Novel compound as NLRP3 inhibitor and pharmaceutical composition comprising same

Abstract

The present invention relates to a compound as an NLRP3 inhibitor, a stereoisomer thereof or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising same as an active ingredient. The compound, the stereoisomer thereof or the pharmaceutically acceptable salt thereof, and the pharmaceutical composition comprising same as an active ingredient can be advantageously used for preventing or treating NLRP3 activity-related diseases.

Description

[0001] Description of the Invention

[0002]

Title of invention

[0003] Novel compound as NLRP3 inhibitor and pharmaceutical composition containing same

[0004]

Technical Field

[0005]

Background Technology

[0006] NOD-like receptor 3 (NLRP3) is a protein-coding gene that belongs to the nucleotide-binding and oligomerization domain (NOD)-like receptor (NLR) family. NLRP3 encodes a protein containing a pyrin domain, a nucleotide-binding site domain (NBD), and leucine-rich repeat (LRR) motifs. In response to sterile inflammatory danger signals, NLRP3 interacts with the adaptor protein, apoptosis-associated speck-like protein (ASC), and pro-caspase-1 to form the NLRP3 inflammasome. Subsequent NLRP3 inflammasome activation can induce a number of related diseases by leading to the release of the proinflammatory cytokines IL-1P and IL-18. Activated cytokines derived from NLRP3 inflammasome activation are important drivers of inflammation and interact with other cytokine pathways to format the immune response to infection and injury. For example, IL-1P signaling induces the secretion of the proinflammatory cytokines IL-6 and TNF. IL-1P and IL-18 synergize with IL-23 to induce IL-17 production by x8 T cells and memory CD4 Th17 cells in the absence of T cell receptor engagement. IL-18 and IL-12 also synergize to induce IFN-x production from memory T cells and NK cells, which promote Th1 responses.

[0007] NLRP3 inflammasome activation is associated with various inflammasome-related diseases / disorders, immune diseases, inflammatory diseases, autoimmune diseases and autoinflammatory diseases, for example, autoinflammatory febrile syndromes such as cryopyrin-associated periodic syndrome (CAPS) (Mor timer et al., Nature Immunol. 2016, 17(10), 1176-1188): sickle cell disease; Systemic lupus erythematosus (SLE); Liver-related diseases / disorders, such as chronic liver disease, viral hepatitis, non-alcoholic steatohepatitis (NASH, Hugh Thomas Nature Reviews Gastroenterology & Hepatology 2017:14, 197), alcoholic steatohepatitis and alcoholic liver disease (Petrasek et al., J. Cl in. Invest.2012, 122, 3476—89; Petrasek et al., Nat. Rev. Gastroenterol. Hepatol.2015, 12, 387—400; Mr i dha, AR et al., J. Hepatol. 2017, 66, 1037-46); Inflammatory arthritis-related disorders, such as gout, pseudogout (chondrocalcinosis), osteoarthritis (Ridker et al., N. Engl. J. Med. 2017, 377, 1119-31) and rheumatoid arthritis (Mathews et al., Ann. Rheum. Dis. 2014, 73, 1202-10), acute or chronic arthropathy; kidney-related diseases such as hyperoxaluria (Knauf et al., Kidney Int. 2013, 84, 895-901), lupus nephritis, hypertensive nephropathy (Krishnan et al., Br. J. Pharmacol.2016, 173, 752-65), hemodialysis-associated inflammation and diabetic nephropathy, also called diabetic kidney disease (which is a kidney-related complication of diabetes (type 1, type 2 and diabetes mellitus)) (Shahzad et al., Kidney Int. 2015, 87, 74-84). Furthermore, the involvement of increased production of IL-1P and IL-18 by NLRP3 inflammasome has been implicated in various diseases, such as neuroinflammation-related disorders, such as brain infection, acute injury, multiple sclerosis, Alzheimer's disease and neurodegenerative diseases (hao et al. , Front. Pharmacol. 2015, 6, 262); cardiovascular / metabolic disorders / diseases, such as cardiovascular risk reduction (CvRR), atherosclerosis, type I and type II diabetes and related complications (e.g. nephropathy, retinopathy), peripheral artery disease (PAD), acute heart failure and hypertension (Ridker et al. , N. Engl. J. Med. 2017, 377, 1119-31); wound healing and scar formation; It has been shown that it may contribute to the development and progression of inflammatory skin diseases such as acne, hidradenitis suppurativa (Sweeney et al., Br. J. Dermatol. 2015, 173, 1361), asthma, sarcoidosis, age-related macular degeneration; and cancer-related diseases / disorders such as myeloproliferative neoplasms, leukemia, myelodysplastic syndrome (MDS), myelofibrosis, lung cancer, and colon cancer (Ridker et al., Lancet 2017, 390, 1833-42). Inherently immune or inflammatory diseases / disorders are generally difficult to diagnose or treat effectively.Most treatments involve treating symptoms, slowing the progression of the disease / disorder, lifestyle changes, and surgery as a last resort (e.g., open heart surgery for advanced forms of atherosclerosis). Recent studies have linked mitochondrial dysfunction and NLRP3 activation in neuroinflammation-related diseases such as Parkinson's disease (Sarkar et al., npj Parkinson's disease 2017, 3:30; Zhou et al., Nature, 2011, 469, 221). One of the major problems associated with mitochondrial modulators is their poor metabolic stability; therefore, selective and stable inhibitors are needed for this type of neuroinflammation (Lee et al., Eur J. Org. Chem. 2017, 141, 240). These inflammasome-related diseases / disorders and others, such as autoinflammatory febrile syndrome cryopyrin-associated periodic syndrome (e.g., CAPS), sickle cell disease, chronic liver disease, nonalcoholic steatohepatitis (NASH), gout, hyperoxaluria, There is a need for inhibitors of the NLRP3 inflammasome pathway to provide new and / or alternative treatments for pseudogout (chondrocalcinosis), type I / type II diabetes and related complications (e.g., nephropathy, retinopathy), neuroinflammation-related disorders (e.g., multiple sclerosis, brain infections, acute injuries, neurodegenerative diseases, Alzheimer's disease), atherosclerosis and cardiovascular risk (e.g., cardiovascular risk reduction (CvRR), hypertension), hidradenitis suppurativa, wound healing and scar formation, and cancer (e.g., colon cancer, lung cancer, myeloproliferative neoplasms, leukemia, myelodysplastic syndromes (MDS), myelofibrosis). [Prior Art Document] [Patent Document].

[0008] (Patent Document 1) International Patent Publication No. W0 2016131098

[0009] (Patent Document 2) International Publication No. W0 2020021447

[0010] (Patent Document 3) International Publication No. W0 2020234715 [Non-patent Document]

[0011] (Non-patent document 1) A critical role for the NLRP3 inf lammasome in NASH, Hugh Thomas Nature Reviews Gastroenterology & Hepatology 2017: 14, 197 (Non-patent document 2) NLRP3 inf lammasome blockade reduces 1 iver inflammation and fibrosis in experimental NASH in mice, Mr i dha, AR et al. ,

[0012] J. Hepatol. 2017, 66, 1037-46

[0013] (Non-patent literature: Mortimer et al., Nature Immunol. 2016, 17(10), 1176 -

[0014] 1188

[0015] (Non-patent literature 4) Petrasek et al., J. Clin. Invest. 2012, 122, 3476-89

[0016] (Non-patent literature 5) Petrasek et al., Nat. Rev. Gastroenterol. Hepatol. 2015,

[0017] 387-400

[0018] (Non-patent literature 6) Ridker et al., N. Engl. J. Med. 2017, 377, 1119-31

[0019] (Non-patent literature 7) Mathews et al., Ann. Rheum. Dis. 2014, 73, 1202-10

[0020] (Non-patent literature 8) Knauf et al., Kidney Int. 2013, 84, 895-901

[0021] (Non-patent literature 9) Kr i shnan et al. , Br. J. Pharmacol. 2016, 173 , 752-65

[0022] (Non-patent document 10) Shahzad et al., Kidney Int. 2015, 87, 74—84

[0023] (Non-patent literature: hao et al., Front. Pharmacol. 2015, 6, 262

[0024] (Non-patent literature 12) Ridker et al., N. Engl. J. Med. 2017, 377, 1119-31

[0025] (Non-patent literature 13) Ridker et al., Lancet 2017, 390, 1833-42

[0026] (Non-patent literature 14) Sarkar et al., npj Parkinson's disease 2017, 3:30

[0027] (Non-patent literature 15) Zhou et al., Nature, 2011, 469, 221

[0028] (Non-patent literature 16) Lee et al., Eur J. Org. Chem. 2017, 141, 240

[0029]

Contents of the invention

[0030]

Technical Problem

[0031] [Technical Solution] The present invention is described in more detail below. All combinations of the various elements disclosed in the present invention fall within the scope of the present invention. Furthermore, the scope of the present invention is not limited by the specific description below. Compound The present invention provides a compound according to any one of the following (1) to (19), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

[0032] (1) A compound represented by the following chemical formula 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof: [Chemical formula 1] In the above chemical formula 1, R1 to R4 are two adjacent ones that form a ring together with the atoms to which they are attached, and the remaining two are each independently H, halogen, C1-C5 alkyl, 0-(Cl-C5 alkyl), C1-C5 haloalkyl or CN, wherein the ring is cycloalkyl, heterocycloalkyl or heteroaryl, and one or more of the cycloalkyl, heterocycloalkyl or heteroaryl may be independently substituted with halogen, C1-C5 alkyl, C1-C5 haloalkyl, OH, 0-CC1-C5 alkyl) or CN, and wherein when R1 and R2 form a ring, the ring is heterocycloalkyl or heteroaryl containing one or more heteroatoms independently selected from the group consisting of N and S,

[0033] R5 is H, C1-C5 alkyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heterocycloalkyl, heterocycloalkenyl, heterocycloalkynyl, aryl, heteroaryl, (C1-C5 alkyl)-cycloalkyl, (C1-C5 alkyl)-cycloalkenyl, (C1-C5 alkyl)-cycloalkynyl, (C1-C5 alkyl)-heterocycloalkyl, (C1-C5 alkyl)-heterocycloalkenyl, (C1-C5 alkyl)-heterocycloalkynyl, (C1-C5 alkyl)-aryl, (C1-C5 alkyl)-heteroaryl, (C1-C5 alkyl) - N (R x )(R y ), (C1-C5 alkyl)- CN or (C1-C5 alkyl)- O(R Z ) and,

[0034] One or more hydrogens of R5 are each independently R A can be replaced by R Ais halogen, OH, CN, C1-C5 alkyl, C2-C5 alkenyl, C2-C5 alkynyl, C1-C5 haloalkyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heterocycloalkyl, heterocycloalkenyl, heterocycloalkynyl, aryl, heteroaryl, (C1-C5 alkyl)-cycloalkyl, (C1-C5 alkyl)-cycloalkenyl, (C1-C5 alkyl)-cycloalkynyl, (C1-C5 alkyl)-heterocycloalkyl, (C1-C5 alkyl)-heterocycloalkenyl, (C1-C5 alkyl)-heterocycloalkynyl, (C1-C5 alkyl)-aryl, (C1-C5 alkyl)-heteroaryl, (C1- C5 alkyl) - N(R x )(R y ), (C1-C5 alkyl)- CN, (C1-C5 alkyl)- O(R Z ), C(=O)R1 or (C1-C5 alkyl) - C(=O)R m And,

[0035] R A One or more hydrogens are each independently R B can be replaced by R B is halogen, CN, C1-C5 alkyl, C1-C5 haloalkyl, N(R x )(R y ), O(R Z ), C(=O)R1 or S(=0)2R n and here R x , R y and R z are each independently H, C1-C5 alkyl or C1-C5 haloalkyl, and R1, Rm and R n are each independently H, OH, C1-C5 alkyl, 0-(Cl- C5 alkyl), N(R a )(R b ) or (C1-C5 alkyl) - N(R c )(R d ) and here R a , R b , R c and R dare each independently H, C1-C5 alkyl or C1-C5 haloalkyl,

[0036] R6 is H, OH, 0-CC1-C5 alkyl) or C1-C5 haloalkyl,

[0037] R7 is H, C1-C5 alkyl or C1-C5 haloalkyl, and halogen is F, Cl, Br or I.

[0038] (2) In the above (1), in the above chemical formula 1, two adjacent ones of R1 to R4 form a ring together with the atoms to which they are attached, and the remaining two are each independently H, halogen, C1-C5 alkyl, 0-(Cl-C5 alkyl), C1-C5 haloalkyl or CN, wherein the ring is cycloalkyl, heterocycloalkyl or heteroaryl, and one or more of the cycloalkyl, heterocycloalkyl or heteroaryl may be independently substituted with halogen, C1-C5 alkyl, C1-C5 haloalkyl, OH, 0-CC1-C5 alkyl) or CN, and wherein when R1 and R2 form a ring, the ring is heterocycloalkyl or heteroaryl including one or more heteroatoms independently selected from the group consisting of N and S,

[0039] R5 is H, C1-C5 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, (C1-C5 alkyl)-cycloalkyl, (C1-C5 alkyl)-heterocycloalkyl, (C1-C5 alkyl)-aryl, (C1-C5 alkyl)-heteroaryl, (C1-C5 alkyl)-N(R x )(R y ) or (C1-C5 alkyl)- 0(R z ) and,

[0040] One or more hydrogens of R5 are each independently R A can be replaced by R Ais halogen, OH, CN, C1-C5 alkyl, C2-C5 alkenyl, C2-C5 alkynyl, C1-C5 haloalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, (C1-C5 alkyl)-cycloalkyl, (C1-C5 alkyl)-heterocycloalkyl, (C1-C5 alkyl)-aryl, (C1-C5 alkyl)-heteroaryl, (C1-C5 alkyl) - N(R x )(R y ), (C1-C5 alkyl)- O(R Z ), C(=O)R1 or (C1-C5 alkyl) - C(=O)R m And,

[0041] R A One or more hydrogens are each independently R B can be replaced by R B is halogen, CN, C1-C5 alkyl, C1-C5 haloalkyl, N(R x )(R y ), O(R Z ), C(=O)R1 or S(=0)2R n and here R x , R y and R z are each independently H, C1-C5 alkyl or C1-C5 haloalkyl, and R1, R m and R n are each independently H, OH, C1-C5 alkyl, 0- (Cl- C5 alkyl), N(R a )(R b ) or (C1-C5 alkyl) - N(R c )(R d ) and here R a , R b , R c and R d are each independently H, C1-C5 alkyl or C1-C5 haloalkyl,

[0042] R6 is H, 0H or 0-CC1-C5 alkyl),

[0043] R7 is H, C1-C5 alkyl or C1-C5 haloalkyl, and the halogen can be F or C1.

[0044] (3) In the above (1) or (2), in the above chemical formula 1, two adjacent ones of R1 to R4 form a ring together with the atoms to which they are attached, and the remaining two are each independently H, halogen or C1-C5 alkyl, wherein the ring is cycloalkyl, heterocycloalkyl or heteroaryl, and one or more of the cycloalkyl, heterocycloalkyl or heteroaryl may be independently substituted with halogen, C1-C5 haloalkyl or 0-CC1-C5 alkyl, and wherein when R1 and R2 form a ring, the ring is heteroaryl including one or more heteroatoms independently selected from the group consisting of N and S,

[0045] R5 is C1-C5 alkyl, cycloalkyl, heterocycloalkyl, (C1-C5 alkyl)-heterocycloalkyl, (C1-C5 alkyl)-aryl, (C1-C5 alkyl)-heteroaryl, (C1-C5 alkyl) - N(R x )(R y ) or (C1-C5 alkyl)- O(R Z ) and,

[0046] One or more hydrogens of R5 are each independently R A can be replaced by R A is halogen, OH, C1-C5 alkyl, C2-C5 alkynyl, C1-C5 haloalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, (C1-C5 alkyl)-cycloalkyl, (C1-C5 alkyl)- O(R Z ), C(=O)R1 or (C1-C5 alkyl) - C(=O)R m And,

[0047] R A One or more hydrogens are each independently R B can be replaced by R B is halogen, CN, C1-C5 alkyl, O(RZ ), C(=O)R1 or S(=OhR n and here R x , R y and R z are each independently H, C1-C5 alkyl or C1-C5 haloalkyl, and R1, R m and R n are each independently OH, C1-C5 alkyl, 0-CC1-C5 alkyl) or N(R a )(R b ) and here R a and R b are each independently H or C1-C5 alkyl,

[0048] R6 is H, 0H or 0-CC1-C5 alkyl),

[0049] R7 is C1-C5 alkyl or C1-C5 haloalkyl, and the halogen can be F or C1.

[0050] (4) In any one of the above (1) to (3), in the above chemical formula 1, two of R1 to R3 are adjacent to each other and form a ring together with the atoms to which they are attached, and the remaining one is shown, wherein the ring is a heteroaryl including one or more heteroatoms independently selected from the group consisting of N and S,

[0051] R4 is visible,

[0052] R5 is C1-C5 alkyl, cycloalkyl, heterocycloalkyl, (C1-C5 alkyl)-heterocycloalkyl, (C1-C5 alkyl)-aryl, (C1-C5 alkyl) - N(R x )(R y ) or (C1-C5 alkyl)- O(R Z ) and,

[0053] One or more hydrogens of R5 are each independently R A can be replaced by R Ais halogen, OH, C1-C5 alkyl, C1-C5 haloalkyl, cycloalkyl, heterocycloalkyl, aryl, (C1-C5 alkyl)-cycloalkyl, (C1-C5 alkyl)- O(R Z ), C(=O)R1 or (C1-C5 alkyl) - C(=O)R m And,

[0054] R A One or more hydrogens are each independently R B can be replaced by R B is halogen, C1-C5 alkyl, O(R Z ) or C(=O)R1, where R x , R y and R z are each independently H, C1-C5 alkyl or C1-C5 haloalkyl, and R1, R m and R n are each independently OH, C1-C5 alkyl, 0-CC1-C5 alkyl) or N(R a )(R b ) and here R a and R b are each independently C1-C5 alkyl,

[0055] R6 is H, 0H or 0- (Cl- C5 alkyl),

[0056] R7 is C1-C5 alkyl and halogen can be F.

[0057] (5) In the above (1) or (2), the compound represented by the chemical formula 1 can be represented by the following chemical formula 1a.

[0058] [Chemical Formula 1a] In the above chemical formula 1a, A is heterocycloalkyl or heteroaryl containing one or more heteroatoms independently selected from the group consisting of N and , and one or more groups of A may be independently substituted with halogen, C1-C5 alkyl, C1-C5 haloalkyl, OH, 0-CC1-C5 alkyl) or ,

[0059] R3 and R4 are each independently H, halogen, C1-C5 alkyl, 0-CC1-C5 alkyl), C1- C5 haloalkyl or CN,

[0060] R5, R6, R7 and halogen are the same as defined in the above chemical formula 1.

[0061] (6) In any one of the above (1) to (3), the compound represented by the chemical formula 1 may be represented by the following chemical formula 1a. [Chemical formula 1a]

[0062] In the above chemical formula 1a,

[0063] A is a heteroaryl containing one or more heteroatoms independently selected from the group consisting of N and , and one or more of A may be independently substituted with halogen, C1-C5 haloalkyl or 0-CC1-C5 alkyl,

[0064] Rs and R4 are each independently H, halogen or C1-C5 alkyl, and R5, R6, R7 and halogen are the same as defined in the above chemical formula 1.

[0065] (7) In any one of the above (1) to (4), the compound represented by the above chemical formula 1 can be represented by the following chemical formula 1a.

[0066] [Chemical Formula 1a] In the above chemical formula 1a,

[0067] A is a heteroaryl containing one or more heteroatoms independently selected from the group consisting of N and ,

[0068] R3 and R4 appear independently, and R5, R6, R7 and halogen are the same as defined in the above chemical formula 1.

[0069] (8) In the above (1) or (2), the compound represented by the chemical formula 1 can be represented by the following chemical formula 1b.

[0070] [Chemical Formula 1b] In the above chemical formula 1b,

[0071] A is cycloalkyl, heterocycloalkyl or heteroaryl, and one or more of A may be independently substituted with halogen, C1-C5 alkyl, C1-C5 haloalkyl, OH, 0-CC1-C5 alkyl) or ash, and R1 and R4 are each independently H, halogen, C1-C5 alkyl, 0-CC1-C5 alkyl), C1-

[0072] C5 haloalkyl or CN, and R5, R6, R7 and halogen are the same as defined in the above chemical formula 1. (9) In one of the above (1) to (3), the compound represented by the above chemical formula 1 can be represented by the following chemical formula 1b.

