Phenyl-substituted dihydronaphthyridine compounds and their preparation and use

Abstract

The present invention discloses phenyl-substituted dihydronaphthyridine compounds and their preparation and use, which belong to the pharmaceutical technical field. The compound disclosed in the present invention is represented by Formula I and is used as a mineralocorticoid receptor antagonist for treating, preventing, or alleviating diseases such as hyperaldosteronism, diabetic nephropathy, hypertension, heart failure (including chronic heart failure), sequelae of myocardial infarction, liver cirrhosis, renal failure, and stroke in patients. (I) TIFF2025526339000245.tif75158

Description

[Technical Field] 【0001】 The present invention belongs to the field of pharmaceutical technology, and more specifically, relates to phenyl-substituted dihydronaphthyridine compounds and their preparation. use In relation to this, the aforementioned compound is used as a mineralocorticoid receptor antagonist. [Background technology] 【0002】 Mineralocorticoid receptors (MRs) are aldosterone-activated nuclear hormone receptors that regulate the expression of many genes involved in electrolyte homeostasis and cardiovascular disease. Increased circulating aldosterone can raise blood pressure due to its effect on urinary sodium excretion and potentially affect the brain, heart, and vascular system. Furthermore, excessive aldosterone intake is associated with many disease physiological processes that lead to kidney and cardiovascular disease. Aldosterone hypertension is usually caused by aldosterone-producing adenomas, but in patients with refractory hypertension, elevated aldosterone levels, often referred to as "aldosterone escape," are observed due to elevated serum potassium levels and residual AT1R activity. Aldosterone escape generally leads to increased MR activity, and MR antagonists act as potent antihypertensive drugs, having been shown to be effective in treating heart failure and primary aldosterone hypertension. Furthermore, MR antagonists have been shown to be effective in preclinical models of kidney disease and can be used in combination with standard medications to reduce proteinuria in patients with kidney disease, including chronic kidney disease such as diabetic nephropathy. 【0003】 Aldosterone is a steroid hormone produced in the adrenal cortex. Its production is highly dependent on and indirectly regulated by renal blood flow. When renal blood flow decreases, renin is released from the kidneys into the circulating blood. This activates the production of angiotensin II, which constricts the arterial vascular system, while simultaneously stimulating the production of aldosterone in the adrenal cortex. As a result, the kidneys act as a blood pressure sensor and, indirectly, a volume sensor in the circulation. A sharp decrease in volume is counteracted by the renin-angiotensin-aldosterone system, which rebalances the vascular system by increasing blood pressure (angiotensin II effect) and by increasing sodium and water reabsorption in the kidneys (aldosterone effect). This regulatory system can be pathologically impaired in various ways. For example, chronically reduced renal blood flow (e.g., as a result of heart failure and associated venous occlusion) leads to excessive aldosterone release. This results in increased blood volume and increased blood supply to the heart, thus weakening its function. Blood obstruction in the lungs, shortness of breath, edema of the extremities, ascites, and pleural effusion may occur, and renal blood flow may be further reduced. In addition, the effects of excessive aldosterone lead to a decrease in potassium concentrations in the blood and extracellular fluid. If concentrations fall below the critical minimum, it can induce arrhythmias that have fatal consequences in myocardium that has been damaged by other means. This is thought to be one of the main causes of sudden cardiac death, which often occurs in patients with heart failure. 【0004】 Furthermore, aldosterone is thought to be involved in many of the myocardial remodeling processes typically observed in heart failure. Therefore, excess aldosterone is key to the pathogenesis and prognosis of heart failure (which is initially induced by various types of injuries, including myocardial infarction, myocarditis, and hypertension). This hypothesis is supported by the fact that extensive clinical studies treating patients with chronic heart failure and acute myocardial infarction with aldosterone antagonists have shown a significant reduction in overall mortality (B. Pitt, F. Zannad, W. J. Remme et al., N. Engl. J. Med. ML 709-717 (1999); B. Pitt, W. Remme, F. Zannad et al., N. Engl. J. Med. 1309-1321 (2003)). 【0005】 Furthermore, in visceral tissues such as the kidneys and intestines, MR regulates sodium retention, potassium efflux, and water balance in response to aldosterone. In the brain, MR expression appears to be involved in neuronal excitability, negative feedback regulation of the hypothalamic-pituitary-adrenal axis, and control of cognitive aspects of behavioral performance (Castren et al., J. of Neuroendocrinology, 3, 461-66 (1993)). 【0006】 Elevated aldosterone levels or hyperstimulation of hydrocorticoid receptors are associated with numerous physiological disorders and pathological conditions, including Conn(s) syndrome, primary and secondary aldosterone overdose, increased sodium retention, increased magnesium and potassium excretion (polyuria), increased fluid retention, hypertensive disorders (such as isolated systolic hypertension and combined systolic / diastolic hypertension), arrhythmias, cardiomyopathy, myocardial infarction, Bart syndrome, and symptoms associated with excessive levels of catecholamines (Hadley, M.E., ENDOCRINOLOGY, 2nd Ed., pp366-81, (1988), and Brilla et al., Journal of Molecular and Cellular Cardiology, 25(5), pp563-75 (1993)). Compounds and / or pharmaceutical compositions with MR antagonist activity have therapeutic value for any of the aforementioned conditions. 【0007】 Despite significant advances in the treatment of hypertensive diseases and heart failure with mineralocorticoid receptor antagonists, current standard treatments are only near-optimal, and there is a significant unmet medical need for other therapeutic / pharmacological interventions. This invention addresses these needs by providing compounds and compositions that can be used for the treatment or prevention of diabetic nephropathy, hypertension, heart failure, other cardiovascular diseases, and other aldosteronisms. [Overview of the Initiative] [Problems that the invention aims to solve] 【0008】 The present invention relates to phenyl-substituted dihydronaphthyridine compounds having mineralocorticoid receptor (MR) antagonistic activity, compound crystals, and the preparation of the said compounds. use The drug provides the treatment, prevention, or alleviation of conditions in patients such as aldosterone excess, diabetic nephropathy, hypertension, heart failure (including chronic heart failure), sequelae of myocardial infarction, cirrhosis, renal failure, and stroke. [Means for solving the problem] 【0009】 On the other hand, the present invention relates to a compound represented by formula (I) and its stereoisomers, geometric isomers, reverse isomers, nitrogen oxides, hydrates, solvates, metabolites, esters, pharmaceutically acceptable salts, or prodrugs. [ka] (I) Here, [ka] teeth, [ka] And, R1, R2, R3, and R4 are independently hydrogen, deuterium, amino, hydroxyl, mercapto, cyano, nitro, C 1~6 alkyl, C 1~6 alkoxy, C 1~6 haloalkyl, C 1~6 haloalkoxy, C 1~6 alkylamino, carboxyl, C 1~6 alkanoyl, C 1~6 alkylsulfonyl, aminoacyl, aminosulfonyl, C 3~8 cycloalkyl, C 6~10 aryl, heterocyclyl consisting of 3 - 8 atoms, or heteroaryl consisting of 5 - 10 atoms, R5 is, 【Chemical formula】 and R6 is hydrogen, deuterium, C 1~6 alkyl, C 1~6 alkoxy, C 1~6 haloalkyl, C 1~6 haloalkoxy, C 1~6 alkylamino, C 3~8 cycloalkyl, C 6~10 aryl, heterocyclyl consisting of 3 - 8 atoms, or heteroaryl consisting of 5 - 10 atoms, 【Chemical formula】 is, 【Chemical formula】 and X is C or N, Y is O or S, R7 is C 1~6 alkyl, C 3~8 cycloalkyl, heterocyclyl consisting of 3 - 8 atoms, heteroaryl consisting of 5 - 6 atoms, C 3~8 cycloalkyl C 1~6 alkyl, (heterocyclyl consisting of 3 - 8 atoms)C 1~6 alkyl, (heteroaryl consisting of 5 - 6 atoms)C1~6 Alkyl, phenyl, or phenyl C 1~6 It is an alkyl group, and R7 is either unsubstituted or substituted with 1, 2, 3, or 4 Rz. Each Rz independently corresponds to =O, deuterium, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, NH2, and C. 1~6 Alkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 1~6 Haloalkyl, C 1~6 Alkylamino, C 1~6 Alkyl sulfonyl, C 1~6 Alkylacyl, C 3~8 Cycloalkyl, heterocyclyl consisting of 3 to 8 atoms, heteroaryl or C consisting of 5 to 6 atoms 6~10 It is an aryl, where each Rz is independently unsubstituted or substituted with 1, 2, 3, or 4 Rws. Each Rw is independently =O, deuterium, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, amino, C 1~6 Alkyl, C 1~6 Alkoxy, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, C 1~6 Alkylamino, C 1~6 Alkyl sulfonyl, C 1~6 Alkylacyl, C 3~8 Cycloalkyl, heterocyclyl consisting of 3 to 8 atoms, heteroaryl or C consisting of 5 to 6 atoms 6~10 It is Ariel. 