Benzotriazole derivatives

Abstract

The present invention provides a compound having a Keap1 inhibitory effect and a pharmaceutical composition containing the same. Specifically, the present invention provides a compound represented by the following general formula (I) [wherein, the symbols have the meanings described in the specification.] or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition containing the same.

Description

Technical Field

[0001] The present invention relates to benzotriazole derivatives and pharmaceutical compositions containing the same, in particular to benzotriazole derivatives and pharmaceutical compositions containing the same for preventing, alleviating and / or treating diseases whose symptoms are improved by inhibiting Keap1. Background Art

[0002] Nrf2 (NF-E2 related factor 2) is a transcription factor belonging to the CNC (cap-n-collar) group of transcription factors that possesses a basic leucine zipper structure (bZIP structure). Keap1 (Kelch-like ECH-associated protein 1) is an adaptor protein that associates with Cullin 3 (Cul3) in the cytoplasm to form the proteasomal degradation E3 enzyme complex. It functions as an inhibitory regulatory factor that promotes Nrf2 degradation through ubiquitination under alkaline conditions. Under oxidative stress conditions caused by electrophilic substances and reactive oxygen species, the Keap1-Cul3 complex is inactivated, leading to Nrf2 activation. Activated Nrf2 undergoes nuclear translocation, forming a heterodimer with the small Maf transcription factor and binding to the antioxidant response element (ARE), activating the gene expression of a group of biodefense enzymes, including NAD(P)H quinone dehydrogenase 1 (NQO1). According to (Non-Patent Document 1), Keap1 inhibitors, which inhibit the binding of Keap1 to Nrf2, are particularly expected to be effective in diseases caused by oxidative stress.

[0003] For the treatment carried out by inducing the antioxidant function by inhibiting the combination of Keap1 and Nrf2, it is expected to be effective for a wide range of diseases. In particular, it has been reported that in chronic kidney disease, methyl bardoxolone (CDDO-Me), an irreversible Keap1 inhibitor, improved renal function in human patients (non-patent document 2), and multiple clinical trials are currently underway. In addition, as a therapeutic drug for relapsing-remitting multiple sclerosis, dimethyl fumarate, which has an Nrf2 activation effect, has been approved in the United States. In reports related to Keap1 inhibitors in the preclinical stage, the possibility of using Keap1 inhibitors as therapeutic drugs in various diseases has been revealed, such as the liver fibrosis inhibitory effect in the NASH model (non-patent document 3), the anti-inflammatory effect in the inflammatory bowel disease model and the chronic obstructive pulmonary disease model (non-patent document 4 and 5), the anti-tumor effect in solid cancers represented by prostate cancer (non-patent document 6), and the clinical score improvement effect in the multiple sclerosis model (non-patent document 7).

[0004] According to reports on transgenic animals or oxidative stress and pathological models related to the Keap1-Nrf2 pathway, further associations with various diseases are revealed. Specifically, chronic lung infection, α1 antitrypsin disease, and cystic fibrosis (non-patent document 8), sepsis-induced acute kidney injury, other acute kidney injury (non-patent document 9), various cardiovascular diseases including atherosclerosis, heart failure, acute coronary syndrome, myocardial infarction, myocardial repair, cardiac remodeling, arrhythmia, heart failure with preserved left ventricular ejection fraction, heart failure with reduced left ventricular ejection fraction and diabetic cardiomyopathy (non-patent document 10), Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (amyotrophic lateral sclerosis) (non-patent document 11), Friedreich's ataxia (non-patent document 12), age-related macular degeneration (age-related macular degeneration), Fuchs' corneal endothelial degeneration, other ocular inflammations including uveitis (Non-Patent Document 13), dermatitis caused by radiation, etc. (Non-Patent Document 14), immunosuppression (Non-Patent Document 15), acute mountain sickness (Non-Patent Document 16), etc.

[0005] Patent Documents 1 to 17 and Non-Patent Documents 17 and 18 have disclosed triazole compounds as compounds having Keap1 inhibitory activity. However, the structures of these compounds are different from those of the present invention.

[0006] Prior art literature

[0007] Patent Literature

[0008] Patent Document 1: International Publication No. 2015 / 092713

[0009] Patent Document 2: International Publication No. 2016 / 202253

[0010] Patent Document 3: International Publication No. 2016 / 203400

[0011] Patent Document 4: International Publication No. 2016 / 203401

[0012] Patent Document 5: International Publication No. 2017 / 060854

[0013] Patent Document 6: International Publication No. 2017 / 060855

[0014] Patent Document 7: International Publication No. 2018 / 104766

[0015] Patent Document 8: International Publication No. 2018 / 109641

[0016] Patent Document 9: International Publication No. 2018 / 109642

[0017] Patent Document 10: International Publication No. 2018 / 109643

[0018] Patent Document 11: International Publication No. 2018 / 109646

[0019] Patent Document 12: International Publication No. 2018 / 109647

[0020] Patent Document 13: International Publication No. 2018 / 109648

[0021] Patent Document 14: International Publication No. 2018 / 109649

[0022] Patent Document 15: International Publication No. 2018 / 181345

[0023] Patent Document 16: International Publication No. 2019 / 224667

[0024] Patent Document 17: International Publication No. 2020 / 041169

[0025] Non-patent literature

[0026] Non-patent literature 1: BBA Molecular Cell Research, 2018, 1865, 721-733.

[0027] Non-patent literature 2: American Journal of Nephrology, 2018, 47, 40-47.

[0028] Non-patent literature 3: Molecular Pharmacology, 2013, 84, 62-70.

[0029] Non-patent literature 4: Scientific Reports, 2016, 6, 26585.

[0030] Non-patent literature 5: The Journal of Pharmacology and Experimantal Therapeutics, 2017, 363, 114-125.

[0031] Non-patent literature 6: Molecular Cancer Therapeutics, 2014, 13, 12, 2968-2977.

[0032] Non-patent document 7: Proceedings of the National Academy of Sciences of the United States of America, 2016, 113, 17, 4777-4782.

[0033] Non-patent document 8: Plos One, 2008, 3, 10, e3367.

[0034] Non-patent document 9: Kidney International, 2013, 84, 1090-1095.

[0035] Non-patent literature 10: Oxidative Medicine and Cellular Longevity, 2013, 2013, 104308.

[0036] Non-patent literature 11: Brain Research, 2012, 1446, 109-118.

[0037] Non-patent literature 12: Plos One, 4, 1, e4253.

[0038] Non-patent literature 13: Investigative Ophthalmology & Visual Science, 2012, 53, 9, 5806-5813.

[0039] Non-patent document 14: Genes and Development, 2010, 24, 1045-1058.

[0040] Non-patent literature 15: Journal of Clinical Investigation, 2014, 124, 2, 730-741.

[0041] Non-patent literature 16: Free Radical Biology and Medicine, 2013, 63, 264-273.

[0042] Non-patent literature 17: Journal of Medicinal Chemistry, 2016, 59, 3991-4006.

[0043] Non-patent literature 18: Journal of Medicinal Chemistry, 2019, 62, 4683-4702. Summary of the Invention

[0044] Problems to be solved by the invention

[0045] The present invention provides novel compounds useful for preventing, alleviating, and / or treating diseases whose symptoms are improved by inhibiting Keap1, and pharmaceutical compositions containing the same.

[0046] Solutions for solving problems

[0047] The present inventors have conducted intensive studies on compounds having Keap1 inhibitory activity and have discovered that a series of benzotriazole derivatives or pharmaceutically acceptable salts thereof having a tricyclic structure within the molecule have excellent Keap1 inhibitory activity and are useful for the prevention, alleviation and / or treatment of diseases whose symptoms are improved by Keap1 inhibition, in particular, for the prevention, alleviation and / or treatment of renal diseases, thereby completing the present invention.

[0048] The present invention provides the following [1] to [4]. [1]

[0050] A compound represented by the following general formula (I) (hereinafter also referred to as compound (I)) or a pharmaceutically acceptable salt thereof.

[0051] [Chemical Formula 1]

[0052]

[0053] [Where,

[0054] R is a hydrogen atom, or an alkyl group optionally substituted by 1 to 5 substituents independently selected from Group E;

[0055] R 1 and R 2 each independently represents a hydrogen atom, an alkyl group optionally substituted by 1 to 5 substituents independently selected from Group E, an alkenyl group optionally substituted by 1 to 5 substituents independently selected from Group E, or an alkynyl group optionally substituted by 1 to 5 substituents independently selected from Group E;

[0056] Or, R 1 and R 2 Together with the carbon atom to which they are bound, they form a monocyclic carbocyclic ring optionally substituted by 1 to 5 substituents independently selected from Group E;

[0057] R 3 、R 4 and R 6 each independently represents a hydrogen atom, a halogen atom, an alkyl group optionally substituted by 1 to 5 substituents independently selected from Group E, an alkenyl group optionally substituted by 1 to 5 substituents independently selected from Group E, an alkynyl group optionally substituted by 1 to 5 substituents independently selected from Group E, an alkoxy group optionally substituted by 1 to 5 substituents independently selected from Group E, a cycloalkyl group optionally substituted by 1 to 5 substituents independently selected from Group E, a non-aromatic heterocyclic group optionally substituted by 1 to 5 substituents independently selected from Group E, an aryl group optionally substituted by 1 to 5 substituents independently selected from Group E, a heteroaryl group optionally substituted by 1 to 5 substituents independently selected from Group E, or a cyano group;

[0058] R 5 is (i) a hydrogen atom, or (ii) an alkyl group optionally substituted by 1 to 5 substituents independently selected from the group consisting of a halogen atom, a hydroxyl group, a cycloalkyl group optionally substituted by 1 to 5 substituents independently selected from Group E, a phenyl group optionally substituted by 1 to 5 substituents independently selected from Group E, and an alkoxy group optionally substituted by 1 to 5 substituents independently selected from Group E;

[0059] A has a structure represented by the following formula (II),

[0060] [Chemical Formula 2]

[0061]

[0062] R 7 and R 8 each independently represents a hydrogen atom, an alkyl group optionally substituted by 1 to 5 substituents independently selected from Group E, an alkenyl group optionally substituted by 1 to 5 substituents independently selected from Group E, or an alkynyl group optionally substituted by 1 to 5 substituents independently selected from Group E;

[0063] Or, R 7 and R8 Together with the carbon atom to which they are bound, they form a monocyclic carbocyclic ring optionally substituted by 1 to 5 substituents independently selected from Group E;

[0064] Ring B is a bicyclic ring optionally substituted by 1 to 5 substituents independently selected from the group consisting of a halogen atom, an alkyl group optionally substituted by 1 to 5 substituents independently selected from Group E, an alkenyl group optionally substituted by 1 to 5 substituents independently selected from Group E, an alkynyl group optionally substituted by 1 to 5 substituents independently selected from Group E, an alkoxy group optionally substituted by 1 to 5 substituents independently selected from Group E, a cycloalkyl group optionally substituted by 1 to 5 substituents independently selected from Group E, a non-aromatic heterocyclic group optionally substituted by 1 to 5 substituents independently selected from Group E, an aryl group optionally substituted by 1 to 5 substituents independently selected from Group E, a heteroaryl group optionally substituted by 1 to 5 substituents independently selected from Group E, and a cyano group;

[0065] [Chemical Formula 3]

[0066]

[0067] The above labels indicate the points of bonding to the rest of the molecule;

[0068] Group E is a group consisting of a halogen atom, a hydroxyl group, and an alkoxy group optionally substituted with 1 to 5 halogen atoms]. [2]

[0070] A pharmaceutical composition comprising the compound described in [1] or a pharmaceutically acceptable salt thereof. [3]

[0072] The pharmaceutical composition according to [2] is used for preventing, alleviating and / or treating a disease that is improved by inhibiting Keap1. [4]

[0074] The pharmaceutical composition according to [3], wherein the disease improved by inhibiting Keap1 is renal disease.

[0075] The present invention also provides the following [5] to

[20] . [5]

[0077] The compound according to [1] or a pharmaceutically acceptable salt thereof, wherein

[0078] R is a hydrogen atom, or an alkyl group optionally substituted by 1 to 5 substituents independently selected from Group E;

[0079] R 1 and R 2are each independently a hydrogen atom, or an alkyl group optionally substituted by 1 to 5 substituents independently selected from Group E;

[0080] Or, R 1 and R 2 Together with the carbon atom to which they are bound, they form a monocyclic carbocyclic ring optionally substituted by 1 to 5 substituents independently selected from Group E;

[0081] R 3 、R 4 and R 6 are each independently a hydrogen atom, a halogen atom, an alkyl group optionally substituted by 1 to 5 substituents independently selected from Group E, or an alkoxy group optionally substituted by 1 to 5 substituents independently selected from Group E;

[0082] R 5 is (i) a hydrogen atom, or (ii) an alkyl group optionally substituted by 1 to 5 substituents independently selected from the group consisting of a halogen atom, a hydroxyl group, a phenyl group optionally substituted by 1 to 5 substituents independently selected from Group E, and an alkoxy group optionally substituted by 1 to 5 substituents independently selected from Group E;

[0083] R 7 and R 8 are each independently a hydrogen atom, or an alkyl group optionally substituted by 1 to 5 substituents independently selected from Group E;

[0084] Or, R 7 and R 8 Together with the carbon atom to which they are bound, they form a monocyclic carbocyclic ring optionally substituted by 1 to 5 substituents independently selected from Group E;

[0085] Ring B is a bicyclic ring optionally substituted by 1 to 5 substituents independently selected from the group consisting of a halogen atom, an alkyl group optionally substituted by 1 to 5 substituents independently selected from Group E, an alkoxy group optionally substituted by 1 to 5 substituents independently selected from Group E, and a cyano group. [6]

[0087] The compound according to [1] or a pharmaceutically acceptable salt thereof, wherein

[0088] R is a hydrogen atom or an alkyl group;

[0089] R 1 and R 2 are each independently a hydrogen atom or an alkyl group;

[0090] Or, R 1 and R 2 Together with the carbon atom to which they are bonded, they form a monocyclic carbocycle;

[0091] R 3 、R 4 and R 6 are each independently a hydrogen atom, a halogen atom, an alkyl group, or an alkoxy group;

[0092] R 5 is (i) a hydrogen atom, or (ii) an alkyl group optionally substituted by 1 to 5 substituents independently selected from the group consisting of a halogen atom, a hydroxyl group, a phenyl group, and an alkoxy group;

[0093] R 7 and R 8 are each independently a hydrogen atom or an alkyl group;

[0094] Or, R 7 and R 8 Together with the carbon atom to which they are bound, they form a monocyclic carbocyclic ring optionally substituted by 1 to 5 substituents independently selected from Group E;

[0095] Ring B is a bicyclic ring optionally substituted by 1 to 5 substituents independently selected from the group consisting of a halogen atom, an alkyl group optionally substituted by 1 to 5 substituents independently selected from Group E, an alkoxy group optionally substituted by 1 to 5 substituents independently selected from Group E, and a cyano group. [7]

[0097] The compound according to any one of [1] or [5] to [6] (hereinafter also referred to as compound (I-1)) or a pharmaceutically acceptable salt thereof, which has a structure represented by the following general formula (I-1),

[0098] [Chemical Formula 4]

[0099]

[0100] R is a hydrogen atom or an alkyl group;

[0101] R 1 and R 2 are each independently a hydrogen atom or an alkyl group;

[0102] Or, R 1 and R 2 Together with the carbon atom to which they are bonded, they form a monocyclic carbocycle;

[0103] R 3 is a hydrogen atom, a halogen atom, an alkyl group, or an alkoxy group;

[0104] R 4 and R 6 are each independently a hydrogen atom, an alkyl group, or an alkoxy group;

[0105] R 5is a hydrogen atom or an alkyl group. [8]

[0107] The compound or pharmaceutically acceptable salt thereof according to any one of [1] or [5] to [7], wherein

[0108] R is a hydrogen atom;

[0109] R 1 and R 2 are each independently a hydrogen atom or an alkyl group;

[0110] Or, R 1 and R 2 Together with the carbon atom to which they are bonded, they form a monocyclic carbocycle;

[0111] R 3 is an alkyl group;

[0112] R 4 is an alkyl group;

[0113] R 5 is an alkyl group;

[0114] R 6 A hydrogen atom.

[0115] [8-1]

[0116] The compound according to [8] or a pharmaceutically acceptable salt thereof, wherein

[0117] R 1 and R 2 Each is independently a hydrogen atom or an alkyl group. [9]

[0119] The compound according to any one of [1] or [5] to [8-1] (hereinafter also referred to as compounds (II-1) to (II-3)) or a pharmaceutically acceptable salt thereof, wherein:

[0120] A has a structure represented by any one of the following formulae (II-1) to (II-3),

[0121] [Chemical Formula 5]

[0122]

[0123] [Where,

[0124] R 7 and R 8 are each independently a hydrogen atom or an alkyl group;

[0125] Or, R 7 and R 8Together with the carbon atom to which they are bound, they form a monocyclic carbocyclic ring optionally substituted by 1 to 5 substituents independently selected from Group E;

[0126] X 1 and X 2 Each independently CR 9 or nitrogen atoms;

[0127] R 9 are each independently a hydrogen atom, a halogen atom, an alkyl group optionally substituted by 1 to 5 substituents independently selected from Group E, an alkoxy group optionally substituted by 1 to 5 substituents independently selected from Group E, or a cyano group;

[0128] Ring D is a 5- to 6-membered carbocyclic ring or a 5- to 6-membered heterocyclic ring, each of which is optionally substituted by 1 to 5 substituents independently selected from the group consisting of a halogen atom, an alkyl group optionally substituted by 1 to 5 substituents independently selected from Group E, an alkoxy group optionally substituted by 1 to 5 substituents independently selected from Group E, and a cyano group].

[10]

[0130] The compound according to any one of [1] or [5] to [8] (hereinafter also referred to as compounds (II-1-1) to (II-3-4)) or a pharmaceutically acceptable salt thereof, wherein:

[0131] A has a structure represented by any one of the following formulas (II-1-1) to (II-3-4),

[0132] [Chemical Formula 6]

[0133]

[0134] [Where,

[0135] R 7 and R 8 are each independently a hydrogen atom or an alkyl group;

[0136] Or, R 7 and R 8 Together with the carbon atom to which they are bound, they form a monocyclic carbocyclic ring optionally substituted by 1 to 5 substituents independently selected from Group E;

[0137] X 1 and X 2 Each independently CR 9 or nitrogen atoms;

[0138] Y 1 、Y 2 、Y 3 and Y 4 Each independently CR 10 or nitrogen atoms;

[0139] R 9 and R 10 are each independently a hydrogen atom, a halogen atom, an alkyl group optionally substituted by 1 to 5 substituents independently selected from Group E, an alkoxy group optionally substituted by 1 to 5 substituents independently selected from Group E, or a cyano group;

[0140] Q 1 and Q 2 Each independently CR 11 R 12 NR 13 , oxygen atom, sulfur atom, SO, or SO2;

[0141] R 11 and R 12 are each independently a hydrogen atom, a halogen atom, or an alkyl group;

[0142] R 13 are each independently a hydrogen atom or an alkyl group;

[0143] Z is NR 14 , oxygen atoms, or sulfur atoms;

[0144] R 14 is a hydrogen atom or an alkyl group;

[0145] Q 3 for (CU 1 U 2 ) n ;

[0146] U 1 and U 2 are each independently a hydrogen atom, a halogen atom, or an alkyl group;

[0147] n is 1, 2, or 3].

[0148] [10-1]

[0149] The compound according to

[10] or a pharmaceutically acceptable salt thereof, wherein

[0150] Q 1 and Q 2 Each independently CR 11 R 12 NR 13 , or oxygen atoms.

[0151] [10-2]

[0152] The compound according to

[10] or [10-1] or a pharmaceutically acceptable salt thereof, wherein

[0153] n is 1 or 2.

[11]

[0155] The compound or pharmaceutically acceptable salt thereof according to any one of

[10] to [10-2], wherein

[0156] A has a structure represented by any one of the following formulas (II-1-1) and (II-3-1).

[0157] [Chemical Formula 7]

[0158]

[12]

[0160] The compound or pharmaceutically acceptable salt thereof according to any one of [1] or [5] to

[11] , wherein

[0161] A has a structure represented by the following formula (II-1-1),

[0162] [Chemical Formula 8]

[0163]

[0164] [Where,

[0165] R 7 and R 8 are each independently a hydrogen atom or an alkyl group;

[0166] Or, R 7 and R 8 Together with the carbon atom to which they are bonded, they form a monocyclic carbocycle;

[0167] X 1 and X 2 Each independently CR 9 ;

[0168] Y 1 、Y 2 、Y 3 and Y 4 Any one of them is a nitrogen atom, and the other three are each independently CR 10 ;

[0169] R 9 are hydrogen atoms;

[0170] R 10 are each independently a hydrogen atom, a halogen atom, an alkyl group, or an alkoxy group].

[0171] [12-1]

[0172] The compound according to

[12] or a pharmaceutically acceptable salt thereof, wherein

[0173] R 7and R 8 are each independently a hydrogen atom or an alkyl group;

[0174] R 10 Each is independently a hydrogen atom, a halogen atom, or an alkyl group.

[13]

[0176] The compound or pharmaceutically acceptable salt thereof according to any one of [1] or [5] to

[11] , wherein

[0177] A has a structure represented by the following formula (II-3-1),

[0178] [Chemical Formula 9]

[0179]

[0180] [Where,

[0181] R 7 and R 8 are each independently a hydrogen atom or an alkyl group;

[0182] X 1 and X 2 One of them is a nitrogen atom and the other is CR 9 ;

[0183] Y 1 、Y 2 、Y 3 and Y 4 Each independently CR 10 ;

[0184] R 9 are hydrogen atoms;

[0185] R 10 are each independently a hydrogen atom, a halogen atom, or an alkyl group].

[14]

[0187] The compound according to [1] (hereinafter also referred to as compound (I-1-1)) or a pharmaceutically acceptable salt thereof, which is represented by the following general formula (I-1-1),

[0188] [Chemical Formula 10]

[0189]

[0190] [Where,

[0191] R is a hydrogen atom or an alkyl group;

[0192] R 1 and R 2 are each independently a hydrogen atom or an alkyl group;

[0193] Or, R 1 and R 2 Together with the carbon atom to which they are bonded, they form a monocyclic carbocycle;

[0194] R 3 、R 4 and R 6 are each independently a hydrogen atom, a halogen atom, an alkyl group, or an alkoxy group;

[0195] R 5 is (i) a hydrogen atom, or (ii) an alkyl group optionally substituted by 1 to 5 substituents independently selected from the group consisting of a halogen atom, a hydroxyl group, a phenyl group, and an alkoxy group;

[0196] R 7 and R 8 are each independently a hydrogen atom or an alkyl group;

[0197] Or, R 7 and R 8 Together with the carbon atom to which they are bound, they form a monocyclic carbocyclic ring optionally substituted by 1 to 5 substituents independently selected from Group E;

[0198] R 10 is a hydrogen atom, a halogen atom, an alkyl group optionally substituted by 1 to 5 substituents independently selected from Group E, an alkoxy group optionally substituted by 1 to 5 substituents independently selected from Group E, or a cyano group;

[0199] Group E is a group consisting of a halogen atom, a hydroxyl group, and an alkoxy group optionally substituted with 1 to 5 halogen atoms].

[15]

[0201] The compound according to

[14] or a pharmaceutically acceptable salt thereof, wherein

[0202] R is a hydrogen atom or an alkyl group;

[0203] R 1 and R 2 are each independently a hydrogen atom or an alkyl group;

[0204] Or, R 1 and R 2 Together with the carbon atom to which they are bonded, they form a monocyclic carbocycle;

[0205] R 3 is a hydrogen atom, a halogen atom, an alkyl group, or an alkoxy group;

[0206] R 4 is a hydrogen atom or an alkyl group;

[0207] R 5 is an alkyl group;

[0208] R 6 is a hydrogen atom;

[0209] R 7 and R 8 are each independently a hydrogen atom or an alkyl group;

[0210] Or, R 7 and R 8 Together with the carbon atom to which they are bonded, they form a monocyclic carbocycle;

[0211] R 10 is a hydrogen atom, a halogen atom, an alkyl group, or an alkoxy group.

[16]

[0213] The compound according to [1] or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of:

[0214] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-6-ethyl-2,2-difluoro-6,7-dihydro-[1,3]dioxolano[4',5':4,5]benzo[1,2-f][1,4]oxazepine-8(9H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate (Example 1-(a));

[0215] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-6-ethyl-2,2-difluoro-6,7-dihydro-[1,3]dioxolano[4',5':4,5]benzo[1,2-f][1,4]oxazepin-8(9H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 1-(b), Example 29 (diastereomer 1), and Example 30 (diastereomer 2));

[0216] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-9-ethyl-2,2-difluoro-8,9-dihydro-[1,3]dioxolano[4′,5′:3,4]benzo[1,2-f][1,4]oxazepin-7(6H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 2-(a));

[0217] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-9-ethyl-2,2-difluoro-8,9-dihydro-[1,3]dioxolano[4′,5′:3,4]benzo[1,2-f][1,4]oxazepin-7(6H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 2-(b));

[0218] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,5,7,8,9-hexahydro-4H-indeno[5,6-f][1,4]oxazepin-4-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 3-(a));

[0219] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,5,7,8,9-hexahydro-4H-indeno[5,6-f][1,4]oxazepin-4-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 3-(b), Example 31 (diastereomer 1), and Example 32 (diastereomer 2));

[0220] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,7,8,9,10-hexahydronaphtho[2,3-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 4-(a));

[0221] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,7,8,9,10-hexahydronaphtho[2,3-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 4-(b), Example 33 (diastereomer 1), and Example 34 (diastereomer 2));

[0222] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-3,4,8,9,10,11-hexahydronaphtho[1,2-f][1,4]oxazepin-2(1H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 5-(a));

[0223] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-3,4,8,9,10,11-hexahydronaphtho[1,2-f][1,4]oxazepin-2(1H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 5-(b));

[0224] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,5,8,9,10-hexahydro-4H-indeno[5,4-f][1,4]oxazepin-4-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 6-(a));

[0225] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,5,8,9,10-hexahydro-4H-indeno[5,4-f][1,4]oxazepin-4-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 6-(b), Example 35 (diastereomer 1), and Example 36 (diastereomer 2));

[0226] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,8,9,10,11-hexahydronaphtho[2,1-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 7-(a));

[0227] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,8,9,10,11-hexahydronaphtho[2,1-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 7-(b));

[0228] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydronaphtho[2,3-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 8-(a));

[0229] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydronaphtho[2,3-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 8-(b));

[0230] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-b]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 9-(a));

[0231] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-b]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 9-(b));

[0232] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-b]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 10-(a));

[0233] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-b]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 10-(b), Example 37 (diastereomer 1), and Example 38 (diastereomer 2));

[0234] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 11-(a));

[0235] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 11-(b), Example 39 (Diastereomer 1), and Example 40 (Diastereomer 2));

[0236] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 12-(a));

[0237] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 12-(b), Example 41 (diastereomer 1), and Example 42 (diastereomer 2));

[0238] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-10-methyl-2,3-dihydro-[1,4]oxazepino[7,6-b]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 13-(a));

[0239] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-10-methyl-2,3-dihydro-[1,4]oxazepino[7,6-b]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 13-(b));

[0240] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-8-methyl-2,3-dihydro-[1,4]oxazepino[7,6-b]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 14-(a));

[0241] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-8-methyl-2,3-dihydro-[1,4]oxazepino[7,6-b]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 14-(b));

[0242] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-8-ethyl-1,5,7,8-tetrahydro-6H-[1,4]oxazepino[6,7-f]indazol-6-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 15-(a));

[0243] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-8-ethyl-1,5,7,8-tetrahydro-6H-[1,4]oxazepino[6,7-f]indazol-6-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 15-(b));

[0244] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-3,4-dihydronaphtho[1,2-f][1,4]oxazepin-2(1H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 16-(a));

[0245] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-3,4-dihydronaphtho[1,2-f][1,4]oxazepin-2(1H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 16-(b));

[0246] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-8-ethyl-8,9-dihydro-[1,4]oxazepino[7,6-h]quinolin-10(11H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 17-(a));

[0247] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-8-ethyl-8,9-dihydro-[1,4]oxazepino[7,6-h]quinolin-10(11H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 17-(b));

[0248] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-3,4-dihydro-[1,4]oxazepino[6,7-f]quinolin-2(1H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 18-(a));

[0249] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-3,4-dihydro-[1,4]oxazepino[6,7-f]quinolin-2(1H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 18-(b));

[0250] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-3,4-dihydro-[1,4]oxazepino[7,6-c]quinolin-2(1H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 19-(a));

[0251] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-3,4-dihydro-[1,4]oxazepino[7,6-c]quinolin-2(1H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 19-(b));

[0252] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-7-ethyl-1,7,8,10-tetrahydro-9H-[1,4]oxazepino[7,6-g]indazol-9-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 20-(a));

[0253] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-7-ethyl-1,7,8,10-tetrahydro-9H-[1,4]oxazepino[7,6-g]indazol-9-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 20-(b), Example 43 (Diastereomer 1), and Example 44 (Diastereomer 2));

[0254] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-7-ethyl-1-methyl-1,7,8,10-tetrahydro-9H-[1,4]oxazepino[7,6-g]indazol-9-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 21-(a));

[0255] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-7-ethyl-1-methyl-1,7,8,10-tetrahydro-9H-[1,4]oxazepino[7,6-g]indazol-9-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 21-(b));

[0256] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-7-ethyl-2-methyl-2,7,8,10-tetrahydro-9H-[1,4]oxazepino[7,6-g]indazol-9-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 22-(a));

[0257] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-7-ethyl-2-methyl-2,7,8,10-tetrahydro-9H-[1,4]oxazepino[7,6-g]indazol-9-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 22-(b));

[0258] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-1,3,4,9,10,11-hexahydro-2H-pyrimido[1′,2′:1,6]pyrido[2,3-f][1,4]oxazepin-2-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 23);

[0259] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydronaphtho[2,1-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 24-(a));

[0260] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydronaphtho[2,1-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 24-(b));

[0261] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-c]isoquinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 25-(a));

[0262] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-c]isoquinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 25-(b), Example 45 (Diastereomer 1), and Example 46 (Diastereomer 2));

[0263] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-c]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 26-(a));

[0264] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-c]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 26-(b), Example 47 (Diastereomer 1), and Example 48 (Diastereomer 2));

[0265] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-h]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 27-(a));

[0266] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-h]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 27-(b));

[0267] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-f]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 28-(a));

[0268] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-f]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 28-(b));

[0269] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-7-fluoro-2,3-dihydronaphtho[2,1-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 49-(a));

[0270] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-7-fluoro-2,3-dihydronaphtho[2,1-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 49-(b));

[0271] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-8-ethyl-1-methyl-1,5,7,8-tetrahydro-6H-[1,4]oxazepino[6,7-f]indazol-6-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 50-(a));

[0272] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-8-ethyl-1-methyl-1,5,7,8-tetrahydro-6H-[1,4]oxazepino[6,7-f]indazol-6-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 50-(b));

[0273] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-8-ethyl-2-methyl-2,5,7,8-tetrahydro-6H-[1,4]oxazepino[6,7-f]indazol-6-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 51-(a));

[0274] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-8-ethyl-2-methyl-2,5,7,8-tetrahydro-6H-[1,4]oxazepino[6,7-f]indazol-6-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 51-(b));

[0275] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-g]isoquinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 52-(a));

[0276] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-g]isoquinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 52-(b));

[0277] 3-(1,4-Dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]isoquinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 53);

[0278] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-7-fluoro-2,3-dihydronaphtho[2,3-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 54-(a));

[0279] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-7-fluoro-2,3-dihydronaphtho[2,3-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 54-(b));

[0280] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-f]isoquinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 55-(a));

[0281] 3-(1,4-Dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-f]isoquinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid trifluoroacetate (Example 55-(b));

[0282] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)propanoic acid ethyl ester (Example 56-(a));

[0283] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)propanoic acid (Example 56-(b));

[0284] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((S)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 57-(a));

[0285] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((S)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 57-(b), Example 57-(c) (Diastereomer 1), and Example 58 (Diastereomer 2));

[0286] 3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-3-(1-ethyl-4-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid methyl ester (Example 59-(a));

[0287] 3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-3-(1-ethyl-4-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid (Example 59-(b));

[0288] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-((2,2-dimethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 60-(a));

[0289] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-((2,2-dimethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 60-(b));

[0290] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-6-ethyl-2,2-dimethyl-6,7-dihydro-[1,3]dioxolano[4′,5′:4,5]benzo[1,2-f][1,4]oxazepin-8(9H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 61-(a));

[0291] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-6-ethyl-2,2-dimethyl-6,7-dihydro-[1,3]dioxolano[4′,5′:4,5]benzo[1,2-f][1,4]oxazepin-8(9H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 61-(b));

[0292] 3-(1,4-Dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-h]isoquinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 62);

[0293] 3-(3-((2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid methyl ester (Example 63-(a));

[0294] 3-(3-((2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid (Example 63-(b));

[0295] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-6-ethyl-1,6,7,9-tetrahydro-8H-[1,4]oxazepino[7,6-f]indazol-8-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 64-(a));

[0296] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-6-ethyl-1,6,7,9-tetrahydro-8H-[1,4]oxazepino[7,6-f]indazol-8-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 64-(b));

[0297] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-6-ethyl-1-methyl-1,6,7,9-tetrahydro-8H-[1,4]oxazepino[7,6-f]indazol-8-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 65-(a));

[0298] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-6-ethyl-1-methyl-1,6,7,9-tetrahydro-8H-[1,4]oxazepino[7,6-f]indazol-8-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 65-(b));

[0299] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-6-ethyl-2-methyl-2,6,7,9-tetrahydro-8H-[1,4]oxazepino[7,6-f]indazol-8-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 66-(a));

[0300] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-6-ethyl-2-methyl-2,6,7,9-tetrahydro-8H-[1,4]oxazepino[7,6-f]indazol-8-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 66-(b));

[0301] 3-(3-(((R)-7-chloro-2-ethyl-2,3-dihydronaphtho[2,1-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid methyl ester (Example 67-(a));

[0302] 3-(3-(((R)-7-chloro-2-ethyl-2,3-dihydronaphtho[2,1-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid (Example 67-(b));

[0303] 3-(3-(((R)-7-chloro-2-ethyl-2,3-dihydronaphtho[2,3-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid methyl ester (Example 68-(a));

[0304] 3-(3-(((R)-7-chloro-2-ethyl-2,3-dihydronaphtho[2,3-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid (Example 68-(b));

[0305] 3-(3-(((R)-10-chloro-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid (Example 69);

[0306] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-10-methoxy-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 70-(a));

[0307] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-10-methoxy-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 70-(b));

[0308] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-10-methyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 71-(a));

[0309] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-10-methyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 71-(b));

[0310] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydrothieno[2′,3′:4,5]benzo[1,2-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 72-(a));

[0311] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydrothieno[2′,3′:4,5]benzo[1,2-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 72-(b));

[0312] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,7,8-tetrahydrothieno[2′,3′:4,5]benzo[1,2-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 73-(a));

[0313] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,7,8-tetrahydrothieno[2′,3′:4,5]benzo[1,2-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 73-(b));

[0314] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-9,9-dioxide-2,3,7,8-tetrahydrothieno[2′,3′:4,5]benzo[1,2-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 74-(a));

[0315] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-9,9-dioxide-2,3,7,8-tetrahydrothieno[2′,3′:4,5]benzo[1,2-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 74-(b));

[0316] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethyl-3-(4-methyl-3-(((R)-2-methyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)phenyl)propanoic acid methyl ester (Example 75-(a));

[0317] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethyl-3-(4-methyl-3-(((R)-2-methyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)phenyl)propanoic acid (Example 75-(b));

[0318] 3-(3-((3'H-spiro[cyclopropane-1,2'-[1,4]oxazepino[7,6-g]quinolin]-4'(5'H)-yl)methyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid methyl ester (Example 76-(a));

[0319] 3-(3-((3'H-spiro[cyclopropane-1,2'-[1,4]oxazepino[7,6-g]quinolin]-4'(5'H)-yl)methyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid (Example 76-(b), Example 85 (Diastereomer 1), and Example 86 (Diastereomer 2));

[0320] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethyl-3-(4-methyl-3-((2-propyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)phenyl)propanoic acid methyl ester (Example 77-(a) and Example 78-(a));

[0321] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethyl-3-(4-methyl-3-((2-propyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)phenyl)propanoic acid (Example 77-(b) and Example 78-(b));

[0322] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)phenyl)-2,2-dimethylpropanoic acid methyl ester (Example 79-(a));

[0323] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)phenyl)-2,2-dimethylpropanoic acid (Example 79-(b));

[0324] 3-(4-chloro-3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)phenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid methyl ester (Example 80-(a));

[0325] 3-(4-chloro-3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)phenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid (Example 80-(b));

[0326] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methoxyphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 81-(a));

[0327] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methoxyphenyl)-2,2-dimethylpropanoic acid (Example 81-(b));

[0328] 3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethyl-3-(1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid methyl ester (Example 82-(a));

[0329] 3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethyl-3-(1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid (Example 82-(b));

[0330] 1-((1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)methyl)cyclopentane-1-carboxylic acid methyl ester (Example 83-(a));

[0331] 1-((1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)methyl)cyclopentane-1-carboxylic acid (Example 83-(b));

[0332] 1-((1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)methyl)cyclobutane-1-carboxylic acid methyl ester (Example 84-(a));

[0333] 1-((1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)methyl)cyclobutane-1-carboxylic acid (Example 84-(b), Example 87 (Diastereomer 1), and Example 88 (Diastereomer 2));

[0334] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((S)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-c]isoquinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester (Example 89-(a)); and

[0335] 3-(1,4-Dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((S)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-c]isoquinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 89-(b) (Diastereomer 1) and Example 90 (Diastereomer 2)).