[0073] [Chemical Formula 1b] In the above chemical formula 1b,

[0074] A is cycloalkyl, heterocycloalkyl or heteroaryl, and one or more of A may be independently substituted with halogen, C1-C5 haloalkyl or 0-CC1-C5 alkyl, R1 and R4 are each independently H, halogen or C1-C5 alkyl, and R5, R6, R7 and halogen are the same as defined in the above chemical formula 1.

[0075] (10) In one of the above (1) to (4), the compound represented by the chemical formula 1 can be represented by the following chemical formula 1b.

[0076] [Chemical Formula 1b]

[0077] In the above chemical formula 1b,

[0078] A is a heteroaryl containing one or more heteroatoms independently selected from the group consisting of N and , R1 and R4 are each independently present, and R5, R6, R7 and halogen are the same as defined in the above chemical formula 1.

[0079] (11) In the above (1) or (2), the compound represented by the chemical formula 1 may be represented by the following chemical formula 1c. [Chemical formula 1c] In the above chemical formula 1C,

[0080] A is cycloalkyl, heterocycloalkyl or heteroaryl, and one or more of A may be independently substituted with halogen, C1-C5 alkyl, C1-C5 haloalkyl, OH, 0-CC1-C5 alkyl) or urethane, and R1 and R2 are each independently H, halogen, C1-C5 alkyl, 0-CC1-C5 alkyl), C1-C5 haloalkyl or CN, and R5, R6, R7 and halogen are the same as defined in the above formula 1.

[0081] (12) In any one of the above (1) to (3), the compound represented by the chemical formula 1 may be represented by the following chemical formula 1c.

[0082] [Chemical Formula 1c] In the above chemical formula 1c,

[0083] A is cycloalkyl, heterocycloalkyl or heteroaryl, and one or more of A may be independently substituted with halogen, C1-C5 haloalkyl or 0-CC1-C5 alkyl, R1 and R2 are each independently H, halogen or C1-C5 alkyl, and R5, R6, R7 and halogen are the same as defined in the above chemical formula 1. (13) In any one of the above (1), (2) and (5), the compound represented by the above chemical formula 1 may be represented by the following chemical formula 1a-1.

[0084] [Chemical Formula 1a-1] In the above chemical formula 1a-1,

[0085] Wi and W2 are each independently CH, CH2, N, NH or S,

[0086] R xis H, halogen, C1-C5 alkyl, C1-C5 haloalkyl, 0H, 0- (Cl- C5 alkyl) or CN,

[0087] R3 and R4 are each independently H, halogen, C1-C5 alkyl, 0-CC1-C5 alkyl), C1- C5 haloalkyl or CN,

[0088] = is each independently a single bond or a double bond, and R5, R6, R7 and halogen are the same as defined in the above chemical formula 1.

[0089] (14) In any one of the above (1) to (3), (5) and (6), the compound represented by the chemical formula 1 may be represented by the following chemical formula 1a-1.

[0090] [Chemical Formula 1a-1]

[0091] In the above chemical formula 1a-1,

[0092] Wi and W2 are each independently CH, CH2, N, NH or S,

[0093] R x is H, halogen, C1-C5 haloalkyl or 0-CC1-C5 alkyl), and R3 and R4 are each independently H, halogen or C1-C5 alkyl,

[0094] = is each independently a single bond or a double bond, and R5, R6, R7 and halogen are the same as defined in the above chemical formula 1.

[0095] (15) In any one of the above (1) to (7), the compound represented by the chemical formula 1 may be represented by the following chemical formula 1a-1.

[0096] [Chemical Formula 1a-1] In the above chemical formula 1a-1, Wi and W2 are each independently CH, CH2, N, NH or S,

[0097] R x is visible,

[0098] Rs and R4 are reported independently,

[0099] = is each independently a single bond or a double bond, and R5, R6, R7 and halogen are the same as defined in the above chemical formula 1.

[0100] (16) In any one of the above (1), (2), (5) and (13), the compound represented by the chemical formula may be represented by the following chemical formula 1a-2 or chemical formula 1a-3.

[0101] [Chemical Formula 1a-2]

[0102] [Chemical Formula 1a-3] In each of the above chemical formula 1a-2 or chemical formula 1a-3, R3 and R4 are each independently H, halogen, C1-C5 alkyl, C1-C5 haloalkyl, 0-

[0103] (C1-C5 alkyl) or CN, and R5, R6, R7 and halogen are the same as defined in the above chemical formula 1. (17) In any one of (1) to (3), (5), (6), (13) and (14), the compound represented by the above chemical formula 1 can be represented by the following chemical formula 1a-2 or chemical formula 1a-3.

[0104] [Chemical Formula 1a-2] [Chemical Formula 1a-3] In each of the above chemical formula 1a-2 or chemical formula 1a-3,

[0105] Rs and R4 are each independently H, halogen or C1-C5 alkyl, and R5, R6, R7 and halogen are the same as defined in the above chemical formula 1.

[0106] (18) In any one of the above (1) to (7) and (13) to (15), the compound represented by the above chemical formula 1 can be represented by the following chemical formula 1a-2 or chemical formula 1a-3.

[0107] [Chemical Formula 1a-2] In each of the above chemical formula 1a-2 or chemical formula 1a-3,

[0108] Rs and R4 appear independently, and R5, R6, R7 and halogen are the same as defined in the above chemical formula 1. In the present invention, “Cm-Cn” (wherein m and n are each independently an integer of 1 or more) means the number of carbons, for example, ‘C1-C5 alkyl’ represents alkyl having 1 to 5 carbon atoms. In the present invention, “alkyl” means a straight-chain or branched-chain saturated hydrocarbon group. In the present invention, alkyl may have 1 to 5 carbon atoms. In one embodiment, alkyl may have 1 to 4 carbon atoms. Examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, isobutyl, n-pentyl, sec-pentyl, tert-pentyl, isopentyl, sec-isopentyl, neo-pentyl, etc. In the present invention, “alkenyl” means a straight-chain or branched unsaturated hydrocarbon group containing one or more double bonds. In the present invention, alkenyl may have 2 to 5 carbon atoms. In one embodiment, alkenyl may have 2 to 4 carbon atoms. Examples of alkenyl include, but are not limited to, ethenyl, allyl, propenyl, etc. In the present invention, “alkynyl” means a straight-chain or branched unsaturated hydrocarbon group containing one or more triple bonds. In the present invention, alkynyl may have 2 to 5 carbon atoms. In one embodiment, alkynyl may have 2 to 4 carbon atoms. Examples of alkynyl include, but are not limited to, ethynyl, propynyl, butynyl, etc. In the present invention, “haloalkyl” means alkyl substituted with a halogen such as F, Cl, Br, I of at least one atom. The meaning of alkyl is as defined above. In the present invention, “cycloalkyl” means a saturated or partially unsaturated hydrocarbon ring having 3 or more carbon atoms, which includes both monocyclic and polycyclic ring structures.For example, in the present invention, the cycloalkyl may be a saturated hydrocarbon ring or a partially unsaturated hydrocarbon ring fused to an aromatic ring (e.g., aryl or heteroaryl). For example, in the present invention, the cycloalkyl may be a ring having 3 to 12, 3 to 10, or 3 to 8 carbon atoms. Examples of cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicyclopentyl, bicyclohexyl, bicycloheptyl, bicyclooctyl, bicyclononyl, spiropentyl, spiroheptyl, spiroctyl, spirononyl, cyclobutyl fused to phenyl, cyclopentyl fused to phenyl, cyclohexyl fused to phenyl, cycloheptyl fused to phenyl, and the like. In the present invention, “cycloalkenyl” means an unsaturated hydrocarbon ring having three or more carbon atoms including one or more double bonds, and includes both monocyclic and polycyclic ring structures. That is, in the present invention, cycloalkenyl may mean a ring structure including one or more carbon-carbon double bonds within the cycloalkyl ring defined above. In the present invention, cycloalkenyl may be a ring having 3 to 12, 3 to 10, or 3 to 8 carbon atoms. Examples of cycloalkenyl include, but are not limited to, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, etc. In the present invention, "cycloalkynyl" means an unsaturated hydrocarbon ring containing one or more triple bonds, and includes both monocyclic and polycyclic ring structures. That is, cycloalkynyl in the present invention may mean a ring structure containing one or more triple bonds within the cycloalkyl ring defined above.Examples of cycloalkynyl include, but are not limited to, cyclooctynyl. In the present invention, “heterocycloalkyl” means a cyclic functional group in which at least one carbon atom forming the cycloalkyl ring defined above is substituted with a heteroatom. Examples of the heteroatom may be nitrogen (N), oxygen (0), or sulfur (S). At this time, the heteroatom contained in the heterocycloalkyl ring may be one or two or more, one or more of one type of heteroatom may be included, and at least one or more of two or more types of heteroatoms may be included. For example, in the present invention, the heterocycloalkyl may be a 3- to 12-membered ring. For example, in the present invention, the heterocycloalkyl may be a 3- to 8-membered ring having 1 to 3 heteroatoms. For example, in the present invention, heterocycloalkyl may be a 4-6 membered ring having 1 or 2 heteroatoms. Examples of heterocycloalkyl include, but are not limited to, oxiranyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl, thiomorpholinyl, tetrahydrothiophenyl, and tetrahydrothiopyranyl. In the present invention, “heterocycloalkenyl” means a cyclic functional group in which at least one carbon atom forming the cycloalkenyl ring defined above is substituted with a heteroatom. Examples of the heteroatom may be nitrogen (N), oxygen (0), or sulfur (S). At this time, the heteroatom included in the heterocycloalkenyl ring may be one type or two or more types, one type of heteroatom may be included one or more than one, and two or more types of heteroatoms may each be included at least one or more. In the present invention, “heterocycloalkynyl” means a cyclic functional group in which at least one carbon atom forming the cycloalkynyl ring defined above is substituted with a heteroatom.Examples of the above heteroatoms include nitrogen (N), oxygen (0), or sulfur (S). At this time, the heteroatoms contained in the heterocycloalkynyl ring may be one or two or more, one or more of one type of heteroatom may be included, and at least one or more of two or more types of heteroatoms may be included. In the present invention, “aryl” means a monocyclic or polycyclic aromatic hydrocarbon ring. For example, in the present invention, aryl may have 6 to 20 carbon atoms. Examples of aryl include, but are not limited to, phenyl, biphenyl, naphthalenyl, etc. In the present invention, “heteroaryl” means a monocyclic or polycyclic aromatic hydrocarbon ring containing at least one heteroatom such as nitrogen (N), oxygen (0), or sulfur (S). For example, in the present invention, the heteroaryl may be a 5- to 12-membered ring. For example, in the present invention, the heteroaryl may be a 5- to 8-membered ring having 1 to 3 heteroatoms. For example, in the present invention, the heteroaryl may be a 5- or 6-membered ring having 1 or 2 heteroatoms. When the heteroaryl contains two or more heteroatoms, the types of the heteroatoms may be the same or different. For example, when the heteroaryl contains two or more heteroatoms selected from nitrogen, oxygen, and sulfur, it means various combinations such as a case where it contains two nitrogens, a case where it contains one nitrogen and one oxygen, a case where it contains two oxygens and one nitrogen, and the like.Examples of heteroaryl include pyridinyl, thiophenyl, triazolyl, tetrazolyl, benzothiazolyl, benzothiophenyl, quinolinyl, indolyl, isoindolyl, benzofuranyl, benzopyrrolyl, furanyl, pyrrolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, oxazolyl, isooxazolyl, pyrazinyl, pyridazinyl, pyrimidinyl, isoquinolinyl, benzoxazolyl, benzoimidazolyl, dihydrobenzothiophenyl, purinyl, indolizinyl, chromenyl, pyrrolopyridinyl, pyrazolopyridinyl, thiadiazolopyridinyl, triazinyl, Triazolopyrimidinyl, triazolopyridinyl, triazolopyridazinyl, indazolyl, imidazopyridinyl, imidazopyridazinyl, oxadiazolopyridinyl, benzothiadiazolyl, benzotriazolyl, benzoxadiazole, isomers thereof, etc. are mentioned, but are not limited thereto. In the present invention, alkyl, alkenyl, alkynyl, haloalkyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, cycloalkynyl, heterocycloalkyl, heterocycloalkenyl, and heterocycloalkynyl refer to all monovalent substituents or divalent or more polyvalent substituents of the chemical structure according to their respective definitions. For example, “alkyl” may include monovalent alkyl or divalent alkyl (alkylene), and “aryl” may include monovalent aryl or divalent aryl (arylene). In the present invention, “halogen” may be F, Cl, Br, or I.

[0109] (19) The compound according to the present invention, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof may be a compound described in Table 1 below.

[0110] [Table 1] In the present invention, “pharmaceutically acceptable salt” means a salt commonly used in the pharmaceutical industry, and can be prepared by a conventional method known to those skilled in the art. In the present invention, the pharmaceutically acceptable salt includes, for example, an inorganic ionic salt prepared with calcium, potassium, sodium, or magnesium; an inorganic acid salt prepared with hydrochloric acid, nitric acid, phosphoric acid, hydrobromic acid, iodic acid, perchloric acid, or sulfuric acid; an organic acid salt prepared with acetic acid, trifluoroacetic acid, citric acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, mandelic acid, propionic acid, lactic acid, glycolic acid, gluconic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid, ascorbic acid, carbonic acid, vanillic acid, hydroiodic acid, and the like; Sulfonate manufactured with methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid or naphthalenesulfonic acid, amino acid salt manufactured with glycine, arginine, lysine, etc.; or amine salt manufactured with trimethylamine, triethylamine, ammonia, pyridine, picoline, etc., but the types of salts meant in the present invention are not limited by these listed salts. In the present invention, “stereoisomer” includes diastereomer and enantiomeric isomer, and enantiomeric isomer includes not only enantiomeric but also mixtures of enantiomeric isomers and racemates. These isomers can be separated by resolution using conventional techniques, for example, column chromatography or HPLC. Alternatively, each stereoisomer of the compound according to any one of (1) to (19) of the present invention can be stereospecifically synthesized using optically pure starting materials and / or reagents of known arrangement.In the present invention, “prevention” means any act of inhibiting or delaying the onset of a disease by administering a compound according to any one of (1) to (19) of the present invention, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. In the present invention, “treatment” means any act of improving or beneficially changing the symptoms of a subject suspected of or suffering from a disease by administering a compound according to any one of (1) to (19) of the present invention, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. In the present invention, “NLRP3” is meant to include nucleic acids, polynucleotides, oligonucleotides, sense and antisense polynucleotide strands, complementary sequences, peptides, polypeptides, proteins, homologous and / or orthologous NLRP3 molecules, isoforms, precursors, mutants, variants, derivatives, splice variants, alleles, other species, and active fragments thereof. The compound according to any one of (1) to (19) of the present invention, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof can be usefully used for the prevention or treatment of NLRP3 activity-related diseases. The compound according to any one of (1) to (19) of the present invention, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof can inhibit NLRP3 or the NLRP3 inflammasome pathway, which may include a decrease in the ability of NLRP3 or the NLRP3 inflammasome pathway to induce the production of IL-1P. The compound according to any one of (1) to (19) of the present invention, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof can exhibit a preventive or therapeutic effect on NLRP3 activity-related diseases at a level similar to or substantially the same as or better than a drug for the prevention or treatment of NLRP3 activity-related diseases known in the art.Composition, Method and Use The present invention provides a pharmaceutical composition comprising a compound according to any one of (1) to (19) of the present invention, a stereoisomer thereof or a pharmaceutically acceptable salt thereof as an active ingredient. The present invention also provides a pharmaceutical composition for preventing or treating a disease associated with NLRP3 activity, comprising a compound according to any one of (1) to (19) of the present invention, a stereoisomer thereof or a pharmaceutically acceptable salt thereof as an active ingredient. That is, a pharmaceutical composition comprising a compound according to any one of (1) to (19) of the present invention, a stereoisomer thereof or a pharmaceutically acceptable salt thereof as an active ingredient can be usefully used for preventing or treating a disease associated with NLRP3 activity. The above NLRP3 activity-related diseases may include inflammation, autoimmune diseases, cancer, infections, central nervous system diseases, metabolic diseases, cardiovascular diseases, respiratory diseases, liver diseases, kidney diseases, eye diseases, skin diseases, lymphatic conditions, psychological disorders, graft-versus-host disease, allodynia, wounds, scars, etc. Inflammation may include inflammation occurring as a result of an inflammatory disorder, such as an autoinflammatory disease, inflammation occurring as a symptom of a non-inflammatory disorder, inflammation occurring as a result of an infection, or inflammation occurring as a result of infection or inflammation secondary to injury or autoimmunity, etc.Autoimmune diseases include acute disseminated encephalitis, Addison's disease, ankylosing spondylitis, antiphospholipid antibody syndrome (APS), antisynthetase antibody syndrome, aplastic anemia, autoimmune adrenalitis, autoimmune infections, autoimmune oophoritis, autoimmune polyglandular insufficiency, autoimmune thyroiditis, celiac disease, Crohn's disease, type 1 diabetes (T1D), Goodpasture syndrome, Graves' disease, Galin-Barré syndrome (GBS), Hashimoto's disease, idiopathic thrombocytopenic purpura, Kawasaki disease, lupus erythematosus including systemic lupus erythematosus (SLE), primary progressive multiple sclerosis (PPMS), secondary progressive multiple sclerosis (SPMS), and Multiple sclerosis (MS) including relapsing remitting multiple sclerosis (RRMS), myasthenia gravis, opsoclonus myoclonus syndrome (OMS), optic neuritis, Ord's thyroiditis, pemphigus, pernicious anemia, polyarthritis, primary biliary cirrhosis, rheumatoid arthritis (R. A), psoriatic arthritis, juvenile idiopathic arthritis or Still's disease, refractory gouty arthritis, Reiter's syndrome, Sjögren's syndrome, multiple sclerosis, systemic connective tissue disorders, Takayasu's arteritis, temporal arteritis, warm autoimmune hemolytic anemia, Wegener's granulomatosis, alopecia universalis, Behcet's disease, Chagas' disease, dysautonomia, endometriosis, hidradenitis suppurativa (HS), interstitial cystitis, neuromyotonia, psoriasis, sarcoidosis, scleroderma, congestive colitis, Schnitzler syndrome, macrophage activation syndrome, Blau syndrome, vitiligo, or vulvar pain. Cancer, including lung cancer, pancreatic cancer, stomach cancer, myelodysplastic syndrome, leukemia including acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML), adrenal cancer, anal cancer, basal squamous cell skin cancer, cholangiocarcinoma, bladder cancer, bone cancer, brain and spinal tumors, breast cancer, cervical cancer, chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), chronic myelomonocytic leukemia (CMML), colorectal cancer, endometrial cancer, esophageal cancer, Ewing series tumor, eye cancer, gallbladder cancer, gastrointestinal carcinoid tumor, gastrointestinal stromal tumor (GIST), gestational trophoblastic disease, glioma, Hodgkin lymphoma, Kaposi sarcoma, kidney cancer, hypopharyngeal cancer, liver cancer, lung carcinoid tumor, lymphoma including cutaneous T-cell lymphoma, malignant mesothelioma, Melanoma skin cancer, Merkel cell skin cancer, multiple myeloma, nasal and paranasal cancer, nasopharyngeal cancer, neuroblastoma, non-Hodgkin's lymphoma, non-small cell lung cancer, oral and oropharyngeal cancer, osteosarcoma, ovarian cancer, penile cancer, pituitary tumor, prostate cancer, retinoblastoma, rhabdomyosarcoma, salivary gland cancer, skin cancer, small cell lung cancer, small intestine cancer, soft tissue sarcoma, stomach cancer, testicular cancer, thymic cancer, thyroid cancer including anaplastic thyroid cancer, uterine sarcoma, vaginal cancer, vulvar cancer, Waldenström macroglobulinemia, Wilms tumor, etc. Infections may include,Viral infections (e.g., influenza virus, human immunodeficiency virus (HIV), alphaviruses (e.g., Chikungunya and Ross River virus), flaviviruses (e.g., Dengue virus and Zika virus), herpes viruses (e.g., Epstein-Barr virus, cytomegalovirus, varicella-zoster virus and KSHV), poxviruses (e.g., vaccinia virus (modified vaccinia virus Ankara) and myxoma virus), adenoviruses (e.g., adenovirus 5 or papillomavirus), bacterial infections (e.g., Staphylococcus aureus, Helicobacter pylori, Bacillus anthracis, Bordatel la pertussis), Burkholderia pseudomallei, Corynebacterium aiptheriae, Clostridium tetani, Clostridium botulinum, Streptococcus pneumoniae, Streptococcus pyogenes, Listeria monocytogenes, Hemophilus influenzae, Pasteurella multicida, Shigella dysenteriae, Mycobacterium tuberculosis, Mycobacterium leprae bacterium leprae), Mycoplasma pneumoniae,Mycoplasma hominis, Neisseria meningitidis, Neisseria gonorrhoeae, Rickettsia rickettsii, Legionella pneumophila, Klebsiella pneumoniae, Pseudomonas aeruginosa, Propionibacterium acnes, Treponema pallidum, Chlamydia trachomatis, Vibrio cholerae, Salmonella typhimurium , Salmonella typhf, Borrelia burgdorferi or Yersinia pestis, fungal infections (e.g., from Candida species or Aspergillus species), protozoan infections (e.g., from malaria parasites, Babesia, Giardia, Entamoeba, Leishmania or Trypanosomes), helminth infections (e.g., from schistosomiasis, roundworms, tapeworms or trematodes), prion infections, etc. Central nervous system diseases may include Parkinson's disease, Alzheimer's disease, dementia, motor neuron disease, Huntington's disease, cerebral malaria, brain damage from pneumococcal meningitis, cerebral aneurysm, traumatic Brain damage and amyotrophic lateral sclerosis may include metabolic diseases such as type 2 diabetes (T2D), atherosclerosis, obesity, gout, pseudogout, etc. Cardiovascular diseases may include hypertension, ischemia,Reperfusion injury including ischemic reperfusion injury after MI, stroke including ischemic stroke, transient ischemic attack, myocardial infarction including recurrent myocardial infarction, renal failure including congestive heart failure and heart failure with preserved ejection fraction, embolism, aneurysm including abdominal aortic aneurysm, or pericarditis including Dressler syndrome, etc. Respiratory diseases may include chronic obstructive pulmonary disease (COPD), asthma (e.g., allergic asthma and steroid-resistant asthma), asbestosis, silicosis, nanoparticle-induced inflammation, cystic fibrosis, idiopathic pulmonary fibrosis, etc. Liver diseases may include non-alcoholic fatty liver disease (NAFLD) including progressive fibrosis stages F3 and F4, non-alcoholic steatohepatitis (NASH), alcoholic fatty liver disease (AFLD), and alcoholic steatohepatitis (ASH). Kidney diseases may include chronic kidney disease, oxalate nephropathy, nephrocalcinosis, glomerulonephritis, and diabetic nephropathy. Eye diseases may include ocular epithelial diseases, age-related macular degeneration (AMD) (dry and wet), uveitis, corneal infections, diabetic retinopathy, optic nerve damage, dry eye, and glaucoma. Skin diseases may include dermatitis (e.g., contact dermatitis and atopic dermatitis), contact hypersensitivity, sunburn, skin lesions, hidradenitis suppurativa (HS), other cyst-induced skin diseases, acne clusters, etc. Lymphatic conditions may include lymphangitis, Castleman's disease, etc. Psychological disorders may include depression, psychological stress, etc. The pharmaceutical composition of the present invention comprises a compound according to any one of (1) to (19) of the present invention,In addition to its stereoisomer or pharmaceutically acceptable salt, it may further comprise one or more pharmaceutically acceptable carriers. Pharmaceutically acceptable carriers are those commonly used in the art, and specifically, may be lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidine, cellulose, water, syrup, methyl cellulose, methyl hydroxybenzonate, propyl hydroxybenzonate, talc, magnesium stearate or mineral oil, but are not limited thereto. The pharmaceutical composition of the present invention may further comprise, in addition to the above components, a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifier, a suspending agent, a preservative, a dispersing agent, a stabilizer, etc. In addition, the pharmaceutical composition of the present invention may be formulated in the form of oral dosage forms such as tablets, powders, granules, pills, capsules, suspensions, emulsions, liquid solutions, emulsions, syrups, etc., external preparations, suppositories, or sterile injectable solutions using pharmaceutically acceptable carriers and excipients, and may be manufactured in unit dosage form or may be manufactured by inserting into a multi-dose container. The preparation may be manufactured by a conventional method used in formulation in the art or by a method disclosed in Remington's Pharmaceutical Science (19th ed., 1995), and may be formulated into various preparations depending on each disease or ingredient. Non-limiting examples of oral administration preparations using the pharmaceutical composition of the present invention include tablets, troches, lozenges, aqueous suspensions, oily suspensions, prepared powders, granules, emulsions, hard capsules, soft capsules, syrups or elixirs. In order to formulate the pharmaceutical composition of the present invention for oral administration, lactose, saccharose, sorbitol, mannitol, starch, amylopectin,Binders such as cellulose or gelatin; excipients such as dicalcium phosphate; disintegrants such as corn starch or sweet potato starch; lubricants such as magnesium stearate, calcium stearate, sodium stearyl fumarate or polyethylene glycol wax; and sweeteners, fragrances, syrups, etc. can be used. Furthermore, in the case of capsules, in addition to the above-mentioned substances, liquid carriers such as fatty oils can be additionally used. Non-limiting examples of parenteral preparations using the pharmaceutical composition of the present invention include injections, suppositories, powders for respiratory inhalation, aerosols for sprays, ointments, powders for application, oils, creams, etc. In order to formulate the pharmaceutical composition of the present invention for parenteral administration, a sterile aqueous solution, non-aqueous solvent, suspension, emulsion, freeze-dried preparation, external preparation, etc. can be used. As the non-aqueous solvent and suspension, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate, etc. can be used, but are not limited thereto. The present invention provides a method for preventing or treating a disease associated with NLRP3 activity, which comprises administering to a subject a compound according to any one of (1) to (19) of the present invention, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. In the present invention, “administration” means introducing a predetermined substance to a subject by an appropriate method. In the present invention, “subject” means all animals, such as rats, mice, livestock, etc., including humans, that have developed or may develop a disease associated with NLRP3 activity, and may specifically be mammals including humans, but is not limited thereto. The method for preventing or treating a disease related to NLRP3 activity of the present invention comprises a compound according to any one of (1) to (19) of the present invention,It may be to administer a stereoisomer thereof or a pharmaceutically acceptable salt thereof in a therapeutically effective amount. In the present invention, the “therapeutically effective amount” means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment and not causing side effects, which can be determined by those skilled in the art based on factors including the patient’s sex, age, weight, health condition, type and severity of the disease, activity of the drug, sensitivity to the drug, administration method, administration time, administration route, excretion rate, treatment period, drugs used in combination or simultaneously, and other factors well known in the medical field. It is preferable to apply a specific therapeutically effective amount for a specific patient differently depending on various factors including the type and degree of response to be achieved, the specific composition including whether other agents are used in some cases, the patient’s age, weight, general health condition, sex and diet, administration time, administration route and excretion rate of the composition, treatment period, drugs used in combination or simultaneously with the specific composition, and similar factors well known in the medical field. The present invention provides a use of a compound according to any one of (1) to (19) of the present invention, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a composition comprising the same, for the prevention or treatment of a disease associated with NLRP3 activity. The present invention provides a use of a compound according to any one of (1) to (19) of the present invention, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a composition comprising the same, for the manufacture of a medicament for the prevention or treatment of a disease associated with NLRP3 activity. For the manufacture of a medicament, a pharmaceutically acceptable adjuvant, diluent, carrier, etc. may be mixed with a compound according to any one of (1) to (19) of the present invention, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and may be manufactured into a composite preparation with other active agents to have a synergistic effect. The compound of the present invention,The matters mentioned in the pharmaceutical composition, treatment method and use apply equally unless they are contradictory.

