4-(methylthio)pyrrole derivative

Abstract

The present disclosure provides a compound represented by chemical formula 1 or a pharmaceutically acceptable salt thereof. [Chemical formula 1] In chemical formula 1, R1 is an optionally substituted heterocyclic group or an optionally substituted phenyl group, and R2 is an optionally substituted heterocyclic group or an optionally substituted phenyl group.

Description

4-methylthiopyrrole derivative

[0001] The present invention relates to a novel gastric acid secretion inhibitor.

[0002] The present disclosure claims the benefit of priority based on Korean Patent Application No. 10-2024-0192864 filed December 20, 2024 and Korean Patent Application No. 10-2025-0204294 filed December 19, 2025, and all contents of Korean Patent Application No. 10-2024-0192864 and Korean Patent Application No. 10-2025-0204294 are incorporated by reference into the present disclosure.

[0003]

[0004] Gastric acid secretion inhibitors are drugs developed to treat or prevent diseases such as gastric ulcers and gastroesophageal reflux disease, and several generations of these drugs have been developed. Initially, antacids were developed to neutralize gastric acid, followed by H2 blockers that inhibit gastric acid secretion by blocking histamine receptors. Next, proton pump inhibitors were developed, which provide a potent and sustained effect by irreversibly blocking the final stage of gastric acid secretion.

[0005] Most recently, potassium-competitive acid secretion inhibitors (CPIS) have been developed, which inhibit gastric acid secretion by competitively binding potassium ions to proton pumps (K+ / H+ ATPases). CPIS possesses advantages such as sustained and potent efficacy, low drug tolerance, the ability to take medication regardless of meals, rapid onset of action, and a low risk of nocturnal acid breakthrough, and are recently gaining market share.

[0006]

[0007] The problem that the technical concept of the present disclosure aims to solve is to provide a novel gastric acid secretion inhibitor.

[0008]

[0009] Exemplary embodiments of the present disclosure capable of solving the above-mentioned problem are as follows.

[0010]

[0011] A compound or a pharmaceutically acceptable salt thereof according to exemplary embodiments may be represented by the following chemical formula 1.

[0012] [Chemical Formula 1]

[0013]

[0014] In the above chemical formula 1,

[0015] R1 is an optionally substituted heterocyclic group or an optionally substituted phenyl group, and

[0016] R2 is an arbitrarily substituted heterocyclic group or an arbitrarily substituted phenyl group.

[0017]

[0018] The above compound can be represented by the following chemical formula 1-1.

[0019] [Chemical Formula 1-1]

[0020]

[0021] In the above chemical formula 1-1,

[0022] X is C or N, and

[0023] R3 and R4 are independently hydrogen, halogen, hydroxyl, and C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl or C 1-4 It is a haloalkyl, and

[0024] R5, R6, and R7 are independently hydrogen, halogen, hydroxyl, and C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl or C 1-4 It is a haloalkyl.

[0025]

[0026] In the above chemical formula 1-1,

[0027] X is C or N, and

[0028] R3 and R4 are independently hydrogen, halogen, and C 1-4 Alkoxy, C 1-4 alkyl or C 1-4 It is a haloalkyl, and

[0029] R5, R6, and R7 can be hydrogen or halogen independently of each other.

[0030]

[0031] The above compound can be represented by the following chemical formula 1-2.

[0032] [Chemical Formula 1-2]

[0033]

[0034] In the above chemical formula 1-2,

[0035] X is C or N, and

[0036] R3 and R4 are independently hydrogen, halogen, hydroxyl, and C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl or C 1-4 It is a haloalkyl, and

[0037] R5, R6, and R7 are independently hydrogen, halogen, hydroxyl, and C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl or C 1-4 It is a haloalkyl.

[0038]

[0039] In the above chemical formula 1-2,

[0040] X is C or N, and

[0041] R3 and R4 are independently hydrogen, halogen, and C 1-4 Alkoxy, C 1-4 alkyl or C 1-4 It is a haloalkyl, and

[0042] R5, R6, and R7 can be hydrogen or halogen independently of each other.

[0043]

[0044] The above compound can be represented by the following chemical formula 1-3.

[0045] [Chemical Formula 1-3]

[0046]

[0047] In the above chemical formula 1-3,

[0048] X is C or N, and

[0049] R3 and R4 are independently hydrogen, halogen, hydroxyl, and C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl or C 1-4 It is a haloalkyl, and

[0050] R5 and R6 are independently hydrogen, halogen, hydroxyl, and C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl or C 1-4 It is a haloalkyl.

[0051]

[0052] In the above chemical formula 1-3,

[0053] X is C or N, and

[0054] R3 and R4 are independently hydrogen, halogen, and C 1-4 Alkoxy, C 1-4 alkyl or C 1-4 It is a haloalkyl, and

[0055] R5 and R6 can be hydrogen or halogen independently of each other.

[0056]

[0057] The above compound can be represented by the following chemical formula 1-4.

[0058] [Chemical Formula 1-4]

[0059]

[0060] In the above chemical formula 1-4,

[0061] X is C or N, and

[0062] R3 and R4 are independently hydrogen, halogen, hydroxyl, and C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl or C 1-4 It is a haloalkyl, and

[0063] R5 and R6 are independently hydrogen, halogen, hydroxyl, and C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl or C 1-4 It is a haloalkyl.

[0064]

[0065] In the above chemical formula 1-4,

[0066] X is C or N, and

[0067] R3 and R4 are independently hydrogen, halogen, and C 1-4 Alkoxy, C 1-4 alkyl or C 1-4 It is a haloalkyl, and

[0068] R5 and R6 can be hydrogen or halogen independently of each other.

[0069]

[0070] The above compound can be represented by the following chemical formula 1-5.

[0071] [Chemical Formula 1-5]

[0072]

[0073] In the above chemical formula 1-5,

[0074] X is C or N, and

[0075] R3 and R4 are independently hydrogen, halogen, hydroxyl, and C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl or C 1-4 It is a haloalkyl, and

[0076] R5 and R6 are independently hydrogen, halogen, hydroxyl, and C 1-4 Alkoxy, amino, C 1-4Alkyl, C 1-4 Carboxyl or C 1-4 It is a haloalkyl.

[0077]

[0078] In the above chemical formula 1-5,

[0079] X is C or N, and

[0080] R3 and R4 are independently hydrogen, halogen, and C 1-4 Alkoxy, C 1-4 alkyl or C 1-4 It is a haloalkyl, and

[0081] R5 and R6 can be hydrogen or halogen independently of each other.

[0082]

[0083] The above compound can be represented by the following chemical formula 1-6.

[0084] [Chemical Formula 1-6]

[0085]

[0086] In the above chemical formula 1-6,

[0087] X is C or N, and

[0088] R3 and R4 are independently hydrogen, halogen, hydroxyl, and C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl or C 1-4 It is a haloalkyl, and

[0089] R5, R6, and R7 are independently hydrogen, halogen, hydroxyl, and C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl or C 1-4 It is a haloalkyl.

[0090]

[0091] In the above chemical formula 1-6,

[0092] X is C or N, and

[0093] R3 and R4 are independently hydrogen, halogen, and C1-4 Alkoxy, C 1-4 alkyl or C 1-4 It is a haloalkyl, and

[0094] R5, R6, and R7 can be hydrogen or halogen independently of each other.

[0095]

[0096] The above compound may be any one selected from the group consisting of the following compounds.

[0097] 1) N-methyl-1-(4-(methylthio)-5-phenyl-1-(phenylsulfonyl)-1H-pyrrole-3-yl)methaneamine

[0098] 2) N-methyl-1-(4-(methylthio)-5-phenyl-1-(pyridine-3-ylsulfonyl)-1H-pyrrole-3-yl)methaneamine

[0099] 3) 1-(1-((3-fluorophenyl)sulfonyl)-4-(methylthio)-5-phenyl-1H-pyrrole-3-yl)-N-methylmethaneamine

[0100] 4) 1-(1-((3-chlorophenyl)sulfonyl)-4-(methylthio)-5-phenyl-1H-pyrrole-3-yl)-N-methylmethaneamine

[0101] 5) 1-(1-((3-methoxyphenyl)sulfonyl)-4-(methylthio)-5-phenyl-1H-pyrrole-3-yl)-N-methylmethaneamine

[0102] 6) N-methyl-1-(4-(methylthio)-5-phenyl-1-((3-(trifluoromethyl)phenyl)sulfonyl)-1H-pyrrole-3-yl)methaneamine

[0103] 7) N-methyl-1-(4-(methylthio)-5-phenyl-1-(m-tolylsulfonyl)-1H-pyrrole-3-yl)methaneamine

[0104] 8) 1-(1-((3-chloro-4-fluorophenyl)sulfonyl)-4-(methylthio)-5-phenyl-1H-pyrrole-3-yl)-N-methylmethaneamine

[0105] 9) 1-(1-((3,4-difluorophenyl)sulfonyl)-4-(methylthio)-5-phenyl-1H-pyrrole-3-yl)-N-methylmethaneamine

[0106] 10) 1-(5-(2-fluorophenyl)-4-(methylthio)-1-(phenylsulfonyl)-1H-pyrrole-3-yl)-N-methylmethaneamine

[0107] 11) 1-(5-(2-fluorophenyl)-4-(methylthio)-1-(pyridine-3-ylsulfonyl)-1H-pyrrole-3-yl)-N-methylmethaneamine

[0108] 12) 1-(5-(2-fluorophenyl)-1-((3-fluorophenyl)sulfonyl)-4-(methylthio)-1H-pyrrole-3-yl)-N-methylmethaneamine

[0109] 13) 1-(1-((3-chlorophenyl)sulfonyl)-5-(2-fluorophenyl)-4-(methylthio)-1H-pyrrole-3-yl)-N-methylmethaneamine

[0110] 14) 1-(5-(2-fluorophenyl)-1-((3-methoxyphenyl)sulfonyl)-4-(methylthio)-1H-pyrrole-3-yl)-N-methylmethaneamine

[0111] 15) 1-(5-(2-fluorophenyl)-4-(methylthio)-1-((3-(trifluoromethyl)phenyl)sulfonyl)-1H-pyrrole-3-yl)-N-methylmethaneamine