[17]

[0337] The compound according to [1] or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of:

[0338] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-6-ethyl-2,2-difluoro-6,7-dihydro-[1,3]dioxolano[4',5':4,5]benzo[1,2-f][1,4]oxazepin-8(9H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 1-(b), Example 29 (Diastereomer 1), and Example 30 (Diastereomer 2));

[0339] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-9-ethyl-2,2-difluoro-8,9-dihydro-[1,3]dioxolano[4′,5′:3,4]benzo[1,2-f][1,4]oxazepin-7(6H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 2-(b));

[0340] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,5,7,8,9-hexahydro-4H-indeno[5,6-f][1,4]oxazepin-4-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 3-(b), Example 31 (diastereomer 1), and Example 32 (diastereomer 2));

[0341] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,7,8,9,10-hexahydronaphtho[2,3-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 4-(b), Example 33 (diastereomer 1), and Example 34 (diastereomer 2));

[0342] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-3,4,8,9,10,11-hexahydronaphtho[1,2-f][1,4]oxazepin-2(1H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 5-(b));

[0343] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,5,8,9,10-hexahydro-4H-indeno[5,4-f][1,4]oxazepin-4-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 6-(b), Example 35 (diastereomer 1), and Example 36 (diastereomer 2));

[0344] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,8,9,10,11-hexahydronaphtho[2,1-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 7-(b));

[0345] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydronaphtho[2,3-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 8-(b));

[0346] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-b]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 9-(b));

[0347] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-b]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 10-(b), Example 37 (diastereomer 1), and Example 38 (diastereomer 2));

[0348] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 11-(b), Example 39 (Diastereomer 1), and Example 40 (Diastereomer 2));

[0349] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 12-(b), Example 41 (diastereomer 1), and Example 42 (diastereomer 2));

[0350] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-10-methyl-2,3-dihydro-[1,4]oxazepino[7,6-b]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 13-(b));

[0351] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-8-methyl-2,3-dihydro-[1,4]oxazepino[7,6-b]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 14-(b));

[0352] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-8-ethyl-1,5,7,8-tetrahydro-6H-[1,4]oxazepino[6,7-f]indazol-6-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 15-(b));

[0353] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-3,4-dihydronaphtho[1,2-f][1,4]oxazepin-2(1H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 16-(b));

[0354] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-8-ethyl-8,9-dihydro-[1,4]oxazepino[7,6-h]quinolin-10(11H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 17-(b));

[0355] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-3,4-dihydro-[1,4]oxazepino[6,7-f]quinolin-2(1H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 18-(b));

[0356] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-3,4-dihydro-[1,4]oxazepino[7,6-c]quinolin-2(1H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 19-(b));

[0357] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-7-ethyl-1,7,8,10-tetrahydro-9H-[1,4]oxazepino[7,6-g]indazol-9-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 20-(b), Example 43 (Diastereomer 1), and Example 44 (Diastereomer 2));

[0358] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-7-ethyl-1-methyl-1,7,8,10-tetrahydro-9H-[1,4]oxazepino[7,6-g]indazol-9-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 21-(b));

[0359] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-7-ethyl-2-methyl-2,7,8,10-tetrahydro-9H-[1,4]oxazepino[7,6-g]indazol-9-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 22-(b));

[0360] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-1,3,4,9,10,11-hexahydro-2H-pyrimido[1′,2′:1,6]pyrido[2,3-f][1,4]oxazepin-2-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 23);

[0361] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydronaphtho[2,1-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 24-(b));

[0362] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-c]isoquinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 25-(b), Example 45 (Diastereomer 1), and Example 46 (Diastereomer 2));

[0363] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-c]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 26-(b), Example 47 (Diastereomer 1), and Example 48 (Diastereomer 2));

[0364] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-h]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 27-(b));

[0365] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-f]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 28-(b));

[0366] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-7-fluoro-2,3-dihydronaphtho[2,1-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 49-(b));

[0367] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-8-ethyl-1-methyl-1,5,7,8-tetrahydro-6H-[1,4]oxazepino[6,7-f]indazol-6-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 50-(b));

[0368] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-8-ethyl-2-methyl-2,5,7,8-tetrahydro-6H-[1,4]oxazepino[6,7-f]indazol-6-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 51-(b));

[0369] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-g]isoquinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 52-(b));

[0370] 3-(1,4-Dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]isoquinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 53);

[0371] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-7-fluoro-2,3-dihydronaphtho[2,3-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 54-(b));

[0372] 3-(1,4-Dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-f]isoquinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid trifluoroacetate (Example 55-(b));

[0373] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)propanoic acid (Example 56-(b));

[0374] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((S)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 57-(b), Example 57-(c) (Diastereomer 1), and Example 58 (Diastereomer 2));

[0375] 3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-3-(1-ethyl-4-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid (Example 59-(b));

[0376] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-((2,2-dimethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 60-(b));

[0377] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-6-ethyl-2,2-dimethyl-6,7-dihydro-[1,3]dioxolano[4′,5′:4,5]benzo[1,2-f][1,4]oxazepin-8(9H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 61-(b));

[0378] 3-(1,4-Dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-h]isoquinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 62);

[0379] 3-(3-((2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid (Example 63-(b));

[0380] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-6-ethyl-1,6,7,9-tetrahydro-8H-[1,4]oxazepino[7,6-f]indazol-8-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 64-(b));

[0381] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-6-ethyl-1-methyl-1,6,7,9-tetrahydro-8H-[1,4]oxazepino[7,6-f]indazol-8-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 65-(b));

[0382] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-6-ethyl-2-methyl-2,6,7,9-tetrahydro-8H-[1,4]oxazepino[7,6-f]indazol-8-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 66-(b));

[0383] 3-(3-(((R)-7-chloro-2-ethyl-2,3-dihydronaphtho[2,1-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid (Example 67-(b));

[0384] 3-(3-(((R)-7-chloro-2-ethyl-2,3-dihydronaphtho[2,3-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid (Example 68-(b));

[0385] 3-(3-(((R)-10-chloro-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid (Example 69);

[0386] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-10-methoxy-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 70-(b));

[0387] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-10-methyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 71-(b));

[0388] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydrothieno[2′,3′:4,5]benzo[1,2-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 72-(b));

[0389] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,7,8-tetrahydrothieno[2′,3′:4,5]benzo[1,2-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 73-(b));

[0390] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-9,9-dioxide-2,3,7,8-tetrahydrothieno[2′,3′:4,5]benzo[1,2-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 74-(b));

[0391] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethyl-3-(4-methyl-3-(((R)-2-methyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)phenyl)propanoic acid (Example 75-(b));

[0392] 3-(3-((3'H-spiro[cyclopropane-1,2'-[1,4]oxazepino[7,6-g]quinolin]-4'(5'H)-yl)methyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid (Example 76-(b), Example 85 (Diastereomer 1), and Example 86 (Diastereomer 2));

[0393] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethyl-3-(4-methyl-3-((2-propyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)phenyl)propanoic acid (Example 77-(b) and Example 78-(b));

[0394] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)phenyl)-2,2-dimethylpropanoic acid (Example 79-(b));

[0395] 3-(4-chloro-3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)phenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid (Example 80-(b));

[0396] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methoxyphenyl)-2,2-dimethylpropanoic acid (Example 81-(b));

[0397] 3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethyl-3-(1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid (Example 82-(b));

[0398] 1-((1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)methyl)cyclopentane-1-carboxylic acid (Example 83-(b));

[0399] 1-((1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)methyl)cyclobutane-1-carboxylic acid (Example 84-(b), Example 87 (Diastereomer 1), and Example 88 (Diastereomer 2)); and

[0400] 3-(1,4-Dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((S)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-c]isoquinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Example 89-(b) (Diastereomer 1) and Example 90 (Diastereomer 2)).

[18]

[0402] A pharmaceutical composition comprising the compound described in any one of [5] to

[17] or a pharmaceutically acceptable salt thereof.

[19]

[0404] The pharmaceutical composition according to

[18] is used for preventing, alleviating and / or treating a disease that can be improved by inhibiting Keap1.

[20]

[0406] The pharmaceutical composition according to

[19] , wherein the disease improved by inhibiting Keap1 is renal disease.

[0407] Effects of the Invention

[0408] The compound represented by general formula (I) of the present invention or a pharmaceutically acceptable salt thereof has the activity of inhibiting Keap1. Therefore, the compound represented by general formula (I) or a pharmaceutically acceptable salt thereof is useful as a preventive, palliative, and / or therapeutic agent for various diseases, such as renal disease, whose symptoms are improved by inhibiting Keap1. DETAILED DESCRIPTION

[0409] The embodiments of the present invention are described below. It should be noted that, in this specification, for convenience, "compounds represented by general formula (I)" are also referred to as "compound (I)" and the like. In addition, compounds (I), as well as compound (I-1), compound (II-1) to (II-3), compound (II-1-1) to (II-3-4), compound (I-1-1), and example compounds included in compound (I) are also collectively referred to as "compounds of the present invention". The various substituents defined or exemplified below can be arbitrarily selected and combined. In addition, embodiments obtained by arbitrarily selecting and combining the various embodiments defined below are also included in the present invention.

[0410] The definitions of the terms used in this specification are as follows.

[0411] The "halogen atom" described in this specification means a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom.

[0412] The "alkyl group" described in this specification refers to a linear or branched saturated hydrocarbon group having 1 to 6 carbon atoms (C1-C6), for example, 1 to 4 carbon atoms (C1-C4), and examples thereof include methyl, ethyl, propyl, isopropyl, n-butyl, tert-butyl, isobutyl, n-pentyl and n-hexyl, as well as various branched isomers thereof.

[0413] The "alkenyl group" described in this specification refers to a linear or branched unsaturated hydrocarbon group having 2 to 6 carbon atoms (C2 to C6), for example, 2 to 4 carbon atoms (C2 to C4), and having one carbon-carbon double bond. Examples thereof include ethenyl, propenyl, isopropenyl, butenyl, and various branched isomers thereof.

[0414] The "alkynyl" described in this specification refers to a linear or branched unsaturated hydrocarbon group having 2 to 6 carbon atoms (C2 to C6), for example, 2 to 4 carbon atoms (C2 to C4), having one carbon-carbon triple bond, and examples thereof include ethynyl, 1-propynyl, 2-butynyl, 4-pentynyl, 5-hexynyl, and various branched isomers thereof.

[0415] The "alkoxy group" described in this specification refers to a group in which an oxygen atom is bonded to the aforementioned linear or branched alkyl group, and examples thereof include methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, isobutoxy, and various branched isomers thereof.

[0416] The "cycloalkyl group" described in this specification refers to a monocyclic alicyclic saturated hydrocarbon group having 3 to 8 ring carbon atoms (C3 to C8), for example, 3 to 6 ring carbon atoms (C3 to C6), and examples thereof include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl.

[0417] The "non-aromatic heterocyclic group" described in this specification refers to a 4- to 8-membered monocyclic non-aromatic heterocyclic group or a 6- to 12-membered bicyclic non-aromatic heterocyclic group containing 1 to 4 heteroatoms selected from oxygen atoms, sulfur atoms, and nitrogen atoms in addition to carbon atoms, and examples thereof include azetidinyl, oxetanyl, thietanyl, pyrrolidinyl, piperidinyl, 1-piperidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiophenyl (i.e., thiolanyl), piperazinyl, morpholinyl, 4-morpholinyl, perhydroazepinyl, perhydroazocinyl, , 6-membered to 12-membered azabicycloalkyl (e.g., azabicyclohexyl, azabicycloheptyl, azabicyclooctyl, azabicyclononyl, azabicyclodecyl, azabicycloundecyl, or azabicyclododecyl), 6-membered to 12-membered azabicycloalkenyl (e.g., azabicyclohexenyl, azabicycloheptenyl, azabicyclooctenyl, azabicyclononenyl, azabicyclodecenyl, azabicycloundecenyl, or azabicyclododecenyl), 6-membered to 12-membered azaspiroalkyl (e.g., azaspirohexyl, azaspiroheptyl, azaspirooctyl, azaspirononyl, azaspirodecanyl, azaspiroundecyl, or azaspirododecyl).

[0418] The "aryl group" described in this specification refers to a group having 6 to 11 ring carbon atoms (C6 to C 11 ) monocyclic or bicyclic aromatic hydrocarbon groups, for example, monocyclic aromatic groups such as phenyl; naphthyl, tetrahydronaphthyl, indenyl, and indanyl, which may be partially saturated and have 9 to 11 ring carbon atoms (C9 to C 11 ) is a bicyclic aromatic group.

[0419] The "heteroaryl group" described in this specification refers to a 5- to 11-membered monocyclic or bicyclic aromatic heterocyclic group containing, in addition to carbon atoms, 1 to 4 hetero atoms selected from oxygen atoms, sulfur atoms, and nitrogen atoms. Examples thereof include: 5- to 6-membered monocyclic heteroaryl groups containing, in addition to carbon atoms, 1 to 4 hetero atoms selected from oxygen atoms, sulfur atoms, and nitrogen atoms, such as pyrrolyl, furyl, thienyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, and triazinyl; indolyl, indole, thiazolyl, pyridazinyl ... 8-11 membered bicyclic heteroaryl groups containing, in addition to carbon atoms, 1 to 4 hetero atoms selected from oxygen atoms, sulfur atoms and nitrogen atoms, such as benzoxazolyl, dihydrobenzoxazolyl, benzothiazolyl, dihydrobenzothiazolyl, quinolyl, tetrahydroquinolyl, isoquinolyl, tetrahydroisoquinolyl, naphthyridinyl, tetrahydronaphthyridinyl, quinoxalinyl, tetrahydroquinoxalinyl and quinazolinyl.

[0420] The "monocyclic carbocycle" described in this specification refers to: 1 R 2 and>CR 7 R 8 (R 1 、R 2 、R 7 and R 8 has the same meaning as above), R 1 With R 2 or R 7 With R 8 A saturated or unsaturated monocyclic hydrocarbon ring formed by bonding to each other and the carbon atoms to which they are bonded, and having 3 to 8 ring carbon atoms (C3-C8), for example, 3 to 6 (C3-C6).

[0421] The "bicyclic ring" described in this specification refers to a saturated or unsaturated 6- to 12-membered, for example, 9- to 10-membered, bicyclic ring that optionally contains 1 to 4 heteroatoms selected from oxygen atoms, sulfur atoms, and nitrogen atoms in addition to carbon atoms. Examples thereof include the following rings composed of ring C and ring D.

[0422] [Chemical Formula 11]

[0423]

[0424] When the bicyclic ring in ring B of compound (I) is the ring composed of ring C and ring D, ring B is bonded to the oxazepine ring at the ring C portion.

[0425] The "5- to 6-membered carbocycle" described herein refers to a 5- or 6-membered monocyclic carbocycle, and examples thereof include rings that belong to ring D in the above-mentioned "bicyclic ring" and do not contain a heteroatom.

[0426] The "5- to 6-membered heterocycle" described in this specification refers to a 5- or 6-membered monocyclic heterocycle containing, in addition to carbon atoms, 1 to 4 heteroatoms selected from oxygen atoms, sulfur atoms, and nitrogen atoms. Examples thereof include rings that belong to ring D in the above-mentioned "bicyclic ring" and contain heteroatoms.

[0427] The following describes the embodiments of each substituent of compound (I). It should be noted that embodiments obtained by arbitrarily selecting and combining the embodiments of the following substituents are also included in the present invention.

[0428] (Embodiment 1) A compound or a pharmaceutically acceptable salt thereof, wherein in any of the compounds of the present invention, R is a hydrogen atom or an alkyl group optionally substituted with 1 to 5 substituents independently selected from Group E.

[0429] (Embodiment 2) A compound or a pharmaceutically acceptable salt thereof, wherein, in any of the compounds of the present invention, R is a hydrogen atom or an alkyl group optionally substituted with 1 to 5 halogen atoms.

[0430] (Embodiment 3) A compound or a pharmaceutically acceptable salt thereof, wherein, in any of the compounds of the present invention, R is a hydrogen atom or an alkyl group.

[0431] (Embodiment 4) A compound or a pharmaceutically acceptable salt thereof, wherein, in any of the compounds of the present invention, R is a hydrogen atom or a methyl group.

[0432] (Embodiment 5) A compound or a pharmaceutically acceptable salt thereof, wherein, in any of the compounds of the present invention, R is a hydrogen atom.

[0433] (Embodiment 6) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 5, R 1 and R 2 are each independently a hydrogen atom, an alkyl group optionally substituted by 1 to 5 substituents independently selected from Group E, an alkenyl group optionally substituted by 1 to 5 substituents independently selected from Group E, or an alkynyl group optionally substituted by 1 to 5 substituents independently selected from Group E, or R 1 and R 2 Together with the carbon atom to which they are bonded, they form a monocyclic carbocyclic ring optionally substituted by 1 to 5 substituents independently selected from Group E.

[0434] (Embodiment 7) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 5, R 1 and R2 are each independently a hydrogen atom, or an alkyl group optionally substituted by 1 to 5 substituents independently selected from Group E, or, R 1 and R 2 Together with the carbon atom to which they are bonded, they form a monocyclic carbocyclic ring optionally substituted by 1 to 5 substituents independently selected from Group E.

[0435] (Embodiment 8) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 5, R 1 and R 2 are each independently a hydrogen atom, or an alkyl group optionally substituted by 1 to 5 substituents independently selected from Group E, or, R 1 and R 2 Together with the carbon atom to which they are bonded, they form a monocyclic carbocycle.

[0436] (Embodiment 9) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 5, R 1 and R 2 are each independently a hydrogen atom or an alkyl group optionally substituted by 1 to 5 halogen atoms, or, R 1 and R 2 Together with the carbon atom to which they are bonded, they form a monocyclic carbocycle.

[0437] (Embodiment 10) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 5, R 1 and R 2 are each independently a hydrogen atom or an alkyl group, or, R 1 and R 2 Together with the carbon atom to which they are bonded, they form a monocyclic carbocycle.

[0438] (Embodiment 11) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 5, R 1 and R 2 Each is independently a hydrogen atom or an alkyl group.

[0439] (Embodiment 12) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 5, R 1 and R 2 are each independently an alkyl group.

[0440] (Embodiment 13) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 5, R 1 and R 2 are all methyl, or, R 1 and R2 Together with the carbon atoms to which they are bonded, they form a cyclobutane ring or a cyclopentane ring.

[0441] (Embodiment 14) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 5, R 1 and R 2 All are methyl.

[0442] (Embodiment 15) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 14, R 3 、R 4 and R 6 Each is independently a hydrogen atom, a halogen atom, an alkyl group optionally substituted by 1 to 5 substituents independently selected from Group E, an alkenyl group optionally substituted by 1 to 5 substituents independently selected from Group E, an alkynyl group optionally substituted by 1 to 5 substituents independently selected from Group E, an alkoxy group optionally substituted by 1 to 5 substituents independently selected from Group E, a cycloalkyl group optionally substituted by 1 to 5 substituents independently selected from Group E, a non-aromatic heterocyclic group optionally substituted by 1 to 5 substituents independently selected from Group E, an aryl group optionally substituted by 1 to 5 substituents independently selected from Group E, a heteroaryl group optionally substituted by 1 to 5 substituents independently selected from Group E, or a cyano group.

[0443] (Embodiment 16) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 14, R 3 、R 4 and R 6 Each is independently a hydrogen atom, a halogen atom, an alkyl group optionally substituted by 1 to 5 substituents independently selected from Group E, or an alkoxy group optionally substituted by 1 to 5 substituents independently selected from Group E.

[0444] (Embodiment 17) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 14, R 3 、R 4 and R 6 Each is independently a hydrogen atom, a halogen atom, an alkyl group optionally substituted by 1 to 5 halogen atoms, or an alkoxy group optionally substituted by 1 to 5 halogen atoms.

[0445] (Embodiment 18) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 14, R 3 、R 4 and R 6 Each is independently a hydrogen atom, a halogen atom, an alkyl group, or an alkoxy group.

[0446] (Embodiment 19) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 14, R 3 is a hydrogen atom, a halogen atom, an alkyl group, or an alkoxy group, R 4 and R 6 Each is independently a hydrogen atom, an alkyl group, or an alkoxy group.

[0447] (Embodiment 20) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 14, R 3 is a hydrogen atom, a halogen atom, an alkyl group, or an alkoxy group, R 4 is a hydrogen atom or an alkyl group, R 6 A hydrogen atom.

[0448] (Embodiment 21) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 14, R 3 is an alkyl group, R 4 is an alkyl group, R 6 A hydrogen atom.

[0449] (Embodiment 22) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 14, R 3 is methyl, R 4 is methyl, R 6 A hydrogen atom.

[0450] (Embodiment 23) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 22, R 5 is (i) a hydrogen atom, or (ii) an alkyl group optionally substituted by 1 to 5 substituents independently selected from the group consisting of a halogen atom, a hydroxyl group, a cycloalkyl group optionally substituted by 1 to 5 substituents independently selected from Group E, a phenyl group optionally substituted by 1 to 5 substituents independently selected from Group E, and an alkoxy group optionally substituted by 1 to 5 substituents independently selected from Group E.

[0451] (Embodiment 24) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 22, R 5 is (i) a hydrogen atom, or (ii) an alkyl group optionally substituted by 1 to 5 substituents independently selected from the group consisting of a halogen atom, a hydroxyl group, a phenyl group optionally substituted by 1 to 5 substituents independently selected from Group E, and an alkoxy group optionally substituted by 1 to 5 substituents independently selected from Group E.

[0452] (Embodiment 25) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 22, R 5 is (i) a hydrogen atom, or (ii) an alkyl group optionally substituted with 1 to 5 substituents independently selected from the group consisting of a halogen atom, a hydroxyl group, a phenyl group, and an alkoxy group.

[0453] (Embodiment 26) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 22, R 5 is a hydrogen atom or an alkyl group.

[0454] (Embodiment 27) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 22, R 5 For alkyl.

[0455] (Embodiment 28) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 22, R 5 It is methyl or ethyl.

[0456] (Embodiment 29) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 28, R 7 and R 8 are each independently a hydrogen atom, an alkyl group optionally substituted by 1 to 5 substituents independently selected from Group E, an alkenyl group optionally substituted by 1 to 5 substituents independently selected from Group E, or an alkynyl group optionally substituted by 1 to 5 substituents independently selected from Group E, or R 7 and R 8 Together with the carbon atom to which they are bonded, they form a monocyclic carbocyclic ring optionally substituted by 1 to 5 substituents independently selected from Group E.

[0457] (Embodiment 30) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 28, R 7 and R 8 are each independently a hydrogen atom, or an alkyl group optionally substituted by 1 to 5 substituents independently selected from Group E, or, R 7 and R 8 Together with the carbon atom to which they are bonded, they form a monocyclic carbocyclic ring optionally substituted by 1 to 5 substituents independently selected from Group E.

[0458] (Embodiment 31) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 28, R 7 and R 8 are each independently a hydrogen atom or an alkyl group, or, R 7 and R8 Together with the carbon atom to which they are bonded, they form a monocyclic carbocyclic ring optionally substituted by 1 to 5 substituents independently selected from Group E.

[0459] (Embodiment 32) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 28, R 7 and R 8 are each independently a hydrogen atom or an alkyl group, or, R 7 and R 8 Together with the carbon atom to which they are bonded, they form a monocyclic carbocycle.

[0460] (Embodiment 33) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 28, R 7 and R 8 Each is independently a hydrogen atom or an alkyl group.

[0461] (Embodiment 34) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 28, R 7 and R 8 are each independently a hydrogen atom, a methyl group, an ethyl group, or a propyl group, or R 7 and R 8 Together with the carbon atom to which they are bonded, they form a cyclopropane ring.

[0462] (Embodiment 35) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 28, R 7 and R 8 Each is independently a hydrogen atom, a methyl group, or an ethyl group.

[0463] (Embodiment 36) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 35, ring B is a bicyclic ring optionally substituted by 1 to 5 substituents independently selected from the group consisting of the following groups: a halogen atom, an alkyl group optionally substituted by 1 to 5 substituents independently selected from Group E, an alkenyl group optionally substituted by 1 to 5 substituents independently selected from Group E, an alkynyl group optionally substituted by 1 to 5 substituents independently selected from Group E, an alkoxy group optionally substituted by 1 to 5 substituents independently selected from Group E, a cycloalkyl group optionally substituted by 1 to 5 substituents independently selected from Group E, a non-aromatic heterocyclic group optionally substituted by 1 to 5 substituents independently selected from Group E, an aryl group optionally substituted by 1 to 5 substituents independently selected from Group E, a heteroaryl group optionally substituted by 1 to 5 substituents independently selected from Group E, and a cyano group.

[0464] (Embodiment 37) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 35, ring B is a bicyclic ring optionally substituted by 1 to 5 substituents independently selected from the group consisting of the following groups: a halogen atom, an alkyl group optionally substituted by 1 to 5 substituents independently selected from Group E, an alkoxy group optionally substituted by 1 to 5 substituents independently selected from Group E, and a cyano group.

[0465] (Embodiment 38) A compound or a pharmaceutically acceptable salt thereof, wherein among the compounds of the present invention or any one of Embodiments 1 to 37, X 1 and X 2 Each independently CR 9 or nitrogen atoms.

[0466] (Embodiment 39) A compound or a pharmaceutically acceptable salt thereof, wherein among the compounds of the present invention or any one of Embodiments 1 to 37, X 1 and X 2 Each independently CR 9 .

[0467] (Embodiment 40) A compound or a pharmaceutically acceptable salt thereof, wherein among the compounds of the present invention or any one of Embodiments 1 to 37, X 1 and X 2 are nitrogen atoms respectively.

[0468] (Embodiment 41) A compound or a pharmaceutically acceptable salt thereof, wherein among the compounds of the present invention or any one of Embodiments 1 to 37, X 1 CR 9 , X 2 A nitrogen atom.

[0469] (Embodiment 42) A compound or a pharmaceutically acceptable salt thereof, wherein among the compounds of the present invention or any one of Embodiments 1 to 37, X 1 is a nitrogen atom, X 2 CR 9 .

[0470] (Embodiment 43) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 42, R 9 Each is independently a hydrogen atom, a halogen atom, an alkyl group optionally substituted by 1 to 5 substituents independently selected from Group E, an alkoxy group optionally substituted by 1 to 5 substituents independently selected from Group E, or a cyano group.

[0471] (Embodiment 44) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 42, R 9Each is independently a hydrogen atom, a halogen atom, or an alkyl group optionally substituted by 1 to 5 halogen atoms.

[0472] (Embodiment 45) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 42, R 9 Each is independently a hydrogen atom, a halogen atom, or an alkyl group.

[0473] (Embodiment 46) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 42, R 9 are each independently a hydrogen atom or a halogen atom.

[0474] (Embodiment 47) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 42, R 9 are each independently a hydrogen atom, a fluorine atom, or a chlorine atom.

[0475] (Embodiment 48) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 42, R 9 are each independently a hydrogen atom or a fluorine atom.

[0476] (Embodiment 49) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 42, R 9 are hydrogen atoms respectively.

[0477] (Embodiment 50) A compound or a pharmaceutically acceptable salt thereof, wherein among the compounds of the present invention or any one of Embodiments 1 to 49, Y 1 、Y 2 、Y 3 and Y 4 Each independently CR 10 or nitrogen atoms.

[0478] (Embodiment 51) A compound or a pharmaceutically acceptable salt thereof, wherein among the compounds of the present invention or any one of Embodiments 1 to 49, Y 1 、Y 2 、Y 3 and Y 4 Each independently CR 10 .

[0479] (Embodiment 52) ​​A compound or a pharmaceutically acceptable salt thereof, wherein among the compounds of the present invention or any one of Embodiments 1 to 49, Y 1 、Y 2 、Y 3 and Y 4Any one of them is a nitrogen atom, and the other three are each independently CR 10 .

[0480] (Embodiment 53) A compound or a pharmaceutically acceptable salt thereof, wherein among the compounds of the present invention or any one of Embodiments 1 to 49, Y 1 、Y 2 、Y 3 and Y 4 Any two of them are nitrogen atoms, and the other two are independently CR 10 .

[0481] (Embodiment 54) A compound or a pharmaceutically acceptable salt thereof, wherein among the compounds of the present invention or any one of Embodiments 1 to 49, Y 1 、Y 2 、Y 3 and Y 4 Any three of them are nitrogen atoms, and the other one is CR 10 .

[0482] (Embodiment 55) A compound or a pharmaceutically acceptable salt thereof, wherein among the compounds of the present invention or any one of Embodiments 1 to 49, Y 1 、Y 2 、Y 3 and Y 4 All are nitrogen atoms.

[0483] (Embodiment 56) A compound or a pharmaceutically acceptable salt thereof, wherein among the compounds of the present invention or any one of Embodiments 1 to 49, Y 1 and Y 2 Each independently CR 10 or nitrogen atoms.

[0484] (Embodiment 57) A compound or a pharmaceutically acceptable salt thereof, wherein among the compounds of the present invention or any one of Embodiments 1 to 49, Y 1 and Y 2 Each independently CR 10 .

[0485] (Embodiment 58) A compound or a pharmaceutically acceptable salt thereof, wherein among the compounds of the present invention or any one of Embodiments 1 to 49, Y 1 and Y 2 One of them is a nitrogen atom and the other is CR 10 .

[0486] (Embodiment 59) A compound or a pharmaceutically acceptable salt thereof, wherein among the compounds of the present invention or any one of Embodiments 1 to 49, Y 1 and Y 2 All are nitrogen atoms.

[0487] (Embodiment 60) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 59, R 10 Each is independently a hydrogen atom, a halogen atom, an alkyl group optionally substituted by 1 to 5 substituents independently selected from Group E, an alkoxy group optionally substituted by 1 to 5 substituents independently selected from Group E, or a cyano group.

[0488] (Embodiment 61) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 59, R 10 Each is independently a hydrogen atom, a halogen atom, an alkyl group optionally substituted by 1 to 5 halogen atoms, or an alkoxy group optionally substituted by 1 to 5 halogen atoms.

[0489] (Embodiment 62) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 59, R 10 Each is independently a hydrogen atom, a halogen atom, or an alkyl group optionally substituted by 1 to 5 halogen atoms.

[0490] (Embodiment 63) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 59, R 10 Each is independently a hydrogen atom, a halogen atom, an alkyl group, or an alkoxy group.

[0491] (Embodiment 64) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 59, R 10 Each is independently a hydrogen atom, a halogen atom, or an alkyl group.

[0492] (Embodiment 65) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 59, R 10 Each is independently a hydrogen atom, a fluorine atom, a chlorine atom, a methyl group, or a methoxy group.

[0493] (Embodiment 66) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 59, R 10 Each is independently a hydrogen atom, a fluorine atom, or a methyl group.

[0494] (Embodiment 67) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 59, R 10 are hydrogen atoms respectively.

[0495] (Embodiment 68) A compound or a pharmaceutically acceptable salt thereof, wherein among the compounds of the present invention or any one of Embodiments 1 to 67, Q 1 and Q 2 Each independently CR 11 R 12 NR 13 , oxygen atom, sulfur atom, SO, or SO2.

[0496] (Embodiment 69) A compound or a pharmaceutically acceptable salt thereof, wherein among the compounds of the present invention or any one of Embodiments 1 to 67, Q 1 and Q 2 Each independently CR 11 R 12 NR 13 , or oxygen atoms.

[0497] (Embodiment 70) A compound or a pharmaceutically acceptable salt thereof, wherein among the compounds of the present invention or any one of Embodiments 1 to 67, Q 1 and Q 2 Each independently CR 11 R 12 .

[0498] (Embodiment 71) A compound or a pharmaceutically acceptable salt thereof, wherein among the compounds of the present invention or any one of Embodiments 1 to 67, Q 1 and Q 2 are oxygen atoms respectively.

[0499] (Embodiment 72) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 71, R 11 and R 12 Each is independently a hydrogen atom, a halogen atom, or an alkyl group.

[0500] (Embodiment 73) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 71, R 11 and R 12 Each is independently a hydrogen atom or an alkyl group.

[0501] (Embodiment 74) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 71, R 11 and R 12 are each independently a hydrogen atom or a methyl group.

[0502] (Embodiment 75) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 71, R 11 and R 12are hydrogen atoms respectively.

[0503] (Embodiment 76) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 75, R 13 Each is independently a hydrogen atom or an alkyl group.

[0504] (Embodiment 77) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 75, R 13 are each independently a hydrogen atom or a methyl group.

[0505] (Embodiment 78) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 75, R 13 are hydrogen atoms respectively.

[0506] (Embodiment 79) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 78, Z is NR 14 , oxygen atom, or sulfur atom.

[0507] (Embodiment 80) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 78, Z is NR 14 .

[0508] (Embodiment 81) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 80, R 14 is a hydrogen atom or an alkyl group.

[0509] (Embodiment 82) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 80, R 14 is a hydrogen atom or a methyl group.

[0510] (Embodiment 83) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 80, R 14 A hydrogen atom.

[0511] (Embodiment 84) A compound or a pharmaceutically acceptable salt thereof, wherein among the compounds of the present invention or any one of Embodiments 1 to 83, Q 3 for (CU 1 U 2 ) n ;U 1 and U 2 are each independently a hydrogen atom, a halogen atom, or an alkyl group; and n is 1, 2, or 3.

[0512] (Embodiment 85) A compound or a pharmaceutically acceptable salt thereof, wherein among the compounds of the present invention or any one of Embodiments 1 to 83, Q 3 for (CU 1 U 2 ) n ;U 1 and U 2 Each is independently a hydrogen atom, a halogen atom, or an alkyl group; and n is 1 or 2.

[0513] (Embodiment 86) A compound or a pharmaceutically acceptable salt thereof, wherein among the compounds of the present invention or any one of Embodiments 1 to 83, Q 3 for (CU 1 U 2 ) n ;U 1 and U 2 are each independently a hydrogen atom, a halogen atom, or an alkyl group; and n is 1.