[0111]

Effect of the invention

[0112]

Mode for carrying out the invention

[0113] Intermediate Synthesis

[0114] [Step 1] Synthesis of Inter-A1 Under a nitrogen atmosphere, (R)-tert-butyl piperidin-3-ylcarbamate (600 mg, 3 mmol) and potassium carbonate (622 mg, 4.5 mmol) were dissolved in acetonitrile (ACN, 6.6 ml), and then iodoethane (0.27 ml, 3.3 mmol) was slowly added at 0°C. The reaction mixture was stirred at room temperature for 16 hours. After completion of the reaction, the reaction mixture was washed with water and an aqueous sodium chloride solution, and the organic layer was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The concentrated reaction mixture was purified by silica gel column chromatography (Me0H / DCM=1 / 10) to obtain the target compound Inter-A1 (567 mg, 83%) as a yellow oil. 1 H NMR (400MHz, DMSO—d6) 5 6.65 (d, J = 7.8Hz, 1H) , 3.32 (s, 1H) , 2.70 (dd, J = 41.0, 9.7Hz, 2H) , 2.29 (q, J = 7.1Hz, 2H) , 1.83-1.53 ​​(m, 4H), 1.48-1.40 (m, IH), 1.37 (s, 9H), 1.11 (qd, J = 11.8, 3.7Hz, IH), 0.96 (t, J = 7.2Hz, 3H); LC / MS: m / z 229.2 (M+H)+(ES). [Step 2] Synthesis of Inter-A2 Under a nitrogen atmosphere, Inter-A1 (567 mg, 2.34 mmol) was added to a 4N hydrochloric acid solution (4N HCI in 1,4-dioxane, 9.6 ml). The reaction mixture was stirred at room temperature for 3 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure to obtain the target compound Inter-A2 (420.78 mg, 89.4%) as a yellow solid.

[0115] 1H NMR (400MHz, DMS0-d6) 5 3.59-3.57 (m, 2H) , 3.43 (br, IH) , 3.17-

[0116] 3.14 (m, 2H), 2.85-2.78 (m, 2H), 2.10-2.08 (m, IH), 1.91-1.90 (m, 2H), 1.55

[0117] (br, IH), 1.26 (t, J = 7.2, 3H); LC / MS: m / z 129.1 (M+H)+(ES). Intermediate Inter—A4

[0118] [Step 1] Synthesis of Inter-A3 Under nitrogen atmosphere, (R)-tert-butyl piperidin-3-ylcarbamate (600 mg,

[0119] 3 mmol) was dissolved in methanol (MeOH, 6 ml), and potassium carbonate (1.66 g, 12 mmol) and 2-bromoethane-1-ol (0.42 ml, 6 mmol) were added. The reaction mixture was stirred at room temperature for 16 hours. After completion of the reaction, the reaction mixture was washed with water and aqueous sodium chloride solution, and the organic layer was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (Me0H / DCM=1 / 10) to obtain the target compound Inter-A3 (663 mg, 91%) as a yellow oil.

[0120] 1 H NMR (400MHz, DMS0-d6) 5 2.73-2.71 (m, 1H) , 2.62-2.59 (m, 1H) , 1.99-1.91 (m, IH), 1.84-1.79 (m, IH) , 1.64-1.56 (m, 2H) , 1.22-1.10 (m, IH); LC / MS: m / z 245.2 (M+H)+(ES).

[0121] [Step 2] Synthesis of Inter-A4 Under nitrogen atmosphere, Inter-A3 (663 mg, 2.71 mmol) was added to 4N hydrochloric acid solution (4N

[0122] HC1 in 1,4-dioxane, 11.1 ml) was added. The reaction mixture was then stirred at room temperature for 3 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure to obtain the target compound Inter-A4 (467 mg, 79%) as a white solid.

[0123] 1 H NMR (400MHz, DMS0-d6) 5 3.80-3.78 (m, 2H) , 3.72-3.68 (m, IH) , 3.57 (s, 2H), 3.52-3.48 (m, IH) , 3.02-2.90 (m, 2H) , 2.09-2.07 (m, IH), 1.91

[0124] -1.87 (m, 2H), 1.60-1.49 (m, IH); LC / MS: m / z 145.1 (M+H)+(ES). Intermediate Inter— A6

[0125] [Step 1] Synthesis of Inter-A5 Under a nitrogen atmosphere, (R)-tert-butyl piperidin-3-ylcarbamate (600 mg, 3 mmol) was dissolved in dichloromethane (DCM, 15 ml), and then sodium triacetoxyborohydride (954 mg, 4.5 mmol) and acetone (0.24 ml, 3.3 mmol) were added. The reaction mixture was stirred at room temperature for 16 hours. After completion of the reaction, the reaction mixture was washed with water and aqueous sodium carbonate solution, and the organic layer was extracted with dichloromethane. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The concentrated reaction mixture was purified by silica gel column chromatography (Me0H / DCM=1 / 10) to obtain the target compound Inter-A5 (461 mg, 63%) as a yellow solid.

[0126] 1 H NMR (400MHz, CDCI3) 8 5.10 (s, IH) , 3.73 (s, IH) , 2.76-2.68 (m, IH), 2.59-2.57 (m, IH) , 2.49-2.37 (m, 2H) , 1.69-1.67 (m, IH) , 1.55-1.50 (m, 3H), 1.45 (s, 9H), 0.99 (d, J = 6.8 Hz, 6H); LC / MS: m / z 243.2 (M+H)+(ES).

[0127] [Step 2] Synthesis of Inter-A6 Under nitrogen atmosphere, Inter-A5 (461 mg, 2.71 mmol) was added to 4N hydrochloric acid solution (4N

[0128] HCI in 1,4-dioxane, 11.1 ml) was added. The reaction mixture was then stirred at room temperature for 3 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure to obtain the target compound Inter-A6 (395 mg, 68%) as a brown solid.

[0129] 1 H NMR (400MHz, CDC13) 8 12.04 (s, 1H) , 9.32 (s, 3H) , 4.54-4.50 (m, 2H) , 4.33-4.30 (m, 3H) , 3.72-3.63 (m, 2H) , 2.90-2.87 (m, 1H) , 2.80-2.71 (m, 2H) , 2.43-2.35 (m, 1H) , 2.04 (d, J = 5.2 Hz, 6H); LC / MS: m / z 143.1 (M+H)+(ES) . Intermediates Inter-A7 to Inter-A12 Inter-A7 to Inter-A12 in Table 2 below were synthesized using a synthetic method substantially identical to that of Inter-A6, except that the carbonyls in Table 2 below were used instead of propan-2-one in the synthetic scheme of Inter-A6 above.

[0130] [Table 2] Intermediate Inter— A14

[0131] [Step 1] Synthesis of Inter-A13 (R)-tert-butyl piperidin-3-ylcarbamate (400 mg, 2 mmol) was dissolved in acetonitrile (ACN, 4 ml), and then sodium carbonate (417 mg, 3 mmol) and bromomethylcyclobutane (0.29 ml, 2.6 mmol) were added. The reaction mixture was stirred at reflux for 16 hours. After completion of the reaction, the reaction mixture was washed with aqueous sodium carbonate solution, and the organic layer was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated under reduced pressure to obtain the target compound Inter-A13 (477 mg, 97%) as a white solid.

[0132] 1 H NMR (400MHz, CDCls) 8 5.00 (s, 1H) , 3.70 (s, 1H) , 2.54-2.38 (m, 3H), 2.34-2.33 (m, 2H) , 2.94-2.21 (m, 2H) , 2.08-2.00 (m, 2H) , 1.92-1.76 (m,

[0133] 2H), 1.70-1.60 (m, 3H), 1.53-1.48 (m, 2H), 1.44 (s, 9H); LC / MS: m / z 269.2

[0134] (M+H)+(ES).

[0135] [Step 2] Synthesis of Inter-A14

[0136] Inter-A13 (477 mg, 1.97 mmol) was added to a 4N hydrochloric acid solution (4N HC1 in 1,4-dioxane, 8 ml). The reaction mixture was stirred at room temperature for 3 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure to obtain the target compound Inter-A14 (437 mg, 92%) as a white solid.

[0137] 1 H NMR (400MHz, DMS0-d6) 5 10.85 (s, IH) , 8.34 (s, 3H) , 3.54-3.46 (m, 2H), 3.18-3.16 (m, 2H) , 2.83-2.75 (m, 3H) , 2.11-2.03 (m, 3H), 1.94-1.78 (m, 7H), 1.51-1.42 (m, IH); LC / MS: m / z 169.1 (M+H)+(ES). Intermediate Inter—A15 Methyl 3-((tert-butoxycarbonyl)amino)bicyclo[1.1.1]pentane-1-carboxylate (200 mg, 0.829 mmol) was added to a 4N hydrochloric acid solution (4N HC1 in 1,4-di oxane, 5.0 ml). The reaction mixture was stirred at room temperature for 2 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure to obtain the target compound Inter-A15 (171 mg, 96.6%) as a white solid.

[0138] 1 H NMR (400MHz, DMS0-d6) 5 8.91 (s, 2H), 3.63 (s, 3H), 2.24 (s, 6H);

[0139] LC / MS: m / z 142.1 (M+H)+(ES).

[0140] [Step 1] Synthesis of Inter-A16

[0141] (R)-tert-butyl azepane-3-ylcarbamate (600 mg, 2.8 mmol), potassium carbonate

[0142] (774 mg, 5.6 mmol) was dissolved in acetonitrile (ACN, 11 ml), and iodomethane (0.2 ml, 3.4 mmol) was added. The reaction mixture was stirred at 80°C for 16 hours. After completion of the reaction, the mixture was filtered using Celite and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (Me0H / MC=1 / 20) to obtain the target compound Inter-A16 (257 mg, 40%) as a yellow liquid.

[0143] 1 H NMR (400MHz, Methanol -d4) 5 3.85-3.81 (m, IH) , 3.39-3.28 (m, 4H), 2.92 (s, 3H), 2.04-1.83 (m, 4H) , 1.77-1.66 (m, 2H) , 1.47 (s, 9H); LC / MS: m / z 229.2 (M+H)+(ES).

[0144] [Step 2] Synthesis of Inter-A17 Under a nitrogen atmosphere, Inter-A16 (257 mg, 1.13 mmol) was added to a 4N hydrochloric acid solution (4N HC1 in 1,4-dioxane, 2.8 ml). The reaction mixture was stirred at room temperature for 4 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure to obtain the target compound Inter-A17 (182 mg, 80.4%) as an orange solid.

[0145] 1H NMR (400MHz, Methanol -d4) 5 3.87-3.84 (m, 1H), 3.58-3.56 (m, 2H), 3.39-3.34 (m, IH), 2.24-2.19 (m, IH), 2.02-1.87 (m, 6H); LC / MS:m / z 129.1 (M+H)+(ES). Intermediates Inter— A18 to Inter— A20 and Inter— A30 to Inter— A33 Inter-A18 to Inter- A20 and Inter- A30 to Inter- A33 in Table 3 were synthesized by substantially the same synthetic method as that of Inter- A4, except that the halides in Table 3 below were used instead of 2-bromoethane-1-ol in the Inter- A4 synthetic scheme.

[0146] [Table 3] Intermediate Inter— A22

[0147] [Step 1] Synthesis of Inter-A21 (R)-tert-butyl piperidin-3-ylcarbamate (600 mg, 3 mmol) was dissolved in acetonitrile (ACN, 6 ml), and potassium carbonate (553 mg, 4 mmol) and methyl chloroacetate (0.53 ml, 6 mmol) were added. The reaction mixture was stirred at room temperature for 16 hours. After completion of the reaction, the reaction mixture was filtered using Celite and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (MeOH / DCM=l:9) to obtain the target compound Inter-A21 (810 mg, 99.1%) as a white solid.

[0148] 1H NMR (400MHz, CDCls) 8 5.06 (s, 1H) , 3.76 (m, 1H) , 3.71 (s, 3H) , 3.22 (s, 2H), 2.68-2.59 (m, 2H) , 2.47-2.45 (m, 2H) , 1.77-1.68 (m, IH), 1.59- 1.54 (m, 3H), 1.44 (s, 9H); LC / MS: m / z 273.1 (M+H)+(ES). [Step 2] Synthesis of Inter-A22 Under a nitrogen atmosphere, Inter-A21 (810 mg, 2.97 mmol) was added to a 4N hydrochloric acid solution (4N HC1 in 1,4-dioxane, 12 ml). The reaction mixture was stirred at room temperature for 16 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure to obtain the target compound Inter-A22 (441 mg, 86.1%) as a white solid.

[0149] 1 H NMR (400MHz, DMS0-d6) 5 8.44 (s, 2H) , 4.13-4.12 (m, 2H) , 3.74 (s, 3H), 3.60-3.39 (m, 3H) , 2.94-2.68 (m, 2H) , 1.99-1.80 (m, 3H), 1.50 (m, IH); LC / MS: m / z 173.1 (M+H)+(ES).

[0150] [Step 1] Synthesis of Inter-A23

[0151] (R)-tert-butyl piperidin-3-ylcarbamate (1.2 g, 6 mmol) was dissolved in acetic acid (AcOH, 3.42 ml) and methanol (48 ml), and then sodium cyanoborohydride (1.51 g, 24 mmol) and (1-ethoxycyclopropoxy)trimethylsilane (1.81 ml, 9 mmol) were added. The reaction mixture was stirred at room temperature for 16 hours. After completion of the reaction, the reaction mixture was filtered using Celite and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (MeOH / DCM=l:9) to obtain the target compound Inter-A23 (860 mg, 62%) as a white solid.