[0112] 16) 1-(5-(2-fluorophenyl)-4-(methylthio)-1-(m-tolylsulfonyl)-1H-pyrrole-3-yl)-N-methylmethaneamine

[0113] 17) 1-(1-((3-chloro-4-fluorophenyl)sulfonyl)-5-(2-fluorophenyl)-4-(methylthio)-1H-pyrrole-3-yl)-N-methylmethaneamine

[0114] 18) 1-(1-((3,4-difluorophenyl)sulfonyl)-5-(2-fluorophenyl)-4-(methylthio)-1H-pyrrole-3-yl)-N-methylmethaneamine

[0115] 19) 1-(5-(2,4-difluorophenyl)-4-(methylthio)-1-(phenylsulfonyl)-1H-pyrrole-3-yl)-N-methylmethaneamine

[0116] 20) N-methyl-1-(4-(methylthio)-1-(phenylsulfonyl)-5-(2,4,6-trifluorophenyl)-1H-pyrrole-3-yl)methaneamine

[0117] 21) 1-(5-(2,6-difluorophenyl)-4-(methylthio)-1-(phenylsulfonyl)-1H-pyrrole-3-yl)-N-methylmethaneamine

[0118] 22) 1-(5-(2,5-difluorophenyl)-4-(methylthio)-1-(phenylsulfonyl)-1H-pyrrole-3-yl)-N-methylmethaneamine

[0119] 23) 1-(5-(4-chloro-2-fluorophenyl)-4-(methylthio)-1-(phenylsulfonyl)-1H-pyrrole-3-yl)-N-methylmethaneamine

[0120] 24) 1-(5-(2-chloro-6-fluorophenyl)-4-(methylthio)-1-(phenylsulfonyl)-1H-pyrrole-3-yl)-N-methylmethaneamine

[0121]

[0122] A pharmaceutical composition according to exemplary embodiments comprises the compound and may be used for the treatment of gastrointestinal diseases, gastroesophageal diseases, gastroesophageal reflux disease (GRED), laryngopharyngeal reflux disease, peptic ulcer, gastric ulcer, duodenal ulcer, non-steroidal anti-inflammatory drug (NSAID)-induced ulcer, gastritis, Helicobacter pylori infection, dyspepsia, functional dyspepsia, Zollinger-Ellison syndrome, non-erosive reflux disease (NERD), visceral referred pain, cancer, heartburn, nausea, esophagitis, dysphagia, drooling, airway obstruction, or asthma.

[0123]

[0124] 4-methylthiopyrrole derivatives according to exemplary embodiments of the present disclosure can inhibit gastric acid secretion.

[0125] The effects of the exemplary embodiments of the present disclosure are not limited to those mentioned above, and other unmentioned effects can be clearly derived and understood by those skilled in the art from the following description. That is, unintended effects resulting from the implementation of the embodiments of the present disclosure can also be clearly derived and understood by those skilled in the art.

[0126]

[0127] Figure 1 is a graph showing the inhibitory effect of 1 μM of Example 11 and Comparative Example (vonoprazan) on proton pump (H+ / K+-ATPase) activity.

[0128]

[0129] Terms or words used in this disclosure should not be interpreted as being limited to their ordinary or dictionary meanings, but should be interpreted in a meaning consistent with the technical concept of this disclosure, based on the principle that the inventor can appropriately define the meaning of terms or words to best describe his own invention.

[0130] In the present disclosure, terms such as “comprising” or “having” are intended to specify the existence of the features, numbers, steps, actions, components, parts, or combinations thereof described in the specification, and should be understood as not precluding the existence or addition of one or more other features, numbers, steps, actions, components, parts, or combinations thereof. Furthermore, when a part such as a layer, film, region, or plate is described as being “on” another part, this includes not only cases where it is “immediately above” the other part, but also cases where there is another part in between. Conversely, when a part such as a layer, film, region, or plate is described as being “under” another part, this includes not only cases where it is “immediately below” the other part, but also cases where there is another part in between.

[0131] In describing the present disclosure, if it is determined that a detailed description of a known configuration or function could obscure the essence of the present disclosure, such detailed description is omitted.

[0132]

[0133] Compounds according to exemplary embodiments can be represented by the following chemical formula 1.

[0134] [Chemical Formula 1]

[0135]

[0136] In the above chemical formula 1,

[0137] R1 is an optionally substituted heterocyclic group or an optionally substituted phenyl group, and

[0138] R2 is an arbitrarily substituted heterocyclic group or an arbitrarily substituted phenyl group.

[0139]

[0140] In the above chemical formula 1, R1 may be an unsubstituted heterocyclic group.

[0141] In the above chemical formula 1, R1 may be an unsubstituted aromatic heterocyclic group.

[0142] In the above chemical formula 1, R1 may be an unsubstituted monocyclic aromatic heterocyclic group.

[0143] In the above chemical formula 1, R1 may be an unsubstituted monocyclic aromatic heterocyclic group containing nitrogen. In the above chemical formula 1, R1 may be an unsubstituted monocyclic aromatic heterocyclic group containing 1 to 4 nitrogen atoms. In the above chemical formula 1, R1 may be an unsubstituted monocyclic aromatic heterocyclic group containing 1 to 2 nitrogen atoms.

[0144] In the above chemical formula 1, R1 may be an unsubstituted 6-membered monocyclic aromatic heterocyclic group containing one nitrogen. In the above chemical formula 1, R1 may be pyridine.

[0145] In the above chemical formula 1, R1 may be an unsubstituted 6-membered monocyclic aromatic heterocyclic group containing two nitrogen atoms. In the above chemical formula 1, R1 may be one of pyridazine, pyrimidine, and pyrazine.

[0146]

[0147] In the above chemical formula 1, R1 may be a substituted heterocyclic group.

[0148] In the above Chemical Formula 1, R1 is one or more halogens (fluorine, chlorine, bromine, iodine, etc.), hydroxyl, C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl and C 1-4 It can be substituted with one or more of the haloalkyls.

[0149] In the above chemical formula 1, R1 may be a substituted aromatic heterocyclic group.

[0150] In the above chemical formula 1, R1 may be a substituted monocyclic aromatic heterocyclic group.

[0151] In the above chemical formula 1, R1 may be a substituted monocyclic aromatic heterocyclic group containing nitrogen. In the above chemical formula 1, R1 may be a substituted monocyclic aromatic heterocyclic group containing 1 to 4 nitrogen atoms. In the above chemical formula 1, R1 may be a substituted monocyclic aromatic heterocyclic group containing 1 to 2 nitrogen atoms.

[0152] In the above Chemical Formula 1, R1 may be a substituted 6-membered monocyclic aromatic heterocyclic group containing one nitrogen. In the above Chemical Formula 1, R1 is one or more halogens (fluorine, chlorine, bromine, iodine, etc.), hydroxy, C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl and C 1-4 It may be pyridine substituted with one or more haloalkyls.

[0153] In the above Chemical Formula 1, R1 may be a substituted 6-membered monocyclic aromatic heterocyclic group containing two nitrogen atoms. In the above Chemical Formula 1, R1 is one or more halogens (fluorine, chlorine, bromine, iodine, etc.), hydroxy, C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl and C 1-4 It may be one of pyridazine, pyrimidine, and pyrazine substituted with one or more haloalkyls.

[0154]

[0155] In the above chemical formula 1, R1 may be an unsubstituted phenyl group.

[0156]

[0157] In the above chemical formula 1, R1 may be a substituted phenyl group.

[0158] In the above Chemical Formula 1, R1 is one or more halogens (fluorine, chlorine, bromine, iodine, etc.), hydroxyl, C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl and C 1-4 It may be a phenyl group substituted with one or more of the haloalkyls.

[0159]

[0160] In the above chemical formula 1, R2 may be an unsubstituted heterocyclic group.

[0161] In the above chemical formula 1, R2 may be an unsubstituted aromatic heterocyclic group.

[0162] In the above chemical formula 1, R2 may be an unsubstituted monocyclic aromatic heterocyclic group.

[0163] In the above chemical formula 1, R2 may be an unsubstituted monocyclic aromatic heterocyclic group containing nitrogen. In the above chemical formula 1, R2 may be an unsubstituted monocyclic aromatic heterocyclic group containing 1 to 4 nitrogen atoms. In the above chemical formula 1, R2 may be an unsubstituted monocyclic aromatic heterocyclic group containing 1 to 2 nitrogen atoms.

[0164] In the above chemical formula 1, R2 may be an unsubstituted 6-membered monocyclic aromatic heterocyclic group containing one nitrogen. In the above chemical formula 1, R2 may be pyridine.

[0165] In the above chemical formula 1, R2 may be an unsubstituted 6-membered monocyclic aromatic heterocyclic group containing two nitrogen atoms. In the above chemical formula 1, R2 may be one of pyridazine, pyrimidine, and pyrazine.

[0166]

[0167] In the above chemical formula 1, R2 may be a substituted heterocyclic group.

[0168] In the above Chemical Formula 1, R2 is one or more halogens (fluorine, chlorine, bromine, iodine, etc.), hydroxyl, C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl and C 1-4 It can be substituted with one or more of the haloalkyls.

[0169] In the above chemical formula 1, R2 may be a substituted aromatic heterocyclic group.

[0170] In the above chemical formula 1, R2 may be a substituted monocyclic aromatic heterocyclic group.

[0171] In the above chemical formula 1, R2 may be a substituted monocyclic aromatic heterocyclic group containing nitrogen. In the above chemical formula 1, R2 may be a substituted monocyclic aromatic heterocyclic group containing 1 to 4 nitrogen atoms. In the above chemical formula 1, R2 may be a substituted monocyclic aromatic heterocyclic group containing 1 to 2 nitrogen atoms.

[0172] In the above Chemical Formula 1, R2 may be a substituted 6-membered monocyclic aromatic heterocyclic group containing one nitrogen. In the above Chemical Formula 1, R2 is one or more halogens (fluorine, chlorine, bromine, iodine, etc.), hydroxy, C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl and C 1-4 It may be pyridine substituted with one or more haloalkyls.