[0514] (Embodiment 87) A compound or a pharmaceutically acceptable salt thereof, wherein among the compounds of the present invention or any one of Embodiments 1 to 83, Q 3 for (CU 1 U 2 ) n ;U 1 and U 2 are each independently a hydrogen atom, a fluorine atom, or a methyl group; and n is 1.

[0515] (Embodiment 88) A compound or a pharmaceutically acceptable salt thereof, wherein among the compounds of the present invention or any one of Embodiments 1 to 83, Q 3 for (CU 1 U 2 ) n ;U 1 and U 2 All are hydrogen atoms; n is 1.

[0516] (Embodiment 89) A compound or a pharmaceutically acceptable salt thereof, wherein among the compounds of the present invention or any one of Embodiments 1 to 83, Q 3 for (CU 1 U 2 ) n ;U 1 and U 2 are all fluorine atoms; n is 1.

[0517] (Embodiment 90) A compound or a pharmaceutically acceptable salt thereof, wherein among the compounds of the present invention or any one of Embodiments 1 to 83, Q 3 for (CU 1 U 2 ) n;U 1 and U 2 All are methyl; n is 1.

[0518] (Embodiment 91) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 90, ring D is a 5- to 6-membered carbocyclic ring or a 5- to 6-membered heterocyclic ring, each of which is optionally substituted by 1 to 5 substituents independently selected from the group consisting of the following groups: a halogen atom, an alkyl group optionally substituted by 1 to 5 substituents independently selected from Group E, an alkoxy group optionally substituted by 1 to 5 substituents independently selected from Group E, and a cyano group.

[0519] (Embodiment 92) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 90, ring D is a 5- to 6-membered carbocyclic ring or a 5- to 6-membered heterocyclic ring, each of which is optionally substituted by 1 to 5 substituents independently selected from the group consisting of the following groups: a halogen atom, and an alkyl group optionally substituted by 1 to 5 halogen atoms.

[0520] (Embodiment 93) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 90, ring D is a 5- to 6-membered carbocyclic ring or a 5- to 6-membered heterocyclic ring, each of which is optionally substituted by 1 to 5 substituents independently selected from the group consisting of halogen atoms and alkyl groups.

[0521] (Embodiment 94) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 90, ring D is a 5- to 6-membered carbocyclic ring or a 5- to 6-membered heterocyclic ring, each of which is optionally substituted by 1 to 5 substituents independently selected from the group consisting of a fluorine atom and a methyl group.

[0522] (Embodiment 95) A compound or a pharmaceutically acceptable salt thereof having a structure represented by the following general formula (I-1).

[0523] [Chemical Formula 12]

[0524]

[0525] [In the formula, the symbols have the same meanings as those defined for the compounds of the present invention or any of Embodiments 1 to 94.]

[0526] (Embodiment 96) A compound or a pharmaceutically acceptable salt thereof, wherein in Compound (I) or Compound (I-1),

[0527] R is a hydrogen atom or an alkyl group;

[0528] R 1 and R 2 are each independently a hydrogen atom or an alkyl group;

[0529] Or, R 1 and R 2 Together with the carbon atom to which they are bonded, they form a monocyclic carbocycle;

[0530] R 3 is a hydrogen atom, a halogen atom, an alkyl group, or an alkoxy group;

[0531] R 4 and R 6 are each independently a hydrogen atom, an alkyl group, or an alkoxy group;

[0532] R 5 is a hydrogen atom or an alkyl group;

[0533] A has the same meaning as defined in the compound of the present invention or any one of Embodiments 1 to 94.

[0534] (Embodiment 97) A compound or a pharmaceutically acceptable salt thereof, wherein in Compound (I) or Compound (I-1),

[0535] R is a hydrogen atom;

[0536] R 1 and R 2 are each independently a hydrogen atom or an alkyl group;

[0537] Or, R 1 and R 2 Together with the carbon atom to which they are bonded, they form a monocyclic carbocycle;

[0538] R 3 is an alkyl group;

[0539] R 4 is an alkyl group;

[0540] R 5 is an alkyl group;

[0541] R 6 is a hydrogen atom;

[0542] A has the same meaning as defined in the compound of the present invention or any one of Embodiments 1 to 94.

[0543] (Embodiment 98) A compound or a pharmaceutically acceptable salt thereof, wherein in Compound (I) or Compound (I-1),

[0544] R is a hydrogen atom;

[0545] R 1 and R 2 are each independently a hydrogen atom or an alkyl group;

[0546] R 3is an alkyl group;

[0547] R 4 is an alkyl group;

[0548] R 5 is an alkyl group;

[0549] R 6 is a hydrogen atom;

[0550] A has the same meaning as defined in the compound of the present invention or any one of Embodiments 1 to 94.

[0551] (Embodiment 99) A compound or a pharmaceutically acceptable salt thereof, wherein, in the compound of the present invention or any one of Embodiments 1 to 98, A has a structure represented by any one of the following formulae (II-1) to (II-3).

[0552] [Chemical Formula 13]

[0553]

[0554] [In the formula, the symbols have the same meanings as those defined for the compounds of the present invention or any of Embodiments 1 to 94.]

[0555] (Embodiment 100) A compound or a pharmaceutically acceptable salt thereof, wherein in the structures represented by formula (II-1) to (II-3),

[0556] R 7 and R 8 are each independently a hydrogen atom or an alkyl group;

[0557] Or, R 7 and R 8 Together with the carbon atom to which they are bound, they form a monocyclic carbocyclic ring optionally substituted by 1 to 5 substituents independently selected from Group E;

[0558] X 1 and X 2 Each independently CR 9 or nitrogen atoms;

[0559] R 9 are each independently a hydrogen atom, a halogen atom, an alkyl group optionally substituted by 1 to 5 substituents independently selected from Group E, an alkoxy group optionally substituted by 1 to 5 substituents independently selected from Group E, or a cyano group;

[0560] Ring D is a 5- to 6-membered carbocyclic ring or a 5- to 6-membered heterocyclic ring, each of which is optionally substituted by 1 to 5 substituents independently selected from the group consisting of a halogen atom, an alkyl group optionally substituted by 1 to 5 substituents independently selected from Group E, an alkoxy group optionally substituted by 1 to 5 substituents independently selected from Group E, and a cyano group.

[0561] (Embodiment 101) A compound or a pharmaceutically acceptable salt thereof, wherein, in the compound of the present invention or any one of Embodiments 1 to 100, A has a structure represented by any one of the following formulas (II-1-1) to (II-3-4).

[0562] [Chemical Formula 14]

[0563]

[0564] [In the formula, the symbols have the same meanings as those defined in the compound of the present invention or any of Embodiments 1 to 100.]

[0565] (Embodiment 102) A compound or a pharmaceutically acceptable salt thereof, wherein in the compound of the present invention or any one of Embodiments 1 to 100, A has a structure represented by any one of the following formulas (II-1-1) or (II-3-1).

[0566] [Chemical Formula 15]

[0567]

[0568] [In the formula, the symbols have the same meanings as those defined in the compound of the present invention or any of Embodiments 1 to 100.]

[0569] (Embodiment 103) A compound or a pharmaceutically acceptable salt thereof, wherein in the structures represented by formula (II-1-1) to (II-3-4),

[0570] R 7 and R 8 are each independently a hydrogen atom or an alkyl group;

[0571] Or, R 7 and R 8 Together with the carbon atom to which they are bound, they form a monocyclic carbocyclic ring optionally substituted by 1 to 5 substituents independently selected from Group E;

[0572] X 1 and X 2 Each independently CR 9 or nitrogen atoms;

[0573] Y 1 、Y 2 、Y 3 and Y 4 Each independently CR 10 or nitrogen atoms;

[0574] R 9 and R 10are each independently a hydrogen atom, a halogen atom, an alkyl group optionally substituted by 1 to 5 substituents independently selected from Group E, an alkoxy group optionally substituted by 1 to 5 substituents independently selected from Group E, or a cyano group;

[0575] Q 1 and Q 2 Each independently CR 11 R 12 NR 13 , oxygen atom, sulfur atom, SO, or SO2;

[0576] R 11 and R 12 are each independently a hydrogen atom, a halogen atom, or an alkyl group;

[0577] R 13 are each independently a hydrogen atom or an alkyl group;

[0578] Z is NR 14 , oxygen atoms, or sulfur atoms;

[0579] R 14 is a hydrogen atom or an alkyl group;

[0580] Q 3 for (CU 1 U 2 ) n ;

[0581] U 1 and U 2 are each independently a hydrogen atom, a halogen atom, or an alkyl group;

[0582] n is 1, 2, or 3.

[0583] (Embodiment 104) The compound according to Embodiment 103 or a pharmaceutically acceptable salt thereof, wherein Q 1 and Q 2 Each independently CR 11 R 12 NR 13 , or oxygen atoms.

[0584] (Embodiment 105) A compound or a pharmaceutically acceptable salt thereof, wherein, in the compound of the present invention or any one of Embodiments 1 to 104, A has a structure represented by the following formula (II-1-1).

[0585] [Chemical Formula 16]

[0586]

[0587] [In the formula, the symbols have the same meanings as those defined in the compounds of the present invention or any of Embodiments 1 to 104.]

[0588] (Embodiment 106) A compound or a pharmaceutically acceptable salt thereof, wherein in the structure represented by formula (II-1-1),

[0589] R 7 and R 8 are each independently a hydrogen atom or an alkyl group;

[0590] Or, R 7 and R 8 Together with the carbon atom to which they are bonded, they form a monocyclic carbocycle;

[0591] X 1 and X 2 Each independently CR 9 ;

[0592] Y 1 、Y 2 、Y 3 and Y 4 Any one of them is a nitrogen atom, and the other three are each independently CR 10 ;

[0593] R 9 are hydrogen atoms;

[0594] R 10 Each is independently a hydrogen atom, a halogen atom, an alkyl group, or an alkoxy group.

[0595] (Embodiment 107) The compound according to Embodiment 106 or a pharmaceutically acceptable salt thereof, wherein R 7 and R 8 are each independently a hydrogen atom or an alkyl group;

[0596] R 10 Each is independently a hydrogen atom, a halogen atom, or an alkyl group.

[0597] (Embodiment 108) A compound or a pharmaceutically acceptable salt thereof, wherein, in the compound of the present invention or any one of Embodiments 1 to 104, A has a structure represented by the following formula (II-3-1).

[0598] [Chemical Formula 17]

[0599]

[0600] [In the formula, the symbols have the same meanings as those defined in the compounds of the present invention or any of Embodiments 1 to 104.]

[0601] (Embodiment 109) A compound or a pharmaceutically acceptable salt thereof, wherein in the structure represented by formula (II-3-1),

[0602] R 7 and R 8 are each independently a hydrogen atom or an alkyl group;

[0603] X 1 and X 2 One of them is a nitrogen atom and the other is CR 9 ;

[0604] Y 1 、Y 2 、Y 3 and Y 4 Each independently CR 10 ;

[0605] R 9 are hydrogen atoms;

[0606] R 10 Each is independently a hydrogen atom, a halogen atom, or an alkyl group.

[0607] (Embodiment 110) A compound or a pharmaceutically acceptable salt thereof having a structure represented by the following general formula (I-1-1).

[0608] [Chemical Formula 18]

[0609]

[0610] [In the formula, the symbols have the same meanings as those defined in the compound of the present invention or any of Embodiments 1 to 94.]

[0611] (Embodiment 111) A compound or a pharmaceutically acceptable salt thereof, wherein in compound (I-1-1),

[0612] R is a hydrogen atom or an alkyl group;

[0613] R 1 and R 2 are each independently a hydrogen atom or an alkyl group;

[0614] Or, R 1 and R 2 Together with the carbon atom to which they are bonded, they form a monocyclic carbocycle;

[0615] R 3 、R 4 and R 6 are each independently a hydrogen atom, a halogen atom, an alkyl group, or an alkoxy group;

[0616] R 5 is (i) a hydrogen atom, or (ii) an alkyl group optionally substituted by 1 to 5 substituents independently selected from the group consisting of a halogen atom, a hydroxyl group, a phenyl group, and an alkoxy group;

[0617] R 7 and R 8 are each independently a hydrogen atom or an alkyl group;

[0618] Or, R 7 and R 8 Together with the carbon atom to which they are bound, they form a monocyclic carbocyclic ring optionally substituted by 1 to 5 substituents independently selected from Group E;

[0619] R 10 is a hydrogen atom, a halogen atom, an alkyl group optionally substituted by 1 to 5 substituents independently selected from Group E, an alkoxy group optionally substituted by 1 to 5 substituents independently selected from Group E, or a cyano group;

[0620] Group E is a group consisting of a halogen atom, a hydroxyl group, and an alkoxy group optionally substituted with 1 to 5 halogen atoms.

[0621] (Embodiment 112) A compound or a pharmaceutically acceptable salt thereof, wherein in compound (I-1-1),

[0622] R is a hydrogen atom or an alkyl group;

[0623] R 1 and R 2 are each independently a hydrogen atom or an alkyl group;

[0624] Or, R 1 and R 2 Together with the carbon atom to which they are bonded, they form a monocyclic carbocycle;

[0625] R 3 is a hydrogen atom, a halogen atom, an alkyl group, or an alkoxy group;

[0626] R 4 is a hydrogen atom or an alkyl group;

[0627] R 5 is an alkyl group;

[0628] R 6 is a hydrogen atom;

[0629] R 7 and R 8 are each independently a hydrogen atom or an alkyl group;

[0630] Or, R 7 and R 8 Together with the carbon atom to which they are bonded, they form a monocyclic carbocycle;

[0631] R 10 is a hydrogen atom, a halogen atom, an alkyl group, or an alkoxy group.

[0632] Method for producing compound (I)

[0633] One embodiment of the present invention provides a method for producing compound (I). In one embodiment, the method for producing compound (I) comprises reacting a compound represented by the following general formula (III) or a salt thereof with a compound represented by the following general formula (IV) or a salt thereof under conditions suitable for producing compound (I).

[0634] [Chemical Formula 19]

[0635]

[0636] [In the formula, the symbols have the same meanings as above.]

[0637] [Chemical Formula 20]

[0638]

[0639] [In the formula, the symbols have the same meanings as above.]

[0640] In one embodiment, in a solvent (for example, amides such as dimethylformamide; ethers such as tetrahydrofuran and 1,4-dioxane; halogenated aliphatic hydrocarbons such as chloroform, dichloromethane, and dichloroethane; aromatic hydrocarbons such as toluene; nitriles such as acetonitrile; carboxylic acids such as acetic acid; and mixtures thereof), in the presence of a reducing agent (for example, sodium triacetoxyborohydride and sodium borohydride), in the presence of a base (for example, alkali metal carbonates such as cesium carbonate, potassium carbonate, sodium carbonate, and sodium bicarbonate; tribasic Compound (I) can be produced by reacting compound (III) with compound (IV) in the presence or absence of an alkali metal phosphate such as potassium phosphate, sodium phosphate, and sodium hydrogen phosphate; an alkali metal fluoride such as cesium fluoride and potassium fluoride; an alkylamine such as triethylamine and N,N-diisopropylethylamine; a pyridine such as pyridine and 4-dimethylaminopyridine; and 1,8-diazabicyclo[5.4.0]-7-undecene, etc., and in the presence or absence of an acid (e.g., acetic acid, etc.).

[0641] In another embodiment, the method for producing compound (I) comprises reacting a compound represented by the following general formula (III') or a salt thereof with a compound represented by the following general formula (IV) or a salt thereof under conditions suitable for producing compound (I).

[0642] [Chemical Formula 21]

[0643]

[0644] [Where, L 1 represents a leaving group such as a halogen atom; other symbols have the same meanings as above.]

[0645] [Chemical Formula 22]

[0646]

[0647] [In the formula, the symbols have the same meanings as above.]

[0648] In one embodiment, compound (I) can be produced by reacting compound (III') with compound (IV) in a solvent (e.g., amides such as dimethylformamide; ethers such as tetrahydrofuran and 1,4-dioxane; halogenated aliphatic hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as toluene; nitriles such as acetonitrile; carboxylic acids such as acetic acid; and mixtures thereof) in the presence or absence of a base (e.g., alkali metal carbonates such as cesium carbonate, potassium carbonate, sodium carbonate, and sodium hydrogencarbonate; alkali metal phosphates such as tribasic potassium phosphate, sodium phosphate, and sodium hydrogenphosphate; alkali metal fluorides such as cesium fluoride and potassium fluoride; alkylamines such as triethylamine and N,N-diisopropylethylamine; pyridines such as pyridine and 4-dimethylaminopyridine; and 1,8-diazabicyclo[5.4.0]-7-undecene).

[0649] The compound (I) of the present invention or its synthetic intermediate may exist in the form of tautomers or mixtures thereof. The compound (I) of the present invention may exist in the form of stereoisomers such as enantiomers or diastereomers, or mixtures thereof. The compound (I) of the present invention includes tautomers, mixtures of stereoisomers, or pure or substantially pure isomers.

[0650] When the compound (I) of the present invention or its synthetic intermediate is obtained in the form of diastereomers or enantiomers, they can be separated by conventional methods known in the art, such as chromatography and fractional crystallization.

[0651] The compound (I) of the present invention or its synthetic intermediate includes the compound (I) of the present invention or its synthetic intermediate including ... 2 H. 3 H. 13 C. 14 C. 15 N. 18 F. 32 P. 35 S. 125 I, etc.) and deuterated transformants thereof.

[0652] Pharmaceutically acceptable salts of compound (I) include: alkali metal salts such as lithium, sodium and potassium; Group 2 metal salts such as magnesium and calcium; salts with aluminum or zinc; salts with amines such as ammonia, choline, diethanolamine, lysine, ethylenediamine, tert-butylamine, tert-octylamine, tris(hydroxymethyl)aminomethane, N-methyl-glucosamine, triethanolamine and dehydroabiethylamine; salts with inorganic acids such as hydrogen chloride, hydrogen bromide, hydrogen iodide, sulfuric acid, nitric acid and phosphoric acid; salts with organic acids such as formic acid, acetic acid, trifluoroacetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, methanesulfonic acid, ethanesulfonic acid and benzenesulfonic acid; or salts with acidic amino acids such as aspartic acid and glutamic acid.

[0653] The synthetic intermediate of compound (I) may be in free form or in salt form. Examples of the salt of the synthetic intermediate of compound (I) include the same salts as those exemplified in the above-mentioned "pharmaceutically acceptable salts of compound (I)" and pharmaceutically unacceptable salts.

[0654] Furthermore, Compound (I) or a pharmaceutically acceptable salt thereof, and a synthetic intermediate of Compound (I) or a salt thereof include intramolecular salts, hydrates, and solvates thereof.

[0655] In this specification, "pharmaceutically acceptable" means that the drug is generally not harmful to the recipient and that the components are compatible with each other when preparing a pharmaceutical composition, and includes not only use as a human medicine but also use in veterinary medicine.

[0656] (use)

[0657] The compound (I) of the present invention defined by the above embodiments and their combinations or its pharmaceutically acceptable salt is useful as an active ingredient of a pharmaceutical composition, and the compound defined by any embodiment and their combination can be administered to a subject (preferably a human). In one embodiment, the compound (I) or its pharmaceutically acceptable salt in which R in any embodiment of the above embodiments and their combinations is a hydrogen atom is administered.

[0658] The compound (I) of the present invention or its pharmaceutically acceptable salt can be administered orally or parenterally alone or in the form of a pharmaceutical composition comprising it and a pharmaceutically acceptable carrier. Preferably, the pharmaceutical composition of the present invention contains the compound (I) of the present invention or its pharmaceutically acceptable salt and a pharmaceutically acceptable carrier. As a pharmaceutically acceptable carrier, it is a carrier conventionally used in the art, for example, diluents, binders (syrup, gum arabic, gelatin, sorbitol, tragacanth gum and polyvinyl pyrrolidone, etc.), excipients (lactose, sucrose, corn starch, potassium phosphate, sorbitol and glycine, etc.), lubricants (magnesium stearate, talc, polyethylene glycol and silicon dioxide, etc.), disintegrants (potato starch, etc.) and wetting agents (sodium lauryl sulfate, etc.). In addition, the dosage form of the pharmaceutical composition is not particularly limited and can be used in the form of pharmaceutical preparations conventionally used in tablets, granules, capsules, powders, injections, inhalants or suppositories.

[0659] The dosage of compound (I) of the present invention or a pharmaceutically acceptable salt thereof (i.e., effective amount) varies depending on the method of administration, age, weight, and condition of the patient, but is generally preferably 0.001 to 500 mg / kg, particularly 0.01 to 10 mg / kg per day, administered once or dividedly in 2 to 4 doses.

[0660] Compound (I) of the present invention or a pharmaceutically acceptable salt thereof has Keap1 (Kelch-like ECH-associated protein 1) inhibitory activity and is effective for preventing, alleviating, and / or treating diseases that are ameliorated by inhibiting Keap1. Examples of such diseases include renal diseases (e.g., chronic renal disease and Alport syndrome).

[0661] One embodiment of the present invention relates to a pharmaceutical composition comprising a compound (I) of the present invention or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition is used to prevent, alleviate and / or treat a disease whose symptoms are improved by Keap1 inhibition. In another embodiment, the pharmaceutical composition is used to prevent, alleviate and / or treat renal disease (e.g., chronic renal disease and Alport syndrome).

[0662] One embodiment of the present invention relates to the use of a compound (I) of the present invention or a pharmaceutically acceptable salt thereof in the manufacture of a pharmaceutical. In one embodiment, the pharmaceutical is used to prevent, alleviate, and / or treat a disease whose symptoms are improved by inhibiting Keap1. In another embodiment, the pharmaceutical is used to prevent, alleviate, and / or treat renal disease (e.g., chronic renal disease and Alport syndrome).

[0663] One embodiment of the present invention relates to a compound (I) of the present invention or a pharmaceutically acceptable salt thereof, which is used for the prevention, alleviation and / or treatment of a disease. One embodiment of the present invention relates to a compound (I) of the present invention or a pharmaceutically acceptable salt thereof, which is used for the prevention, alleviation and / or treatment of a disease whose symptoms are improved by Keap1 inhibition. Another embodiment of the present invention relates to a compound (I) of the present invention or a pharmaceutically acceptable salt thereof, which is used for the prevention, alleviation and / or treatment of kidney disease (e.g., chronic kidney disease and Alport syndrome).

[0664] One embodiment of the present invention relates to a method for preventing, alleviating, and / or treating a disease whose symptoms are ameliorated by inhibition of Keap1, comprising administering a compound (I) of the present invention or a pharmaceutically acceptable salt thereof. Another embodiment of the present invention relates to a method for preventing, alleviating, and / or treating a kidney disease (e.g., chronic kidney disease and Alport syndrome), comprising administering a compound (I) of the present invention or a pharmaceutically acceptable salt thereof.

[0665] Compound (I) or a pharmaceutically acceptable salt thereof can be produced by the following method, but is not limited thereto. In addition, the steps in the following production method can be combined as appropriate and carried out.

[0666] In each manufacturing process of compound (I) described below, when it is necessary to protect the functional group contained in the compound, it can be suitably implemented by the method specifically described below or a conventional method. The common description about protecting groups and their use is recorded in TW Greene et al., " Protective Groups in Organic Synthesis ", John Wiley & Sons, New York, Fifth Edition. Protecting groups can be removed in the subsequent process using the method specifically described below or a conventional method. In addition, carboxylic acid compounds or their salts and amine compounds or their salts can each be converted into each other by the method specifically described below or a conventional salt-forming process or a desalting process.

[0667] Manufacturing method 1

[0668] Compound (I) can be produced, for example, according to the following scheme.

[0669] [Chemical Formula 23]

[0670]

[0671] [In the formula, the symbols have the same meanings as above.]

[0672] Compound (I) can be produced by reacting Compound (III) with Compound (IV) in a solvent in the presence of a reducing agent, in the presence or absence of a base, or in the presence or absence of an acid. Compound (IV) may be in the form of a free form or a salt such as hydrochloride.

[0673] The solvent may be any solvent that does not affect the reaction, and examples thereof include amides such as dimethylformamide; ethers such as tetrahydrofuran and 1,4-dioxane; alcohols such as methanol, ethanol and isopropanol; halogenated aliphatic hydrocarbons such as chloroform, dichloromethane and dichloroethane; aromatic hydrocarbons such as toluene; nitriles such as acetonitrile; carboxylic acids such as acetic acid; and mixtures thereof.

[0674] Examples of the reducing agent include sodium triacetoxyborohydride and sodium borohydride.

[0675] Examples of the base include alkali metal carbonates such as cesium carbonate, potassium carbonate, sodium carbonate, and sodium hydrogencarbonate; alkali metal phosphates such as tribasic potassium phosphate, sodium phosphate, and sodium hydrogenphosphate; alkali metal fluorides such as cesium fluoride and potassium fluoride; alkylamines such as triethylamine and N,N-diisopropylethylamine; pyridines such as pyridine and 4-dimethylaminopyridine; and 1,8-diazabicyclo[5.4.0]-7-undecene.

[0676] Examples of the acid include acetic acid.

[0677] The amount of compound (IV) used can be 1.0 to 3.0 equivalents, preferably 1.0 to 2.0 equivalents, based on a molar ratio of compound (III).

[0678] The amount of the reducing agent used can be 1.0 to 5.0 equivalents, preferably 1.5 to 3.0 equivalents, based on a molar ratio to compound (III).

[0679] The amount of the base used can be 1.0 to 5.0 equivalents, preferably 1.0 to 3.0 equivalents, based on a molar ratio to compound (III).

[0680] The amount of the acid used can be 1.0 to 3.0 equivalents, preferably 1.0 to 2.0 equivalents, based on a molar ratio to compound (III).

[0681] This reaction can be carried out at room temperature to under heating, for example, room temperature to 100°C, preferably at room temperature.

[0682] Alternatively, a compound whose ring B portion of compound (IV) is a precursor of ring B may be used as a starting material instead of compound (IV) and reacted in the same manner as above to produce a compound whose ring B portion of compound (I) is a precursor of ring B, and then form ring B to produce compound (I).

[0683] Manufacturing method 2

[0684] Compound (I) can also be produced according to the following scheme.

[0685] [Chemical Formula 24]

[0686]

[0687] [In the formula, the symbols have the same meanings as above.]

[0688] Compound (I) can be produced by reacting Compound (III') with Compound (IV) in a solvent in the presence or absence of a base. Compound (IV) may be in the form of a free form or a salt such as hydrochloride.

[0689] The solvent may be any solvent that does not affect the reaction, and examples thereof include amides such as dimethylformamide; ethers such as tetrahydrofuran and 1,4-dioxane; halogenated aliphatic hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as toluene; nitriles such as acetonitrile; and mixtures thereof.

[0690] Examples of the base include alkali metal carbonates such as cesium carbonate, potassium carbonate, sodium carbonate, and sodium hydrogencarbonate; alkali metal phosphates such as tribasic potassium phosphate, sodium phosphate, and sodium hydrogenphosphate; alkali metal fluorides such as cesium fluoride and potassium fluoride; alkylamines such as triethylamine and N,N-diisopropylethylamine; pyridines such as pyridine and 4-dimethylaminopyridine; and 1,8-diazabicyclo[5.4.0]-7-undecene.

[0691] The amount of compound (IV) used can be 1.0 to 3.0 equivalents, preferably 1.0 to 2.0 equivalents, based on a molar ratio of compound (III').

[0692] The amount of the base used can be 1.0 to 6.0 equivalents, preferably 1.0 to 4.5 equivalents, based on a molar ratio to compound (III').

[0693] This reaction can be carried out at room temperature to under heating, for example, at room temperature to 150°C, preferably at room temperature to 100°C.

[0694] Alternatively, a compound whose ring B portion of compound (IV) is a precursor of ring B may be used as a starting material instead of compound (IV) and reacted in the same manner as above to produce a compound whose ring B portion of compound (I) is a precursor of ring B, and then form ring B to produce compound (I).

[0695] Reference manufacturing method 1

[0696] Compound (III) can be produced, for example, according to the following scheme.

[0697] [Chemical Formula 25]

[0698]

[0699] [In the formula, the symbols have the same meanings as above.]

[0700] Compound (III) can be produced by reacting Compound (III-1) in a solvent in the presence of an oxidizing agent.

[0701] The solvent may be any solvent that does not affect the reaction, and examples thereof include amides such as dimethylformamide; ethers such as tetrahydrofuran and 1,4-dioxane; halogenated aliphatic hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as toluene; nitriles such as acetonitrile; carboxylic acids such as acetic acid; and mixtures thereof.

[0702] Examples of the oxidizing agent include Dess-Martin reagent, 2,2,6,6-tetramethylpiperidine-1-oxide, iodobenzene diacetate, and mixtures thereof.

[0703] The amount of the oxidizing agent used can be 1.0 to 5.0 equivalents, preferably 1.0 to 3.0 equivalents, based on a molar ratio with respect to compound (III-1).

[0704] This reaction can be carried out under ice-cooling to heating, for example, under ice-cooling to 100°C, preferably under ice-cooling to room temperature.

[0705] Reference Manufacturing Method 2

[0706] Compound (III') can be produced, for example, according to the following scheme.

[0707] [Chemical Formula 26]

[0708]

[0709] [In the formula, the symbols have the same meanings as above.]

[0710] By reacting compound (III-1) with L in a solvent 1 The donor reaction can produce compound (III').

[0711] The solvent may be any solvent that does not affect the reaction, and examples thereof include ethers such as tetrahydrofuran and 1,4-dioxane; halogenated aliphatic hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as toluene; nitriles such as acetonitrile; and mixtures thereof.

[0712] As L 1 Examples of the donor include halogenating agents such as thionyl chloride.

[0713] L1 The amount of the donor used can be 1.0 to 5.0 equivalents, preferably 1.0 to 3.0 equivalents, based on a molar ratio with respect to compound (III-1).

[0714] This reaction can be carried out at room temperature to under heating, for example, room temperature to 100°C, preferably at room temperature.

[0715] Reference Manufacturing Method 3

[0716] Compound (III-1) can be produced, for example, according to the following scheme.

[0717] [Chemical Formula 27]

[0718]

[0719] [Where V 1 represents a halogen atom such as a bromine atom; P 1 represents a protecting group such as 4-methoxybenzyl; P 2 represents a protecting group such as trimethylsilyl; other symbols have the same meanings as above.]

[0720] Process 1

[0721] Compound (III-7) is reacted with P in a solvent in the presence of a base. 1 Compound (III-6) can be produced by the donor reaction. Compound (III-7) can be produced from a commercially available substance or by a known method.

[0722] The solvent may be any solvent that does not affect the reaction, and examples thereof include amides such as dimethylformamide; ethers such as tetrahydrofuran and 1,4-dioxane; halogenated aliphatic hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as toluene; nitriles such as acetonitrile; and mixtures thereof.

[0723] Examples of the base include alkali metal carbonates such as sodium carbonate, potassium carbonate, and sodium bicarbonate; alkali metal hydrides such as sodium hydride; alkylamines such as triethylamine and N,N-diisopropylethylamine; pyridines such as pyridine and 4-dimethylaminopyridine; and 1,8-diazabicyclo[5.4.0]-7-undecene.

[0724] As P 1 Examples of the donor include 4-methoxybenzyl chloride.

[0725] P 1 The amount of the donor used can be 1.0 to 3.0 equivalents, preferably 1.0 to 2.0 equivalents, based on a molar ratio with respect to compound (III-7).

[0726] The amount of the base used can be 1.0 to 5.0 equivalents, preferably 1.0 to 2.0 equivalents, based on a molar ratio to compound (III-7).

[0727] This reaction can be carried out under ice-cooling to heating, for example, under ice-cooling to 100°C, preferably under ice-cooling to room temperature.

[0728] Process 2

[0729] Compound (III-4) can be produced by reacting Compound (III-6) with Compound (III-5) in a solvent in the presence of an alkyllithium. Compound (III-5) can be a commercially available substance or can be produced from a commercially available substance by a known method.

[0730] The solvent may be any solvent that does not affect the reaction, and examples thereof include ethers such as tetrahydrofuran and 1,4-dioxane; aromatic hydrocarbons such as toluene; and mixtures thereof.

[0731] Examples of the alkyllithium include n-butyllithium and the like.

[0732] The amount of compound (III-5) used can be 0.8 to 3.0 equivalents, preferably 1.0 to 2.0 equivalents, based on a molar ratio of compound (III-6).

[0733] The amount of the alkyl lithium used can be 0.8 to 3.0 equivalents, preferably 0.8 to 2.0 equivalents, based on a molar ratio to compound (III-6).

[0734] This reaction can be carried out at -100°C to heating, for example, -100°C to 100°C, preferably -80°C to room temperature.

[0735] Process 3

[0736] Compound (III-2) can be produced by reacting compound (III-4) in a solvent in the presence of trichloroacetonitrile and a base, followed by reacting with compound (III-3) in the presence of trifluoromethanesulfonimide. Compound (III-3) can be commercially available or produced from commercially available materials using known methods.

[0737] The solvent may be any solvent that does not affect the reaction, and examples thereof include amides such as dimethylformamide; ethers such as tetrahydrofuran and 1,4-dioxane; halogenated aliphatic hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as toluene; nitriles such as acetonitrile; and mixtures thereof.

[0738] Examples of the base include alkali metal carbonates such as sodium carbonate, potassium carbonate, and sodium bicarbonate; alkali metal hydrides such as sodium hydride; alkyl lithiums such as n-butyl lithium; alkylamines such as triethylamine and N,N-diisopropylethylamine; pyridines such as pyridine and 4-dimethylaminopyridine; and 1,8-diazabicyclo[5.4.0]-7-undecene.

[0739] The amount of compound (III-3) used can be 1.0 to 10.0 equivalents, preferably 1.0 to 6.0 equivalents, based on a molar ratio of compound (III-4).

[0740] The amount of trichloroacetonitrile used can be 1.0 to 5.0 equivalents, preferably 1.0 to 3.0 equivalents, based on a molar ratio with respect to compound (III-4).

[0741] The amount of the base used can be 0.05 to 1.0 equivalents, preferably 0.05 to 0.5 equivalents, based on a molar ratio with respect to compound (III-4).

[0742] The amount of trifluoromethanesulfonimide used can be 0.05 to 1.0 equivalents, preferably 0.05 to 0.5 equivalents, based on a molar ratio with respect to compound (III-4).

[0743] This reaction can be carried out under ice-cooling to heating, for example, under ice-cooling to 100°C, preferably at room temperature.

[0744] Process 4

[0745] Compound (III-1) can be produced by reacting Compound (III-2) in a solvent in the presence of an oxidizing agent.

[0746] The solvent may be any solvent that does not affect the reaction, and examples thereof include amides such as dimethylformamide; ethers such as tetrahydrofuran and 1,4-dioxane; halogenated aliphatic hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as toluene; nitriles such as acetonitrile; carboxylic acids such as acetic acid; water; and mixtures thereof.

[0747] Examples of the oxidizing agent include ammonium cerium (IV) nitrate and the like.

[0748] The amount of the oxidizing agent used can be 1.0 to 5.0 equivalents, preferably 1.0 to 2.0 equivalents, based on a molar ratio with respect to compound (III-2).

[0749] This reaction can be carried out under ice-cooling to heating, for example, under ice-cooling to 100°C, preferably at room temperature.

[0750] Compound (III-4) can also be produced according to the following scheme.

[0751] [Chemical Formula 28]

[0752]

[0753] [Where, L 2 represents a leaving group such as a halogen atom; V 2 represents a halogen atom such as a bromine atom; other symbols have the same meanings as above.]

[0754] Process 1

[0755] Compound (III-11) can be produced by reacting compound (III-13) with compound (III-12) in a solvent in the presence of a base. Compound (III-13) and compound (III-12) can use commercially available substances, or can also be produced from commercially available substances using a known method. In addition, compound (III-12) can be a free form or a salt form such as hydrochloride.

[0756] The solvent may be any solvent that does not affect the reaction, and examples thereof include amides such as dimethylformamide; ethers such as tetrahydrofuran and 1,4-dioxane; alcohols such as methanol, ethanol, and isopropanol; halogenated aliphatic hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as toluene; nitriles such as acetonitrile; carboxylic acids such as acetic acid; and mixtures thereof.

