Compound 6-aminopyrazolopyrimidine and pharmaceuticals containing this compound.

Abstract

The invention relates to a compound of 6-aminopyrazolopyrimidine, or its pharmaceutical salt, exhibiting inhibitory activity against the NLRP3 inflammasome, a pharmaceutical composition containing this compound, etc. Compounds with the formula [IA]: or its pharmaceutical salt, in which the partial structure: is the structure with the following formula: where R4 is hydrogen or C1-4 alkyl, where the alkyl can be arbitrarily substituted by hydroxy or cyano, the CyA ring group is the group with the following formula: where each R6 and R7 are independently hydrogen, hydroxy, cyano, C1-6 alkyl, etc., each R8 and R9 are independently hydrogen, C1-4 alkyl, or C1-4 haloalkyl, R10 is hydrogen, cyano, C1-6 alkyl, etc.), R1 is hydrogen or C1-4 alkyl, each R2A and R3A are independently hydrogen, C1-6 alkyl, etc., 225 In addition, R2A and R3A can combine with the nitrogen atom to which they are attached and the -NR2AR 3A group can form heterocycloalkyl with 4 to 7 sides. It's up to you, etc.

Description

6-aminopyrazolopyrimidine compounds and their medical uses

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

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

[0006] Myelin Oligodendrocyte Glycoprotein (MOG) was generated 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. 35-55 In 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 the disease suppressed motor dysfunction (Non-Patent Document 7). Therefore, NLRP3 inflammasome inhibitors are considered to be a therapeutic agent 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, NLRP3 knockout has been reported to suppress 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 NLRP3 activation, is elevated in the intestinal mucosa of IBD patients, and increased IL-1β secretion from the colon has been shown to be positively correlated with worsening disease (Non-Patent Document 11). Furthermore, dysfunction of CARD8, which negatively regulates inflammasome activity, has been reported to increase susceptibility to Crohn's disease and to activate the NLRP3 inflammasome, leading to enhanced IL-1β production from monocytes (Non-Patent Document 12). In a TNBS-induced colitis model, NLRP3 deficiency has been reported to suppress intestinal pathology (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 potential 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). These results suggest that NLRP3 inflammasome inhibitors could be used to treat 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 membrane 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 membrane of collagen-induced arthritis, a model of rheumatoid arthritis (Non-Patent Document 25). Based on these results, NLRP3 inflammasome inhibitors are considered to be potential therapeutic agents for rheumatoid arthritis.

[0014] Trinitrochlorobenzene, which induces contact dermatitis, increases IL-1β production from human skin keratinocytes through 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 patients with dry eye (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] Increased expression of the ASC domain of the NLRP3 inflammasome has been reported 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, increased expression of NLRP3 inflammasome-related genes was observed in the infarcted area, and knockdown of the NLRP3 gene was reported to reduce infarct size and myocardial contractility (Non-Patent Document 30). Based on these results, NLRP3 inflammasome inhibitors are considered to be potential therapeutic agents for ischemic heart disease, including 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 with an activating mutation in the NLRP3 gene, pristane administration 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. Because the NLRP3 inflammasome is involved in the production of inflammatory cytokines such as IL-1β, NLRP3 inflammasome inhibitors are thought to be therapeutic agents 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). Furthermore, it has 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 associated with 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 downregulation 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, microglia show increased expression of NLRP3 inflammasome-related molecules and NLRP3 inflammasome activation (Non-Patent Document 52). The NLRP3 inhibitor MCC950 suppresses NLRP3 activation in the substantia nigra and inhibits dopamine neuron death in α-synuclein PFF-injected mice (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 in the striatum is increased (Non-Patent Document 54). The NLRP3 inhibitor MCC950 suppresses NLRP3 inflammasome activation in the striatum of R6 / 2 mice, suppressing neuronal death in the striatum and slowing symptom progression (Non-Patent Document 55). Therefore, NLRP3 inflammasome inhibitors are considered to be potential 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 SOD1G93A- and TDP-43-induced NLRP3 activation in microglia, 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 inhibits disease progression and extends survival (Non-Patent Document 58). Therefore, NLRP3 inflammasome inhibitors are considered to be potential treatments for ALS.

[0026] The expression 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 of the NLRP3 inflammasome is also increased, along with the expression of IL-1β and IL-18 (Non-Patent Document 61). The NLRP3 inhibitor MCC950 suppresses IL-1β production and suppresses the development of neurological symptoms after brain trauma in TBI model mice (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 (ICH) (Non-Patent Documents 63, 64). Furthermore, the NLRP3 inhibitor MCC950 demonstrated neuroprotective effects in MCAO and ICH rat models. 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 and 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, and 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, 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 and IL-1β expression are increased, indicating NLRP3 activation (Non-Patent Documents 73 and 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, promoting 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 of sepsis, increased expression and activation of the NLRP3 inflammasome or IL-1β in the brain occurs, resulting in hippocampal neuronal damage and memory impairment, a symptom of septic encephalopathy (Non-Patent Documents 75 and 76). Administration of the NLRP3 inhibitor MCC950 to the 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 of IL-1β and NLRP3 inflammasome-related molecules is increased in spinal glial cells and neurons (Non-Patent Document 77). Furthermore, in the paclitaxel-induced pain model, a neuropathic pain model of anticancer drug-induced neuropathy, the expression of NLRP3 inflammasome-related molecules is increased in the dorsal root ganglion and sciatic nerve (Non-Patent Document 78). Furthermore, in an animal model of trigeminal neuralgia, the expression 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 potential 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.

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[0036] The present invention provides a 6-aminopyrazolopyrimidine compound or a pharmaceutically acceptable salt thereof having NLRP3 inflammasome inhibitory activity, a pharmaceutical composition containing the same, and pharmaceutical uses thereof. That is, the present invention includes the following exemplary embodiments.

[0037] [Item 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]"). {In the formula, substructure: is expressed by the formula (1): {In the formula, R ４ is hydrogen or C １－４ alkyl (wherein the alkyl may be substituted with hydroxy or cyano)}, or (2) a structure represented by the formula: [In the formula, R ５ is C １－６alkyl {wherein the alkyl is: (a) hydroxy, (b) cyano, (c) C １－４ alkoxy, or (d) C ３－６ cycloalkyl, optionally substituted with １－４ The ring group Cy is a structure represented by the formula (1): (In the formula, R ６ and R ７ are each independently: (a) hydrogen, (b) hydroxy, (c) cyano, (d) C １－６ alkyl {wherein the alkyl is: (1) hydroxy, (2) C １－４ Alkoxy, and (3) C ３－６ cycloalkyl; and (e) C １－６ Alkoxy (wherein the alkoxy is C ３－６ (f) halogen; (g) C １－４ haloalkyl, (h) —CHO, (i) —O—C １－４ haloalkyl, (j) —O—C ３－６ cycloalkyl, (k) —CO—C １－４ Alkyl, (m)-CO-C ３－６ cycloalkyl, (n)-NR １１ R １２ (where R １１ and R １２ are each independently hydrogen or 2,4-dimethoxybenzyl, or R １１ and R １２ together with the nitrogen atom to which they are attached, form -NR １１ R １２ (o) the groups may form a 5- to 6-membered heterocycloalkyl containing 1 or 2 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms; or (o) C ３－６ cycloalkyl, and R ８ and R ９ are each independently: (a) hydrogen; (b) C １－４ alkyl, or (c) C １－４ haloalkyl, and R １０is (a) hydrogen, (b) cyano, (c) C １－６ alkyl, (d) C ２－６ alkenyl, (e) C ２－５ alkynyl, (f) C １－４ (g) halogen; (h) C １－６ haloalkyl, (i) C ２－６ haloalkenyl, (j) —O—C １－４ haloalkyl, (k) C ３－６ Cycloalkyl (wherein the cycloalkyl is C １－４ (m) C ５－６ (n) a 4- to 6-membered heterocycloalkyl containing 1 or 2 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms, (2) a group represented by the formula: {In the formula, R １３ and R １４ are each independently hydrogen or C １－４ alkyl, R １５ is C １－４ Haloalkyl or C ３－６ (3) a group represented by the formula: (In the formula, R １６ is C １－６ alkyl or halogen, R １７ is a halogen or C １－４ (4) a group represented by the formula: R １ is hydrogen or C １－４ alkyl, R ２ and R ３ are each independently: (1) hydrogen, (2) C １－６ alkyl {wherein the alkyl is: (a) C １－４ (b) alkoxy, ３－６ (c) phenyl, wherein the phenyl is C １－４ (3) C １－４ Alkoxy, (4) C １－４ Haloalkyl, (5)-CD３ , (6)-CO-C １－４ alkyl, (7) C ３－６ (8) 4- to 6-membered heterocycloalkyl containing 1 or 2 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms, wherein the heterocycloalkyl is C １－４ (9) phenyl, or (10) a group of the formula: or R ２ and R ３ together with the nitrogen atom to which they are attached, form -NR ２ R ３ (a) a 4- to 7-membered heterocycloalkyl containing from 1 to 3 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur atoms, wherein the heterocycloalkyl is selected from the group consisting of: (1) hydroxy, (2) cyano, (3) C １－６ alkyl {wherein the alkyl is: (a) hydroxy, (b) C １－４ (c) phenyl, or (4) C １－４ (5) halogen; (6) C １－４ haloalkyl, (7) —O—C １－４ Haloalkyl, (8) —CO—C １－４ Alkyl (wherein the alkyl is C １－４ (9) -CO-C １－６ Alkoxy, (10)-CO-C ３－６ cycloalkyl, (11)-CONH-C １－４ alkyl, (12)-NHCO-C １－４ alkyl, (13)-NR １８ R １９ (where R １８ and R １９ are each independently C １－４ alkyl), (14) -SO ２ -C １－４ alkyl, (15)-SO ２ -C ３－６ cycloalkyl, (16) C ３－６(17) phenyl, (18) a compound of the formula: and (19) oxo, (b) a 7- to 9-membered spiroheterocycloalkyl containing 1 to 3 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms, wherein the spiroheterocycloalkyl is optionally substituted with hydroxy; (c) a 6- to 9-membered saturated or partially unsaturated fused ring group containing 1 or 2 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms {wherein the fused ring group is selected from the group consisting of: (1) halogen, (2) —CO—C １－４ alkyl, and (3) —CO—C １－６ (d) a 6- to 8-membered bridged heterocycloalkyl containing 1 or 2 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms, wherein the bridged heterocycloalkyl is: (1) halogen, (2) —CO—C １－４ Alkyl (wherein the alkyl is C １－４ (3) -SO ２ -C １－４ alkyl, and may be substituted with 1 or 2 substituents independently selected from the group consisting of However, (1) formula: (In the formula, R ４ [Item 3] The compound according to Item 1, wherein R has the structure represented by the formula: １ [Item 4] The compound according to item 1 or 2, or a pharmaceutically acceptable salt thereof, wherein R is hydrogen. ４ [Item 5] The compound or a pharmaceutically acceptable salt thereof according to any one of items 1 to 3, wherein the ring group Cy is a group represented by the formula (1): (wherein each symbol has the same meaning as in item 1) The compound according to any one of items 1 to 4, which is a group represented by the formula:

[0022] or a pharmaceutically acceptable salt thereof.

[0023] [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. (wherein each symbol has the same meaning as in item 1) [item 7] R ８ and R ９ [Item 8] The compound according to any one of items 1 to 7, or a pharmaceutically acceptable salt thereof, represented by formula [IIa]: (In the formula, R ６ , R ７ , and R １０ has the same meaning as in item 1, and the ring group Cy １ (1) a 4- to 7-membered heterocycloalkyl containing from 1 to 3 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur atoms, wherein the heterocycloalkyl is selected from the group consisting of: (a) hydroxy, (b) cyano, (c) C １－６ alkyl {wherein the alkyl is: (1) hydroxy, (2) C １－４ (3) phenyl, or (d) C １－４ (e) halogen; (f) C １－４ haloalkyl, (g) —O—C １－４ haloalkyl, (h) —CO—C １－４ Alkyl (wherein the alkyl is C １－４ (i) -CO-C １－６ Alkoxy, (j) —CO—C ３－６ cycloalkyl, (k) -CONH-C １－４ alkyl, (m)-NHCO-C １－４ alkyl, (n)-NR １８ R １９ (where R １８ and R １９ are each independently C １－４ alkyl), (o) —SO ２ -C １－４ alkyl, (p)-SO２ -C ３－６ cycloalkyl, (q) C ３－６ (r) phenyl; (s) a group of the formula: and (t) oxo, (2) a 7- to 9-membered spiroheterocycloalkyl containing 1 to 3 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms, wherein the spiroheterocycloalkyl is optionally substituted with hydroxy; (3) a 6- to 9-membered saturated or partially unsaturated fused ring group containing 1 or 2 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms {wherein the fused ring group is selected from the group consisting of: (a) halogen, (b) -CO-C １－４ alkyl, and (c) —CO—C １－６ (4) a 6- to 8-membered bridged heterocycloalkyl containing 1 or 2 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms {wherein the bridged heterocycloalkyl is (a) halogen, (b) —CO—C １－４ Alkyl (wherein the alkyl is C １－４ (optionally substituted with alkoxy), and (c) —SO ２ -C １－４[Item 9] A pharmaceutical composition comprising the compound according to any one of items 1 to 8 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. [Item 10] An NLRP3 inflammasome inhibitor comprising the compound according to any one of items 1 to 8 or a pharmaceutically acceptable salt thereof. [Item 11] A therapeutic or preventive agent for a disease selected from the group consisting 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, and chronic infantile neurological, cutaneous, and articular syndrome / 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, relapsing pericarditis, adult-onset Still's disease (e.g., hemophagocytic lymphohistiocytosis and macrophage activation syndrome), Schnitzler syndrome, IL-1 receptor antagonist deficiency, familial Mediterranean fever, mevalonate kinase deficiency, hyper-IgD syndrome, and TNF receptor-associated periodic syndrome. [Item 12] A method for inhibiting NLRP3 inflammasome, comprising administering a therapeutically effective amount of the compound according to any one of Items 1 to 8 or a pharmaceutically acceptable salt thereof to a mammal.[Section 13] A method for treating or preventing a disease selected from the group consisting 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, and chronic infantile neurological, cutaneous, and articular syndrome / 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, familial Mediterranean fever, mevalonate kinase deficiency, hyper-IgD syndrome, and TNF receptor-associated periodic syndrome, comprising administering to a mammal a therapeutically effective amount of the compound according to any one of items 1 to 8 or a pharmaceutically acceptable salt thereof. [Item 14] Use of the compound according to any one of items 1 to 8 or a pharmaceutically acceptable salt thereof for the manufacture of an NLRP3 inflammasome inhibitor. [Item 15] Use of the compound according to any one of Items 1 to 8 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, 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, and chronic infantile neurological, cutaneous, and articular syndrome / 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, familial Mediterranean fever, mevalonate kinase deficiency, hyper-IgD syndrome, and TNF receptor-associated periodic syndrome. [Item 16] The compound according to any one of Items 1 to 8 or a pharmaceutically acceptable salt thereof for use in inhibiting NLRP3 inflammasome.[Item 17] The compound according to any one of Items 1 to 8, or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a disease selected from the group consisting 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, and chronic infantile neurological, cutaneous, and articular syndrome / 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, familial Mediterranean fever, mevalonate kinase deficiency, hyper-IgD syndrome, and TNF receptor-associated periodic syndrome. [Item 18] Item 10. A commercial package comprising the pharmaceutical composition according to Item 9 and 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 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, and chronic infantile neurological, cutaneous, and articular syndrome / 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, familial Mediterranean fever, mevalonate kinase deficiency, hyper-IgD syndrome, and TNF receptor-associated periodic syndrome.[Section 19] Item 10. A commercial kit comprising the pharmaceutical composition according to Item 9 and 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 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, and chronic infantile neurological, cutaneous, and articular syndrome / 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, familial Mediterranean fever, mevalonate kinase deficiency, hyper-IgD syndrome, and TNF receptor-associated periodic syndrome.