[0173] In the above Chemical Formula 1, R2 may be a substituted 6-membered monocyclic aromatic heterocyclic group containing two nitrogen atoms. In the above Chemical Formula 1, R2 may be one or more halogens (fluorine, chlorine, bromine, iodine, etc.), hydroxy, C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl and C 1-4 It may be one of pyridazine, pyrimidine, and pyrazine substituted with one or more haloalkyls.

[0174]

[0175] In the above chemical formula 1, R2 may be an unsubstituted phenyl group.

[0176]

[0177] In the above Chemical Formula 1, R2 may be a substituted phenyl group. In the above Chemical Formula 1, R2 is one or more halogens (fluorine, chlorine, bromine, iodine, etc.), hydroxy, C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl and C 1-4 It may be a phenyl group substituted with one or more of the haloalkyls.

[0178]

[0179] Compounds according to exemplary embodiments can be represented by the following chemical formula 1-1.

[0180] [Chemical Formula 1-1]

[0181]

[0182] In the above chemical formula 1-1,

[0183] X is C or N, and

[0184] R3 and R4 independently consist of hydrogen, halogens (fluorine, chlorine, bromine, iodine, etc.), hydroxyl, and C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl or C 1-4 It is a haloalkyl, and

[0185] R5, R6, and R7 independently consist of hydrogen, halogens (fluorine, chlorine, bromine, iodine, etc.), hydroxyl, and C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl or C 1-4 It can be a haloalkyl.

[0186]

[0187] In the above chemical formula 1-1,

[0188] X is C or N, and

[0189] R3 and R4 independently contain hydrogen, halogens (fluorine, chlorine, bromine, iodine, etc.), and C 1-4 Alkoxy, C 1-4 alkyl or C 1-4 It is a haloalkyl, and

[0190] R5, R6, and R7 can be hydrogen or halogens (fluorine, chlorine, bromine, iodine, etc.) independently of each other.

[0191]

[0192] In the above chemical formula 1-1,

[0193] X is C or N, and

[0194] R3 and R4 are independently hydrogen, fluorine, chlorine, methoxy, methyl, or trifluoromethyl, and

[0195] R5, R6, and R7 can be hydrogen, fluorine, or chlorine independently of each other.

[0196]

[0197] Compounds according to exemplary embodiments can be represented by the following chemical formula 1-2.

[0198] [Chemical Formula 1-2]

[0199]

[0200] In the above chemical formula 1-2,

[0201] X is C or N, and

[0202] R3 and R4 independently consist of hydrogen, halogens (fluorine, chlorine, bromine, iodine, etc.), hydroxyl, and C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl or C 1-4 It is a haloalkyl, and

[0203] R5, R6, and R7 independently consist of hydrogen, halogens (fluorine, chlorine, bromine, iodine, etc.), hydroxyl, and C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl or C 1-4 It can be a haloalkyl.

[0204]

[0205] In the above chemical formula 1-2,

[0206] X is C or N, and

[0207] R3 and R4 independently contain hydrogen, halogens (fluorine, chlorine, bromine, iodine, etc.), and C 1-4 Alkoxy, C 1-4 alkyl or C 1-4 It is a haloalkyl, and

[0208] R5, R6, and R7 can be hydrogen or halogens (fluorine, chlorine, bromine, iodine, etc.) independently of each other.

[0209]

[0210] In the above chemical formula 1-2,

[0211] X is C or N, and

[0212] R3 and R4 are independently hydrogen, fluorine, chlorine, methoxy, methyl, or trifluoromethyl, and

[0213] R5, R6, and R7 can be hydrogen, fluorine, or chlorine independently of each other.

[0214]

[0215] Compounds according to exemplary embodiments can be represented by the following chemical formula 1-3.

[0216] [Chemical Formula 1-3]

[0217]

[0218] In the above chemical formula 1-3,

[0219] X is C or N, and

[0220] R3 and R4 independently consist of hydrogen, halogens (fluorine, chlorine, bromine, iodine, etc.), hydroxyl, and C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl or C 1-4 It is a haloalkyl, and

[0221] R5 and R6 independently consist of hydrogen, halogens (fluorine, chlorine, bromine, iodine, etc.), hydroxyl, and C 1-4 Alkoxy, amino, C 1-4 Alkyl, C1-4 Carboxyl or C 1-4 It can be a haloalkyl.

[0222]

[0223] In the above chemical formula 1-3,

[0224] X is C or N, and

[0225] R3 and R4 independently contain hydrogen, halogens (fluorine, chlorine, bromine, iodine, etc.), and C 1-4 Alkoxy, C 1-4 alkyl or C 1-4 It is a haloalkyl, and

[0226] R5 and R6 can independently be hydrogen or halogens (fluorine, chlorine, bromine, iodine, etc.).

[0227]

[0228] In the above chemical formula 1-3,

[0229] X is C or N, and

[0230] R3 and R4 are independently hydrogen, fluorine, chlorine, methoxy, methyl, or trifluoromethyl, and

[0231] R5 and R6 can be hydrogen, fluorine, or chlorine independently of each other.

[0232]

[0233] Compounds according to exemplary embodiments can be represented by the following chemical formula 1-4.

[0234] [Chemical Formula 1-4]

[0235]

[0236] In the above chemical formula 1-4,

[0237] X is C or N, and

[0238] R3 and R4 independently consist of hydrogen, halogens (fluorine, chlorine, bromine, iodine, etc.), hydroxyl, and C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl or C 1-4 It is a haloalkyl, and

[0239] R5 and R6 independently consist of hydrogen, halogens (fluorine, chlorine, bromine, iodine, etc.), hydroxyl, and C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl or C 1-4 It can be a haloalkyl.

[0240]

[0241] In the above chemical formula 1-4,

[0242] X is C or N, and

[0243] R3 and R4 independently contain hydrogen, halogens (fluorine, chlorine, bromine, iodine, etc.), and C 1-4 Alkoxy, C 1-4 alkyl or C 1-4 It is a haloalkyl, and

[0244] R5 and R6 can independently be hydrogen or halogens (fluorine, chlorine, bromine, iodine, etc.).

[0245]

[0246] In the above chemical formula 1-4,

[0247] X is C or N, and

[0248] R3 and R4 are independently hydrogen, fluorine, chlorine, methoxy, methyl, or trifluoromethyl, and

[0249] R5 and R6 can be hydrogen, fluorine, or chlorine independently of each other.

[0250]

[0251] Compounds according to exemplary embodiments can be represented by the following chemical formula 1-5.

[0252] [Chemical Formula 1-5]

[0253]

[0254] In the above chemical formula 1-5,

[0255] X is C or N, and

[0256] R3 and R4 independently consist of hydrogen, halogens (fluorine, chlorine, bromine, iodine, etc.), hydroxyl, and C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl or C 1-4 It is a haloalkyl, and

[0257] R5 and R6 independently consist of hydrogen, halogens (fluorine, chlorine, bromine, iodine, etc.), hydroxyl, and C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl or C 1-4 It can be a haloalkyl.

[0258]

[0259] In the above chemical formula 1-5,

[0260] X is C or N, and

[0261] R3 and R4 independently contain hydrogen, halogens (fluorine, chlorine, bromine, iodine, etc.), and C 1-4 Alkoxy, C 1-4 alkyl or C 1-4 It is a haloalkyl, and

[0262] R5 and R6 can independently be hydrogen or halogens (fluorine, chlorine, bromine, iodine, etc.).

[0263]

[0264] In the above chemical formula 1-5,

[0265] X is C or N, and

[0266] R3 and R4 are independently hydrogen, fluorine, chlorine, methoxy, methyl, or trifluoromethyl, and

[0267] R5 and R6 can be hydrogen or fluorine independently of each other.

[0268]

[0269] Compounds according to exemplary embodiments can be represented by the following chemical formula 1-6.

[0270] [Chemical Formula 1-6]

[0271]

[0272] In the above chemical formula 1-6,

[0273] X is C or N, and

[0274] R3 and R4 independently consist of hydrogen, halogens (fluorine, chlorine, bromine, iodine, etc.), hydroxyl, and C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl or C 1-4 It is a haloalkyl, and

[0275] R5, R6, and R7 independently consist of hydrogen, halogens (fluorine, chlorine, bromine, iodine, etc.), hydroxyl, and C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl or C 1-4 It can be a haloalkyl.

[0276]

[0277] In the above chemical formula 1-6,

[0278] X is C or N, and

[0279] R3 and R4 independently contain hydrogen, halogens (fluorine, chlorine, bromine, iodine, etc.), and C 1-4 Alkoxy, C 1-4 alkyl or C 1-4 It is a haloalkyl, and

[0280] R5, R6, and R7 can be hydrogen or halogens (fluorine, chlorine, bromine, iodine, etc.) independently of each other.

[0281]

[0282] In the above chemical formula 1-6,

[0283] X is C or N, and

[0284] R3 and R4 are independently hydrogen, fluorine, chlorine, methoxy, methyl, or trifluoromethyl, and

[0285] R5, R6, and R7 can be hydrogen, fluorine, or chlorine independently of each other.

[0286]

[0287] Compounds represented by Chemical Formula 1, Chemical Formula 1-1, Chemical Formula 1-2, Chemical Formula 1-3, Chemical Formula 1-4, Chemical Formula 1-5, or Chemical Formula 1-6 may have substituents containing asymmetric atoms.

[0288] Compounds represented by Chemical Formula 1, Chemical Formula 1-1, Chemical Formula 1-2, Chemical Formula 1-3, Chemical Formula 1-4, Chemical Formula 1-5, or Chemical Formula 1-6 include optical isomers such as R, S, and racemic mixtures.

[0289]

[0290] In the present disclosure, a pharmaceutically acceptable salt means a salt commonly used in the pharmaceutical industry and is not particularly limited. As a non-limiting example, a pharmaceutically acceptable salt may be a salt derived from an inorganic acid such as hydrochloric acid, hydrobromide, sulfuric acid, sulfamic acid, phosphoric acid, or nitric acid. As a non-limiting example, a pharmaceutically acceptable salt may be a salt derived from an organic acid such as acetic acid, propionic acid, succinic acid, glycolic acid, stearic acid, maleic acid, hydroxymaleic acid, phenylacetic acid, glutamic acid, benzoic acid, salicylic acid, sulfanilic acid, 2-acetoxybenzoic acid, fumaric acid, toluenesulfonic acid, methanedisulfonic acid, ethanedisulfonic acid, oxalic acid, or trifluoroacetic acid.