【0010】 [ka] teeth, [ka] And, R8 and R9 are hydrogen, deuterium, and C 1~6 Alkyl, C 1~6 Alkoxy, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, C 1~6Alkylamino, C 3~8 Cycloalkyl, C 6~10 Aryls are heterocyclyls consisting of 3 to 8 atoms or heteroaryls consisting of 5 to 10 atoms. 【0011】 On the other hand, the present invention relates to a compound represented by formula (I) and its stereoisomers, geometric isomers, reverse isomers, nitrogen oxides, hydrates, solvates, metabolites, esters, pharmaceutically acceptable salts, or prodrugs. [ka] (I) Here, [ka] teeth [ka] or [ka] And, R1, R2, R3, and R4 are independently hydrogen, deuterium, amino, hydroxyl, mercapto, cyano, nitro, and C. 1~6 Alkyl, C 1~6 Alkoxy, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, C 1~6 Alkylamino, carboxyl, C 1~6 Alkanoyl, C 1~6 Alkyl sulfonyl, aminoacyl, aminosulfonyl, C 3~8 Cycloalkyl, C 6~10 These are aryls, heterocyclines consisting of 3 to 8 atoms, or heteroaryls consisting of 5 to 10 atoms. R5 is [ka] And, R6 is hydrogen, deuterium, C 1~6 Alkyl, C 1~6 Alkoxy, C1~6 Haloalkyl, C 1~6 Haloalkoxy, C 1~6 Alkylamino, C 3~8 Cycloalkyl, C 6~10 These are aryls, heterocyclines consisting of 3 to 8 atoms, or heteroaryls consisting of 5 to 10 atoms. [ka] teeth, [ka] And, X is either C or N, Y is either O or S, R7 is C 1~6 Alkyl, C 3~8 Cycloalkyl, heterocyclyl consisting of 3-8 atoms, heteroaryl consisting of 5-6 atoms, C 3~8 Cycloalkyl C 1~6 Alkyl, (heterocyclyl consisting of 3 to 8 atoms) C 1~6 Alkyl, (heteroaryl, consisting of 5-6 atoms) C 1~6 Alkyl, phenyl, or phenyl C 1~6 It is an alkyl group, and R7 is either unsubstituted or substituted with 1, 2, 3, or 4 Rz. Each Rz independently corresponds to O, deuterium, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, NH2, and C. 1~6 Alkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 1~6 Haloalkyl, C 1~6 Alkylamino, C 1~6 Alkyl sulfonyl, C 1~6 Alkylacyl, C 3~8 Cycloalkyl, heterocyclyl consisting of 3 to 8 atoms, heteroaryl or C consisting of 5 to 6 atoms 6~10 It is an aryl, where each Rz is independently unsubstituted or substituted with 1, 2, 3, or 4 Rws. Each Rw is independently O, deuterium, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, amino, C 1~6 alkyl, C 1~6 alkoxy, C 1~6 haloalkyl, C 1~6 haloalkoxy, C 1~6 alkylamino, C 1~6 alkylsulfonyl, C 1~6 alkylacyl, C 3~8 cycloalkyl, heterocyclyl consisting of 3 to 8 atoms, heteroaryl consisting of 5 to 6 atoms or C 6~10 aryl, 【Chem.】 is 【Chem.】 and is R8 and R9 are hydrogen, deuterium, C 1~6 alkyl, C 1~6 alkoxy, C 1~6 haloalkyl, C 1~6 haloalkoxy, C 1~6 alkylamino, C 3~8 cycloalkyl, C 6~10 aryl, heterocyclyl consisting of 3 to 8 atoms or heteroaryl consisting of 5 to 10 atoms, R 10 and R 11 are each independently selected from -CH2- or O, and at least one is O, R 12 is -CH2- or -CH2-CH2-, R 12 is -CH2-, R 10 and R 11 are each independently selected from -CH2- or O, and at least one is O, R 12 is -CH2-CH2-, R 10 and R 11 are simultaneously O, or R 10 is -CH2-, R 11 is O. 【0012】 In some embodiments, the compound represented by formula (I) described in the present invention is selected from the compounds represented by formula (Ia) or formula (Ib), more preferably the compound represented by formula (Ia), 【Chemical formula】 (Ia) 【Chemical formula】 (Ib). 【0013】 In some embodiments, the compound represented by formula (I) described in the present invention is selected from the compounds represented by formula (Ia) or formula (Ib), more preferably the compound represented by formula (Ia), 【Chemical formula】 (Ia) 【Chemical formula】 (Ib). 【0014】 Here, 【Chemical formula】 , 【Chemical formula】 , 【Chemical formula】 , R1, R2, R3, R4, R5, R6, R7, R8, R9, X and Y have the meanings described in the present invention. 【0015】 In some embodiments, each of R1, R2, R3 and R4 is independently hydrogen, deuterium, amino, hydroxyl, mercapto, cyano, nitro, C 1~4 alkyl, C 1~4 alkoxy, C 1~4 haloalkyl, C 1~4 haloalkoxy, C1~4 Alkylamino, carboxyl, C 1~4 Alkanoyl, C 1~4 Alkyl sulfonyl, aminoacyl, aminosulfonyl, C 3~6 Cycloalkyl, C 6~10 These are aryls, heterocyclines consisting of 3 to 6 atoms, or heteroaryls consisting of 5 to 6 atoms. R6 is hydrogen, deuterium, C 1~4 Alkyl, C 1~4 Alkoxy, C 1~4 Haloalkyl, C 1~4 Haloalkoxy, C 1~4 Alkylamino, C 3~6 Cycloalkyl, C 6~10 These are aryls, heterocyclines consisting of 3 to 6 atoms, or heteroaryls consisting of 5 to 6 atoms. Each of R8 and R9 is independently hydrogen, deuterium, halogen, cyano, and C. 1~4 Alkoxyacyl, carboxyl, C 1~4 Alkyl, C 1~4 Alkoxy, C 1~4 Haloalkyl, C 1~4 Haloalkoxy, C 1~4 Alkylamino, C 1~4 Alkanoyl, C 1~4 Alkyl sulfonyl, aminoacyl, or aminosulfonyl, In some embodiments, each R1, R2, R3, and R4 is independently hydrogen, deuterium, amino, hydroxyl, mercapto, cyano, nitro, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, butoxy, trifluoromethyl, difluoromethyl, monofluoromethyl, 2,2-difluoroethyl, 1,2-difluoroethyl, trifluoroethyl, trifluoromethoxy, difluoromethoxy, monofluoromethoxy, methylamino, dimethylamino, carboxyl, methylacyl, ethylacyl, methylsulfonyl, aminoacyl, or aminosulfonyl. R6 is hydrogen, deuterium, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, butoxy, trifluoromethyl, difluoromethyl, monofluoromethyl, 2,2-difluoroethyl, 1,2-difluoroethyl, trifluoroethyl, trifluoromethoxy, difluoromethoxy, monofluoromethoxy, methylamino, dimethylamino, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthalenyl, cyclohexylethyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholino, pyridinyl, pyrrolidinyl, thiazole, pyrazole, or pyrimidinyl. R8 is hydrogen, deuterium, cyano, methylacyl, ethylacyl, propylacyl, methoxyacyl, ethoxyacyl, propoxyacyl, carboxyl, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, butoxy, trifluoromethyl, difluoromethyl, monofluoromethyl, 2,2-difluoroethyl, 1,2-difluoroethyl, trifluoroethyl, trifluoromethoxy, difluoromethoxy, monofluoromethoxy, methylamino, or dimethylamino. 【0016】 In some embodiments, the compounds described in the present invention are selected from the compounds represented by formula (II). [ka] (II). 【0017】 In some embodiments, the compounds described in the present invention are selected from compounds represented by formula (IIa) or formula (IIb). [ka] (IIa) [ka] (IIb) 【0018】 In some embodiments, R7 is C 3~6Cycloalkyl, heterocyclyl consisting of 3-6 atoms, heteroaryl consisting of 5-6 atoms, C 3~6 Cycloalkyl C 1~4 Alkyl, (heterocyclyl consisting of 3-6 atoms) C 1~4 Alkyl or (heteroaryl) C (consisting of 5-6 atoms) 1~4 It is an alkyl group, where R7 is either unsubstituted or substituted with 1, 2, 3, or 4 Rz atoms. 【0019】 In some embodiments, R7 is C 1~3 The alkyl group is such that R7 is either unsubstituted or substituted with 1, 2, 3, or 4 Rz values, preferably R7 is methyl, ethyl, or isopropyl, where R7 is either unsubstituted or substituted with 1, 2, 3, or 4 Rz values. 【0020】 In some embodiments, R7 is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ethylene oxide, azetidinyl, oxetidinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, thiazolidinyl, pyrazolidinyl, oxazolidinyl, imidazolidinyl, isoxazolidinyl, piperidinyl, piperazinyl, morpholino, pyrrolidinyl, furanyl, thiophene, thiazole, pyrazole, pyridinyl, pyrimidinyl, cyclopropylmethyl, cyclopropylethyl, cyclopropylmethyl, cyclopropylethyl, cyclopentylmethyl, cyclopentylethyl, cyclohexylmethyl, cyclohexylethyl, azetidinylmethyl, azetidinylethyl, oxetidinylmethyl, oxetidinylethyl, pyrrolidinylmethyl, pylori Dinyl ethyl, tetrahydrofuranylmethyl, tetrahydrofuranylethyl, tetrahydrothienylmethyl, tetrahydrothienylethyl, piperidinyl methyl, piperidinyl ethyl, piperadinyl methyl, piperadinyl ethyl, morpholinomethyl, morpholinoethyl, pyrrolidinyl methyl, pyrrolidinyl ethyl, furanyl methyl, furanyl ethyl, thiophene methyl, thiophene ethyl, thiazole methyl, thiazole ethyl, pyrazole methyl, pyrazole ethyl, imidazolyl methyl, imidazolyl ethyl, triazolyl methyl, triazolyl ethyl, tetrazolyl methyl, tetrazolyl ethyl, pyridinyl methyl, pyridinyl ethyl, pyrimidinyl methyl, or pyrimidinyl ethyl, where R7 is unsubstituted or substituted with 1, 2, 3 or 4 Rz. 【0021】 In some embodiments, each Rz is independently =O, deuterium, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, NH2, C 1~4 Alkyl, C 1~4 Alkoxy, C 1~4 Haloalkoxy, C 1~4 Haloalkyl, C 1~4 Alkylamino, C 1~4 Alkyl sulfonyl, C 1~4 Alkylacyl, C 3~6Cycloalkyl, heterocyclyl consisting of 3-6 atoms, heteroaryl or C consisting of 5-6 atoms 6~10 It is an aryl compound, where each Rz is independently unsubstituted or substituted with 1, 2, 3, or 4 Rws, and each Rw is independently =O, deuterium, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, NH2, C 1~4 Alkyl, C 1~4 Alkoxy, C 1~4 Haloalkyl, C 1~4 Haloalkoxy, C 1~4 Alkylamino, C 1~4 Alkyl sulfonyl, C 1~4 Alkylacyl, C 3~6 Cycloalkyl, heterocyclyl consisting of 3-6 atoms, heteroaryl or C consisting of 5-6 atoms 6~10 It is Ariel. 