[0152] 1 H NMR (400MHz, CDCls) 8 5.23-4.75 (m, 1H), 3.80-3.60 (m, 1H), 2.80-2.10 (m, 4H), 1.75-1.25 (m, 13H), 0.75-0.25 (m, 4H); LC / MS: m / z 241.1 (M+H)+(ES).

[0153] [Step 2] Synthesis of Inter-A24 Under a nitrogen atmosphere, Inter-A23 (860.4 mg, 3.58 mmol) was added to a 4N hydrochloric acid solution (4N HC1 in 1,4-dioxane, 14.7 ml). The reaction mixture was stirred at room temperature for 3 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure to obtain the target compound Inter-A24 (787 mg, 75%) as a white solid.

[0154] 1H NMR (400MHz, Methanol -d4) 5 3.69-3.62 (m, 3H) , 3.21-3.18 (m, 2H), 2.86 (s, IH), 2.15-1.92 (m, 3H) , 1.66 (s, IH) , 1.14-1.11 (m, 2H) , 0.97-0.91 (m, 2H); LC / MS: m / z 141.1 (M+H)+(ES). Intermediate Sieve Inter—A26

[0155] [Step 1] Synthesis of Inter-A25 Under a nitrogen atmosphere, 2,2,2-trifluoroethyl trifluoromethanesulfonate (1.68 g, 7.2 mmol) was dissolved in ethyl acetate (6 ml) and water (6 ml), and then sodium bicarbonate (3.8 g, 30 mmol) was added. Then, (R)-tert-butyl piperidin-3-ylcarbamate (1.2 g, 6 mmol) dissolved in ethyl acetate (4 ml) was slowly added, and the mixture was stirred at 50°C for 16 hours. After completion of the reaction, the reaction mixture was washed with water and aqueous sodium chloride solution, and the organic layer was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (Me0H / DCM=1 / 10) to obtain the target compound Inter-A25 (1.36 g, 81%) as a white solid.

[0156] 1 H NMR (400 MHz, CDCI3) 8 4.97 (s, 1H) , 3.75 (s, 1H) , 2.98 (q, J = 9.4 Hz, 2H), 2.82 (d, J = 11.7 Hz, IH) , 2.64-2.76 (m, IH) , 2.46-2.64 (m, 2H) , 1.66-1.81 (m, IH), 1.60 (m„ 3H) , 1.45 (s, 9H); LC / MS: m / z 283.1 (M+H)+(ES).

[0157] [Step 2] Synthesis of Inter-A26 Under a nitrogen atmosphere, Inter-A25 (1.36 g, 4.82 mmol) was added to a 4N hydrochloric acid solution (4N HC1 in 1,4-dioxane, 19.8 ml). The reaction mixture was stirred at room temperature for 3 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure to obtain the target compound Inter-A26 (1.1 g, 86%) as a white solid.

[0158] 1 H NMR (400MHz, DMS0-d6) 5 8.27 (s. , 3H) , 3.39 (q, J= 10.2 Hz, 2H) , 3.15-3.27 (m, IH) , 3.10 (dd, J= 11.3, 3.0 Hz, IH) , 2.83 (d,J= 11.7 Hz, IH) , 2.56 (d, J= 10.2 Hz, IH) , 2.45 (d, J= 9.8 Hz, IH) , 1.83-2.04 (m, IH) , 1.62- 1.83 (m, IH), 1.45-1.62 (m, IH) , 1.25-1.45 (m, IH); LC / MS: m / z 183.1 (M+H)+(ES).

[0159]

[0160] [Step 1] Synthesis of Inter-A27 Under a nitrogen atmosphere, ethyl (S)-(-)-2-(tert-butyldimethylsilyloxy) propionate (330 |iL, 1 mmol) was dissolved in dichloromethane (5 ml), and then diisobutylaluminum hydride (1.2 ml, 1.2 mmol) was slowly added at -78°C. The reaction mixture was stirred at -78°C for 2 hours, and then methanol and an aqueous solution of potassium sodium tartrate were added to terminate the reaction. The reaction mixture was then extracted with hexane, and the organic layer was dried over magnesium sulfate and concentrated under reduced pressure to obtain the target compound Inter-A27 (188 mg, 92%) as a transparent liquid.

[0161] 1 H NMR (400MHz, DMS0-d6) 5 9.54 (d, J= 0.7 Hz, 1H) , 4.25 (qd, J= 6.9, 0.7 Hz, IH), 1.21 (d, J= 3.0 Hz, 3H) , 0.89 (s, 9H) , 0.08 (d, J= 4.6 Hz, 6H).

[0162] [Step 2] Synthesis of Inter-A28 Under a nitrogen atmosphere, Inter-A27 (47 mg, crude) was dissolved in dichloromethane (1 ml), and then sodium triacetoxyborohydride (85 mg, 0.4 mmol) and (R)-tert-butyl piperidin-3-ylcarbamate (46 mg, 0.23 mmol) were added. The reaction mixture was stirred at room temperature for 16 hours. After completion of the reaction, the reaction mixture was extracted with water and dichloromethane, and the organic layer was dried over sodium sulfate and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (Me0H / DCM=1 / 10) to obtain the target compound Inter-A28 (65 mg, 76%) as a white solid.

[0163] 1 H NMR (400MHz, CDC13) 8 5.02 (br, 1H) , 3.92-3.84 (m, 1H) , 3.72 (br, 1H), 2.50 (br, 2H) , 2.33-2.26 (m, 3H) , 2.18-2.14 (m, IH) , 1.67 (br, IH), 1.56 (s, 3H), 1.45 (s, 9H), 1.13 (d, J = 6.0Hz, 3H), 0.89 (s, 9H), 0.06 (s, 6H); LC / MS: m / z 273.3 (M+H)+(ES).

[0164] [Step 3] Under a synthetic nitrogen atmosphere of Inter-A29, Inter-A28 (70 mg, 0.19 mmol) was added to and dissolved in tetrahydrofuran (1.2 ml), and then tetrabutylammonium fluoride (282 μl, 0.28 mmol) was added. Subsequently, the reaction mixture was stirred at room temperature for 16 hours. After the reaction was completed, the reaction mixture was extracted with water and dichloromethane, the organic layer was dried using sodium sulfate, and then concentrated under reduced pressure. Subsequently, 4N hydrochloric acid solution (4N HCl in 1,4-dioxane, 1.5 ml) was added to the reaction concentrate, and the reaction mixture was stirred at room temperature for 4 hours. After the reaction was completed, the reaction mixture was concentrated under reduced pressure to obtain the target compound Inter-A29 (44 mg, 99.1%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 8.42 (s, 3H), 5.49 (br, 1H), 4.15 (br, 1H), 3.22 - 2.85 (m, 4H), 2.07 - 1.75 (m, 1H), 1.53 - 1.48 (m, 3H), 1.11 (s, 3H); LC / MS: m / z 159.1 (M+H)+(ES). Intermediate Inter-A35 lnter-A35

[0165] [Step 1] Synthesis of Inter-A34

[0166] 1,1-Dimethylethyl N-[(1R)-4-hydroxy-1-

[0167] (Hydroxymethyl)butyl]carbamate (836 mg, 3.81 mmol) was dissolved in dichloromethane (DCM, 13.1 mL), and triethylamine (TEA, 2.7 ml, 19.1 mmol) and methanesulfonyl chloride (0.71 ml, 9.2 mmol) were added at 0°C. The reaction mixture was stirred at room temperature for 2 hours. After completion of the reaction, the reaction mixture was washed with an aqueous sodium bicarbonate solution, and the organic layer was extracted with dichloromethane. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. To the reaction concentrate, tert-butyl amine (6 ml, 57.2 mmol) was added. The reaction mixture was stirred at room temperature for 16 hours. After completion of the reaction, the reaction mixture was washed with an aqueous sodium carbonate solution, and the organic layer was extracted with dichloromethane. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (MeOH / DCM=lO:l) to obtain the target compound Inter-A34 (500 mg, 51%) as a brown liquid.

[0168] 1 H NMR (400MHz, Methanol -d4) 5 3.57-3.54 (m, 1H) , 3.06-3.04 (m, 1H), 2.90-2.87 (m, IH) , 2.22-2.17 (m, IH) , 2.05-2.02 (m, IH) , 1.85-1.81 (m, IH), 1.77-1.71 (m, IH), 1.63-1.54 (m, IH), 1.45 (s, 9H), 1.271.15 (m, IH), 1.12 (s, 9H); LC / MS: m / z 257.1 (M+H)+(ES).

[0169] [Step 2] Synthesis of Inter-A35

[0170] Inter-A34 (500 mg, 1.95 mmol) was dissolved in methanol (MeOH, 7.8 mL), and hydrochloric acid (HC1, 0.78 ml) was added at 0°C. The reaction mixture was stirred at room temperature for 3 days. After completion of the reaction, the reaction mixture was concentrated under reduced pressure to obtain the target compound Inter-A35 (376 mg, 98%) as a white solid.

[0171] LC / MS: m / z 157.1 (M+H)+(ES). Intermediate Inter—A37 [Step 1] Synthesis of Inter-A36 Under a nitrogen atmosphere, tert-butyl (3R,5R)-5-fluoropiperidin-3-ylcarbamate (400 mg, 1.83 mmol) and potassium carbonate (380 mg, 2.75 mmol) were dissolved in acetonitrile (ACN, 4 ml), and then iodoethane (0.16 ml, 2.02 mmol) was slowly added at 0°C. The reaction mixture was stirred at room temperature for 16 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure, and the concentrated product was purified by silica gel column chromatography (Me0H / DCM=1 / 10) to obtain the target compound Inter-A36 (422 mg, 94%) as a yellow solid.

[0172] 1 H NMR (400MHz, CDCls) 8 4.89-4.69 (m, 2H) , 3.99 (bs, 1H) , 2.86 (m, 1H), 2.54-2.44 (m, 4H) , 2.33-2.30 (m, IH) , 2.05 (m, IH) , 1.74-1.82 (m, IH), 1.45 (s, 9H), 1.06 (t, J= 7.2 Hz, 3H); LC / MS: m / z 247.1 (M+H)+(ES).

[0173] [Step 2] Synthesis of Inter-A37 Under a nitrogen atmosphere, Inter-A36 (422 mg, 1.71 mmol) was added to a 4N hydrochloric acid solution (4N HC1 in 1,4-dioxane, 5 ml). The reaction mixture was stirred at room temperature for 16 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure to obtain the target compound Inter-A37 (486 mg, 100%) as a light-colored solid.

[0174] LC / MS: m / z 147.1 (M+H)+(ES). Intermediate Inter— A38 to Inter— A40 Inter-A38 to Inter-A40 in Table 4 were synthesized using a synthetic method substantially identical to that of Inter-A37, except that the halides in Table 4 below were used instead of ethyl iodide in the synthetic scheme of Inter-A37.

[0175] [Table 4] Intermediate Inter-A42 lnter-A41 lnter-A42

[0176] [Step 1] Synthesis of Inter-A41 Under a nitrogen atmosphere, tert-butyl (3R, 5R)-5-fluoropiperidin-3-ylcarbamate (400 mg, 1.83 mmol) was dissolved in dichloromethane (DCM, 6 ml), and then sodium triacetoxyborohydride (437 mg, 2.06 mmol) and cyclobutanone (0.11 ml, 1.51 mmol) were added. The reaction mixture was stirred at room temperature for 16 hours. After completion of the reaction, the reaction mixture was washed with water and aqueous sodium carbonate solution, and the organic layer was extracted with dichloromethane. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (Me0H / DCM=1 / 10) to obtain the target compound Inter-A41 (266 mg, 71%) as a yellow solid.

[0177] 1 H NMR (400MHz, CDCls) 8 4.88-4.66 (m, 2H) , 3.97 (bs, 1H) , 2.80-2.74 (m, 2H), 2.32-2.27 (m, 2H) , 2.11-1.97 (m, 4H) , 1.91-1.60 (m, 8H), 1.74-1.82 (m, IH), 1.45 (s, 9H); LC / MS: m / z 273.1 (M+H)+(ES).

[0178] [Step 2] Synthesis of Inter-A42 Under a nitrogen atmosphere, Inter-A41 (266 mg, 0.977 mmol) was added to a 4N hydrochloric acid solution (4N HC1 in 1,4-dioxane, 7 ml). The reaction mixture was stirred at room temperature for 16 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure to obtain the target compound Inter-A42 (239 mg, 100%) as a white solid.

[0179] LC / MS: m / z 173.1 (M+H)+(ES). Intermediate Inter— A43 Inter— A43 in Table 5 below was synthesized using a synthetic method substantially identical to that of Inter— A42, except that the carbonyls in Table 5 below were used instead of cyclobutanone in the synthetic scheme of Inter— A42 above. [Table 5] Intermediate Inter— A47

[0180] [Step 1] Synthesis of Inter-A44 Under a nitrogen atmosphere, diisobutyl aluminum hydride solution (1 M DIBAL in toluene, 24 ml) was dissolved in toluene (10 ml), and then 1-(tert-butyl-dimethyl-silanyloxy)-cyclopropanecarboxylic acid methyl ester (1 g, 4.34 mmol) was added at -78°C. The mixture was stirred for 3 hours at -78°C. The reaction was quenched using methanol and sodium potassium tartrate solution, and the reaction mixture was stirred at room temperature for 10 minutes. The reaction mixture was washed with aqueous sodium bicarbonate solution, and the organic layer was extracted with diethyl ether. The organic layer was dried using sodium sulfate and concentrated under reduced pressure to obtain the target compound Inter-A44 (512 mg, 58.3%) as a transparent liquid.

[0181] 1 H NMR (400MHz, CDCls) 8 3.43-2.42 (m, 2H) , 2.23 (s, 4H) , 1.68 (t, J = 6.0 Hz, IH), 1.48 (s, 2H), 0.75 (s, 9H) , 0.67-0.64 (m, 2H) , 0.48-0.45 (m, 2H); LC / MS: m / z 203.1 (M+H)+(ES).

[0182] [Step 2] Synthesis of Inter-A45 Under a nitrogen atmosphere, dimethyl sulfoxide (DMS0, 0.4 ml) was added to dichloromethane (DCM, 8.6 ml) at -78°C, followed by slow addition of oxalyl chloride (0.2 ml, 2.8 mmol) and Inter-A44 (512 mg, 2.53 mmol). The mixture was stirred at -78°C for 1 hour, and triethylamine (TEA, 1.76 ml) was added. After completion of the reaction, the reaction mixture was warmed to 0°C, washed with 1 N hydrochloric acid solution (IN HC1), and the organic layer was extracted with dichloromethane to obtain the target compound Inter-A45 (849.5 mg) as a transparent liquid.

[0183] 1 H NMR (400MHz, CDCI3) 8 8.92 (s, IH), 1.29-1.08 (m, 4H), 0.77 (s, 9H), 0.59 (s, 6H); LC / MS: m / z 201.1 (M+H)+(ES).

[0184] [Step 3] Synthesis of Inter-A46 Under a nitrogen atmosphere, Inter-A45 (849.5 mg, 4.2 mmol) was dissolved in dichloromethane (DCM, 19 ml), and then sodium triacetoxyborohydride (1.06 g, 5 mmol) and (R)-tert-butyl piperidin-3-ylcarbamate (771 mg, 3.85 mmol) were added. The reaction mixture was stirred at room temperature for 16 hours. After completion of the reaction, the reaction mixture was washed with water and an aqueous sodium carbonate solution, and the organic layer was extracted with dichloromethane. The organic layer was dried over sodium sulfate and concentrated under reduced pressure to obtain the target compound Inter-A46 (667 mg, 85%) as a white solid.

[0185] 1H NMR (400MHz, CDCls) 8 5.16 (br, 1H) , 3.74 (br, 1H) , 2.66-2.61 (br, 2H), 2.46-2.40 (m, IH) , 2.33-2.29 (m, IH) , 2.20 (br, IH) , 1.86 (br, IH) , 1.74-1.65 (m, IH), 1.59-1.48 (m, 3H) , 1.44 (s, 9H) , 0.86 (s, 9H) , 0.71-0.68 (m, 2H), 0.46-0.44 (m, 2H) , 0.11-0.10 (m, 6H); LC / MS: m / z 385.3 (M+H)+(ES).

[0186] [Step 4] Synthesis of Inter-A47 Under a nitrogen atmosphere, Inter-A46 (667 mg, 1.73 mmol) was added to tetrahydrofuran (THF, 7.3 ml), followed by the addition of tetrabutylammonium fluoride solution (TBAF in THF, 3.4 ml). The reaction mixture was stirred at room temperature for 16 hours. After completion of the reaction, the reaction mixture was washed with water, and the organic layer was extracted with dichloromethane. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. Thereafter, under a nitrogen atmosphere, the reaction mixture was added to a 4N hydrochloric acid solution (4N HC1 in 1,4-dioxane, 13.6 ml). The reaction mixture was stirred at room temperature for 4 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure to obtain the target compound Inter-A47 (387 mg, 92%) as a white solid.

[0187] LC / MS: m / z 171.1 (M+H)+(ES). Intermediate Inter—A49

[0188] [Step 1] Synthesis of compound Inter-A48 Under a nitrogen atmosphere, tert-butyl (3R,5R)-5-fluoropiperidin-3-ylcarbamate (400 mg, 1.83 mmol) and diisopropylethylamine (DIPEA, 0.958 mL, 5.50 mmol) were dissolved in acetonitrile (ACN, 4 ml), and then ethyl chloroformate (0.21 ml, 2.75 mmol) was slowly added at 0°C. The reaction mixture was stirred at room temperature for 16 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure, and the concentrated product was purified by silica gel column chromatography (Me0H / DCM=1 / 10) to obtain the target compound Inter-A48 (523 mg, 99%) as a yellow solid.

[0189] 1 H NMR (400MHz, Methanol -d4) 5 4.91-4.79 (m, 1H) , 4.18-4.13 (m, 4H) , 3.76 (bs, IH), 3.07 (dd, J= 21.6 Hz, 14.4 Hz, IH) , 2.75-2.65 (m, IH) , 1.72- 1.46 (m, 10H), 1.28 (t, J= 6.8 Hz, 7.2H); LC / MS: m / z 291.1 (M+H)+(ES).

[0190] [Step 2] Synthesis of Compound Inter-A49 Under a nitrogen atmosphere, compound Inter-A48 (523 mg, 1.80 mmol) was added to a 4N hydrochloric acid solution (4N HCl in 1,4-dioxane, 10 ml). The reaction mixture was then stirred at room temperature for 16 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure to obtain the target compound Inter-A49 (423 mg, 89.4%) as an off-white solid.

[0191] LC / MS: m / z 191.1 (M+H)+(ES). Intermediate Inter—B5

[0192] [Step 1] Synthesis of Inter-Bl CuBr2 (73.3 g, 328 mmol)> Add to ethyl acetate (EA, 100 ml),

[0193] The mixture was stirred at 80°C for 30 minutes. Afterwards, 4, 5, 6, 7-tetrahydrobenzothiophen-4-one (10 g, 65.6 mmol) was dissolved in chloroform (CHCh, 100 ml) and slowly added at 80°C. The reaction mixture was then stirred at 80°C for 16 hours. After completion of the reaction, the reaction mixture was filtered using Celite and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (EA / Hexane=1 / 10) to obtain the target compound Inter-Bl (18.1 g, 89%) as a brown solid.

[0194] 1 H NMR (400MHz, CDCls) 8 7.07 (d, J = 3.6Hz, 1H) , 6.75 (s, 1H) , 6.30

[0195] (d, J = 3.6Hz, IH), 4.33 (q, J = 7.2Hz, 2H), 1.37 (t, J = 7.2Hz, 3H); LC / MS: m / z 242.0 (M+H)+(ES).

[0196] [Step 2] Synthesis of Inter-B2 Compound Inter-Bl (18.1 g, 58.4 mmol) was dissolved in dimethylformamide (DMF, 180 ml), and lithium carbonate (25.9 g, 350 mmol) was added. The reaction mixture was stirred at 100°C for 6 hours. After completion of the reaction, the reaction mixture was washed with water and an aqueous ammonium chloride solution, and the organic layer was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated under reduced pressure to obtain the target compound Inter-B2 (13 g, 97%) as a purple solid.

[0197] 1H NMR (400MHz, CDCls) 8 8.67 (br, 1H) , 6.75 (s, 1H) , 6.32 (s, 1H) , 4.34 (q, J = 7.2Hz, 2H) , 1.37 (t, J = 7.2Hz, 3H); LC / MS: m / z 214.0 (M+H)+(ES).

[0198] [Step 3] Synthesis of Inter-B3 Compound Inter-B2 (13.0 g, 56.7 mmol) was dissolved in acetone (130 ml), and potassium carbonate (15.7 g, 113 mmol) and iodomethane (7.07 ml, 113 mmol) were added. The reaction mixture was stirred at 40°C for 16 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (EA / Hexane=1 / 10) to obtain the target compound Inter-B3 (9.41 g, 68%) as a white solid.