[0038] [Item 1A] A compound of formula [IA] or a pharmaceutically acceptable salt thereof (hereinafter, in this specification, "a compound of formula [IA] or a pharmaceutically acceptable salt thereof" may also be referred to as "compound [IA]"). {In the formula, substructure: is expressed by the formula (1): {In the formula, R ４ is hydrogen or C １－４ alkyl (wherein the alkyl may be substituted with hydroxy or cyano)}, or (2) a structure represented by the formula: [In the formula, R ５ is C １－６ alkyl {wherein the alkyl is: (a) hydroxy, (b) cyano, (c) C １－４ alkoxy, or (d) C ３－６ cycloalkyl, optionally substituted with １－４ and the ring group Cy is a haloalkyl. Ａ is expressed by the formula (1): (In the formula, R ６ and R ７ are each independently: (a) hydrogen, (b) hydroxy, (c) cyano, (d) C １－６alkyl {wherein the alkyl is: (1) hydroxy, (2) C １－４ Alkoxy, and (3) C ３－６ cycloalkyl; and (e) C １－６ Alkoxy (wherein the alkoxy is C ３－６ (f) halogen; (g) C １－４ haloalkyl, (h) —CHO, (i) —O—C １－４ haloalkyl, (j) —O—C ３－６ cycloalkyl, (k) —CO—C １－４ Alkyl, (m)-CO-C ３－６ cycloalkyl, (n)-NR １１ R １２ (where R １１ and R １２ are each independently hydrogen or 2,4-dimethoxybenzyl, or R １１ and R １２ together with the nitrogen atom to which they are attached, form -NR １１ R １２ (o) the groups may form a 5- to 6-membered heterocycloalkyl containing 1 or 2 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms; or (o) C ３－６ cycloalkyl, and R ８ and R ９ are each independently: (a) hydrogen; (b) C １－４ alkyl, or (c) C １－４ haloalkyl, and R １０ is (a) hydrogen, (b) cyano, (c) C １－６ alkyl, (d) C ２－６ alkenyl, (e) C ２－５ alkynyl, (f) C １－４ (g) halogen; (h) C １－６ haloalkyl, (i) C ２－６ haloalkenyl, (j) —O—C １－４ haloalkyl, (k) C ３－６ Cycloalkyl (wherein the cycloalkyl is C １－４(m) C ５－６ (n) a 4- to 6-membered heterocycloalkyl containing 1 or 2 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms, (2) a group represented by the formula: {In the formula, R １３ and R １４ are each independently hydrogen or C １－４ alkyl, R １５ is C １－４ Haloalkyl or C ３－６ (3) a group represented by the formula: (In the formula, R １６ is C １－６ alkyl or halogen, R １７ is a halogen or C １－４ (4) a group represented by the formula: or (5) a group represented by formula: (In the formula, R ２０ and R ２１ are each independently C １－４ Alkyl or C １－４ haloalkyl, R ２２ is C １－６ Alkyl or C ３－６ is a cycloalkyl group, １ is hydrogen or C １－４ alkyl, R ２A and R ３A are each independently: (1) hydrogen, (2) C １－６ alkyl {wherein the alkyl is: (a) hydroxy, (b) C １－４ alkoxy (wherein the alkoxy may be substituted with hydroxy); (c) C ３－６ cycloalkyl, or (d) phenyl, wherein the phenyl is C １－４ (3) C １－４ Alkoxy, (4) C １－４ Haloalkyl, (5)-CD ３ , (6)-CO-C １－４ alkyl, (7) C３－６ (8) 4- to 6-membered heterocycloalkyl containing 1 or 2 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms, wherein the heterocycloalkyl is C １－４ (9) phenyl, or (10) a group of the formula: or R ２A and R ３A together with the nitrogen atom to which they are attached, form -NR ２A R ３A (a) a 4- to 7-membered heterocycloalkyl containing from 1 to 3 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur atoms, wherein the heterocycloalkyl is selected from the group consisting of: (1) hydroxy, (2) cyano, (3) C １－６ alkyl {wherein the alkyl is: (a) hydroxy, (b) C １－４ (c) phenyl, or (4) C １－４ (5) halogen; (6) C １－４ haloalkyl, (7) —O—C １－４ Haloalkyl, (8) —CO—C １－４ Alkyl (wherein the alkyl is C １－４ (9) -CO-C １－６ Alkoxy, (10)-CO-C ３－６ cycloalkyl, (11)-CONH-C １－４ alkyl, (12)-NHCO-C １－４ alkyl, (13)-NR １８ R １９ (where R １８ and R １９ are each independently C １－４ alkyl), (14) -SO ２ -C １－４ alkyl, (15)-SO ２ -C ３－６ cycloalkyl, (16) C ３－６ (17) phenyl, (18) a compound of the formula: and (19) oxo, (b) a 7- to 9-membered spiroheterocycloalkyl containing 1 to 3 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms, wherein the spiroheterocycloalkyl is optionally substituted with hydroxy; (c) a 6- to 9-membered saturated or partially unsaturated fused ring group containing 1 or 2 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms {wherein the fused ring group is selected from the group consisting of: (1) halogen, (2) —CO—C １－４ alkyl, and (3) —CO—C １－６ (d) a 6- to 8-membered bridged heterocycloalkyl containing 1 or 2 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms {wherein the bridged heterocycloalkyl is: (1) halogen, (2) —CO—C １－４ Alkyl (wherein the alkyl is C １－４ (3) -SO ２ -C １－４ alkyl, optionally substituted with 1 or 2 substituents independently selected from the group consisting of: [Item 2A] Partial structure: However, (1) formula: (In the formula, R ４ [Item 3A] The compound according to Item 1A, wherein R has the structure represented by the formula: １ [Item 4A] The compound according to Item 1A or 2A, or a pharmaceutically acceptable salt thereof, wherein R is hydrogen. ４ [Item 5A] The compound or a pharmaceutically acceptable salt thereof according to any one of Items 1A to 3A, wherein the ring group Cy is hydrogen. Ａ However, (1) formula: (wherein each symbol has the same meaning as in item 1A) or a pharmaceutically acceptable salt thereof. [Item 6A] The compound according to any one of items 1A to 5A, which is represented by formula [IIA] or a pharmaceutically acceptable salt thereof. (wherein each symbol has the same meaning as in item 1A) [Item 7A] R ８ and R ９ [Item 8A] The compound according to any one of Items 1A to 6A, or a pharmaceutically acceptable salt thereof, wherein is hydrogen. [Item 8A] The compound according to any one of Items 1A to 7A, or a pharmaceutically acceptable salt thereof, represented by formula [IIIA]. (In the formula, R ６ , R ７ , and R １０ has the same meaning as in item 1A, and the ring group Cy Ｂ (1) a 4- to 7-membered heterocycloalkyl containing from 1 to 3 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur atoms, wherein the heterocycloalkyl is selected from the group consisting of: (a) hydroxy, (b) cyano, (c) C １－６ alkyl {wherein the alkyl is: (1) hydroxy, (2) C １－４ (3) phenyl, or (d) C １－４ (e) halogen; (f) C １－４ haloalkyl, (g) —O—C １－４ haloalkyl, (h) —CO—C １－４ Alkyl (wherein the alkyl is C １－４ (i) -CO-C １－６ Alkoxy, (j) —CO—C ３－６ cycloalkyl, (k) -CONH-C １－４ alkyl, (m)-NHCO-C １－４ alkyl, (n)-NR １８ R １９ (where R １８ and R １９ are each independently C １－４ alkyl), (o) —SO ２ -C １－４alkyl, (p)-SO ２ -C ３－６ cycloalkyl, (q) C ３－６ (r) phenyl; (s) a group of the formula: and (t) oxo, (2) a 7- to 9-membered spiroheterocycloalkyl containing 1 to 3 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms, wherein the spiroheterocycloalkyl is optionally substituted with hydroxy; (3) a 6- to 9-membered saturated or partially unsaturated fused ring group containing 1 or 2 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms {wherein the fused ring group is selected from the group consisting of: (a) halogen, (b) -CO-C １－４ alkyl, and (c) —CO—C １－６ (4) a 6- to 8-membered bridged heterocycloalkyl containing 1 or 2 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms {wherein the bridged heterocycloalkyl is (a) a halogen, (b) —CO—C １－４ Alkyl (wherein the alkyl is C １－４ (optionally substituted with alkoxy), and (c) —SO ２ -C １－４ alkyl, optionally substituted with 1 or 2 substituents independently selected from the group consisting of: [Item 9A] A ring group Cy Ｂ (1) a 4- to 7-membered heterocycloalkyl containing 1 to 3 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur atoms, wherein the heterocycloalkyl is selected from the group consisting of: (a) hydroxy, (b) cyano, (c) C １－６ alkyl {wherein the alkyl is: (1) hydroxy, (2) C １－４ (3) phenyl, or (d) C １－４ (e) halogen; (f) C １－４haloalkyl, (g) —O—C １－４ haloalkyl, (h) —CO—C １－４ Alkyl (wherein the alkyl is C １－４ (i) -CO-C １－６ Alkoxy, (j) —CO—C ３－６ cycloalkyl, (k) -CONH-C １－４ alkyl, (m)-NHCO-C １－４ alkyl, (n)-NR １８ R １９ (where R １８ and R １９ are each independently C １－４ alkyl), (o) —SO ２ -C １－４ alkyl, (p)-SO ２ -C ３－６ cycloalkyl, (q) C ３－６ (r) phenyl; (s) a group of the formula: and (t) oxo; or (2) a 6- to 8-membered bridged heterocycloalkyl containing 1 or 2 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms, wherein the bridged heterocycloalkyl is (a) a halogen, (b) —CO—C １－４ Alkyl (wherein the alkyl is C １－４ (optionally substituted with alkoxy), and (c) —SO ２ -C １－４ [Item 10A] The compound or a pharmaceutically acceptable salt thereof according to Item 8A, wherein the ring group Cy is Ｂ is a 4- to 7-membered heterocycloalkyl containing 1 to 3 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur atoms, wherein the heterocycloalkyl is selected from the group consisting of: (1) hydroxy, (2) cyano, (3) C １－６ alkyl {wherein the alkyl is: (a) hydroxy, (b) C １－４(c) phenyl, or (4) C １－４ (5) halogen; (6) C １－４ haloalkyl, (7) —O—C １－４ Haloalkyl, (8) —CO—C １－４ Alkyl (wherein the alkyl is C １－４ (9) -CO-C １－６ Alkoxy, (10)-CO-C ３－６ cycloalkyl, (11)-CONH-C １－４ alkyl, (12)-NHCO-C １－４ alkyl, (13)-NR １８ R １９ (where R １８ and R １９ are each independently C １－４ alkyl), (14) -SO ２ -C １－４ alkyl, (15)-SO ２ -C ３－６ cycloalkyl, (16) C ３－６ (17) phenyl, (18) a compound of the formula: (19) oxo, and (20) a ring group Cy, optionally substituted with 1 to 4 substituents independently selected from the group consisting of: Ｂ is a 4- to 7-membered heterocycloalkyl containing 1 to 3 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur atoms, wherein the heterocycloalkyl is: (1) cyano, (2) C １－６ Alkyl {wherein the alkyl is hydroxy, or C １－４ (3) C １－４ Alkoxy, (4) halogen, (5) —CO—C １－４ Alkyl (wherein the alkyl is C １－４ (6) -CO-C １－６ Alkoxy, (7) -CO-C ３－６cycloalkyl, (8)-SO ２ -C １－４ Alkyl, (9) -SO ２ -C ３－６ cycloalkyl, (10) a group of the formula: (11) a group represented by the following structural formula: and (12) a pharmaceutically acceptable salt thereof. [Item 13A] A pharmaceutical composition comprising the compound according to any one of items 1A to 12A or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. [Item 14A] An NLRP3 inflammasome inhibitor comprising the compound according to any one of items 1A to 12A or a pharmaceutically acceptable salt thereof. [Item 15A] Item 1A to 12A, or a pharmaceutically acceptable salt thereof, for the treatment 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 disease, A therapeutic or preventive agent for a disease selected from the group consisting of inflammatory bowel disease (e.g., hemophagocytic lymphohistiocytosis 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, and TNF receptor-associated periodic syndrome. [Item 16A] The therapeutic or preventive agent according to Item 15A, wherein the inflammatory bowel disease is ulcerative colitis or Crohn's disease. [Item 17A] The therapeutic or preventive agent 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. [Item 18A] A method for inhibiting NLRP3 inflammasome, comprising administering a therapeutically effective amount of the compound according to any one of Items 1A to 12A or a pharmaceutically acceptable salt thereof to a mammal.[Item 19A] 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 lymphohistiocytosis and macrophage activation syndrome), or Schnitzler's disease, comprising administering a therapeutically effective amount of the compound according to any one of Items 1A to 12A or a pharmaceutically acceptable salt thereof to a mammal. A method for treating or preventing a disease selected from the group consisting of inflammatory bowel disease, 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. [Item 20A] The method according to Item 19A, wherein the inflammatory bowel disease is ulcerative colitis or Crohn's disease. [Item 21A] The method according to Item 19A, 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 system inflammatory disease. [Item 22A] Use of the compound according to any one of Items 1A to 12A or a pharmaceutically acceptable salt thereof for the manufacture of an NLRP3 inflammasome inhibitor.[Item 23A] 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 Use of the compound or a pharmaceutically acceptable salt thereof according to any one of Items 1A to 12A for the manufacture of a therapeutic or preventive agent for a disease selected from the group consisting of inflammatory bowel disease (IGD), 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. [Item 24A] The use according to Item 23A, wherein the inflammatory bowel disease is ulcerative colitis or Crohn's disease. [Item 25A] The use according to Item 23A, 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. [Item 26A] The compound or a pharmaceutically acceptable salt thereof according to any one of Items 1A to 12A, for use in inhibiting NLRP3 inflammasome.[Item 27A] 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 disease [Item 28A] The compound or a pharmaceutically acceptable salt thereof according to any one of Items 1A to 12A for use in the treatment or prevention of a disease selected from the group consisting of inflammatory bowel disease (IBD), 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. [Item 28A] The compound or a pharmaceutically acceptable salt thereof according to Item 27A, wherein the inflammatory bowel disease is ulcerative colitis or Crohn's disease. [Item 29A] The compound or a pharmaceutically acceptable salt thereof according to Item 27A, 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.[Item 30A] The pharmaceutical composition according to Item 13A, and 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 lymphohistiocytosis and macrophage activation syndrome), and a method for treating adult-onset Still's disease (e.g., hemophagocytic lymphohistiocytosis and macrophage activation syndrome). 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.[Item 31A] The pharmaceutical composition according to Item 13A, and 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 lymphohistiocytosis and macrophage leukemia), and other conditions. 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 (IGD), 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.

[0039] The definitions of terms used in this specification are as follows.

[0040] In the chemical formula: The wavy line indicates the bonding site of the structure or group shown in the chemical formula.

[0041] "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.

[0042] "C １－６ "Alkyl" means a linear or branched 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. Methyl is preferred.

[0043] "C ２－６ "Alkenyl" means a straight or branched chain unsaturated hydrocarbon group containing from 2 to 6 carbon atoms and containing at least one double bond. ２－６ "Alkenyl" includes, for example, vinyl, allyl, 1-propenyl, isopropenyl, 2-methyl-1-propenyl, 1-butenyl, 2-butenyl, 1,3-butadienyl, 3-methyl-2-butenyl, 1,1-dimethyl-2-propenyl, 4-methyl-2-pentenyl, 4-methyl-3-pentenyl, and 1-methyl-2-butenyl.

[0044] "C ２－５ "Alkynyl" means a straight or branched chain unsaturated hydrocarbon group containing from 2 to 5 carbon atoms and containing at least one triple bond. ２－５ "Alkynyl" includes, for example, ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, and 2-pentynyl.

[0045] "C １－４ The term "alkoxy" refers to the above-mentioned "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.

[0046] "C １－６ The term "alkoxy" refers to the above-mentioned "C １－６ "C" means a group in which "alkyl" is bonded to an oxygen atom. １－６"Alkoxy" includes, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, isobutoxy, tert-butoxy, pentyloxy, isopentyloxy, neopentyloxy, 2-methylbutoxy, 1,1-dimethylpropoxy, 1-ethylpropoxy, hexyloxy, isohexyloxy, 1,1-dimethylbutoxy, 2,2-dimethylbutoxy, 3,3-dimethylbutoxy, and 2-ethylbutoxy.

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

[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, 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.

[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, 3,3,3-trifluoropropyl, 4,4,4-trifluorobutyl, 5,5,5-trifluoropentyl, and 6,6,6-trifluorohexyl.

[0050] "C ２－６ "Haloalkenyl" refers to the above "C" substituted with 1 to 9 halogens independently selected from the above "halogen" group. ２－６ "C" means "alkenyl". ２－６ "Haloalkenyl" includes, for example, 2-fluoroethenyl, 3-chloropropenyl, 2-fluoropropenyl, 1-trifluoromethylethenyl, and 4,4,4-trifluoro-2-butenyl.

[0051] "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. Preferably, it is cyclopropyl.

[0052] "C ５－６ "Cycloalkenyl" means a monocyclic partially unsaturated hydrocarbon ring group having 5 to 6 carbon atoms and containing at least one double bond. ５－６ "Cycloalkenyl" includes, for example, cyclopentenyl, cyclopentadienyl, cyclohexenyl, and cyclohexadienyl.

[0053] "4- to 6-membered heterocycloalkyl containing 1 or 2 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms" refers to a 4- to 6-membered monocyclic saturated heterocyclic group containing, in addition to carbon atoms, 1 or 2 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms as ring-constituting atoms. Examples of "4- to 6-membered heterocycloalkyl containing 1 or 2 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms" include azetidinyl, oxetanyl, diazetidinyl, dioxetanyl, pyrrolidinyl, tetrahydrofuranyl, imidazolidinyl, pyrazolidinyl, oxazolidinyl, isoxazolidinyl, dioxolanyl, piperidinyl, tetrahydropyranyl, 1,3-diazacyclohexanyl, piperazinyl, morpholinyl, tetrahydro-1,2-oxazinyl, and dioxanyl.