[0757] Examples of the base include alkali metal carbonates such as cesium carbonate, potassium carbonate, sodium carbonate, and sodium hydrogencarbonate; alkali metal phosphates such as tribasic potassium phosphate, sodium phosphate, and sodium hydrogenphosphate; alkali metal fluorides such as cesium fluoride and potassium fluoride; alkylamines such as triethylamine and N,N-diisopropylethylamine; pyridines such as pyridine and 4-dimethylaminopyridine; 1,8-diazabicyclo[5.4.0]-7-undecene; and mixtures thereof.

[0758] The amount of compound (III-12) used can be 1.0 to 10.0 equivalents, preferably 1.0 to 5.0 equivalents, based on a molar ratio of compound (III-13).

[0759] The amount of the base used can be 1.0 to 5.0 equivalents, preferably 1.0 to 3.0 equivalents, based on a molar ratio with respect to compound (III-13).

[0760] This reaction can be carried out at room temperature to under heating, for example, room temperature to 150°C, preferably 50 to 100°C.

[0761] Process 2

[0762] Compound (III-10) can be produced by reacting compound (III-11) in a solvent in the presence of a catalyst and in the presence of an acid or a salt thereof.

[0763] The solvent may be any solvent that does not affect the reaction, and examples thereof include amides such as dimethylformamide; ethers such as tetrahydrofuran and 1,4-dioxane; alcohols such as methanol, ethanol, and isopropanol; halogenated aliphatic hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as toluene; nitriles such as acetonitrile; carboxylic acids such as acetic acid; water; and mixtures thereof.

[0764] Examples of the catalyst include iron, zinc, and tin.

[0765] Examples of the acid or its salt include ammonium chloride, hydrochloric acid, and acetic acid.

[0766] The amount of the catalyst used can be 1.0 to 15.0 equivalents, preferably 1.0 to 10.0 equivalents, based on a molar ratio to compound (III-11).

[0767] The amount of the acid or its salt to be used can be 1.0 to 10.0 equivalents, preferably 1.0 to 5.0 equivalents, based on a molar ratio to compound (III-11).

[0768] This reaction can be carried out at room temperature to under heating, for example, room temperature to 150°C, preferably 50 to 100°C.

[0769] Process 3

[0770] Compound (III-9) can be produced by reacting compound (III-10) with a diazotizing agent in a solvent in the presence of an acid.

[0771] The solvent may be any solvent that does not affect the reaction, and examples thereof include amides such as dimethylformamide; ethers such as tetrahydrofuran and 1,4-dioxane; alcohols such as methanol, ethanol, and isopropanol; halogenated aliphatic hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as toluene; nitriles such as acetonitrile; carboxylic acids such as acetic acid; water; and mixtures thereof.

[0772] Examples of the acid include sulfuric acid.

[0773] Examples of the diazotizing agent include sodium nitrite and nitrite esters.

[0774] The amount of the acid used can be 0.1 to 10.0 equivalents, preferably 1.0 to 5.0 equivalents, based on a molar ratio with respect to compound (III-10).

[0775] The amount of the diazotizing agent used can be 1.0 to 5.0 equivalents, preferably 1.0 to 2.0 equivalents, based on a molar ratio with respect to compound (III-10).

[0776] This reaction can be carried out under ice-cooling to heating, for example, under ice-cooling to 50°C, preferably under ice-cooling to room temperature.

[0777] Process 4

[0778] Compound (III-4) can be produced by reacting compound (III-9) with compound (III-8) in a solvent in the presence of an alkyllithium and a Grignard reagent. Compound (III-8) can be a commercially available substance or can be produced from a commercially available substance by a known method.

[0779] The solvent may be any solvent that does not affect the reaction, and examples thereof include ethers such as tetrahydrofuran and 1,4-dioxane; aromatic hydrocarbons such as toluene; and mixtures thereof.

[0780] Examples of the alkyllithium include n-butyllithium and the like.

[0781] Examples of the Grignard reagent include isopropylmagnesium chloride.

[0782] The amount of compound (III-8) used can be 1.0 to 3.0 equivalents, preferably 1.0 to 2.0 equivalents, based on a molar ratio of compound (III-9).

[0783] The amount of the base used can be 1.0 to 5.0 equivalents, preferably 1.0 to 3.0 equivalents, based on a molar ratio to compound (III-9).

[0784] The amount of the Grignard reagent used can be 1.0 to 5.0 equivalents, preferably 1.0 to 3.0 equivalents, based on a molar ratio to compound (III-9).

[0785] This reaction can be carried out at -100°C to heating, for example, at -80°C to room temperature, and preferably at -50°C to ice-cooling.

[0786] Reference Manufacturing Method 4

[0787] In compound (III-1), R 1 and R 2 Compound (III-1') in which all the atoms are hydrogen atoms can also be produced according to the following scheme.

[0788] [Chemical Formula 29]

[0789]

[0790] [In the formula, the symbols have the same meanings as above.]

[0791] Process 1

[0792] Compound (III-15) can be produced by reacting compound (III-9) with compound (III-16) in a solvent in the presence of a base, in the presence of a catalyst, in the presence of a ligand, or in the absence of a ligand. Compound (III-16) can be produced using commercially available materials or by known methods from commercially available materials.

[0793] The solvent may be any solvent that does not affect the reaction, and examples thereof include amides such as dimethylformamide; ethers such as tetrahydrofuran and 1,4-dioxane; alcohols such as methanol, ethanol, and isopropanol; halogenated aliphatic hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as toluene; nitriles such as acetonitrile; and mixtures thereof.

[0794] Examples of the base include alkali metal carbonates such as cesium carbonate, potassium carbonate, sodium carbonate, and sodium hydrogencarbonate; alkali metal phosphates such as tribasic potassium phosphate, sodium phosphate, and sodium hydrogenphosphate; alkali metal fluorides such as cesium fluoride and potassium fluoride; alkylamines such as triethylamine and N,N-diisopropylethylamine; pyridines such as pyridine and 4-dimethylaminopyridine; 1,8-diazabicyclo[5.4.0]-7-undecene; and mixtures thereof.

[0795] Examples of the catalyst include palladium (II) acetate and the like.

[0796] Examples of the ligand include tri-o-tolylphosphine and the like.

[0797] The amount of compound (III-16) used can be 1.0 to 10.0 equivalents, preferably 1.0 to 5.0 equivalents, based on a molar ratio with respect to compound (III-9).

[0798] The amount of the base used can be 1.0 to 5.0 equivalents, preferably 1.0 to 3.0 equivalents, based on a molar ratio to compound (III-9).

[0799] The amount of the catalyst used can be 0.01 to 1.0 equivalents, preferably 0.05 to 0.5 equivalents, based on a molar ratio to compound (III-9).

[0800] The amount of the ligand used can be 0.01 to 1.0 equivalents, preferably 0.05 to 0.5 equivalents, based on a molar ratio with respect to compound (III-9).

[0801] This reaction can be carried out at room temperature to under heating, for example, at 50 to 200°C, preferably at 100 to 150°C.

[0802] Process 2

[0803] Compound (III-1') can be produced by reacting Compound (III-15) with Compound (III-14) in a solvent in the presence of a base and a catalyst. Compound (III-14) can be a commercially available substance or can be produced from a commercially available substance by a known method.

[0804] The solvent may be any solvent that does not affect the reaction, and examples thereof include amides such as dimethylformamide; ethers such as tetrahydrofuran and 1,4-dioxane; alcohols such as methanol, ethanol, and isopropanol; halogenated aliphatic hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as toluene; nitriles such as acetonitrile; water; and mixtures thereof.

[0805] Examples of the base include alkali metal carbonates such as cesium carbonate, potassium carbonate, sodium carbonate, and sodium hydrogencarbonate; alkali metal phosphates such as tribasic potassium phosphate, sodium phosphate, and sodium hydrogenphosphate; alkali metal fluorides such as cesium fluoride and potassium fluoride; alkylamines such as triethylamine and N,N-diisopropylethylamine; pyridines such as pyridine and 4-dimethylaminopyridine; 1,8-diazabicyclo[5.4.0]-7-undecene; and mixtures thereof.

[0806] Examples of the catalyst include di-μ-chlorobis[(η-cycloocta-1,5-diene)rhodium (I)] and the like.

[0807] The amount of compound (III-14) used can be 1.0 to 3.0 equivalents, preferably 1.0 to 2.0 equivalents, based on a molar ratio of compound (III-15).

[0808] The amount of the base used can be 1.0 to 5.0 equivalents, preferably 1.0 to 3.0 equivalents, based on a molar ratio with respect to compound (III-15).

[0809] The amount of the catalyst used can be 0.01 to 1.0 equivalents, preferably 0.01 to 0.5 equivalents, based on a molar ratio to compound (III-15).

[0810] This reaction can be carried out at room temperature to under heating, for example, room temperature to 150°C, preferably 50 to 100°C.

[0811] Reference Manufacturing Method 5

[0812] Among the compounds (IV), compound (IV-1) can be produced, for example, according to the following scheme.

[0813] [Chemical formula 30]

[0814]

[0815] [In the formula, the symbols have the same meanings as above.]

[0816] [Chemical Formula 31]

[0817]

[0818] [Where, L 3 represents a leaving group such as a halogen atom; other symbols have the same meanings as above.]

[0819] Process 1

[0820] Compound (IV-1-1) can be produced by reacting compound (IV-1-2) with compound (V) in a solvent in the presence of a reducing agent. Compound (IV-1-2) and compound (V) can be commercially available or produced from commercially available materials using known methods.

[0821] The solvent may be any solvent that does not affect the reaction, and examples thereof include amides such as dimethylformamide; ethers such as tetrahydrofuran and 1,4-dioxane; alcohols such as methanol, ethanol, and isopropanol; halogenated aliphatic hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as toluene; nitriles such as acetonitrile; and mixtures thereof.

[0822] Examples of the reducing agent include sodium triacetoxyborohydride and sodium borohydride.

[0823] The amount of compound (V) used can be 1.0 to 3.0 equivalents, preferably 1.0 to 2.0 equivalents, based on a molar ratio of compound (IV-1-2).

[0824] The amount of the reducing agent used can be 1.0 to 5.0 equivalents, preferably 1.0 to 3.0 equivalents, based on a molar ratio with respect to compound (IV-1-2).

[0825] This reaction can be carried out at room temperature to under heating, for example, at room temperature to 100°C, preferably at room temperature to 70°C.

[0826] Process 2

[0827] Compound (IV-1) can be produced by reacting compound (IV-1-1) in a solvent in the presence or absence of a copper catalyst, in the presence or absence of dimethylglycine, and in the presence of a base. Compound (IV-1) may be in the form of a free form or a salt such as hydrochloride.

[0828] The solvent may be any solvent that does not affect the reaction, and examples thereof include amides such as N-methylpyrrolidone and dimethylformamide; ethers such as tetrahydrofuran and 1,4-dioxane; alcohols such as methanol, ethanol, and isopropanol; aromatic hydrocarbons such as toluene; nitriles such as acetonitrile; dimethyl sulfoxide; carboxylic acids such as acetic acid; water; and mixtures thereof.

[0829] Examples of the copper catalyst include copper (I) iodide.

[0830] Examples of the base include alkali metal carbonates such as cesium carbonate, potassium carbonate, sodium carbonate, and sodium hydrogencarbonate; alkali metal phosphates such as tribasic potassium phosphate, sodium phosphate, and sodium hydrogenphosphate; alkali metal fluorides such as cesium fluoride and potassium fluoride; alkali metal salts of tert-butoxide such as sodium tert-butoxide and potassium tert-butoxide; alkali metal hydrides such as sodium hydride; alkylamines such as triethylamine and N,N-diisopropylethylamine; pyridines such as pyridine and 4-dimethylaminopyridine; and 1,8-diazabicyclo[5.4.0]-7-undecene.

[0831] The amount of the copper catalyst used can be 0.01 to 1.0 equivalents, preferably 0.05 to 1.0 equivalents, based on a molar ratio with respect to compound (IV-1-1).

[0832] The amount of dimethylglycine used can be 0.05 to 1.0 equivalents, preferably 0.1 to 0.5 equivalents, based on a molar ratio with respect to compound (IV-1-1).

[0833] The amount of the base used can be 1.0 to 5.0 equivalents, preferably 1.0 to 3.0 equivalents, based on a molar ratio with respect to compound (IV-1-1).

[0834] This reaction can be carried out under ice-cooling or heating, for example, at 0 to 150°C, preferably at room temperature to 100°C.

[0835] Alternatively, you can also 3 Donor (P 3 The nitrogen atom on the oxazepine ring of compound (IV-1) is protected by a protecting group P 3 The protected compound is then reacted in the presence of a dioxane solution of hydrochloric acid or the like to carry out deprotection, thereby producing compound (IV-1).

[0836] Alternatively, a compound in which the ring D portion of compound (IV-1-2) is a precursor of ring D can be used instead of compound (IV-1-2) as a starting material, and the reaction can be carried out in the same manner as above to produce a compound in which the ring D portion of compound (IV-1-1) is a precursor of ring D, or to produce a compound in which the ring D portion of compound (IV-1) is a precursor of ring D and then form ring D, thereby producing compound (IV-1).

[0837] Compound (IV-1-1) can also be produced according to the following scheme.

[0838] [Chemical Formula 32]

[0839]

[0840] [Where V 3 represents a halogen atom such as a bromine atom; other symbols have the same meanings as above.]

[0841] Process 1

[0842] Compound (IV-1-3) can be produced by reacting compound (IV-1-4) with a halogenating agent in a solvent in the presence of a radical initiator. Compound (IV-1-4) can be a commercially available substance or produced from a commercially available substance by a known method.

[0843] The solvent may be any solvent that does not affect the reaction, and examples thereof include amides such as dimethylformamide; ethers such as tetrahydrofuran and 1,4-dioxane; halogenated aliphatic hydrocarbons such as chloroform, dichloromethane, and dichloroethane; aromatic hydrocarbons such as toluene and chlorobenzene; nitriles such as acetonitrile; and mixtures thereof.

[0844] Examples of the radical initiator include 2,2'-azobisisobutyronitrile and 2,2'-azobis(2,4-dimethylvaleronitrile).

[0845] Examples of the halogenating agent include N-bromosuccinimide and the like.

[0846] The amount of the radical initiator used can be 0.05 to 1.0 equivalents, preferably 0.05 to 0.5 equivalents, based on a molar ratio with respect to compound (IV-1-4).

[0847] The amount of the halogenating agent used can be 1.0 to 5.0 equivalents, preferably 1.0 to 3.0 equivalents, based on a molar ratio with respect to compound (IV-1-4).

[0848] This reaction can be carried out at room temperature to under heating, for example, at room temperature to 200°C, preferably at 50 to 150°C.

[0849] Process 2

[0850] Compound (IV-1-1) can be produced by reacting compound (IV-1-3) with compound (V) in a solvent in the presence of a base. Compound (V) can be a commercially available substance or can be produced from a commercially available substance by a known method.

[0851] The solvent may be any solvent that does not affect the reaction, and examples thereof include amides such as dimethylformamide; ethers such as tetrahydrofuran and 1,4-dioxane; halogenated aliphatic hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as toluene; nitriles such as acetonitrile; and mixtures thereof.

[0852] Examples of the base include alkali metal carbonates such as cesium carbonate, potassium carbonate, sodium carbonate, and sodium hydrogencarbonate; alkali metal phosphates such as tribasic potassium phosphate, sodium phosphate, and sodium hydrogenphosphate; alkali metal fluorides such as cesium fluoride and potassium fluoride; alkylamines such as triethylamine and N,N-diisopropylethylamine; pyridines such as pyridine and 4-dimethylaminopyridine; and 1,8-diazabicyclo[5.4.0]-7-undecene.

[0853] The amount of compound (V) used can be 1.0 to 5.0 equivalents, preferably 1.0 to 3.0 equivalents, based on a molar ratio of compound (IV-1-3).

[0854] The amount of the base used can be 1.0 to 5.0 equivalents, preferably 1.5 to 3.0 equivalents, based on a molar ratio with respect to compound (IV-1-3).

[0855] This reaction can be carried out at room temperature to under heating, for example, room temperature to 100°C, preferably at room temperature.

[0856] Alternatively, a compound in which the ring D portion of compound (IV-1-4) is a precursor of ring D can be used instead of compound (IV-1-4) as a starting material, and the reaction can be carried out in the same manner as above to produce a compound in which the ring D portion of compound (IV-1-3) is a precursor of ring D, or to produce a compound in which the ring D portion of compound (IV-1-1) is a precursor of ring D and then form ring D, thereby producing compound (IV-1-1).

[0857] Compound (IV-1-2) can also be produced according to the following scheme.

[0858] [Chemical Formula 33]

[0859]

[0860] [In the formula, the symbols have the same meanings as above.]

[0861] Compound (IV-1-2-1) can be reacted with a formylating agent in a solvent in the presence of a base to produce compound (IV-1-2-1). Compound (IV-1-2-1) can be a commercially available compound or can be produced from a commercially available compound by a known method.

[0862] The solvent may be any solvent that does not affect the reaction, and examples thereof include ethers such as tetrahydrofuran and 1,4-dioxane; halogenated aliphatic hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as toluene; nitriles such as acetonitrile; and mixtures thereof.

[0863] Examples of the base include Knochel-Hauser base.

[0864] Examples of the formylating agent include dimethylformamide and the like.

[0865] The amount of the base used can be 1.0 to 5.0 equivalents, preferably 1.0 to 3.0 equivalents, based on a molar ratio with respect to compound (IV-1-2-1).

[0866] The amount of the formylating agent used can be 1.0 to 5.0 equivalents, preferably 1.0 to 3.0 equivalents, based on a molar ratio with respect to compound (IV-1-2-1).

[0867] This reaction can be carried out under ice-cooling to heating, for example, under ice-cooling to 50°C, preferably under ice-cooling to room temperature.

[0868] Alternatively, a compound in which the ring D portion of compound (IV-1-2-1) is a precursor of ring D can be used instead of compound (IV-1-2-1) as a starting material, and a reaction can be carried out in the same manner as above to produce a compound in which the ring D portion of compound (IV-1-2) is a precursor of ring D, and then ring D can be formed to produce compound (IV-1-2).

[0869] Reference Manufacturing Method 6

[0870] Compound (IV-1) can also be produced according to the following scheme.

[0871] [Chemical Formula 34]

[0872]

[0873] [Where P 4 represents a protecting group such as tert-butyloxycarbonyl and benzyloxycarbonyl; other symbols have the same meanings as above.]

[0874] Process 1

[0875] The compound (IV-1-3') is reacted with the compound (V) in a solvent in the presence of a reducing agent and in the presence or absence of an acid, and then reacted with P in a solvent in the presence of a base. 4 Compound (IV-1-2') can be produced by the donor reaction. Compound (IV-1-3') and Compound (V) can use commercially available substances or can be produced from commercially available substances by a known method.

[0876] The solvent may be any solvent that does not affect the reaction. Examples of the solvent used for the reaction with compound (V) include: amides such as dimethylformamide; ethers such as tetrahydrofuran and 1,4-dioxane; alcohols such as methanol, ethanol, and isopropanol; halogenated aliphatic hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as toluene; nitriles such as acetonitrile; and mixtures thereof. 4 Examples of the solvent for the donor reaction include ethers such as tetrahydrofuran and 1,4-dioxane; alcohols such as methanol, ethanol, and isopropanol; aromatic hydrocarbons such as toluene; nitriles such as acetonitrile; water; and mixtures thereof.

[0877] Examples of the reducing agent include sodium triacetoxyborohydride and sodium borohydride.

[0878] Examples of the acid include acetic acid.

[0879] Examples of the base include alkali metal carbonates such as cesium carbonate, potassium carbonate, sodium carbonate, and sodium hydrogen carbonate; alkali metal hydroxides such as sodium hydroxide; alkylamines such as triethylamine and N,N-diisopropylethylamine; pyridines such as pyridine and 4-dimethylaminopyridine; and 1,8-diazabicyclo[5.4.0]-7-undecene.

[0880] As P 4 Examples of the donor include di-tert-butyl dicarbonate and benzyl chloroformate.

[0881] The amount of compound (V) used can be 1.0 to 3.0 equivalents, preferably 1.0 to 2.0 equivalents, based on a molar ratio of compound (IV-1-3').

[0882] P 4 The amount of the donor used can be 1.0 to 30.0 equivalents, preferably 1.0 to 20.0 equivalents, based on a molar ratio with respect to compound (IV-1-3').

[0883] The amount of the reducing agent used can be 1.0 to 5.0 equivalents, preferably 1.3 to 4.0 equivalents, based on a molar ratio with respect to compound (IV-1-3').

[0884] The amount of the acid used can be 1.0 to 3.0 equivalents, preferably 1.0 to 2.0 equivalents, based on a molar ratio to compound (IV-1-3').

[0885] The amount of the base used can be 1.0 to 100.0 equivalents, preferably 2.0 to 60.0 equivalents, based on a molar ratio to compound (IV-1-3').

[0886] This reaction can be carried out at room temperature to under heating, for example, room temperature to 100°C, preferably at room temperature.

[0887] Process 2

[0888] Compound (IV-1-1') can be produced by reacting compound (IV-1-2') in a solvent in the presence of an azodicarboxylic acid derivative and a phosphine derivative.

[0889] The solvent may be any solvent that does not affect the reaction, and examples thereof include ethers such as tetrahydrofuran and 1,4-dioxane; halogenated aliphatic hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as toluene; nitriles such as acetonitrile; and mixtures thereof.

[0890] Examples of the azodicarboxylic acid derivatives include dialkyl azodicarboxylates such as diethyl azodicarboxylate and diisopropyl azodicarboxylate; and azodicarbonamides such as (E)-N1,N1,N2,N2-tetramethylazo-1,2-dicarbonamide.

[0891] Examples of the phosphine derivative include triarylphosphines such as triphenylphosphine and trialkylphosphines such as tri-n-butylphosphine.

[0892] The amount of the azodicarboxylic acid derivative used can be 1.0 to 5.0 equivalents, preferably 1.0 to 3.0 equivalents, based on a molar ratio to compound (IV-1-2').

[0893] The amount of the phosphine derivative used can be 1.0 to 5.0 equivalents, preferably 1.0 to 3.0 equivalents, based on a molar ratio to compound (IV-1-2').

[0894] This reaction can be carried out under ice-cooling to heating, for example, under ice-cooling to 50°C, preferably under ice-cooling to room temperature.

[0895] Process 3

[0896] P 4 When it is tert-butoxycarbonyl or the like, compound (IV-1) can be produced by reacting compound (IV-1-1') in a solvent in the presence of an acid. Compound (IV-1) may be in the form of a free form or a salt such as hydrochloride.

[0897] The solvent may be any solvent that does not affect the reaction, and examples thereof include ethers such as tetrahydrofuran, 1,4-dioxane, tert-butyl methyl ether, and cyclopentyl methyl ether; halogenated aliphatic hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as toluene; nitriles such as acetonitrile; and mixtures thereof.

[0898] Examples of the acid include hydrogen chloride.

[0899] The amount of the acid used can be 1.0 to 100.0 equivalents, preferably 2.0 to 60.0 equivalents, based on a molar ratio to compound (IV-1-1′).

[0900] This reaction can be carried out under ice-cooling to heating, for example, under ice-cooling to 150°C, preferably at 0°C to 100°C.

[0901] Or, P 4 In the case of a tert-butoxycarbonyl group or the like, compound (IV-1) can also be produced by reacting compound (IV-1-1') in a solvent in the presence of a base and an additive.

[0902] The solvent may be any solvent that does not affect the reaction, and examples thereof include ethers such as tetrahydrofuran, 1,4-dioxane, tert-butyl methyl ether, and cyclopentyl methyl ether; halogenated aliphatic hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as toluene; nitriles such as acetonitrile; and mixtures thereof.

[0903] Examples of the base include 2,6-lutidine and triethylamine.

[0904] Examples of the additive include trimethylsilyl trifluoromethanesulfonate and the like.

[0905] The amount of the base used can be 1.0 to 10.0 equivalents, preferably 1.0 to 5.0 equivalents, based on a molar ratio to compound (IV-1-1′).

[0906] The amount of the additive used can be 1.0 to 10.0 equivalents, preferably 1.0 to 5.0 equivalents, based on a molar ratio with respect to compound (IV-1-1′).

[0907] This reaction can be carried out under ice-cooling to heating, for example, under ice-cooling to 100°C, preferably under ice-cooling to room temperature.

[0908] P 4 In the case of a benzyloxycarbonyl group or the like, compound (IV-1) can be produced by treating compound (IV-1-1') with a catalyst in a solvent under a hydrogen atmosphere.

[0909] The solvent may be any solvent that does not affect the reaction, and examples thereof include ethers such as tetrahydrofuran and 1,4-dioxane; alcohols such as methanol, ethanol, and isopropanol; aromatic hydrocarbons such as toluene; nitriles such as acetonitrile; carboxylic acids such as acetic acid; water; and mixtures thereof.

[0910] Examples of the catalyst include palladium carbon.

[0911] The amount of the catalyst used can be 0.01 to 20.0 equivalents, preferably 0.01 to 10.0 equivalents, based on a molar ratio to compound (IV-1-1').

[0912] This reaction can be carried out at room temperature to under heating, for example, room temperature to 100°C, preferably at room temperature.

[0913] Alternatively, compound (IV-1-1) can be produced by using a compound in which the ring D portion of compound (IV-1-3') is a precursor of ring D instead of compound (IV-1-3') as a starting material, and reacting in the same manner as above to produce a compound in which the ring D portion of compound (IV-1-2') is a precursor of ring D, or a compound in which the ring D portion of compound (IV-1-1') is a precursor of ring D, or a compound in which the ring D portion of compound (IV-1) is a precursor of ring D, and then forming ring D, thereby producing compound (IV-1).

[0914] Compound (IV-1-3') can also be produced according to the following scheme.

[0915] [Chemical Formula 35]

[0916]

[0917] [In the formula, the symbols have the same meanings as above.]

[0918] Compound (IV-1-3'-1) can be produced by reacting compound (IV-1-3'-1) in a solvent in the presence of hexamethylenetetramine. Compound (IV-1-3'-1) can be a commercially available compound or can be produced from a commercially available compound by a known method.

[0919] The solvent may be any solvent that does not affect the reaction, and examples thereof include acids such as acetic acid and trifluoroacetic acid, and mixtures thereof.

[0920] The amount of hexamethylenetetramine used can be 1.0 to 3.0 equivalents, preferably 1.0 to 2.0 equivalents, based on a molar ratio with respect to compound (IV-1-3′-1).

[0921] This reaction can be carried out at room temperature to under heating, for example, at room temperature to 150°C, preferably at room temperature to 100°C.

[0922] Alternatively, compound (IV-1-3') can also be produced by reacting compound (IV-1-3'-1) with paraformaldehyde in a solvent in the presence of magnesium chloride and a base.

[0923] The solvent may be any solvent that does not affect the reaction, and examples thereof include ethers such as tetrahydrofuran, 1,4-dioxane, and tert-butyl methyl ether; halogenated aliphatic hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as toluene; nitriles such as acetonitrile; and mixtures thereof.

[0924] Examples of the base include alkali metal carbonates such as cesium carbonate, potassium carbonate, sodium carbonate, and sodium hydrogencarbonate; alkali metal phosphates such as tribasic potassium phosphate, sodium phosphate, and sodium hydrogenphosphate; alkali metal fluorides such as cesium fluoride and potassium fluoride; alkylamines such as triethylamine and N,N-diisopropylethylamine; pyridines such as pyridine and 4-dimethylaminopyridine; and 1,8-diazabicyclo[5.4.0]-7-undecene.

[0925] The amount of magnesium chloride used can be 1.0 to 5.0 equivalents, preferably 1.0 to 3.0 equivalents, based on a molar ratio of compound (IV-1-3′-1).

[0926] The amount of the base used can be 1.0 to 5.0 equivalents, preferably 1.0 to 4.0 equivalents, based on a molar ratio to compound (IV-1-3′-1).

[0927] The amount of paraformaldehyde used can be 1.0 to 15.0 equivalents, preferably 1.0 to 10.0 equivalents, based on a molar ratio to compound (IV-1-3′-1).

[0928] This reaction can be carried out at room temperature to under heating, for example, at room temperature to 150°C, preferably at room temperature to 100°C.

[0929] Alternatively, compound (IV-1-3') can also be produced by reacting compound (IV-1-3'-1) in the presence of chloroform and a base.

[0930] Examples of the base include alkali metal hydroxides such as sodium hydroxide.

[0931] The amount of the base used can be 1.0 to 20.0 equivalents, preferably 1.0 to 15.0 equivalents, based on a molar ratio to compound (IV-1-3′-1).

[0932] This reaction can be carried out at room temperature to under heating, for example, at room temperature to 150°C, preferably at room temperature to 100°C.

[0933] Alternatively, compound (IV-1-3') can also be produced by reacting compound (IV-1-3'-1) with a formylating agent in a solvent in the presence of a catalyst.

[0934] The solvent may be any solvent that does not affect the reaction, and examples thereof include ethers such as tetrahydrofuran, 1,4-dioxane, diethyl ether, and tert-butyl methyl ether; halogenated aliphatic hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as toluene; nitriles such as acetonitrile; water; and mixtures thereof.

[0935] Examples of the catalyst include aluminum (III) chloride.

[0936] Examples of the formylating agent include triethyl orthoformate.

[0937] The amount of the catalyst used can be 0.01 to 1.0 equivalents, preferably 0.05 to 0.5 equivalents, based on a molar ratio to compound (IV-1-3′-1).

[0938] The amount of the formylating agent used can be 1.0 to 5.0 equivalents, preferably 1.0 to 3.0 equivalents, based on a molar ratio to compound (IV-1-3′-1).

[0939] This reaction can be carried out at room temperature to under heating, for example, at room temperature to 150°C, preferably at room temperature to 100°C.

[0940] Alternatively, a compound whose ring D portion of compound (IV-1-3'-1) is a precursor of ring D can be used instead of compound (IV-1-3'-1) as a starting material, and a reaction can be carried out in the same manner as above to produce a compound whose ring D portion of compound (IV-1-3') is a precursor of ring D, and then ring D can be formed to produce compound (IV-1-3').

[0941] Reference Manufacturing Method 7

[0942] Compound (IV-1) can also be produced according to the following scheme.

[0943] [Chemical Formula 36]

[0944]

[0945] [Where R 15 represents an alkyl group such as a methyl group or an ethyl group; other symbols have the same meanings as above.]

[0946] Process 1

[0947] Compound (IV-1-1") can be produced by reacting compound (IV-1-2") in a solvent in the presence of a base. Compound (IV-1-2") may be in the form of a free form or a salt such as hydrochloride.

[0948] The solvent may be any solvent that does not affect the reaction, and examples thereof include ethers such as tetrahydrofuran and 1,4-dioxane; alcohols such as methanol, ethanol, and isopropanol; aromatic hydrocarbons such as toluene; nitriles such as acetonitrile; water; and mixtures thereof.

[0949] Examples of the base include alkali metal carbonates such as sodium carbonate, potassium carbonate, and sodium bicarbonate; alkali metal hydrides such as sodium hydride; alkylamines such as triethylamine and N,N-diisopropylethylamine; pyridines such as pyridine and 4-dimethylaminopyridine; and 1,8-diazabicyclo[5.4.0]-7-undecene.

[0950] The amount of the base used can be 1.0 to 10.0 equivalents, preferably 1.0 to 5.0 equivalents, based on a molar ratio to compound (IV-1-2″).

[0951] This reaction can be carried out under ice-cooling to heating, for example, under ice-cooling to 100°C, preferably under ice-cooling to room temperature.

[0952] Process 2

[0953] Compound (IV-1) can be produced by reacting compound (IV-1-1") in a solvent in the presence of a reducing agent.

[0954] The solvent may be any solvent that does not affect the reaction, and examples thereof include ethers such as tetrahydrofuran and 1,4-dioxane; alcohols such as methanol, ethanol, and isopropanol; aromatic hydrocarbons such as toluene; nitriles such as acetonitrile; and mixtures thereof.

[0955] Examples of the reducing agent include sodium cyanoborohydride, sodium borohydride, lithium aluminum hydride, and a borane-tetrahydrofuran complex.

[0956] The amount of the reducing agent used can be 1.0 to 10.0 equivalents, preferably 1.0 to 5.0 equivalents, based on a molar ratio with respect to compound (IV-1-1”).

[0957] This reaction can be carried out under ice-cooling to heating, for example, under ice-cooling to 100°C, preferably under ice-cooling to 80°C.

[0958] Alternatively, a compound in which the ring D portion of compound (IV-1-2") is a precursor of ring D can be used instead of compound (IV-1-2") as a starting material, and the compound in which the ring D portion of compound (IV-1-1") is a precursor of ring D can be produced by reacting in the same manner as above, or a compound in which the ring D portion of compound (IV-1) is a precursor of ring D can be produced, and then ring D can be formed to produce compound (IV-1).

[0959] Compound (IV-1-2") can be produced, for example, according to the following scheme.

[0960] [Chemical Formula 37]

[0961]

[0962] [Where P 5 represents a protecting group such as tert-butoxycarbonyl; other symbols have the same meanings as above.]

[0963] Process 1

[0964] By reacting compound (V) with P in a solvent 5 The donor reaction can produce compound (IV-1-2"-3). Compound (V) can use a commercially available substance, or can be produced from a commercially available substance by a known method.

[0965] The solvent may be any solvent that does not affect the reaction, and examples thereof include ethers such as tetrahydrofuran and 1,4-dioxane; halogenated aliphatic hydrocarbons such as chloroform and dichloromethane; alcohols such as methanol, ethanol, and isopropanol; aromatic hydrocarbons such as toluene; nitriles such as acetonitrile; carboxylic acids such as acetic acid; water; and mixtures thereof.

[0966] As P 5 Examples of the donor include di-tert-butyl dicarbonate.

[0967] P 5 The amount of the donor used can be 1.0 to 3.0 equivalents, preferably 1.0 to 2.0 equivalents, based on a molar ratio with respect to compound (V).

[0968] This reaction can be carried out at room temperature to under heating, for example, room temperature to 100°C, preferably at room temperature.

[0969] Process 2

[0970] Compound (IV-1-2"-1) can be produced by reacting compound (IV-1-2"-3) with compound (IV-1-2"-2) in a solvent in the presence of an azodicarboxylic acid derivative and a phosphine derivative. Compound (IV-1-2"-2) can be produced using a commercially available substance or from a commercially available substance using a known method.

[0971] The solvent may be any solvent that does not affect the reaction, and examples thereof include ethers such as tetrahydrofuran and 1,4-dioxane; halogenated aliphatic hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as toluene; nitriles such as acetonitrile; and mixtures thereof.

[0972] Examples of the azodicarboxylic acid derivatives include dialkyl azodicarboxylates such as diethyl azodicarboxylate and diisopropyl azodicarboxylate; and azodicarbonamides such as (E)-N1,N1,N2,N2-tetramethylazo-1,2-dicarbonamide.

[0973] Examples of the phosphine derivative include triarylphosphines such as triphenylphosphine and trialkylphosphines such as tri-n-butylphosphine.

[0974] The amount of compound (IV-1-2"-2) used can be 1.0 to 3.0 equivalents, preferably 1.0 to 2.0 equivalents, based on the molar ratio of compound (IV-1-2"-3).

[0975] The amount of the azodicarboxylic acid derivative used can be 1.0 to 5.0 equivalents, preferably 1.0 to 3.0 equivalents, based on a molar ratio of compound (IV-1-2"-3).

[0976] The amount of the phosphine derivative used can be 1.0 to 5.0 equivalents, preferably 1.0 to 3.0 equivalents, based on a molar ratio with respect to compound (IV-1-2"-3).

[0977] This reaction can be carried out under ice-cooling to heating, for example, under ice-cooling to 50°C, preferably under ice-cooling to room temperature.