[0291] Pharmaceutically acceptable salts of compounds represented by Chemical Formula 1, Chemical Formula 1-1, Chemical Formula 1-2, Chemical Formula 1-3, Chemical Formula 1-4, Chemical Formula 1-5, or Chemical Formula 1-6 may be hydrochloride or fumarate.

[0292]

[0293] Compounds represented by Chemical Formula 1, Chemical Formula 1-1, Chemical Formula 1-2, Chemical Formula 1-3, Chemical Formula 1-4, Chemical Formula 1-5, or Chemical Formula 1-6, or pharmaceutically acceptable salts thereof, can be used to treat various diseases including gastrointestinal diseases, gastroesophageal diseases, gastroesophageal reflux disease (GRED), laryngopharyngeal reflux disease, peptic ulcer, gastric ulcer, duodenal ulcer, non-steroidal anti-inflammatory drug (NSAID)-induced ulcer, gastritis, Helicobacter pylori infection, dyspepsia, functional dyspepsia, Zollinger-Ellison syndrome, non-erosive reflux disease (NERD), visceral referred pain, cancer, heartburn, nausea, esophagitis, dysphagia, drooling, airway obstruction, or asthma by inhibiting gastric acid secretion.

[0294] Pharmaceutical compositions according to exemplary embodiments may comprise a compound represented by Formula 1, Formula 1-1, Formula 1-2, Formula 1-3, Formula 1-4, Formula 1-5, or Formula 1-6, or a pharmaceutically acceptable salt thereof. Pharmaceutical compositions according to exemplary embodiments may be used to treat various diseases including gastrointestinal diseases, gastroesophageal diseases, gastroesophageal reflux disease (GRED), laryngopharyngeal reflux disease, peptic ulcer, gastric ulcer, duodenal ulcer, non-steroidal anti-inflammatory drug (NSAID)-induced ulcer, gastritis, Helicobacter pylori infection, dyspepsia, functional dyspepsia, Zollinger-Ellison syndrome, non-erosive reflux disease (NERD), visceral referred pain, cancer, heartburn, nausea, esophagitis, dysphagia, drooling, airway obstruction, or asthma.

[0295] In the present disclosure, the term "treatment" includes all of the following: reversing, alleviating, suppressing, preventing, and treating the progression of a disorder or disease, or one or more symptoms of a disorder or disease.

[0296]

[0297] The compound represented by the above chemical formula 1-1 can be prepared in the same manner as the following reaction scheme 1.

[0298] [Reaction Equation 1]

[0299]

[0300]

[0301]

[0302] In the above reaction scheme 1, X is C or N, and R3 and R4 are independently hydrogen, halogen, hydroxyl, or C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl or C 1-4 It is a haloalkyl, and R5, R6, and R7 are independently hydrogen, halogen, hydroxyl, C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl or C 1-4 It is a haloalkyl. In exemplary examples, R3 and R4 are independently hydrogen, halogen, C 1-4 Alkoxy, C 1-4 alkyl or C 1-4 It is a haloalkyl. In exemplary examples, R5, R6, and R7 are independently hydrogen or halogen.

[0303]

[0304] In STEP 1, a formamide group may be substituted for the aldehyde group of the compound represented by 2, and then an isocyanide group may be introduced. In STEP 1, the compound represented by 2 may be reacted with formamide and formic acid at about 180 °C for about 2 hours, and then the amide may be dehydrogenated using phosphorus oxychloride.

[0305] In STEP 2, the compound represented by 4 can be reacted with a basic substance such as carbon disulfide and potassium carbonate in an organic solvent such as dimethylformamide, and a substitution reaction with methyl iodide can be carried out.

[0306] STEP 3 can be performed using potassium tert-butoxide in an organic solvent such as tetrahydrofuran for about 2 to 3 hours. A pyrrole ring can be formed as shown in the compound indicated by 6 in STEP 3.

[0307] STEP 4 can be performed for about 2 to 3 hours using 15-Crown-5, which can combine with basic substances such as sodium hydroxide and sodium ions in an organic solvent such as tetrahydrofuran.

[0308] STEP 5 is a step of reducing and then oxidizing the compound represented by 8. The reduction of the compound represented by 8 can be performed for about 30 minutes to about 1 hour using a reducing agent such as diisobutylaluminum hydride in an organic solvent such as dichloromethane. The oxidation of the reduced compound represented by 8 can be performed for about 1 hour to about 2 hours using an oxidizing agent such as Dess-Martin periodinane in an organic solvent such as dichloromethane.

[0309] STEP 6 is a step of reacting the compound represented by 9 with methylamine, and is a reducing amination reaction step. In STEP 6, the substance obtained by reacting the compound represented by 9 with methylamine for about 30 minutes to about 1 hour using a reducing agent such as sodium borohydride in an organic solvent such as tetrahydrofuran can be obtained in the form of a hydrochloride salt using an aqueous solution of hydrogen chloride and methanol.

[0310]

[0311] Example 11

[0312] 1-(5-(2-fluorophenyl)-4-(methylthio)-1-(pyridine-3-ylsulfonyl)-1H-pyrrole-3-yl)-N-methylmethaneamine hydrochloride

[0313]

[0314]

[0315] (Step 1) Preparation of 2-fluorobenzyl isothianide

[0316] 2-fluorobenzaldehyde (13, 10 mL, 94.9 mmol), formamide (45 mL, 1139 mmol, 12 eq.), and formic acid (28.6 mL, 759.3 mmol, 8 eq.) were placed in a 50 mL round-bottom flask, and a reflux condenser was installed. The reaction mixture was heated at 180 °C for 2 hours. After the reaction was complete, the mixture was cooled to room temperature, water and dichloromethane were added, and the organic layer was extracted (3 times). Anhydrous magnesium sulfide was added to the extracted organic layer, and after filtering and concentration, N-(2-fluorobenzyl)formamide (12 g, 78.3 mmol, 82%) was obtained as a white solid (it remains a solid when stored at low temperatures). Subsequently, N-(2-fluorobenzyl)formamide (12 g, 78.35 mmol) was placed in a 250 mL round-bottom flask, the mixture was switched to argon, and 39 mL of anhydrous dichloromethane was added. Triethylamine (54.6 mL, 392 mmol) was added to this mixture, and after cooling to 0 °C, phosphorus oxychloride (98.5 mL, 78.35 mmol) was slowly added dropwise. The reaction was carried out at room temperature for 3 hours, after which the reaction was monitored by TLC. The reaction mixture was cooled to 0 °C, and a saturated aqueous sodium bicarbonate solution was slowly added. After extraction with dichloromethane, anhydrous magnesium sulfide was added to the organic layer, and the mixture was filtered and concentrated to obtain 2-fluorobenzyl isocyanate (9.2 g, 68.1 mmol, 94%) as a red liquid.

[0317] 1 H-NMR (400 MHz, CDCl3) δ 7.47 (dd,J= 7.8, 6.9 Hz, 1H), 7.31-7.37 (m, 1H), 7.18-7.22 (m, 1H), 7.05-7.10 (m, 1H), 4.68 (s, 2H) ppm.

[0318]

[0319] (Step 2) Preparation of diethyl-2-(bis(methylthio)methylene)malonate

[0320] Potassium carbonate (12 g, 86.9 mmol, 2.2 eq.) was placed in a 100 mL round-bottom flask, followed by the addition of 15.8 mL of DMF. Diethyl malonate (6.0 mL, 39.5 mmol) was added to this mixture, and the solution was cooled to 0 °C. Carbon disulfide (0.22 mL, 3.62 mmol, 1.1 eq.) was added and stirred for 30 minutes, after which methyl iodide (5.4 mL, 86.9 mmol, 2.2 eq.) was slowly added dropwise. The reaction mixture was allowed to react at room temperature for 18 hours. After the reaction was complete, water was added to the mixture to terminate the reaction, and the organic layer was extracted with ethyl malonate. Anhydrous magnesium sulfide was added to the extracted organic layer, and after filtering and concentration, diethyl-2-(bis(methylthio)methylene)malonate (10 g, 37.8 mmol, 96%) was obtained as a yellow liquid.

[0321] 1 H-NMR (400 MHz, CDCl3) δ 4.24 (q,J= 7.2 Hz, 4H), 2.42 (s, 6H), 1.28 (t,J= 7.1 Hz, 6H) ppm.

[0322]

[0323] (Step 3) Ethyl 5-(2-fluorophenyl)-4-(methylthio)-1H-pyrrole-3-carboxylate

[0324] 38 mL of anhydrous THF was added to a 100 mL round-bottom flask and replaced with argon, after which diethyl 2-(bis(methylthio)methylene)malonate (12 g, 45.4 mmol) and 2-fluorobenzyl isothianate (9.2 mg, 68.1 mmol) were added. After cooling the reaction solution to -78 °C, potassium tertbutoxide (10 g, 90.8 mmol, 2 eq.) was slowly added. The reaction mixture was stirred at room temperature for 2 hours. After the reaction was complete, an aqueous solution of ammonium chloride saturated with chloroform was added to the compound, and the organic layer was extracted. The extracted organic layer was treated with anhydrous magnesium sulfate, filtered, and concentrated to obtain ethyl 5-(2-fluorophenyl)-4-(methylthio)-1-(pyridine-3-ylsulfonyl)-1-H-pyrrole-3-carboxylate (9.0 g, 32.22 mmol, 71%) as a white or light red solid using dichloromethane and hexane.

[0325] 1 H-NMR (400 MHz, CDCl3) δ 8.85 (s, 1H), 7.89 (td,J= 7.7, 1.7 Hz, 1H), 7.54 (d,J= 3.7 Hz, 1H), 7.29-7.35 (m, 1H), 7.21 (m, 1H), 7.14 (ddd,J= 11.4, 8.2, 0.9 Hz, 1H), 4.32 (q,J= 7.2 Hz, 2H), 2.34 (s, 3H), 1.62 (s, 1H), 1.36 (t,J= 7.1 Hz, 3H) ppm.

