,6-dichloro-5-(dimethoxymethyl)pyrimidine (29 g) and toluene (230 mL). The reaction mixture was stirred for an additional 1 hour and then slowly added dropwise to an ice-cooled aqueous solution (93 mL) of potassium phosphate tripotassium (28 g). The organic layer was separated, and saturated brine was added to the aqueous layer, followed by extraction with ethyl acetate. All organic layers were washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was then evaporated under reduced pressure to give the crude title compound (26 g). LC-MS (MH+): 372.

[0104] Step 2-4: 2-(4-bromo-2,6-dimethylphenyl)-6-chloro-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one [ka] To a mixture of crude 2-(4-bromo-2,6-dimethylphenyl)-4,6-dichloro-2H-pyrazolo[3,4-d]pyrimidine (24 g) and tetrahydrofuran (200 mL), 4 M aqueous sodium hydroxide (49 mL) was added and stirred at 65°C for 5 hours. The reaction mixture was cooled in an ice bath, and 2 M hydrochloric acid (66 mL) was slowly added dropwise. The reaction mixture was extracted with ethyl acetate, and the aqueous layer was extracted again with ethyl acetate. All organic layers were washed with saturated brine and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. Diisopropyl ether (200 mL) was added to the resulting crude product, and the mixture was stirred for 30 minutes. The solid was collected by filtration to give the title compound (21 g). 1 H-NMR (DMSO-D6) δ: 12.88 (1H, br s), 8.81 (1H, s), 7.53 (2H, s), 1.95 (6H, s). LC-MS (MH+): 354.

[0105] Step 2-5: 6-Methoxy-2-(4-methoxy-2,6-dimethylphenyl)-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one [ka] Under an argon atmosphere, a 5 M solution of sodium methoxide in methanol (3.4 mL) was added to a mixture of 2-(4-bromo-2,6-dimethylphenyl)-6-chloro-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (1.0 g) and N,N-dimethylformamide (10 mL) and refluxed at 120°C for 1 hour. Copper(I) bromide (0.41 g) was added to the reaction mixture, and the mixture was refluxed at 120°C for 2 hours. The reaction mixture was acidified with 1 M hydrochloric acid and extracted with ethyl acetate. The resulting organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (eluent: 20 vol% to 100 vol% ethyl acetate / hexane) to give the title compound (520 mg). 1 H-NMR (DMSO-D6) δ: 11.81 (1H, br s), 8.52 (1H, s), 6.80 (2H, s), 3.91 (3H, s), 3.78 (3H, s), 1.93 (7H, s). LC-MS (MH+): 301.

[0106] [Production Example 3]: Synthesis of 2-(4-(difluoromethoxy)-2,6-dimethylphenyl)-6-methoxy-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (Example 39) [ka] Step 3-1: 4-chloro-6-(2-(4-(difluoromethoxy)-2,6-dimethylphenyl)hydrazinyl)-2-methoxypyrimidine-5-carbaldehyde [ka] To a mixture of (4-(difluoromethoxy)-2,6-dimethylphenyl)hydrazine hydrochloride (50 mg), N,N-diisopropylethylamine (0.15 mL), tetrahydrofuran (0.75 ml), and water (0.25 ml), 4,6-dichloro-2-methoxypyrimidine-5-carbaldehyde (48 mg) was added and stirred at room temperature for 1 hour. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, which was then extracted with ethyl acetate. The resulting organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was then evaporated under reduced pressure to give the title compound as a crude product (80 mg). LC-MS(MH):371.

[0107] Step 3-2: 2-(4-(difluoromethoxy)-2,6-dimethylphenyl)-6-methoxy-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one [ka] Under an argon atmosphere, trifluoroacetic acid (33 μL) was added to a mixture of crude 4-chloro-6-(2-(4-(difluoromethoxy)-2,6-dimethylphenyl)hydrazinyl)-2-methoxypyrimidine-5-carbaldehyde (80 mg) and toluene (0.80 mL), and the mixture was stirred at room temperature for 3 hours. The reaction mixture was purified by column chromatography (developing solvent: 10 vol% to 100 vol% ethyl acetate / hexane) to obtain the title compound (48 mg). 1 H-NMR (DMSO-D6) δ: 11.85 (1H, br s), 8.60 (1H, s), 7.30 (1H, t, J = 73.8 Hz), 7.09 (2H, s), 3.92 (3H, s), 1.97 (6H, s). LC-MS (MH+): 337.