[0978] Process 3

[0979] Compound (IV-1-2") can be produced by reacting compound (IV-1-2"-1) in a solvent in the presence of an acid.

[0980] The solvent may be any solvent that does not affect the reaction, and examples thereof include ethers such as tetrahydrofuran, 1,4-dioxane, and cyclopentyl methyl ether; halogenated aliphatic hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as toluene; nitriles such as acetonitrile; and mixtures thereof.

[0981] Examples of the acid include hydrogen chloride.

[0982] The amount of the acid used can be 1.0 to 10.0 equivalents, preferably 1.0 to 5.0 equivalents, based on a molar ratio with respect to compound (IV-1-2"-1).

[0983] This reaction can be carried out under ice-cooling to heating, for example, under ice-cooling to 100°C, preferably under ice-cooling to 80°C.

[0984] When a protecting group such as tetrahydropyranyl group exists on ring D of compound (IV-1-2"-1), the protecting group on ring D can also be removed by this reaction.

[0985] Alternatively, a compound in which the ring D portion of compound (IV-1-2"-2) is a precursor of ring D can be used instead of compound (IV-1-2"-2) as a starting material, and the reaction can be carried out in the same manner as above to produce a compound in which the ring D portion of compound (IV-1-2"-1) is a precursor of ring D, or to produce a compound in which the ring D portion of compound (IV-1-2") is a precursor of ring D and then form ring D, thereby producing compound (IV-1-2").

[0986] Reference Manufacturing Method 8

[0987] Among compound (IV), for compound (IV-2), compound (IV-2-2), compound (IV-2-4), compound (IV-2-2-1), compound (IV-2-3'), compound (IV-2-3'-1), or compound (IV-2-2"-2) can be used instead of compound (IV-1-2), compound (IV-1-4), compound (IV-1-2-1), compound (IV-1-3'), compound (IV-1-3'-1), or compound (IV-1-2"-2), or a compound in which the ring D portion of these compounds is a precursor of ring D can be used as a starting material and produced by the same method as described in Reference Production Method 5, 6, or 7.

[0988] [Chemical Formula 38]

[0989]

[0990] [In the formula, the symbols have the same meanings as above.]

[0991] [Chemical Formula 39]

[0992]

[0993] [In the formula, the symbols have the same meanings as above.]

[0994] Reference Manufacturing Method 9

[0995] Among compound (IV), for compound (IV-3), compound (IV-3-2), compound (IV-3-4), compound (IV-3-2-1), compound (IV-3-3'), compound (IV-3-3'-1), or compound (IV-3-2"-2) can be used instead of compound (IV-1-2), compound (IV-1-4), compound (IV-1-2-1), compound (IV-1-3'), compound (IV-1-3'-1), or compound (IV-1-2"-2), or a compound in which the ring D portion of these compounds is a precursor of ring D can be used as a starting material and produced by the same method as described in Reference Production Method 5, 6, or 7.

[0996] [Chemical Formula 40]

[0997]

[0998] [In the formula, the symbols have the same meanings as above.]

[0999] [Chemical Formula 41]

[1000]

[1001] [In the formula, the symbols have the same meanings as above.]

[1002] The obtained target compound can be isolated and purified as needed by an appropriate combination of conventional methods such as recrystallization, reprecipitation, filtration, concentration, drying, or methods commonly used in the separation and purification of organic compounds (eg, column chromatography).

[1003] In addition to being produced by the above-mentioned production methods, the compounds (I) and intermediates of the present invention can also be produced according to the methods described in the Examples and Reference Examples described below. Furthermore, the compounds (I) and intermediates of the present invention can be converted into other target compounds or intermediates by the above-mentioned production methods, the methods described in the Examples and Reference Examples described below, and / or known methods, or combinations thereof. Such methods include, for example, the methods described in (1) to (26) below.

[1004] (1) Conversion from alkoxycarbonyl to carboxyl

[1005] By reacting a compound having an alkoxycarbonyl group in a solvent (e.g., dimethyl sulfoxide, tetrahydrofuran, methanol, ethanol, water, and mixtures thereof) in the presence of a base (e.g., potassium hydroxide and lithium hydroxide) or an acid (e.g., sulfuric acid), the corresponding compound having a carboxyl group can be produced.

[1006] (2) Alkylation of nitrogen atoms in nitrogen-containing rings

[1007] By reacting a compound having a nitrogen-containing ring with an alkylating agent (e.g., a methylating agent such as iodomethane) in a solvent (e.g., dimethylformamide) in the presence of a base (e.g., sodium hydride), the corresponding compound in which the nitrogen atom of the nitrogen-containing ring is alkylated can be produced.

[1008] (3) Conversion from nitro group to tert-butyl carbamate group

[1009] By reacting a compound having a nitro group with a tert-butyl donor (e.g., di-tert-butyl dicarbonate) in a solvent (e.g., ethanol) under a hydrogen atmosphere in the presence of a catalyst (e.g., palladium on carbon), the corresponding compound having a tert-butyl carbamate group can be produced.

[1010] (4) Acetylation of amino groups

[1011] The amino group can be acetylated by reacting a compound having an amino group in a solvent (eg, ethyl acetate) with an acetylating agent (eg, acetic anhydride).

[1012] (5) Removal of N-acetyl groups

[1013] The acetyl group can be removed by reacting a compound having an N-acetyl group in a solvent (for example, tetrahydrofuran) in the presence of a base (for example, sodium hydroxide).

[1014] (6) Conversion of 8-acetamido-7-methyl-2,3-dihydrobenzo[f][1,4]oxazepinyl to 1-acetyl-8-ethyl-1,5,7,8-tetrahydro-6H-[1,4]oxazepin[6,7-f]indazolyl

[1015] By reacting a compound having an 8-acetamido-7-methyl-2,3-dihydrobenzo[f][1,4]oxazepinyl group in a solvent (e.g., ethyl acetate) in the presence of a base (e.g., potassium acetate), a diazotizing agent (e.g., n-amyl nitrite), a catalyst (e.g., tetrabutylammonium bromide), and acetic anhydride, the corresponding compound having a 1-acetyl-8-ethyl-1,5,7,8-tetrahydro-6H-[1,4]oxazepino[6,7-f]indazolyl group can be produced.

[1016] (7) Conversion from cyano to formyl

[1017] By reacting a compound having a cyano group in a solvent (eg, toluene) in the presence of a reducing agent (eg, diisobutylaluminum hydride), the corresponding compound having a formyl group can be produced.

[1018] (8) Conversion from alkoxycarbonyl to hydroxymethyl

[1019] By reacting a compound having an alkoxycarbonyl group in a solvent (e.g., toluene and tert-butyl methyl ether) in the presence of a reducing agent (e.g., diisobutylaluminum hydride and sodium bis(2-methoxyethoxy)aluminum hydride), the corresponding compound having a hydroxymethyl group can be produced.

[1020] (9) Conversion from hydroxymethyl to formyl

[1021] By reacting a compound having a hydroxymethyl group in a solvent (eg, dichloromethane) in the presence of an oxidizing agent (eg, Dess-Martin reagent), the corresponding compound having a formyl group can be produced.

[1022] (10) Conversion from halogen atoms to azetidin-1-yl

[1023] By reacting a compound having a halogen atom with azetidine in a solvent (e.g., toluene), in the presence of a base (e.g., sodium tert-butoxide), a catalyst (e.g., tris(dibenzylideneacetone)dipalladium(0), etc.), and a ligand (e.g., 4,5-bis(diphenylphosphine)-9,9-dimethylxanthene (Xantphos), etc.), the corresponding compound having an azetidine-1-yl group can be produced.

[1024] (11) Conversion from azetidin-1-yl to 3-halopropylamino

[1025] By reacting a compound having an azetidin-1-yl group in a solvent (eg, 1,4-dioxane) in the presence of a hydrogen halide (eg, hydrogen chloride), the corresponding compound having a 3-halopropylamino group can be produced.

[1026] (12) Conversion of 7-((3-chloropropyl)amino)-2,3-dihydropyrido[2,3-f][1,4]oxazepinyl to 1,3,4,9,10,11-hexahydro-2H-pyrimido[1',2':1,6]pyrido[2,3-f][1,4]oxazepinyl

[1027] By reacting a compound having a 7-((3-chloropropyl)amino)-2,3-dihydropyrido[2,3-f][1,4]oxazepinyl group in a solvent (e.g., acetonitrile), the corresponding compound having a 1,3,4,9,10,11-hexahydro-2H-pyrimido[1',2':1,6]pyrido[2,3-f][1,4]oxazepinyl group can be produced.

[1028] (13) Halogen atom exchange reaction

[1029] By reacting a compound having a halogen atom with a hydrogen halide (e.g., hydrogen chloride) in a solvent (e.g., tetrahydrofuran), and then reacting it with a halogenating agent having other halogen atoms (e.g., sodium iodide) in a solvent (e.g., acetonitrile), the corresponding compound having other halogen atoms can be produced.

[1030] (14) Conversion from formylphenyl to isoquinolyl

[1031] A compound having a formylphenyl group can be reacted with 2,2-dimethoxyethane-1-amine in a solvent (eg, toluene) and then reacted in the presence of a condensing agent (eg, polyphosphoric acid) to produce the corresponding compound having an isoquinoline group.

[1032] (15) Conversion of halogen atoms to formyl groups

[1033] By reacting a compound having a halogen atom with a formylating agent (e.g., dimethylformamide) in a solvent (e.g., diethyl ether and tetrahydrofuran) in the presence of an organometallic reagent (e.g., alkyl lithium such as n-butyl lithium; and a Grignard reagent), the corresponding compound having a formyl group can be produced.

[1034] (16) Conversion from alkoxy to hydroxy

[1035] By reacting a compound having an alkoxy group in a solvent (eg, dichloromethane) in the presence of a dealkylating agent (eg, boron tribromide), the corresponding compound having a hydroxy group can be produced.

[1036] (17) Conversion of 1,2-dihydroxyphenyl to 2,2-dimethylbenzo[d][1,3]dioxolane A compound having a 1,2-dihydroxyphenyl group can be reacted with 2,2-dimethoxypropane in a solvent (e.g., toluene) in the presence of a catalyst (e.g., pyridinium p-toluenesulfonate) to produce the corresponding compound having a 2,2-dimethylbenzo[d][1,3]dioxolane group.

[1037] (18) Protection of nitrogen atoms of nitrogen-containing rings based on tetrahydropyranyl groups

[1038] The nitrogen atom of the nitrogen-containing ring can be protected with a tetrahydropyranyl group by reacting a compound having a nitrogen-containing ring with dihydropyran in a solvent (e.g., dichloromethane, tetrahydrofuran, and mixtures thereof) in the presence of an acid (e.g., methanesulfonic acid).

[1039] (19) Conversion of halogen atoms to (trimethylsilyl)ethynyl groups

[1040] By reacting a compound having a halogen atom with ethynyltrimethylsilane in a solvent (e.g., triethylamine) in the presence of a catalyst (e.g., bis(triphenylphosphine)palladium(II) dichloride and copper(I) iodide, and mixtures thereof), the corresponding compound having a (trimethylsilyl)ethynyl group can be produced.

[1041] (20) Conversion from formyl to (methoxycarbonyl)vinyl

[1042] By reacting a compound having a formyl group with methyl diethylphosphoacetate in a solvent (eg, tetrahydrofuran) in the presence of a base (eg, sodium hydride), the corresponding compound having a (methoxycarbonyl)vinyl group can be produced.

[1043] (21) Removal of trimethylsilyl groups

[1044] The trimethylsilyl group can be removed by reacting a compound having a trimethylsilyl group in a solvent (for example, methanol) in the presence of a base (for example, potassium carbonate).

[1045] (22) Conversion of 1-ethynyl-2-(methoxycarbonyl)vinylphenyl to 2-hydroxy-3-methoxycarbonylnaphthyl

[1046] By reacting a compound having a 1-ethynyl-2-(methoxycarbonyl)vinylphenyl group with 2,2-dimethoxypropane in a solvent (e.g., chlorobenzene, etc.), in the presence of an oxidizing agent (e.g., pyridine-N-oxide, etc.) and a catalyst (e.g., bis(1,5-cyclooctadiene)rhodium(I) trifluoromethanesulfonate, etc.), and in the presence or absence of a ligand (e.g., tri-p-tolylphosphine), the corresponding compound having a 2-hydroxy-3-methoxycarbonylnaphthyl group can be produced.

[1047] (23) Conversion from alkoxycarbonyl to benzyloxycarbonyl

[1048] By reacting a compound having an alkoxycarbonyl group with benzyl alcohol, a corresponding compound having a benzyloxycarbonyl group can be produced.

[1049] (24) Conversion from carboxyl to alkoxycarbonyl

[1050] By reacting a compound having a carboxyl group with an alcohol (eg, methanol, ethanol, etc.) in the presence of an acid (eg, sulfuric acid, etc.) or a base (eg, sodium hydroxide, etc.), a corresponding compound having an alkoxycarbonyl group can be produced.

[1051] (25) Conversion from carboxyl to benzyloxycarbonyl

[1052] The corresponding compound having a benzyloxycarbonyl group can be produced by reacting a compound having a carboxyl group with benzyl alcohol in a solvent (e.g., chloroform) in the presence of an activating agent (e.g., 4-dimethylaminopyridine) and a condensing agent (e.g., 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride). Alternatively, the corresponding compound having a benzyloxycarbonyl group can be produced by reacting a compound having a carboxyl group with a halogenated toluene (e.g., bromotoluene) in a solvent (e.g., dimethylformamide) in the presence of a base (e.g., cesium carbonate).

[1053] (26) Transesterification of alkoxycarbonyl groups

[1054] By reacting a compound having an alkoxycarbonyl group with an alcohol containing another alkyl group (such as methanol and ethanol) in the presence of an acid (such as sulfuric acid) or a base (such as sodium hydroxide), a corresponding compound having another alkoxycarbonyl group can be produced.

[1055] Furthermore, other compounds (I) or intermediates of the present invention can be produced by using starting materials different from those described in the above-mentioned production methods and the starting materials described in the Examples and Reference Examples described below and using the above-mentioned production methods, the methods described in the Examples and Reference Examples described below, and / or known methods, or using a combination thereof.

[1056] Example

[1057] The present invention will be further specifically described below with reference to Examples, Reference Examples, and Test Examples, but the present invention is not limited thereto.

[1058] "DIOL silica gel" in silica gel column chromatography refers to CHROMATOREX (trade name) DIOL manufactured by Fuji Silysia Chemical Ltd.

[1059] “Bond Elut” refers to Bond Elut C18 (trade name) manufactured by Agilent Technologies.

[1060] When multiple mass spectrometry values ​​are observed due to the presence of isotopes, only the value with the smallest m / z is reported. The "DUIS" ionization mode of the mass spectrometer refers to a mixed mode of ESI and APCI.

[1061] 1 Unless otherwise specified, H-NMR spectra are expressed as chemical shifts (δ) using tetramethylsilane as the internal standard (0 ppm), and coupling constants (J values) are expressed in Hz. The abbreviations for the splitting patterns of each peak have the following meanings: s: singlet, d: doublet, t: triplet, br: broad, and m: multiplet.

[1062] The abbreviations described in Examples, Reference Examples, and chemical structural formulas generally have the meanings generally used in the fields of organic chemistry or pharmacy. Specifically, those skilled in the art will understand each abbreviation as follows.

[1063] Boc: tert-Butoxycarbonyl

[1064] Cbz: benzyloxycarbonyl

[1065] DMSO: dimethyl sulfoxide

[1066] PMB: p-methoxybenzyl

[1067] TFA: trifluoroacetic acid

[1068] THP: Tetrahydropyranyl

[1069] tert-: uncle

[1070] n-: positive

[1071] M: molar concentration

[1072] ESI: electrospray ionization

[1073] APCI: Atmospheric Pressure Chemical Ionization

[1074] (Example)

[1075] Example 1-(a)

[1076] Production of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-6-ethyl-2,2-difluoro-6,7-dihydro-[1,3]dioxolano[4',5':4,5]benzo[1,2-f][1,4]oxazepin-8(9H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate

[1077] [Chemical Formula 42]

[1078]

[1079] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-formyl-4-methylphenyl)-2,2-dimethylpropanoate (20 mg) prepared in the same manner as Reference Example 1-(i) in dichloromethane (1 mL) was added (R)-6-ethyl-2,2-difluoro-6,7,8,9-tetrahydro-[1,3]dioxolano[4',5':4,5]benzo[1,2-f][1,4]oxazepine hydrochloride (24 mg) prepared in Reference Example 1-(d) while stirring at room temperature under an argon stream. The mixture was stirred at room temperature for 1 hour. Subsequently, sodium triacetoxyborohydride (25 mg) was added while stirring at room temperature, and the mixture was stirred at room temperature for 3 hours. After completion of the reaction, saturated aqueous sodium bicarbonate solution was added to the reaction solution, and the mixture was extracted twice with dichloromethane. The organic layer was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (developing solvent: hexane:ethyl acetate) to obtain the title compound (24 mg) as a colorless oil.

[1080] As another method, the target compound was produced by the following method.

[1081] (1) To a dichloromethane (4 mL) solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(hydroxymethyl)-4-methylphenyl)-2,2-dimethylpropanoate (200 mg) prepared in the same manner as in Reference Example 1-(h) was added thionyl chloride (0.077 mL) at room temperature while stirring under an argon stream, and the mixture was stirred at room temperature for 1 hour. After completion of the reaction, the reaction solution was concentrated under reduced pressure to obtain a crude product containing methyl 3-(3-(chloromethyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoate.

[1082] (2) To a solution of the crude product of methyl 3-(3-(chloromethyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoate prepared in (1) in acetonitrile (4 mL) was added (R)-6-ethyl-2,2-difluoro-6,7,8,9-tetrahydro-[1,3]dioxolano[4',5':4,5]benzo[1,2-f][1,4]oxazepine (162 mg) prepared in Reference Example 1-(k) while stirring under an argon gas stream, and the mixture was stirred at room temperature for 1 hour. Then, the mixture was stirred at 60°C for 2.5 hours. After completion of the reaction, the reaction solution was diluted with ethyl acetate, washed with water and saturated brine in that order, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (elution solvent: hexane:ethyl acetate) to obtain the target compound (260 mg) as a white foamy substance.

[1083] Mass spectrum (ESI, m / z): 621 [M+H] +

[1084] 1 H-NMR spectrum (400 MHz, DMSO-d6) δ: 7.63-7.53 (m, 2H), 7.15-6.99 (m, 5H), 4.78-4.71 (m, 1H), 4.28-4.20 (m, 3H), 3.93-3.85 (m, 1H), 3.81-3.55 (m, 2H), 3.53-3.38 (m, 5H), 2.77-2.62 (m, 5H), 2.25-2.16 (m, 3H), 1.47-1.35 (m, 1H), 1.33-1.08 (m, 7H), 0.97-0.78 (m, 3H)

[1085] Example 1-(b)

[1086] Production of 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-6-ethyl-2,2-difluoro-6,7-dihydro-[1,3]dioxolano[4',5':4,5]benzo[1,2-f][1,4]oxazepin-8(9H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid

[1087] [Chemical Formula 43]

[1088]

[1089] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-6-ethyl-2,2-difluoro-6,7-dihydro-[1,3]dioxolano[4',5':4,5]benzo[1,2-f][1,4]oxazepin-8(9H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate (23 mg) prepared in Example 1-(a) in dimethyl sulfoxide (2 mL), a 1M aqueous potassium hydroxide solution (0.371 mL) was added dropwise at room temperature while stirring, and the mixture was stirred at 70°C for 2 hours. After completion of the reaction, water (5 mL) was added to the reaction solution, and the pH was adjusted to 5.0 with 1M hydrochloric acid, followed by stirring overnight. The solid was separated by filtration, washed with water, and dried under reduced pressure at 65°C to obtain the title compound (16 mg) as a white solid.

[1090] Mass spectrum (ESI, m / z): 607 [M+H] +

[1091] 1 H-NMR spectrum (400 MHz, CD3OD) δ: 7.77-7.68 (m, 1H), 7.53-7.46 (m, 1H), 7.24-7.17 (m, 1H), 7.11-7.06 (m, 1H), 7.04-6.97 (m, 1H), 6.88-6.83 (m, 1H), 6.71-6.62 (m, 1H), 4.97 -4.71(m,1H),4.30-4.24(m,3H),3.92-3.82(m,1H),3.77-3.64(m,1H),3.60-3.45 (m,3H),2.90-2.66(m,5H),2.30-2.23(m,3H),1.55-1.12(m,8H),1.01-0.87(m,3H)

[1092] Example 2-(a)

[1093] Production of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-9-ethyl-2,2-difluoro-8,9-dihydro-[1,3]dioxolano[4',5':3,4]benzo[1,2-f][1,4]oxazepin-7(6H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate

[1094] [Chemical Formula 44]

[1095]

[1096] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-formyl-4-methylphenyl)-2,2-dimethylpropanoate (20 mg) prepared in the same manner as Reference Example 1-(i) in dichloromethane (1 mL) was added (R)-9-ethyl-2,2-difluoro-6,7,8,9-tetrahydro-[1,3]dioxolano[4',5':3,4]benzo[1,2-f][1,4]oxazepine (23 mg) prepared in Reference Example 2-(d) while stirring at room temperature under an argon stream. The mixture was stirred at room temperature for 1 hour. Subsequently, sodium triacetoxyborohydride (25 mg) was added while stirring at room temperature, and the mixture was stirred at room temperature overnight. After completion of the reaction, saturated aqueous sodium bicarbonate solution was added to the reaction solution, and the resulting mixture was extracted twice with dichloromethane. The organic layer was concentrated under reduced pressure, and the resulting residue was purified using a silica gel column (developing solvent; hexane:ethyl acetate) to obtain the title compound (35 mg) as a colorless oil.

[1097] Mass spectrum (ESI, m / z): 621 [M+H] +

[1098] 1 H-NMR spectrum (400 MHz, DMSO-d6) δ: 7.60-7.54 (m, 2H), 7.15-6.97 (m, 3H), 6.95-6.81 (m, 1H), 6.73-6.56 (m, 1H), 4.78-4.71 (m, 1H), 4.28-4.21 (m, 3H), 4.07-3.82 (m, 2H), 3.68-3.56 (m, 1H), 3.49-3.38 (m, 5H), 2.83-2.77 (m, 2H), 2.72-2.63 (m, 3H), 2.21 (s, 3H), 1.55-1.39 (m, 1H), 1.36-1.14 (m, 7H), 0.96-0.88 (m, 3H)

[1099] Example 2-(b)

[1100] Production of 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-9-ethyl-2,2-difluoro-8,9-dihydro-[1,3]dioxolano[4',5':3,4]benzo[1,2-f][1,4]oxazepin-7(6H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid

[1101] [Chemical Formula 45]

[1102]

[1103] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-9-ethyl-2,2-difluoro-8,9-dihydro-[1,3]dioxolano[4',5':3,4]benzo[1,2-f][1,4]oxazepin-7(6H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate (33 mg) prepared in Example 2-(a) in dimethyl sulfoxide (2 mL) was added dropwise 1M potassium hydroxide aqueous solution (0.532 mL) at room temperature while stirring, and the mixture was stirred at 70°C for 2 hours. After completion of the reaction, water (5 mL) was added to the reaction solution, and the pH was adjusted to 5.0 with 1M hydrochloric acid, followed by stirring overnight. The resulting solid was separated by filtration, washed with water, and dried under reduced pressure at 65°C to obtain the title compound (23 mg) as a white solid.

[1104] Mass spectrum (ESI, m / z): 607 [M+H] +

[1105] 1 H-NMR spectrum (400 MHz, CD3OD) δ: 7.73-7.68 (m, 1H), 7.52-7.46 (m, 1H), 7.24-7.17 (m, 1H), 7.11-7.05 (m, 1H), 7.04-6.94 (m, 1H), 6.62-6.30 (m, 2H), 4.96-4.79 (m, 1H), 4.31 -4.24(m,3H),3.92-3.77(m,2H),3.63-3.44(m,3H),2.96-2.79(m,2H),2.77-2.68 (m,3H),2.30-2.22(m,3H),1.61-1.47(m,1H),1.42-1.20(m,7H),1.03-0.94(m,3H)

[1106] Example 3-(a)

[1107] Production of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,5,7,8,9-hexahydro-4H-indeno[5,6-f][1,4]oxazepin-4-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate

[1108] [Chemical Formula 46]

[1109]

[1110] A solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-formyl-4-methylphenyl)-2,2-dimethylpropanoate (54 mg) prepared in the same manner as Reference Example 1-(i) and (R)-2-ethyl-3,4,5,7,8,9-hexahydro-2H-indeno[5,6-f][1,4]oxazepine (46 mg) prepared in Reference Example 3-(d) in dichloromethane (1 mL) was stirred at room temperature for 0.5 hours under an argon stream. Subsequently, sodium triacetoxyborohydride (63 mg) was added with stirring at room temperature, and the mixture was stirred overnight at room temperature. After completion of the reaction, a saturated aqueous sodium bicarbonate solution was added to the reaction solution, and the resulting mixture was extracted twice with dichloromethane. The organic layer was concentrated under reduced pressure, and the resulting residue was purified using a silica gel column (developing solvent; hexane:ethyl acetate) to obtain the title compound (72 mg) as a colorless oil.

[1111] As another method, the target compound was produced by the following method.

[1112] To a solution of methyl 3-(3-(chloromethyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoate (235 mg) prepared in the same manner as Reference Example 10-(c) in acetonitrile (5 mL) was added (R)-2-ethyl-3,4,5,7,8,9-hexahydro-2H-indeno[5,6-f][1,4]oxazepine (150 mg) prepared in the same manner as Reference Example 3-(d) and N,N-diisopropylethylamine (0.307 mL) in this order at room temperature while stirring under an argon stream. The mixture was stirred at room temperature for 6.5 hours and then at 60°C for 2 hours. After completion of the reaction, the reaction solution was concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluting solvent: hexane:ethyl acetate) to obtain the title compound (291 mg) as a colorless oil.

[1113] Mass spectrum (ESI, m / z): 581 [M+H] +

[1114] 1H-NMR spectrum (400 MHz, DMSO-d6) δ: 7.63-7.53 (m, 2H), 7.14-7.01 (m, 3H), 6.85-6.76 (m, 2H), 4.78-4.73 (m, 1H), 4.26-4.21 (m, 3H), 3.83-3.75 (m, 1H), 3.69-3.17 (m, 7H), 2.84-2.64 (m, 9H), 2.24-2.17 (m, 3H), 2.05-1.97 (m, 2H), 1.49-1.35 (m, 1H), 1.34-1.08 (m, 7H), 0.95-0.87 (m, 3H)

[1115] Example 3-(b)

[1116] Production of 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,5,7,8,9-hexahydro-4H-indeno[5,6-f][1,4]oxazepin-4-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid

[1117] [Chemical Formula 47]

[1118]

[1119] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,5,7,8,9-hexahydro-4H-indeno[5,6-f][1,4]oxazepin-4-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate (72 mg) prepared in Example 3-(a) in dimethyl sulfoxide (4 mL) was added dropwise 1M potassium hydroxide aqueous solution (1.04 mL) at room temperature while stirring, and the mixture was stirred at 70°C for 2 hours. After completion of the reaction, water (5 mL) was added to the reaction solution, the pH was adjusted to 5.0 with 1M hydrochloric acid, and the mixture was stirred overnight. The resulting solid was separated by filtration, washed with water, and dried under reduced pressure at 65°C to obtain the title compound (53 mg) as a white solid.

[1120] Mass spectrum (ESI, m / z): 567 [M+H] +

[1121] 1H-NMR spectrum (400 MHz, CD3OD) δ: 7.78-7.68 (m, 1H), 7.51-7.45 (m, 1H), 7.25-7.17 (m, 1H), 7.13-7.06 (m, 2H), 6.85-6.69 (m, 2H), 4.96-4.78 (m, 1H), 4.27 (s, 3H), 3.94-3 .86(m,1H),3.72-3.53(m,4H),2.94-2.70(m,9H),2.29-2.23(m,3H),2.11-2.02( m,2H),1.52-1.42(m,1H),1.42-1.36(m,3H),1.36-1.17(m,4H),1.02-0.93(m,3H)

[1122] Example 4-(a)

[1123] Production of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,7,8,9,10-hexahydronaphtho[2,3-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate

[1124] [Chemical Formula 48]

[1125]

[1126] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-formyl-4-methylphenyl)-2,2-dimethylpropanoate (27 mg) prepared in the same manner as Reference Example 1-(i) in dichloromethane (1.0 mL) was added (R)-2-ethyl-2,3,4,5,7,8,9,10-octahydronaphtho[2,3-f][1,4]oxazepine hydrochloride (21 mg) prepared in Reference Example 4-(d) and triethylamine (0.025 mL) while stirring at room temperature under an argon atmosphere. The mixture was stirred at room temperature for 2 hours. Subsequently, sodium triacetoxyborohydride (30 mg) was added portionwise with stirring under ice cooling, and the mixture was stirred at room temperature for 16 hours. Furthermore, sodium triacetoxyborohydride (30 mg) was added with stirring at room temperature, and the mixture was stirred at room temperature for 24 hours. After the reaction was completed, water was added to the reaction solution, followed by a saturated aqueous sodium bicarbonate solution, and the resulting mixture was extracted with dichloromethane. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluting solvent: hexane:ethyl acetate) to obtain the title compound (35 mg) as a colorless oil.

[1127] As another method, the target compound was produced by the following method.

[1128] To a solution of methyl 3-(3-(chloromethyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoate (231 mg) prepared in the same manner as Reference Example 10-(c) in acetonitrile (10 mL) was added (R)-2-ethyl-2,3,4,5,7,8,9,10-octahydronaphtho[2,3-f][1,4]oxazepine hydrochloride (187 mg) and N,N-diisopropylethylamine (0.415 mL) prepared in the same manner as Reference Example 4-(d) in acetonitrile (10 mL) while stirring at room temperature under an argon stream. The mixture was stirred at room temperature for 16.5 hours. After completion of the reaction, saturated aqueous ammonium chloride was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The obtained residue was purified by silica gel column (elution solvent; hexane:ethyl acetate) to obtain the target compound (314 mg) as a colorless oil.

[1129] Mass spectrum (ESI, m / z): 595 [M+H] +

[1130] 1 H-NMR spectrum (400 MHz, CDCl3) δ: 7.66-7.57 (m, 1H), 7.29-7.21 (m, 1H), 7.08-6.98 (m, 3H), 6.75-6.71 (m, 1H), 6.70-6.63 (m, 1H), 4.86-4.80 (m, 1H), 4.26-4.21 (m, 3H), 3.93-3.85 (m, 1H),3.76-3.62(m,1H),3.56-3.39(m,6H),2.86-2.61(m,9H),2.28-2.23(m,3H),1.83- 1.72(m,4H),1.61-1.47(m,2H),1.42-1.35(m,3H),1.34-1.29(m,3H),1.03-0.94(m,3H)

[1131] Example 4-(b)

[1132] Production of 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,7,8,9,10-hexahydronaphtho[2,3-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid

[1133] [Chemical Formula 49]

[1134]

[1135] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,7,8,9,10-hexahydronaphtho[2,3-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate (35 mg) prepared in Example 4-(a) in dimethyl sulfoxide (1.2 mL) was added 1 M aqueous potassium hydroxide solution (0.600 mL) at room temperature while stirring, and the mixture was stirred at 70°C for 4 hours. Water (2.0 mL) was then added to the reaction solution, and the pH was adjusted to 5.0 with 1 M hydrochloric acid. The precipitated solid was separated by filtration and dried under reduced pressure at 50°C to obtain a white solid.

[1136] To a solution of the obtained solid in dimethyl sulfoxide (1.2 mL), a 1M aqueous potassium hydroxide solution (0.600 mL) was added while stirring at room temperature, and the mixture was stirred at 70°C for 4 hours. After the reaction was completed, water (2.0 mL) was added to the reaction solution, and the pH was adjusted to 5.0 with 1M hydrochloric acid. The precipitated solid was separated by filtration and dried under reduced pressure at 50°C to obtain the title compound (26 mg) as a white solid.

[1137] Mass spectrum (ESI, m / z): 581 [M+H] +

[1138] 1 H-NMR spectrum (400 MHz, CD3OD) δ: 7.80-7.67 (m, 1H), 7.51-7.44 (m, 1H), 7.21-7.13 (m, 1H), 7.11-7.03 (m, 2H), 6.68-6.56 (m, 2H), 4.96-4.77 (m, 1H), 4.29-4.24 (m, 3H), 3.86 -3.78(m,1H),3.71-3.45(m,4H),2.91-2.81(m,1H),2.77-2.57(m,8H),2.29-2.21 (m,3H),1.82-1.71(m,4H),1.51-1.35(m,4H),1.32-1.14(m,4H),0.99-0.89(m,3H)

[1139] Example 5-(a)

[1140] Production of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-3,4,8,9,10,11-hexahydronaphtho[1,2-f][1,4]oxazepin-2(1H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate

[1141] [Chemical Formula 50]

[1142]

[1143] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-formyl-4-methylphenyl)-2,2-dimethylpropanoate (33 mg) prepared in the same manner as Reference Example 1-(i) in dichloromethane (1.0 mL) was added (R)-4-ethyl-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-f][1,4]oxazepine hydrochloride (25 mg) prepared in Reference Example 5-(d) and triethylamine (0.030 mL) at room temperature while stirring under an argon atmosphere. The mixture was stirred at room temperature for 2 hours. Subsequently, sodium triacetoxyborohydride (36 mg) was added portionwise with stirring under ice-cooling, and the mixture was stirred at room temperature for 16 hours. Furthermore, sodium triacetoxyborohydride (36 mg) was added at room temperature while stirring, and the mixture was stirred at room temperature for 24 hours. After the reaction was completed, water was added to the reaction solution, followed by a saturated aqueous sodium bicarbonate solution, and the resulting mixture was extracted with dichloromethane. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluting solvent: hexane:ethyl acetate) to obtain the title compound (44 mg) as a colorless oil.

[1144] Mass spectrum (ESI, m / z): 595 [M+H] +

[1145] 1H-NMR spectrum (400MHz, CDCl3) δ: 7.69-7.59(m,1H),7.29-7.21(m,1H),7.13-6.97( m,3H),6.88-6.82(m,1H),6.80-6.74(m,1H),4.86-4.80(m,1H),4.26-4.21(m, 3H),3.88-3.78(m,1H),3.70-3.53(m,3H),3.49-3.38(m,4H),2.85-2.62(m,7 H),2.36-2.07(m,5H),1.69-1.43(m,5H),1.41-1.23(m,7H),1.04-0.95(m,3H)

[1146] Example 5-(b)

[1147] Production of 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-3,4,8,9,10,11-hexahydronaphtho[1,2-f][1,4]oxazepin-2(1H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid

[1148] [Chemical Formula 51]

[1149]

[1150] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-3,4,8,9,10,11-hexahydronaphtho[1,2-f][1,4]oxazepin-2(1H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate (44 mg) prepared in Example 5-(a) in dimethyl sulfoxide (1.4 mL) was added 1M aqueous potassium hydroxide solution (0.750 mL) at room temperature while stirring, and the mixture was stirred at 70°C for 4 hours. After completion of the reaction, water (2.0 mL) was added to the reaction solution, and the pH was adjusted to 5.0 with 1M hydrochloric acid. The resulting solid was separated by filtration and dried under reduced pressure at 50°C to obtain the title compound (32 mg) as a white solid.