【0022】 In some embodiments, each Rz is independently =O, deuterium, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, NH2, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, trifluoromethoxy, monofluoromethoxy, difluoromethoxy, trifluoromethyl, difluoromethyl, monofluoromethyl, methylamino, ethylamino, dimethylamino, methylethylamino, diethylamino, methylsulfonyl, ethylsulfonyl, methylacyl, ethyl These are syl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ethylene oxide, azetidinyl, oxetidinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, thiazolidinyl, pyrazolidinyl, oxazolidinyl, imidazolidinyl, isoxazolidinyl, piperidinyl, piperazinyl, morpholino, pyrrolidinyl, furanyl, thiophene, thiazole, pyrazole, pyridinyl, pyrimidinyl, or phenyl, where each Rz is independently unsubstituted. It is either substituted with 1, 2, 3 or 4 Rws, each Rw independently being =O, deuterium, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, NH2, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, trifluoromethoxy, monofluoromethoxy, difluoromethoxy, trifluoromethyl, difluoromethyl, monofluoromethyl, methylamino, ethylamino, dimethylamino, methylethylamino, diethylamino, methylsulfonyl, ethylsulfonyl These are honyl, methylacyl, ethylacyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ethylene oxide, azetidinyl, oxetidinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, thiazolidinyl, pyrazolidinyl, oxazolidinyl, imidazolidinyl, isoxazolidinyl, piperidinyl, piperazinyl, morpholino, pyrrolidinyl, furanyl, thiophene, thiazole, pyrazole, pyridinyl, pyrimidinyl, or phenyl. 【0023】 In some embodiments, a compound is selected from those represented by formula (III), [ka] (III) Here, R5 is [Chemical formula] selected from 【0024】 In some embodiments, R1, R2, R3, R4 are independently hydrogen, deuterium, C 1~6 alkoxy, R5 is [Chemical formula] and R6 is selected from hydrogen, deuterium, C 1~6 alkyl. 【0025】 In some embodiments, R1, R2, R3, R4 are independently hydrogen, deuterium, C 1~3 alkoxy, R5 is [Chemical formula] and R6 is selected from hydrogen, deuterium, C 1~3 alkyl. 【0026】 In some embodiments, R1, R2, R3, R4 are independently hydrogen, deuterium, methoxyl, R5 is [Chemical formula] and R6 is selected from hydrogen, deuterium, methyl. 【0027】 In some embodiments, selected from the compounds represented by formula (IV), [Chemical formula] (IV) Here, [ka] teeth [ka] And, R1, R2, R3, and R4 are independently hydrogen, deuterium, and C 1~6 It is an alkoxy, R5 is [ka] Selected from, R6 is C 1~6 It is alkyl, R7 is C 1~6 It is alkyl, R8 and R9 are hydrogen, deuterium, and C 1~6 It is alkyl, Y is selected from O, X is selected from C. 【0028】 In some embodiments, R1, R2, R3, and R4 are independently hydrogen, deuterium, and C 1~3 It is an alkoxy, R6 is C 1~3 It is alkyl, R7 is C 1~3 It is alkyl, R8 and R9 are hydrogen, deuterium, and C 1~3 It is alkyl. 【0029】 In some embodiments, a compound is selected from those represented by formula (V), [ka] (V) Here, [ka] teeth [ka] And, R3 and R4 are independently hydrogen and deuterium. R5 is [ka] Selected from, R6 is C 1~6 It is alkyl, R7 is C 1~6 Alkyl, C 3~8 Cycloalkyl, C 3~8 Cycloalkyl C 1~6 It is an alkyl group, where R7 is either unsubstituted or substituted with 1, 2, 3, or 4 Rz atoms, each Rz atom independently being a halogen. R8 and R9 are hydrogen, deuterium, and C 1~6 It is alkyl, X is selected from C, Y is selected from O. 【0030】 In some embodiments, R6 is C 1~3 It is alkyl, R7 is C 1~3 Alkyl, C 3~5 Cycloalkyl, C 3-4 Cycloalkyl C 1~3 It is an alkyl group, where R7 is either unsubstituted or substituted with 1, 2, 3, or 4 Rz atoms, each Rz atom independently being fluorine, chlorine, bromine, or iodine. R8 and R9 are hydrogen, deuterium, and C 1~3 It is alkyl. 【0031】 In some embodiments, R6 is C 1~3 It is alkyl, R7 is C 1~3 Alkyl, C 3~5 Cycloalkyl, C 3-4 Cycloalkyl C 1~3 It is an alkyl group, where R7 is either unsubstituted or substituted with 1, 2, 3, or 4 Rz atoms, each Rz atom independently being fluorine. R8 and R9 are hydrogen and methyl, respectively. 【0032】 In some embodiments, a compound is selected from those represented by formula (V), [ka] (V) Here, [ka] teeth [ka] And, R3 and R4 are independently hydrogen and deuterium. R5 is [ka] Selected from, R6 is C 1~6 It is alkyl, R7 is C 1~6 Alkyl, C 3~8 Cycloalkyl, C 3~8 Cycloalkyl C 1~6 It is an alkyl group, where R7 is either unsubstituted or substituted with 1, 2, 3, or 4 Rz, each Rz independently of a halogen, C 1~6 It is alkyl, R8 and R9 are hydrogen, deuterium, and C 1~6 It is alkyl, X is selected from C, Y is selected from O. 【0033】 In some embodiments, a compound is selected from those represented by formula (Va) or formula (Vb), [ka] (Va) (Vb) Here, [ka] teeth [ka] And, R3 and R4 are independently hydrogen and deuterium. R5 is [ka] Selected from, R6 is C 1~6 It is alkyl, R7 is C 1~6 Alkyl, C 3~8 Cycloalkyl, C 3~8 Cycloalkyl C 1~6 It is an alkyl group, where R7 is either unsubstituted or substituted with 1, 2, 3, or 4 Rz, each Rz independently of a halogen, C 1~6 It is alkyl, R8 and R9 are hydrogen, deuterium, and C 1~6 It is alkyl, X is selected from C, Y is selected from O. 【0034】 In the above equations (V), (Va), and (Vb), R6 is C 1~3 It is alkyl, R7 is C 1~3 Alkyl, C 3~5 Cycloalkyl, C 3-4 Cycloalkyl C 1~3 It is an alkyl group, where R7 is either unsubstituted or substituted with 1, 2, 3, or 4 Rz atoms, each Rz atom independently of fluorine, chlorine, bromine, iodine, or C. 1~4 It is alkyl, R8 and R9 are hydrogen, deuterium, and C 1~3 It is alkyl. 【0035】 moreover, R6 is C 1~3 It is alkyl, R7 is C 1~3 Alkyl, C 3~5 Cycloalkyl, C 3-4 Cycloalkyl C1~3 It is an alkyl group, where R7 is either unsubstituted or substituted with 1, 2, 3, or 4 Rz atoms, each Rz atom independently being fluorine or methyl. R8 and R9 are hydrogen and methyl, respectively. 【0036】 In some embodiments, the compound is selected from the compounds represented by formula (VI), formula (VIa), or formula (VIb), [ka] R 10 and R 11 Each is independently selected from -CH2- or O, and at least one is O. R 12 is -CH2- or -CH2-CH2-, and R 12 is -CH2-, and R 10 and R 11 Each is independently selected from -CH2- or O, with at least one being O, and R 12 is -CH2-CH2-, and R 10 and R 11 It is O at the same time, or R 10 is -CH2-, and R 11 is O, R7 is C 1~3 Alkyl, C 3~6 Cycloalkyl, heterocyclyl consisting of 3-6 atoms, heteroaryl consisting of 5-6 atoms, C 3~6 Cycloalkyl C 1~4 Alkyl, (heterocyclyl consisting of 3-6 atoms) C 1~4 Alkyl or (heteroaryl) C (consisting of 5-6 atoms) 1~4 It is an alkyl group, where R7 is either unsubstituted or substituted with 1, 2, 3, or 4 Rz atoms. Preferably, R7 is methyl, ethyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ethylene oxide, azetidinyl, oxetidinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, thiazolidinyl, pyrazolidinyl, oxazolidinyl, imidazolidinyl, isoxazolidinyl, piperidinyl, piperazinyl, morpholino, pyrrolidinyl, furanyl, thiophene, thiazole, pyrazole, pyridinyl, pyrimidinyl, cyclopropylmethyl, cyclopropylethyl, cyclopropylmethyl, cyclopropylethyl, cyclopentylmethyl, cyclopentylethyl, cyclohexylmethyl, cyclohexylethyl, azetidinylmethyl, azetidinylethyl, oxetidinylmethyl, oxetidinylethyl, pyrrolidinylmethyl , pyrrolidinyl ethyl, tetrahydrofuranylmethyl, tetrahydrofuranyl ethyl, tetrahydrothienylmethyl, tetrahydrothienyl ethyl, piperidinyl methyl, piperidinyl ethyl, piperadinyl methyl, piperadinyl ethyl, morpholinomethyl, morpholinoethyl, pyrrolidinyl methyl, pyrrolidinyl ethyl, furanyl methyl, furanyl ethyl, thiophene methyl, thiophene ethyl, thiazole methyl, thiazole ethyl, pyrazole methyl, pyrazole ethyl, imidazolyl methyl, imidazolyl ethyl, triazolyl methyl, triazolyl ethyl, tetrazolyl methyl, tetrazolyl ethyl, pyridinyl methyl, pyridinyl ethyl, pyrimidinyl methyl or pyrimidinyl ethyl, where R7 is unsubstituted or substituted with 1, 2, 3 or 4 Rz values. Preferably, each Rz is independently O, deuterium, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, NH2, C 1~4 Alkyl, C 1~4 Alkoxy, C 1~4 Haloalkoxy, C 1~4 Haloalkyl, C 1~4 Alkylamino, C 1~4 Alkyl sulfonyl, C 1~4 Alkylacyl, C 3~6 Cycloalkyl, heterocyclyl consisting of 3-6 atoms, heteroaryl or C consisting of 5-6 atoms 6~10It is an aryl compound, where each Rz is independently unsubstituted or substituted with 1, 2, 3, or 4 Rws, each Rw independently being O, deuterium, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, NH2, or C 1~4 Alkyl, C 1~4 Alkoxy, C 1~4 Haloalkyl, C 1~4 Haloalkoxy, C 1~4 Alkylamino, C 1~4 Alkyl sulfonyl, C 1~4 Alkylacyl, C 3~6 Cycloalkyl, heterocyclyl consisting of 3-6 atoms, heteroaryl or C consisting of 5-6 atoms 6~10 It is Ariel, Preferably, each Rz is independently O, deuterium, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, NH2, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, trifluoromethoxy, monofluoromethoxy, difluoromethoxy, trifluoromethyl, difluoromethyl, monofluoromethyl, methylamino, ethylamino, dimethylamino, methylethylamino, diethylamino, methylsulfonyl, ethylsulfonyl, methylacyl, ethylacyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ethylene oxide, azetidinyl, oxetidinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, thiazolidinyl, pyrazolidinyl, oxazolidinyl, imidazolidinyl, isoxazolidinyl, piperidinyl, piperazinyl, morpholino, pyrrolidinyl, furanyl, thiophene, thiazole, pyrazole, pyridinyl, pyrimidinyl, or phenyl, where each Rz is independently unsubstituted. or substituted with 1, 2, 3 or 4 Rw, each Rw independently of O, deuterium, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, NH2, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, trifluoromethoxy, monofluoromethoxy, difluoromethoxy, trifluoromethyl, difluoromethyl, monofluoromethyl, methylamino, ethylamino, dimethylamino, methylethylamino, diethylamino, methylsulfonyl, ethylsulfonyl These include methylacyl, ethylacyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ethylene oxide, azetidinyl, oxetidinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, thiazolidinyl, pyrazolidinyl, oxazolidinyl, imidazolidinyl, isoxazolidinyl, piperidinyl, piperazinyl, morpholino, pyrrolidinyl, furanyl, thiophene, thiazole, pyrazole, pyridinyl, pyrimidinyl, or phenyl. 