[0054] "4- to 7-membered heterocycloalkyl containing 1 to 3 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur atoms" means a 4- to 7-membered monocyclic saturated heterocyclic group containing, in addition to carbon atoms, 1 to 3 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur atoms as ring-constituting atoms. Examples of "4- to 7-membered heterocycloalkyl containing 1 to 3 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur atoms" include azetidinyl, oxetanyl, thietanyl, diazetidinyl, dioxetanyl, dithietanyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, imidazolidinyl, pyrazolidinyl, oxazolidinyl, isoxazolidinyl, thiazolidinyl, isothiazolidinyl, dioxolanyl, and dithiolanyl. , piperidinyl, tetrahydropyranyl, 1,3-diazacyclohexanyl, piperazinyl, morpholinyl, tetrahydro-1,2-oxazinyl, thiomorpholinyl, dioxanyl, hexahydrotriazinyl, azepanyl, oxepanyl, diazepanyl (e.g., 1,4-diazepanyl), oxazepanyl (e.g., 1,4-oxazepanyl and 1,2-oxazepanyl), dioxazepanyl (e.g., 1,5,2-dioxazepanyl), and thiazepanyl. Preferred is morpholinyl.

[0055] "5- to 6-membered heterocycloalkyl containing 1 or 2 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms" means a 5- to 6-membered monocyclic saturated heterocyclic group containing, in addition to carbon atoms, 1 or 2 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms as ring-constituting atoms. Examples of "5- to 6-membered heterocycloalkyl containing 1 or 2 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms" include pyrrolidinyl, tetrahydrofuranyl, imidazolidinyl, pyrazolidinyl, oxazolidinyl, isoxazolidinyl, dioxolanyl, piperidinyl, tetrahydropyranyl, 1,3-diazacyclohexanyl, piperazinyl, morpholinyl, tetrahydro-1,2-oxazinyl, and dioxanyl.

[0056] "7- to 9-membered spiroheterocycloalkyl containing 1 to 3 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms" means a 7- to 9-membered spiro-type saturated heterocyclic group containing, in addition to carbon atoms as ring-constituting atoms, 1 to 3 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms. "7- to 9-membered spiroheterocycloalkyl containing 1 to 3 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms" includes, for example, the following groups: Includes:

[0057] The term "6- to 9-membered saturated or partially unsaturated fused ring group containing one or two heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms" refers to a 6- to 9-membered fused heterocyclic group containing, in addition to carbon atoms as ring-constituting atoms, one or two heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms, and wherein the ring constituting the fused ring contains at least one saturated ring. Examples of the "6- to 9-membered saturated or partially unsaturated fused ring group containing one or two heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms" include the following groups: Includes:

[0058] "6- to 8-membered bridged heterocycloalkyl containing 1 or 2 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms" means a 6- to 8-membered bridged saturated heterocyclic group containing, in addition to carbon atoms as ring-constituting atoms, 1 or 2 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms. "6- to 8-membered bridged heterocycloalkyl containing 1 or 2 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms" includes, for example, the following groups: Preferably, the following groups are included: is.

[0059] 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.

[0060] Specific embodiments of each substituent of the compound of formula [I] are exemplified below, but the substituents of the compound of formula [I] are not limited to these 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.

[0061] Substructure: is preferably of the formula: (In the formula, R ４ is as defined above).

[0062] The ring group Cy is preferably represented by the formula (1): (wherein each symbol has the same meaning as defined above), (2) a group represented by the formula: (wherein each symbol has the same meaning as defined above), or (3) a group represented by the formula: (wherein each symbol has the same meaning as defined above)

[0063] R １ is preferably hydrogen.

[0064] R ２ and R ３ are preferably each independently: (1) hydrogen; (2) C １－６ alkyl {wherein the alkyl is: (a) C １－４ (b) alkoxy, ３－６ (c) phenyl, wherein the phenyl is C １－４ (3) C １－４ Alkoxy, (4) C １－４ Haloalkyl, (5)-CD ３ , (6)-CO-C １－４ alkyl, (7) C ３－６ (8) 4- to 6-membered heterocycloalkyl containing 1 or 2 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms, wherein the heterocycloalkyl is C １－４ (9) phenyl, or R ２ and R ３ together with the nitrogen atom to which they are attached, form -NR ２ R ３ (a) a 4- to 7-membered heterocycloalkyl containing from 1 to 3 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur atoms, wherein the heterocycloalkyl is selected from the group consisting of: (1) hydroxy, (2) cyano, (3) C １－６ alkyl {wherein the alkyl is: (a) hydroxy, (b) C １－４ (c) phenyl, or (4) C １－４ (5) halogen; (6) C １－４ haloalkyl, (7) —O—C １－４ Haloalkyl, (8) —CO—C １－４ Alkyl (wherein the alkyl is C １－４ (9) -CO-C １－６ Alkoxy, (10)-CO-C ３－６ cycloalkyl, (11)-CONH-C １－４alkyl, (12)-NHCO-C １－４ alkyl, (13)-NR １８ R １９ (where R １８ and R １９ are each independently C １－４ alkyl), (14) -SO ２ -C １－４ alkyl, (15)-SO ２ -C ３－６ cycloalkyl, (16) C ３－６ (17) phenyl, (18) a compound of the formula: and (19) oxo, (b) a 7- to 9-membered spiroheterocycloalkyl containing 1 to 3 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms, wherein the spiroheterocycloalkyl is optionally substituted with hydroxy; (c) a 6- to 9-membered saturated or partially unsaturated fused ring group containing 1 or 2 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms {wherein the fused ring group is selected from the group consisting of: (1) halogen, (2) —CO—C １－４ alkyl, and (3) —CO—C １－６ (d) a 6- to 8-membered bridged heterocycloalkyl containing 1 or 2 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms, wherein the bridged heterocycloalkyl is: (1) halogen, (2) —CO—C １－４ Alkyl (wherein the alkyl is C １－４ (3) -SO ２ -C １－４ alkyl, optionally substituted with 1 or 2 substituents independently selected from the group consisting of:

[0065] Specific embodiments of each substituent of the compound of formula [IA] are exemplified below, but the substituents of the compound of formula [IA] are not limited to these specific embodiments, and the compound of formula [IA] also includes embodiments in which any two or more of the specific embodiments of each substituent are combined.

[0066] Substructure: is preferably of the formula: (In the formula, R ４ is as defined above).

[0067] R ４ is preferably hydrogen.

[0068] cyclic group Cy Ａ is preferably of the formula: (wherein each symbol has the same meaning as defined above)

[0069] R ６ and R ７ Preferred embodiments of the formula (I) are each independently hydrogen, C １－６ Alkyl, C １－６ Alkoxy, halogen, C １－４ Haloalkyl, —O—C １－４ Haloalkyl or C ３－６ is cycloalkyl. ６ and R ７ A more preferred embodiment of the above is that each independently represents hydrogen, C １－６ R is alkyl or halogen. ６ and R ７ Preferred examples of each independently are methyl, fluorine, or chlorine.

[0070] R ８ and R ９ is preferably hydrogen.

[0071] R １０ A preferred embodiment of １－６ Alkyl, C １－４ Alkoxy, halogen, C １－６ Haloalkyl, —O—C １－４ Haloalkyl or C ３－６ is cycloalkyl. １０A more preferred embodiment of is a halogen or C ３－６ is cycloalkyl. １０ Preferred examples of are bromine or cyclopropyl.

[0072] cyclic group Cy Ａ is preferably of the formula: is a group represented by the formula: ６ and R ７ are each independently hydrogen, C １－６ Alkyl, C １－６ Alkoxy, halogen, C １－４ Haloalkyl, —O—C １－４ Haloalkyl or C ３－６ cycloalkyl; R ８ and R ９ is hydrogen; R １０ is C １－６ Alkyl, C １－４ Alkoxy, halogen, C １－６ Haloalkyl, —O—C １－４ Haloalkyl or C ３－６ It is cycloalkyl.

[0073] cyclic group Cy Ａ is more preferably of the formula: is a group represented by the formula: ６ and R ７ are each independently hydrogen, C １－６ alkyl or halogen; R ８ and R ９ is hydrogen; R １０ is a halogen or C ３－６ It is cycloalkyl.

[0074] R １ is preferably hydrogen.

[0075] R ２A and R ３A is preferably R ２A and R ３A together with the nitrogen atom to which they are attached, form -NR ２A R ３AThe groups form: (1) a 6-membered heterocycloalkyl containing two heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur atoms; or (2) a 7-membered bridged heterocycloalkyl containing two heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms.

[0076] One preferred embodiment of the compound of formula [I] is a compound having the partial structure: But the formula: (In the formula, R ４ has the same meaning as defined above); the ring group Cy is represented by the formula (1): (wherein each symbol has the same meaning as defined above), (2) a group represented by the formula: (wherein each symbol has the same meaning as defined above), or (3) a group represented by the formula: (wherein each symbol has the same meaning as defined above); R １ is hydrogen; R ２ and R ３ are each independently: (1) hydrogen; (2) C １－６ alkyl {wherein the alkyl is: (a) C １－４ (b) alkoxy, ３－６ (c) phenyl, wherein the phenyl is C １－４ (3) C １－４ Alkoxy, (4) C １－４ Haloalkyl, (5)-CD ３ , (6)-CO-C １－４ alkyl, (7) C ３－６ (8) 4- to 6-membered heterocycloalkyl containing 1 or 2 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms, wherein the heterocycloalkyl is C １－４ (9) phenyl, or R ２ and R ３ together with the nitrogen atom to which they are attached, form -NR ２ R ３(a) a 4- to 7-membered heterocycloalkyl containing from 1 to 3 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur atoms, wherein the heterocycloalkyl is selected from the group consisting of: (1) hydroxy, (2) cyano, (3) C １－６ alkyl {wherein the alkyl is: (a) hydroxy, (b) C １－４ (c) phenyl, or (4) C １－４ (5) halogen; (6) C １－４ haloalkyl, (7) —O—C １－４ Haloalkyl, (8) —CO—C １－４ Alkyl (wherein the alkyl is C １－４ (9) -CO-C １－６ Alkoxy, (10)-CO-C ３－６ cycloalkyl, (11)-CONH-C １－４ alkyl, (12)-NHCO-C １－４ alkyl, (13)-NR １８ R １９ (where R １８ and R １９ are each independently C １－４ alkyl), (14) -SO ２ -C １－４ alkyl, (15)-SO ２ -C ３－６ cycloalkyl, (16) C ３－６ (17) phenyl, (18) a compound of the formula: and (19) oxo, (b) a 7- to 9-membered spiroheterocycloalkyl containing 1 to 3 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms, wherein the spiroheterocycloalkyl is optionally substituted with hydroxy; (c) a 6- to 9-membered saturated or partially unsaturated fused ring group containing 1 or 2 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms {wherein the fused ring group is selected from the group consisting of: (1) halogen, (2) —CO—C １－４alkyl, and (3) —CO—C １－６ (d) a 6- to 8-membered bridged heterocycloalkyl containing 1 or 2 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms, wherein the bridged heterocycloalkyl is: (1) halogen, (2) —CO—C １－４ Alkyl (wherein the alkyl is C １－４ (3) -SO ２ -C １－４ alkyl, and optionally substituted with 1 or 2 substituents independently selected from the group consisting of

[0077] One preferred embodiment of the compound of formula [IA] is the compound represented by the partial structure: But the formula: R ４ is hydrogen; Ａ But the formula: is a group represented by the formula: ６ and R ７ are each independently hydrogen, C １－６ alkyl or halogen; R ８ and R ９ is hydrogen; R １０ is halogen or C ３－６ cycloalkyl; R １ is hydrogen; R ２A and R ３A together with the nitrogen atom to which they are attached, form -NR ２A R ３A The compounds of formula [IA] are those in which the groups form a 6-membered heterocycloalkyl containing two heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur atoms.

[0078] Another preferred embodiment of the compound of formula [IA] is a compound having the partial structure: But the formula: R ４ is hydrogen; ＡBut the formula: is a group represented by the formula: ６ and R ７ are each independently hydrogen, C １－６ alkyl or halogen; R ８ and R ９ is hydrogen; R １０ is halogen or C ３－６ cycloalkyl; R １ is hydrogen; R ２A and R ３A together with the nitrogen atom to which they are attached, form -NR ２A R ３A The groups form a 7-membered bridged heterocycloalkyl containing two heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms.

[0079] 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, organic acids, inorganic bases, and 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, pp. 6665-6672 (2007). A pharmaceutically acceptable salt thereof can be obtained by reacting a compound of formula [I] or formula [IA] with an inorganic acid, an organic acid, an inorganic base, or an organic base according to a method known per se.

[0080] 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. Examples of 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, hydroxynaphthoic 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.

[0081] Examples of salts with inorganic bases include salts with lithium, sodium, potassium, magnesium, calcium, barium, aluminum, zinc, bismuth, or ammonium. Preferably, salts with sodium, potassium, calcium, magnesium, or zinc are used. 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.

[0082] Compound [I] or compound [IA] may exist as a solvate. A solvate is, for example, a compound [I] or compound [IA] coordinated with solvent molecules. The solvate may be any pharmaceutically acceptable solvate, and examples thereof include a hydrate, acetate solvate, acetone solvate, ethanol solvate, and dimethyl sulfoxide solvate of compound [I] or compound [IA]. Specific examples include the hemihydrate, monohydrate, dihydrate, monoacetate solvate, monoacetone solvate, or monoethanol solvate of the compound of formula [I] or formula [IA], or the monohydrate, monoacetone solvate, or 2 / 3 ethanol solvate of the dihydrochloride salt of the compound of formula [I] or formula [IA]. These solvates can be obtained according to known methods.

[0083] Compound [I] or compound [IA] may exist as a tautomer. In that case, compound [I] or compound [IA] may exist as an individual tautomer or a mixture of tautomers. For example, the compound [I] or compound [IA] may exist as a tautomer of the following formula: Unless otherwise noted, the structure shown in (1) (2) (3) (4) (5) This means that the compound [I] or [IA] can exist as and / or be represented as a mixture thereof. Compound [I] or [IA] may have a carbon-carbon double bond. In such a case, compound [I] or [IA] may exist as an E-isomer, a Z-isomer, or a mixture of E- and Z-isomers. Compound [I] or [IA] may exist as stereoisomers known as cis / trans isomers. In such a case, compound [I] or [IA] may exist as a cis-isomer, a trans-isomer, or a mixture of cis- and trans-isomers. Compound [I] or [IA] may have one or more asymmetric carbon atoms. In such a case, compound [I] or [IA] may exist as a single enantiomer, a single diastereomer, a mixture of enantiomers, or a mixture of diastereomers. Compound [I] or [IA] may exist as an atropisomer. In this case, Compound [I] or Compound [IA] may exist as an individual atropisomer or a mixture of atropisomers. Compound [I] or Compound [IA] may simultaneously contain multiple structural features that give rise to the above isomers. Furthermore, Compound [I] or Compound [IA] may contain the above isomers in any ratio.

[0084] In this specification, formulae, chemical structures or compound names expressed without specifying stereochemistry include all of the above-mentioned possible isomers unless otherwise noted.

[0085] 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.

[0086] 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.

[0087] 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.

[0088] Compound [I] or compound [IA] may contain an isotope ( ２ H(D), ３ H. １４ C. ３５ For example, when the compound of formula [I] or formula [IA] has a methyl group, the methyl group may be labeled with -CD ３ The compounds thus obtained are also included in the present invention.

[0089] Compound [I] or compound [IA] is preferably a substantially purified compound [I] or compound [IA], more preferably a compound [I] or compound [IA] purified to a purity of 80% or more.

[0090] The pharmaceutical composition of the present invention may be prepared by appropriately mixing Compound [I] or Compound [IA] 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] or Compound [IA] 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.

[0091] The dosage form of compound [I] or compound [IA] includes 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.

[0092] 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, sweeteners, etc. may be used, if necessary.

[0093] Examples of "excipients" include lactose, sucrose, D-mannitol, D-sorbitol, corn starch, dextrin, microcrystalline cellulose, crystalline cellulose, carmellose, carmellose calcium, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, and gum arabic. Examples of "disintegrants" include carmellose, carmellose calcium, carmellose sodium, carboxymethyl starch sodium, croscarmellose sodium, crospovidone, low-substituted hydroxypropyl cellulose, hydroxypropyl methylcellulose, and crystalline cellulose. Examples of "binders" include hydroxypropyl cellulose, hydroxypropyl methylcellulose, povidone, crystalline cellulose, sucrose, dextrin, starch, gelatin, carmellose sodium, and gum arabic. Examples of "flow agents" include light anhydrous silicic acid and magnesium stearate. Examples of "lubricants" include magnesium stearate, calcium stearate, and talc. 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, etc. Examples of "suspending agents" include benzalkonium chloride, carmellose, hydroxypropyl cellulose, propylene glycol, povidone, methylcellulose, glycerin monostearate, etc. Examples of "isotonic agents" include glucose, D-sorbitol, sodium chloride, D-mannitol, etc. Examples of "buffering agents" include sodium hydrogen phosphate, sodium acetate, sodium carbonate, sodium citrate, etc. Examples of "soothing agents" include benzyl alcohol, etc.Examples of the "base" 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 esters thereof, 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 (methyl cellulose, carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, 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 "preservatives" include ethyl parahydroxybenzoate, chlorobutanol, benzyl alcohol, sodium dehydroacetate, sorbic acid, etc. Examples of "antioxidants" include sodium sulfite, ascorbic acid, etc. Examples of "coloring agents" include food dyes (Food Red No. 2 or No. 3, Food Yellow No. 4 or No. 5, etc.), β-carotene, etc. Examples of "sweeteners" include saccharin sodium, dipotassium glycyrrhizinate, aspartame, etc.