[1151] Mass spectrum (ESI, m / z): 581 [M+H] +

[1152] 1H-NMR spectrum (400 MHz, CD3OD) δ: 7.90-7.73 (m, 1H), 7.52-7.42 (m, 1H), 7.28-7.16 (m, 2H), 7.10-7.04 (m, 1H), 6.84-6.78 (m, 1H), 6.72-6.64 (m, 1H), 4.97-4.90 (m, 1H), 4.29-4.24 (m, 3H), 3.88-3 .56(m,3H),3.54-3.41(m,2H),3.01-2.91(m,1H),2.80-2.68(m,4H),2.62-2.53(m,2H),2.27- 2.18(m,3H),2.17-2.06(m,0.5H),1.94-1.67(m,1.5H),1.61-1.23(m,12H),1.06-0.97(m,3H)

[1153] Example 6-(a)

[1154] Production of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,5,8,9,10-hexahydro-4H-indeno[5,4-f][1,4]oxazepin-4-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate

[1155] [Chemical Formula 52]

[1156]

[1157] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-formyl-4-methylphenyl)-2,2-dimethylpropanoate (41 mg) prepared in the same manner as Reference Example 1-(i) in dichloromethane (1.0 mL) was added (R)-2-ethyl-3,4,5,8,9,10-hexahydro-2H-indeno[5,4-f][1,4]oxazepine hydrochloride (30 mg) prepared in Reference Example 6-(d) and triethylamine (0.040 mL) at room temperature while stirring under an argon atmosphere. The mixture was stirred at room temperature for 2 hours. Subsequently, sodium triacetoxyborohydride (46 mg) was added portionwise with stirring under ice-cooling, and the mixture was stirred at room temperature for 16 hours. Furthermore, sodium triacetoxyborohydride (91 mg) was added at room temperature while stirring, and the mixture was stirred at room temperature for 3 hours. Then, 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-formyl-4-methylphenyl)-2,2-dimethylpropionic acid methyl ester (41 mg) prepared in the same manner as Reference Example 1-(i) was added under stirring at room temperature and stirred for 16 hours at room temperature. After the reaction was completed, water was added to the reaction solution, followed by a saturated aqueous sodium bicarbonate solution, and the resulting mixed solution was extracted with dichloromethane. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel column (eluting solvent; hexane:ethyl acetate) to obtain the target compound (62 mg) as a white foam.

[1158] As another method, the target compound was produced by the following method.

[1159] To a solution of methyl 3-(3-(chloromethyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoate (188 mg) prepared in the same manner as Reference Example 10-(c) in acetonitrile (5 mL) was added (R)-2-ethyl-3,4,5,8,9,10-hexahydro-2H-indeno[5,4-f][1,4]oxazepine hydrochloride (143 mg) and N,N-diisopropylethylamine (0.241 mL) prepared in the same manner as Reference Example 6-(d) at room temperature while stirring under an argon stream. The mixture was stirred at 60°C for 2 hours and then at 80°C for 1 hour. After completion of the reaction, saturated aqueous ammonium chloride solution was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by silica gel column (eluting solvent: hexane:ethyl acetate) to obtain the target compound (247 mg) as a white foam.

[1160] Mass spectrum (ESI, m / z): 581 [M+H] +

[1161] 1 H-NMR spectrum (400MHz, CDCl3) δ: 7.62-7.55 (m, 1H), 7.28-7.22 (m, 1H), 7.11-6.99 (m, 2.5H), 6.98-6.95 (m, 0.5H), 6.78-6.73 (m, 0.5H), 6.68-6.61 (m, 1H), 6.43-6.39 (m, 0.5H), 4.87-4.82 (m, 1H), 4.26-4.22(m,3H),3.93-3.82(m,1H),3.79-3.64(m,1H),3.58-3.39(m,6H),2.99-2.77(m,9H) ,2.28-2.24(m,3H),2.16-1.98(m,2H),1.65-1.50(m,1H),1.42-1.22(m,7H),1.08-0.99(m,3H)

[1162] Example 6-(b)

[1163] Production of 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,5,8,9,10-hexahydro-4H-indeno[5,4-f][1,4]oxazepin-4-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid

[1164] [Chemical Formula 53]

[1165]

[1166] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,5,8,9,10-hexahydro-4H-indeno[5,4-f][1,4]oxazepin-4-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate (62 mg) prepared in Example 6-(a) in dimethyl sulfoxide (2.20 mL) was added 1 M aqueous potassium hydroxide solution (1.10 mL) at room temperature while stirring, and the mixture was stirred at 70°C for 2 hours. After completion of the reaction, water (2.0 mL) was added to the reaction solution, and the pH was adjusted to 5.0 with 1 M hydrochloric acid. The resulting solid was separated by filtration and dried under reduced pressure at 50°C to obtain the title compound (48 mg) as a white solid.

[1167] Mass spectrum (ESI, m / z): 567 [M+H] +

[1168] 1 H-NMR spectrum (400 MHz, CD3OD) δ: 7.74-7.66 (m, 1H), 7.53-7.45 (m, 1H), 7.27-7.18 (m, 1H), 7.12-6.95 (m, 2H), 6.72-6.65 (m, 0.5H), 6.64-6.58 (m, 0.5H), 6.56-6.49 (m, 0.5H), 6.35-6.29 (m, 0.5H), 5.02-4.71 (m,1H),4.31-4.22(m,3H),3.86-3.63(m,2H),3.61-3.44(m,3H),2.97-2.68(m,9H),2.31-2.22(m,3 H),2.15-1.95(m,2H),1.57-1.42(m,1H),1.41-1.34(m,3H),1.34-1.20(m,4H),1.01(t,J=7.4Hz,3H)

[1169] Example 7-(a)

[1170] Production of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,8,9,10,11-hexahydronaphtho[2,1-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate

[1171] [Chemical Formula 54]

[1172]

[1173] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-formyl-4-methylphenyl)-2,2-dimethylpropanoate (40 mg) prepared in the same manner as Reference Example 1-(i) in dichloromethane (2 mL) was added (R)-2-ethyl-2,3,4,5,8,9,10,11-octahydronaphtho[2,1-f][1,4]oxazepine hydrochloride (37 mg) prepared in Reference Example 7-(d) while stirring at room temperature under an argon stream. Triethylamine (0.019 mL) was then added, followed by acetic acid (0.009 mL) while stirring at room temperature, and the mixture was stirred at room temperature for 30 minutes. Subsequently, sodium triacetoxyborohydride (45 mg) was added all at once while stirring at room temperature, and the mixture was stirred at room temperature for 16 hours. After the reaction was completed, saturated aqueous sodium bicarbonate solution was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluting solvent: hexane:ethyl acetate) to obtain the title compound (58 mg) as a colorless foam.

[1174] Mass spectrum (ESI, m / z): 595 [M+H] +

[1175] 1 H-NMR spectrum (400 MHz, DMSO-d6) δ: 7.61-7.53 (m, 2H), 7.15-7.09 (m, 1H), 7.07-7.03 (m, 1H), 7.00-6.95 (m, 1H), 6.56-6.39 (m, 2H), 4.77-4.73 (m, 1H), 4.27-4.23 (m, 3H), 3.77-3.62 (m, 2H), 3.47-3.37 (m, 6H), 2.86-2.78 (m, 1H), 2.74-2.64 (m, 8H), 2.21 (s, 3H), 1.84-1.63 (m, 4H), 1.59-1.21 (m, 8H), 0.97-0.89 (m, 3H)

[1176] Example 7-(b)

[1177] Production of 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,8,9,10,11-hexahydronaphtho[2,1-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid

[1178] [Chemical Formula 55]

[1179]

[1180] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,8,9,10,11-hexahydronaphtho[2,1-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate (58 mg) prepared in Example 7-(a) in dimethyl sulfoxide (2 mL), a 1 M aqueous potassium hydroxide solution (0.975 mL) was added at room temperature while stirring under an argon stream, and the mixture was stirred at 70°C for 2 hours. After completion of the reaction, 1 M hydrochloric acid (0.975 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The obtained residue was purified by silica gel column (DIOL silica gel, elution solvent; hexane:ethyl acetate) to obtain the target compound (45 mg) as a white solid.

[1181] Mass spectrum (ESI, m / z): 581 [M+H] +

[1182] 1 H-NMR spectrum (400 MHz, DMSO-d6) δ: 12.30 (s, 1H), 7.66-7.52 (m, 2H), 7.19-7.11 (m, 1H), 7.08-7.01 (m, 1H), 6.98-6.87 (m, 1H), 6.55-6.33 (m, 2H), 4.78 (s, 1H), 4.31-4.19 (m, 3H), 3.80-3.59 (m, 2H), 3.45-3.19 (m, 3H), 2.86-2.77 (m, 1H), 2.75-2.61 (m, 8H), 2.20 (s, 3H), 1.82-1.61 (m, 4H), 1.56-1.14 (m, 8H), 0.97-0.89 (m, 3H)

[1183] Example 8-(a)

[1184] Production of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydronaphtho[2,3-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate

[1185] [Chemical Formula 56]

[1186]

[1187] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-formyl-4-methylphenyl)-2,2-dimethylpropanoate (40 mg) prepared in the same manner as Reference Example 1-(i) in dichloromethane (3 mL) was added (R)-2-ethyl-2,3,4,5-tetrahydronaphtho[2,3-f][1,4]oxazepine (34 mg) prepared in Reference Example 8-(d) while stirring at room temperature under an argon stream. The mixture was stirred at room temperature for 30 minutes. Subsequently, sodium triacetoxyborohydride (45 mg) was added all at once while stirring at room temperature, and the mixture was stirred at room temperature for 24 hours. After completion of the reaction, saturated aqueous sodium bicarbonate solution was added to the reaction solution, and the mixture was extracted twice with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The obtained residue was purified by silica gel column (elution solvent; hexane:ethyl acetate) to obtain the target compound (53 mg) as a white solid.

[1188] Mass spectrum (ESI, m / z): 591 [M+H] +

[1189] 1 H-NMR spectrum (400MHz, CDCl3) δ: 7.78-7.55(m,3H),7.48-7.35(m,4H),7.23-7.16(m,1H),7. 11-6.99(m,3H),4.87-4.81(m,1H),4.24-4.18(m,3H),4.16-4.09(m,1H),3.88-3.72(m, 2H),3.62-3.52(m,1H),3.49-3.41(m,4H),2.97-2.84(m,2H),2.82-2.73(m,3H),2.29- 2.22(m,3H),1.69-1.49(m,1H),1.44-1.36(m,3H),1.35-1.23(m,4H),1.12-1.01(m,3H)

[1190] Example 8-(b)

[1191] Production of 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydronaphtho[2,3-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid

[1192] [Chemical Formula 57]

[1193]

[1194] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydronaphtho[2,3-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate (53 mg) prepared in Example 8-(a) in dimethyl sulfoxide (2.5 mL), a 1M aqueous potassium hydroxide solution (0.897 mL) was added dropwise at room temperature while stirring under an argon stream. The mixture was stirred at 70°C for 3 hours. After completion of the reaction, water (5 mL) was added, and the pH was adjusted to 5.2 with 1M hydrochloric acid. The mixture was stirred at room temperature for 1 hour, and the resulting solid was separated by filtration, washed with water, and dried under reduced pressure at 60°C to obtain the title compound (47 mg) as a white solid.

[1195] Mass spectrum (ESI, m / z): 577 [M+H] +

[1196] 1 H-NMR spectrum (400 MHz, CD3OD) δ: 7.81-7.63 (m, 3H), 7.49-7.32 (m, 5H), 7.25-7.14 (m, 1H), 7.12-7.03 (m, 2H), 4.98-4.78 (m, 1H), 4.27-4.18 (m, 3H), 4.07-3.97 (m, 1H), 3.85-3.67 (m, 2H), 3.64-3.46 (m, 2H), 2.96-2.77 (m, 2H), 2.71-2.67 (m, 3H), 2.30-2.22 (m, 3H), 1.61-1.47 (m, 1H), 1.42-1.19 (m, 7H), 1.07-0.97 (m, 3H)

[1197] Example 9-(a)

[1198] Production of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-b]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate

[1199] [Chemical Formula 58]

[1200]

[1201] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-formyl-4-methylphenyl)-2,2-dimethylpropanoate (40 mg) prepared in the same manner as Reference Example 1-(i) in dichloromethane (5 mL) was added (R)-2-ethyl-2,3,4,5-tetrahydro-[1,4]oxazepino[7,6-b]quinoline (72 mg) prepared in Reference Example 9-(b) while stirring at room temperature under an argon stream. The mixture was stirred at room temperature for 30 minutes. Subsequently, sodium triacetoxyborohydride (45 mg) was added while stirring at room temperature, and the mixture was stirred at room temperature for 24 hours. After completion of the reaction, saturated aqueous sodium bicarbonate solution was added to the reaction solution, and the mixture was extracted twice with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The obtained residue was purified by silica gel column (elution solvent; hexane:ethyl acetate) to obtain the target compound (56 mg) as a colorless oil.

[1202] Mass spectrum (ESI, m / z): 592 [M+H] +

[1203] 1 H-NMR spectrum (400MHz, CDCl3) δ: 8.01-7.92(m,1H),7.79-7.71(m,1H),7.69-7.55(m,3H),7.50-7.41(m,1H) ),7.22-7.15(m,1H),7.13-7.03(m,3H),4.88-4.81(m,1H),4.24-4.03(m,4H),3.97-3.87(m,1H),3.86 -3.77(m,1H),3.66-3.51(m,2H),3.49-3.42(m,3H),3.03-2.89(m,2H),2.82-2.74(m,3H),2.30-2.23 (m,3H),1.86-1.70(m,1H),1.67-1.49(m,1H),1.43-1.36(m,3H),1.35-1.23(m,3H),1.07-0.95(m,3H)

[1204] Example 9-(b)

[1205] Production of 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-b]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid

[1206] [Chemical Formula 59]

[1207]

[1208] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-b]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate (56 mg) prepared in Example 9-(a) in dimethyl sulfoxide (2.5 mL) was added dropwise with stirring under an argon stream at room temperature. The mixture was stirred at 70°C for 3 hours. After completion of the reaction, the mixture was cooled to room temperature, water (5 mL) was added, and the pH was adjusted to 5.2 with 1M hydrochloric acid. The mixture was stirred at room temperature for 1 hour, and the resulting solid was separated by filtration, washed with water, and dried under reduced pressure at 60°C to obtain the title compound (49 mg) as a white solid.

[1209] Mass spectrum (ESI, m / z): 578 [M+H] +

[1210] 1 H-NMR spectrum (400 MHz, CD3OD) δ: 7.97-7.89 (m, 1H), 7.87-7.62 (m, 4H), 7.55-7.46 (m, 1H), 7.43-7.33 (m, 1H), 7.24-7.05 (m, 3H), 4.96-4.81 (m, 1H), 4.26-4.17 (m, 3H), 4.16-3.99 (m, 1H),3.94-3.80(m,2H),3.70-3.56(m,2H),2.99-2.86(m,2H),2.72-2.63(m,3H),2.32- 2.23(m,3H),1.73-1.59(m,1H),1.55-1.41(m,1H),1.41-1.23(m,6H),1.06-0.94(m,3H)

[1211] Example 10-(a)

[1212] Production of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-b]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate

[1213] [Chemical Formula 60]

[1214]

[1215] To a solution of methyl 3-(3-(chloromethyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoate (52 mg) prepared in Reference Example 10-(c) in acetonitrile (3 mL) was added (R)-2-ethyl-2,3,4,5-tetrahydro-[1,4]oxazepino[6,7-b]quinoline (27 mg) prepared in Reference Example 10-(b) and N,N-diisopropylethylamine (0.061 mL) in this order at room temperature while stirring under an argon stream. The mixture was stirred at room temperature for 15 hours and then at 60°C for 2 hours. After completion of the reaction, saturated aqueous ammonium chloride was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (developing solvent: hexane:ethyl acetate) to obtain the target compound (39 mg) as a white foamy substance.

[1216] Mass spectrum (DUIS, m / z): 592 [M+H] +

[1217] 1 H-NMR spectrum (400MHz, CDCl3) δ: 8.08-8.00(m,1H),7.80-7.58(m,4H),7.55-7.47(m,1H),7.29- 7.14(m,1H),7.12-6.98(m,3H),4.84-4.77(m,1H),4.36-4.27(m,1H),4.23-4.14(m,4H),3 .88-3.71(m,1H),3.70-3.61(m,1H),3.58-3.48(m,1H),3.46-3.38(m,3H),2.90-2.81(m,2 H),2.78-2.71(m,3H),2.27(s,3H),1.67-1.48(m,1H),1.41-1.20(m,7H),1.07-0.95(m,3H)

[1218] Example 10-(b)

[1219] Production of 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-b]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid

[1220] [Chemical Formula 61]

[1221]

[1222] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-b]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate (39 mg) prepared in Example 10-(a) in dimethyl sulfoxide (2.5 mL), a 1M aqueous potassium hydroxide solution (0.66 mL) was added dropwise at room temperature while stirring under an argon stream. The mixture was stirred at 70°C for 3 hours. After completion of the reaction, the mixture was cooled to room temperature, water (5 mL) was added, and the pH was adjusted to 5.2 with 1M hydrochloric acid. The mixed solution was extracted three times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The obtained residue was purified by silica gel column (eluting solvent: hexane:ethyl acetate), and the fraction containing the target compound was concentrated under reduced pressure. The obtained residue was dissolved in a mixed solvent of acetonitrile / water and freeze-dried to obtain the target compound (12 mg) as a white solid.

[1223] As another method, the target compound was produced by the following method.

[1224] A solution of 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-formyl-4-methylphenyl)-2,2-dimethylpropanoic acid (135 mg) prepared in the same manner as Reference Example 23-(g) and (R)-2-ethyl-2,3,4,5-tetrahydro-[1,4]oxazepino[6,7-b]quinoline (95 mg) prepared in the same manner as Reference Example 10-(b) in dichloromethane (2 mL) was stirred at room temperature for 1 hour under an argon stream. Subsequently, sodium triacetoxyborohydride (146 mg) was added with stirring at room temperature, and the mixture was stirred overnight at room temperature. After completion of the reaction, saturated aqueous sodium bicarbonate solution was added to the reaction solution, and the mixture was extracted with dichloromethane. The organic layer was then concentrated under reduced pressure. The obtained residue was purified by silica gel column (elution solvent; hexane:ethyl acetate) to obtain the target compound (18 mg) as a pale yellow oil.

[1225] Mass spectrum (ESI, m / z): 578 [M+H] +

[1226] 1H-NMR spectrum (400 MHz, CD3OD) δ: 8.00-7.91 (m, 1H), 7.89-7.82 (m, 2H), 7.81-7.71 (m, 1H), 7.69-7.61 (m, 1H), 7.60-7.52 (m, 1H), 7.41-7.35 (m, 1H), 7.19-7.09 (m, 2H), 7.08-7.02 (m, 1H), 4.92-4.79 (m, 1H), 4.26 -4.17(m,4H),4.16-4.08(m,1H),3.89-3.72(m,1H),3.72-3.64(m,1H),3.60-3.51(m,1H),2.92-2.78 (m,2H),2.72-2.63(m,3H),2.31-2.23(m,3H),1.64-1.46(m,1H),1.40-1.18(m,7H),1.02-0.93(m,3H)

[1227] Example 11-(a)

[1228] Production of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate

[1229] [Chemical Formula 62]

[1230]

[1231] To a dichloromethane (1 mL) solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-formyl-4-methylphenyl)-2,2-dimethylpropanoate (30 mg) prepared in the same manner as Reference Example 1-(i) was added (R)-2-ethyl-2,3,4,5-tetrahydro-[1,4]oxazepino[6,7-g]quinoline dihydrochloride (32 mg) prepared in Reference Example 11-(c) under an argon stream, and the mixture was stirred at room temperature for 0.5 hours. Subsequently, sodium triacetoxyborohydride (35 mg) was added with stirring at room temperature, and the mixture was stirred overnight at room temperature. After completion of the reaction, saturated aqueous sodium bicarbonate solution was added to the reaction solution, and the mixture was extracted twice with dichloromethane. The organic layer was concentrated under reduced pressure and purified using a silica gel column (eluting solvent; hexane:ethyl acetate) to obtain the title compound (18 mg) as a pale yellow oil.

[1232] Mass spectrum (ESI, m / z): 592 [M+H] +

[1233] 1 H-NMR spectrum (400 MHz, DMSO-d6) δ: 8.87-8.82 (m, 1H), 8.25-8.18 (m, 1H), 7.67-7.49 (m, 4H), 7.47-7.42 (m, 1H), 7.13-7.03 (m, 3H), 4.78-4.72 (m, 1H), 4.26-4.19 (m, 3H), 4.1 0-3.99(m,1H),3.95-3.80(m,2H),3.60-3.19(m,5H),2.84-2.76(m,2H),2.70-2.59 (m,3H),2.24-2.20(m,3H),1.58-1.45(m,1H),1.35-1.14(m,7H),1.01-0.93(m,3H)

[1234] Example 11-(b)

[1235] Production of 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid

[1236] [Chemical Formula 63]

[1237]

[1238] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate (18 mg) prepared in Example 11-(a) in dimethyl sulfoxide (1 mL), a 1M aqueous potassium hydroxide solution (0.304 mL) was added dropwise at room temperature while stirring, and the mixture was stirred at 70°C for 2 hours. After completion of the reaction, water (5 mL) was added to the reaction solution, the pH was adjusted to 5.0 with 1M hydrochloric acid, and the mixture was stirred overnight. The resulting solid was separated by filtration, washed with water, and dried under reduced pressure at 65°C to obtain the title compound (11 mg) as a white solid.

[1239] Mass spectrum (ESI, m / z): 578 [M+H] +

[1240] 1H-NMR spectrum (400 MHz, CD3OD) δ: 8.84-8.71 (m, 1H), 8.25-8.15 (m, 1H), 7.80-7.65 (m, 1H), 7.59-7.38 (m, 4H), 7.24-7.15 (m, 1H), 7.13-7.03 (m, 2H), 4.97-4.75 (m, 1H), 4.29-4.20 (m, 3H),4.07-3.97(m,1H),3.94-3.75(m,2H),3.65-3.50(m,2H),2.97-2.82(m,2H),2.73- 2.64(m,3H),2.30-2.22(m,3H),1.65-1.51(m,1H),1.42-1.23(m,7H),1.08-0.96(m,3H)

[1241] Example 12-(a)

[1242] Production of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate

[1243] [Chemical Formula 64]

[1244]

[1245] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-formyl-4-methylphenyl)-2,2-dimethylpropanoate (50 mg) prepared in the same manner as Reference Example 1-(i) in dichloromethane (3 mL) was added (R)-2-ethyl-2,3,4,5-tetrahydro-[1,4]oxazepino[7,6-g]quinoline (38 mg) prepared in Reference Example 12-(c) while stirring at room temperature under an argon stream. The mixture was stirred at room temperature for 30 minutes. Subsequently, sodium triacetoxyborohydride (45 mg) was added while stirring at room temperature, and the mixture was stirred at room temperature for 24 hours. After completion of the reaction, saturated aqueous sodium bicarbonate solution was added to the reaction solution, and the mixture was extracted twice with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (developing solvent: hexane:ethyl acetate) to obtain the title compound (59 mg) as a colorless oil.

[1246] As another method, the target compound was produced by the following method.

[1247] To a solution of methyl 3-(3-(chloromethyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoate (0.171 g) prepared in the same manner as Reference Example 10-(c) in acetonitrile (5 mL) was added (R)-2-ethyl-2,3,4,5-tetrahydro-[1,4]oxazepino[7,6-g]quinoline (0.108 g) and N,N-diisopropylethylamine (0.219 mL) prepared in the same manner as Reference Example 12-(c) in acetonitrile (5 mL) while stirring at room temperature under an argon stream. The mixture was stirred at room temperature for 1.25 hours. The mixture was then stirred at 60°C for 3 hours, at room temperature for 15 hours, and at 60°C for 1 hour. After completion of the reaction, saturated aqueous ammonium chloride solution was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by silica gel column (eluting solvent: hexane:ethyl acetate) to obtain the target compound (0.177 g) as a white foam.

[1248] Mass spectrum (ESI, m / z): 592 [M+H] +

[1249] 1 H-NMR spectrum (400 MHz, CDCl3) δ: 8.85-8.79 (m, 1H), 8.06 (d, J = 8.2 Hz, 1H), 7.79-7.71 (m, 1H), 7.67-7.55 (m, 1H), 7.41-7.38 (m, 1H), 7.36 (dd, J = 4.3, 8.2 Hz, 1H), 7.33-7.23 (m, 1H), 7.10-6.99 (m, 3H), 4.89-4.80 (m, 1H),4.26-4.20(m,3H),4.20-4.09(m,1H),3.93-3.75(m,2H),3.65-3.54(m,1H),3.50-3.40(m,4H),2.9 5-2.83(m,2H),2.80-2.74(m,3H),2.23(s,3H),1.70-1.50(m,1H),1.42-1.23(m,7H),1.09-0.98(m,3H)

[1250] Example 12-(b)

[1251] Production of 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid

[1252] [Chemical Formula 65]

[1253]

[1254] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate (59 mg) prepared in Example 12-(a) in dimethyl sulfoxide (2.5 mL), a 1M aqueous potassium hydroxide solution (0.997 mL) was added dropwise at room temperature while stirring under an argon stream. The mixture was stirred at 70°C for 3 hours. After completion of the reaction, the mixture was cooled to room temperature, water (5 mL) was added, and the pH was adjusted to 5.2 with 1M hydrochloric acid. The mixture was stirred at room temperature for 1 hour, and the resulting solid was separated by filtration, washed with water, and dried under reduced pressure at 60°C to obtain the title compound (52 mg) as a white solid.

[1255] Mass spectrum (ESI, m / z): 578 [M+H] +

[1256] 1 H-NMR spectrum (400 MHz, CD3OD) δ: 8.77-8.70 (m, 1H), 8.31-8.23 (m, 1H), 7.80-7.66 (m, 2H), 7.52-7.42 (m, 3H), 7.21-7.02 (m, 3H), 4.99-4.73 (m, 1H), 4.27-4.22 (m, 3H), 4.13-4.02 (m, 1H), 3.96 -3.86(m,1H),3.86-3.70(m,1H),3.68-3.59(m,1H),3.56-3.49(m,1H),2.94-2.77(m,2H),2 .73-2.66(m,3H),2.27-2.21(m,3H),1.64-1.46(m,1H),1.41-1.20(m,7H),1.05-0.95(m,3H)

[1257] Example 13-(a)

[1258] Production of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-10-methyl-2,3-dihydro-[1,4]oxazepino[7,6-b]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate

[1259] [Chemical Formula 66]

[1260]

[1261] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-formyl-4-methylphenyl)-2,2-dimethylpropanoate (35 mg) prepared in the same manner as Reference Example 1-(i) in dichloromethane (3 mL) was added (R)-2-ethyl-10-methyl-2,3,4,5-tetrahydro-[1,4]oxazepino[7,6-b]quinoline (31 mg) prepared in Reference Example 13-(b) while stirring at room temperature under an argon stream. The mixture was stirred at room temperature for 30 minutes. Subsequently, sodium triacetoxyborohydride (40 mg) was added while stirring at room temperature, and the mixture was stirred at room temperature for 24 hours. After completion of the reaction, saturated aqueous sodium bicarbonate solution was added to the reaction solution, and the mixture was extracted twice with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluting solvent: hexane:ethyl acetate) to obtain the target compound (50 mg) as a white solid.

[1262] Mass spectrum (ESI, m / z): 606 [M+H] +

[1263] 1 H-NMR spectrum (400 MHz, CDCl3) δ: 7.73-7.68 (m, 1H), 7.64-7.55 (m, 1H), 7.53-7.46 (m, 2H), 7.37-7.30 (m, 1H), 7.22-7.15 (m, 1H), 7.12-7.01 (m, 3H), 4.86-4.81 (m, 1H), 4.22-4.17 (m, 3H), 4.15-4.00 (m, 1H), 3.95-3.86 (m, 1H),3.82-3.74(m,1H),3.66-3.51(m,2H),3.49-3.42(m,3H),3.01-2.89(m,2H),2.81-2.72(m,6H),2.29- 2.23(m,3H),1.83-1.71(m,1H),1.60-1.44(m,1H),1.42-1.36(m,3H),1.35-1.22(m,3H),1.08-0.97(m,3H)

[1264] Example 13-(b)

[1265] Production of 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-10-methyl-2,3-dihydro-[1,4]oxazepino[7,6-b]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid

[1266] [Chemical Formula 67]

[1267]

[1268] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-10-methyl-2,3-dihydro-[1,4]oxazepino[7,6-b]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate (50 mg) prepared in Example 13-(a) in dimethyl sulfoxide (3 mL), a 1M aqueous potassium hydroxide solution (0.825 mL) was added dropwise at room temperature while stirring under an argon stream, and the mixture was stirred at 70°C for 3 hours. After completion of the reaction, water (5 mL) was added and the pH was adjusted to 5.2 with 1M hydrochloric acid. The mixture was stirred at room temperature for 1 hour, and the resulting solid was separated by filtration, washed with water, and dried under reduced pressure at 60°C to obtain the title compound (45 mg) as a white solid.

[1269] Mass spectrum (ESI, m / z): 592 [M+H] +

[1270] 1 H-NMR spectrum (400 MHz, CD3OD) δ: 7.85 (d, J = 9.8 Hz, 1H), 7.77-7.63 (m, 1H), 7.61-7.50 (m, 2H), 7.42-7.32 (m, 2H), 7.23-7.15 (m, 1H), 7.13-7.04 (m, 2H), 4.95-4.78 (m, 1H), 4.24-4.17 (m, 3H), 4. 13-3.97(m,1H),3.90-3.80(m,2H),3.69-3.54(m,2H),2.99-2.84(m,2H),2.71-2.63(m,6H), 2.31-2.23(m,3H),1.75-1.60(m,1H),1.56-1.41(m,1H),1.40-1.22(m,6H),1.01-0.92(m,3H)

[1271] Example 14-(a)

[1272] Production of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-8-methyl-2,3-dihydro-[1,4]oxazepino[7,6-b]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate

[1273] [Chemical Formula 68]

[1274]

[1275] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-formyl-4-methylphenyl)-2,2-dimethylpropanoate (35 mg) prepared in the same manner as Reference Example 1-(i) in dichloromethane (3 mL) was added (R)-2-ethyl-8-methyl-2,3,4,5-tetrahydro-[1,4]oxazepino[7,6-b]quinoline (31 mg) prepared in Reference Example 14-(b) while stirring at room temperature under an argon stream. The mixture was stirred at room temperature for 30 minutes. Subsequently, sodium triacetoxyborohydride (39 mg) was added while stirring at room temperature, and the mixture was stirred at room temperature for 24 hours. After completion of the reaction, saturated aqueous sodium bicarbonate solution was added to the reaction solution, and the mixture was extracted twice with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluting solvent: hexane:ethyl acetate) to obtain the target compound (54 mg) as a white foam.

[1276] Mass spectrum (ESI, m / z): 606 [M+H] +

[1277] 1 H-NMR spectrum (400 MHz, CDCl3) δ: 7.90-7.82 (m, 1H), 7.67-7.55 (m, 2H), 7.52-7.38 (m, 2H), 7.23-7.15 (m, 1H), 7.13-7.02 (m, 3H), 4.88-4.81 (m, 1H), 4.26-4.16 (m, 3H), 4.16-4.00 (m, 1H), 3.96-3.87 (m, 1H),3.83-3.75(m,1H),3.65-3.41(m,5H),3.03-2.87(m,2H),2.85-2.74(m,3H),2.59-2.48(m,3 H),2.33-2.23(m,3H),1.84-1.70(m,1H),1.67-1.49(m,1H),1.44-1.22(m,6H),1.07-0.94(m,3H)

[1278] Example 14-(b)

[1279] Production of 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-8-methyl-2,3-dihydro-[1,4]oxazepino[7,6-b]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid

[1280] [Chemical Formula 69]

[1281]

[1282] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-8-methyl-2,3-dihydro-[1,4]oxazepino[7,6-b]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate (54 mg) prepared in Example 14-(a) in dimethyl sulfoxide (3 mL), a 1M aqueous potassium hydroxide solution (0.891 mL) was added dropwise at room temperature while stirring under an argon stream, and the mixture was stirred at 70°C for 3 hours. After completion of the reaction, water (5 mL) was added and the pH was adjusted to 5.2 with 1M hydrochloric acid. The mixture was stirred at room temperature for 1 hour, and the resulting solid was separated by filtration, washed with water, and dried under reduced pressure at 60°C to obtain the title compound (50 mg) as a white solid.

[1283] Mass spectrum (ESI, m / z): 592 [M+H] +

[1284] 1 H-NMR spectrum (400 MHz, CD3OD) δ: 7.85-7.62 (m, 3H), 7.58-7.48 (m, 2H), 7.42-7.32 (m, 1H), 7.24-7.04 (m, 3H), 4.95-4.82 (m, 1H), 4.24-4.16 (m, 3H), 4.12-3.95 (m, 1H), 3.90-3.77 (m, 2H),3.69-3.54(m,2H),2.98-2.81(m,2H),2.72-2.63(m,3H),2.56-2.48(m,3H),2.30- 2.22(m,3H),1.73-1.57(m,1H),1.53-1.40(m,1H),1.40-1.22(m,6H),1.04-0.93(m,3H)

[1285] Example 15-(a)

[1286] Production of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-8-ethyl-1,5,7,8-tetrahydro-6H-[1,4]oxazepino[6,7-f]indazol-6-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate

[1287] [Chemical Formula 70]

[1288]

[1289] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-formyl-4-methylphenyl)-2,2-dimethylpropanoate (25 mg) prepared in the same manner as Reference Example 1-(i) in dichloromethane (2 mL) was added (R)-8-ethyl-5,6,7,8-tetrahydro-1H-[1,4]oxazepino[6,7-f]indazole (16 mg) prepared in Reference Example 15-(j) at room temperature while stirring under an argon stream. The mixture was stirred at room temperature for 1 hour. Subsequently, sodium triacetoxyborohydride (30 mg) was added at room temperature while stirring, and the mixture was stirred at room temperature for 20 hours. After completion of the reaction, saturated aqueous sodium bicarbonate solution was added to the reaction solution, and the mixture was extracted with dichloromethane. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel column (eluting solvent; hexane:ethyl acetate) to obtain the title compound (29 mg) as a colorless oil.

[1290] Mass spectrum (ESI, m / z): 581 [M+H] +

[1291] 1 H-NMR spectrum (400 MHz, CD3OD) δ: 7.93-7.83 (m, 1H), 7.76-7.57 (m, 1H), 7.52-7.38 (m, 1H), 7.33-6.97 (m, 5H), 4.91-4.82 (m, 1H), 4.27-4.19 (m, 3H), 3.97-3.88 (m, 1H), 3.79-3.39 (m, 7H), 2.93-2.63 (m, 5H), 2.29-2.15 (m, 3H), 1.65-1.16 (m, 8H), 1.04-0.95 (m, 3H)

[1292] Example 15-(b)

[1293] Production of 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-8-ethyl-1,5,7,8-tetrahydro-6H-[1,4]oxazepino[6,7-f]indazol-6-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid

[1294] [Chemical Formula 71]

[1295]

[1296] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-8-ethyl-1,5,7,8-tetrahydro-6H-[1,4]oxazepino[6,7-f]indazol-6-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate (29 mg) prepared in Example 15-(a) in dimethyl sulfoxide (2 mL), a 2M aqueous potassium hydroxide solution (0.250 mL) was added while stirring at room temperature, and the mixture was stirred at 70°C for 5 hours. After completion of the reaction, 1M hydrochloric acid was added to the reaction solution to adjust the pH to around 5, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified on a silica gel column (DIOL silica gel, eluting solvent; hexane:ethyl acetate), and the fractions containing the target compound were concentrated under reduced pressure. The obtained residue was dissolved in a mixed solvent of acetonitrile / water and freeze-dried to obtain the target compound (17 mg) as a white solid.