[0199] 1 H NMR (400MHz, DMS0-d6) 5 11.47 (br, IH), 9.36 (s, IH), 6.77 (s, IH), 6.65 (s, IH), 4.35 (br, 2H); LC / MS: m / z 200.0 (M+H)+(ES).

[0200] [Step 4] Synthesis of Inter-B4 Compound Inter-B3 (500 mg, 2.06 mmol) was dissolved in 1,4-dioxane (15 ml), and Pd(PPh3)4 (713 mg, 0.617 mmol), bis(pinacolato)diboron (2.09 g, 8.23 ​​mmol), and potassium acetate (808 mg, 8.23 ​​mmol) were added. The reaction mixture was stirred at 100°C for 16 hours. After completion of the reaction, the reaction mixture was filtered using Celite and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (EA / Hexane=1 / 4) to obtain the target compound Inter-B4 (358 mg, 60%) as a white solid.

[0201] 1 H NMR (400MHz, CDC13) 8 9.05 (br, 1H) , 7.15 (s, 1H) , 6.59 (s, 1H) , 3.21 (sixt, J = 6.8, 13.6 Hz, IH) , 1.40 (d, J = 6.8Hz, 6H); LC / MS: m / z 251.9 (M+H)+(ES).

[0202] [Step 5] Synthesis of Inter-B5 Compound Inter-B4 (350 mg, 1.21 mmol) was dissolved in dichloromethane (DCM, 20 ml), and 1 M boron tribromide (1 M BBrs in DCM, 2.41 ml, 2.41 mmol) was added at 0°C. The reaction mixture was stirred at 0°C for 1 hour. - The reaction was quenched by slowly adding ice water at 15°C, and the organic layer was extracted using ethyl acetate. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. The concentrated reaction mixture was purified by silica gel column chromatography (MeOH / DCM=l:9) to obtain the target compound Inter-B5 (125 mg, 53%) as a white solid.

[0203] 1H NMR (400MHz, CDCI3) 8 7.13 (s, IH) , 6.58 (s, IH) , 6.42 (d, J = 6.8 Hz, IH), 4.68 (s, 2H) , 4.00 (sixt, J = 8 Hz, IH) , 3.20 (sept, J = 6.8 Hz, IH), 2.53-2.48 (m, 2H), 2.04-1.98 (m, 2H), 1.40 (d, J = 6.4 Hz, 6H), 1.36 (s, 3H); LC / MS: m / z 393.0 (M+H)+(ES). Intermediate Inter- B7

[0204] [Step 1] Synthesis of Inter-B6 Compound Inter-B2 (466 mg, 2.03 mmol) was dissolved in dichloromethane (DCM, 1.65 ml), and N,N-diisopropylethylamine (DIPEA, 0.57 ml, 3.25 mmol) and chloromethyl methyl ether (0.23 g, 3.05 mmol) were slowly added at 0°C. The reaction mixture was stirred at room temperature for 16 hours. After completion of the reaction, the reaction mixture was washed with water and an aqueous sodium chloride solution, and the organic layer was extracted with dichloromethane. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (EA / Hexane=1 / 10) to obtain the target compound Inter-B6 (412 mg, 74%) as a clear liquid.

[0205] 1 H NMR (400MHz, CDCls) 8 7.51-7.47 (m, 3H) , 7.43-7.42 (m, 1H) , 5.27

[0206] (s, 2H), 3.70 (s, 3H). [Step 2] Synthesis of Inter-B7 Under a nitrogen atmosphere, Inter-B6 (412 mg, 1.51 mmol), Pd(dppf)C12 (55 mg, 0.08 mmol), bis(pinacolato)diboron (766 mg, 3.02 mmol), potassium acetate (444 mg, 4.52 mmol) were added to 1,4-dioxane (1,4-dioxane, 4.9 ml). The reaction mixture was then stirred at 100°C for 16 hours. After completion of the reaction, the reaction mixture was filtered using Celite and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (EA / Hexane=1 / 10) to obtain the target compound Inter-B7 (340 mg, 70%) as a white solid.

[0207] 1 H NMR (400 MHz, CDCls) 8 7.71 (d, J = 8.0 Hz, 1H) , 7.63 (dd, J = 8.2, 0.6 Hz, IH), 7.55 (dd, J = 5.6, 0.8 Hz, IH) , 7.35 (d, 5.6 Hz, IH) , 5.25

[0208] (s, 2H), 3.62 (s, 3H), 1.37 (s, 12H). Intermediate Inter- B13

[0209]

[0210] [Step 1] Synthesis of Inter-B8

[0211] 6, 7 -dehydro-4-benzo[b]thiophene (6 g, 39.42 mmol), potassium hydroxide (8 g,

[0212] 141.91 mmol) was dissolved in ethylene glycol (62 ml), and then hydrazine monohydrate (NH2NH2-H20, 6.35 ml, 130.08 mmol) was added. After that, the reaction was stirred at 190°C.

[0213] The mixture was stirred for 4 hours. After the reaction was completed, the reaction mixture was washed with water, and the organic layer was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (EA / Hexane=1 / 30) to obtain the target compound Inter-B8 (1.96 g, 36%) as a transparent liquid.

[0214] 1 H NMR (400MHz, CDCls) 8 7.03 (d, J = 5.2 Hz, 1H) , 6.74 (d, J = 5.2 Hz, IH), 2.77 (t, J = 5.8 Hz, 2H), 2.62 (t, J = 6.0 Hz, 2H) , 1.86-1.78 (m, 4H).

[0215] [Step 2] Synthesis of Inter-B9

[0216] Inter-B8 (1.96 g, 14.18 mmol) was dissolved in acetic acid (AcOH, 58 ml), and then ammonium cerium (IV) nitrate (31.09 g, 56.72 mmol) dissolved in water OW, 19 ml) was added. The reaction mixture was stirred at room temperature for 5 hours. After completion of the reaction, the reaction mixture was washed with water, and the organic layer was extracted with dichloromethane. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (EA / Hexane=1 / 20) to obtain the target compound Inter-B9 (1.10 g, 51%) as a red liquid.

[0217] 1 H NMR (400 MHz, CDCls) 8 7.61 (d, J = 4.8 Hz, 1H) , 6.97 (d, J = 4.8 Hz, IH), 2.77 (t, J = 5.8 Hz, 2H) , 2.62 (t, J = 6.0 Hz, 2H) , (quin, J = 12.3, 6.3 Hz, 2H).

[0218] [Step 3] Synthesis of Inter-BIO

[0219] CuBr2 (9.68 g, 43.361 mmol) was dissolved in ethyl acetate (EA, 24 ml), and then Inter-B9 (1.10 g, 7.23 mmol) dissolved in chloroform (CHCh, 24 ml) was added. The reaction mixture was stirred at 80°C for 16 hours. After completion of the reaction, the reaction mixture was filtered using Celite and concentrated under reduced pressure. The reaction concentrate was washed with water, and the organic layer was extracted using ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (EA / Hexane=1 / 10) to obtain the target compound Inter-B10 (1.61 g, 72%) as a pink solid. 1 H NMR (400MHz, CDCls) 8 7.74 (d, J = 4.8 Hz, 1H) , 6.99 (d, J = 4.8 Hz, IH), 3.12 (t, J = 5.8 Hz, 2H) , 3.00 (t, J = 6.0 Hz, 2H) .

[0220] [Step 4] Synthesis of Inter-Bll

[0221] Inter-B10 (1.61 g, 5.35 mmol) and lithium carbonate (2.37 g, 32.09 mmol) were added to dimethylformamide (DMF, 19 ml). The reaction mixture was then stirred at 100°C for 6 hours. After completion of the reaction, the reaction mixture was washed with water, aqueous ammonium chloride solution, and aqueous sodium chloride solution, and the organic layer was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (EA / Hexane=1 / 20) to obtain the target compound Inter-B11 (863 mg, 70%) as a pink solid. P NMR (400MHz, CDCI3) 8 7.45-7.42 (m, 2H) , 7.32-7.29 (m, 2H) , 5.93 (s, IH).

[0222] [Step 5] Synthesis of Inter-B12

[0223] Inter-B12 (353 mg, 1.54 mmol) and potassium carbonate (426 mg, 3.08 mmol) were dissolved in acetone (4 ml), and iodomethane (0.19 ml, 3.08 mmol) was added. The reaction mixture was stirred at room temperature for 3 hours. After completion of the reaction, the reaction mixture was filtered using Celite and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (EA / Hexane=1 / 30) to obtain the target compound Inter-B12 (289 mg, 77%) as an orange liquid. NI NMR (400MHz, CDCI3) 8 7.50 (d, J = 8.4Hz, IH), 7.45-7.42 (m, 2H), 7.31 (d, J = 5.6Hz, IH), 4.05 (s, 3H). [Step 6] Synthesis of Inter-B13 Under nitrogen atmosphere, 1,4-dioxane (1,4-dioxane, 2.4 ml) was added to Inter-B12 (100 mg, 0.41mmo1), bis(pinacolato)diboron (157 mg, 0.62mmo1), Pd(PPhs)2C12 (58 mg, 0.08mmo1), and potassium acetate (121 mg, 1.23 mmol). Afterwards, the reaction mixture was stirred at 90°C for 16 hours. After completion of the reaction, the reaction mixture was filtered using Celite and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (EA / Hexane=1 / 30) to obtain the target compound Inter-B13 (18 mg, 15%) as a white solid.

[0224] 1H NMR (400MHz, CDCI3) 8 7.70 (d, J = 8.0 Hz, 1H) , 7.55 (d, J = 8.0 Hz, IH), 7.49 (d, J = 5.2 Hz, IH) , 7.34 (d, J = 5.2 Hz, IH) , 4.05 (s, 3H), 1.39 (s, 12H); LC / MS: m / z 291.1 (M+H)+(ES). [Step 1] Synthesis of Inter- B14 Compound 6-bromobenzo[b]thiophene- 7-ol (1.93 g, 8.43 mmol) was dissolved in dichloromethane (DCM, 7 ml), and then N,N-diisopropylethylamine (DIPEA, 2.35 ml, 13.48 mmol) and chloromethyl methyl ether (1.02 g, 12.64 mmol) were slowly added at > 0°C. The reaction mixture was stirred at room temperature for 16 hours. After completion of the reaction, the reaction mixture was washed with water and an aqueous sodium chloride solution, and the organic layer was extracted with dichloromethane. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (EA / Hexane=1 / 10) to obtain the target compound Inter- B14 (2.06 g, 90%) as a clear liquid.

[0225] 1 H NMR (400MHz, CDCls) 8 7.52 (d, J = 8.4 Hz, 1H) , 7.45 (d, J = 8.4 Hz, IH), 7.42 (d, J = 5.6 Hz, IH) , 7.30 (d, J = 5.2 Hz, IH) , 5.34 (s, 2H), 3.73 (s, 3H).

[0226] [Step 2] Synthesis of Inter-B15 Under a nitrogen atmosphere, Inter-B14 (500 mg, 1.83 mmol), Pd(dppf hCl / DCM (75 mg, 0.09 mmol), bis(pinacolato)diboron (930 mg, 3.66 mmol), potassium acetate (538 mg, 5.50 mmol) were added to 1,4-dioxane (1,4-dioxane, 6 ml). The reaction mixture was stirred at 100 °C for 16 hours. After completion of the reaction, the reaction mixture was filtered using Celite and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (EA / Hexane=1 / 10) to give the target compound Inter-B15 as a white solid.

[0227] (373 mg, 64%) was obtained. 1 H NMR (400MHz, CDCls) 8 7.73 (d, J = 8.0 Hz, 1H) , 7.58 (d, J = 8.0

[0228] Hz, 1H), 7.50 (d, J = 5.6 Hz, IH), 7.33 (d, J = 5.2 Hz, IH), 5.30 (s, 2H), 3.68 (s, 3H), 1.37 (s, 12H); LC / MS: m / z 321.1 (M+H)+(ES). Intermediate Inter—B19

[0229] [Step 1] Synthesis of Inter-B16

[0230] 5-Bromo-2-fluoro-4-methoxybenzaldehyde (300 mg, 1.29 mmol), methyl thioglycolate (0.12 ml, 1.35 mmol), and potassium carbonate (267 mg, 1.93 mmol) were added to dimethylformamide (DMF, 3 ml). The reaction mixture was then stirred at 60°C for 1 hour. After completion of the reaction, the reaction mixture was washed with water, aqueous ammonium chloride solution, and aqueous sodium chloride solution, and the organic layer was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (EA / Hexane=1 / 20) to obtain the target compound Inter-B16 (122 mg, 32%) as a white solid. 1 H NMR (400MHz, CDCls) 8 8.04 (s, 1H) , 7.91 (s, 1H) , 7.30 (s, 1H) , 3.99 (s, 3H), 3.93 (s, 3H); LC / MS: m / z 301.0, 303.0 (M+H)+(ES).

[0231] [Step 2] Synthesis of Inter-B17 Under a nitrogen atmosphere, Inter-B16 (39 mg, 0.13 mmol) and lithium hydroxide monohydrate (Li0H-H20, 54 mg, 1.30 mmol) were added to tetrahydrofuran (THF, 0.5 ml) and water (CeO, 0.2 ml). The reaction mixture was stirred at 60°C for 3 hours. After completion of the reaction, acetic acid and water were added to the reaction mixture, and the resulting solid was filtered. After drying in vacuo, the target compound Inter-B17 (23 mg, 62.1%) was obtained as a white solid.

[0232] 1 H NMR (400MHz, CDCI3) 8 8.26 (s, IH) , 7.98 (s, IH) , 7.80 (s, IH) , 3.94 (s, 3H).

[0233] [Step 3] Synthesis of Inter-B18 Under a nitrogen atmosphere, Inter-B17 (28 mg, 0.10 mmol) o} Cu (11 mg, 0.17 mmol) was added to quinoline (0.3 ml). The reaction mixture was then stirred at 190°C for 3 hours. After completion of the reaction, the reaction mixture was washed with a 4N aqueous hydrochloric acid solution, and the organic layer was extracted with ethyl acetate. The organic layer was dried with magnesium sulfate and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (EA / Hexane=1 / 20) to obtain the target compound Inter-B18 (10 mg, 42%) as a white solid.

[0234] 1 H NMR (400MHz, CDCI3) 8 8.12 (s, IH) , 7.77 (s, IH) , 7.62 (d, J = 5.2 Hz, IH), 7.34 (d, J = 5.6 Hz, IH) , 3.91 (s, 3H) . [Step 4] Synthesis of Inter-B19 Under a nitrogen atmosphere, 1,4-dioxane (0.9 ml) was added to Inter-B18 (66 mg, 0.27 mmol), bis(pinacolato)diboron (138 mg, 0.54 mmol), Pd(dppf)2C12 (10 mg, 0.01 mmol), and potassium acetate (80 mg, 0.81 mmol). The reaction mixture was stirred at 100°C for 16 hours. After completion of the reaction, the reaction mixture was filtered using Celite and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (EA / Hexane=1 / 9) to obtain the target compound Inter-B19 (58 mg, 74%) as a white solid. I NMR (400MHz, CDC13) 6 8.13 (s, 1H), 7.31 (s, 1H), 7.24-7.20 (m,

[0235] 2H), 3.90 (s, 3H), 1.39 (s, 12H); LC / MS: m / z 291.1 (M+H)+(ES). Intermediate Inter- B23

[0236] [Step 1] Synthesis of Inter-B20

[0237] 5,6-Dihydrobenzo[(1]thiazol-7(s1)-one (300 mg, 1.96 mmol) was dissolved in acetic acid (AcOH, 2.6 ml), and then 48% aqueous bromic acid solution (0.17 ml, 0.98 mmol) was slowly added. Bromine (0.2 ml, 3.92 mmol) was slowly added, and the reaction mixture was stirred at 45°C for 16 hours. After completion of the reaction, the reaction mixture was basified with aqueous sodium bicarbonate solution, and the organic layer was extracted with ethyl acetate. The organic layer was dried with magnesium sulfate and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (EA / Hexane=1 / 2) to obtain the target compound Inter-B20 (450 mg, 73%) as a yellow solid.

[0238] 1 H NMR (400MHz, CDC13) 8 9.08 (s, 1H) , 3.24 (t, J = 6.0 Hz, 2H) , 3.17 (t, J = 5.4 Hz, 2H).

[0239] [Step 2] Synthesis of Inter-B21

[0240] Inter-B20 (100 mg, 0.32 mmol) was dissolved in tetrahydrofuran (THF, 1.6 ml), and then DBU (0.14 ml, 0.96 mmol) was added. The reaction mixture was stirred at room temperature for 2 hours. After completion of the reaction, the reaction mixture was washed with 1 N aqueous hydrochloric acid, and the organic layer was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (EA / Hexane=1 / 1) to obtain the target compound Inter-621 (58 mg, 79%) as a white solid. Ni NMR (400 MHz, CDCI3) 8 8.98 (s, IH), 7.62 (q, J = 9.6 Hz, 2H), 6.09 (s, IH).

[0241] [Step 3] Synthesis of Inter-B22

[0242] Inter-B21 (58 mg, 0.25 mmol) and potassium carbonate (70 mg, 0.50 mmol) were dissolved in acetone (0.6 ml), and iodomethane (0.03 ml, 0.50 mmol) was added. The reaction mixture was stirred at room temperature for 3 hours. After completion of the reaction, the reaction mixture was filtered using Celite and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (EA / Hexane=1 / 1) to obtain the target compound Inter-B22 (47 mg, 77%) as a white solid.

[0243] 1 H NMR (400MHz, CDCls) 8 8.96 (s, 1H) , 7.77 (d, J = 8.8 Hz, 1H) , 7.67 (d, J = 8.8 Hz, 1H) , 4.05 (s, 3H) .

[0244] [Step 4] Synthesis of Inter-B23 Under a nitrogen atmosphere, Inter-B22 (75 mg, 0.31 mmol), bis(pinacolato)diboron (156 mg, 0.61 mmol), Pd(dppf)2612 (11 mg, 0.02 mmol), and potassium acetate (90 mg, 0.92 mmol) were dissolved in 1,4-dioxane (1.0 ml). The reaction mixture was stirred at 100°C for 16 hours. After completion of the reaction, the reaction mixture was filtered using Celite and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (EA / Hexane=1 / 5) to obtain the target compound Inter-B23 (60 mg, 66%) as a white solid.

[0245] 1 H NMR (400MHz, CDCI3) 8 9.02 (s, 1H) , 7.86 (d, J = 2.4 Hz, 2H),

[0246] 4.04 (s, 3H), 1.39 (s, 12H); LC / MS: m / z 292.1 (M+H)+(ES). Intermediate Inter— B28 lnter-B27 lnter-B28

[0247] [Step 1] Synthesis of Inter-B24 Sodium hydroxide (4.5 g, 120 mmol) was dissolved in water (OW, 40 ml), and bromine (1.4 ml, 27.3 mmol) was added. The reaction mixture was stirred at 50°C for 3 hours, and 2,4-dinitroaniline (1 g, 5.46 mmol) and potassium hydroxide (460 mg, 8.20 mmol) were dissolved in methanol (MeOH, 20 ml), and then slowly added. The reaction mixture was stirred at 50°C for 30 minutes. After completion of the reaction, the reaction mixture was cooled to room temperature, and the resulting solid was filtered to obtain the target compound Inter-B24 (301 mg,

[0248] 19%) was obtained. 1H NMR (400MHz, DMS0-d6) 5 7.46 (d, J = 9.2Hz, 1H), 7.19 (d, J =

[0249] 9.2 Hz, 1H), 4.32 (s, 3H) .

[0250] [Step 2] Synthesis of Inter-B25 Under a hydrogen atmosphere, compound Inter-B24 (224 mg, 0.91 mmol) was dissolved in ethyl acetate (EA, 10 ml), and Pd / C (33 mg, 10 wt%) was added. The reaction mixture was stirred at room temperature for 16 hours. After completion of the reaction, the reaction mixture was filtered using Celite and concentrated under reduced pressure to obtain Inter-B25 (127 mg, 65%) as a black solid.

[0251] 1 H NMR (400MHz, CDCls) 8 7.80 (d, J = 8.4Hz, 1H), 6.36 (d, J = 8.4Hz, 1H), 3.80-3.77 (m, 5H), 3.65-3.62 (m, 2H); LC / MS: m / z 217.0 (M+H)+(ES).

[0252] [Step 3] Synthesis of Inter-B26 Compound Inter-B25 (50 mg, 0.230 mmol) was added to formic acid (2 ml). The reaction mixture was stirred at 100°C for 16 hours. After completion of the reaction, the pH of the reaction mixture was adjusted to 8 using a 2 M aqueous sodium hydroxide solution. The mixture was washed with water, and the organic layer was extracted using ethyl acetate. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (MeOH / DCM=l:9) to obtain the target compound Inter-B26 (32 mg, 61.5%)* as a brown solid.