[0326]

[0327] (Step 4) Preparation of ethyl 5-(2-fluorophenyl)-4-(methylthio)-1-(pyridine-3-ylsulfonyl)-1H-pyrrole-3-carboxylate

[0328] Sodium hydride (3.87 g, 0.39 mmol) was placed in a 500 mL round-bottom flask and flushed with argon. The sodium hydride was washed twice with 3 mL of nucleic acid. 30 mL of anhydrous tetrahydrofuran was added to the mixture and cooled to 0 °C. Then, ethyl 5-(2-fluorophenyl)-4-(methylthio)-1H-pyrrole-3-carboxylate (9.0 g, 32.22 mmol) dissolved in 180 mL of anhydrous tetrahydrofuran was slowly added dropwise and stirred for 30 minutes. 15-Crown-5 (9.74 mL, 96.7 mmol) and pyridine-3-sulfanyl chloride (9.80 μL, 80.5 mmol) were added to the reaction solution and stirred for 1 hour. Water was slowly added to the reaction solution to terminate the reaction, and the organic layer was extracted with ethyl acetate. After washing the organic layer with an aqueous sodium bicarbonate solution, anhydrous sodium sulfate was added, filtered, and concentrated. The concentrated material was purified by column chromatography (silica gel, EA : MeOH = 100 : 0 to 80 : 20) to obtain ethyl 5-(2-fluorophenyl)-4-(methylthio)-1-(pyridine-3-ylsulfonyl)-1-H-pyrrole-3-carboxylate (47.9 mg, 88%) as yellow oil.

[0329] 1 H-NMR (400 MHz, CDCl3) δ 8.79 (dd,J= 4.8, 1.6 Hz, 1H), 8.52 (d,J= 2.3 Hz, 1H), 8.16 (d,J= 11.2 Hz, 1H), 7.67 (dt,J= 8.4, 2.1 Hz, 1H), 7.44-7.50 (m, 1H), 7.35 (dd,J= 8.0, 4.8 Hz, 1H), 7.17-7.21 (m, 1H), 7.11 (td,J= 7.3, 1.8 Hz, 1H), 6.98 (t,J= 8.7 Hz, 1H), 4.35 (q,J= 7.2 Hz, 2H), 2.16 (s, 3H), 1.38 (t,J= 7.1 Hz, 3H) ppm.

[0330]

[0331] (Step 5) Preparation of 5-(2-fluorophenyl)-4-(methylthio)-1-(pyridine-3-ylsulfonyl)-1H-pyrrole-3-carboaldehyde

[0332] Ethyl 5-(2-fluorophenyl)-4-(methylthio)-1-(pyridine-3-ilsulfonyl)-1-H-pyrrole-3-carboxylate (47.9 mg, 0.114 mmol) was dissolved in dichloromethane (0.6 mL) and cooled to -78 °C. Diisobutylaluminum hydride (DIBAL-H (1 M in toluene, 0.13 mL, 0.13 mmol)) was slowly added dropwise to the solution, and the mixture was stirred for 1 hour. After the reaction was complete, water was added to the solution, followed by the addition of 1N aqueous hydrochloric acid to extract the organic layer. Then, anhydrous magnesium sulfate was added, and the solution was filtered and concentrated to obtain (5-(2-fluorophenyl)-4-(methylthio)-1-(pyridine-3-ilsulfonyl)-1H-pyrrole-3-nyl)methanol (38.5 mg, 0.102 mmol). 5-(2-fluorophenyl)-4-(methylthio)-1-(pyridine-3-ilsulfonyl)-1H-pyrrole-3-nyl)methanol (6.5 mg, 0.017 mmol) was dissolved in dichloromethane (0.5 mL) and cooled to 0 °C. Dess-Martin periodinane (10.9 mg, 0.026 mmol) was added to the reaction solution and stirred for 1 hour. After the reaction was complete, water was added to the solution to extract the organic layer, anhydrous magnesium sulfate was added, and the solution was filtered and concentrated to obtain 5-(2-fluorophenyl)-4-(methylthio)-1-(pyridine-3-ilsulfonyl)-1-H-pyrrole-3-carboaldehyde (4.6 mg, 71%).

[0333] 1H-NMR (400 MHz, CDCl3) δ 10.04 (s, 1H), 8.81 (dd,J= 5.0, 1.4 Hz, 1H), 8.51 (d,J= 2.3 Hz, 1H), 8.18 (s, H), 7.67 (dt,J= 8.2, 1.8 Hz, 1H), 7.46-7.52 (m, 1H), 7.35 (dd,J= 8.2, 5.0 Hz, 1H), 7.19-7.23 (m, 1H), 7.14 (td,J= 7.3, 1.8 Hz, 1H), 7.00 (t,J= 8.9 Hz, 1H), 2.14 (s, 3H)

[0334]

[0335] (Step 6) Preparation of 1-(5-(2-fluorophenyl)-4-(methylthio)-1-(pyridine-3-ylsulfonyl)-1H-pyrrole-3-yl)-N-methylmethaneamine hydrochloride

[0336] 5-(2-fluorophenyl)-4-(methylthio)-1-(pyridine-3-ilsulfonyl)-1-H-pyrrole-3-carboaldehyde (4.6 mg, 0.012 mmol) was dissolved in THF / MeOH (anhydrous, 1:1, 0.2 mL), then an aqueous methylamine solution (33% in EtOH, 0.02 mL, 0.12 mmol) was added and stirred for 30 minutes. Sodium borohydride (1.0 mg, 0.024 mmol) was added and stirred for 1 hour. The reaction mixture was concentrated under reduced pressure, water and dichloromethane were added to extract the organic layer, magnesium sulfate was added, and the mixture was filtered and concentrated. The concentrate was purified by column chromatography under basic conditions (NH-silica, EA : Hx = 0 : 100 to 100 : 0) to obtain 1-(5-(2-fluorophenyl)-4-(methylthio)-1-(pyridine-3-ylsulfonyl)-1H-pyrrole-3-yl)-N-methylmethaneamine (1.6 mg, 0.004 mmol, 33%). 1-(5-(2-fluorophenyl)-4-(methylthio)-1-(pyridine-3-ylsulfonyl)-1H-pyrrole-3-yl)-N-methylmethaneamine (16.0 mg, 0.043 mmol) was dissolved in methanol (0.5 mL), then HCl in MeOH (0.25 N, 1 mL) was added and stirred, then diethyl ether was slowly added, and the resulting solid was filtered to obtain 1-(5-(2-fluorophenyl)-4-(methylthio)-1-(pyridine-3-ylsulfonyl)-1H-pyrrole-3-yl)-N-methylmethaneamine hydrochloride (6.1 mg, 34%) as a white solid.

[0337] 1H-NMR (400 MHz, CDCl3) δ 9.50 (d,J= 26.5 Hz, 2H), 8.87 (dd,J= 4.8, 1.6 Hz, 1H), 8.51 (d,J= 2.3 Hz, 1H), 8.08 (s, 1H), 7.91 (dq,J= 8.2, 1.4 Hz, 1H), 7.50-7.61 (m, 2H), 7.17-7.23 (m, 2H), 7.02 (td,J= 7.3, 1.8 Hz, 1H), 4.05 (t,J= 5.5 Hz, 2H), 2.57 (t,J= 5.3 Hz, 3H), 1.96 (s, 3H) ppm.

[0338]

[0339]

[0340] Example 1

[0341] N-methyl-1-(4-(methylthio)-5-phenyl-1-(phenylsulfonyl)-1H-pyrrole-3-yl)methaneamine hydrochloride

[0342]

[0343] 1 H NMR (400 MHz, DMSO-D6) δ 8.90 (s, 2H), 7.85 (s, 1H), 7.70 (t,J= 7.6 Hz, 1H), 7.49 (t,J= 7.8 Hz, 2H), 7.42 (t,J= 7.4 Hz, 1H), 7.30-7.34 (m, 4H), 6.95 (d,J= 7.4 Hz, 2H), 4.06 (t,J= 5.3 Hz, 2H), 2.60 (t,J= 5.1 Hz, 3H), 1.91 (s, 3H)

[0344] The compound of Example 1 was prepared in substantially the same way as in Example 11.

[0345]

[0346] Example 2

[0347] N-methyl-1-(4-(methylthio)-5-phenyl-1-(pyridine-3-ylsulfonyl)-1H-pyrrole-3-yl)methaneamine hydrochloride

[0348]

[0349] 1 H NMR (400 MHz, DMSO) δ 9.35 (s, 2H), 8.84 (d,J= 4.1 Hz, 1H), 8.41 (d,J= 2.3 Hz, 1H), 7.97 (s, 1H), 7.80 (d,J= 7.8 Hz, 1H), 7.55 (dd,J= 8.0, 4.8 Hz, 1H), 7.43 (t,J= 7.3 Hz, 1H), 7.34 (t,J= 7.3 Hz, 2H), 6.97 (d,J= 7.3 Hz, 2H), 4.04 (t,J= 5.7 Hz, 2H), 2.57 (t,J= 5.3 Hz, 3H), 1.92 (s, 3H)

[0350] The compound of Example 2 was prepared in substantially the same manner as in Example 11.

[0351]

[0352] Example 3

[0353] 1-(1-((3-fluorophenyl)sulfonyl)-4-(methylthio)-5-phenyl-1H-pyrrole-3-yl)-N-methylmethaneamine hydrochloride

[0354]

[0355] 1 H NMR (400 MHz, DMSO-D6) δ 9.19 (s, 2H), 7.91 (s, 1H), 7.54-7.62 (m, 2H), 7.41-7.45 (m, 1H), 7.34 (t,J= 7.5 Hz, 2H), 7.20-7.24 (m, 1H), 7.05-7.08 (m, 1H), 6.96-6.98 (m, 2H), 4.05 (s, 2H), 2.58 (s, 3H), 1.92 (s, 3H)

[0356] The compound of Example 3 was prepared in substantially the same manner as in Example 11.