[1297] Mass spectrum (ESI, m / z): 567 [M+H] +

[1298] 1 H-NMR spectrum (400MHz, CD3OD) δ: 7.93-7.86(m,1H),7.78-7.66(m,1H),7.50-7 .40(m,1H),7.36-7.16(m,2H),7.12-7.00(m,3H),4.96-4.77(m,1H),4.29 -4.22(m,3H),4.03-3.92(m,1H),3.82-3.44(m,4H),2.93-2.65(m,5H),2 .29-2.19(m,3H),1.60-1.46(m,1H),1.43-1.19(m,7H),1.05-0.96(m,3H)

[1299] Example 16-(a)

[1300] Production of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-3,4-dihydronaphtho[1,2-f][1,4]oxazepin-2(1H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate

[1301] [Chemical Formula 72]

[1302]

[1303] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-formyl-4-methylphenyl)-2,2-dimethylpropanoate (40 mg) prepared in the same manner as Reference Example 1-(i) in dichloromethane (2 mL) was added (R)-4-ethyl-1,2,3,4-tetrahydronaphtho[1,2-f][1,4]oxazepine (36 mg) prepared in Reference Example 16-(d) while stirring at room temperature under an argon stream. Acetic acid (0.009 mL) was then added while stirring at room temperature, and the mixture was stirred at room temperature for 30 minutes. Sodium triacetoxyborohydride (46 mg) was then added while stirring at room temperature, and the mixture was stirred at room temperature for 4 hours. After the reaction was completed, saturated aqueous sodium bicarbonate was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (developing solvent: hexane:ethyl acetate) to obtain the target compound (60 mg) as a colorless foamy substance.

[1304] Mass spectrum (ESI, m / z): 591 [M+H] +

[1305] 1H-NMR spectrum (400 MHz, DMSO-d6) δ: 7.88-7.82 (m, 1H), 7.80-7.73 (m, 1H), 7.65-7.43 (m, 3H), 7.36-7.28 (m, 1H), 7.28-7.07 (m, 4H), 7.06-6.97 (m, 1H), 4.81-4.65 (m, 1H), 4.40-4.31 (m, 1H), 4.23 (s, 3H), 3.96- 3.86(m,1H),3.85-3.76(m,1H),3.69-3.51(m,2H),3.44-3.36(m,3H),2.94-2.70(m,2H),2.65-2.55( m,3H),2.17-2.11(m,3H),1.65-1.48(m,1H),1.45-1.30(m,1H),1.29-1.18(m,6H),1.04-0.92(m,3H)

[1306] Example 16-(b)

[1307] Production of 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-3,4-dihydronaphtho[1,2-f][1,4]oxazepin-2(1H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid

[1308] [Chemical Formula 73]

[1309]

[1310] A solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-3,4-dihydronaphtho[1,2-f][1,4]oxazepin-2(1H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate (59 mg) in dimethyl sulfoxide (2 mL) was added with stirring under an argon stream at room temperature, followed by stirring at 70°C for 2 hours. After completion of the reaction, 1M hydrochloric acid (1.0 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified on a silica gel column (DIOL silica gel, eluting solvent; hexane:ethyl acetate) to obtain the title compound (36 mg) as a white solid.

[1311] Mass spectrum (ESI, m / z): 577 [M+H] +

[1312] 1 H-NMR spectrum (400 MHz, DMSO-d6) δ: 12.18 (s, 1H), 7.87-7.81 (m, 1H), 7.80-7.73 (m, 1H), 7.72-7.56 (m, 1H), 7.54-7.43 (m, 2H), 7.36-7.29 (m, 1H), 7.26-7.07 (m, 4H), 7.05-6.97 (m, 1H), 4.85-4.71 (m, 1H), 4. 41-4.31(m,1H),4.22(s,3H),3.95-3.85(m,1H),3.84-3.75(m,1H),3.67-3.48(m,2H),2.94-2.72(m ,2H),2.64-2.56(m,3H),2.18-2.08(m,3H),1.66-1.47(m,1H),1.43-1.14(m,7H),1.02-0.93(m,3H)

[1313] Example 17-(a)

[1314] Production of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-8-ethyl-8,9-dihydro-[1,4]oxazepino[7,6-h]quinolin-10(11H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate

[1315] [Chemical Formula 74]

[1316]

[1317] To a solution of methyl 3-(3-(chloromethyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoate (31 mg) prepared in the same manner as Reference Example 10-(c) in acetonitrile (3 mL) was added (R)-8-ethyl-8,9,10,11-tetrahydro-[1,4]oxazepino[7,6-h]quinoline dihydrochloride (28 mg) and N,N-diisopropylethylamine (0.040 mL) in sequence at room temperature while stirring under an argon stream. The mixture was stirred at room temperature for 15 hours and then at 60°C for 2 hours. After completion of the reaction, saturated aqueous ammonium chloride was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (developing solvent: hexane:ethyl acetate) to obtain the target compound (38 mg) as a white foamy substance.

[1318] Mass spectrum (ESI, m / z): 592 [M+H] +

[1319] 1 H-NMR spectrum (400 MHz, CDCl3) δ: 8.83-8.76 (m, 1H), 8.12-8.04 (m, 1H), 7.69-7.62 (m, 1H), 7.61-7.51 (m, 1H), 7.34-7.22 (m, 2H), 7.22-7.16 (m, 1H), 7.15-7.08 (m, 1H), 7.04-6.92 (m, 2H), 5.09-5.01 (m, 1H), 4.79-4. 71(m,1H),4.42-4.32(m,1H),4.23(s,3H),4.04-3.93(m,1H),3.75-3.57(m,2H),3.46-3.36(m,3H),2.9 1-2.78(m,2H),2.73-2.65(m,3H),2.26(s,3H),1.69-1.47(m,1H),1.45-1.18(m,7H),1.04-0.95(m,3H)

[1320] Example 17-(b)

[1321] Production of 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-8-ethyl-8,9-dihydro-[1,4]oxazepino[7,6-h]quinolin-10(11H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid

[1322] [Chemical Formula 75]

[1323]

[1324] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-8-ethyl-8,9-dihydro-[1,4]oxazepino[7,6-h]quinolin-10(11H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate (38 mg) prepared in Example 17-(a) in dimethyl sulfoxide (2.5 mL), a 1M aqueous potassium hydroxide solution (0.642 mL) was added dropwise at room temperature while stirring under an argon stream, and the mixture was stirred at 70°C for 3 hours. After completion of the reaction, water (5 mL) was added and the pH was adjusted to 5.2 with 1M hydrochloric acid. The mixture was stirred at room temperature for 1 hour, and the resulting solid was separated by filtration, washed with water, and dried under reduced pressure at 60°C to obtain the title compound (27 mg) as a white solid.

[1325] Mass spectrum (ESI, m / z): 578 [M+H] +

[1326] 1 H-NMR spectrum (400MHz, CD3OD) δ: 8.75-8.67(m,1H),8.27-8.19(m,1H),7.82-7.57( m,2H),7.43-7.24(m,3H),7.18-6.99(m,3H),5.05-4.75(m,2H),4.33-4.19(m, 4H),4.04-3.89(m,1H),3.79-3.66(m,2H),2.94-2.78(m,2H),2.64-2.55(m,3 H),2.32-2.23(m,3H),1.65-1.49(m,1H),1.41-1.09(m,7H),1.03-0.93(m,3H)

[1327] Example 18-(a)

[1328] Production of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-3,4-dihydro-[1,4]oxazepino[6,7-f]quinolin-2(1H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate

[1329] [Chemical Formula 76]

[1330]

[1331] To a solution of methyl 3-(3-(chloromethyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoate (49 mg) prepared in the same manner as Reference Example 10-(c) in acetonitrile (2.5 mL) was added (R)-4-ethyl-1,2,3,4-tetrahydro-[1,4]oxazepino[6,7-f]quinoline (23 mg) prepared in Reference Example 18-(c) while stirring at room temperature under an argon stream. The mixture was stirred at room temperature for 1 hour, at 60°C for 3.5 hours, and at room temperature for 14.5 hours. After completion of the reaction, saturated aqueous ammonium chloride solution was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel column (eluting solvent; hexane:ethyl acetate) to obtain the target compound (44 mg) as a white foam.

[1332] Mass spectrum (ESI, m / z): 592 [M+H]+

[1333] 1 H-NMR spectrum (400MHz, CDCl3) δ: 8.73-8.62(m,1H),7.98-7.90(m,1H),7.65-7.41(m,3H),7.21-6.96(m,5H),4.88-4.81(m,1H),4.32-4.18(m,4H),3 .98-3.82(m,2H),3.73-3.41(m,5H),3.03-2.92(m,2H),2.81-2.74(m,3 H),2.16-2.09(m,3H),1.55(m,2H),1.39-1.23(m,6H),1.14-1.02(m,3H)

[1334] Example 18-(b)

[1335] Production of 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-3,4-dihydro-[1,4]oxazepino[6,7-f]quinolin-2(1H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid

[1336] [Chemical Formula 77]

[1337]

[1338] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-3,4-dihydro-[1,4]oxazepino[6,7-f]quinolin-2(1H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate (44 mg) prepared in Example 18-(a) in dimethyl sulfoxide (2 mL), a 1M aqueous potassium hydroxide solution (0.744 mL) was added dropwise at room temperature while stirring under an argon stream, and the mixture was stirred at 70°C for 4 hours. After completion of the reaction, the reaction solution was cooled to room temperature, water (4 mL) was added, and 1M hydrochloric acid (0.744 mL) was added, followed by stirring at room temperature for 1 hour. The resulting solid was separated by filtration, washed with water, and dried under reduced pressure at 60°C to obtain the title compound (15 mg) as a white solid.

[1339] Mass spectrum (ESI, m / z): 578 [M+H] +

[1340] 1H-NMR spectrum (400 MHz, CD3OD) δ: 8.56-8.46 (m, 1H), 7.89-7.83 (m, 1H), 7.83-7.63 (m, 1H), 7.56-7.50 (m, 1H), 7.49-7.44 (m, 1H), 7.43-7.19 (m, 3H), 7.09-6.98 (m, 2H), 4.95 -4.80(m,1H),4.31-4.20(m,4H),3.96-3.54(m,4H),3.11-2.86(m,2H),2.69-2.65 (m,3H),2.16-2.09(m,3H),1.72-1.41(m,2H),1.37-1.21(m,6H),1.12-1.03(m,3H)

[1341] Example 19-(a)

[1342] Production of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-3,4-dihydro-[1,4]oxazepino[7,6-c]quinolin-2(1H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate

[1343] [Chemical Formula 78]

[1344]

[1345] To a solution of methyl 3-(3-(chloromethyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoate (49 mg) prepared in the same manner as Reference Example 10-(c) in acetonitrile (3 mL) was added (R)-4-ethyl-1,2,3,4-tetrahydro-[1,4]oxazepino[7,6-c]quinoline dihydrochloride (56 mg) prepared in Reference Example 19-(d) and N,N-diisopropylethylamine (0.085 mL) in this order at room temperature while stirring under an argon stream. The mixture was stirred at 60°C for 2 hours and then at 80°C for 1 hour. After completion of the reaction, saturated aqueous ammonium chloride was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (developing solvent: hexane:ethyl acetate) to obtain the target compound (67 mg) as a white foamy substance.

[1346] Mass spectrum (ESI, m / z): 592 [M+H] +

[1347] Example 19-(b)

[1348] Production of 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-3,4-dihydro-[1,4]oxazepino[7,6-c]quinolin-2(1H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid

[1349] [Chemical Formula 79]

[1350]

[1351] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-3,4-dihydro-[1,4]oxazepino[7,6-c]quinolin-2(1H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate (67 mg) prepared in Example 19-(a) in dimethyl sulfoxide (3 mL), a 1M aqueous potassium hydroxide solution (1.13 mL) was added dropwise at room temperature while stirring under an argon stream, and the mixture was stirred at 70°C for 3 hours. After completion of the reaction, water (5 mL) was added to the reaction solution, and the pH was adjusted to 5.2 with 1M hydrochloric acid. The mixed solution was extracted three times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified using a silica gel column (eluting solvent: ethyl acetate: methanol) to obtain a crude product of the target compound (25 mg) as a pale yellow foam. The crude product was dissolved in methanol and purified using an ODS column (eluting solvent: water: acetonitrile). Fractions containing the target compound were combined. This solution was freeze-dried to obtain the target compound (15 mg) as a white solid.

[1352] Mass spectrum (ESI, m / z): 578 [M+H] +

[1353] 1H-NMR spectrum (400 MHz, CD3OD) δ: 8.53 (s, 1H), 7.96-7.88 (m, 1H), 7.82-7.64 (m, 1H), 7.57-7.48 (m, 1H), 7.43-7.24 (m, 3H), 7.23-7.09 (m, 2H), 7.03-6.95 (m, 1H), 5.01-4.79 (m, 1H), 4.40-4.31 (m, 1H), 4.23 (s, 3H ),3.98-3.84(m,2H),3.77-3.67(m,1H),3.67-3.56(m,1H),3.04-2.85(m,2H),2.68-2.60(m,3H),2.15 (s,3H),1.69-1.55(m,1H),1.51-1.38(m,1H),1.35-1.24(m,3H),1.22-1.15(m,3H),1.08-0.98(m,3H)

[1354] Example 20-(a)

[1355] Production of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-7-ethyl-1,7,8,10-tetrahydro-9H-[1,4]oxazepino[7,6-g]indazol-9-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate

[1356] [Chemical formula 80]

[1357]

[1358] To a dichloromethane (2 mL) solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-formyl-4-methylphenyl)-2,2-dimethylpropanoate (10 mg) prepared in the same manner as Reference Example 1-(i) and (R)-7-ethyl-7,8,9,10-tetrahydro-1H-[1,4]oxazepino[7,6-g]indazole dihydrochloride (8 mg) prepared in Reference Example 20-(d) was added N,N-diisopropylethylamine (0.010 mL) at room temperature while stirring under an argon stream. The mixture was stirred at room temperature for 1 hour. Subsequently, sodium triacetoxyborohydride (13 mg) was added at room temperature while stirring, and the mixture was stirred at room temperature for 19 hours. After completion of the reaction, saturated aqueous sodium bicarbonate solution was added to the reaction solution, and the mixture was extracted with dichloromethane. The organic layer was concentrated under reduced pressure. The obtained residue was purified by silica gel column (developing solvent; hexane:ethyl acetate) to obtain the target compound (13 mg) as a colorless oil.

[1359] Mass spectrum (ESI, m / z): 581 [M+H] +

[1360] 1 H-NMR spectrum (400 MHz, DMSO-d6) δ: 13.13-12.87 (br s,1H),8.01(s,1H),7.77-7.43(m,3H),7.16-6.95(m,3H),6.88-6.74(m ,1H),4.75-4.63(m,1H),4.44-4.32(m,1H),4.30-4.17(m,3H),4.11-3. 98(m,1H),3.88-3.71(m,1H),3.66-3.49(m,2H),3.48-3.26(m,3H),2.8 0-2.43(m,5H),2.35-2.12(m,3H),1.70-0.99(m,8H),0.95-0.71(m,3H)

[1361] Example 20-(b)

[1362] Production of 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-7-ethyl-1,7,8,10-tetrahydro-9H-[1,4]oxazepino[7,6-g]indazol-9-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid

[1363] [Chemical Formula 81]

[1364]

[1365] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-7-ethyl-1,7,8,10-tetrahydro-9H-[1,4]oxazepino[7,6-g]indazol-9-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate (12 mg) prepared in Example 20-(a) in dimethyl sulfoxide (1 mL), a 1M aqueous potassium hydroxide solution (0.210 mL) was added dropwise at room temperature while stirring, and the mixture was stirred at 70°C for 5 hours. After completion of the reaction, water (5 mL) was added to the reaction solution, and the pH was adjusted to 5.0 with 1M hydrochloric acid, followed by stirring overnight. The solid was separated by filtration, washed with water, and dried under reduced pressure at 65°C to obtain the title compound (6 mg) as a white solid.

[1366] Mass spectrum (ESI, m / z): 567 [M+H] +

[1367] 1H-NMR spectrum (400 MHz, CD3OD) δ: 7.99-7.92 (m, 1H), 7.74-7.61 (m, 1H), 7.60-7.53 (m, 1H), 7.44-7.36 (m, 1H), 7.19-7.07 (m, 2H), 7.05-7.00 (m, 1H), 6.89-6.81 (m, 1H), 5 .07-4.43(m,1H),4.32-4.21(m,4H),4.08-3.98(m,1H),3.89-3.71(m,1H),3.64( s,2H),2.87-2.59(m,5H),2.30-2.19(m,3H),1.54-1.06(m,8H),1.00-0.80(m,3H)

[1368] Example 21-(a)

[1369] Production of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-7-ethyl-1-methyl-1,7,8,10-tetrahydro-9H-[1,4]oxazepino[7,6-g]indazol-9-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate

[1370] [Chemical Formula 82]

[1371]

[1372] To a solution of methyl 3-(3-(chloromethyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoate (53 mg) prepared in the same manner as Reference Example 10-(c) in acetonitrile (2 mL) was added (R)-7-ethyl-1-methyl-7,8,9,10-tetrahydro-1H-[1,4]oxazepino[7,6-g]indazole dihydrochloride (38 mg) and N,N-diisopropylethylamine (0.065 mL) in sequence at room temperature while stirring under an argon stream. The mixture was stirred at 60°C for 5 hours and then at room temperature overnight. After completion of the reaction, the reaction solution was concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluting solvent: hexane:ethyl acetate) to obtain the title compound (77 mg) as a colorless oil.

[1373] Mass spectrum (ESI, m / z): 595 [M+H] +

[1374] 1H-NMR spectrum (400MHz, CD3OD) δ: 7.76-7.54(m,2H),7.49-7.25(m,3H),7.23-7.14( m,1H),7.10-6.99(m,1H),6.86-6.76(m,1H),4.92-4.81(m,1H),4.27-4.15(m, 4H),3.85-3.60(m,3H),3.60-3.39(m,4H),3.17-2.95(m,4H),2.87-2.64(m,4 H),2.20-2.07(m,3H),1.69-1.55(m,1H),1.53-1.16(m,7H),1.12-0.97(m,3H)

[1375] Example 21-(b)

[1376] Production of 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-7-ethyl-1-methyl-1,7,8,10-tetrahydro-9H-[1,4]oxazepino[7,6-g]indazol-9-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid

[1377] [Chemical Formula 83]

[1378]

[1379] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-7-ethyl-1-methyl-1,7,8,10-tetrahydro-9H-[1,4]oxazepino[7,6-g]indazol-9-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate (77 mg) prepared in Example 21-(a) in dimethyl sulfoxide (2 mL), a 2M aqueous potassium hydroxide solution (0.58 mL) was added while stirring at room temperature, and the mixture was stirred at 70°C for 5 hours. After completion of the reaction, 1M hydrochloric acid was added to the reaction solution to adjust the pH to around 5. The precipitated solid was filtered, washed with water, and dried under reduced pressure at 40°C to obtain the title compound (36 mg) as a white solid.

[1380] Mass spectrum (ESI, m / z): 581 [M+H] +

[1381] 1H-NMR spectrum (400 MHz, CD3OD) δ: 7.77-7.59 (m, 2H), 7.52-7.47 (m, 1H), 7.44-7.19 (m, 3H), 7.12-7.04 (m, 1H), 6.88-6.82 (m, 1H), 4.98-4.77 (m, 1H), 4.32-4.22 (m, 4H), 3.86-3.71 (m, 3H),3.61-3.52(m,1H),3.16-3.06(m,4H),2.93-2.84(m,1H),2.78-2.69(m,3H),2.22- 2.13(m,3H),1.72-1.59(m,1H),1.56-1.44(m,1H),1.39-1.18(m,6H),1.14-1.04(m,3H)

[1382] Example 22-(a)

[1383] Production of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-7-ethyl-2-methyl-2,7,8,10-tetrahydro-9H-[1,4]oxazepino[7,6-g]indazol-9-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate

[1384] [Chemical formula 84]

[1385]

[1386] To a solution of methyl 3-(3-(chloromethyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoate (42 mg) prepared in the same manner as Reference Example 10-(c) in acetonitrile (2 mL) was added (R)-7-ethyl-2-methyl-7,8,9,10-tetrahydro-2H-[1,4]oxazepino[7,6-g]indazole dihydrochloride (30 mg) and N,N-diisopropylethylamine (0.052 mL) in sequence at room temperature while stirring under an argon stream. The mixture was stirred at 60°C for 5 hours and then at room temperature overnight. After completion of the reaction, the reaction solution was concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluting solvent: hexane:ethyl acetate) to obtain the title compound (40 mg) as a pale yellow oil.

[1387] Mass spectrum (ESI, m / z): 595 [M+H] +

[1388] 1H-NMR spectrum (400 MHz, CD3OD) δ: 8.07-7.98 (m, 1H), 7.69-7.54 (m, 1H), 7.52-7.43 (m, 1H), 7.40-7.30 (m, 1H), 7.20-6.99 (m, 3H), 6.84-6.73 (m, 1H), 4.82-4.75 (m, 1H), 4.44-4.31 (m, 1H), 4.27-4.15 (m, 3H),4.13-4.04(m,3H),4.03-3.95(m,1H),3.93-3.77(m,1H),3.73-3.59(m,2H),3.45-3.35(m,3 H),2.83-2.55(m,5H),2.32-2.20(m,3H),1.54-1.40(m,1H),1.36-1.12(m,7H),0.99-0.80(m,3H)

[1389] Example 22-(b)

[1390] Production of 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-7-ethyl-2-methyl-2,7,8,10-tetrahydro-9H-[1,4]oxazepino[7,6-g]indazol-9-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid

[1391] [Chemical Formula 85]

[1392]

[1393] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-7-ethyl-2-methyl-2,7,8,10-tetrahydro-9H-[1,4]oxazepino[7,6-g]indazol-9-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate (40 mg) prepared in Example 22-(a) in dimethyl sulfoxide (8 mL), a 2M aqueous potassium hydroxide solution (0.30 mL) was added while stirring at room temperature, and the mixture was stirred at 70°C for 5 hours. After completion of the reaction, 1M hydrochloric acid was added to the reaction solution to adjust the pH to around 5, and the precipitated solid was separated by filtration. The filtrate was concentrated, and the resulting residue was combined with the solid and purified using Bond Elut (elution solvent; water:acetonitrile). The fraction containing the target product was then freeze-dried. The obtained residue was purified by preparative chromatography (apparatus name: LC-Forte / R, column: T-2000, eluent: acetone). The fractions containing the target product were concentrated under reduced pressure, and the obtained residue was dissolved in a mixed solvent of acetonitrile / water and freeze-dried to obtain the target compound (8 mg) as a pale yellow solid.

[1394] Mass spectrum (ESI, m / z): 581 [M+H] +

[1395] 1 H-NMR spectrum (400 MHz, CD3OD) δ: 8.10-8.03 (m, 1H), 7.76-7.61 (m, 1H), 7.53-7.46 (m, 1H), 7.41-7.35 (m, 1H), 7.18-7.02 (m, 3H), 6.83-6.77 (m, 1H), 4.96-4.79 (m, 1H), 4.47-4.37 (m, 1H), 4 .25(s,3H),4.15-4.08(m,3H),4.05-3.96(m,1H),3.94-3.76(m,1H),3.75-3.66(m,2H),2. 88-2.68(m,2H),2.64-2.59(m,3H),2.31-2.25(m,3H),1.55-1.15(m,8H),0.97-0.88(m,3H)

[1396] Example 23

[1397] Production of 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-1,3,4,9,10,11-hexahydro-2H-pyrimido[1',2':1,6]pyrido[2,3-f][1,4]oxazepin-2-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid

[1398] [Chemical Formula 86]

[1399]

[1400] A solution of 3-(3-(((R)-7-((3-chloropropyl)amino)-2-ethyl-2,3-dihydropyrido[2,3-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid (50 mg) prepared in Reference Example 23-(h) in acetonitrile (4 mL) was stirred at 90°C for 4.5 hours under an argon stream. After completion of the reaction, triethylamine (0.010 mL) was added and stirred, and the reaction solution was concentrated under reduced pressure. The resulting residue was purified using Bond Elut (elution solvent; water:acetonitrile), and the fraction containing the target compound was concentrated under reduced pressure to obtain the target compound (42 mg) as a yellow solid.

[1401] Mass spectrum (DUIS, m / z): 583 [M+H] +

[1402] 1 H-NMR spectrum (400MHz, CD3OD) δ: 7.70-7.53(m,1H),7.51-7.26(m,3H),7.17-6.99(m,2H),6.72-6.65(m,1H),4.94-4.79(m,1H),4.30-4.25(m, 3H),3.98-3.39(m,7H),3.24-2.99(m,2H),2.89-2.76(m,5H),2.28-2.22(m,3H),1.95-1.45(m,4H),1.41-1.16(m,6H),1.08-0.98(m,3H)

[1403] Example 24-(a)

[1404] Production of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydronaphtho[2,1-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate

[1405] [Chemical Formula 87]

[1406]

[1407] To a solution of methyl 3-(3-(chloromethyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoate (51 mg) in acetonitrile (2 mL), (R)-2-ethyl-2,3,4,5-tetrahydronaphtho[2,1-f][1,4]oxazepine (27 mg) and N,N-diisopropylethylamine (0.062 mL) prepared in Reference Example 24-(c) were added sequentially at room temperature while stirring under an argon stream. The mixture was stirred at 60°C for 5 hours and then at room temperature overnight. After completion of the reaction, the reaction solution was concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluting solvent: hexane:ethyl acetate) to obtain the title compound (51 mg) as a pale yellow foam.

[1408] Mass spectrum (ESI, m / z): 591 [M+H] +

[1409] 1 H-NMR spectrum (400 MHz, DMSO-d6) δ: 8.30-8.21 (m, 1H), 7.92-7.85 (m, 1H), 7.61-7.47 (m, 4H), 7.46-7.37 (m, 1H), 7.17-6.90 (m, 4H), 4.75 (s, 1H), 4.32-4.19 (m, 3H), 4.0 4-3.86(m,2H),3.79-3.66(m,1H),3.63-3.11(m,5H),2.97-2.81(m,2H),2.75-2 .38(m,3H),2.22(s,3H),1.80-1.63(m,1H),1.54-1.12(m,7H),1.10-0.99(m,3H)

[1410] Example 24-(b)

[1411] Production of 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydronaphtho[2,1-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid

[1412] [Chemical Formula 88]

[1413]

[1414] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydronaphtho[2,1-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate (50 mg) prepared in Example 24-(a) in dimethyl sulfoxide (2 mL), a 2M aqueous potassium hydroxide solution (0.402 mL) was added at room temperature while stirring, and the mixture was stirred at 70°C for 3 hours. After completion of the reaction, water was added to the reaction solution, and the pH was adjusted to approximately 5.6 with 2M hydrochloric acid. The mixture was stirred at room temperature for 1 hour. The resulting solid was separated by filtration, washed with water, dried under reduced pressure, and air-dried overnight to obtain the title compound (45 mg) as a white solid.

[1415] Mass spectrum (ESI, m / z): 577 [M+H] +

[1416] 1 H-NMR spectrum (400 MHz, CD3OD) δ: 8.36-8.23 (m, 1H), 7.90-7.65 (m, 2H), 7.56-7.19 (m, 5H), 7.18-7.00 (m, 2H), 6.90-6.61 (m, 1H), 5.04-4.71 (m, 1H), 4.33-4.18 (m, 3H), 4.03 -3.80(m,2H),3.80-3.52(m,3H),3.07-2.83(m,2H),2.82-2.64(m,3H),2.38-2.21 (m,3H),1.83-1.68(m,1H),1.59-1.46(m,1H),1.44-1.19(m,6H),1.14-1.01(m,3H)

[1417] Example 25-(a)

[1418] Production of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-c]isoquinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate

[1419] [Chemical Formula 89]

[1420]

[1421] To a solution of methyl 3-(3-(chloromethyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoate (32 mg) prepared in the same manner as Reference Example 10-(c) in acetonitrile (3 mL) was added (R)-2-ethyl-2,3,4,5-tetrahydro-[1,4]oxazepino[6,7-c]isoquinoline dihydrochloride (29 mg) prepared in Reference Example 25-(c) and N,N-diisopropylethylamine (0.041 mL) in this order at room temperature while stirring under an argon stream. The mixture was stirred at 60°C for 2 hours and then at 80°C for 1 hour. After completion of the reaction, saturated aqueous ammonium chloride was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (developing solvent: hexane:ethyl acetate) to obtain the target compound (47 mg) as a white foamy substance.

[1422] Mass spectrum (DUIS, m / z): 592 [M+H] +

[1423] 1 H-NMR spectrum (400 MHz, CDCl3) δ: 8.90 (s, 1H), 8.32-8.23 (m, 1H), 8.00-7.92 (m, 1H), 7.76-7.55 (m, 3H), 7.22-7.15 (m, 1H), 7.12-6.99 (m, 3H), 4.85-4.77 (m, 1H), 4.28-4.17 (m, 5H), 4.05 -3.86(m,1H),3.70-3.51(m,2H),3.47-3.39(m,3H),2.95-2.85(m,2H),2.80-2.72(m,3H) ,2.28(s,3H),1.83-1.70(m,1H),1.61-1.40(m,1H),1.40-1.19(m,6H),1.14-1.02(m,3H)

[1424] Example 25-(b)

[1425] Production of 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-c]isoquinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid

[1426] [Chemical formula 90]

[1427]

[1428] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-c]isoquinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate (47 mg) prepared in Example 25-(a) in dimethyl sulfoxide (2.5 mL), a 1M aqueous potassium hydroxide solution (0.794 mL) was added dropwise at room temperature while stirring under an argon stream, and the mixture was stirred at 70°C for 3 hours. After completion of the reaction, water (5 mL) was added, and 1M hydrochloric acid was added to the reaction solution to adjust the pH to 5.2, followed by stirring at room temperature for 15 hours. The resulting solid was separated by filtration, washed with water, and dried under reduced pressure at 60°C to obtain the title compound (40 mg) as a white solid.

[1429] Mass spectrum (DUIS, m / z): 578 [M+H] +

[1430] 1 H-NMR spectrum (400 MHz, CD3OD) δ: 8.90-8.80 (m, 1H), 8.32-8.25 (m, 1H), 8.12-8.05 (m, 1H), 7.85-7.63 (m, 3H), 7.42-7.31 (m, 1H), 7.19-7.11 (m, 2H), 7.09-7.03 (m, 1H), 4.91-4.79 (m, 1H), 4.26 -4.06(m,5H),4.06-3.88(m,1H),3.72-3.56(m,2H),3.02-2.82(m,2H),2.72-2.62(m,3H),2 .30-2.24(m,3H),1.80-1.65(m,1H),1.56-1.40(m,1H),1.39-1.21(m,6H),1.11-1.00(m,3H)

[1431] Example 26-(a)

[1432] Production of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-c]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate

[1433] [Chemical Formula 91]

[1434]

[1435] To a solution of methyl 3-(3-(chloromethyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoate (36 mg) prepared in the same manner as Reference Example 10-(c) in acetonitrile (3 mL) was added (R)-2-ethyl-2,3,4,5-tetrahydro-[1,4]oxazepino[6,7-c]quinoline dihydrochloride (32 mg) prepared in Reference Example 26-(c) and N,N-diisopropylethylamine (0.046 mL) in this order at room temperature while stirring under an argon stream. The mixture was stirred at 60°C for 2 hours and then at 80°C for 1 hour. After completion of the reaction, saturated aqueous ammonium chloride was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (developing solvent: hexane:ethyl acetate) to obtain the target compound (36 mg) as a white foamy substance.

[1436] As another method, the target compound was produced by the following method.

[1437] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-formyl-4-methylphenyl)-2,2-dimethylpropanoate (225 mg) prepared in the same manner as Reference Example 1-(i) in dichloromethane (5 mL) was added (R)-2-ethyl-2,3,4,5-tetrahydro-[1,4]oxazepino[6,7-c]quinoline (142 mg) prepared in Reference Example 26-(h) while stirring at room temperature under an argon stream. The mixture was stirred at room temperature for 30 minutes. Subsequently, sodium triacetoxyborohydride (251 mg) was added while stirring at room temperature, and the mixture was stirred at room temperature for 10 hours. After completion of the reaction, saturated aqueous sodium bicarbonate solution was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (elution solvent: hexane:ethyl acetate) to obtain the target compound (388 mg) as a white foamy substance.

[1438] Mass spectrum (ESI, m / z): 592 [M+H] +

[1439] 1H-NMR spectrum (400 MHz, CDCl3) δ: 8.46-8.33 (m, 1H), 8.32-8.26 (m, 1H), 8.10-8.01 (m, 1H), 7.75-7.65 (m, 1H), 7.62-7.50 (m, 2H), 7.23-7.16 (m, 1H), 7.11-7.00 (m, 3H), 4.87-4.80 (m, 1H), 4.27-4.19 (m, 3H), 4.19 -4.06(m,1H),4.03-3.83(m,2H),3.66-3.51(m,2H),3.49-3.42(m,3H),3.03-2.90(m,2H),2.80-2.73 (m,3H),2.30-2.21(m,3H),1.88-1.74(m,1H),1.65-1.48(m,1H),1.43-1.22(m,6H),1.14-1.04(m,3H)

[1440] Example 26-(b)

[1441] Production of 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-c]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid

[1442] [Chemical Formula 92]

[1443]

[1444] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-c]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate (36 mg) prepared in Example 26-(a) in dimethyl sulfoxide (2.5 mL), a 1M aqueous potassium hydroxide solution (0.608 mL) was added dropwise at room temperature while stirring under an argon stream, and the mixture was stirred at 70°C for 3 hours. After completion of the reaction, water (5 mL) was added, and 1M hydrochloric acid was added to the reaction solution to adjust the pH to 5.2. The mixture was stirred at room temperature for 1 hour, and the precipitated solid was separated by filtration, washed with water, and dried under reduced pressure at 60°C to obtain the title compound (31 mg) as a white solid.

[1445] Mass spectrum (ESI, m / z): 578 [M+H] +

[1446] 1H-NMR spectrum (400 MHz, CD3OD) δ: 8.41-8.27 (m, 2H), 8.01-7.93 (m, 1H), 7.80-7.56 (m, 3H), 7.41-7.27 (m, 1H), 7.21-7.11 (m, 2H), 7.11-7.03 (m, 1H), 4.95-4.80 (m, 1H), 4.29-4.15 (m, 4H), 4 .11-3.98(m,1H),3.90-3.79(m,1H),3.72-3.60(m,2H),3.04-2.87(m,2H),2.73-2.63(m,3 H),2.27(s,3H),1.82-1.68(m,1H),1.64-1.49(m,1H),1.41-1.23(m,6H),1.10-1.00(m,3H)

[1447] Example 27-(a)

[1448] Production of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-h]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate

[1449] [Chemical Formula 93]

[1450]

[1451] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(hydroxymethyl)-4-methylphenyl)-2,2-dimethylpropanoate (50 mg) prepared in the same manner as Reference Example 1-(h) in dichloromethane (2 mL) was added thionyl chloride (0.011 mL) at room temperature under an argon stream, and the mixture was stirred at room temperature for 1 hour. Thionyl chloride (0.003 mL) was further added, and after completion of the reaction, the reaction solution was concentrated under reduced pressure. Acetonitrile (2 mL) was added to the resulting residue, followed by (R)-2-ethyl-2,3,4,5-tetrahydro-[1,4]oxazepino[6,7-h]quinoline dihydrochloride (40 mg) prepared in Reference Example 27-(c) and N,N-diisopropylethylamine (69 mL) at room temperature, and the mixture was stirred at 80°C for 7 hours. After the reaction, ethyl acetate was added to the reaction solution, which was washed with water and saturated brine in sequence, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by silica gel column (eluting solvent: hexane:ethyl acetate) to obtain the title compound (60 mg) as a white foam.