[0094] The pharmaceutical compositions of the present invention can be administered orally or parenterally (topically, rectally, intravenously, intramuscularly, subcutaneously, etc.) to mammals other than humans (e.g., 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 for oral administration to an adult patient is typically in the range of about 0.01 mg to 1 g per day of the active ingredient, the compound of formula [I] or a pharmaceutically acceptable salt thereof, or the compound of formula [IA] or a pharmaceutically acceptable salt thereof. These amounts can be administered in one or several divided doses.

[0095] Compound [I] or compound [IA] has an NLRP3 inflammasome inhibitory effect and is therefore useful for the treatment and / or prevention of various diseases or conditions that can be expected to be improved by regulating NLRP3 inflammasome activity. Examples of various diseases or conditions that can be expected to be improved by regulating 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 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 and diseases selected from the group consisting of Still's disease (e.g., hemophagocytic lymphohistiocytosis 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, and TNF receptor-associated periodic syndrome.

[0096] "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."

[0097] As used herein, "treatment" includes alleviating symptoms, preventing aggravation, maintaining remission, preventing relapse, and even preventing recurrence. As used herein, "prevention" includes suppressing and delaying the onset of symptoms.

[0098] 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.

[0099] [General Production Method] General production methods for the compound of formula [I] or a pharmaceutically acceptable salt thereof, or the compound of formula [IA] or a pharmaceutically acceptable salt thereof are exemplified below. However, the production method for the compound of formula [I] or a pharmaceutically acceptable salt thereof, or the compound of formula [IA] or a pharmaceutically acceptable salt thereof is not limited to these production methods. The compound 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, it can proceed to the next step without isolation and / or purification. In this specification, room temperature refers to a temperature in an uncontrolled state, and one embodiment is 1°C to 40°C.

[0100] Production Method A1: Production method for compound [IA] or a salt thereof, or compound [IB] or a salt thereof The compound [IA] or a salt thereof, or compound [IB] or a salt thereof can be produced, for example, by the following Production Method A1. {In the formula, Cy, R ２ , R ３ , and R ５ is as defined above, R ５Ａ is C １－４ alkyl, wherein the alkyl is optionally substituted with hydroxy or cyano; L Ａ１１is a leaving group (e.g., halogen, methanesulfonyloxy, and p-toluenesulfonyloxy)} (Step A1-1) Compound [IA] or a salt thereof, or compound [IB] or a salt thereof, can be produced by reacting compound [IC] or a salt thereof with compound [A1-1] or a salt thereof in a solvent in the presence of a base. Examples of the base include sodium hydride and potassium carbonate. A preferred base is sodium hydride. Examples of the solvent include 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. Compound [A1-1] or a salt thereof is commercially available, or may be produced from a commercially available product by a known method.

[0101] Production method A1A: Method for producing compound [IA-A] or a salt thereof, or compound [IA-B] or a salt thereof Compound [IA-A] or a salt thereof, or compound [IA-B] or a salt thereof can be produced in the same manner as in Production method A1, except for using compound [IA-C] or a salt thereof instead of compound [IC] or a salt thereof. (wherein each symbol has the same meaning as defined above)

[0102] Production Method A2: Production Method for Compound [IC] or a Salt Thereof The compound [IC] or a salt thereof can be produced, for example, by the following Production Method A2. {In the formula, Cy, R ２ , and R ３ is as defined above, R Ａ２１ are each independently C １－４ is alkyl, and L Ａ２１ , L Ａ２２ , and L Ａ２３are each independently a leaving group (e.g., halogen, methanesulfonyloxy, and p-toluenesulfonyloxy)} (Step A2-1) Compound [A2-3] or a salt thereof can be produced by reacting compound [A2-1] or a salt thereof with compound [A2-2] in a solvent in the presence of an acid catalyst. Examples of the acid catalyst include sulfuric acid, hydrochloric acid, formic acid, perchloric acid, methanesulfonic acid, and p-toluenesulfonic acid. A preferred acid catalyst is sulfuric acid or p-toluenesulfonic acid. Examples of the solvent include toluene, methanol, ethanol, isopropanol, tetrahydrofuran, 1,4-dioxane, and mixed solvents thereof. A preferred solvent is toluene. The reaction temperature is, for example, 0°C to 150°C, preferably 5°C to 40°C. Compound [A2-1] or a salt thereof is commercially available, or may be produced from a commercially available product by a known method. Compound [A2-2] is commercially available, or may be prepared from a commercially available product by a known method. (Step A2-2) Compound [A2-5] or a salt thereof can be prepared by reacting compound [A2-3] or a salt thereof with compound [A2-4] or a salt thereof in a solvent in the presence of a base. Examples of the base include triethylamine, diazabicycloundecene, and diisopropylethylamine. A preferred base is triethylamine or diisopropylethylamine. Examples of the solvent include methanol, ethanol, tetrahydrofuran, and a mixed solvent thereof. A preferred solvent is methanol. The reaction temperature is, for example, −78° C. to 100° C., preferably 0° C. to 20° C. Compound [A2-4] or a salt thereof is commercially available, or may be prepared from a commercially available product by a known method. (Step A2-3) Compound [A2-6] or a salt thereof can be produced by reacting compound [A2-5] or a salt thereof in a solvent in the presence of an acid catalyst. Examples of the acid catalyst include trifluoroacetic acid, sulfuric acid, and triethylsilyl trifluoromethanesulfonate. A preferred acid catalyst is trifluoroacetic acid. Examples of the solvent include toluene, tetrahydrofuran, dichloromethane, and mixed solvents thereof. A preferred solvent is toluene.The reaction temperature is, for example, −78° C. to 50° C., preferably 0° C. to 20° C. (Step A2-4) Compound [A2-7] or a salt thereof can be produced by reacting compound [A2-6] or a salt thereof in a solvent in the presence of a base. Examples of the base include sodium hydroxide and potassium hydroxide. A preferred base is sodium hydroxide. Examples of the solvent include tetrahydrofuran, 1,4-dioxane, chloroform, and mixed solvents thereof. A preferred solvent is tetrahydrofuran. The reaction temperature is, for example, 0° C. to 150° C., preferably 50° C. to 100° C. (Step A2-5) Compound [IC] or a salt thereof can be produced by reacting compound [A2-7] or a salt thereof with compound [A2-8] or a salt thereof in a solvent. A base may be added as necessary. Examples of the solvent include N-methylpyrrolidinone, N,N-dimethylformamide, 1,4-dioxane, tetrahydrofuran, and a mixture thereof. A preferred solvent is N-methylpyrrolidone. Examples of the base include triethylamine, diisopropylethylamine, and diazabicycloundecene. A preferred base is diisopropylethylamine. The reaction temperature is, for example, 0°C to 200°C, preferably 80°C to 180°C. Compound [A2-8] or a salt thereof is commercially available, or may be produced from a commercially available product by a known method. In this production method, instead of compound [A2-4] or a salt thereof, a compound having a functional group or a protected substituent that can be converted into various substituents on ring Cy by known reactions, or a salt thereof, may be used to perform this production method, thereby obtaining a compound corresponding to compound [IC] or a salt thereof, and then converting the functional group or protected substituent into the various substituents to produce compound [IC] or a salt thereof. For example, the compound [A2-4] or a salt thereof may be replaced with L described below. Ａ５１ or a salt thereof, to obtain a compound corresponding to compound [IC], i.e., compound [IE] or a salt thereof, and then, by Production Method A5, Ａ５１ to the ring Cy Ａ５１The compound [IF] or a salt thereof may be prepared by converting the compound [IF] into the following compound.

[0103] Production method A2A: Method for producing compound [IA-C] or a salt thereof Compound [IA-C] or a salt thereof can be produced in the same manner as in Production method A2, except for using compound [A2A-4] or a salt thereof instead of compound [A2-4] or a salt thereof, and compound [A2A-8] or a salt thereof instead of compound [A2-8] or a salt thereof. (wherein each symbol has the same meaning as defined above) Compound [A2A-4] or a salt thereof is commercially available, or may be prepared from a commercially available product by a known method. Compound [A2A-8] or a salt thereof is commercially available, or may be prepared from a commercially available product by a known method. In this preparation method, instead of compound [A2A-4] or a salt thereof, ring Cy is prepared by a known reaction. Ａ This production method may be carried out using a compound or a salt thereof having a functional group or a protected substituent that can be converted into the above-mentioned various substituents to obtain a compound or a salt thereof corresponding to compound [IA-C], and then the functional group or protected substituent may be converted into the various substituents to produce compound [IA-C] or a salt thereof. For example, compound [IA-C] or a salt thereof may be produced by using a compound having a functional group or a protected substituent that can be converted into the above-mentioned various substituents instead of compound [A2A-4] or a salt thereof, Ａ５１ or a salt thereof, to obtain a compound corresponding to compound [IA-C], i.e., compound [IA-E] or a salt thereof, and then, using Production Method A5A, Ａ５１ to the ring Cy Ａ５１ The compound [IA-F] or a salt thereof may be prepared by converting the compound [IA-F] into the following compound.

[0104] Production Method A3: Production Method for Compound [IC] or a Salt Thereof The compound [IC] or a salt thereof can be produced, for example, by the following Production Method A3. {In the formula, Cy, R ２ , and R ３ is as defined above, R Ａ３１ and R Ａ３２ are each independently C １－４ is alkyl, and L Ａ３１is a leaving group (e.g., halogen and trifluoromethanesulfonyloxy)} (Step A3-1) Compound [A3-3] or a salt thereof can be produced by reacting compound [A3-1] or a salt thereof with compound [A3-2] or a salt thereof in a solvent in the presence of a catalyst and a base. Examples of the catalyst include copper(I) iodide and copper(I) bromide. A preferred catalyst is copper(I) iodide. Examples of the base include cesium carbonate and potassium carbonate. A preferred base is cesium carbonate. Examples of the solvent include dimethyl sulfoxide, 1,4-dioxane, and mixed solvents thereof. A preferred solvent is dimethyl sulfoxide. The reaction temperature is, for example, 10°C to 200°C, preferably 120°C to 180°C. Compound [A3-1] or a salt thereof is commercially available, or may be produced from a commercially available product by a known method. Compound [A3-2] or a salt thereof is commercially available, or may be prepared from a commercially available product by a known method. (Step A3-2) Compound [A3-5] or a salt thereof can be prepared by reacting compound [A3-3] or a salt thereof with compound [A3-4] or a salt thereof in a solvent. Examples of the solvent include acetonitrile, dichloromethane, chloroform, and a mixture thereof. A preferred solvent is acetonitrile. The reaction temperature is, for example, 0°C to 80°C, preferably 0°C to 40°C. Compound [A3-4] or a salt thereof is commercially available, or may be prepared from a commercially available product by a known method. (Step A3-3) Compound [A3-7] or a salt thereof can be prepared by reacting compound [A3-5] or a salt thereof with compound [A3-6] or a salt thereof in a solvent in the presence of a condensing agent and a base. Examples of the base include triethylamine, diazabicycloundecene, and diisopropylethylamine. A preferred base is triethylamine. Condensing agents include, for example, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and N,N'-dicyclohexylcarbodiimide. A preferred condensing agent is 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride.Examples of the solvent include chloroform, dichloromethane, tetrahydrofuran, and mixed solvents thereof. A preferred solvent is chloroform. The reaction temperature is, for example, 0°C to 100°C, preferably 10°C to 50°C. Compound [A3-6] or a salt thereof is commercially available, or may be prepared from a commercially available product by a known method. (Step A3-4) Compound [IC] or a salt thereof can be prepared by reacting compound [A3-7] or a salt thereof in a solvent in the presence of an acid catalyst. Examples of the acid catalyst include trifluoroacetic acid, hydrochloric acid, and sulfuric acid. A preferred acid catalyst is trifluoroacetic acid. Examples of the solvent include water, tetrahydrofuran, and mixed solvents thereof. A preferred solvent is water. The reaction temperature is, for example, 0°C to 150°C, preferably 80°C to 120°C. In this production method, instead of compound [A3-2] or a salt thereof, a compound having a functional group or a protected substituent that can be converted to various substituents on ring Cy by known reactions, or a salt thereof, may be used to carry out this production method to obtain a compound corresponding to compound [IC] or a salt thereof, and then the functional group or protected substituent may be converted to various substituents to produce compound [IC] or a salt thereof. For example, instead of compound [A3-2] or a salt thereof, Ａ３１ and L, which will be described later. Ａ５１ or a salt thereof, to obtain a compound corresponding to compound [IC], i.e., compound [IE] or a salt thereof, and then, by Production Method A5, Ａ５１ to the ring Cy Ａ５１ The compound [IF] or a salt thereof may be prepared by converting the compound [IF] into the following compound.

[0105] Production method A3A: Method for producing compound [IA-C] or a salt thereof Compound [IA-C] or a salt thereof can be produced in the same manner as in Production method A3, except for using compound [A3A-2] or a salt thereof instead of compound [A3-2] or a salt thereof, and compound [A3A-6] or a salt thereof instead of compound [A3-6] or a salt thereof. (wherein each symbol has the same meaning as defined above) Compound [A3A-2] or a salt thereof is commercially available, or may be prepared from a commercially available product by a known method. Compound [A3A-6] or a salt thereof is commercially available, or may be prepared from a commercially available product by a known method. In this preparation method, instead of compound [A3A-2] or a salt thereof, ring Cy is prepared by a known reaction. Ａ This production method may be carried out using a compound or a salt thereof having a functional group or a protected substituent that can be converted into the above-mentioned various substituents to obtain a compound or a salt thereof corresponding to compound [IA-C], and then the functional group or protected substituent may be converted into the various substituents to produce compound [IA-C] or a salt thereof. For example, instead of compound [A3A-2] or a salt thereof, Ａ３１ and L, which will be described later. Ａ５１ or a salt thereof, to obtain a compound corresponding to compound [IA-C], i.e., compound [IA-E] or a salt thereof, and then, by Production Method A5A, Ａ５１ to the ring Cy Ａ５１ The compound [IA-F] or a salt thereof may be prepared by converting the compound [IA-F] into the following compound.

[0106] Production Method A4: Production Method for Compound [ID] or a Salt Thereof Compound [ID] or a salt thereof can be produced, for example, by the following Production Method A4. {In the formula, Cy, R １ , R ２ , and R ３ is as defined above, and L Ａ４１ and L Ａ４２are each independently a leaving group (e.g., halogen, methanesulfonyloxy, and p-toluenesulfonyloxy).} (Step A4-1) Compound [A4-3] or a salt thereof can be produced by reacting compound [A4-1] or a salt thereof with compound [A4-2] or a salt thereof in a solvent in the presence of a base. Examples of the base include triethylamine, diisopropylethylamine, and diazabicycloundecene. A preferred base is triethylamine. Examples of the solvent include methanol, ethanol, tetrahydrofuran, toluene, and mixed solvents thereof. A preferred solvent is ethanol. The reaction temperature is, for example, −78° C. to 150° C., preferably 0° C. to 120° C. Compound [A4-1] or a salt thereof is commercially available, or may be produced from a commercially available product by a known method. Compound [A4-2] or a salt thereof is commercially available, or may be produced from a commercially available product by a known method. (Step A4-2) Compound [I-D] or a salt thereof can be produced by reacting compound [A4-3] or a salt thereof in a solvent in the presence of a base. Examples of the base include sodium hydroxide and potassium hydroxide. A preferred base is sodium hydroxide. Examples of the solvent include water, dioxane, 1,2-dimethoxyethane, and a mixed solvent thereof. A preferred solvent is a mixed solvent of dioxane and water. The reaction temperature is, for example, 0°C to 150°C, preferably 80°C to 120°C. 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 into various substituents on ring Cy by known reactions, or a salt thereof, may be used to carry out this production method, thereby obtaining a compound corresponding to compound [I-D] or a salt thereof, and then converting the functional group or protected substituent into the various substituents to produce compound [I-D] or a salt thereof. For example, instead of the compound [A4-2] or a salt thereof, Ａ５１ or a salt thereof, to obtain a compound corresponding to compound [ID], i.e., compound [IE] or a salt thereof, and then, by Production Method A5, Ａ５１to the ring Cy Ａ５１ The compound [IF] or a salt thereof may be prepared by converting the compound [IF] into the following compound.