【0037】 In some embodiments, the compounds represented by (I) provided by the present invention are compounds represented by formulas (I-10), (I-11), or (I-12) and their stereoisomers, geometric isomers, reverse isomers, nitrogen oxides, hydrates, solvates, metabolites, esters, pharmaceutically acceptable salts, or prodrugs. [ka] (I-10) [ka] (I-11) [ka] (I-12) Here, [ka] teeth [ka] R3 and R4 are arbitrarily selected from hydrogen, deuterium, and C. 1~6 It is an alkyl group, and R7 is C 1~6 Alkyl, C 3~8 Cycloalkyl, C 3~8 Cycloalkyl C 1~6 It is an alkyl group, where R7 is unsubstituted or substituted with 1, 2, 3 or 4 Rz values, each Rz independently being O, deuterium, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, or NH2, and R8 and R9 are hydrogen, deuterium, or C 1~6 It is alkyl, In the compounds shown in (I-10), (I-11), or (I-12) above, R6 is C 1~4 It is an alkyl group, and further selected from hydrogen, methyl, ethyl, propyl, and propyl. In the compounds shown in (I-10), (I-11), or (I-12) above, each R8 and R9 is independently hydrogen, deuterium, halogen, or C 1~4 It is alkyl, In the compounds shown in (I-10), (I-11), or (I-12) above, R8 is independently hydrogen, methyl, ethyl, propyl, or butyl, and R9 is independently hydrogen or deuterium. In the compounds shown in (I-10), (I-11), or (I-12) above, R7 is C 3~6 Cycloalkyl, C 3~8 Cycloalkyl, C 3~5 Cycloalkyl C 1~3 It is an alkyl group, where R7 is unsubstituted or substituted with 1, 2, 3, or 4 Rz atoms, each Rz atom independently being O, deuterium, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, or NH2. In the compounds shown in (I-10), (I-11), or (I-12) above, R7 is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclopropylethyl, cyclopropylmethyl, cyclopropylethyl, cyclopentylmethyl, cyclopentylethyl, cyclohexylmethyl, or cyclohexylethyl. 【0038】 In the compounds represented by (I'-10), (I'-11), or (I'-12) above, R7 is methyl or ethyl. 【0039】 In the compounds represented by (I'-10), (I'-11), or (I'-12), R7 is substituted with 1 to 3 F atoms. 【0040】 In some embodiments, the compound is selected from the following: [ka] [ka] [ka] [ka] 【0041】 In this invention, there are no compounds in which R1, R2, and R3 are hydrogen, R4 is methoxy, R5 is -CONH2, and R6 is hydrogen. 【0042】 On the other hand, the present invention provides a crystal of a compound, and the structural formula of compound 36 is as follows. [ka] 36 【0043】 Here, the crystal of compound 36 has a monoclinic crystal structure, belonging to the C2 space group, with cell parameters a=23.1853(2) [Å], b=8.74723(7) [Å], c=10.94032(10) [Å], α=90°, β=112.7428(8)°, γ=90°, and cell volume V=2046.27(3) [Å]. 3 The minimum number of asymmetric units within a cell is Z=4. 【0044】 Here, the crystal or crystalline form of compound 36 has an XRPD pattern as shown in Figure 4 or substantially as shown in Figure 4, where substantially means that the difference in the number of peak shapes is within 85%. 【0045】 The present invention further provides crystals of another compound 62, the structural formula of which is as follows. [ka] 62 【0046】 Here, the crystal of compound 62 has a monoclinic crystal structure, belonging to the C2 space group, with cell parameters a=24.92890(19) [Å], b=8.89441(5) [Å], c=21.18548(18) [Å], α=90°, β=121.6750(10)°, γ=90°, and cell volume V=3997.68(6) [Å]. 3 The minimum number of asymmetric units within a cell is Z = 8. 【0047】 Here, the crystal or crystalline form of compound 62 has an XRPD pattern shown in Figure 8 or substantially shown in Figure 8, where substantially means that the difference in the number of peak shapes is within 85%. 【0048】 Specifically, regarding the crystalline form, the present invention provides a crystal of a compound, which is compound 36, whose structural formula is shown in the above figure, and the crystal of compound 36 has a monoclinic crystal structure, belonging to the C2 space group, with cell parameters a=23.1853(2) [Å], b=8.74723(7) [Å], c=10.94032(10) [Å], α=90°, β=112.7428(8)°, γ=90°, cell volume V=2046.27(3) [Å]3, and the minimum number of asymmetric units in the cell Z=4, and furthermore, the crystal of compound 36 or its crystalline form has an XRPD pattern shown in Figure 4 or substantially as shown in Figure 4, where substantially means that the difference in the number of peak shapes is within 85%. The present invention further provides crystals of another compound 62, whose structure is monoclinic, belonging to the C2 space group, with cell parameters a=24.92890(19) [Å], b=8.89441(5) [Å], c=21.18548(18) [Å], α=90°, β=121.6750(10)°, γ=90°, cell volume V=3997.68(6) [Å]3, and minimum number of asymmetric units in the cell Z=8, and further, the crystal or crystalline form of compound 62 has an XRPD pattern shown in Figure 8 or substantially shown in Figure 8, where substantially means that the difference in the number of peak shapes is within 85%. The present invention relates to the crystals of the compound in the preparation of drugs. use The present invention further provides that the drug is a drug for treating or preventing diseases or conditions related to mineralocorticoids, or a drug for treating, preventing or alleviating conditions in patients such as diabetic nephropathy, aldosterone excess, hypertension, heart failure, sequelae of myocardial infarction, cirrhosis of the liver, renal failure, or stroke, or the drug is used as a mineralocorticoid receptor antagonist. 【0049】 On the other hand, in the preparation of drugs of the compounds described in the present invention and their stereoisomers, geometric isomers, reverse isomers, nitrogen oxides, hydrates, solvates, metabolites, esters, pharmaceutically acceptable salts, or prodrugs, use In relation to, or in the preparation of drugs for treating or preventing diseases or conditions relating to the compounds described in the present invention and their stereoisomers, geometric isomers, reverse isomers, nitrogen oxides, hydrates, solvates, metabolites, esters, pharmaceutically acceptable salts, or prodrugs or mineralocorticoids use Regarding. 【0050】 Herein, the drug is used to treat, prevent or alleviate diseases in patients such as diabetic nephropathy, aldosterone excess, hypertension, heart failure, sequelae of myocardial infarction, cirrhosis of the liver, renal failure, or stroke. 【0051】 Alternatively, the drug may be used here as a mineralocorticoid receptor antagonist. 【0052】 The aforementioned mineralocorticoid-related diseases or conditions are selected from among conditions such as diabetic nephropathy, aldosterone excess, hypertension, heart failure, sequelae of myocardial infarction, cirrhosis of the liver, renal failure, or stroke. 【0053】 (Definitions and common terms) Next, specific embodiments of the present invention will be described in detail, with examples illustrated by the accompanying structural and chemical formulas. The present invention is intended to cover all alternative, modified, and equivalent technical solutions that fall within the scope of the present invention as defined by the claims. Those skilled in the art should recognize that many methods and materials similar or equivalent to those described herein are available for use in the practice of the present invention. The present invention is by no means limited to the methods and materials described herein. In the event that one or more combined documents, patents, and similar materials differ from or conflict with this application (including, but not limited to, defined terms, application of terms, and described techniques), this application shall prevail. 【0054】 It should be further recognized that certain features of the present invention, described in multiple separate embodiments for clarity and visibility, may also be provided in combination in a single embodiment. Conversely, various features of the present invention, described in a single embodiment for brevity, may be provided individually or in any suitable subcombination. 