[0108] The compounds of the other examples were obtained by the same methods as those in the above-mentioned production methods and production examples, or by using known methods as necessary. The structural formula and physical property data of each example compound are shown in the table below. [Table 1] TIFF2025169332000034.tif226151 TIFF2025169332000035.tif229151 TIFF2025169332000036.tif213151 TIFF2025169332000037.tif238151 TIFF2025169332000038.tif222152 TIFF2025169332000039.tif229153 TIFF2025169332000040.tif231151 TIFF2025169332000041.tif234151 TIFF2025169332000042.tif234152 TIFF2025169332000043.tif233153 TIFF2025169332000044.tif213150 TIFF2025169332000045.tif210151

[0109] Test Example 1: Evaluation of NLRP3 inflammasome inhibitory effect The inhibitory effect of test substances on NLRP3 inflammasome activity was evaluated by their suppression of IL-1β production in THP1-Null cells (product number thp-null, InvivoGen). Cells were maintained and cultured in RPMI-1640 medium containing 10% (v / v) fetal bovine serum, 25 mmol / L HEPES, 100 U / mL penicillin, 100 μg / mL streptomycin, 100 μg / mL normocin, and 200 μg / mL hygromycin B at 37°C in a 5% CO2 / 95% air atmosphere. Cells suspended in assay medium (RPMI-1640 medium containing 10% (v / v) fetal bovine serum, 100 U / mL penicillin, and 100 μg / mL streptomycin) containing 0.5 μmol / L PMA were seeded onto Corning® 384-well Flat Clear Bottom Black Polystyrene TC-treated Microplates (25,000 cells / 25 μL / well) and cultured overnight at 37°C in 5% CO2 / 95% air. The culture supernatant was removed, and assay medium containing 1 μg / mL Lipopolysaccharides (product number L2654, Sigma-Aldrich®) was added (25 μL / well). The culture was then cultured for 3 hours at 37°C in 5% CO2 / 95% air. The culture supernatant was removed, and a medium solution prepared with Opti-MEM™ medium (product number 31985-070, Invitrogen) was added (20 μL / well) to blank and control wells and incubated for 15 minutes (37°C, 5% CO2 / 95% air). Test substance solution was added (20 μL / well) to test substance wells. Furthermore, Opti-MEM™ medium containing Nigericin (product number N7143, Sigma-Aldrich®) was added (5 μL / well) to control and test substance wells and incubated for 1.5 hours (37°C, 5% CO2 / 95% air). The final concentration of Nigericin was 7.5 μmol / L. Opti-MEM™ medium was added (5 μL / well) to blank wells. The culture supernatant was stored frozen (-20°C) until IL-1β measurement. The IL-1β in the culture supernatant was quantified using AlphaLISA (registered trademark) Human IL-1β Detection Kit (product number AL220C, Perkin Elmer). Fluorescence intensity was measured using a microplate reader EnSpier (product number 2300-00J, Perkin Elmer) or EnSight (product number HH34000000, Perkin Elmer) according to the attached operating instructions. The inhibition rate of the test substance well was calculated by setting the blank well as 100% and the control well as 0%. The IC of the test substance 50 The values ​​(50% inhibitory concentration) were calculated by logistic regression analysis. The results for each example compound are shown in the table below.

[0110] [Table 2] TIFF2025169332000047.tif196102 TIFF2025169332000048.tif211103

[0111] Examples of the formulation of the present invention include the following formulations: However, the present invention is not limited to these formulation examples. Formulation Example 1 (Capsule Production) (1) 30 mg of the compound of Example 1 (2) Microcrystalline cellulose 10 mg (3) Lactose 19mg (4) Magnesium stearate 1 mg (1), (2), (3) and (4) are mixed and filled into a gelatin capsule.