[0107] Production method A4A: Production method for compound [IA-D] or a salt thereof Compound [IA-D] or a salt thereof can be produced in the same manner as in Production method A4, except that compound [A4A-1] or a salt thereof is used instead of compound [A4-1] or a salt thereof, and compound [A4A-2] or a salt thereof is used instead of compound [A4-2] or a salt thereof. (wherein each symbol has the same meaning as defined above) Compound [A4A-1] or a salt thereof is commercially available, or may be prepared from a commercially available product by a known method. Compound [A4A-2] or a salt thereof is commercially available, or may be prepared from a commercially available product by a known method. In this preparation method, instead of compound [A4A-2] or a salt thereof, ring Cy is prepared by a known reaction. Ａ The present production method may be carried out using a compound or a salt thereof having a functional group or a protected substituent that can be converted into the above-mentioned various substituents to obtain a compound or a salt thereof corresponding to compound [IA-D], and then the functional group or the protected substituent may be converted into the various substituents to produce compound [IA-D] or a salt thereof. For example, compound [IA-D] or a salt thereof may be prepared by using a compound having a functional group or a protected substituent that can be converted into the above-mentioned various substituents instead of compound [A4A-2] or a salt thereof, as described below. Ａ５１ or a salt thereof, to obtain a compound corresponding to compound [IA-D], i.e., compound [IA-E] or a salt thereof, and then, by Production Method A5A, Ａ５１ to the ring Cy Ａ５１ The compound [IA-F] or a salt thereof may be prepared by converting the compound [IA-F] into the following compound.

[0108] Production Method A5: Production Method for Compound [IF] or a Salt Thereof Compound [IF] or a salt thereof can be produced, for example, by the following Production Method A5. {In the formula, R ２ and R ３ is as defined above, and Cy Ａ５１ is C ３－６ Cycloalkyl (wherein the cycloalkyl is C １－４ and L is optionally substituted with haloalkyl;Ａ５１ is a leaving group (e.g., halogen, methanesulfonyloxy, and trifluoromethanesulfonyloxy). The leaving group is bonded to the ortho- or para-position of the benzene ring. (Step A5-1) Compound [I-F] or a salt thereof can be produced by reacting compound [I-E] or a salt thereof with compound [A5-1] 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(diphenylphosphine)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 solvents 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 [I-E] or a salt thereof may be produced from a commercially available product by a known method. Compound [I-E] or a salt thereof may be produced, for example, by the aforementioned production method. Compound [A5-1] or a derivative thereof is commercially available, or may be produced from a commercially available product by a known method.

[0109] Production Method A5A: Method for producing compound [IA-F] or a salt thereof Compound [IA-F] or a salt thereof can be produced in the same manner as in Production Method A5, except for using compound [IA-E] or a salt thereof instead of compound [IE] or a salt thereof. (wherein each symbol is as defined above.) Compound [IA-E] or a salt thereof may be produced from commercially available products by known methods. Compound [IA-E] or a salt thereof may be produced, for example, by the production method described above.

[0110] Next, the method for producing the compound of formula [I] or a pharmaceutically acceptable salt thereof, or the compound of formula [IA] or a pharmaceutically acceptable salt thereof will be specifically explained using Preparation Examples. However, the method for producing the compound of formula [I] or a pharmaceutically acceptable salt thereof, or the compound of formula [IA] or a pharmaceutically acceptable salt thereof is not limited to these Preparation Examples. NMR was measured at 400 MHz.

[0111] [Production Example 1]: Synthesis of 6-(pyrrolidin-1-yl)-2-(o-tolyl)-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (Example 3) Step 1-1: 4-chloro-6-(pyrrolidin-1-yl)-2-(o-tolyl)-2H-pyrazolo[3,4-d]pyrimidine Under an argon atmosphere, 4,6-dichloro-2-(pyrrolidin-1-yl)pyrimidine-5-carbaldehyde (200 mg) was added to a mixture of o-tolylhydrazine (120 mg), triethylamine (0.23 mL), and ethanol (4.0 mL) at -78°C, and the mixture was stirred overnight while naturally warming to room temperature. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The resulting organic layer was washed with saturated aqueous sodium bicarbonate and saturated brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (eluent: hexane / ethyl acetate) to give the title compound (97 mg). 1 H-NMR (CDCl) δ: 7.96 (1H, s), 7.41-7.28 (4H, m), 3.70-3.69 (4H, m), 2.32 (3H, s), 2.01-1.97 (4H, m). Step 1-2: 6-(pyrrolidin-1-yl)-2-(o-tolyl)-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one To a mixture of 4-chloro-6-(pyrrolidin-1-yl)-2-(o-tolyl)-2H-pyrazolo[3,4-d]pyrimidine (97 mg) and 1,2-dimethoxyethane (1.5 mL), 2 M aqueous sodium hydroxide (1.5 mL) was added and stirred at 110°C for 6 hours. The reaction mixture was allowed to cool to room temperature and neutralized with 2 M hydrochloric acid. The resulting mixture was extracted with an ethyl acetate / tetrahydrofuran mixture, washed with saturated brine, and the solvent was evaporated under reduced pressure. The residue was stirred with an ethyl acetate / hexane mixture at room temperature for 10 minutes, and the resulting solid was collected by filtration to give the title compound (55 mg). 1 LC-MS (MH+): 296.

[0112] [Production Example 2]: Synthesis of 2-(2,6-dichlorophenyl)-6-(pyrrolidin-1-yl)-2,5-dihydro-4H-pyrazole[3,4-d]pyrimidin-4-one (Example 30) Step 2-1: 2-(2,6-dichlorophenyl)-6-(pyrrolidin-1-yl)-2,5-dihydro-4H-pyrazole[3,4-d]pyrimidin-4-one Under an argon atmosphere, 4,6-dichloro-2-(pyrrolidin-1-yl)pyrimidine-5-carbaldehyde (80 mg) was added to a mixture of (2,6-dichlorophenyl)hydrazine hydrochloride (76 mg), triethylamine (0.14 mL), and ethanol (1.6 mL) at 0°C. The mixture was heated under reflux and stirred for 3 hours, after which the solvent was evaporated under reduced pressure. The residue was mixed with acetic acid (2.0 mL) and stirred under reflux for 3 hours, after which the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (eluent: hexane / ethyl acetate) and solidified with an ethyl acetate / hexane mixture to give the title compound (26 mg). 1H-NMR (DMSO-D6) δ: 10.60 (1H, br s), 8.57 (1H, s), 7.71 (2H, dd, J = 8.2, 0.8 Hz), 7.60 (1H, dd, J = 8.9, 7.3 Hz), 3.48-3.46 (4H, m), 1.90-1.87 (4H, m). LC-MS (MH+): 350.

[0113] [Production Example 3]: Synthesis of 2-(4-bromo-2-methylphenyl)-5-methyl-6-morpholino-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (Example 88) Step 3-1: 4-(2-(4-bromo-2-methylphenyl)hydrazinyl)-2,6-dichloro-5-(dimethoxymethyl)pyrimidine 2,4,6-Trichloro-5-(dimethoxymethyl)pyrimidine (1.5 g), synthesized in the same manner as in Step 5-1 of Preparation Example 5, was added to a mixture of (4-bromo-2-methylphenyl)hydrazine hydrochloride (1.4 g), triethylamine (2.4 mL), and methanol (30 mL) under an argon atmosphere at 0°C, and the mixture was stirred at room temperature for 1 hour. The solvent was evaporated under reduced pressure, and the residue was purified by column chromatography (developing solvent: hexane / ethyl acetate) to obtain the title compound (2.4 g). 1 H-NMR (CDCl3) δ: 8.31 (1H, d, J = 4.6 Hz), 7.24-7.23 (1H, m), 7.19 (1H, d, J = 8.6 Hz), 6.70 (1H, d, J = 8.6 Hz), 6.15 (1H, d, J = 4.6 Hz), 5.64 (1H, d, J = 0.7 Hz), 3.52 (6H, s), 2.29 (3H, s). Step 3-2: 2-(4-Bromo-2-methylphenyl)-4,6-dichloro-2H-pyrazolo[3,4-d]pyrimidine To a mixture of 4-(2-(4-bromo-2-methylphenyl)hydrazinyl)-2,6-dichloro-5-(dimethoxymethyl)pyrimidine (2.4 g) and tetrahydrofuran (50 mL), trifluoroacetic acid (10 mL) was added and the mixture was stirred at room temperature for 10 minutes. After removing the solvent under reduced pressure, the resulting solid was washed with a mixture of hexane / ethyl acetate (v / v = 1 / 1) to give the title compound (1.4 g). 1 H-NMR (DMSO-D6) δ: 9.39 (1H, s), 7.78 (1H, d, J = 2.1 Hz), 7.66 (1H, dd, J = 8.6, 2.3 Hz), 7.54 (1H, d, J = 8.6 Hz), 2.22 (3H, s). Step 3-3: 2-(4-Bromo-2-methylphenyl)-6-chloro-2,5-dihydro-4H-pyrazolo[3,4-d]pyridin-4-one To a mixture of 2-(4-bromo-2-methylphenyl)-4,6-dichloro-2H-pyrazolo[3,4-d]pyrimidine (1.0 g) and tetrahydrofuran (20 mL), 2M aqueous sodium hydroxide (5.6 mL) was added and stirred at 80°C for 2 hours. The reaction mixture was neutralized with 2M hydrochloric acid, and water was added. The resulting solid was filtered. The resulting solid was purified by slurrying with ethanol to give the title compound (920 mg). 1 H-NMR (DMSO-D6) δ: 12.86 (1H, br s), 8.91 (1H, s), 7.71 (1H, d, J = 2.1 Hz), 7.59 (1H, dd, J = 8.4, 2.2 Hz), 7.43 (1H, d, J = 8.3 Hz), 2.20 (3H, s). LC-MS (MH+): 341. Step 3-4: 2-(4-Bromo-2-methylphenyl)-6-morpholino-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one To a mixture of 2-(4-bromo-2-methylphenyl)-6-chloro-2,5-dihydro-4H-pyrazolo[3,4-d]pyridin-4-one (50 mg) and tetrahydrofuran (1.0 mL), morpholine (64 mg) was added and stirred at 80°C for 2 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The resulting organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The resulting solid was washed with hexane / ethyl acetate (v / v = 1 / 1) to give the title compound (56 mg). 1 H-NMR (CDCl3) δ: 10.17 (1H, br s), 8.07 (1H, s), 7.49 (1H, d, J = 1.8 Hz), 7.44-7.42 (1H, m), 7.27 (1H, s), 3.81-3.80 (4H, m), 3.69-3.68 (4H, m), 2.29 (3H, s). LC-MS (MH+): 390. Step 3-5: 2-(4-Bromo-2-methylphenyl)-5-methyl-6-morpholino-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one Under an argon atmosphere, sodium hydride (60% in oil, 4.3 mg) was added to a mixture of 2-(4-bromo-2-methylphenyl)-6-morpholino-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (28 mg) and N,N-dimethylformamide (0.56 mL). The mixture was stirred at room temperature for 2 hours, followed by methyl iodide (0.013 mL) and stirring for 2 hours. Acetic acid and water were added to the reaction mixture, which was then extracted with ethyl acetate. The resulting organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by preparative TLC (hexane / ethyl acetate) to give the title compound (6 mg). 1H-NMR (CDCl3) δ: 8.15 (1H, s), 7.51 (1H, d, J = 2.1 Hz), 7.45 (1H, dd, J = 8.8, 2.1 Hz), 7.27 (1H, d, J = 8.8 Hz), 3.90-3.85 (4H, m), 3.57 (3H, s), 3.32-3.26 (4H, m), 2.30 (3H, s). LC-MS (MH+): 404.

[0114] [Production Example 4]: Synthesis of 4-(2-(4-bromo-2-methylphenyl)-4-methoxy-2H-pyrazolo[3,4-d]pyrimidin-6-yl)morpholine (Example 89) Step 4-1: 4-(2-(4-bromo-2-methylphenyl)hydrazinyl)-2,6-dichloro-5-(dimethoxymethyl)pyrimidine 2,4,6-Trichloro-5-(dimethoxymethyl)pyrimidine (1.5 g), synthesized in the same manner as in Step 5-1 of Preparation 5, was added to a mixture of (4-bromo-2-methylphenyl)hydrazine hydrochloride (1.4 g), triethylamine (2.4 mL) and methanol (30 mL) at 0°C under an argon atmosphere, and the mixture was stirred at room temperature for 1 hour. The solvent was evaporated under reduced pressure, and the residue was purified by column chromatography (developing solvent: hexane / ethyl acetate) to obtain the title compound (2.4 g). 1 H-NMR (CDCl3) δ: 8.31 (1H, d, J = 4.6 Hz), 7.24-7.23 (1H, m), 7.19 (1H, d, J = 8.6 Hz), 6.70 (1H, d, J = 8.6 Hz), 6.15 (1H, d, J = 4.6 Hz), 5.64 (1H, d, J = 0.7 Hz), 3.52 (6H, s), 2.29 (3H, s). Step 4-2: 2-(4-Bromo-2-methylphenyl)-4,6-dichloro-2H-pyrazolo[3,4-d]pyrimidine To a mixture of 4-(2-(4-bromo-2-methylphenyl)hydrazinyl)-2,6-dichloro-5-(dimethoxymethyl)pyrimidine (2.4 g) and tetrahydrofuran (50 mL), trifluoroacetic acid (10 mL) was added and the mixture was stirred at room temperature for 10 minutes. After removing the solvent under reduced pressure, the resulting solid was washed with a mixture of hexane / ethyl acetate (v / v = 1 / 1) to give the title compound (1.4 g). 1 H-NMR (DMSO-D6) δ: 9.39 (1H, s), 7.78 (1H, d, J = 2.1 Hz), 7.66 (1H, dd, J = 8.6, 2.3 Hz), 7.54 (1H, d, J = 8.6 Hz), 2.22 (3H, s). Step 4-3: 2-(4-Bromo-2-methylphenyl)-6-chloro-2,5-dihydro-4H-pyrazolo[3,4-d]pyridin-4-one To a mixture of 2-(4-bromo-2-methylphenyl)-4,6-dichloro-2H-pyrazolo[3,4-d]pyrimidine (1.0 g) and tetrahydrofuran (20 mL), 2M aqueous sodium hydroxide (5.6 mL) was added and stirred at 80°C for 2 hours. The reaction mixture was neutralized with 2M hydrochloric acid, and water was added. The resulting solid was filtered. The resulting solid was purified by slurrying with ethanol to give the title compound (920 mg). 1 H-NMR (DMSO-D6) δ: 12.86 (1H, br s), 8.91 (1H, s), 7.71 (1H, d, J = 2.1 Hz), 7.59 (1H, dd, J = 8.4, 2.2 Hz), 7.43 (1H, d, J = 8.3 Hz), 2.20 (3H, s). LC-MS (MH+): 341. Step 4-4: 2-(4-Bromo-2-methylphenyl)-6-morpholino-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one To a mixture of 2-(4-bromo-2-methylphenyl)-6-chloro-2,5-dihydro-4H-pyrazolo[3,4-d]pyridin-4-one (50 mg) and tetrahydrofuran (1.0 mL), morpholine (64 mg) was added and stirred at 80°C for 2 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The resulting organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The resulting solid was washed with hexane / ethyl acetate (v / v = 1 / 1) to give the title compound (56 mg). 1 H-NMR (CDCl3) δ: 10.17 (1H, br s), 8.07 (1H, s), 7.49 (1H, d, J = 1.8 Hz), 7.44-7.42 (1H, m), 7.27 (1H, s), 3.81-3.80 (4H, m), 3.69-3.68 (4H, m), 2.29 (3H, s). LC-MS (MH+): 390. Step 4-5: 4-(2-(4-Bromo-2-methylphenyl)-4-methoxy-2H-pyrazolo[3,4-d]pyrimidin-6-yl)morpholine Under an argon atmosphere, sodium hydride (60% in oil, 4.3 mg) was added to a mixture of 2-(4-bromo-2-methylphenyl)-6-morpholino-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (28 mg) and N,N-dimethylformamide (0.56 mL). The mixture was stirred at room temperature for 2 hours, followed by methyl iodide (0.013 mL) and stirring for 2 hours. Acetic acid and water were added to the reaction mixture, which was then extracted with ethyl acetate. The resulting organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by preparative TLC (hexane / ethyl acetate) to give the title compound (13 mg). 1H-NMR (CDCl3) δ: 7.89 (1H, s), 7.50 (1H, d, J = 2.0 Hz), 7.43 (1H, dd, J = 8.3, 2.0 Hz), 7.28 (1H, d, J = 8.3 Hz), 4.08 (3H, s), 3.96-3.91 (4H, m), 3.81-3.76 (4H, m), 2.30 (3H, s). LC-MS (MH+): 404.