【0055】 Unless otherwise specified, all technical terms and concepts used in this invention have the same meaning as those generally understood by those skilled in the art to which this invention pertains. All patents and publications covered by this invention are incorporated herein by reference in their entirety. 【0056】 Unless otherwise specified, the following definitions used herein apply. For the purposes of this invention, chemical elements are consistent with the CAS edition of the Periodic Table and the Handbook of Chemistry and Physics, 75th edition, 1994. Furthermore, the general principles of organic chemistry are described in "Organic Chemistry," Thomas Sorrell, University Science Books, Sausalito: 1999, and "March's Advanced Organic Chemistry" by Michael B. Smith and Jerry March, John Wiley & Sons, New York: 2007, all of which are incorporated herein by reference. 【0057】 Unless otherwise indicated, or unless there is a clear inconsistency in the context, the articles “one,” “one (kind),” and “the foregoing” as used herein are intended to include “at least one” or “one or more.” Thus, as used herein, these articles refer to one or more (i.e., at least one) objects. For example, “component” refers to one or more components, i.e., there may be one or more components intended to be adopted or used in the embodiments described. 【0058】 As used in this invention, the term "patient" refers to a human (including adults and children) or other animal. In some embodiments, "patient" refers to a human. 【0059】 The term "includes" is open-ended, meaning it includes what is shown in this invention but does not exclude other embodiments. 【0060】 Stereoisomers are compounds that have the same chemical structure but differ in the spatial arrangement of atoms or groups. Stereoisomers include enantiomers, diastereomers, conformational isomers (rotational isomers), geometric isomers (cis / trans) isomers, and blocking isomers. 【0061】 An "enantiomer" refers to two isomers of a compound that cannot overlap but are mirror images of each other. 【0062】 Diastereomers are stereoisomers that possess two or more chiral centers and whose molecules are not mirror images of each other. Diastereomers differ in physical properties such as melting point, boiling point, spectroscopic properties, and reactivity. Mixtures of diastereomers can be separated by high-resolution analytical operations such as electrophoresis and chromatography (HPLC). 【0063】 The definitions and rules of stereochemistry used in this invention generally follow those in S.P. Parker, Ed., McGraw-Hill Dictionary of Chemical Terms (1984), McGraw-Hill Book Company, New York, and Eliel, E. and Wilen, S., "Stereochemistry of Organic Compounds," John Wiley & Sons, Inc., New York, 1994. 【0064】 Any of the chiral atoms (e.g., carbon) of the compounds disclosed in the present invention may exist in racemic or enantiomerically enriched forms, such as (R)-, (S)-, or (R,S)- configurations. In some embodiments, each chiral atom has at least 50% enantiomer excess, at least 60% enantiomer excess, at least 70% enantiomer excess, at least 80% enantiomer excess, at least 90% enantiomer excess, at least 95% enantiomer excess, or at least 99% enantiomer excess with respect to the (R)- or (S)- configuration. 【0065】 The resulting mixture of stereoisomers can be separated into pure or substantially pure geometric isomers, enantiomers, and diastereomers based on differences in the physicochemical properties of the components, for example, by chromatography and / or stepwise crystallization. 【0066】 The term "reverse isomer" or "tautomer" refers to structural isomers with different energies that can be interconverted over a low-energy barrier. If isomerization is possible (e.g., in solution), then chemical equilibrium between the isomers can be achieved. For example, proton tautomers (prototropic tautomers) include interconversions by proton transfer, such as keto-enol isomerization and imine-enamine isomerization. Valence tautomers include interconversions by the recombination of some bonding electrons. A specific example of keto-enol isomerization is the interconversion of pentane-2,4-dione and 4-hydroxypento-3-en-2-one isomers. Another example of tautomerism is phenol-keto interconversion isomers. A specific example of phenol-ketone interconversion is the interconvertible isomers of pyridine-4-ol and pyridine-4(1H)-one. Unless otherwise specified, all interisomers of the compounds of the present invention are within the scope of the present invention. 【0067】 Similar to those described in the present invention, the compounds of the present invention may be optionally substituted with one or more substituents, as in the compounds of the above general formula, or as in the specific examples, subclasses, and classes of compounds included in the present invention in the examples. 【0068】 Furthermore, unless otherwise explicitly stated, in this invention, "each...independently," "...each independently," and "...independently" are interchangeable and should be understood in a broad sense, meaning that specific options expressed between the same symbols of different groups do not affect each other, or that specific options expressed between the same symbols of the same group do not affect each other. Similarly, the term "independent" in the phrase "...independently, arbitrarily" should be understood in the broad sense described above. 【0069】 The term "optional" or "optional" means that the events or circumstances described thereafter may exist, but are not necessarily so; that is, this specification includes not only the circumstances in which the events or circumstances described exist, but also the circumstances in which they do not exist. 【0070】 In each part of this specification, substituents of the compounds disclosed herein are disclosed according to the type or range of the group. In particular, it should be noted that the present invention encompasses separate subcombinations of each member of these types and ranges of groups. For example, the terms "C1-C6 alkyl" or "C 1~6 "Alkyl" specifically refers to methyl, ethyl, C3 alkyl, C4 alkyl, C5 alkyl and C6 alkyl, which are disclosed independently. 1~4 "Alkyl" specifically refers to methyl, ethyl, C3 alkyl (i.e., propyl including n-propyl and isopropyl) and C4 alkyl (i.e., butyl including n-butyl, isobutyl, sec-propyl and tert-propyl), which are disclosed independently. 【0071】 In each part of the present invention, linking substituents are described. Where a structure clearly requires a linking group, the Marksch variables listed for that group should be understood as linking groups. For example, if a structure requires a linking group and the definition of Marksch groups for that variable lists "alkyl" or "aryl," then "alkyl" or "aryl" represents a linked alkylidene group or arylidene group, respectively. 【0072】 As used in this invention, the term "alkyl" or "alkyl group" refers to a saturated linear or branched monovalent hydrocarbon group containing 1 to 20 carbon atoms, wherein the alkyl group may be substituted with one or more substituents as described in this invention. In some embodiments, the alkyl group contains 1 to 12 carbon atoms, and in other embodiments, the alkyl group contains 1 to 6 carbon atoms, i.e., C 1~6 It contains alkyl, and in yet another embodiment, the alkyl group has 1 to 4 carbon atoms, i.e., C 1~4 It contains alkyl, and in some other embodiments, the alkyl group has 1 to 3 carbon atoms, i.e., C 1~3 Contains alkyl. In some examples, C according to the present invention 1~6 Alkyl is C 1~4 Alkyl is included, and in some other embodiments, C described in the present invention 1~6 Alkyl is C 1~3 Contains alkyl. 【0073】 Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl (including n-propyl and isopropyl), propyl (including n-butyl, isobutyl, sec-butyl, and tert-propyl), n-pentyl, 2-pentyl, 3-pentyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 3-methyl-1-butyl, 2-methyl-1-butyl, n-hexyl, 2-hexyl, 3-hexyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 3-methyl-3-pentyl, 2-methyl-3-pentyl, 2,3-dimethyl-2-butyl, 3,3-dimethyl-2-butyl, n-heptyl, and n-octyl. 【0074】 The term "alkoxy" indicates that an alkyl group is bonded to the rest of the molecule by an oxygen atom, where alkyl group has the meanings set forth herein. Examples of alkoxy groups include, but are not limited to, methoxy, ethoxy, propoxy (including 1-propoxy or 2-propoxy), and butoxy (including n-butoxy, isobutoxy, sec-butoxy, and tert-butoxy). 【0075】 The terms "haloalkyl" or "haloalkoxy" indicate that an alkyl or alkoxy group is substituted with one or more halogen atoms, examples of which include trifluoromethyl, trifluoromethoxy, chloroethyl (e.g., 2-chloroethyl), trifluoroethyl (including, but not limited to, 2,2,2-trifluoroethyl), 2,2-difluoroethyl, and 2-chloro-1-methylethyl. 【0076】 The term "amino" refers to the group -NH2. The term "carboxyl" refers to the group -COOH. The terms "hydroxyl," "cyano," "nitro," and "mercapto" represent the groups -OH, -CN, -NO2, and -SH, respectively. The term "oxo" represents the group =O. 