[0357]

[0358] Example 4

[0359] 1-(1-((3-chlorophenyl)sulfonyl)-4-(methylthio)-5-phenyl-1H-pyrrole-3-yl)-N-methylmethaneamine hydrochloride

[0360]

[0361] 1 H-NMR (400 MHz, DMSO-D6) δ 8.86 (s, 2H), 7.85 (s, 1H), 7.78-7.80 (m, 1H), 7.55 (t,J= 8.0 Hz, 1H), 7.45 (t,J= 7.4 Hz, 1H), 7.35 (t,J= 7.6 Hz, 3H), 7.15 (t,J= 1.8 Hz, 1H), 6.96-6.98 (m, 2H), 4.06 (s, 2H), 2.60 (s, 3H), 1.93 (s, 3H)

[0362] The compound of Example 4 was prepared in substantially the same manner as in Example 11.

[0363]

[0364] Example 5

[0365] 1-(1-((3-methoxyphenyl)sulfonyl)-4-(methylthio)-5-phenyl-1H-pyrrole-3-yl)-N-methylmethaneamine hydrochloride

[0366]

[0367] 1 H-NMR (400 MHz, DMSO-D6) δ 8.83 (s, 2H), 7.84 (s, 1H), 7.43 (t,J= 8.0 Hz, 2H), 7.34 (t,J= 7.6 Hz, 2H), 7.25 (dd,J= 8.5, 2.1 Hz, 1H), 6.97-6.99 (m, 3H), 6.71 (t,J= 2.1 Hz, 1H), 4.05 (s, 2H), 3.67 (s, 3H), 2.59 (s, 3H), 1.92 (s, 3H)

[0368] The compound of Example 5 was prepared in substantially the same way as in Example 11.

[0369]

[0370] Example 6

[0371] N-methyl-1-(4-(methylthio)-5-phenyl-1-((3-(trifluoromethyl)phenyl)sulfonyl)-1H-pyrrole-3-yl)methaneamine hydrochloride

[0372]

[0373] 1 H NMR (400 MHz, DMSO-D6) δ 9.06 (s, 2H), 8.09-8.12 (m, 1H), 7.93 (s, 1H), 7.79-7.82 (m, 2H), 7.41-7.45 (m, 1H), 7.31 (t,J= 7.5 Hz, 3H), 6.93-6.95 (m, 2H), 4.05 (s, 2H), 2.58 (s, 3H), 1.92 (s, 3H)

[0374] The compound of Example 6 was prepared in substantially the same manner as in Example 11.

[0375]

[0376] Example 7

[0377] N-methyl-1-(4-(methylthio)-5-phenyl-1-(m-tolylsulfonyl)-1H-pyrrole-3-yl)methaneamine hydrochloride

[0378]

[0379] 1 H NMR (400 MHz, DMSO-D6) δ 9.10 (s, 2H), 7.87 (s, 1H), 7.32-7.51 (m, 5H), 7.19 (d,J= 7.8 Hz, 1H), 7.03 (s, 1H), 6.95 (d,J= 6.9 Hz, 2H), 4.05 (s, 2H), 2.58 (s, 3H), 2.23 (s, 3H), 1.91 (s, 3H)

[0380] The compound of Example 7 was prepared in substantially the same way as in Example 11.

[0381]

[0382] Example 8

[0383] 1-(1-((3-chloro-4-fluorophenyl)sulfonyl)-4-(methylthio)-5-phenyl-1H-pyrrole-3-yl)-N-methylmethaneamine hydrochloride

[0384]

[0385] 1 H NMR (400 MHz, DMSO-D6) δ 8.93 (s, 2H), 7.86 (s, 1H), 7.59 (t,J= 8.7 Hz, 1H), 7.40-7.48 (m, 2H), 7.31-7.38 (m, 3H), 6.98-7.00 (m, 2H), 4.05 (s, 2H), 2.59 (s, 3H), 1.93 (s, 3H)

[0386] The compound of Example 8 was prepared in substantially the same way as in Example 11.

[0387]

[0388] Example 9

[0389] 1-(1-((3,4-difluorophenyl)sulfonyl)-4-(methylthio)-5-phenyl-1H-pyrrole-3-yl)-N-methylmethaneamine hydrochloride

[0390]

[0391] 1 H NMR (400 MHz, DMSO-D6) δ 8.91 (s, 2H), 7.79 (s, 1H), 7.54 (m, 1H), 7.35-7.44 (m, 2H), 7.21-7.40 (m, 3H), 6.94-6.97 (m, 2H), 3.89 (s, 2H), 2.47 (s, 3H), 1.94 (s, 3H)

[0392] The compound of Example 9 was prepared in substantially the same way as in Example 11.

[0393]

[0394] Example 10

[0395] 1-(5-(2-fluorophenyl)-4-(methylthio)-1-(phenylsulfonyl)-1H-pyrrole-3-yl)-N-methylmethaneamine hydrochloride

[0396]

[0397] 1 H-NMR (400 MHz, DMSO-D6) δ 8.96 (s, 2H), 7.91 (d,J= 7.4 Hz, 1H), 7.70-7.75 (m, 1H), 7.52 (t,J= 7.4 Hz, 2H), 7.41 (d,J= 7.8 Hz, 2H), 7.14-7.20 (m, 1H), 6.99 (dd,J= 15.2, 6.9 Hz, 2H), 4.05 (s, 2H), 2.59 (s, 3H), 1.94 (s, 3H)

[0398] The compound of Example 10 was prepared in substantially the same manner as in Example 11.

[0399]

[0400] Example 12

[0401] 1-(5-(2-fluorophenyl)-1-((3-fluorophenyl)sulfonyl)-4-(methylthio)-1H-pyrrole-3-yl)-N-methylmethaneamine hydrochloride

[0402]

[0403] 1 H NMR (400 MHz, DMSO-D6) δ 9.18 (s, 2H), 7.99 (s, 1H), 7.58-7.65 (m, 2H), 7.51-7.56 (m, 1H), 7.29-7.31 (m, 1H), 7.17-7.23 (m, 3H), 7.02 (td, J = 7.5, 1.5 Hz, 1H), 4.06 (t, J = 5.7 Hz, 2H), 2.59 (t, J = 5.3 Hz, 3H), 1.96 (s, 3H)

[0404] The compound of Example 12 was prepared in substantially the same manner as in Example 11.

[0405]

[0406] Example 13

[0407] 1-(1-((3-chlorophenyl)sulfonyl)-5-(2-fluorophenyl)-4-(methylthio)-1H-pyrrole-3-yl)-N-methylmethaneamine hydrochloride

[0408]

[0409] 1 H NMR (400 MHz, DMSO-D6) δ 9.02 (s, 2H), 7.95 (s, 1H), 7.83 (dd,J= 8.3, 1.4 Hz, 1H), 7.53-7.62 (m, 2H), 7.44 (d,J= 8.7 Hz, 1H), 7.27 (t,J= 1.8 Hz, 1H), 7.17-7.24 (m, 2H), 7.03 (td,J= 7.5, 1.7 Hz, 1H), 4.07 (t,J= 6.0 Hz, 2H), 2.60 (t,J= 5.5 Hz, 3H), 1.96 (s, 3H)

[0410] The compound of Example 13 was prepared in substantially the same manner as in Example 11.

[0411]

[0412] Example 14

[0413] 1-(5-(2-fluorophenyl)-1-((3-methoxyphenyl)sulfonyl)-4-(methylthio)-1H-pyrrole-3-yl)-N-methylmethaneamine hydrochloride

[0414]

[0415] 1 H NMR (400 MHz, DMSO-D6) δ 9.03 (s, 2H), 7.94 (s, 1H), 7.53 (dd, J = 13.9, 5.4 Hz, 1H), 7.46 (t,J= 8.0 Hz, 1H), 7.28 (dd,J= 8.0, 2.1 Hz, 1H), 7.17-7.23 (m, 2H), 6.99-7.05 (m, 2H), 6.80 (t,J= 2.1 Hz, 1H), 4.06 (t,J= 5.1 Hz, 2H), 3.71 (s, 3H), 2.59 (s, 3H), 1.95 (s, 3H)

[0416] The compound of Example 14 was prepared in substantially the same manner as in Example 11.

[0417]

[0418] Example 15

[0419] 1-(5-(2-fluorophenyl)-4-(methylthio)-1-((3-(trifluoromethyl)phenyl)sulfonyl)-1H-pyrrole-3-yl)-N-methylmethaneamine hydrochloride

[0420]

[0421] 1 H NMR (400 MHz, DMSO-D6) δ 8.90 (s, 2H), 8.15 (d,J= 7.4 Hz, 1H), 7.97 (s, 1H), 7.81-7.87 (m, 2H), 7.54 (dd,J= 13.4, 5.9 Hz, 1H), 7.46 (s, 1H), 7.13-7.22 (m, 2H), 7.02 (dd,J= 7.4, 6.0 Hz, 1H), 4.07 (s, 2H), 2.60 (s, 3H), 1.96 (s, 3H)

[0422] The compound of Example 15 was prepared in substantially the same manner as in Example 11.

[0423]

[0424] Example 16

[0425] 1-(5-(2-fluorophenyl)-4-(methylthio)-1-(m-tolylsulfonyl)-1H-pyrrole-3-yl)-N-methylmethaneamine hydrochloride

[0426]

[0427] 1H-NMR (400 MHz, DMSO-D6) δ 8.84 (s, 2H), 7.87 (s, 1H), 7.53 (t,J= 6.9 Hz, 3H), 7.41 (q,J= 3.8 Hz, 1H), 7.16-7.26 (m, 3H), 7.09 (s, 1H), 6.98 (t,J= 7.4 Hz, 1H), 4.07 (s, 2n), 2.61 (s, 3H), 2.26 (s, 2H), 1.95 (s, 3H)

[0428] The compound of Example 16 was prepared in substantially the same manner as in Example 11.