[1452] Mass spectrum (ESI, m / z): 592 [M+H] +

[1453] 1 H-NMR spectrum (400 MHz, CD3OD) δ: 8.88-8.81 (m, 1H), 8.33-8.24 (m, 1H), 7.69-7.59 (m, 1H), 7.55-7.47 (m, 1H), 7.47-7.29 (m, 2H), 7.20-7.12 (m, 1H), 7.11-7.04 (m, 2H), 7.01-6.83 (m, 1H), 4.90-4.85 (m, 1H), 4.27-4.22 (m, 3H), 4.04 -3.89(m,2H),3.86-3.70(m,1H),3.69-3.55(m,2H),3.47-3.43(m,3H),3.06-2.90(m,2H),2.75-2.65(m,3H),2 .31-2.24(m,3H),1.87-1.73(m,1H),1.60-1.45(m,1H),1.42-1.36(m,3H),1.31-1.27(m,3H),1.00-0.93(m,3H)

[1454] Example 27-(b)

[1455] Production of 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-h]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid

[1456] [Chemical Formula 94]

[1457]

[1458] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-h]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate (55 mg) prepared in Example 27-(a) in dimethyl sulfoxide (3 mL), a 1M aqueous potassium hydroxide solution (0.232 mL) was added dropwise at room temperature while stirring, and the mixture was stirred at 75°C for 6 hours. After completion of the reaction, 1M hydrochloric acid was added to the reaction solution to adjust the pH to 5.5. The mixed solution was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified using a silica gel column (DIOL silica gel, elution solvent; hexane:ethyl acetate), and the fraction containing the target product was concentrated under reduced pressure. A small amount of acetonitrile was added to the obtained residue to dissolve it, and then water was added to precipitate a solid. The solid was separated by filtration, washed with water, and dried under reduced pressure at 60°C to obtain the target compound (27 mg) as a white solid.

[1459] Mass spectrum (ESI, m / z): 578 [M+H] +

[1460] 1 H-NMR spectrum (400 MHz, CD3OD) δ: 8.87-8.82 (m, 1H), 8.32-8.26 (m, 1H), 7.72-7.65 (m, 1H), 7.53-7.48 (m, 1H), 7.47-7.29 (m, 2H), 7.26-7.18 (m, 1H), 7.11-7.05 (m, 2H), 7.03-6.83 (m, 1H), 4.94-4.90 (m, 1H), 4.26-4.21 (m,3H),4.04-3.90(m,2H),3.88-3.72(m,1H),3.69-3.56(m,2H),3.07-2.91(m,2H),2.75-2.67(m,3H),2 .31-2.25(m,3H),1.87-1.74(m,1H),1.60-1.44(m,1H),1.38(s,3H),1.30-1.24(m,3H),1.00-0.93(m,3H)

[1461] Example 28-(a)

[1462] Production of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-f]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate

[1463] [Chemical Formula 95]

[1464]

[1465] To a solution of methyl 3-(3-(chloromethyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoate (52 mg) prepared in the same manner as Reference Example 10-(c) in acetonitrile (2.5 mL) was added (R)-2-ethyl-2,3,4,5-tetrahydro-[1,4]oxazepino[7,6-f]quinoline (72 mg) prepared in Reference Example 28-(b) and N,N-diisopropylethylamine (0.045 mL) at room temperature while stirring under an argon stream. The mixture was stirred at 60°C for 3 hours. After completion of the reaction, saturated aqueous ammonium chloride was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (developing solvent: hexane:ethyl acetate) to obtain the target compound (53 mg) as a white foamy substance.

[1466] Mass spectrum (ESI, m / z): 592 [M+H] +

[1467] 1 H-NMR spectrum (400 MHz, CDCl3) δ: 8.93-8.86 (m, 1H), 8.69-8.61 (m, 1H), 7.72-7.56 (m, 2H), 7.46-7.37 (m, 1H), 7.31-6.98 (m, 5H), 4.87-4.79 (m, 1H), 4.29-4.19 (m, 3H), 4.08-3.89 (m, 2H),3.84-3.69(m,1H),3.63-3.39(m,5H),3.05-2.93(m,2H),2.84-2.74(m,3H),2.31- 2.19(m,3H),1.89-1.75(m,1H),1.66-1.47(m,1H),1.44-1.29(m,6H),1.17-1.05(m,3H)

[1468] Example 28-(b)

[1469] Production of 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-f]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid

[1470] [Chemical Formula 96]

[1471]

[1472] To a solution of methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-f]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoate (53 mg) prepared in Example 28-(a) in dimethyl sulfoxide (1.8 mL), a 1M aqueous potassium hydroxide solution (0.896 mL) was added dropwise at room temperature while stirring under an argon stream, and the mixture was stirred at 70°C for 4 hours. After completion of the reaction, 1M hydrochloric acid was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified on a silica gel column (DIOL silica gel, eluting solvent; hexane:ethyl acetate) to obtain the target compound (20 mg) as a white solid.

[1473] Mass spectrum (ESI, m / z): 578 [M+H] +

[1474] 1 H-NMR spectrum (400 MHz, CD3OD) δ: 8.84-8.78 (m, 1H), 8.76-8.68 (m, 1H), 7.76-7.68 (m, 1H), 7.58-7.49 (m, 2H), 7.48-7.40 (m, 1H), 7.26-7.00 (m, 4H), 4.95-4.81 (m, 1H), 4.30-4.21 (m,3H),4.03-3.88(m,2H),3.86-3.75(m,1H),3.65-3.52(m,2H),3.06-2.86(m,2H),2 .74-2.66(m,3H),2.28(s,3H),1.83-1.44(m,2H),1.42-1.19(m,6H),1.11-1.01(m,3H)

[1475] Example 29

[1476] 3-(1,4-Dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-6-ethyl-2,2-difluoro-6,7-dihydro-[1,3]dioxolano[4',5':4,5]benzo[1,2-f][1,4]oxazepin-8(9H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Diastereomer 1)

[1477] and

[1478] Example 30

[1479] 3-(1,4-Dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-6-ethyl-2,2-difluoro-6,7-dihydro-[1,3]dioxolano[4',5':4,5]benzo[1,2-f][1,4]oxazepin-8(9H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Diastereomer 2)

[1480] [Chemical Formula 97]

[1481]

[1482] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-6-ethyl-2,2-difluoro-6,7-dihydro-[1,3]dioxolano[4',5':4,5]benzo[1,2-f][1,4]oxazepin-8(9H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (275 mg) produced in the same manner as in Example 1-(b) was separated and purified by supercritical fluid chromatography (column: CHIRALPAK IG, mobile phase: CO2:methanol = 85:15). The fraction containing the first-eluting diastereomer was concentrated under reduced pressure, and the resulting residue was dissolved in a mixed solvent of acetonitrile / water and freeze-dried to obtain the compound of Example 29 (93 mg) as a white solid. Separately, the fraction containing the later-eluting diastereomer was concentrated under reduced pressure, and the obtained residue was dissolved in a mixed solvent of acetonitrile / water and freeze-dried to obtain the compound of Example 30 (97 mg) as a white solid.

[1483] (High Performance Liquid Chromatography Analysis)

[1484] Column: CHIRALPAK IC-3 4.6×150mm

[1485] Eluent: 0.1% formic acid aqueous solution / acetonitrile, acetonitrile ratio (%) = 10 (0 min) → 90 (10 min)

[1486] Flow rate: 0.8 mL / min

[1487] Temperature: 40℃

[1488] Detection wavelength: 254nm

[1489] Retention time: 7.59 min for Example 29, 8.03 min for Example 30

[1490] (Example 29)

[1491] Mass spectrum (ESI, m / z): 607 [M+H] +

[1492] 1 H-NMR spectrum (400MHz, CD3OD) δ: 7.74 (d, J = 8.9 Hz, 1H), 7.50 (d, J = 8.9 Hz, 1H), 7.20 (dd, J = 1.9, 7.9 Hz, 1H), 7.0 8(d,J=7.9Hz,1H),6.98(d,J=1.9Hz,1H),6.85(s,1H),6.68(s,1H),4.98-4.75(m,1H),4.27(s,3H),3.88( d,J=14.2Hz,1H),3.72-3.61(m,1H),3.56(d,J=14.2Hz,1H),3.54-3.43(m,2H),2.89-2.71(m,2H),2.70( s,3H),2.27(s,3H),1.51-1.38(m,1H),1.37(s,3H),1.27(s,3H),1.25-1.14(m,1H),0.93(t,J=7.3Hz,3H)

[1493] (Example 30)

[1494] Mass spectrum (ESI, m / z): 607 [M+H] +

[1495] 1H-NMR spectrum (400MHz, CD3OD) δ: 7.70 (d, J = 8.9 Hz, 1H), 7.48 (d, J = 8.9 Hz, 1H), 7.21 (dd, J = 1.7, 7.8 Hz, 1H) ,7.08(d,J=7.8Hz,1H),6.99(d,J=1.7Hz,1H),6.86(s,1H),6.63(s,1H),4.96-4.76(m,1H),4.27(s,3 H),3.86(d,J=14.3Hz,1H),3.77-3.67(m,1H),3.56-3.45(m,3H),2.90-2.81(m,1H),2.80-2.71(m,1H ),2.71(s,3H),2.26(s,3H),1.53-1.40(m,1H),1.37(s,3H),1.31-1.19(m,4H),0.96(t,J=7.3Hz,3H)

[1496] Example 31

[1497] 3-(1,4-Dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,5,7,8,9-hexahydro-4H-indeno[5,6-f][1,4]oxazepin-4-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Diastereomer 1)

[1498] and

[1499] Example 32

[1500] 3-(1,4-Dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,5,7,8,9-hexahydro-4H-indeno[5,6-f][1,4]oxazepin-4-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Diastereomer 2)

[1501] [Chemical Formula 98]

[1502]

[1503] 3-(1,4-Dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,5,7,8,9-hexahydro-4H-indeno[5,6-f][1,4]oxazepin-4-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (243 mg) produced in the same manner as in Example 3-(b) was separated and purified by supercritical fluid chromatography (column: CHIRALPAK IB, mobile phase: CO2:methanol, methanol ratio (%) = 30 (0 min) → 10 (3 min) → 10 (28 min) → 30 (28.1 min) → 30 (30 min)). The fraction containing the first-eluting diastereomer was concentrated under reduced pressure, and the resulting residue was dissolved in a mixed solvent of acetonitrile / water and freeze-dried to obtain the compound of Example 31 (103 mg) as a white solid. Separately, the fraction containing the later-eluting diastereomer was concentrated under reduced pressure, and the resulting residue was dissolved in a mixed solvent of acetonitrile / water and freeze-dried to obtain the compound of Example 32 (108 mg) as a white solid.

[1504] (High Performance Liquid Chromatography Analysis)

[1505] Column: CHIRALPAK IC-3 4.6×150mm

[1506] Eluent: 0.1% formic acid aqueous solution / acetonitrile, acetonitrile ratio (%) = 20 (0 min) → 60 (10 min) → 60 (15 min)

[1507] Flow rate: 0.8 mL / min

[1508] Temperature: 40℃

[1509] Detection wavelength: 254nm

[1510] Retention time: 8.61 min for Example 31, 9.06 min for Example 32

[1511] (Example 31)

[1512] Mass spectrum (ESI, m / z): 567 [M+H] +

[1513] 1H-NMR spectrum (400 MHz, CD3OD) δ: 7.76 (d, J = 8.7 Hz, 1H), 7.47 (d, J = 8.7 Hz, 1H), 7.20-7.15 (m, 1H), 7.08-7.04 (m, 1H), 7.02-6.98 (m, 1H), 6.80 (s, 1H), 6.67 (s, 1H), 4.86 (m, 1H) ,4.26(s,3H),3.83(d,J=13.8Hz,1H),3.64-3.56(m,1H),3.55-3.45(m,3H),2.89-2 .67(m,9H),2.26(s,3H),2.11-2.01(m,2H),1.49-1.10(m,8H),0.94(t,J=7.4Hz,3H)

[1514] (Example 32)

[1515] Mass spectrum (ESI, m / z): 567 [M+H] +

[1516] 1 H-NMR spectrum (400 MHz, CD3OD) δ: 7.70 (d, J = 8.8 Hz, 1H), 7.46 (d, J = 8.8 Hz, 1H), 7.22-7.15 (m, 1H), 7.11-7.02 (m, 2H), 6.85-6.78 (m, 2H), 4.87 (m, 1H), 4.27 (s, 3H), 3.86 (d, J = 13.8 Hz, 1H), 3.70-3.45 (m, 4H), 2.91-2.67 (m, 9H), 2.25 (s, 3H), 2.13-2.01 (m, 2H), 1.52-1.16 (m, 8H), 0.96 (t, J = 7.4 Hz, 3H)

[1517] Example 33

[1518] 3-(1,4-Dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,7,8,9,10-hexahydronaphtho[2,3-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Diastereomer 1)

[1519] and

[1520] Example 34

[1521] 3-(1,4-Dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,7,8,9,10-hexahydronaphtho[2,3-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (Diastereomer 2)

[1522] [Chemical Formula 99]

[1523]

[1524] 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,7,8,9,10-hexahydronaphtho[2,3-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid (272 mg) produced in the same manner as in Example 4-(b) was separated and purified by supercritical fluid chromatography (column: CHIRALPAK IB, mobile phase: CO2:methanol, methanol ratio (%) = 30 (0 min) → 5 (7 min) → 5 (15 min) → 30 (16 min) → 30 (19 min)). The fraction containing the first-eluting diastereomer was concentrated under reduced pressure, and the resulting residue was dissolved in a mixed solvent of acetonitrile / water and freeze-dried to obtain the compound of Example 33 (111 mg) as a white solid. Separately, the fraction containing the later-eluting diastereomer was concentrated under reduced pressure, and the obtained residue was dissolved in a mixed solvent of acetonitrile / water and freeze-dried to obtain the compound of Example 34 (109 mg) as a white solid.

[1525] (High Performance Liquid Chromatography Analysis)

[1526] Column: CHIRALPAK IG-3 4.6×150mm

[1527] Eluent: Hexane / ethanol, ethanol ratio (%) = 10 (0 min) → 90 (10 min) → 90 (15 min) Flow rate: 0.8 mL / min

[1528] Temperature: 40℃

[1529] Detection wavelength: 254nm ...

Claims

1. A compound represented by the following general formula (I-1) or a pharmaceutically acceptable salt thereof, In the formula, R is a hydrogen atom; R 1 and R 2 Each is independently a hydrogen atom or an alkyl group having 1 to 6 carbon atoms; Or, R 1 and R 2 Together with the carbon atoms to which they are bonded, they form a saturated monocyclic hydrocarbon ring having 3 to 8 ring carbon atoms; R 3 is a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, or an alkoxy group having 1 to 6 carbon atoms; R 4 and R 6 Each is independently a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, or an alkoxy group having 1 to 6 carbon atoms; R 5 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms; A has a structure represented by any one of the following formulae (II-1) to (II-3), In the formula, R 7 and R 8 Each is independently a hydrogen atom or an alkyl group having 1 to 6 carbon atoms; Or, R 7 and R 8 Together with the carbon atoms to which they are bonded, they form a saturated monocyclic hydrocarbon ring having 3 to 8 ring carbon atoms; X 1 and X 2 Each independently is CR 9 or nitrogen atoms; R 9 are each independently a hydrogen atom or a halogen atom; Ring D is a 5- to 6-membered monocyclic carbocyclic ring, or a 5- to 6-membered monocyclic heterocyclic ring containing 1 to 4 heteroatoms selected from oxygen atoms, sulfur atoms and nitrogen atoms in addition to carbon atoms, each of which is optionally substituted by 1 to 5 substituents independently selected from the group consisting of a halogen atom, an alkyl group having 1 to 6 carbon atoms, or an alkoxy group having 1 to 6 carbon atoms; mark Indicates the point of bonding to the rest of the molecule.

2. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R is a hydrogen atom; R 1 and R 2 Each is independently a hydrogen atom or an alkyl group having 1 to 6 carbon atoms; Or, R 1 and R 2 Together with the carbon atoms to which they are bonded, they form a saturated monocyclic hydrocarbon ring having 3 to 8 ring carbon atoms; R 3 is an alkyl group having 1 to 6 carbon atoms; R 4 is an alkyl group having 1 to 6 carbon atoms; R 5 is an alkyl group having 1 to 6 carbon atoms; R 6 A hydrogen atom.

3. The compound according to claim 1 or 2 or a pharmaceutically acceptable salt thereof, wherein: A has a structure represented by any one of the following formulae (II-1-1) to (II-3-4), In the formula, R 7 and R 8 Each is independently a hydrogen atom or an alkyl group having 1 to 6 carbon atoms; Or, R 7 and R 8 Together with the carbon atoms to which they are bonded, they form a saturated monocyclic hydrocarbon ring having 3 to 8 ring carbon atoms; X 1 and X 2 Each independently is CR 9 or nitrogen atoms; Y 1 , Y 2 , Y 3 , and Y 4 Each independently is CR 10 or nitrogen atoms; R 9 are each independently a hydrogen atom or a halogen atom; R 10 Each is independently a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, or an alkoxy group having 1 to 6 carbon atoms; Q 1 and Q 2 Each independently is CR 11 R 12 NR 13 , oxygen atoms, or sulfur atoms; R 11 and R 12 Each is independently a hydrogen atom, a halogen atom, or an alkyl group having 1 to 6 carbon atoms; R 13 Each is independently a hydrogen atom or an alkyl group having 1 to 6 carbon atoms; Z is NR 14 , oxygen atoms, or sulfur atoms; R 14 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms; Q 3 For (with 1 U 2 ) n ; U 1 and U 2 Each is independently a hydrogen atom, a halogen atom, or an alkyl group having 1 to 6 carbon atoms; n is 1 or 2.

4. The compound according to claim 3 or a pharmaceutically acceptable salt thereof, wherein A has a structure represented by the following formula (II-1-1), In the formula, R 7 and R 8 Each is independently a hydrogen atom or an alkyl group having 1 to 6 carbon atoms; Or, R 7 and R 8 Together with the carbon atoms to which they are bonded, they form a saturated monocyclic hydrocarbon ring having 3 to 8 ring carbon atoms; X 1 and X 2 Each independently is CR 9 ; Y 1 , Y 2 , Y 3 , and Y 4 Any one of them is a nitrogen atom, and the other three are each independently CR 10 ; R 9 They are hydrogen atoms; R 10 Each is independently a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, or an alkoxy group having 1 to 6 carbon atoms.

5. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, which is represented by the following general formula (I-1-1): In the formula, R is a hydrogen atom; R 1 and R 2 Each is independently a hydrogen atom or an alkyl group having 1 to 6 carbon atoms; Or, R 1 and R 2 Together with the carbon atoms to which they are bonded, they form a saturated monocyclic hydrocarbon ring having 3 to 8 ring carbon atoms; R 3 is a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, or an alkoxy group having 1 to 6 carbon atoms; R 4 and R 6 Each is independently a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, or an alkoxy group having 1 to 6 carbon atoms; R 5 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms; R 7 and R 8 Each is independently a hydrogen atom or an alkyl group having 1 to 6 carbon atoms; Or, R 7 and R 8 Together with the carbon atoms to which they are bonded, they form a saturated monocyclic hydrocarbon ring having 3 to 8 ring carbon atoms; R 10 It is a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, or an alkoxy group having 1 to 6 carbon atoms.

6. The compound according to claim 5 or a pharmaceutically acceptable salt thereof, wherein R is a hydrogen atom; R 1 and R 2 Each is independently a hydrogen atom or an alkyl group having 1 to 6 carbon atoms; Or, R 1 and R 2 Together with the carbon atoms to which they are bonded, they form a saturated monocyclic hydrocarbon ring having 3 to 8 ring carbon atoms; R 3 is a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, or an alkoxy group having 1 to 6 carbon atoms; R 4 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms; R 5 is an alkyl group having 1 to 6 carbon atoms; R 6 is a hydrogen atom; R 7 and R 8 Each is independently a hydrogen atom or an alkyl group having 1 to 6 carbon atoms; Or, R 7 and R 8 Together with the carbon atoms to which they are bonded, they form a saturated monocyclic hydrocarbon ring having 3 to 8 ring carbon atoms; R 10 It is a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, or an alkoxy group having 1 to 6 carbon atoms.

7. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of: 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-6-ethyl-2,2-difluoro-6,7-dihydro-[1,3]dioxolano[4',5':4,5]benzo[1,2-f][1,4]oxazepin-8(9H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-6-ethyl-2,2-difluoro-6,7-dihydro-[1,3]dioxolano[4',5':4,5]benzo[1,2-f][1,4]oxazepin-8(9H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-9-ethyl-2,2-difluoro-8,9-dihydro-[1,3]dioxolano[4',5':3,4]benzo[1,2-f][1,4]oxazepin-7(6H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-9-ethyl-2,2-difluoro-8,9-dihydro-[1,3]dioxolano[4',5':3,4]benzo[1,2-f][1,4]oxazepin-7(6H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,5,7,8,9-hexahydro-4H-indeno[5,6-f][1,4]oxazepin-4-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,5,7,8,9-hexahydro-4H-indeno[5,6-f][1,4]oxazepin-4-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,7,8,9,10-hexahydronaphtho[2,3-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,7,8,9,10-hexahydronaphtho[2,3-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-3,4,8,9,10,11-hexahydronaphtho[1,2-f][1,4]oxazepin-2(1H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-3,4,8,9,10,11-hexahydronaphtho[1,2-f][1,4]oxazepin-2(1H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,5,8,9,10-hexahydro-4H-indeno[5,4-f][1,4]oxazepin-4-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,5,8,9,10-hexahydro-4H-indeno[5,4-f][1,4]oxazepin-4-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,8,9,10,11-hexahydronaphtho[2,1-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,8,9,10,11-hexahydronaphtho[2,1-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydronaphtho[2,3-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydronaphtho[2,3-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-b]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-b]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-b]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-b]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-10-methyl-2,3-dihydro-[1,4]oxazepino[7,6-b]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-10-methyl-2,3-dihydro-[1,4]oxazepino[7,6-b]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-8-methyl-2,3-dihydro-[1,4]oxazepino[7,6-b]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-8-methyl-2,3-dihydro-[1,4]oxazepino[7,6-b]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-8-ethyl-1,5,7,8-tetrahydro-6H-[1,4]oxazepino[6,7-f]indazol-6-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-8-ethyl-1,5,7,8-tetrahydro-6H-[1,4]oxazepino[6,7-f]indazol-6-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-3,4-dihydronaphtho[1,2-f][1,4]oxazepin-2(1H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-3,4-dihydronaphtho[1,2-f][1,4]oxazepin-2(1H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-8-ethyl-8,9-dihydro-[1,4]oxazepino[7,6-h]quinolin-10(11H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-8-ethyl-8,9-dihydro-[1,4]oxazepino[7,6-h]quinolin-10(11H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-3,4-dihydro-[1,4]oxazepino[6,7-f]quinolin-2(1H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-3,4-dihydro-[1,4]oxazepino[6,7-f]quinolin-2(1H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-3,4-dihydro-[1,4]oxazepino[7,6-c]quinolin-2(1H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-3,4-dihydro-[1,4]oxazepino[7,6-c]quinolin-2(1H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-7-ethyl-1,7,8,10-tetrahydro-9H-[1,4]oxazepino[7,6-g]indazol-9-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-7-ethyl-1,7,8,10-tetrahydro-9H-[1,4]oxazepino[7,6-g]indazol-9-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-7-ethyl-1-methyl-1,7,8,10-tetrahydro-9H-[1,4]oxazepino[7,6-g]indazol-9-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-7-ethyl-1-methyl-1,7,8,10-tetrahydro-9H-[1,4]oxazepino[7,6-g]indazol-9-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-7-ethyl-2-methyl-2,7,8,10-tetrahydro-9H-[1,4]oxazepino[7,6-g]indazol-9-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-7-ethyl-2-methyl-2,7,8,10-tetrahydro-9H-[1,4]oxazepino[7,6-g]indazol-9-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-1,3,4,9,10,11-hexahydro-2H-pyrimido[1',2':1,6]pyrido[2,3-f][1,4]oxazepin-2-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydronaphtho[2,1-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydronaphtho[2,1-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-c]isoquinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-c]isoquinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-c]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-c]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-h]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-h]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-f]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-f]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-7-fluoro-2,3-dihydronaphtho[2,1-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-7-fluoro-2,3-dihydronaphtho[2,1-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-8-ethyl-1-methyl-1,5,7,8-tetrahydro-6H-[1,4]oxazepino[6,7-f]indazol-6-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-8-ethyl-1-methyl-1,5,7,8-tetrahydro-6H-[1,4]oxazepino[6,7-f]indazol-6-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-8-ethyl-2-methyl-2,5,7,8-tetrahydro-6H-[1,4]oxazepino[6,7-f]indazol-6-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-8-ethyl-2-methyl-2,5,7,8-tetrahydro-6H-[1,4]oxazepino[6,7-f]indazol-6-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-g]isoquinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-g]isoquinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]isoquinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-7-fluoro-2,3-dihydronaphtho[2,3-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-7-fluoro-2,3-dihydronaphtho[2,3-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-f]isoquinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-f]isoquinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid 2-trifluoroacetate; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)propanoic acid ethyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)propanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((S)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((S)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-3-(1-ethyl-4-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid methyl ester; 3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-3-(1-ethyl-4-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-((2,2-dimethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-((2,2-dimethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-6-ethyl-2,2-dimethyl-6,7-dihydro-[1,3]dioxolano[4',5':4,5]benzo[1,2-f][1,4]oxazepin-8(9H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-6-ethyl-2,2-dimethyl-6,7-dihydro-[1,3]dioxolano[4',5':4,5]benzo[1,2-f][1,4]oxazepin-8(9H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-h]isoquinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(3-((2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid methyl ester; 3-(3-((2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-6-ethyl-1,6,7,9-tetrahydro-8H-[1,4]oxazepino[7,6-f]indazol-8-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-6-ethyl-1,6,7,9-tetrahydro-8H-[1,4]oxazepino[7,6-f]indazol-8-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-6-ethyl-1-methyl-1,6,7,9-tetrahydro-8H-[1,4]oxazepino[7,6-f]indazol-8-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-6-ethyl-1-methyl-1,6,7,9-tetrahydro-8H-[1,4]oxazepino[7,6-f]indazol-8-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-6-ethyl-2-methyl-2,6,7,9-tetrahydro-8H-[1,4]oxazepino[7,6-f]indazol-8-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-6-ethyl-2-methyl-2,6,7,9-tetrahydro-8H-[1,4]oxazepino[7,6-f]indazol-8-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(3-(((R)-7-chloro-2-ethyl-2,3-dihydronaphtho[2,1-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid methyl ester; 3-(3-(((R)-7-chloro-2-ethyl-2,3-dihydronaphtho[2,1-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid; 3-(3-(((R)-7-chloro-2-ethyl-2,3-dihydronaphtho[2,3-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid methyl ester; 3-(3-(((R)-7-chloro-2-ethyl-2,3-dihydronaphtho[2,3-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid; 3-(3-(((R)-10-chloro-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-10-methoxy-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-10-methoxy-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-10-methyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-10-methyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydrothieno[2',3':4,5]benzo[1,2-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydrothieno[2',3':4,5]benzo[1,2-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,7,8-tetrahydrothieno[2',3':4,5]benzo[1,2-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,7,8-tetrahydrothieno[2',3':4,5]benzo[1,2-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-9,9-dioxide-2,3,7,8-tetrahydrothieno[2',3':4,5]benzo[1,2-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-9,9-dioxide-2,3,7,8-tetrahydrothieno[2',3':4,5]benzo[1,2-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethyl-3-(4-methyl-3-(((R)-2-methyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)phenyl)propanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethyl-3-(4-methyl-3-(((R)-2-methyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)phenyl)propanoic acid; 3-(3-((3'H-spiro[cyclopropane-1,2'-[1,4]oxazepino[7,6-g]quinolin]-4'(5'H)-yl)methyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid methyl ester; 3-(3-((3'H-spiro[cyclopropane-1,2'-[1,4]oxazepino[7,6-g]quinolin]-4'(5'H)-yl)methyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethyl-3-(4-methyl-3-((2-propyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)phenyl)propanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethyl-3-(4-methyl-3-((2-propyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)phenyl)propanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)phenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)phenyl)-2,2-dimethylpropanoic acid; 3-(4-chloro-3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)phenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid methyl ester; 3-(4-chloro-3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)phenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methoxyphenyl)-2,2-dimethylpropanoic acid methyl ester; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methoxyphenyl)-2,2-dimethylpropanoic acid; 3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethyl-3-(1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid methyl ester; 3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethyl-3-(1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 1-((1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)methyl)cyclopentane-1-carboxylic acid methyl ester; 1-((1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)methyl)cyclopentane-1-carboxylic acid; 1-((1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)methyl)cyclobutane-1-carboxylic acid methyl ester; 1-((1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)methyl)cyclobutane-1-carboxylic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((S)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-c]isoquinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid methyl ester; and 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((S)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-c]isoquinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid.

8. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of: 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-6-ethyl-2,2-difluoro-6,7-dihydro-[1,3]dioxolano[4',5':4,5]benzo[1,2-f][1,4]oxazepin-8(9H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-9-ethyl-2,2-difluoro-8,9-dihydro-[1,3]dioxolano[4',5':3,4]benzo[1,2-f][1,4]oxazepin-7(6H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,5,7,8,9-hexahydro-4H-indeno[5,6-f][1,4]oxazepin-4-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,7,8,9,10-hexahydronaphtho[2,3-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-3,4,8,9,10,11-hexahydronaphtho[1,2-f][1,4]oxazepin-2(1H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,5,8,9,10-hexahydro-4H-indeno[5,4-f][1,4]oxazepin-4-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,8,9,10,11-hexahydronaphtho[2,1-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydronaphtho[2,3-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-b]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-b]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-10-methyl-2,3-dihydro-[1,4]oxazepino[7,6-b]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-8-methyl-2,3-dihydro-[1,4]oxazepino[7,6-b]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-8-ethyl-1,5,7,8-tetrahydro-6H-[1,4]oxazepino[6,7-f]indazol-6-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-3,4-dihydronaphtho[1,2-f][1,4]oxazepin-2(1H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-8-ethyl-8,9-dihydro-[1,4]oxazepino[7,6-h]quinolin-10(11H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-3,4-dihydro-[1,4]oxazepino[6,7-f]quinolin-2(1H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-3,4-dihydro-[1,4]oxazepino[7,6-c]quinolin-2(1H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-7-ethyl-1,7,8,10-tetrahydro-9H-[1,4]oxazepino[7,6-g]indazol-9-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-7-ethyl-1-methyl-1,7,8,10-tetrahydro-9H-[1,4]oxazepino[7,6-g]indazol-9-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-7-ethyl-2-methyl-2,7,8,10-tetrahydro-9H-[1,4]oxazepino[7,6-g]indazol-9-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-1,3,4,9,10,11-hexahydro-2H-pyrimido[1',2':1,6]pyrido[2,3-f][1,4]oxazepin-2-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydronaphtho[2,1-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-c]isoquinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-c]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-h]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-f]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-7-fluoro-2,3-dihydronaphtho[2,1-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-8-ethyl-1-methyl-1,5,7,8-tetrahydro-6H-[1,4]oxazepino[6,7-f]indazol-6-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-8-ethyl-2-methyl-2,5,7,8-tetrahydro-6H-[1,4]oxazepino[6,7-f]indazol-6-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-g]isoquinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]isoquinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-7-fluoro-2,3-dihydronaphtho[2,3-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-f]isoquinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid 2-trifluoroacetate; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)propanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((S)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-3-(1-ethyl-4-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-((2,2-dimethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-6-ethyl-2,2-dimethyl-6,7-dihydro-[1,3]dioxolano[4',5':4,5]benzo[1,2-f][1,4]oxazepin-8(9H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-h]isoquinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(3-((2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-6-ethyl-1,6,7,9-tetrahydro-8H-[1,4]oxazepino[7,6-f]indazol-8-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-6-ethyl-1-methyl-1,6,7,9-tetrahydro-8H-[1,4]oxazepino[7,6-f]indazol-8-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-6-ethyl-2-methyl-2,6,7,9-tetrahydro-8H-[1,4]oxazepino[7,6-f]indazol-8-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(3-(((R)-7-chloro-2-ethyl-2,3-dihydronaphtho[2,1-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid; 3-(3-(((R)-7-chloro-2-ethyl-2,3-dihydronaphtho[2,3-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid; 3-(3-(((R)-10-chloro-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-10-methoxy-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-10-methyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydrothieno[2',3':4,5]benzo[1,2-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3,7,8-tetrahydrothieno[2',3':4,5]benzo[1,2-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-9,9-dioxide-2,3,7,8-tetrahydrothieno[2',3':4,5]benzo[1,2-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethyl-3-(4-methyl-3-(((R)-2-methyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)phenyl)propanoic acid; 3-(3-((3'H-spiro[cyclopropane-1,2'-[1,4]oxazepino[7,6-g]quinolin]-4'(5'H)-yl)methyl)-4-methylphenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethyl-3-(4-methyl-3-((2-propyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)phenyl)propanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)phenyl)-2,2-dimethylpropanoic acid; 3-(4-chloro-3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)phenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethylpropanoic acid; 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methoxyphenyl)-2,2-dimethylpropanoic acid; 3-(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethyl-3-(1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 1-((1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)methyl)cyclopentane-1-carboxylic acid; 1-((1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)(3-(((R)-2-ethyl-2,3-dihydro-[1,4]oxazepino[7,6-g]quinolin-4(5H)-yl)methyl)-4-methylphenyl)methyl)cyclobutane-1-carboxylic acid; and 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((S)-2-ethyl-2,3-dihydro-[1,4]oxazepino[6,7-c]isoquinolin-4(5H)-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid.

9. A compound represented by the following general formula (I-1) or a pharmaceutically acceptable salt thereof, In the formula, R is a hydrogen atom; R 1 and R 2 Each is independently a hydrogen atom or an alkyl group having 1 to 6 carbon atoms; Or, R 1 and R 2 Together with the carbon atoms to which they are bonded, they form a saturated monocyclic hydrocarbon ring having 3 to 8 ring carbon atoms; R 3 is a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, or an alkoxy group having 1 to 6 carbon atoms; R 4 and R 6 Each is independently a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, or an alkoxy group having 1 to 6 carbon atoms; R 5 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms; A has a structure represented by any one of the following formulae (II-1-1) to (II-3-4), In the formula, R 7 and R 8 Each is independently a hydrogen atom or an alkyl group having 1 to 6 carbon atoms; Or, R 7 and R 8 Together with the carbon atoms to which they are bonded, they form a saturated monocyclic hydrocarbon ring having 3 to 8 ring carbon atoms; X 1 and X 2 Each independently is CR 9 or nitrogen atoms; Y 1 , Y 2 , Y 3 , and Y 4 Each independently is CR 10 or nitrogen atoms; R 9 are each independently a hydrogen atom or a halogen atom; R 10 Each is independently a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, or an alkoxy group having 1 to 6 carbon atoms; Q 1 and Q 2 Each independently is CR 11 R 12 NR 13 , oxygen atom, sulfur atom, SO, or SO2; R 11 and R 12 Each is independently a hydrogen atom, a halogen atom, or an alkyl group having 1 to 6 carbon atoms; R 13 Each is independently a hydrogen atom or an alkyl group having 1 to 6 carbon atoms; Z is NR 14 , oxygen atoms, or sulfur atoms; R 14 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms; Q 3 For (with 1 U 2 ) n ; U 1 and U 2 Each is independently a hydrogen atom, a halogen atom, or an alkyl group having 1 to 6 carbon atoms; n is 1, 2, or 3; mark Indicates the point of bonding to the rest of the molecule. 10 . A pharmaceutical composition comprising the compound according to claim 1 or a pharmaceutically acceptable salt thereof. The pharmaceutical composition according to claim 10, which is used for preventing, alleviating and / or treating a disease that can be improved by inhibiting Keap1.

12. The pharmaceutical composition according to claim 11, wherein The disease that is improved by inhibiting Keap1 is kidney disease.

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