【0077】 The term "alkylamino" means that the -NH2 group is substituted with one or two alkyl groups, i.e., the alkylamino includes monoalkylamino and dialkylamino, where the alkyl has the meaning described in this invention. Examples of alkylamino groups include, but are not limited to, methylamino, ethylamino, methylethylamino, and dimethylamino. 【0078】 The term "cycloalkyl" refers to a saturated monocyclic, bicyclic, or tricyclic compound containing 3 to 12 ring carbon atoms. In some embodiments, the cycloalkyl compound contains 3 to 10 ring carbon atoms, for example, C 3-10 It includes cycloalkyls, and in some other embodiments, the cycloalkyl has 3 to 8 ring carbon atoms, for example C3~8 The cycloalkyl group comprises, in some further embodiments, the cycloalkyl group consists of 3 to 6 ring carbon atoms, for example, C 3~6 It includes cycloalkyl groups. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Herein, as described in the present invention, C 3~8 Cycloalkyl is C 3~6 The C comprises a cycloalkyl group. 3~6 Cycloalkyls include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. The cycloalkyls may be substituted with one or more substituents as described in the present invention. 【0079】 The term "heterocyclyl" refers to a saturated or partially unsaturated monocyclic, bicyclic, or tricyclic compound containing 3 to 12 ring atoms, where at least one ring atom is selected from nitrogen, sulfur, and oxygen atoms, and the heterocyclyl is non-aromatic and does not contain an aromatic ring. Unless otherwise specified, the heterocyclyl may be carbon or nitrogen-based, and the -CH2- group may optionally be replaced with -C(=O)-. The sulfur atom of the ring may optionally be oxidized to an S-oxide. The nitrogen atom of the ring may optionally be oxidized to an N-oxide. The term "heterocyclyl" may be used interchangeably with the term "heterocyclic." Examples of heterocyclines include, but are not limited to, ethylene oxide, azetidinyl, oxetidinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, thiazolidinyl, pyrazolidinyl, oxazolidinyl, imidazolidinyl, isoxazolidinyl, piperidinyl, piperazinyl, or morpholino. As described in the present invention, the heterocycline consists of 3 to 8 atoms or 3 to 6 atoms, wherein the atoms are C, N, O, or S, and at least one atom is N, O, or S, where the heterocycline consisting of 3 to 8 atoms is a heterocycline consisting of 3 to 6 atoms, and the heterocycline consisting of 3 to 6 atoms is a heterocycline consisting of 3 to 5 atoms, specifically, the heterocycline consisting of 3 to 6 atoms is ethylene oxide [ka] Aziridine [ka] Azetidinil [ka] Oxetidinil [ka] Pirolizini [ka] Tetrahydrofuranyl [ka] Tetrahydrothienyl [ka] Thiazolidinil [ka] Pyrazolidinil [ka] Pyrazolinyl [ka] Oxazolidinyl [ka] Imidazolidinil [ka] piperidinil [ka] Piperazinil [ka] or morpholino [ka] This includes, but is not limited to, the heterocyclyls described herein. The heterocyclyl may optionally be substituted with one or more substituents described in this invention. 【0080】 The term "halogen" refers to fluorine (F), chlorine (Cl), bromine (Br), or iodine (I). 【0081】 The term "aryl" refers to monocyclic, bicyclic, and tricyclic carbocyclic systems containing 6 to 14 ring atoms, or 6 to 12 ring atoms, or 6 to 10 ring atoms, where at least one is aromatic and the rest of the molecule has one or more bonding sites. The term "aryl" may be used interchangeably with the terms "aromatic ring" or "aryl ring". Examples of aryl groups include phenyl, 2,3-dihydro-1H-indenyl, naphthalenyl, and anthracenyl. The aryl group may optionally be substituted with one or more substituents described in the present invention. Unless otherwise specified, "C 6~10 The "aryl" group refers to an aryl group containing 6 to 10 ring carbon atoms. 【0082】 The term "heteroaryl" refers to monocyclic, bicyclic, and tricyclic structures containing 5 to 12 ring atoms, or 5 to 10 ring atoms, or 5 to 6 ring atoms, where at least one is aromatic and at least one is 1, 2, 3, or 4 cycloheteroatoms selected from nitrogen, oxygen, and sulfur, and simultaneously, the heteroaryl has one or more bonding sites on the rest of the molecule. If a -CH2- group is present on the heteroaryl group, the -CH2- group may optionally be replaced with -C(=O)-. Unless otherwise specified, the heteroaryl group may be bonded to the rest of the molecule (e.g., the main structure in the general formula) via any reasonable site (which may be C in CH or N in NH). The term "heteroaryl" may be used interchangeably with the terms "heteroaryl ring" or "heteroaryl compound". Examples of heteroaryl groups include, but are not limited to, furanyl, imidazolyl, isoxazolyl, oxazolyl, pyrrolidinyl, pyrazole, pyridinyl, pyrimidinyl, pyridadinyl, pyrazinyl, thiophene, thiazole, triazolyl, and tetrazolyl. The heteroaryl group may optionally be substituted with one or more substituents described in the present invention. In some embodiments, the heteroaryl is a heteroaryl comprising 5 to 10 atoms, and it is shown that the heteroaryl comprises 1 to 9 ring carbon atoms and 1, 2, 3, or 4 cycloheteroatoms selected from O, S, and N. In some other embodiments, the heteroaryl is a heteroaryl comprising 5 to 6 atoms, and it is shown that the heteroaryl comprises 1 to 5 ring carbon atoms and 1, 2, 3, or 4 cycloheteroatoms selected from O, S, and N. Examples of heteroaryls comprising 5 to 6 atoms include, but are not limited to, furanyl, imidazolyl, isoxazolyl, oxazolyl, pyrrolidinyl, pyrazole, pyridinyl, pyrimidinyl, pyridadinyl, pyrazinyl, thiophene, thiazole, and the like. 【0083】 The term "consisting of j to k atoms (where j and k are independent non-zero natural numbers, and k > j)" indicates that the cyclic group consists of j to k ring atoms, where the ring atoms consist of carbon atoms and / or heteroatoms such as O, N, S, and P, and "j to k" includes j, k, and any natural number between them. For example, "consisting of 3 to 8 atoms," "consisting of 5 to 10 atoms," or "consisting of 5 to 6 atoms" indicates that the cyclic group consists of 3 to 8, 5 to 10, or 5 to 6 ring atoms, where the ring atoms include carbon atoms and / or heteroatoms such as O, N, S, and P. 【0084】 In this specification, when a complex group is formed by the linkage of two or more groups, the linkage site follows the general principles of chemistry, namely, the linkage point refers to the last noun group in the name of the complex group. For example, "C 3~8 Cycloalkyl C 1~6 Alkyl, 3-8 heterocycloalkyl C 1~6 Alkyl, Phenylen C 1~6 Alkyl, 5-6 heteroaryl C 1~6 When alkyl occurs, the main structural group or the linking site with other groups is always "C 1~6 The group is an alkyl group, and other types of groups are understood by referring to the subprinciple unless otherwise specified. 【0085】 The "heterocycline consisting of 3 to 8 atoms" and the "heterocycline consisting of 3 to 6 atoms" described in the present invention refer to a heterocycline consisting of 3 to 8 ring atoms or a heterocycline consisting of 3 to 6 ring atoms, where the heterocycline consists of 1, 2, 3 or 4 heteroatoms selected from N, O, and S, the CH2 in the heterocycline can be further oxidized to form C(=O), and similarly, the S or N in the heteroring can be further oxidized to form S(=O), S(=O)2 or N(=O). 【0086】 The "heteroaryls consisting of 5 to 10 atoms" and "heteroaryls consisting of 5 to 6 atoms" described in the present invention refer to heteroaryls consisting of 5 to 10 ring atoms and heteroaryls consisting of 5 to 6 ring atoms, respectively, where the heteroaryl contains 1, 2, 3, or 4 heteroatoms selected from N, O, and S. In some embodiments, specific examples of the "heteroaryls consisting of 5 to 10 atoms" or "heteroaryls consisting of 5 to 6 atoms" described in the present invention include, but are not limited to, pyridinyl, pyrimidinyl, pyrazinyl, thiophene, thiazole, furanyl, pyrrolidinyl, pyrazole, imidazolyl, triazolyl, and the like. 【0087】 The terms "alkanoyl" or "alkylacyl" refer to -C(=O)-alkyl groups, where the alkyl group has the meaning described in this invention. Such examples include, but are not limited to, methylacyl (-C(=O)CH3) and ethylacyl (-C(=O)CH2CH3). 【0088】 The term "alkoxyalkyl" refers to a -C(=O)-R group, where R is alkoxy, and the alkoxy has the meaning described in this invention. Such examples include, but are not limited to, methoxylacyl (-C(=O)OCH3) and ethoxylacyl (-C(=O)OCH2CH3). 【0089】 The term "alkylsulfonyl" refers to an -S(=O)2-alkyl group, where the alkyl group has the meaning described in this invention, and such examples include, but are not limited to, methylsulfonyl (-S(=O)2CH3) and ethylsulfonyl (-S(=O)2CH2CH3). 【0090】 The term "aminosulfonyl" refers to the -S(=O)2NH2 group, while the term "aminoacyl" refers to the -C(=O)NH2 group. 【0091】 The term “pharmaceutically acceptable” refers to molecular entities and compositions that, when administered to humans, are physiologically acceptable and generally do not cause allergic or similar adverse reactions, such as gastrointestinal discomfort or dizziness. Preferably, as used herein, the term “pharmaceutically acceptable” refers to those approved by a federal regulatory agency or national government for use in animals, particularly humans, or those listed in the United States Pharmacopeia or other generally accepted pharmacopoeias. 