[0253] 1H NMR (400MHz, DMS0-d6) 5 12.72 (bs, IH) , 8.21 (s, IH) , 7.33 (d, J = 8.4 Hz, IH), 7.17 (d, J = 8.4 Hz, IH) , 4.26 (s, 3H); LC / MS: m / z 226.9, 228.9 (M+H)+(ES).

[0254] [Step 4] Synthesis of Inter-B27 Compound Inter-B26 (100 mg, 0.44 mmol) was dissolved in tetrahydrofuran (THF, 2 ml), and then di-tertbutyl dicarbonate (116 mg, 0.53 mmol), triethylamine (TEA, 0.09 ml, 0.66 mmol), and 4-dimethylaminopyridine (5.4 mg, 0.04 mmol) were added. The reaction mixture was stirred at room temperature for 4 hours. After completion of the reaction, the reaction mixture was washed with water, and the organic phase was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated under reduced pressure to obtain the target compound Inter-B27 (120 mg, 83%) as a yellow solid.

[0255] 1 H NMR (400MHz, DMS0-d6) 5 8.64 (s, 1H) , 7.57 (q, J = 8.0Hz, 8.8Hz, 2H), 4.31 (s, 3H), 1.65 (s, 9H); LC / MS: m / z 226.9, 228.9, 270.9, 272.9 (M+H)+(ES). [Step 5] Synthesis of Inter- B28 Compound Inter-B27 (50 mg, 0.15 mmol) was dissolved in 1,4-dioxane (1,4-

[0256] After adding and dissolving in 1 ml of Pd(dppf)2C12 (12 mg, 0.0153 mmol), bis(pinacolato)diboron (78 mg, 0.306 mmol), and potassium acetate (45 mg, 0.458 mmol) were added. The reaction mixture was stirred at 100°C for 16 hours. After completion of the reaction, the reaction mixture was filtered using Celite and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (EA / Hexane=1 / 4) to obtain the target compound Inter-B28 (57 mg, 32%) as a clear liquid.

[0257] 1 H NMR (400MHz, CDC13) 8 8.32 (s, IH), 7.66 (q, J = 7.2 Hz, 8.0 Hz, 2H), 4.30 (s, 3H), 1.69 (s, 9H), 1.38 (s, 12H); LC / MS: m / z 319.1 (M+H)+(ES). Intermediate Inter-B31

[0258]

[0259] [Step 1] Synthesis of Inter-B29

[0260] 1-Benzothiophen-5-ol (61 mg, 0.41 mmol) was dissolved in acetic acid (1.4 ml), and then a solution of bromine (17 pl, 0.41 mmol) in acetic acid (0.7 ml) was slowly added. The reaction mixture was stirred at room temperature for 1 hour. After completion of the reaction, a saturated sodium thiosulfate solution was added to form a solid, which was filtered to obtain the solid. The filtrate was washed with water and dried under vacuum to obtain the target compound Inter-B29 (55 mg, 59%) as a white solid.

[0261] 1H NMR (400MHz, CDC13) 8 7.68 (d, J = 8.8 Hz, 1H) , 7.53 (d, J = 5.6 Hz, IH), 7.35 (d, J = 5.2 Hz, IH) , 7.09 (d, J = 8.4 Hz, IH) , 5.54 (s, IH) .

[0262] [Step 2] Synthesis of Inter-B30 Compound Inter-B29 (1.42 g, 6.18 mmol) was dissolved in dichloromethane (DCM, 5 ml), and then chloromethyl methyl ether (0.70 ml, 9.27 mmol) and diisopropylethylamine (DIPEA, 1.72 ml, 9.89 mmol) were added. The reaction mixture was stirred at room temperature for 16 hours. After the reaction was completed, the reaction mixture was filtered using Celite and concentrated under reduced pressure. The organic layer was extracted with water and dichloromethane. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (EA / Hexane=1 / 20) to obtain the target compound Inter-B30 (750 mg, 44%) as a yellow liquid.

[0263] 1 H NMR (400 MHz, CDCls) 8 7.73 (d, J = 8.8 Hz, 1H) , 7.52 (d, J = 5.2 Hz, IH), 7.46 (d, J = 5.6 Hz, IH) , 7.24 (d, J = 8.8 Hz, IH) , 5.29 (s, 2H), 3.55 (s, 3H).

[0264] [Step 3] Synthesis of Inter-B31 Compound Inter-B30 (750 mg, 2.75 mmol) was dissolved in 1,4-dioxane (1,4-dioxane, 9 ml), and Pd(dppf)2C12'DCM (112 mg, 0.14 mmol), bis(pinacolato)diboron (1.39 g, 5.49 mmol), and potassium acetate (808 mg, 8.24 mmol) were added. The reaction mixture was stirred at 100°C for 16 hours. After completion of the reaction, the reaction mixture was filtered using Celite and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (EA / Hexane=1 / 20) to obtain the target compound Inter-B31 (715 mg, 81%) as a transparent solid.

[0265] 1 H NMR (400MHz, CDCI3) 8 7.83 (d, J = 8.8 Hz, IH) , 7.71 (d, J = 5.6 Hz, IH), 7.46 (d, J = 5.2 Hz, IH) , 7.12 (d, J = 8.8 Hz, IH) , 5.20 (s, 2H), 3.55 (s, 3H), 1.42 (s, 12H) . Intermediate Inter-B36

[0266]

[0267] [Step 1] Synthesis of Inter-B32

[0268] 2-Bromo-6-methoxyaniline (5 g, 24.7 mmol) was added to acetone (80 mL), and benzoyl isothiocyanate (4.01 mL, 29.7 mmol) was added dropwise. Acetone (40 mL) was further added, and the mixture was stirred at room temperature for 16 hours. After completion of the reaction, the solvent was removed by concentration under reduced pressure, and then filtered under reduced pressure to obtain the target compound Inter-B32 (8.55 g, 94.6%) as a light-colored solid.

[0269] 1H NMR (400MHz, CDCls) 8 13.12 (s, 1H) , 9.09 (s, 1H) , 8.82 (dd, J = 8 Hz, 7.2 Hz, IH), 7.94-7.91 (m, 2H) , 7.68-7.64 (m, IH) , 7.68-7.54 (m, 2H), 7.44 (dd, J = 1.2 Hz, 6.4 Hz, IH), 7.07 (t, J = 8Hz, IH), 3.97 (s, 3H); LC / MS: m / z 365.0, 367.0 (M+H)+(ES).

[0270] [Step 2] Synthesis of Inter-B33

[0271] Inter-B32 (8.55 g, 23.4 mmol) was dissolved in methanol (MeOH, 100 mL), and then 2 M aqueous sodium hydroxide solution (36 mL, 70.2 mmol) was added. The reaction mixture was stirred at 65°C for 2 hours. After completion of the reaction, 2 M aqueous hydrochloric acid solution and water were added to the reaction mixture, and the organic layer was extracted with ethyl acetate. The mixture was concentrated under reduced pressure to obtain the target compound Inter-B33 (1.58 g, 25.9%) as a light brown solid.

[0272] 1 H NMR (400MHz, DMS0-d6) 5 9.30 (s, 1H) , 7.85 (dd, J = 1.6 Hz, 7.2 Hz, IH), 7.94-7.91 (m, 2H) , 7.42 (dd, J = 1.6 Hz, 6.4 Hz, IH) , 7.05 (t, J = 8Hz, IH), 3.74 (s, 3H); LC / MS: m / z 260.9 262.9 (M+H)+(ES).

[0273] [Step 3] Synthesis of Inter-B34

[0274] Inter-B33 (1.44 g, 5.51 mmol) was dissolved in chloroform (CHCh, 20 mL), and bromine (0.213 mL, 11.0 mmol) was added dropwise at 0°C. The reaction mixture was stirred at room temperature for 16 h. After completion of the reaction, the reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (MeOH / DCM=1 / 3O) to obtain the target compound Inter-B34 (1.10 g, 76.9%) as a pale yellow solid.

[0275] 1 H NMR (400MHz, CDCls) 8 7.29 (d, J = 8.4 Hz, IH), 7.19 (d, J = 8.4 Hz, IH), 5.43 (bs, 2H), 4.07 (s, 3H); LC / MS: m / z 258.9, 260.9 (M+H)+(ES).

[0276] [Step 4] Synthesis of Inter-B35

[0277] Inter-B34 (1.10 g, 4.25 mmol) was dissolved in DMF (7 mL), and tert-butyl nitrite (1.8 mL, 15.3 mmol) was added. The reaction mixture was stirred at 60°C for 6 hours. After completion of the reaction, the reaction mixture was washed with aqueous ammonium chloride solution, and the organic layer was extracted with ethyl acetate. The organic layer was dried with sodium sulfate and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (EA / Hexane=1 / 10) to obtain the target compound Inter-B35 (610 mg, 58.7%) as a yellow liquid. Ni NMR (400MHz, CDCls) 8 8.94 (s, 1H) , 7.60 (d, J = 8.4 Hz, 1H) , 7.53 (d, J = 8.4 Hz, 1H) , 4.30 (s, 3H); LC / MS: m / z 243.9, 245.9 (M+H)+(ES).

[0278] [Step 5] Synthesis of Inter-B36 Under a nitrogen atmosphere, 1,4-dioxane (6 ml) was added to Inter-B35 (610 mg, 2.54 mmol), bis(pinacolato)diboron (1.29 g, 5.08 mmol), Pd(dppf hCl / DCM (104 mg, 0.127 mmol), and potassium acetate (748 mg, 7.62 mmol). The reaction mixture was stirred at 90°C for 16 hours. After completion of the reaction, the reaction mixture was filtered using Celite and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (EA / Hexane=1 / 10) to obtain the target compound Inter-B36 (553 mg, 74.7%) as a yellow solid. P NMR (400 MHz, CDCI3) 8 8.91 (s, 1H) , 7.73 (d, J = 8.0 Hz, 1H) , 7.65 (d, J = 8.4 Hz, 1H) , 4.23 (s, 3H) , 1.39 (s, 12H); LC / MS: m / z 292.3 (M+H)+(ES). Intermediate Inter—C2

[0279] [Step 1] Synthesis of Inter-Cl Under a nitrogen atmosphere, 3, 5, 6-trichloro 1,2, 4-triazine (3 g, 16.27 mmol) was dissolved in tetrahydrofuran (THF, 160 ml) and cooled to -78°C. Then, 3M methylmagnesium bromide solution (3M MeMgBr in THF, 8.1 ml, 24.40 mmol) was slowly added. The reaction mixture was stirred at room temperature for 16 hours. After the reaction was terminated by adding aqueous ammonium chloride solution at 0°C, ethyl acetate was extracted using the organic layer. The organic layer was dried using magnesium sulfate and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (EA / Hexane=1 / 20) to obtain the target compound Inter-Cl (1.51 g, 57%) as a yellow solid.

[0280] 1 H NMR (400MHz, CDCls) 8 2.70 (s, 3H); LC / MS: m / z 164.0, 166.0 (M+H)+(ES).

[0281] [Step 2] Synthesis of Inter-C2

[0282] Inter-Cl (90 mg, 0.55 mmol) was dissolved in dimethyl sulfoxide (DMSO, 1.1 ml), and (R)-1-methylpiperidin-3-amine (366 uL, 2.92 mmol) and N,N-diisopropylethylamine (DIPEA, 0.93 ml, 5.37 mmol) were added. The reaction mixture was stirred at room temperature for 2 hours. After completion of the reaction, the reaction mixture was washed with water, and the organic layer was extracted with dichloromethane. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (MeOH / DCM=l:2) to obtain the target compound Inter-C2 (68 mg, 51%) as a dark brown solid.

[0283] 1 H NMR (400MHz, Methanol -d4) 5 4.10-4.05 (m, 1H) , 3.01 (d, J = 9.2 Hz, IH), 2.73 (d, J = 10.0 Hz, IH) , 2.47 (s, 3H) , 2.31 (s, 3H) , 2.17-1.96 (m, 3H), 1.86-1.78 (m, IH), 1.74-1.63 (m, IH), 1.46-1.38 (m, IH); LC / MS: m / z

[0284] 242.1, 244.1 (M+H)+(ES). Intermediates Inter— C3 to Inter— C48 and Inter— C53 to Inter— C63 Inter-C3 to Inter-C48 and Inter-C53 to Inter-C63 were synthesized in substantially the same synthetic method as that of Inter-C2, except that the amine or the hydrochloride of the amine was used in place of (R)-1-methylpiperidin-3-amine in the Inter-C2 synthetic scheme.

[0285] [Table 6] Intermediate Inter— C50

[0286] [Step 1] Synthesis of Inter- C49 Tert-butyl (S)-2-(((6-chloro-5-methyl-1,2,4-triazin-3-yl)amino)methyl)pyrrolidine-1-carboxylate (705 mg, 2.15 mmol) was dissolved in dichloromethane (DCM, 43 ml), and then trifluoroacetic acid (1.7 ml, 21.5 mmol) was added. The reaction mixture was stirred at room temperature for 16 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure to obtain the target compound Inter- 049 (730 mg, 98%) as an orange solid.

[0287] LC / MS: m / z 228.1, 230.1 (M+H)+(ES).

[0288] [Step 2] Synthesis of Inter-C50

[0289] Inter-C49 (300 mg, 0.88 mmol) was dissolved in methanol (MeOH, 1.0 ml), and formaldehyde (37% in H2O, 0.52 ml) and sodium cyanoborohydride (155 mg, 2.47 mmol) were added at 0°C. The reaction mixture was stirred at room temperature for 16 hours. After the reaction was completed, the pH was adjusted to 9 by adding aqueous potassium hydroxide solution to the reaction mixture, and the organic layer was extracted using dichloromethane. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (Me0H / DCM=1 / 10) to obtain the target compound Inter-C50 (71 mg, 33%) as a yellow-brown solid.

[0290] 1H NMR (400MHz, CDCI3) 8 6.06 (br, 1H) , 3.72 (m, 1H) , 3.48-3.43 (m, 1H), 3.19-3.16 (m, IH) , 2.64-2.62 (m, IH) , 2.46 (s, 3H) , 2.40 (s, 3H), 2.37-2.30 (m, IH), 2.04-1.93 (m, IH), 1.86-1.65 (m, 3H); LC / MS: m / z 242.1, 244.1 (M+H)+(ES). Intermediate Inter- C52

[0291] [Step 1] Synthesis of Inter- C51 Tert-butyl (3S, 4S)-3-((6-chloro-5-methyl-1,2,4-triazin-3-yl)amino)-4-hydroxypiperidine-1-carboxylate (593 mg, 1.73 mmol) was dissolved in dichloromethane (DCM, 8.6 ml), and then 4N hydrochloric acid solution (4N HCI in 1,4-dioxane, 2.2 ml) was added. The reaction mixture was stirred at room temperature for 16 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure to obtain the target compound Inter- C51 (546 mg, 98%) as a reddish brown solid.

[0292] [Step 2] Synthesis of Inter-C52 Inter-C51 (496 mg, 1.77 mmol) was dissolved in acetonitrile (ACN, 3.9 ml), and potassium carbonate (734 mg, 5.31 mmol) and iodoethane (0.16 ml, 1.95 mmol) were slowly added at 0°C. The reaction mixture was stirred at room temperature for 16 hours. After completion of the reaction, the reaction mixture was washed with water and an aqueous sodium chloride solution, and the organic layer was extracted with dichloromethane. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (Me0H / DCM=1 / 10) to give the target compound Inter-C52 as an ivory solid.

[0293] (130 mg, 27%) was obtained. 1 H NMR (400MHz, Methanol -d4) 5 3.97-3.92 (m, IH) , 3.52-3.46 (m, IH) , 3.09-3.06 (m, IH) , 2.88-2.84 (m, IH) , 2.42 (q, J = 7.2 Hz, 2H) , 2.36 (s, 3H) , 2.13-2.08 (m, IH) , 1.99-1.90 (m, 2H) , 1.64-1.56 (m, IH) , 1.02 (t J = 7.2 Hz, 3H) : NH peak and 0-H peak are not observed. LC / MS: m / z 272.0, 274.1 (M+H)+(ES). Intermediate Inter—C64

[0294] 3, 6 -Dichloro - 5 -methyl - 1,2, 4 -triazine (264 mg, 1.61 mmol) was dissolved in acetonitrile (ACN, 7 ml), and methyl (3R, 5R) - 3 -amino - 5 -fluoropiperidine - 1-carboxylate dihydrochloride (423 mg, 1.61 mmol) and potassium carbonate (890 mg, 6.43 mmol) were added. The reaction mixture was stirred at room temperature for 16 hours. After the reaction was completed, the reaction mixture was washed with water, and the organic layer was extracted with dichloromethane. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (Me0H / DCM = 10 / l) to obtain the target compound Inter-C64 (82 mg, 16%) as a brown oil.

[0295] 1H NMR (400MHz, Methanol -d4) 5 4.28-4.13 (m, 5H) , 3.18 (dd, J= 20.4 Hz, 12.0 Hz, IH), 2.92-2.83 (m, IH) , 2.50 (s, 3H) , 2.37-2.34 (m, IH) , 1.90- 1.80 (m, IH), 1.27 (t. J= 7.2 z, 3H); LC / MS: m / z 304.0, 306.0 (M+H)+(ES).

[0296] <Example> Example 1: (3R,4S)-4-((6-(4-hydroxybenzo[b]thiophene-5-yl)-5-methyl-1,2,4-triazin-3-yl)amino)tetrahydrofuran-3-ol Under a nitrogen atmosphere, (3R,4S)-4-((6-chloro-5-methyl-1,2,4-triazin-3-yl)amino)tetrahydrofuran-3-ol (24 mg, 0.10 mmol), (4-hydroxybenzo[b]thiophen-5-yl)boronic acid (34 mg, 0.18 mmol), Pd(dppf)2C12'DCM (17 mg, 0.02 mmol), and potassium carbonate (69 mg, 0.50 mmol) were added to 1,4-dioxane (1,4-dioxane, 0.6 ml) and water (EbO, 0.3 ml). The reaction mixture was then stirred at 90°C for 16 h. After completion of the reaction, the reaction mixture was filtered using Celite and magnesium sulfate and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (Me0H / DCM=1 / 10) to obtain the target compound 1 (11 mg, 29%) as a yellow solid.

[0297] 1 H NMR (400MHz, Methanol -d4) 5 7.62 (dd, J = 5.6, 0.8 Hz, 1H) , 7.57-

[0298] 7.54 (m, 2H), 7.28 (d, J = 8.4 Hz, IH), 4.41-4.38 (m, 2H), 4.25 (dd, J = 9.4, 5.0 Hz, 1H), 4.10 (dd, J = 9.8, 4.2 Hz, 1H), 3.87 (dd, J = 9.4, 2.6 Hz, 1H),

[0299] 3.77 (dd, J = 9.6, 2.0 Hz, 1H) , 2.38 (s, 3H) ; LC / MS: m / z 345.1 (M+H)+(ES). Synthesis of Examples 2 to 4 Except that Inter-C4 to Inter-C6 of Table 6 were used instead of (3R,4S)-4-((6-chloro-5-methyl-1,2,4-triazin-3-yl)amino)tetrahydrofuran-3-ol of Example 1, respectively, the compounds of Examples 2 to 4 of Table 7 were synthesized using a synthetic method substantially identical to that of Example 1.

[0300] [Table 7] Examples 5 and 6: (R)-6-(4-methoxybenzo[b]thiophene-5-yl)-5-methyl-N-(l-methylpiperidin-3-yl)~! , 2, 4 —triazine-3-amine and (R)~5~(5 "methyl—3~((l-methylpiperidin-3-yl)amino)-1,2, 4 -triazin-6-yl)benzo[b]thiophene-4-ol

[0301]

[0302] 6

[0303] [Step 1] Synthesis of compound 5 Under a nitrogen atmosphere, (R)-6-chloro-5-methyl-N-(l-methylpiperidin-3-yl)-1,2,4-triazin-3-amine (30 mg, 0.12 mmol), 2-(4-methoxybenzo[b]thiophene-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (61 mg, 0.21 mmol), Pd(dppf hCl / DCM

[0304] (20 mg, 0.03 mmol), potassium carbonate (20 mg, 0.60 mmol) were added to 1,4-dioxane (1,4-dioxane, 0.72 ml) and water (H2O, 0.36 ml). The reaction mixture was stirred at 90°C for 16 hours. After completion of the reaction, the reaction mixture was filtered using celite and magnesium sulfate and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (MeOH / DCM=1 / 5) to give the target compound 5 (33 mg,

[0305] 70%) was obtained.