[0115] [Production Example 5]: Synthesis of 2-(4-bromo-2,6-dimethylphenyl)-6-morpholino-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (Example 94) Step 5-1: 2,4,6-trichloro-5-(dimethoxymethyl)pyrimidine Under a nitrogen atmosphere, trimethyl orthoformate (300 mL) and sulfuric acid (0.63 mL) were added to a mixture of 2,4,6-trichloropyrimidine-5-carbaldehyde (100 g) and toluene (600 mL), and the mixture was stirred at room temperature for 1.5 hours. Basic silica gel (Fuji Silicia, 200 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 (1.5 L), and the solvent was evaporated under reduced pressure to give the title compound (108 g). 1 H-NMR (CDCl3) δ: 5.68 (1H, s), 3.49 (6H, s). Step 5-2: 4-(2-(4-bromo-2,6-dimethylphenyl)hydrazinyl)-2,6-dichloro-5-(dimethoxymethyl)pyrimidine Under a nitrogen atmosphere, 2,4,6-trichloro-5-(dimethoxymethyl)pyrimidine (61 g) was added to a mixture of (4-bromo-2,6-dimethylphenyl)hydrazine hydrochloride (60 g) and methanol (420 mL), and the reaction mixture was cooled to below 2°C in an ice bath. Triethylamine (100 mL) was added to the reaction mixture over 25 minutes while maintaining the temperature below 9°C, and the mixture was stirred at the same temperature for 3 hours. The resulting solid was collected by filtration and washed successively with methanol (150 mL) and hexane (100 mL) to obtain the title compound (93.3 g). 1H-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. Step 5-3: 2-(4-Bromo-2,6-dimethylphenyl)-4,6-dichloro-2H-pyrazolo[3,4-d]pyrimidine Under a nitrogen atmosphere, trifluoroacetic acid (33 mL) was slowly added dropwise to a mixture of 4-(2-(4-bromo-2,6-dimethylphenyl)hydrazinyl)-2,6-dichloro-5-(dimethoxymethyl)pyrimidine (93.3 g) and toluene (750 mL) over 40 minutes while maintaining the temperature below 24°C. The reaction mixture was stirred for another 1 hour, and then added dropwise to an ice-cooled mixture of tripotassium phosphate (91 g) in water / tetrahydrofuran (300 mL / 500 mL) over 20 minutes while maintaining the temperature below 10°C. After separating the organic layers, saturated brine was added to the aqueous layer, and the mixture was extracted 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 (80.9 g). LC-MS (MH+): 372. Step 5-4: 2-(4-bromo-2,6-dimethylphenyl)-6-chloro-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one To a mixture of crude 2-(4-bromo-2,6-dimethylphenyl)-4,6-dichloro-2H-pyrazolo[3,4-d]pyrimidine (80.9 g) and tetrahydrofuran (640 mL) was added 4 M aqueous sodium hydroxide (160 mL) at room temperature and stirred at 66°C for 5 hours. The reaction mixture was cooled to below 2°C in an ice bath, and 2 M hydrochloric acid (220 mL) was slowly added dropwise while maintaining the temperature below 12°C. The reaction mixture was extracted with ethyl acetate and washed with saturated brine. All the aqueous layers were washed with ethyl acetate and then saturated brine. All the aqueous layers were combined and extracted again with an ethyl acetate / tetrahydrofuran mixture (v / v = 3 / 1) and washed with saturated brine. All the organic layers were combined and dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. Diisopropyl ether (650 mL) was added to the obtained crude product, and the mixture was stirred for 30 minutes. The solid was collected by filtration to obtain the title compound (68.6 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. Step 5-5: 2-(4-Bromo-2,6-dimethylphenyl)-6-morpholino-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one acetone solvate Under a nitrogen atmosphere, morpholine (49 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 (66.6 g) and 1-methylpyrrolidin-2-one (270 mL). The mixture was stirred at 105°C for 1 hour and then cooled to 55°C in a water bath. Water (1000 mL) was slowly added dropwise to the reaction mixture, which was then stirred overnight at room temperature. The resulting solid was collected by filtration and washed successively with water and hexane to give crude 2-(4-bromo-2,6-dimethylphenyl)-6-morpholino-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (65.5 g). 1-Methylpyrrolidin-2-one (160 mL) was added to the crude 2-(4-bromo-2,6-dimethylphenyl)-6-morpholino-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (65.5 g) and stirred at 85°C for 40 minutes. The resulting solution was then filtered to remove dust. While stirring at 65°C, acetone (1000 mL) was added over 40 minutes, followed by the slow dropwise addition of water (390 mL) over 20 minutes. The resulting mixture was stirred overnight while cooling. The resulting solid was collected by filtration and washed with an acetone / water mixture (v / v = 1 / 2, 100 mL). The resulting solid was then stirred in an ethanol / acetone (v / v = 1 / 2, 840 mL) mixture at 63°C for 2 hours and then stirred overnight while cooling. The solid was collected by filtration and washed with an ethanol / acetone mixture (v / v = 1 / 1, 50 mL) to give a mixture of the title compound and 2-(4-bromo-2,6-dimethylphenyl)-6-morpholino-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (56.5 g). 1 H-NMR (DMSO-D6) δ: 10.95 (1H, br s), 8.49 (1H, s), 7.49 (2H, s), 3.65-3.64 (4H, m), 3.53-3.52 (4H, m), 2.07 (6H, s), 1.96 (6H, s). Step 5-6: 2-(4-Bromo-2,6-dimethylphenyl)-6-morpholino-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one A mixture of 2-(4-bromo-2,6-dimethylphenyl)-6-morpholino-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one acetone solvate and 2-(4-bromo-2,6-dimethylphenyl)-6-morpholino-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (56.5 g) was ball milled (wet with acetone) and then dehydrated by desolvation under vacuum at 90°C to give crystals of the title compound (49.1 g). 1 H-NMR (DMSO-D6) δ: 10.95 (1H, br s), 8.50 (1H, s), 7.49 (2H, s), 3.65-3.64 (4H, m), 3.53-3.52 (4H, m), 1.96 (6H, s). LC-MS (MH+):404.

[0116] Preparation Example 6: Synthesis of 2-(4-methyl-6-(trifluoromethyl)pyridin-3-yl)-6-morpholino-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (Example 98) Step 6-1: methyl 3-amino-1-(4-methyl-6-(trifluoromethyl)pyridin-3-yl)-1H-pyrazole-4-carboxylate To a mixture of methyl 3-amino-1H-pyrazole-4-carboxylate (300 mg) and dimethyl sulfoxide (2.0 mL), 5-bromo-4-methyl-2-(trifluoromethyl)pyridine (510 mg), trans-N,N'-dimethylcyclohexane-1,2-diamine (0.13 mL), copper(I) iodide (81 mg), and cesium carbonate (690 mg) were added and stirred at 140 °C overnight. After cooling to room temperature, methyl iodide (0.27 mL) was added and stirred at room temperature for 1 hour. The reaction mixture was purified by column chromatography (eluent: hexane / ethyl acetate) to give the title compound (89 mg). 1H-NMR (CDCl) δ: 8.65 (1H, s), 7.88 (1H, s), 7.62 (1H, s), 4.85 (2H, br s), 3.85 (3H, s), 2.49 (3H, s). Step 6-2: Methyl 3-(3-(ethoxycarbonyl)thioureido)-1-(4-methyl-6-(trifluoromethyl)pyridin-3-yl)-1H-pyrazole-4-carboxylate Under an argon atmosphere, ethoxycarbonyl isothiocyanate (0.042 mL) was added to a mixture of methyl 3-amino-1-(4-methyl-6-(trifluoromethyl)pyridin-3-yl)-1H-pyrazole-4-carboxylate (89 mg) and acetonitrile (1.0 mL). The mixture was stirred at room temperature for 1 hour, and the solvent was evaporated under reduced pressure to give the crude title compound (128 mg). LC-MS (MH+): 432. Step 6-3: Methyl 3-((((ethoxycarbonyl)amino)(morpholino)methylene)amino)-1-(4-methyl-6-(trifluoromethyl)pyridin-3-yl)-1H-pyrazole-4-carboxylate To a mixture of crude methyl 3-(3-(ethoxycarbonyl)thioureido)-1-(4-methyl-6-(trifluoromethyl)pyridin-3-yl)-1H-pyrazole-4-carboxylate (64 mg) and chloroform (2.0 mL), morpholine (0.021 mL), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (54 mg), and triethylamine (0.052 mL) were added. The mixture was stirred at room temperature for 3 hours, and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (eluent: hexane / ethyl acetate) to give the title compound (60 mg). LC-MS (MH+): 485. Step 6-4: 2-(4-methyl-6-(trifluoromethyl)pyridin-3-yl)-6-morpholino-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one To methyl 3-((((ethoxycarbonyl)amino)(morpholino)methylene)amino)-1-(4-methyl-6-(trifluoromethyl)pyridin-3-yl)-1H-pyrazole-4-carboxylate (60 mg), water (0.5 mL) and trifluoroacetic acid (2.0 mL) were added and the mixture was stirred at 120°C overnight. After the solvent was evaporated under reduced pressure, tetrahydrofuran (2.0 mL) and saturated aqueous sodium bicarbonate (6.0 mL) were added and the mixture was stirred at 60°C for 3 hours. The reaction mixture was extracted with ethyl acetate, 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: hexane / ethyl acetate), and the resulting solid was washed with a mixed solution of ethyl acetate / diisopropyl ether to give the title compound (27 mg). 1 H-NMR (DMSO-D6) δ: 11.02 (1H, br s), 8.84 (1H, s), 8.83 (1H, s), 8.08 (1H, s), 3.66-3.65 (4H, m), 3.56-3.55 (4H, m), 2.46 (3H, s). LC-MS (MH+): 381.

[0117] [Production Example 7]: Synthesis of 2-(4-bromo-2,6-dimethylphenyl)-6-morpholino-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (Example 124) Step 7-1: 2,4,6-trichloro-5-(dimethoxymethyl)pyrimidine 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 (Fuji Silysia Chemical Ltd., 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). Step 7-2: 4-(2-(4-bromo-2,6-dimethylphenyl)hydrazinyl)-2,6-dichloro-5-(dimethoxymethyl)pyrimidine Under a nitrogen atmosphere, 2,4,6-trichloro-5-(dimethoxymethyl)pyrimidine (46 g) was added to a mixture of (4-bromo-2,6-dimethylphenyl)hydrazine hydrochloride (45 g) and methanol (320 mL), and the reaction mixture was cooled to below 2°C in an ice bath. Triethylamine (75 mL) was slowly added to the reaction mixture while maintaining the temperature below 9°C, and the mixture was stirred at the same temperature for 2 hours. The resulting solid was collected by filtration and washed successively with methanol (120 mL) and hexane (100 mL) to obtain the title compound (69.8 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. Step 7-3: 2-(4-Bromo-2,6-dimethylphenyl)-4,6-dichloro-2H-pyrazolo[3,4-d]pyrimidine Under a nitrogen atmosphere, trifluoroacetic acid (25 mL) was slowly added dropwise to a mixture of 4-(2-(4-bromo-2,6-dimethylphenyl)hydrazinyl)-2,6-dichloro-5-(dimethoxymethyl)pyrimidine (69.8 g) and toluene (560 mL) over 40 minutes while maintaining the temperature below 24°C. The reaction mixture was stirred for an additional hour, and then slowly added dropwise to an ice-cooled solution of tripotassium phosphate (68 g) in water (230 mL) over 10 minutes while maintaining the temperature below 10°C. The reaction mixture was extracted with an ethyl acetate / tetrahydrofuran mixture, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to give the crude title compound (61.8 g). LC-MS (MH+): 372. Step 7-4: 2-(4-bromo-2,6-dimethylphenyl)-6-chloro-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one A mixture of crude 2-(4-bromo-2,6-dimethylphenyl)-4,6-dichloro-2H-pyrazolo[3,4-d]pyrimidine (59.5 g) and tetrahydrofuran (480 mL) was added with 4 M aqueous sodium hydroxide (120 mL) at room temperature and stirred at 65°C for 4 hours. The reaction mixture was cooled to below 2°C in an ice bath, and 2 M hydrochloric acid (220 mL) was slowly added dropwise while maintaining the temperature below 10°C. The reaction mixture was extracted with ethyl acetate and washed sequentially with a mixture of saturated aqueous sodium bicarbonate and saturated brine (v / v = 1 / 1) and saturated brine. All aqueous layers used for washing were extracted with ethyl acetate and tetrahydrofuran (v / v = 2 / 1). All organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. Diisopropyl ether (600 mL) was added to the obtained crude product and stirred for 1 hour. The solid was then collected by filtration and washed with diisopropyl ether (200 mL) to obtain the title compound (51.7 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. Step 7-5: 2-(4-Bromo-2,6-dimethylphenyl)-6-morpholino-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one Under a nitrogen atmosphere, morpholine (38 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 (51.7 g) and 1-methylpyrrolidin-2-one (210 mL). The mixture was stirred at 105°C for 1.5 hours and then cooled to 55°C in a water bath. Water (800 mL) was slowly added dropwise to the reaction mixture, and the mixture was stirred at room temperature for 1 hour. After stirring in a water bath for an additional hour, the resulting solid was collected by filtration and washed successively with water and hexane. A mixture of the resulting solid and methanol (130 mL) was stirred at 65°C for 3 hours, gradually cooled to room temperature over 2 hours, and then stirred at room temperature for an additional hour. The solid was collected by filtration and washed with methanol to give the title compound (47.1 g). 1H-NMR (DMSO-D6) δ: 10.95 (1H, br s), 8.50 (1H, s), 7.49 (2H, s), 3.65-3.64 (4H, m), 3.53-3.52 (4H, m), 1.96 (6H, s). LC-MS (MH+): 404. Step 7-6: 2-(4-Bromo-2,6-dimethylphenyl)-6-morpholino-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one Under an argon atmosphere, a solution of 2-(4-bromo-2,6-dimethylphenyl)-6-morpholino-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (20 g), cyclopropylboronic acid (12 g), [1,1'-bis(di-tert-butylphosphino)ferrocene]palladium(II) dichloride (970 mg), and toluene (200 mL) was added to a solution of tripotassium phosphate (32 g) in water (40 mL). The mixture was stirred at 90°C for 2 hours, then tetrahydrofuran (250 mL) was added at 60°C and allowed to cool to room temperature. The organic layers were separated, and the aqueous layer was extracted with ethyl acetate. All organic layers were washed with saturated brine, then tetrahydrofuran (50 mL) was added, and the mixture was dried over anhydrous sodium sulfate and anhydrous magnesium sulfate. After filtering off the anhydrous sodium sulfate and anhydrous magnesium sulfate, N1-(2-aminoethyl)ethane-1,2-diamine (2.0 mL) was added and stirred for 30 minutes. Silica gel (Kanto Chemical Co., Inc., Silica Gel 60N, 40 g) was added and stirred at room temperature for 1.5 hours. The silica gel was filtered off and washed with ethyl acetate. The solvent was evaporated under reduced pressure to give the crude title compound (23.2 g). Using 2-(4-bromo-2,6-dimethylphenyl)-6-morpholino-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (5 g and 20 g), the crude title compound (5.5 g and 23.9 g, respectively) was obtained by the same procedure. A mixture of the resulting crude title compound (40.6 g) in methanol (200 mL) was stirred at 65°C for 4 hours and then at room temperature for 3 hours. The solid collected by filtration was washed with methanol (50 mL). A mixture of the obtained solid and methanol (200 mL) was stirred at 65°C for 4 hours and then at room temperature for 2.5 hours. The solid collected by filtration was washed with methanol (40 mL). A mixture of the obtained solid and methanol (260 mL) was stirred at 70°C for 8 hours and then at room temperature for 1 hour. The solid collected by filtration was washed with methanol (20 mL). A mixture of the obtained solid and ethyl acetate (460 mL) was stirred at 70°C for 4 hours and then at room temperature for 2 hours. The solid collected by filtration was washed with ethyl acetate (50 mL) to give the title compound (26.2 g). 1H-NMR (CDCl3) δ: 9.87 (1H, br s), 7.92 (1H, s), 6.84 (2H, s), 3.86-3.79 (4H, m), 3.75-3.68 (4H, m), 2.03 (6H, s), 1.93-1.84 (1H, m), 1.04-0.96 (2H, m), 0.76-0.70 (2H, m). LC-MS (MH+): 366.