【0092】 The term "carrier" refers to a diluent, adjuvant, excipient, or matrix administered together with the compound. These drug carriers may be water or sterile liquids such as oils, including peanut oil, soybean oil, mineral oil, and sesame oil, derived from petroleum, animal, plant, or synthetic sources. Water and aqueous solutions (e.g., aqueous saline solution, aqueous glucose solution, aqueous glycerol solution) are preferred as carriers, particularly for use as injectable solutions. Suitable drug carriers are listed in EW Martin's "Remington's Pharmaceutical Sciences". 【0093】 As used in this invention, the term "prodrug" refers to the in vivo conversion of a compound to the compound represented by formula (I). Such conversion is influenced by hydrolysis of the precursor drug in the blood or enzymatic conversion to the parent structure in the blood or tissue. The precursor drug compounds of this invention may be esters, and existing inventions have shown that esters usable as precursor drugs include phenyl esters and aliphatic (C) esters. 1~24These include esters, acyloxymethyl esters, carbonates, carbamates, and amino acid esters. For example, one of the compounds of the present invention contains a hydroxyl group, which can be acylated to obtain a precursor drug form of the compound. Other precursor drug forms include phosphate esters, and phosphate ester compounds can be obtained by phosphorylating the hydroxyl group on the parent compound. For a complete review of precursor drugs, refer to the following publications: T. Higuchi and V. Stella, Pro-drugs as Novel Delivery Systems, Vol. 14 of the A.C.S. Symposium Series; Edward B. Roche, ed., Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press, 1987; J. Rautio et al., Prodrugs: Design and Clinical Applications, Nature Review Drug Discovery, 2008, 7, 255-270; and S.J. Hecker et al., Prodrugs of Phosphates and Phosphonates, Journal of Medicinal Chemistry, 2008, 51, 2328-2345. 【0094】 "Metabolites" refer to products obtained when a specific compound or a salt thereof is metabolized in the body. Metabolites of compounds can be identified by techniques known in the art, and their activity can be characterized by experimental methods such as those described in the present invention. Such products can be obtained by oxidation, reduction, hydrolysis, acylation, deacylation, esterification, defatting, enzymatic cleavage, etc., of the administered compound. Accordingly, the present invention encompasses metabolites of compounds, including metabolites resulting from sufficient exposure of mammals to the compounds of the present invention for a certain period of time. 【0095】 As used in this invention, "pharmaceutically acceptable salts" refers to organic and inorganic salts of the compounds of this invention. pharmaceutically acceptable salts are well known in their respective fields and are described in detail, for example, in SMBerge et al., *Describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 1977, 66:1-19*. pharmaceutically acceptable salts formed from non-toxic acids include, but are not limited to, inorganic salts such as hydrochlorides, hydrobroms, phosphates, sulfates, and perchlorates, organic salts such as acetates, oxalates, maleates, tartrates, citrates, succinates, and malons, or salts obtained by other methods described in the literature, such as ion exchange. Other pharmaceutically acceptable salts include adipine, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, cyclopentylpropionate, digluconate, dodecyl sulfate, ethylsulfonate, formate, transbutylenedioate, glucoheptanate, glycerophosphate, gluconate, hemitosulfate, heptanoate, hexanoate, and hydriodate. This includes 2-hydroxyethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, methanesulfonate, 2-naphthalenesulfonate, nicotinic acid, nitrate, oleate, palmitate, pomiate, pectinate, persulfate, 3-phenylpropionate, picrate, pivalate, propionate, stearate, thiocyanate, p-toluene, sulfonate, undecanoate, pentanoate, etc. Salts obtained by reaction with a suitable base include alkali metals, alkaline earth metals, ammonium and N + (C 1~4The present invention also intends to conceive of quaternary ammonium salts formed from any compound containing an N group. Water-soluble, oil-soluble, or dispersible products can be obtained by quaternization. Alkali metals or alkaline earth metals that can form salts include sodium, lithium, potassium, calcium, magnesium, and the like. Pharmaceutically acceptable salts further include suitable and non-toxic ammonium salts, quaternary ammonium salts, and amine cations resistant to equilibrium ion formation, such as halides, hydroxides, carboxylates, sulfates, phosphates, nitrates, and C 1~8 Contains sulfonates and aromatic sulfonates. 【0096】 In this invention, "solvate" refers to an aggregate formed by one or more solvent molecules and the compound of the present invention. The solvents that form the solvate include, but are not limited to, water, isopropanol, ethanol, methanol, dimethyl sulfoxide, ethyl acetate, acetic acid, and aminoethanol. The term "hydrate" refers to an aggregate formed with water as the solvent molecule. 【0097】 In this invention, "ester" refers to an ester that is hydrolyzable in the body, formed from a compound containing hydroxyl or carboxyl. Such esters are pharmaceutically acceptable esters that are hydrolyzed in the body of humans or animals, for example, to produce a parent alcohol or acid. The compound of formula (I) of this invention comprises a suitable group, such as carboxyl, and an ester that is hydrolyzable in the body, and such groups include, but are not limited to, alkyl and arylalkyl groups. 【0098】 In this invention, "nitrogen oxide" refers to a compound containing multiple amine functional groups, in which one or more nitrogen atoms are oxidized to form N - This means that oxides can be formed. - A specific example of an oxide is the N of tertiary amines. - N of oxides or nitrogen-containing heterocyclic nitrogen atoms - It is an oxide. The corresponding amine is treated with an oxidizing agent such as hydrogen peroxide or a peracid (e.g., peroxycarboxylic acid) and N -Oxides can be formed (see Advanced Organic Chemistry, Wiley Interscience, 4th edition, Jerry March, pages). In particular, N - The oxide was prepared by LWDeady's method (Syn.Comm.1977,7,509~514), in which an amine compound was reacted with m-chloroperoxybenzoic acid (MCPBA) in an inert solvent such as dichloromethane. 【0099】 The terms "compound of the present invention," "compound described in the present invention," "compound described in the present invention," or similar expressions used in this invention refer to any compound represented by the general formula structure described in this invention. For example, a compound of the present invention may refer to a compound represented by formula (I), formula (Ia), formula (Ib), formula (IIa), formula (IIb), formula (III), or formula (IV) of the present invention. A compound of the present invention includes specific compounds of any example. 【0100】 The term “treat” any disease or condition as used in the present invention means, in some embodiments, to improve the disease or condition (i.e., to reduce, prevent, or alleviate the progression of the disease or at least one clinical symptom). In some other embodiments, “treat” means to alleviate or improve at least one physical parameter, including a physical parameter that may not be apparent to the patient. In some other embodiments, “treat” means to modulate the disease or condition physically (e.g., to stabilize detectable symptoms), physiologically (e.g., to stabilize a physical parameter), or both. In some other embodiments, “treat” means to prevent or delay the onset, occurrence, or exacerbation of the disease or condition. 【0101】 Furthermore, the structural formulas given in this invention are intended to represent these compounds in both isotopically unenriched and isotopically enriched forms. The isotopically enriched compounds have the structure described by the general formulas given in this invention, except that one or more atoms are substituted with atoms having selected atomic weights or mass numbers. Exemplary isotopes that can be introduced into the compounds of this invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, io, fluorine, and chlorine, such as 2H, 3H, 11C, 13C, 14C, 15N, 17O, 18O, 18F, 31P, 32P, 35S, 36Cl, and 125I. 