[0112] Formulation Example 2 (Tablet Production) (1) Compound of Example 1 10 g (2) Lactose 50g (3) 15g corn starch (4) Carmellose calcium 44g (5) Magnesium stearate 1g The total amount of (1), (2), and (3) and 30 g of (4) are kneaded with water, vacuum dried, and then sized. 14 g of (4) and 1 g of (5) are mixed with this sized powder and compressed into tablets using a tablet press. 1,000 tablets, each containing 10 mg of the compound of Example 1, are thus obtained. [Industrial Applicability]

[0113] The compound of formula [I] or a pharmaceutically acceptable salt thereof has an inhibitory effect on the NLRP3 inflammasome, and is thereby effective in treating a variety of diseases, including multiple sclerosis, chronic kidney disease, inflammatory bowel disease (e.g., ulcerative colitis and Crohn's disease), arteriosclerosis, cryopyrin-associated periodic fever syndrome (e.g., familial cold autoinflammatory syndrome, Muckle-Wells syndrome, chronic infantile neurological cutaneous and articular syndrome, and neonatal-onset multi-organ inflammatory disease), non-alcoholic steatohepatitis, gout, gouty arthritis, rheumatoid arthritis, contact dermatitis, dry eye, ischemic heart disease (e.g., acute myocardial infarction), systemic lupus erythematosus, systemic juvenile idiopathic arthritis, recurrent pericarditis, adult-onset Still's disease (e.g., hemophagocytic lymphohistiocytosis and macrophage leukemia), and other conditions. The compound is expected to be useful as a therapeutic or preventive agent for a disease selected from the group consisting of phage activation syndrome, Schnitzler syndrome, IL-1 receptor antagonist molecule deficiency, familial Mediterranean fever, mevalonate kinase deficiency, hyper-IgD syndrome, Behçet's disease, lung cancer, psoriasis, hypertension, diabetic retinopathy, Alzheimer's disease, mild cognitive impairment, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, cerebral infarction, cerebral hemorrhage, epilepsy, depression, autism spectrum disorder, spinal cord injury, septic encephalopathy, neuropathic pain, COVID-19, frontotemporal dementia, age-related macular degeneration, diabetic macular edema, hereditary transient corneal endotheliitis, and TNF receptor-associated periodic syndrome.