[0118] [Preparation Example 8]: Synthesis of 6-((1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)-2-(4-cyclopropyl-2,6-dimethylphenyl)-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (Example 209) Step 8-1: 2,4,6-trichloro-5-(dimethoxymethyl)pyrimidine Under a nitrogen atmosphere, trimethyl orthoformate (75 mL) and sulfuric acid (0.16 mL) were added to a mixture of 2,4,6-trichloropyrimidine-5-carbaldehyde (25 g) and toluene (150 mL), and the mixture was stirred at room temperature for 1 hour. Basic silica gel (Fuji Silysia Chemical Ltd., 50 g) was added to the reaction mixture, and after stirring for 30 minutes, the added silica gel was removed by filtration. The silica gel was washed with ethyl acetate (150 mL), and the solvent was evaporated under reduced pressure to give the title compound (29 g). 1 H-NMR (CDCl3) δ: 5.68 (1H, s), 3.49 (6H, s). Step 8-2: 4-(2-(4-bromo-2,6-dimethylphenyl)hydrazinyl)-2,6-dichloro-5-(dimethoxymethyl)pyrimidine To a mixture of (4-bromo-2,6-dimethylphenyl)hydrazine hydrochloride (16 g) and methanol (160 mL) under a nitrogen atmosphere, 2,4,6-trichloro-5-(dimethoxymethyl)pyrimidine (16 g) was added, followed by triethylamine (27 mL) over 5 minutes while maintaining the temperature below 40°C. The mixture was then stirred at the same temperature for 1 hour. The resulting solid was collected by filtration and washed with methanol (150 mL) to give the title compound (21 g). 1H-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. Step 8-3: 2-(4-Bromo-2,6-dimethylphenyl)-4,6-dichloro-2H-pyrazolo[3,4-d]pyrimidine Under a nitrogen atmosphere, trifluoroacetic acid (21 mL) was slowly added dropwise to a mixture of 4-(2-(4-bromo-2,6-dimethylphenyl)hydrazinyl)-2,6-dichloro-5-(dimethoxymethyl)pyrimidine (21 g) and toluene (170 mL) over 5 minutes while maintaining the temperature below 30°C. The reaction mixture was stirred for an additional 30 minutes, and the solvent was evaporated under reduced pressure to give the crude title compound (24.5 g). LC-MS (MH+): 372. Step 8-4: 2-(4-bromo-2,6-dimethylphenyl)-6-chloro-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one To a mixture of crude 2-(4-bromo-2,6-dimethylphenyl)-4,6-dichloro-2H-pyrazolo[3,4-d]pyrimidine (24.5 g) and tetrahydrofuran (180 mL), 2 M aqueous sodium hydroxide (100 mL) was added at room temperature and stirred at 65°C for 1.5 hours. 2 M hydrochloric acid (100 mL) was slowly added dropwise to the reaction mixture while maintaining the temperature below 30°C. The reaction mixture was extracted with ethyl acetate, and the organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was then evaporated under reduced pressure. Diisopropyl ether (130 mL) was added to the crude product, and the mixture was stirred for 20 minutes. The solid was collected by filtration to give the title compound (12 g). 1H-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. Step 8-5: 6-((1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)-2-(4-bromo-2,6-dimethylphenyl)-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one Under an argon atmosphere, a mixture of 2-(4-bromo-2,6-dimethylphenyl)-6-chloro-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (60 mg) and 1-methylpyrrolidin-2-one (1.2 mL) was added with (1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptane hydrochloride (35 mg) and triethylamine (0.071 mL), and the mixture was stirred at 100°C for 3 hours. The reaction mixture was purified by reversed-phase C18 column chromatography (eluent: acetonitrile / water) to give the title compound (80 mg). 1 H-NMR (DMSO-D6) δ: 10.82 (1H, s), 8.47 (1H, s), 7.50 (2H, s), 4.97 (1H, s), 4.65 (1H, s), 3.81-3.72 (2H, m), 3.52 (1H, dd, J = 10.2, 1.0 Hz), 3.41-3.38 (1H, m), 1.98 (6H, s), 1.93-1.83 (2H, m). LC-MS (MH+): 416. Step 8-6: 6-((1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)-2-(4-cyclopropyl-2,6-dimethylphenyl)-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one To a mixture of 6-((1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)-2-(4-bromo-2,6-dimethylphenyl)-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (71 mg), cyclopropylboronic acid (44 mg), [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride dichloromethane adduct (28 mg), and 1,2-dimethoxyethane (2.1 mL) was added 2M aqueous potassium phosphate (0.26 mL) under an argon atmosphere. The mixture was stirred at 100°C for 2 hours, and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (eluent: methanol / ethyl acetate) and reverse-phase C18 column chromatography (eluent: acetonitrile / water) to give the title compound (29 mg). 1 H-NMR (DMSO-D6) δ: 10.79 (1H, s), 8.38 (1H, d, J = 1.2 Hz), 6.92 (2H, s), 4.96 (1H, s), 4.65 (1H, s), 3.76 (2H, dd, J = 11.9, 7.5 Hz), 3.51 (1H, d, J = 10.6 Hz), 3.39 (1H, d, J = 10.9 Hz), 1.93-1.83 (9H, m), 0.97 (2H, dd, J = 13.4, 4.9 Hz), 0.72 (2H, q, J = 5.0 Hz). LC-MS (MH+): 378.

[0119] [Production Example 9]: Synthesis of 2-(4-(difluoromethoxy)-2,6-dimethylphenyl)-6-morpholino-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (Example 298) Step 9-1: 5-(difluoromethoxy)-1,3-dimethyl-2-nitrobenzene Under an argon atmosphere, cesium carbonate (2.9 g) and sodium chlorodifluoroacetate (2.3 g) were added to a mixture of 3,5-dimethyl-4-nitrophenol (1.0 g) and N,N-dimethylformamide (10 mL), and the mixture was stirred at 100°C for 2 hours. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The resulting organic layer was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (eluent: hexane / ethyl acetate) to give the title compound (750 mg). 1 H-NMR (CDCl3) δ: 6.87 (2H, s), 6.51 (1H, t, J = 73.1 Hz), 2.32 (6H, s). Step 9-2: 4-(difluoromethoxy)-2,6-dimethylaniline To a mixture of 5-(difluoromethoxy)-1,3-dimethyl-2-nitrobenzene (750 mg) and ethanol (10 mL), 10% palladium on carbon (75 mg) was added and the mixture was stirred overnight at room temperature under a hydrogen atmosphere (atmospheric pressure). The palladium catalyst was removed by filtration through Celite, and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (eluent: hexane / ethyl acetate) to give the title compound (720 mg). 1 H-NMR (CDCl) δ: 6.74 (2H, s), 6.35 (1H, t, J = 75.1 Hz), 3.50 (2H, br s), 2.16 (6H, s). Step 9-3: (4-(difluoromethoxy)-2,6-dimethylphenyl)hydrazine hydrochloride To a mixture of 4-(difluoromethoxy)-2,6-dimethylaniline (720 mg) and 6 M hydrochloric acid (3.6 mL), concentrated hydrochloric acid (2.1 mL) was added and the mixture was cooled to −16 °C. At the same temperature, a solution of sodium nitrite (280 mg) in water (7.2 mL) was slowly added dropwise over 3 minutes, followed by stirring for an additional 70 minutes. At the same temperature, a solution of tin(II) chloride dihydrate (1.8 g) in concentrated hydrochloric acid (1.6 mL) was added dropwise over 5 minutes, followed by stirring for 1 hour. The refrigerant was removed, and the mixture was stirred for an additional 2 hours. The resulting solid was collected by filtration and washed with a small amount of 2 M hydrochloric acid and diisopropyl ether to give the title compound (560 mg). 1 H-NMR (DMSO-D6) δ: 9.49 (3H, br s), 7.19 (1H, t, J = 74.1 Hz), 6.93 (2H, s), 6.77 (1H, br s), 2.37 (6H, s). Step 9-4: 2,4-dichloro-6-(2-(4-(difluoromethoxy)-2,6-dimethylphenyl)hydrazinyl)-5-(dimethoxymethyl)pyrimidine Under an argon atmosphere, triethylamine (0.98 mL) was added to a mixture of 2,4,6-trichloro-5-(dimethoxymethyl)pyrimidine (600 mg), (4-(difluoromethoxy)-2,6-dimethylphenyl)hydrazine hydrochloride (560 mg), and methanol (5.6 mL), which was synthesized in the same manner as in Step 5-1 of Preparation Example 5, and the mixture was stirred at room temperature for 1 hour. After the solvent was evaporated under reduced pressure, ethyl acetate was added, and the resulting salt was removed using Celite to obtain the crude title compound. LC-MS (MH+): 423. Step 9-5: 4,6-Dichloro-2-(4-(difluoromethoxy)-2,6-dimethylphenyl)-2H-pyrazolo[3,4-d]pyrimidine Under an argon atmosphere, trifluoroacetic acid (1.0 mL) was added dropwise to a mixture of the crude product of 2,4-dichloro-6-(2-(4-(difluoromethoxy)-2,6-dimethylphenyl)hydrazinyl)-5-(dimethoxymethyl)pyrimidine and toluene (7.9 mL), and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was neutralized with 4 M aqueous sodium hydroxide solution and extracted with ethyl acetate. The resulting organic layer was washed successively with saturated aqueous sodium bicarbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to obtain the crude product of the title compound. LC-MS (MH+): 359. Step 9-6: 6-chloro-2-(4-(difluoromethoxy)-2,6-dimethylphenyl)-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one To a mixture of the crude product of 4,6-dichloro-2-(4-(difluoromethoxy)-2,6-dimethylphenyl)-2H-pyrazolo[3,4-d]pyrimidine and tetrahydrofuran (8.4 mL), 2 M aqueous sodium hydroxide solution (4.7 mL) was added and stirred at 85°C for 1.5 hours. The reaction mixture was neutralized with 2 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: hexane / ethyl acetate), and the resulting solid was washed with diisopropyl ether to give the title compound (150 mg). 1 H-NMR (DMSO-D6) δ: 12.87 (1H, br s), 8.80 (1H, s), 7.31 (1H, t, J = 73.8 Hz), 7.11 (2H, s), 1.96 (6H, s). Step 9-7: 2-(4-(difluoromethoxy)-2,6-dimethylphenyl)-6-morpholino-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one Under an argon atmosphere, morpholine (0.023 mL) was added to a mixture of 6-chloro-2-(4-(difluoromethoxy)-2,6-dimethylphenyl)-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (30 mg) and 1-methylpyrrolidin-2-one (1.0 mL), and the mixture was stirred at 100°C for 1 hour. The reaction mixture was purified by column chromatography (eluent: hexane / ethyl acetate), and the resulting solid was washed with water to give the title compound (14 mg). 1 H-NMR (DMSO-D6) δ: 10.94 (1H, br s), 8.48 (1H, s), 7.29 (1H, t, J = 73.8 Hz), 7.07 (2H, s), 3.66-3.64 (4H, m), 3.54-3.52 (4H, m), 1.97 (6H, s). LC-MS (MH+): 392.

[0120] [Production Example 10]: Synthesis of (4-cyclopropyl-2,6-dimethylphenyl)hydrazine hydrochloride Step 10-1: Benzyl 2-(4-bromo-2,6-dimethylphenyl)hydrazine-1-carboxylate Under an argon atmosphere, N,N-diisopropylethylamine (38.2 mL) and benzyl chloroformate (14.2 mL) were slowly added over 2 minutes to a mixture of (4-bromo-2,6-dimethylphenyl)hydrazine hydrochloride (25 g) in tetrahydrofuran (250 mL) at 0°C, and the mixture was stirred at room temperature for 1 hour. Hexane (100 mL) was added to the reaction mixture, which was then washed sequentially with water (100 mL) and saturated brine. The resulting organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. Hexane was added to the residue, and the mixture was stirred for 20 minutes. The resulting solid was collected by filtration to give the title compound (30.3 g). 1 H-NMR (CDCl) δ: 7.32 (5H, br s), 7.09 (2H, s), 6.52 (1H, br s), 5.67 (1H, br s), 5.06 (2H, s), 2.33 (6H, br s). Step 10-2: Benzyl 2-(4-cyclopropyl-2,6-dimethylphenyl)hydrazine-1-carboxylate Under an argon atmosphere, tripotassium phosphate (21.3 g) was dissolved in water (40 mL), followed by the addition of toluene (100 mL), benzyl 2-(4-bromo-2,6-dimethylphenyl)hydrazine-1-carboxylate (10 g), cyclopropylboronic acid (6.91 g), and bis(diphenylphosphino)ferrocene dichloropalladium(II) dichloromethane complex (700 mg). The mixture was stirred at 105°C for 4 hours. The reaction mixture was allowed to cool to room temperature, neutralized with 6 M hydrochloric acid (40 mL), and extracted twice with ethyl acetate. The resulting organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and filtered. ISOLUTE Si-TMT (metal scavenging silica gel, Biotage, 0.49 mmol TMT / g, 5.25 g) was added to the organic layer, and the mixture was stirred at room temperature for 1.5 hours. The silica gel was then filtered off, and the solvent was removed under reduced pressure. Hexane (50 mL) was added to the residue and stirred, and the resulting solid was collected by filtration to give the title compound (6.3 g). 1 H-NMR (CDCl) δ: 7.31 (5H, br s), 6.68 (2H, s), 6.48 (1H, br s), 5.65 (1H, br s), 5.06 (2H, s), 2.32 (6H, br s), 1.80-1.73 (1H, m), 0.87-0.84 (2H, m), 0.61-0.59 (2H, m). Step 10-3: (4-Cyclopropyl-2,6-dimethylphenyl)hydrazine hydrochloride Under an argon atmosphere, a mixture of benzyl 2-(4-cyclopropyl-2,6-dimethylphenyl)hydrazine-1-carboxylate (6.0 g) in ethanol (48 mL) was added with 4 M aqueous sodium hydroxide (48 mL) and stirred at 80 °C for 4 hours. After cooling, the reaction mixture was added with acetic acid (5.5 mL) and extracted twice with toluene. The resulting organic layer was dried over anhydrous magnesium sulfate and concentrated to approximately one-third of its original volume. To the resulting mixture was added a 4 M solution of hydrogen chloride in dioxane (4.6 mL) and stirred at room temperature for 10 minutes. The resulting solid was collected by filtration and washed with hexane to give the title compound (3.7 g). 1H-NMR (DMSO-d6) δ: 9.50 (3H, br s), 6.79 (2H, s), 6.66 (1H, br s), 2.33 (6H, s), 1.83-1.81 (1H, m), 0.97-0.84 (2H, m), 0.65-0.62 (2H, m).

[0121] [Production Example 11]: Synthesis of 2-(1-isopropyl-3,5-dimethyl-1H-pyrazol-4-yl)-6-(pyrrolidin-1-yl)-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (Example 343) Step 11-1: 4-iodo-1-isopropyl-3,5-dimethyl-1H-pyrazole To a mixture of 4-iodo-3,5-dimethyl-1H-pyrazole (2.0 g) and N,N-dimethylformamide (20 mL), cesium carbonate (7.0 g) and 2-iodopropane (1.1 mL) were added and stirred at room temperature overnight. The reaction mixture was stirred at 50 °C for an additional 2 hours, after which water was added and the mixture was extracted with ethyl acetate. The resulting organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was then evaporated under reduced pressure to give the title compound (2.1 g). 1 H-NMR (DMSO-D6) δ: 4.53-4.44 (1H, m), 2.23 (3H, s), 2.09 (3H, s), 1.31 (6H, d, J = 6.5 Hz). Step 11-2: Di-tert-butyl 1-(1-isopropyl-3,5-dimethyl-1H-pyrazol-4-yl)hydrazine-1,2-dicarboxylate Under an argon atmosphere, a 1.56 M n-butyllithium hexane solution (3.2 mL) was added to a mixture of 4-iodo-1-isopropyl-3,5-dimethyl-1H-pyrazole (1.0 g) and tetrahydrofuran (20 mL) at -78 °C, followed by stirring at the same temperature for 1 hour. Di-tert-butyl (E)-diazene-1,2-dicarboxylate (1.3 g) was added to the reaction mixture, which was then warmed to room temperature and stirred 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 dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue was purified by column chromatography (eluent: hexane / ethyl acetate) to obtain the title compound (1.0 g). LC-MS (MH+): 369. Step 11-3: 4-Hydrazinyl-1-isopropyl-3,5-dimethyl-1H-pyrazole hydrochloride Di-tert-butyl 1-(1-isopropyl-3,5-dimethyl-1H-pyrazol-4-yl)hydrazine-1,2-dicarboxylate (1.0 g) was added to a 4 M solution of hydrogen chloride in cyclopropyl methyl ether (10 mL) and the mixture was stirred at room temperature overnight. The solvent was evaporated under reduced pressure to give the title compound (570 mg). 1 H-NMR (DMSO-D6) δ: 9.36 (3H, br s), 4.44-4.37 (1H, m), 4.09 (1H, br s), 2.23 (3H, s), 2.17 (3H, s), 1.31 (6H, d, J = 6.5 Hz). Step 11-4: 2,4-Dichloro-5-(dimethoxymethyl)-6-(2-(1-isopropyl-3,5-dimethyl-1H-pyrazol-4-yl)hydrazinyl)pyrimidine To a mixture of 2,4,6-trichloro-5-(dimethoxymethyl)pyrimidine (710 mg) synthesized in the same manner as in Step 5-1 of Preparation 5 and methanol (11 mL), triethylamine (3.1 mL) was added and stirred at room temperature for 15 minutes. 4-Hydrazinyl-1-isopropyl-3,5-dimethyl-1H-pyrazole hydrochloride (570 mg) was added to the reaction mixture, and after stirring at room temperature for 1.5 hours, the solvent was evaporated under reduced pressure to obtain the crude title compound. LC-MS (MH+): 389. Step 11-5: 4,6-Dichloro-2-(1-isopropyl-3,5-dimethyl-1H-pyrazol-4-yl)-2H-pyrazolo[3,4-d]pyrimidine To a mixture of the crude product of 2,4-dichloro-5-(dimethoxymethyl)-6-(2-(1-isopropyl-3,5-dimethyl-1H-pyrazol-4-yl)hydrazinyl)pyrimidine and toluene (11 mL), trifluoroacetic acid (0.85 mL) was added and stirred at room temperature for 1 hour. After that, the mixture was neutralized with 2 M aqueous sodium hydroxide solution (8.3 mL). The resulting mixture was diluted with water and ethyl acetate and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to obtain the crude product of the title compound. LC-MS (MH+): 325. Step 11-6: 6-chloro-2-(1-isopropyl-3,5-dimethyl-1H-pyrazol-4-yl)-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one To a mixture of crude 4,6-dichloro-2-(1-isopropyl-3,5-dimethyl-1H-pyrazol-4-yl)-2H-pyrazolo[3,4-d]pyrimidine and tetrahydrofuran (9.0 mL), 4 M aqueous sodium hydroxide (2.8 mL) was added and stirred at 75 °C for 1.5 hours. The mixture was then allowed to cool to room temperature. The reaction mixture was neutralized with 2 M hydrochloric acid, diluted with water and ethyl acetate, and extracted with ethyl acetate. The resulting organic layer was dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue was purified by reverse-phase column chromatography (eluent: acetonitrile / water) to give the title compound (130 mg). LC-MS (MH+): 307. Step 11-7: 2-(1-Isopropyl-3,5-dimethyl-1H-pyrazol-4-yl)-6-(pyrrolidin-1-yl)-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one To a mixture of 6-chloro-2-(1-isopropyl-3,5-dimethyl-1H-pyrazol-4-yl)-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (130 mg) and tetrahydrofuran (1.3 mL), pyrrolidine (0.17 mL) was added and stirred at 80 °C for 1 hour. The reaction mixture was allowed to cool to room temperature, and the solvent was evaporated under reduced pressure. The residue was purified by reverse-phase column chromatography (eluent: acetonitrile / water) and column chromatography (eluent: hexane / ethyl acetate) to give the title compound (19 mg). 1 H-NMR (DMSO-D6) δ: 10.50 (1H, s), 8.37 (1H, s), 4.53-4.47 (1H, m), 3.47 (4H, t, J = 6.7 Hz), 2.20 (3H, s), 2.10 (3H, s), 1.90 (4H, t, J = 6.6 Hz), 1.38 (6H, d, J = 6.7 Hz). LC-MS (MH+):342.