[0306] 1 H NMR (400MHz, CDCls) 8 7.72 (d, J = 8.4 Hz, 1H) , 7.51 (d, J = 5.6 Hz, IH), 7.47 (d, J = 5.6 Hz, IH) , 7.36 (d, J = 8.4 Hz, IH) , 5.83 (br, IH) , 4.32 (br, 1H), 3.72 (s, 3H), 2.69 (m, 1H), 2.46-2.34 (m, 3H), 2.96 (s, 3H), 2.29 (s, 3H), 1.86-1.67 (m, 4H); LC / MS: m / z 370.2 (M+H)+(ES).

[0307] [Step 2] Synthesis of Compound 6 Compound 5 (32 mg, 0.09 mmol) was dissolved in dichloromethane (DCM, 2.0 ml), and 1 M boron tribromide (IM BBr3 in DCM, 0.08 ml, 0.90 mmol) was added at -78°C. The reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was quenched with methanol and concentrated under reduced pressure. The concentrated reaction mixture was purified by silica gel column chromatography (MeOH / DCM=1 / 5) to obtain the target compound 6 (7.8 mg, 25%) as a pale yellow solid.

[0308] 1H NMR (400 MHz, CDCls) 8 11.5 (br, 1H) , 7.66 (dd, J = 5.4, 0.6 Hz, 1H), 7.44 (dd, J = 8.4, 0.8 Hz, IH) , 7.37-7.34 (m, 2H) , 5.91 (br, IH) , 4.29 (br, IH), 2.61 (s, 3H), 2.57-2.45 (m, 3H), 2.30 (m, 4H), 1.86-1.63 (m, 4H); LC / MS: m / z 356.2 (M+H)+(ES). Synthesis of Examples 7 to 13, 73 and 74 Compounds of Examples 7 to 13, 73 and 74 in Table 8 below were synthesized using substantially the same synthetic method as that of Example 6, except that Inter-B4, Inter-B13, Inter-B19, Inter-B23, Inter-B28 and Inter-B36 were used instead of 2-(4-methoxybenzo[b]thiophene-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane of Example 6, and Inter-C2, Inter-C5, Inter-C7 to Inter-C9 and Inter-C17 were used instead of (R)-6-chloro-5-methyl-N-(l-methylpiperidin-3-yl)-1,2,4-triazin-3-amine.

[0309] [Table 8] Example 14: 5-(3-(((IS, 2S)-2-hydroxycyclohexyl)amino)-5-methyl-,2,4-triazin-6-yl)benzo[b]thiophene-4-ol

[0310]

[0311] [Step 1] Synthesis of Compound A1 Under nitrogen atmosphere, (1S,2S)-2-((6-chloro-5-methyl-1,2,4-triazin-3-yl)amino)cyclohexan-1-ol (30.0 mg, 0.12 mmol), 2-(4-(methoxymethoxy)benzo[b]thiophen-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

[0312] (59 mg, 0.19 mmol), Pd(dppf hCl / DCM (20 mg, 0.03 mmol), potassium carbonate (82 mg, 0.6 mmol) were added 1,4-dioxane (1,4-di oxane, 0.72 ml) and water (H2O, 0.04 ml). The reaction mixture was stirred at 90°C for 16 hours. After completion of the reaction, the reaction mixture was filtered using celite and magnesium sulfate and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (EA / Hexane=1 / 1) to obtain the target compound A1 (26 mg, 52%) as a sticky transparent liquid. Ni NMR (400 MHz, CDCls) 8 7.75 (d, J = 8.4 Hz, 1H), 7.54 (dd, J =

[0313] 0.6, 5.6 Hz, 1H), 7.48 (d, J = 5.6 Hz, 1H), 7.35 (d, J = 8.0 Hz, 1H), 5.84 (br, 1H), 4.95 (s, 2H), 3.88 (m, 1H), 3.54 (dt, J = 4.4, 10.0 Hz, 1H) , 3.26 (s, 3H), 2.32 (s, 3H), 2.21-2.18 (m, 1H) , 2.13-2.10 (m, 1H) , 1.79-1.75 (m, 2H), 1.49-1.35 (m, 4H) .

[0314] [Step 2] Synthesis of Compound 14 Compound A1 (26 mg, 0.07 mmol) was dissolved in dichloromethane (DCM, 1.3 ml), and trifluoroacetic acid (0.05 ml, 0.65 mmol) was added at 0°C. The reaction mixture was stirred at room temperature for 6 hours. After completion of the reaction, the reaction mixture was washed with an aqueous sodium bicarbonate solution, and the organic layer was extracted with dichloromethane. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The concentrated reaction mixture was purified by silica gel column chromatography (EA / Hexane=5 / 1) to obtain the target compound 14 (7 mg, 30%) as a yellow solid.

[0315] 1H NMR (400 MHz, Methanol -d4) 5 7.61 (d, J = 5.2 Hz, 1H) , 7.54 (dd, J = 8.2, 0.6 Hz, IH), 7.53 (d, J = 5.6, Hz, IH) , 7.27 (d, J = 8.4 Hz, IH), 3.94-3.88 (m, IH), 3.58-3.52 (m, IH), 2.36 (s, 3H), 2.19-2.07 (m, 2H), 1.82-1.76 (m, 2H), 1.50-1.28 (m, 4H); LC / MS: m / z 357.1 (M+H)+(ES). Synthesis of Examples 15 to 35, 37 to 49, 68 to 72, 75, 92, 93 and 100 to 106 Except that Inter-C10 to Inter-C16, Inter-C19 to Inter-C30, Inter-C32 to Inter-C48, Inter-C50 and Inter-C52 to Inter-C62 were used instead of (1S,2S)-2-((6-chloro-5-methyl-1,2,4-triazin-3-yl)amino)cyclohexan-1-ol of Example 14, respectively, Examples 15 to 35, 37 to 49, 68 to 72, 75, 92, 93 and 100 to 106 were synthesized using substantially the same synthetic method as that of Example 14, as shown in Table 9 below.

[0316] Compounds 72, 75, 92, 93, and 100 to 106 were synthesized respectively.

[0317] [Table 9]

[0318] Example 36: 5-(3-((3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl)amino)-5-methyl-1,2,4-triazin-6-yl)benzo[b]thiophene-4-ol Methyl 3-((6-(4-hydroxybenzo[b]thiophen-5-yl)-5-methyl-1,2,4-triazin-3-yl)amino)bicyclo[1.1.1]pentane-1-carboxylate (10 mg, 0.0261 mmol) was added to tetrahydrofuran (THF, 1 ml). Lithium aluminum hydride (LAH, 2.2 mg, 0.0575 mmol) was added at 0°C, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was slowly poured into ice water at 0°C to stop the reaction, and an aqueous solution of ammonium chloride and an aqueous solution of sodium potassium tartrate were added. The organic layer was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (EA / Hexane=5 / 1) to obtain the target compound 36 (2.77 mg, 29.9%) as a yellow solid.

[0319] 1 H NMR (400 MHz, CDCls) 8 11.54 (s, 1H) , 7.66 (dd, J = 5.6 Hz, 4 Hz, 1H), 7.44 (dd, J = 8.0 Hz, 0.4 Hz, IH) , 7.38 (d, J = 5.6 Hz, IH) , 7.36 (d, J = 8.4 Hz, IH), 5.84 (s, IH), 3.80- (s, IH), 2.66 (s, H), 2.18 (s, 6H); LC / MS: m / z 355.1 (M+H)+(ES). Example 50: (R)-2-(3-((6-(4-hydroxybenzo[b]thiophene-5-yl)-5-methyl-

[0320] 1,2,4-triazine-3-yl)amino)piperidine-1-yl)acetic acid Methyl (R)-2-(3-((6-(4-hydroxybenzo[b]thiophen-5-yl)-5-methyl-1,2,4-triazin-3-yl)amino)piperidin-1-yl)acetate (50 mg, 0.12 mmol) was dissolved in methanol (MeOH, 3 ml), and 2 M aqueous sodium hydroxide solution (0.18 mL, 0.363 mmol) was added. The reaction mixture was stirred at room temperature for 16 h. After completion of the reaction, the aqueous layer was washed with ethyl acetate, and the pH was adjusted to 3 with 1 M aqueous hydrochloric acid solution. After concentrating the aqueous layer under reduced pressure, tetrahydrofuran (THF) was added, dried using sodium sulfate, and concentrated under reduced pressure to obtain compound 50 (21.1 mg, 41.7%) as a yellow solid.

[0321] 1 H NMR (400MHz, Methanol -d4) 5 1H NMR (400 MHz, CDC13) 5 7.65 (dd,

[0322] J = 5.6 Hz, 8Hz, 1H), 7.60-7.58 (m, 2H) , 7.29 (d, J = 8.4 Hz, 1H) , 4.52-4.50 (m, 2H), 4.50-3.38 (m, 1H) , 3.18 (s, 2H) , 3.95-3.85 (m, 2H) , 3.71- 3(m, 1H) , 3.19 (m, 1H), 2.54-2.31 (m, 4H) , (2.27-2.18 (m, 4H) , 2.55-2.07 (m, 3H) , 2.03- 1.79 (m, 5H); LC / MS: m / z 400.1 (M+H)+(ES). Synthesis of Examples 51 to 66 Instead of 2-(4-(methoxymethoxy)benzo[b]thiophene-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane of the above Example 14, 2-(7-(methoxymethoxy)benzo[b]thiophene-6-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane was used, and instead of (1S,2S)-2-((6-chloro-5-methyl-1,2,4-triazin-3-yl)amino)cyclohexan-1-ol, Inter-C5 to Inter-C11, Inter— C19, Inter— C24 to Inter— C26, Inter— C28, Compounds of Examples 51 to 66 in Table 10 below were each synthesized using a synthetic method substantially identical to that of Example 14, except that Inter-C33, Inter-35, Inter-C40, and Inter-C41 were used.

[0323] [Table 1 Example 67: (R)-2-(3-((6-(4-hydroxybenzo[b]thiophene-5-yl)-5-methyl-

[0324] 1,2,4-triazine-3-yl)amino)piperidine-1-yl)-N-methylacetamide Methyl (R)-2-(3-((6-(4-hydroxybenzo[b]thiophene-5-yl)-5-methyl-1,2,4-triazin-3-yl)amino)piperidine—1—yl)acetate (50 mg, 0.12 mmol) was dissolved in a 33% methylamine solution (33%MeNH2 in ethanol, 5 ml), and stirred at room temperature for 16 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (Me0H / DCM=1 / 10) to obtain a yellow solid compound.

[0325] 67 (39 mg, 79.7%) was obtained.

[0326] 1 H NMR (400 MHz, CDCls) 8 11.42 (br, 1H) , 7.51 (dd, J = 5,2 Hz, 0.4

[0327] Hz, IH), 7.45 (dd, J = 8.4 Hz, 0.8 Hz, IH), 7.39-7.34 (m, 2H), 7.06 (br, IH),

[0328] 4.29 (br, IH), 3.04 (s, 2H), 2.97-2.90 (m, IH), 2.86 (d, J = 4.8 Hz, 2H),

[0329] 2.64 (s, 3H), 2.54-2.44 (m. 2H), 1.92-1.83 (m, 2H), 1.75-1.65 (m, 6H); LC / MS: m / z 413.1 (M+H)+(ES). Example 76: (R)-5-(3-((1-((1-hydroxycyclopropyl)methyl)piperidine ~

[0330] 3-yl)amino)-5-methyl-1,2,4-triazin-6-yl)benzo[b]thiophene-4-ol

[0331] [Step 1] Synthesis of compound Bl Under nitrogen atmosphere, (R)-1-((3-((6-chloro-5-methyl-1,2,4-triazin-3-yl)amino)piperidin-1-yl)methyl)cyclopropan-1-ol (133 mg, 0.45 mmol), 2-(4-(methoxymethoxy)benzo[b]thiophen-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (218 mg, 0.68 mmol), Pd(dppf hCl / DCM (66 mg, 0.09 mmol), potassium carbonate (193 mg, 1.4 mmol) were added to 1,4-dioxane (1,4-di oxane, 0.53 ml) and water. (H2O, 0.27 ml) was added. The reaction mixture was then stirred at 90°C for 16 hours. After completion of the reaction, the reaction mixture was filtered using Celite and magnesium sulfate and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (MeOH / DCM=1 / 5) to obtain the target compound B1 (127 mg, 62%) as a yellow solid.

[0332] 1 H NMR (400 MHz, Methanol -d4) 5 7.86 (dd, J = 8.2 Hz, 0.64 Hz, 1H) , 7.69 (d, J = 5.5 Hz, IH) , 7.57 (dd, J = 5.6 Hz, 0.6 Hz, IH) , 7.37 (d, J = 8.2 Hz, IH), 5.52 (s, IH) , 5.01 (s, 2H) , 4.22 (br, IH) , 3.60-3.57 (m, 2H), 3.37 (s, 3H), 3.13 (s, 3H) , 3.10 (br, IH) , 2.77 (br, IH) , 2.71-2.61 (m, 2H) , 2.31 (s, 3H), 1.99-1.96 (m, IH) , 1.92-1.80 (m, IH) , 1.76-1.70 (m, IH) , 1.53- 1.51 (m, IH); LC / MS: m / z 456.2 (M+H)+(ES).

[0333] [Step 2] Synthesis of compound 76

[0334] (R)- 1-((3- ((6- (4-(methoxymethoxy)benzo [b] thiophen- 5 -yl)- 5 -methyl- 1,2,4- triazin-3 -yl) amino) piperidin- 1-yl) methyl) cyclopropan-1-ol (127 mg, 0.75 mmol) was dissolved in dichloromethane (DCM, 1.6 ml) and methanol (MeOH, 0.8 ml), and then 4 N hydrochloric acid solution (4 N HC1 in 1,4-di oxane, 1.9 ml) was slowly added at 0 °C. The reaction mixture was stirred at room temperature for 16 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure to obtain the target compound 76 (52 mg, 47%) as a yellow solid. 1 H NMR (400MHz, Methanol -d4) 5 7.62 (dd, J = 5.6 Hz, 1H) , 7.56-7.54 (m, 2H), 7.28 (d, J = 8.4 Hz, IH) , 4.39-4.28 (m, IH) , 4.03-3.99 (m, IH) , 3.54-3.48 (m, IH) , 2.89-2.83 (m, IH) , 2.52-2.51 (m, 3H) , 2.36 (s, 3H) , 1.99- 1.91 (m, 2H), 1.79-1.73 (m, IH) , 1.67-1.63 (m, IH), 1.20-1.17 (m, 3H); LC / MS: m / z 412.1 (M+H)+(ES). Example 107: 5-(3-(((3R,5R)-5-fluoropiperidin-3-yl)amino)-5-methyl-

[0335] 1,2,4-triazine-6-yl)benzo[b]thiophene-4-ol

[0336] [Step 1] Synthesis of compound Cl Methyl (3R, 5R)-3-((6-chloro-5-methyl-1,2,4-triazin-3-yl)amino)-5-fluoropiperidine-1-carboxylate (82 mg, 0.26 mmol), 2-(4-methoxymethoxy)benzo[b]thiophene-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (124 mg, 0.39 mmol), Pd(dppf)Cl2 (38 mg, 0.05 mmol), potassium carbonate (107 mg, 0.77 mmol) were added to 1,4-dioxa]in (1,4-di oxane, 2 ml) and ethanol (EtOH, 1 ml). Afterwards, the reaction mixture was stirred at 100°C for 16 hours. After completion of the reaction, the reaction mixture was filtered using Celite and magnesium sulfate and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (Me0H / DCM=1 / 10) to obtain the target compound C1 (73 mg, 60%) as a brown solid.

[0337] 1 H NMR (400MHz, Methanol -d4) 5 7.71 (d, J = 8.0 Hz, 1H) , 7.54 (d, J = 7.2 Hz, IH), 7.43 (d 7 = 7.2 Hz, IH) , 7.24 (d 7 = 8.4 Hz, IH) , 4.87 (s, 2H), 4.14-4.05 (m, 3H) , 3.01 (s, 3H) , 2.76-2.74 (m, IH) , 2.31-2.28 (m, IH) , 2.19 (s, 2H), 1.84-1.67 (m, IH) , 1.13 (t 7 = 7.2 Hz 3H); LC / MS: m / z 476.1 (M+H)+(ES).

[0338] [Step 2] Synthesis of Compound C2 Compound Cl (73 mg, 0.15 mmol) was dissolved in dichloromethane (DCM, 2 mL) and methanol (MeOH, 1 mL), and then hydrochloric acid solution (4N HC1 in 1,4-di oxane, 0.39 ml) was added at 0°C. The reaction mixture was stirred at room temperature for 16 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure to obtain the target compound C2 (58 mg, 89%) as a light-colored solid.

[0339] 1 H NMR (400MHz, Methanol -d4) 5 7.62 (d, J = 5.6 Hz, IH) , 7.56-7.54 (m, 2H), 7.28 (d, J = 8.0 Hz, IH) , 4.44-4.38 (m, 2H) , 4.30-4.17 (m, 2H) , 3.73 (s, 2H), 2.97-2.88 (m, IH), 2.45-2.36 (m, 4H), 2.00-1.81 (m, IH), 1.84-1.67 (m, IH), 1.31-1.22 (m, 3H); LC / MS: m / z 432.1 (M+H)+(ES).

[0340] [Step 3] Synthesis of Compound 107 Compound C2 (58 mg, 0.13 mmol) was dissolved in ethanol (EtOH, 3 mL), and 2 M aqueous sodium hydroxide solution (0.1 mL, 6.5 mmol) was added. The reaction mixture was stirred at 80°C for 16 hours. After completion of the reaction, the reaction mixture was filtered using Celite and magnesium sulfate and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (Me0H / DCM=1 / 10) to obtain the target compound 107 (36 mg, 74%) as a yellow solid.

[0341] 1H NMR (400MHz, Methanol -d4) 5 7.62 (d, J = 0.8 Hz, 1H) , 7.61-7.53 (m, 2H), 7.28 (d, J = 8.0 H, IH) , 4.44-4.36 (m, IH) , 3.15 (t, J = 13.2 Hz, IH), 2.88-2.75 (m, IH), 2.57 (t, J = 10.8 Hz, IH), 2.50-2.34 m, 4H), 1.97- 1.80 (m, IH); LC / MS: m / z 360.0 (M+H)+(ES). Example 108: (R)-6-(Benzo[b]thiophene-5-yl)-5-methyl-N-(l-propylpiperidine-3-y1)-1,2,4-triazin-3-amine 108 (R)-6-chloro-5-methyl-N-(1-propylpiperidin-3-yl)-1,2,4-triazin-3-amine

[0342] (51 mg, 0.19 mmol), benzo[b]thiophene-5-ylboronic acid (52 mg, 0.29 mmol), Pd(dppf)C12 (29 mg, 0.04 mmol), and potassium carbonate (79 mg, 0.57 mmol) were added to 1,4-dioxane (1,4-di oxane, 0.3 ml) and water (EbO, 0.1 ml). The reaction mixture was stirred at 100°C for 16 hours. After completion of the reaction, the reaction mixture was filtered using celite and magnesium sulfate and concentrated under reduced pressure. The reaction concentrate was purified by silica gel column chromatography (Me0H / DCM=1 / 10) to obtain the target compound 108 (39 mg, 56%) as a brown solid.

[0343] 1 H NMR (400MHz, Methanol -d4) 5 7.73 (m, 2H) , 7.65 (s, 1H) , 6.99 (t,

[0344] J = 72.8 Hz, IH), 4.20 (m, IH), 3.09 (m, IH), 2.77 (m, IH), 2.35 (s, 3H),

[0345] 2.26 (s, 3H), 2.18-2.14 (m, 2H), 2.05-2.03 (m, IH), 1.89-1.83 (m, IH), 1.78-

[0346] 1.67 (m, IH), 1.50-1.41 (m, IH); LC / MS: m / z 368.2 (M+H)+(ES).

[0347] <Experimental Example> Experimental Example 1: ELISA for interleukin-lg (IL-1(3)) Mouse cell line J774A.1 (ATCC) was cultured in DMEM medium [DMEM (Hyclone) + 10% fetal bovine serum (Hyclone) + 1% penicillin-streptomycin (Hyclone)]. Human cell line THP-1 (ATCC) was cultured in RPMI medium [RPMI (Hyclone) + 10% fetal bovine serum (Hyclone) + 1% penicillin-streptomycin (Hyclone) + 0.05 mM 2-mecaptoethanol].

[0348] J774A.1 cells were seeded at a density of 100,000 cells / well in a 96-well plate (tissue culture plate, 96 well, Falcon), treated with LPS (Sigma) (2 ug / ml) for 4 hours, and then treated with each of the compounds of the present invention (0.001 to 10,000 nM) for 30 minutes. Thereafter, inflammasome was induced by treatment with ATP (Sigma) (5 mM) for 1 hour.