Claims

1. A compound of formula [I] or a pharmaceutically acceptable salt thereof. 【Chemistry 1】 {During the ceremony, The ring group Cy is (1) Formula: 【Chemistry 2】 (In the formula, R ４ and R ５ are each independently (a) hydrogen, (b) cyano, (c) C １－６ alkyl {wherein the alkyl is (1) hydroxy, (2) C １－４ Alkoxy, and (3) C ３－６ cycloalkyl; (d) C １－４ Alkoxy, (e) halogen, (f) C １－４ haloalkyl, (g) -O-C １－４ haloalkyl, (h) -O-CD ３ , or (i) C ３－６ cycloalkyl, R ６ and R ７ are each independently (a) hydrogen, (b) C １－４ Alkyl, (c) C １－４ alkoxy, or (d) a halogen; R ８ teeth, (a) hydrogen, (b) C １－６ alkyl (wherein the alkyl is hydroxy or C １－４ optionally substituted with alkoxy); (c) C １－４ Alkoxy, (d) halogen, (e) C １－６ haloalkyl, (f) -O-C １－４ haloalkyl, or (g) C ３－６ cycloalkyl, wherein the cycloalkyl is optionally substituted with one or two hydroxy or halogen groups; or R ８ is R ６ or R ７ and together with the carbon atom to which they are attached may form a 5- to 7-membered heterocycloalkene containing 1 or 2 oxygen atoms. or a group represented by (2) Formula: 【Transformation 3】 (In the formula, R ９ and R １０ are each independently C １－４ Alkyl or C １－４ is haloalkyl, R １１ is C １－６ alkyl) is a group represented by R １ teeth, (1) hydrogen, (2) cyano, (3) C １－４ Alkyl, (4) halogen, or (5) C ３－６ cycloalkyl, R ２ is hydrogen or C １－４ is alkyl, R ３ teeth, (1) C １－６ alkyl {wherein the alkyl is (a) hydroxy, (b) cyano, (c) C １－４ Alkoxy, (d)-NR １２ R １３ (where R １２ and R １３ are each independently C １－４ alkyl), (e) -SO ２ -C １－６ Alkyl, (f) C ３－６ Cycloalkyl (wherein the cycloalkyl is cyano, or C １－４ C optionally substituted with alkoxy １－４ optionally substituted with alkyl); (g) 4- to 6-membered heterocycloalkyl containing one oxygen or sulfur atom, wherein the heterocycloalkyl is optionally substituted with one or two oxo; and (h) phenyl, optionally substituted with 1 or 2 substituents independently selected from the group consisting of: (2) C １－６ haloalkyl (wherein the haloalkyl is optionally substituted with hydroxy); (3)-CD ３ 、 (4) C ３－６ Cycloalkyl (wherein the cycloalkyl is —SO ２ -C １－４ optionally substituted with alkyl, or (5) a 4- to 6-membered heterocycloalkyl containing one oxygen or sulfur atom, wherein the heterocycloalkyl is optionally substituted with one or two oxo groups.

2. R １ 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein is hydrogen.

3. R ２ 3. The compound according to claim 1 or 2, or a pharmaceutically acceptable salt thereof, wherein is hydrogen.

4. The ring group Cy is (1) Formula: 【Chemistry 4】 (In the formula, R ４ , R ５ , R ６ , R ７ and R ８ has the same meaning as in claim 1) 4. The compound according to claim 1, wherein R is a group represented by the formula: or a pharmaceutically acceptable salt thereof.

5. R ６ and R ７ 5. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein is hydrogen.

6. The compound according to any one of claims 1 to 5, which is represented by formula [II] or a pharmaceutically acceptable salt thereof. 【Transformation 5】 (In the formula, R ３ , R ４ , R ５ and R ８ has the same meaning as in claim 1)

7. R ４ and R ５ At least one of (1) cyano, (2) C １－６ alkyl {wherein the alkyl is (a) hydroxy, (b) C １－４ Alkoxy, and (c) C ３－６ cycloalkyl; (3) C １－４ Alkoxy, (4) halogens, (5) C １－４ haloalkyl, (6) -O-C １－４ haloalkyl, (7) -O-CD ３ , or (8) C ３－６ 7. The compound of claim 1, or a pharmaceutically acceptable salt thereof, which is cycloalkyl.

8. R ３ but (1) C １－６ alkyl {wherein the alkyl is (a) hydroxy, (b) cyano, (c) C １－４ Alkoxy, (d)-NR １２ R １３ (where R １２ and R １３ are each independently C １－４ alkyl), (e) -SO ２ -C １－６ Alkyl, (f) C ３－６ Cycloalkyl (wherein the cycloalkyl is cyano, or C １－４ C optionally substituted with alkoxy １－４ optionally substituted with alkyl); (g) 4- to 6-membered heterocycloalkyl containing one oxygen or sulfur atom, wherein the heterocycloalkyl is optionally substituted with one or two oxo; and (h) phenyl, optionally substituted with 1 or 2 substituents independently selected from the group consisting of; (2) A compound according to any one of claims 1 to 7, which is a 4- to 6-membered heterocycloalkyl containing one oxygen or sulfur atom (wherein the heterocycloalkyl is optionally substituted with one or two oxo groups), or a pharmaceutically acceptable salt thereof.

9. The following structural formula: 【Transformation 6】 2. The compound of claim 1, selected from the group consisting of: or a pharmaceutically acceptable salt thereof.