[0122] [Preparation Example 12]: Synthesis of 2-(4-cyclopropyl-2,6-dimethylphenyl)-6-(1,5,2-dioxazepan-2-yl)-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (Example 349) Step 12-1: 2,4,6-trichloro-5-(dimethoxymethyl)pyrimidine To a mixture of 2,4,6-trichloropyrimidine-5-carbaldehyde (170 g) and toluene (1.0 L), trimethyl orthoformate (500 mL) and sulfuric acid (1.1 mL) were added under a nitrogen atmosphere and stirred at room temperature for 1.5 hours. Basic silica gel (Fuji Silicia, 330 g) was added to the reaction mixture, and after stirring for 1.5 hours, the added silica gel was removed by filtration. After washing the silica gel with ethyl acetate, the solvent was evaporated under reduced pressure to give the title compound (180 g). 1 H-NMR (CDCl3) δ: 5.68 (1H, s), 3.49 (6H, s). Step 12-2: 4-(2-(4-bromo-2,6-dimethylphenyl)hydrazinyl)-2,6-dichloro-5-(dimethoxymethyl)pyrimidine Under a nitrogen atmosphere, 2,4,6-trichloro-5-(dimethoxymethyl)pyrimidine (82 g) was added to a mixture of (4-bromo-2,6-dimethylphenyl)hydrazine hydrochloride (80 g) and methanol (560 mL), and the reaction mixture was cooled in an ice bath. Triethylamine (130 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 (150 mL) and hexane (100 mL) to give the title compound (69.8 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. Step 12-3: 2-(4-Bromo-2,6-dimethylphenyl)-4,6-dichloro-2H-pyrazolo[3,4-d]pyrimidine Under a nitrogen atmosphere, trifluoroacetic acid (43 mL) was slowly added dropwise over 10 minutes to a mixture of 4-(2-(4-bromo-2,6-dimethylphenyl)hydrazinyl)-2,6-dichloro-5-(dimethoxymethyl)pyrimidine (120 g) and toluene (970 mL) while maintaining the temperature below 26 °C. The reaction mixture was stirred for an additional 30 minutes and then slowly added dropwise to an ice-cooled solution of potassium phosphate tribasic (120 g) in water (400 mL). Ethyl acetate (100 mL) and tetrahydrofuran (640 mL) were added, and the organic layer was separated. The aqueous layer was extracted 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 (109 g). LC-MS (MH+): 372. Step 12-4: 2-(4-bromo-2,6-dimethylphenyl)-6-chloro-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one To a mixture of crude 2-(4-bromo-2,6-dimethylphenyl)-4,6-dichloro-2H-pyrazolo[3,4-d]pyrimidine (109 g) and tetrahydrofuran (830 mL), 4 M aqueous sodium hydroxide (210 mL) was added at room temperature and stirred at 80 °C for 5 h. 2 M hydrochloric acid (280 mL) was slowly added dropwise to the reaction mixture in an ice bath, and the reaction mixture was extracted with ethyl acetate. The aqueous layer was further extracted with a tetrahydrofuran / ethyl acetate mixture (v / v = 4 / 1). All organic layers were washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. Diisopropyl ether (550 mL) and ethyl acetate (150 mL) were added to the crude product, and the mixture was stirred for 1 h. The solid was collected by filtration to give the title compound (79 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. Step 12-5: 2-(4-Bromo-2,6-dimethylphenyl)-6-(1,5,2-dioxazepan-2-yl)-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one Under a nitrogen atmosphere, 1,5,2-dioxazepane hydrochloride (1.8 g) and N,N-diisopropylethylamine (3.0 mL) were added to a mixture of 2-(4-bromo-2,6-dimethylphenyl)-6-chloro-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (3.0 g) and 1-methylpyrrolidin-2-one (10 mL). The mixture was stirred at 140 °C for 2.5 hours and then allowed to cool to room temperature. Water (20 mL) was slowly added dropwise to the reaction mixture, and the resulting solid was collected by filtration and washed successively with water and hexane. A mixture of the resulting solid and diisopropyl ether (10 mL) was stirred at room temperature for 1 hour. The solid was collected by filtration and washed with diisopropyl ether to give the title compound (3.5 g). 1 H-NMR (DMSO-D6) δ: 11.26 (1H, s), 8.56 (1H, s), 7.50 (2H, s), 4.13-4.11 (2H, m), 3.88 (4H, s), 3.80-3.78 (2H, m), 1.96 (6H, s). LC-MS (MH+): 420. Step 12-6: 2-(4-Cyclopropyl-2,6-dimethylphenyl)-6-(1,5,2-dioxazepan-2-yl)-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one A mixture of 2-(4-bromo-2,6-dimethylphenyl)-6-(1,5,2-dioxazepan-2-yl)-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (3.5 g), cyclopropylboronic acid (1.6 g), [1,1'-bis(di-tert-butylphosphino)ferrocene]palladium(II) dichloride (540 mg), and toluene (35 mL) was added to a solution of tripotassium phosphate (5.2 g) in water (7 mL) under an argon atmosphere. The mixture was stirred at 105 °C for 3 h and then allowed to cool to room temperature. ISOLUTE Si-TMT (metal scavenging silica gel, Biotage, 0.47 mmol TMT / g, 5.0 g) was added and stirred at room temperature for 2 h. Silica gel (25 mL) was then added and the mixture was stirred for an additional 1 h. The added silica gel was filtered off and washed with ethyl acetate, and the solvent was evaporated under reduced pressure. A mixture of the residue and ethyl acetate (15 mL) was stirred at 80 °C for 1 hour and then allowed to cool to room temperature. Diisopropyl ether (15 mL) was added, and the mixture was stirred at room temperature for an additional 30 minutes. The solid was collected by filtration and washed with diisopropyl ether to give the title compound (2.6 g). 1 H-NMR (DMSO-D6) δ: 11.21 (1H, br s), 8.48 (1H, s), 6.92 (2H, s), 4.13-4.11 (2H, m), 3.88 (4H, s), 3.80-3.78 (2H, m), 1.94-1.89 (7H, m), 0.97-0.95 (2H, m), 0.72-0.70 (2H, m). LC-MS (MH+):382.

[0123] 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.

[0124] Test Example 1: Evaluation of NLRP3 inflammasome inhibitory activity The NLRP3 inflammasome inhibitory activity of test substances was evaluated based on 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 (37°C, 5% CO2 / 95% air). 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 (Part Number L2654, Sigma-Aldrich®) was added (25 μL / well) and 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 at 37°C in 5% CO2 / 95% air. Test substance solution was added (20 μL / well) to test substance wells. 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 at 37°C in 5% CO2 / 95% air. The final nigericin concentration 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 assay.IL-1β in the culture supernatant was quantified using the AlphaLISA® 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 instruction manual. The inhibition rate of the test substance well was calculated, with the blank well set as 100% and the control well set as 0%. 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.

[0125]

[0126]

[0127]

[0128] The following formulations are examples of the formulations of the present invention. However, the present invention is not limited to these formulations. Formulation Example 1 (Production of Capsules) (1) Compound of Example 1 30 mg (2) Microcrystalline cellulose 10 mg (3) Lactose 19 mg (4) Magnesium stearate 1 mg (1), (2), (3), and (4) are mixed and filled into a gelatin capsule.

[0129] Formulation Example 2 (Tablet Production) (1) Compound of Example 1 10 g (2) Lactose 50 g (3) Cornstarch 15 g (4) Carmellose calcium 44 g (5) Magnesium stearate 1 g The total amount of (1), (2), and (3) and 30 g of (4) were kneaded with water, vacuum dried, and then sized. 14 g of (4) and 1 g of (5) were mixed with this sized powder and compressed into tablets using a tablet press. In this way, 1,000 tablets containing 10 mg of the compound of Example 1 per tablet were obtained.

[0130] The compound of formula [I] or a pharmaceutically acceptable salt thereof, or the compound of formula [IA] or a pharmaceutically acceptable salt thereof, has an NLRP3 inflammasome inhibitory activity, and is therefore effective 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., idiopathic pulmonary fibrosis, ... The compound is expected to be useful for the treatment or prevention of a disease selected from the group consisting of hemophagocytic lymphohistiocytosis 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, and TNF receptor-associated periodic syndrome.

Claims

1. A compound of formula [IA] or a pharma- ceutically acceptable salt thereof. may form a group represented by the formula 2. Substructure: (In the formula, R ４ The compound according to claim 1, which has the structure represented by the formula: embedded image or a pharma- ceutically acceptable salt thereof.

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

4. R ４ The compound according to any one of claims 1 to 3, or a pharma- ceutically acceptable salt thereof, wherein is hydrogen.

5. Ring group Cy Ａ But, (1) formula:

5. The compound according to claim 1 , which is a group represented by the formula: wherein each symbol has the same meaning as in claim 1 , or a pharma- ceutically acceptable salt thereof.

6. A compound according to any one of claims 1 to 5, represented by the formula [IIA] or a pharma- ceutically acceptable salt thereof. (wherein each symbol has the same meaning as in claim 1) 7. R ８ and R ９ 7. The compound according to claim 1 , or a pharma- ceutically acceptable salt thereof, wherein is hydrogen.

8. A compound according to any one of claims 1 to 7, represented by formula [IIIA] or a pharma- ceutically acceptable salt thereof. is a group represented by the formula 9. Ring group Cy Ｂ (1) a 4- to 7-membered heterocycloalkyl containing from 1 to 3 heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur atoms, wherein the heterocycloalkyl is: (a) hydroxy, (b) cyano, (c) C １－６ (1) hydroxy, (2) C １－４ (3) phenyl, optionally substituted with １－４ (e) halogen; (f) C １－４ haloalkyl, (g) —O—C １－４ haloalkyl, (h) —CO—C １－４ Alkyl, wherein the alkyl is １－４ (i) -CO-C １－６ Alkoxy, (j) -CO-C ３－６ Cycloalkyl, (k) -CONH-C １－４ Alkyl, (m) -NHCO-C １－４ Alkyl, (n) -NR １８ R １９ (Here, R １８ and R １９ are each independently １－４ (o) -SO ２ -C １－４ Alkyl, (p)-SO ２ -C ３－６ cycloalkyl, (q) C ３－６ (r) phenyl, (s) a group of the formula: and (t) oxo; or (2) a 6- to 8-membered bridged heterocycloalkyl containing 1 or 2 heteroatoms independently selected from the group consisting of nitrogen and oxygen atoms, wherein the bridged heterocycloalkyl is: (a) a halogen, (b) —CO—C １－４ Alkyl, wherein the alkyl is １－４ (c) -SO ２ -C １－４ 9. The compound according to claim 8, wherein the compound is: embedded image wherein the alkyl group is aryl, aryl, aryl, or aryl; 10. Ring group Cy Ｂ (c) a 4- to 7-membered heterocycloalkyl containing 1 to 3 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur atoms, wherein the heterocycloalkyl is: (1) hydroxy, (2) cyano, (3) C １－６ (a) hydroxy, (b) C １－４ (c) phenyl, or １－４ (5) halogen; (6) C １－４ Haloalkyl, (7) —O—C １－４ Haloalkyl, (8) -CO-C １－４ Alkyl, wherein the alkyl is １－４ (9) -CO-C １－６ Alkoxy, (10) -CO-C ３－６ Cycloalkyl, (11) -CONH-C １－４ Alkyl, (12) -NHCO-C １－４ alkyl, (13)-NR １８ R １９ (Here, R １８ and R １９ are each independently １－４ (14) -SO ２ -C １－４ Alkyl, (15)-SO ２ -C ３－６ cycloalkyl, (16) C ３－６ (17) cycloalkyl, (18) a compound of the formula: (19) oxo; and (20) a substituted or unsubstituted ring structure; 11. Ring group Cy Ｂ (c) a 4- to 7-membered heterocycloalkyl group containing 1 to 3 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur atoms, wherein the heterocycloalkyl group is selected from the group consisting of: (1) cyano, (2) C １－６ Alkyl {wherein the alkyl is hydroxy, or C １－４ (3) C １－４ (4) halogen; (5) —CO—C １－４ Alkyl, wherein the alkyl is １－４ (6) -CO-C １－６ Alkoxy, (7) -CO-C ３－６ Cycloalkyl, (8)-SO ２ -C １－４ Alkyl, (9) -SO ２ -C ３－６ Cycloalkyl, (10) Formula: (11) oxo; and (12) a substituted or unsubstituted ring structure; or a pharma- ceutically acceptable salt thereof.

12. A compound having the following structural formula:

2. The compound of claim 1, selected from the group consisting of:

13. A pharmaceutical composition comprising a compound according to any one of claims 1 to 12, or a pharma- ceutically acceptable salt thereof, and a pharma- ceutically acceptable carrier.

14. An NLRP3 inflammasome inhibitor comprising a compound according to any one of claims 1 to 12 or a pharma- ceutically acceptable salt thereof.

15. 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 12 or a pharma-ceutical acceptable salt thereof.

16. The therapeutic or preventive agent according to claim 15, wherein the inflammatory bowel disease is ulcerative colitis or Crohn's disease.

17. The therapeutic or preventive agent according to claim 15, 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.

18. A method for inhibiting the NLRP3 inflammasome, comprising administering to a mammal a therapeutically effective amount of a compound described in any one of claims 1 to 12 or a pharma- ceutically acceptable salt thereof.

19. 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 to a mammal a therapeutically effective amount of a compound according to any one of claims 1 to 12 or a pharma-ceutical acceptable salt thereof.

20. The method of claim 19, wherein the inflammatory bowel disease is ulcerative colitis or Crohn's disease.

21. The method of claim 19, wherein the cryopyrin-associated periodic fever syndrome is familial cold autoinflammatory syndrome, Muckle-Wells syndrome, chronic infantile neurological cutaneous articular syndrome, or neonatal onset multisystem inflammatory disease.

22. Use of a compound according to any one of claims 1 to 12 or a pharma- ceutically acceptable salt thereof for the manufacture of an NLRP3 inflammasome inhibitor.

23. Use of the compound according to any one of claims 1 to 12 or a pharma- ceutical acceptable salt thereof for the manufacture of a therapeutic or prophylactic agent for a disease selected from the group consisting of multiple sclerosis, inflammatory bowel disease, arteriosclerosis, cryopyrin-associated periodic fever syndrome, nonalcoholic steatohepatitis, gout, ischemic heart disease, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and traumatic brain injury.

24. The use according to claim 23, wherein the inflammatory bowel disease is ulcerative colitis or Crohn's disease.

25. The use according to claim 23, wherein the cryopyrin-associated periodic fever syndrome is familial cold autoinflammatory syndrome, Muckle-Wells syndrome, chronic infantile neurological, cutaneous, articular syndrome or neonatal-onset multisystem inflammatory disease.

26. A compound according to any one of claims 1 to 12, or a pharma- ceutically acceptable salt thereof, for use in inhibiting the NLRP3 inflammasome.

27. A compound according to any one of claims 1 to 12 or a pharma- ceutically 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, nonalcoholic steatohepatitis, gout, ischemic heart disease, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and traumatic brain injury.

28. The compound according to claim 27, or a pharma- ceutically acceptable salt thereof, wherein the inflammatory bowel disease is ulcerative colitis or Crohn's disease.

29. The compound according to claim 27 or a pharma- ceutically 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.