[0349] THP-1 cells were seeded at a density of 50,000 cells / well in a 96-well plate (tissue culture plate, 96 well, Falcon), treated with LPS (sigma) (2 ug / ml) for 4 hours, and then treated with each of the compounds of the present invention (0.001 to 10,000 nM) for 30 minutes. Thereafter, inflammasomes were induced by treatment with nigericin (sigma) (5 uM).

[0350] IL-ip was measured using an ELISA kit (Invitrogen) according to the manufacturer's instructions, and absorbance was measured at 450 nm using a spectrophotometric microplate reader (BioTek, Synergy H4). IC50 values ​​were calculated based on inflammasome-induced and non-induced samples. The results are shown in Table 11 below.

[0351] [Table 11] As can be confirmed in Table 11 above, the compound of the present invention exhibits inflammasome inhibitory activity. Experimental Example 2: Evaluation of CYP (Cytrochrome P450) activity inhibition ability 7} In order to evaluate the activity inhibition ability of the compound of the present invention against CYP (Cytochrome P450), the inhibitory activity of the compound of the present invention against drug metabolizing enzymes, CYP3A4 and CYP2C9, which are known to be important in drug metabolism in humans, was evaluated. Specifically, the inhibitory activity analysis of CYP3A4 and CYP2C9 was performed using Invitrogen (P2861, P2858) kits. In the case of the above Invitrogen kit, the compound of the present invention was prepared by diluting it in Vivid CYP450 reaction buffer (lx) to 2.5X the final experimental concentration, and the P450 BACULOSOMES sample and the Regenerat ion system (100x) were prepared by diluting it in Vivid CYP450 reaction buffer (lx) to a concentration appropriate for the CYP450 type. In a U-bottom 96-well plate, 40 M of the compound of the present invention prepared at 2.5X the final experimental concentration and 50 seeds of the diluted P450 BACULOSOMES sample mixture were mixed, and pre-incubation was performed for 20 to 30 minutes. After diluting Vivid CYP450 Substrate and NADP+ (100>〈 ) in Vivid CYP450 reaction buffer (IX) at a concentration appropriate for the CYP450 and substrate types, 10 M of Substrate-NADP+ mix was added to the plate where the pre-reaction was completed and reacted for 30 minutes to 1 hour.After the reaction was completed, the reactants were transferred to a white plate and the fluorescence wavelengths were read in a microplate reader (1A2, 2B6, 2C9, 2C19, 2D6, 3A4 excitation 409 nm, emission 460 nm, 2C8 excitation 485 nm, emission 535 nm). The experimental results were calculated as (1-(test substance fluorescence value / vehicle fluorescence value)) X 100% and are shown in Table 12 below.

[0352] [Table 12] In general, if a compound at a concentration of 10 iiM inhibits the activity of a CYP enzyme by more than 50%, it is predicted to be a substance requiring attention regarding the activity of the CYP enzyme. As can be confirmed in Table 12 above, the compound of the present invention is confirmed to be a substance with an inhibitory ability of less than 50% for CYP3A4 and CYP2C9. Experimental Example 3: Evaluation of In vivo Interleukin-13 (IL-13) Inhibitory Ability In order to evaluate the inflammasome activity inhibitory ability of the compound of the present invention, the following was performed. After orally administering the compound of the present invention to 6-8 week old C57BL / 6J male mice, one hour later, LPS (Lipopoly saccharide, Invivogen) dissolved in saline was intraperitoneally injected at 50 drops per mouse. Two hours after LPS injection, inflammasomes were induced by intraperitoneal injection of 12.5 mg of ATP (adenosine triphosphate, Sigma) dissolved in saline per mouse. Thirty minutes after ATP injection, blood was collected through a capillary tube from the orbital vein of the mice. The blood was collected in 1.7 ml tubes and centrifuged at 6000 g, 4 °C, and 5 min to separate the plasma. To measure IL-1P in the plasma, the absorbance was measured at 450 nm using an ELISA kit (Invitrogen) and a spectrophotometric microplate reader according to the manufacturer's instructions. The concentration of IL-1P in the plasma was calculated from the absorbance, and the inflammasome inhibition efficacy was indicated as the ratio of the decrease in IL-1P compared to the vehicle (0.5% methylcellulose). The results are shown in Table 13 below.

[0353] [Table 13] As can be confirmed in Table 13 above, the compound of the present invention can inhibit the release of IL-1P induced by inflammasome. That is, the compound of the present invention exhibits inflammasome inhibitory activity. Experimental Example 4: Evaluation of hERG channel binding inhibition ability In order to evaluate the binding inhibition ability of the compound of the present invention to the hERG channel, the binding inhibition ability was evaluated using the Predictor hERG fluorescence polarization assay kit (Invitrogen). In the case of the Invitrogen kit, the hERG tracer and membrane fraction were prepared by melting at room temperature before use. The tracer and hERG assay buffer were diluted 1:62.5. The negative control group was used with the hERG assay buffer. The positive control E-4031 was prepared by diluting 1:25 with the hERG assay buffer. The compound of the present invention was prepared by diluting it in the hERG assay buffer (lx) to 4x the final experimental concentration. Each diluted compound solution was dispensed into 384-well low-volume flat-bottom microplates at 10 μl. Twenty-five microliters of each membrane fraction was dispensed into each well. Ten microliters of each hERG tracer was dispensed. The plates were incubated at 25°C for 2 hours in a light-blocking manner. Fluorescence polarization (MP) was measured using a microplate reader (Bioteck Synergy H4) at Excitation 530 nm and Emission 590 nm. The experimental results were calculated as (compound MP - negative control MP) / (positive control MP - negative control MP) X 100% and are shown in Table 14 below.

[0354] [Table 14] In general, if a compound at a concentration of 10 11M inhibits hERG inhibition by more than 50%, hERG K + It is judged to be a substance that causes cardiotoxicity by CHANNEL inhibition. As can be confirmed in Table 14 above, the inhibition rate of the compound of the present invention at a concentration of 10 iiM is less than 50%, indicating that hERG K + It is judged to be safe for inducing cardiotoxicity by CHANNEL binding. Experimental Example 5: To determine the NASH inhibitory efficacy of the NASH efficacy evaluation compound, the following is performed. 5-week-old male C57BL / 6J mice were housed under standard conditions (24 °C, 50% humidity, 12:12 light / dark cycle) and had a one-week acclimation period with normal food and water. In order to induce NASH in the mice, the mice were fed an MCD (Methionine-Chol ine Deficient) diet for 4 weeks, and thereafter, the vehicle, positive control drug, and the compound of the present invention were administered orally for 4 weeks simultaneously with the MCD diet. On the last day of the study, the mice were anesthetized with an isoprene solution, and blood was collected through the abdominal vena cava, and the mice were sacrificed by C02 asphyxiation to collect the liver. The collected blood was placed in a 1.7 ml tube and centrifuged at 6000 g, 4 ° C, for 5 minutes to separate the plasma. Liver values ​​such as ALT and AST and the concentration of neutral fat in the blood were tested using a plasma and blood biochemistry analyzer. The liver was immediately treated with a formalin solution and stained later to determine the degree of fibrosis. While the present invention has been described in detail, it will be apparent to those skilled in the art that such specific descriptions are merely preferred embodiments and that the scope of the present invention is not limited thereby. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.

Claims

【Scope of Claims】 【

1. A compound represented by the following chemical formula 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof: [Chemical formula 1] In the above chemical formula 1, R1 to R4 are two adjacent ones that form a ring together with the atoms to which they are attached, and the remaining two are each independently H, halogen, C1-C5 alkyl, 0-(Cl-C5 alkyl), C1-C5 haloalkyl or CN, wherein the ring is cycloalkyl, heterocycloalkyl or heteroaryl, and one or more of the cycloalkyl, heterocycloalkyl or heteroaryl may be independently substituted with halogen, C1-C5 alkyl, C1-C5 haloalkyl, OH, 0-CC1-C5 alkyl) or CN, and wherein when R1 and R2 form a ring, the ring is heterocycloalkyl or heteroaryl containing one or more heteroatoms independently selected from the group consisting of N and S, R5 is H, C1-C5 alkyl, cycloalkyl, cycloalkenyl, cycloalkynyl, Heterocycloalkyl, heterocycloalkenyl, heterocycloalkynyl, aryl, heteroaryl, (C1-C5 alkyl)-cycloalkyl, (C1-C5 alkyl)-cycloalkenyl, (C1-C5 alkyl)-cycloalkynyl, (C1-C5 alkyl)-heterocycloalkyl, (C1-C5 alkyl)-heterocycloalkenyl, (C1-C5 alkyl)-heterocycloalkynyl, (C1-C5 alkyl)-aryl, (C1-C5 alkyl)-heteroaryl, (C1-C5 alkyl) - N (R x )(R y ), (C1-C5 alkyl)- CN or (C1-C5 alkyl)- O(R Z ) and, One or more hydrogens of R5 are each independently R A can be replaced by R A is halogen, OH, CN, C1-C5 alkyl, C2-C5 alkenyl, C2-C5 alkynyl, C1-C5 haloalkyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heterocycloalkyl, heterocycloalkenyl, heterocycloalkynyl, aryl, heteroaryl, (C1-C5 alkyl)-cycloalkyl, (C1-C5 alkyl)-cycloalkenyl, (C1-C5 alkyl)-cycloalkynyl, (C1-C5 alkyl)-heterocycloalkyl, (C1-C5 alkyl)-heterocycloalkenyl, (C1-C5 alkyl)-heterocycloalkynyl, (C1-C5 alkyl)-aryl, (C1-C5 alkyl)-heteroaryl, (C1- C5 alkyl) - N(R x )(R y ), (C1-C5 alkyl)- CN, (C1-C5 alkyl)- O(R Z ), C(=O)R1 or (C1-C5 alkyl) - C(=O)R m And, R A One or more hydrogens are each independently R B can be replaced by R B is halogen, CN, C1-C5 alkyl, C1-C5 haloalkyl, N(R x )(R y ), O(R Z ), C(=O)R1 or S(=0)2R n and here R x , R y and R z are each independently H, C1-C5 alkyl or C1-C5 haloalkyl, and R1, Rm and R n are each independently H, OH, C1-C5 alkyl, 0-(Cl- C5 alkyl), N(R a )(R b ) or (C1-C5 alkyl) - N(R c )(R d ) and here R a , R b , R c and R d are each independently H, C1-C5 alkyl or C1-C5 haloalkyl, R6 is H, OH, 0-CC1-C5 alkyl) or C1-C5 haloalkyl, R7 is H, C1-C5 alkyl or C1-C5 haloalkyl, and halogen is F, Cl, Br or I. 【

2. In claim 1, the compound represented by the chemical formula 1 is a compound represented by the following chemical formula 1a, a compound represented by the chemical formula 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof: [Chemical Formula 1a] In the above chemical formula 1a, A is a heterocycloalkyl or heteroaryl containing one or more heteroatoms independently selected from the group consisting of N and , and one or more groups of A are each independently halogen, C1-C5 alkyl, C1-C5 haloalkyl, OH, 0-CC1-C5 alkyl) or can be substituted with , R3 and R4 are each independently H, halogen, C1-C5 alkyl, 0-CC1-C5 alkyl), C1- C5 haloalkyl or CN, and R5, R6, R7 and halogen are the same as defined in the above chemical formula 1. 【

3. In claim 1, the compound represented by the chemical formula 1 is a compound represented by the following chemical formula 1b, a compound represented by the chemical formula 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof: [Chemical Formula 1b] In the above chemical formula 1b, A is cycloalkyl, heterocycloalkyl or heteroaryl, and one or more groups of A may be independently substituted with halogen, C1-C5 alkyl, C1-C5 haloalkyl, OH, 0-CC1-C5 alkyl) or ash, and R1 and R4 are each independently H, halogen, C1-C5 alkyl, 0-CC1-C5 alkyl) or C1- C5 haloalkyl or CN, R5, R6, R7 and halogen are the same as defined in the above chemical formula 1. 【

4. In claim 1, the compound represented by the chemical formula 1 is a compound represented by the following chemical formula 1c, a compound represented by the chemical formula 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof: [Chemical Formula 1c] In the above chemical formula 1C, A is cycloalkyl, heterocycloalkyl or heteroaryl, and one or more of A may be independently substituted with halogen, C1-C5 alkyl, C1-C5 haloalkyl, OH, 0-CC1-C5 alkyl) or CN, and R1 and R2 are each independently H, halogen, C1-C5 alkyl, 0-CC1-C5 alkyl) or C1- C5 haloalkyl or CN, R5, R6, R7 and halogen are the same as defined in the above chemical formula 1. 【

5. In claim 1, the compound represented by the chemical formula 1 is a compound represented by the following chemical formula 1a-1, a compound represented by the chemical formula 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof: [Chemical Formula 1a-1] In the above chemical formula 1a-1, W1 and W2 are each independently CH, CH2, N, NH or S, R x is H, halogen, C1-C5 alkyl, C1-C5 haloalkyl, 0H, O-(C1- C5 alkyl) or CN, and R y And R4 are each independently H, halogen, C1-C5 alkyl, 0-CC1-C5 alkyl), C1- C5 haloalkyl or CN, are each independently a single bond or a double bond, and R5, R6, R7 and halogen are the same as defined in the above chemical formula 1. 【

6. In claim 1, the compound represented by the chemical formula 1 is a compound represented by the following chemical formula 1a-2 or chemical formula 1a-3, a compound represented by the chemical formula 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof: [Chemical Formula 1a-2] [Chemical Formula 1a-3] In each of the above chemical formula 1a-2 or chemical formula 1a-3, R3 and R4 are each independently H, halogen, C1-C5 alkyl, C1-C5 haloalkyl, 0- (C1-C5 alkyl) or CN, and R5, R6, R7 and halogen are the same as defined in the above chemical formula 1. 【

7. In claim 1, R1 to R4 are two adjacent ones that form a ring together with the atoms to which they are attached, and the remaining two are each independently H, halogen, C1-C5 alkyl, 0-(Cl-C5 alkyl), C1-C5 haloalkyl or CN, wherein the ring is cycloalkyl, heterocycloalkyl or heteroaryl, and one or more of the cycloalkyl, heterocycloalkyl or heteroaryl may be independently substituted with halogen, C1-C5 alkyl, C1-C5 haloalkyl, OH, 0-CC1-C5 alkyl) or CN, and wherein when R1 and R2 form a ring, the ring is heterocycloalkyl or heteroaryl containing one or more heteroatoms independently selected from the group consisting of N and S, R5 is H, C1-C5 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, (C1-C5 alkyl)-cycloalkyl, (C1-C5 alkyl)-heterocycloalkyl, (C1-C5 alkyl)-aryl, (C1-C5 alkyl)-heteroaryl, (C1-C5 alkyl)-N(R x )(R y ) or (C1-C5 alkyl)- 0(R z ) and, One or more hydrogens of R5 are each independently R A can be replaced by R A is halogen, OH, CN, C1-C5 alkyl, C2-C5 alkenyl, C2-C5 alkynyl, C1-C5 haloalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, (C1-C5 alkyl)- Cycloalkyl, (C1-C5 alkyl)-heterocycloalkyl, (C1-C5 alkyl)-aryl, (C1-C5 alkyl)-heteroaryl, (C1-C5 alkyl) - N(R x )(R y ), (C1-C5 alkyl)- O(R Z ), C(=O)R1 or (C1-C5 alkyl) - C(=O)R m And, R A One or more hydrogens are each independently R B can be replaced by R B is halogen, CN, C1-C5 alkyl, C1-C5 haloalkyl, N(R x )(R y ), O(R Z ), C(=O)R1 or S(=0)2R n and here R x , R y and R z are each independently H, C1-C5 alkyl or C1-C5 haloalkyl, and R1, Rm and R n are each independently H, OH, C1-C5 alkyl, 0- (Cl- C5 alkyl), N(R a )(R b ) or (C1-C5 alkyl) - N(R c )(R d ) and here R a , R b , R c and R d are each independently H, C1-C5 alkyl or C1-C5 haloalkyl, R6 is H, OH or O-(C1-C5 alkyl), A compound represented by formula 1, wherein R7 is H, C1-C5 alkyl or C1-C5 haloalkyl, and halogen is F or Cl, a stereoisomer thereof or a pharmaceutically acceptable salt thereof. 【

8. In claim 1, two adjacent ones of R1 to R4 form a ring together with the atoms to which they are attached, and the remaining two are each independently H, halogen or C1-C5 alkyl, wherein the ring is cycloalkyl, heterocycloalkyl or heteroaryl, One or more of cycloalkyl, heterocycloalkyl or heteroaryl may be independently substituted with halogen, C1-C5 haloalkyl or 0-CC1-C5 alkyl, wherein when R1 and R2 form a ring, the ring is a heteroaryl containing one or more heteroatoms independently selected from the group consisting of N and S, R5 is C1-C5 alkyl, cycloalkyl, heterocycloalkyl, (C1-C5 alkyl)-heterocycloalkyl, (C1-C5 alkyl)-aryl, (C1-C5 alkyl)-heteroaryl, (C1-C5 alkyl) - N(R x )(R y ) or (C1-C5 alkyl)- O(R Z ) and, One or more hydrogens of R5 are each independently R A can be replaced by R A is halogen, OH, C1-C5 alkyl, C2-C5 alkynyl, C1-C5 haloalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, (C1-C5 alkyl)-cycloalkyl, (C1-C5 alkyl)- O(R Z ), C(=O)R1 or (C1-C5 alkyl) - C(=O)R m And, R A One or more hydrogens are each independently R B can be replaced by R B is halogen, CN, C1-C5 alkyl, O(R Z ), C(=O)R1 or S(=O)2R n and here R x , R y and R z are each independently H, C1-C5 alkyl or C1-C5 haloalkyl, and R1, R m and R n are each independently OH, C1-C5 alkyl, 0-CC1-C5 alkyl) or N(R a )(R b ) and here R a and R b are each independently H or C1-C5 alkyl, R6 is H, 0H or 0-CC1-C5 alkyl), A compound represented by the formula 1, wherein R7 is C1-C5 alkyl or C1-C5 haloalkyl, and halogen is F or Cl, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof Acceptable salt. 【In claim 1, R1 to RD are two of which are adjacent and form a ring together with the atoms to which they are attached, and the remaining one is shown, wherein the ring is a heteroaryl containing one or more heteroatoms independently selected from the group consisting of N and S, R4 is visible, R5 is C1-C5 alkyl, cycloalkyl, heterocycloalkyl, (C1-C5 alkyl)-heterocycloalkyl, (C1-C5 alkyl)-aryl, (C1-C5 alkyl) - N(R x )(R y ) or (C1-C5 alkyl)- 0(R z ) and, One or more hydrogens of R5 are each independently R A can be replaced by R A is halogen, OH, C1-C5 alkyl, C1-C5 haloalkyl, cycloalkyl, heterocycloalkyl, aryl, (C1-C5 alkyl)-cycloalkyl, (C1-C5 alkyl)- 0(R z ), C(=0)R1 or (C1-C5 alkyl) - C(=0)R m And, R A One or more hydrogens are each independently R B can be replaced by R B is halogen, C1-C5 alkyl, 0(R z ) or C(=0)R1, where R x , R y and R z are each independently H, C1-C5 alkyl or C1-C5 haloalkyl, and R1, R m and R n are each independently OH, C1-C5 alkyl, O-CC1-C5 alkyl) or N(R a )( R b ) and here R a and R b are each independently C1-C5 alkyl, R6 is H, 0H or 0-(Cl- C5 alkyl), A compound represented by chemical formula 1, wherein R7 is C1-C5 alkyl and halogen is F, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

10. A compound described in the table below, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof: 【

11. A pharmaceutical composition comprising a compound according to any one of claims 1 to 10, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. 【

12. A pharmaceutical composition according to claim 11, wherein the pharmaceutical composition is for the prevention or treatment of a disease related to NLRP3 activity.

13. A pharmaceutical composition according to claim 12, wherein the NLRP3 activity-related disease comprises at least one disease selected from inflammation, autoimmune disease, cancer, infection, central nervous system disease, metabolic disease, cardiovascular disease, respiratory disease, liver disease, kidney disease, eye disease, skin disease, lymphatic disease, psychological disorder, graft-versus-host disease, allodynia, wounds, and scars.

14. A method for preventing or treating a disease associated with NLRP3 activity, comprising administering a therapeutically effective amount of a compound according to any one of claims 1 to 10, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

15. Use of a compound according to any one of claims 1 to 10, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof for the prevention or treatment of a disease associated with NLRP3 activity.

16. Use of a compound according to any one of claims 1 to 10, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for the prevention or treatment of a disease associated with NLRP3 activity.

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