10. 10. A pharmaceutical composition comprising a compound according to any one of claims 1 to 9 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

11. 10. An NLRP3 inflammasome inhibitor comprising the compound of any one of claims 1 to 9 or a pharmaceutically acceptable salt thereof.

12. A therapeutic or preventive agent for a disease selected from the group consisting of multiple sclerosis, inflammatory bowel disease, arteriosclerosis, cryopyrin-associated periodic fever syndrome, non-alcoholic steatohepatitis, gout, ischemic heart disease, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and traumatic brain injury, comprising the compound according to any one of claims 1 to 9 or a pharmaceutically acceptable salt thereof.

13. The therapeutic or prophylactic agent according to claim 12, wherein the inflammatory bowel disease is ulcerative colitis or Crohn's disease.

14. The therapeutic or preventive agent according to claim 12, wherein the cryopyrin-associated periodic fever syndrome is familial cold autoinflammatory syndrome, Muckle-Wells syndrome, chronic infantile neurological cutaneous and articular syndrome, or neonatal-onset multi-organ inflammatory disease.

15. A method for inhibiting the NLRP3 inflammasome, comprising administering to a mammal a therapeutically effective amount of a compound according to any one of claims 1 to 9 or a pharmaceutically acceptable salt thereof.

16. A method for treating or preventing a disease selected from the group consisting of multiple sclerosis, inflammatory bowel disease, arteriosclerosis, cryopyrin-associated periodic fever syndrome, non-alcoholic steatohepatitis, gout, ischemic heart disease, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and traumatic brain injury, comprising administering a therapeutically effective amount of the compound according to any one of claims 1 to 9 or a pharmaceutically acceptable salt thereof to a mammal.

17. 17. The method of claim 16, wherein the inflammatory bowel disease is ulcerative colitis or Crohn's disease.

18. 17. The method of claim 16, wherein the cryopyrin-associated periodic fever syndrome is familial cold autoinflammatory syndrome, Muckle-Wells syndrome, chronic infantile neurological cutaneous and articular syndrome, or neonatal-onset multisystem inflammatory disease.

19. Use of a compound according to any one of claims 1 to 9 or a pharmaceutically acceptable salt thereof for the manufacture of an NLRP3 inflammasome inhibitor.

20. Use of the compound according to any one of claims 1 to 9 or a pharmaceutically acceptable salt thereof for the manufacture of an agent for the treatment or prevention of a disease selected from the group consisting of multiple sclerosis, inflammatory bowel disease, arteriosclerosis, cryopyrin-associated periodic fever syndrome, non-alcoholic steatohepatitis, gout, ischemic heart disease, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and traumatic brain injury.

21. 21. The use according to claim 20, wherein the inflammatory bowel disease is ulcerative colitis or Crohn's disease.

22. 21. The use according to claim 20, wherein the cryopyrin-associated periodic fever syndrome is familial cold autoinflammatory syndrome, Muckle-Wells syndrome, chronic infantile neurological cutaneous and articular syndrome, or neonatal-onset multisystem inflammatory disease.

23. 10. A compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof, for use in inhibiting the NLRP3 inflammasome.

24. 10. The compound according to any one of claims 1 to 9 or a pharmaceutically acceptable salt thereof for use in the treatment or prevention of a disease selected from the group consisting of multiple sclerosis, inflammatory bowel disease, arteriosclerosis, cryopyrin-associated periodic fever syndrome, non-alcoholic steatohepatitis, gout, ischemic heart disease, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and traumatic brain injury.

25. 25. The compound of claim 24, or a pharmaceutically acceptable salt thereof, wherein the inflammatory bowel disease is ulcerative colitis or Crohn's disease.

26. 25. The compound according to claim 24, or a pharmaceutically acceptable salt thereof, wherein the cryopyrin-associated periodic fever syndrome is familial cold autoinflammatory syndrome, Muckle-Wells syndrome, chronic infantile neurological cutaneous and articular syndrome, or neonatal-onset multisystem inflammatory disease.

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