[0429]

[0430] Example 17

[0431] 1-(1-((3-chloro-4-fluorophenyl)sulfonyl)-5-(2-fluorophenyl)-4-(methylthio)-1H-pyrrole-3-yl)-N-methylmethaneamine hydrochloride

[0432]

[0433] 1 H NMR (400 MHz, DMSO) δ 9.29 (s, 2H), 8.01 (s, 1H), 7.46-7.65 (m, 4H), 7.19-7.24 (m, 2H), 7.05 (t,J= 7.3 Hz, 1H), 4.05 (s, 2H), 2.58 (s, 3H), 1.97 (s, 3H)

[0434] The compound of Example 17 was prepared in substantially the same manner as in Example 11.

[0435]

[0436] Example 18

[0437] 1-(1-((3,4-difluorophenyl)sulfonyl)-5-(2-fluorophenyl)-4-(methylthio)-1H-pyrrole-3-yl)-N-methylmethaneamine hydrochloride

[0438]

[0439] 1H NMR (400 MHz, DMSO) δ 9.26 (d,J= 24.2 Hz, 2H), 7.99 (s, 1H), 7.66 (q,J= 8.8 Hz, 1H), 7.48-7.57 (m, 2H), 7.33 (d,J= 8.7 Hz, 1H), 7.19-7.23 (m, 2H), 7.02-7.05 (m, 1H), 4.06 (t,J= 5.3 Hz, 2H), 2.59 (t,J= 5.3 Hz, 3H), 1.97 (s, 3H)

[0440] The compound of Example 18 was prepared in substantially the same manner as in Example 11.

[0441]

[0442] Example 19

[0443] 1-(5-(2,4-difluorophenyl)-4-(methylthio)-1-(phenylsulfonyl)-1H-pyrrole-3-yl)-N-methylmethaneamine hydrochloride

[0444]

[0445] 1 H NMR (400 MHz, DMSO) δ 9.37 (s, 2H), 8.02 (s, 1H), 7.72 (t,J= 7.3 Hz, 1H), 7.45-7.56 (m, 4H), 7.25 (td,J= 9.4, 2.1 Hz, 1H), 7.01-7.12 (m, 2H), 4.04 (s, 2H), 2.56 (s, 3H), 1.96 (s, 3H)

[0446] The compound of Example 19 was prepared in substantially the same manner as in Example 11.

[0447]

[0448] Example 20

[0449] N-methyl-1-(4-(methylthio)-1-(phenylsulfonyl)-5-(2,4,6-trifluorophenyl)-1H-pyrrole-3-yl)methaneamine hydrochloride

[0450]

[0451] 1H NMR (400 MHz, DMSO) δ 9.35 (s, 2H), 8.09 (d,J= 9.6 Hz, 1H), 7.71-7.76 (m, 1H), 7.55 (dt,J= 15.6, 7.2 Hz, 4H), 7.26 (dd,J= 9.1, 7.8 Hz, 2H), 4.06 (s, 2H), 2.58 (s, 3H), 1.99 (s, 3H)

[0452] The compound of Example 20 was prepared in substantially the same manner as in Example 11.

[0453]

[0454] Example 21

[0455] 1-(5-(2,6-difluorophenyl)-4-(methylthio)-1-(phenylsulfonyl)-1H-pyrrole-3-yl)-N-methylmethaneamine hydrochloride

[0456]

[0457] 1 H NMR (400 MHz, DMSO) δ 9.24 (s, 2H), 8.06 (s, 1H), 7.74 (t,J= 7.3 Hz, 1H), 7.48-7.64 (m, 5H), 7.12 (t,J= 8.0 Hz, 2H), 4.06 (t,J= 5.7 Hz, 2H), 2.59 (t,J= 5.3 Hz, 3H), 1.98 (s, 3H)

[0458] The compound of Example 21 was prepared in substantially the same manner as in Example 11.

[0459]

[0460] Example 22

[0461] 1-(5-(2,5-difluorophenyl)-4-(methylthio)-1-(phenylsulfonyl)-1H-pyrrole-3-yl)-N-methylmethaneamine hydrochloride

[0462]

[0463] 1H NMR (400 MHz, DMSO) δ 9.30 (d,J= 30.8 Hz, 2H), 8.01 (s, 1H), 7.73 (t,J= 7.1 Hz, 1H), 7.55 (t,J= 7.8 Hz, 2H), 7.48 (d, J = 7.8 Hz, 2H), 7.38 (t, J = 8.5 Hz, 1H), 7.24 (td,J= 8.8, 4.3 Hz, 1H), 6.83-6.87 (m, 1H), 4.05 (s, 2H), 2.57 (t,J= 4.8 Hz, 3H), 1.98 (s, 3H)

[0464] The compound of Example 22 was prepared in substantially the same manner as in Example 11.

[0465]

[0466] Example 23

[0467] 1-(5-(4-chloro-2-fluorophenyl)-4-(methylthio)-1-(phenylsulfonyl)-1H-pyrrole-3-yl)-N-methylmethaneamine hydrochloride

[0468]

[0469] 1 H NMR (400 MHz, DMSO) δ 9.28 (d,J= 19.7 Hz, 2H), 8.01 (s, 1H), 7.73 (t,J= 7.5 Hz, 1H), 7.45-7.57 (m, 5H), 7.31 (dd,J= 8.2, 2.3 Hz, 1H), 7.03 (t,J= 8.2 Hz, 1H), 4.05 (s, 2H), 2.57 (s, 3H), 1.96 (s, 3H)

[0470] The compound of Example 23 was prepared in substantially the same manner as in Example 11.

[0471]

[0472] Example 24

[0473] 1-(5-(2-chloro-6-fluorophenyl)-4-(methylthio)-1-(phenylsulfonyl)-1H-pyrrole-3-yl)-N-methylmethaneamine hydrochloride

[0474]

[0475] 1 H NMR (400 MHz, DMSO) δ 9.25 (s, 2H), 8.06 (s, 1H), 7.74 (t,J= 7.1 Hz, 1H), 7.49-7.60 (m, 5H), 7.36 (d,J= 8.2 Hz, 1H), 7.26 (t,J= 8.7 Hz, 1H), 4.08 (t,J= 5.7 Hz, 2H), 2.58 (t,J= 5.0 Hz, 3H), 2.00 (s, 3H)

[0476] The compound of Example 24 was prepared in substantially the same manner as in Example 11.

[0477]

[0478] Experimental Example 1

[0479] The inhibitory effect of Examples 1 to 24 and Comparative Example (vonoprazan) on proton pump (H+ / K+-ATPase) activity was measured as follows.

[0480] Gastric vesicles were prepared from hog stomachs according to a known method (Edd C. Rabon et al., Preparation of Gastric H+, K+-ATPase., Methods in enzymology, vol.157 Academic Press Inc., (1988), pp.649-654). The protein content of the prepared gastric vesicles was quantified using the Bradford protein quantification method (Bio-Rad Laboratories).

[0481] All reactions were performed at 37°C with a reaction volume of 100 μL and measured in a 96-well plate. DMSO or test compounds at various concentrations (final DMSO concentration 1%) were added to each well in 50 mM Tris-HEPES buffer (pH 6.5) containing 2.5 mg / L porcine gastrointestinal vesicles, 5 mM MgCl2, 8 mM KCl, and 10 μM Valinomycin, and the samples were pre-incubated at 37°C for 30 minutes.

[0482] Subsequently, 0.2 mM adenosine triphosphate (ATP) was added to each well of the above reaction buffer, and the enzymatic reaction was carried out at 37°C for 40 minutes. The reaction was stopped by adding 20 μL of malachite green solution, and after being left at room temperature for 30 minutes, the amount of inorganic phosphate was measured by a colorimetric assay [Malachite Green Phosphate Assay Kit, sigma]. For colorimetric analysis, the Optical Density (OD) value was measured at 620 nm using a microplate reader (Innite M200 PRO microplate reader, Tecan).

[0483] The inhibitory effect on proton pump (H+ / K+-ATPase) activity (inhibition rate (% inhibition)) was derived from the OD values ​​of the control group and the OD values ​​of various concentrations of the test compound, and was calculated as shown in Equation 1 based on the pump activity in the presence of K+ ions, excluding the pump activity in the absence of K+ ions.

[0484] [Equation 1]

[0485] % inhibition = [1-((OD value of test compound treatment group - OD value of KCl-treated control group) / (OD value of DMSO-treated control group - OD value of KCl-treated control group))] X 100.

[0486]

[0487] IC of the test compound 50 The % inhibition value was analyzed using the GraphPad Prism 10 program, and in the case of unstable value, it was calculated on a linear regression curve. The results are shown in Table 1 below.

[0488]

[0489] Test Compound IC 50 Example 1B Example 2B Example 3C Example 4C Example 5A Example 6C Example 7A Example 8C Example 9C Example 10A Example 11A Example 12A Example 13A Example 14A Example 15B Example 16C Example 17A Example 18C Example 19A Example 20C Example 21A Example 22A Example 23C Example 24B Comparative Example (Vonoprazan) B

[0490] (A < 50 nM, 50 nM ≤ B < 100 nM, 100 nM ≤ C)

[0491]

[0492] It was confirmed that Examples 1 to 24 have an inhibitory effect on proton pump (H+ / K+-ATPase) activity. In particular, it was confirmed that Examples 5, 7, 10, 11, 12, 13, 14, 17, 19, 21, and 22 have a superior inhibitory effect on proton pump (H+ / K+-ATPase) activity compared to the Comparative Example (vonoprazan). Meanwhile, it was confirmed that Examples 1, 2, 15, and 24 have an inhibitory effect on proton pump (H+ / K+-ATPase) activity equivalent to that of the Comparative Example (vonoprazan).

[0493] In addition, the inhibitory effect of 1 μM of Example 11 and Comparative Example (vonoprazan) on proton pump (H+ / K+-ATPase) activity was compared. It was confirmed that Example 11 had a superior inhibitory effect on proton pump (H+ / K+-ATPase) activity compared to Comparative Example (vonoprazan) (see Fig. 1).

[0494]

[0495] The foregoing description is merely for illustrative purposes only. The scope of the rights of the present disclosure shall be interpreted by the claims, and all technical ideas within the scope equivalent or equivalent thereto shall be interpreted as being included within the scope of the rights of the present disclosure.

Claims

1. A compound represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof: [Chemical Formula 1] In the above chemical formula 1, R1 is an optionally substituted heterocyclic group or an optionally substituted phenyl group, and R2 is an arbitrarily substituted heterocyclic group or an arbitrarily substituted phenyl group.

2. In Paragraph 1, The above compound is a compound represented by the following chemical formula 1-1 or a pharmaceutically acceptable salt thereof: [Chemical Formula 1-1] In the above chemical formula 1-1, X is C or N, and R3 and R4 are independently hydrogen, halogen, hydroxyl, and C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl or C 1-4 It is a haloalkyl, and R5, R6, and R7 are independently hydrogen, halogen, hydroxyl, and C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl or C 1-4 It is a haloalkyl.

3. In Paragraph 2, In the above chemical formula 1-1, X is C or N, and R3 and R4 are independently hydrogen, halogen, and C 1-4 Alkoxy, C 1-4 alkyl or C 1-4 It is a haloalkyl, and R5, R6, and R7 are independently hydrogen or halogens. A compound or a pharmaceutically acceptable salt thereof.

4. In Paragraph 2, The above compound is a compound represented by the following chemical formula 1-2 or a pharmaceutically acceptable salt thereof: [Chemical Formula 1-2] In the above chemical formula 1-2, X is C or N, and R3 and R4 are independently hydrogen, halogen, hydroxyl, and C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl or C 1-4 It is a haloalkyl, and R5, R6, and R7 are independently hydrogen, halogen, hydroxyl, and C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl or C 1-4 It is a haloalkyl.

5. In Paragraph 4, In the above chemical formula 1-2, X is C or N, and R3 and R4 are independently hydrogen, halogen, and C 1-4 Alkoxy, C 1-4 alkyl or C 1-4 It is a haloalkyl, and R5, R6, and R7 are independently hydrogen or halogens. A compound or a pharmaceutically acceptable salt thereof.

6. In Paragraph 4, The above compound is a compound represented by the following chemical formula 1-3 or a pharmaceutically acceptable salt thereof: [Chemical Formula 1-3] In the above chemical formula 1-3, X is C or N, and R3 and R4 are independently hydrogen, halogen, hydroxyl, and C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl or C 1-4 It is a haloalkyl, and R5 and R6 are independently hydrogen, halogen, hydroxyl, and C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl or C 1-4 It is a haloalkyl.

7. In Paragraph 6, In the above chemical formula 1-3, X is C or N, and R3 and R4 are independently hydrogen, halogen, and C 1-4 Alkoxy, C 1-4 alkyl or C 1-4 It is a haloalkyl, and R5 and R6 are independently hydrogen or halogens A compound or a pharmaceutically acceptable salt thereof.

8. In Paragraph 4, The above compound is a compound represented by the following chemical formula 1-4 or a pharmaceutically acceptable salt thereof: [Chemical Formula 1-4] In the above chemical formula 1-4, X is C or N, and R3 and R4 are independently hydrogen, halogen, hydroxyl, and C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl or C 1-4 It is a haloalkyl, and R5 and R6 are independently hydrogen, halogen, hydroxyl, and C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl or C 1-4 It is a haloalkyl.

9. In Paragraph 8, In the above chemical formula 1-4, X is C or N, and R3 and R4 are independently hydrogen, halogen, and C 1-4 Alkoxy, C 1-4 alkyl or C 1-4 It is a haloalkyl, and R5 and R6 are independently hydrogen or halogens A compound or a pharmaceutically acceptable salt thereof.

10. In Paragraph 4, The above compound is a compound represented by the following chemical formula 1-5 or a pharmaceutically acceptable salt thereof: [Chemical Formula 1-5] In the above chemical formula 1-5, X is C or N, and R3 and R4 are independently hydrogen, halogen, hydroxyl, and C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl or C 1-4 It is a haloalkyl, and R5 and R6 are independently hydrogen, halogen, hydroxyl, and C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl or C 1-4 It is a haloalkyl.

11. In Paragraph 10, In the above chemical formula 1-5, X is C or N, and R3 and R4 are independently hydrogen, halogen, and C 1-4 Alkoxy, C 1-4 alkyl or C 1-4 It is a haloalkyl, and R5 and R6 are independently hydrogen or halogens A compound or a pharmaceutically acceptable salt thereof.

12. In Paragraph 4, The above compound is a compound represented by the following chemical formula 1-6 or a pharmaceutically acceptable salt thereof: [Chemical Formula 1-6] In the above chemical formula 1-6, X is C or N, and R3 and R4 are independently hydrogen, halogen, hydroxyl, and C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl or C 1-4 It is a haloalkyl, and R5, R6, and R7 are independently hydrogen, halogen, hydroxyl, and C 1-4 Alkoxy, amino, C 1-4 Alkyl, C 1-4 Carboxyl or C 1-4 It is a haloalkyl.

13. In Paragraph 12, In the above chemical formula 1-6, X is C or N, and R3 and R4 are independently hydrogen, halogen, and C 1-4 Alkoxy, C 1-4 alkyl or C 1-4 It is a haloalkyl, and R5, R6, and R7 are independently hydrogen or halogens. A compound or a pharmaceutically acceptable salt thereof.

14. In Paragraph 1, The above compound is any one of the compounds selected from the group consisting of the following compounds or a pharmaceutically acceptable salt thereof: 1) N-methyl-1-(4-(methylthio)-5-phenyl-1-(phenylsulfonyl)-1H-pyrrole-3-yl)methaneamine 2) N-methyl-1-(4-(methylthio)-5-phenyl-1-(pyridine-3-ylsulfonyl)-1H-pyrrole-3-yl)methaneamine 3) 1-(1-((3-fluorophenyl)sulfonyl)-4-(methylthio)-5-phenyl-1H-pyrrole-3-yl)-N-methylmethaneamine 4) 1-(1-((3-chlorophenyl)sulfonyl)-4-(methylthio)-5-phenyl-1H-pyrrole-3-yl)-N-methylmethaneamine 5) 1-(1-((3-methoxyphenyl)sulfonyl)-4-(methylthio)-5-phenyl-1H-pyrrole-3-yl)-N-methylmethaneamine 6) N-methyl-1-(4-(methylthio)-5-phenyl-1-((3-(trifluoromethyl)phenyl)sulfonyl)-1H-pyrrole-3-yl)methaneamine 7) N-methyl-1-(4-(methylthio)-5-phenyl-1-(m-tolylsulfonyl)-1H-pyrrole-3-yl)methaneamine 8) 1-(1-((3-chloro-4-fluorophenyl)sulfonyl)-4-(methylthio)-5-phenyl-1H-pyrrole-3-yl)-N-methylmethaneamine 9) 1-(1-((3,4-difluorophenyl)sulfonyl)-4-(methylthio)-5-phenyl-1H-pyrrole-3-yl)-N-methylmethaneamine 10) 1-(5-(2-fluorophenyl)-4-(methylthio)-1-(phenylsulfonyl)-1H-pyrrole-3-yl)-N-methylmethaneamine 11) 1-(5-(2-fluorophenyl)-4-(methylthio)-1-(pyridine-3-ylsulfonyl)-1H-pyrrole-3-yl)-N-methylmethaneamine 12) 1-(5-(2-fluorophenyl)-1-((3-fluorophenyl)sulfonyl)-4-(methylthio)-1H-pyrrole-3-yl)-N-methylmethaneamine 13) 1-(1-((3-chlorophenyl)sulfonyl)-5-(2-fluorophenyl)-4-(methylthio)-1H-pyrrole-3-yl)-N-methylmethaneamine 14) 1-(5-(2-fluorophenyl)-1-((3-methoxyphenyl)sulfonyl)-4-(methylthio)-1H-pyrrole-3-yl)-N-methylmethaneamine 15) 1-(5-(2-fluorophenyl)-4-(methylthio)-1-((3-(trifluoromethyl)phenyl)sulfonyl)-1H-pyrrole-3-yl)-N-methylmethaneamine 16) 1-(5-(2-fluorophenyl)-4-(methylthio)-1-(m-tolylsulfonyl)-1H-pyrrole-3-yl)-N-methylmethaneamine 17) 1-(1-((3-chloro-4-fluorophenyl)sulfonyl)-5-(2-fluorophenyl)-4-(methylthio)-1H-pyrrole-3-yl)-N-methylmethaneamine 18) 1-(1-((3,4-difluorophenyl)sulfonyl)-5-(2-fluorophenyl)-4-(methylthio)-1H-pyrrole-3-yl)-N-methylmethaneamine 19) 1-(5-(2,4-difluorophenyl)-4-(methylthio)-1-(phenylsulfonyl)-1H-pyrrole-3-yl)-N-methylmethaneamine 20) N-methyl-1-(4-(methylthio)-1-(phenylsulfonyl)-5-(2,4,6-trifluorophenyl)-1H-pyrrole-3-yl)methaneamine 21) 1-(5-(2,6-difluorophenyl)-4-(methylthio)-1-(phenylsulfonyl)-1H-pyrrole-3-yl)-N-methylmethaneamine 22) 1-(5-(2,5-difluorophenyl)-4-(methylthio)-1-(phenylsulfonyl)-1H-pyrrole-3-yl)-N-methylmethaneamine 23) 1-(5-(4-chloro-2-fluorophenyl)-4-(methylthio)-1-(phenylsulfonyl)-1H-pyrrole-3-yl)-N-methylmethaneamine 24) 1-(5-(2-chloro-6-fluorophenyl)-4-(methylthio)-1-(phenylsulfonyl)-1H-pyrrole-3-yl)-N-methylmethaneamine 15. A pharmaceutical composition for treating gastrointestinal disease, gastroesophageal disease, gastroesophageal reflux disease (GRED), laryngopharyngeal reflux disease, peptic ulcer, gastric ulcer, duodenal ulcer, non-steroidal anti-inflammatory drug (NSAID)-induced ulcer, gastritis, Helicobacter pylori infection, dyspepsia, functional dyspepsia, Zollinger-Ellison syndrome, non-erosive reflux disease (NERD), visceral referred pain, cancer, heartburn, nausea, esophagitis, dysphagia, drooling, airway obstruction, or asthma, comprising a compound according to any one of claims 1 to 14 or a pharmaceutically acceptable salt thereof.

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