【0102】 Furthermore, substitution with heavier isotopes, particularly deuterium (i.e., 2H or D), may offer certain therapeutic benefits arising from greater metabolic stability. These may include, for example, increased half-life in vivo, reduced dosage, or improved therapeutic index. It should be understood that deuterium in this invention is considered a substituent of the compound of formula (I). The isotopic enrichment factor can be used to define the concentration of such heavier isotopes, particularly deuterium. As used in this invention, the term “isotopic enrichment factor” means the ratio of the isotopic abundance of a specified isotope to its natural abundance. When a substituent of the compound of the present invention is specified as deuterium, the compound has an isotopic enrichment factor of at least 3500 (deuterium doping rate of 52.5% for each specified deuterium atom), at least 4000 (deuterium doping rate of 60%), at least 4500 (deuterium doping rate of 67.5%), at least 5000 (deuterium doping rate of 75%), at least 5500 (deuterium doping rate of 82.5%), at least 6000 (deuterium doping rate of 90%), at least 6333.3 (deuterium doping rate of 95%), at least 6466.7 (deuterium doping rate of 97%), at least 6600 (deuterium doping rate of 99%), or at least 6633.3 (deuterium doping rate of 99.5%) for each specified deuterium atom. The pharmaceutically usable solvates of the present invention include those in which the crystallization solvent may be isotope-substituted, such as D2O, acetone-d6, and DMSO-d6. 【0103】 Unless otherwise specified, all tautomerized forms of the compounds of the present invention are included within the scope of the invention. Furthermore, unless otherwise specified, the structural formulas of the compounds described in the present invention include enriched isotopes of one or more different atoms. 【0104】 Any abbreviations for protecting groups, amino acids, and other compounds used in this invention are based on commonly used and accepted abbreviations, or refer to the IUPAC-IUB Commission on Biochemical Nomenclature (Biochem. 1972, 11:942-944), unless otherwise specified. 【0105】 (Description of the compound of the present invention) The present invention relates to phenyl-substituted dihydronaphthyridine compounds that competitively antagonize the aldosterone receptor (MR), their drug compositions, and the preparation of the compound or drug composition. use The drug provides the treatment, prevention, or alleviation of conditions in patients such as diabetic nephropathy, aldosterone excess, hypertension, heart failure (including chronic heart failure), sequelae of myocardial infarction, cirrhosis, renal failure, and stroke. 【0106】 On the other hand, the present invention relates to a compound represented by formula (I) or stereoisomers, geometric isomers, reverse isomers, nitrogen oxides, hydrates, solvates, metabolites, esters, pharmaceutically acceptable salts or prodrugs of a compound represented by formula (I). [ka] (I) 【0107】 On the other hand, the present invention relates to the preparation of drugs using the compound or drug composition described in the present invention. use In this regard, the drug is used to treat, prevent or alleviate diseases in patients such as diabetic nephropathy, aldosterone excess, hypertension, heart failure (including chronic heart failure), sequelae of myocardial infarction, cirrhosis of the liver, renal failure, or stroke. 【0108】 On the other hand, the present invention further relates to the preparation of drugs using the compounds or drug compositions described in the present invention. use In this regard, the drug is used here as a mineralocorticoid receptor antagonist. 【0109】 On the other hand, the compounds or drug compositions described in the present invention are used to treat, prevent or alleviate diseases in patients such as diabetic nephropathy, aldosterone excess, hypertension, heart failure (including chronic heart failure, etc.), sequelae of myocardial infarction, liver cirrhosis, renal failure, or stroke. 【0110】 On the other hand, the compounds or drug compositions described in the present invention are used to antagonize mineralocorticoid receptors. 【0111】 On the other hand, the present invention relates to a method for treating, preventing, or alleviating diseases in patients such as diabetic nephropathy, aldosterone excess, hypertension, heart failure (including chronic heart failure, etc.), sequelae of myocardial infarction, cirrhosis of the liver, renal failure, or stroke, using the compound or drug composition described in the present invention, wherein the method includes treating the patient with a therapeutically effective amount of the compound or drug composition described in the present invention. 【0112】 On the other hand, the present invention further relates to a method for antagonizing mineralocorticoid receptors using the compounds or drug compositions described in the present invention, the method comprising contacting a living organism (inside or outside the body) with an effective amount of the compounds or drug compositions described in the present invention. 【0113】 The compounds or drug compositions described in the present invention may be useful agents for treating and preventing diseases associated with elevated aldosterone levels by competitively antagonizing aldosterone receptors (MR). 【0114】 The compounds or drug compositions described in the present invention are useful for treating or preventing aldosterone receptor-mediated diseases. The present invention also includes methods for treating or alleviating aldosterone receptor-mediated diseases in patients or for being susceptible to such conditions, the methods comprising treating the patient with a therapeutically effective amount of the compounds or drug compositions of the present invention. 【0115】 The present invention relates to the compound of the present invention and its pharmaceutically acceptable salt. use The present invention comprises a drug composition comprising an effective therapeutic amount necessary for the binding of a compound represented by formula (I) to at least one pharmaceutically acceptable carrier, excipient, diluent, adjuvant, or mediator. 【0116】 Unless otherwise specified, all hydrates, solvates, and pharmaceutically acceptable salts of the compounds of the present invention are included within the scope of the present invention. 【0117】 Specifically, the salt is a pharmaceutically acceptable salt. The term "pharmaceutically acceptable" means that the substance or composition must be chemically or toxicologically appropriate in relation to the other components of the preparation and the mammal for which it is intended to be used. 【0118】 The salts of the compounds of the present invention include salts for preparing or purifying intermediates of the compounds represented by formula (I), formula (Ia), formula (Ib), formula (IIa), formula (IIb), formula (III), or formula (IV), or enantiomer isomers isolated from the compounds represented by formula (I), formula (Ia), formula (Ib), formula (IIa), formula (IIb), formula (III), or formula (IV), but the salts do not necessarily have to be pharmaceutically acceptable. 【0119】 Salts of the compounds of the present invention can be obtained by any suitable method provided in the literature, for example, using inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid and phosphoric acid, or organic acids such as acetic acid, maleic acid, succinic acid, mandelic acid, fumaric acid, malonic acid, pyruvic acid, oxalic acid, hydroxyacetic acid and salicylic acid, pyranotic acids such as glucuronic acid and galacturonic acid, α-hydroxy acids such as citric acid and tartaric acid, amino acids such as aspartic acid and glutamic acid, aromatic acids such as benzoic acid and cinnamic acid, and sulfonic acids such as p-toluenesulfonic acid and ethylsulfonic acid. 【0120】 The biological activity of the compounds of the present invention can be evaluated using any conventionally known method. Suitable assays are well known in the art. For example, the compounds of the present invention can be assayed for MR antagonistic activity, pharmacokinetic activity and / or liver microsome stability, etc., by suitable conventional methods. The assays presented herein are given only as examples and are not intended to limit the invention. The compounds of the present invention are active in at least one of the assays provided herein. For example, the compounds of the present invention have good antagonistic activity against, better pharmacokinetic properties such as better absorption and exposure and higher bioavailability, and, for example, the compounds of the present invention have lower toxic side effects. 【0121】 (Administration of the compound of the present invention and use ) The therapeutically effective amount of the compound of the present invention should be present in the above pharmaceutical formulation at a concentration of about 0.1 to 99.5% by weight, preferably about 0.5 to 95% by weight, of the total mixture. The therapeutically effective dose can first be estimated using various methods well known in the art. The initial dose for use in animal studies can be based on the effective concentration established in cell culture assays. The appropriate dose range for human subjects can be determined, for example, using data obtained from animal studies and cell culture assays. In some embodiments, the compound of the present invention can be prepared as a drug for oral administration. An exemplary dose of the compound of the present invention in a drug for oral administration is about 0.01 to about 100 mg / kg (where kg is the body weight of the subject). In some embodiments, the drug contains about 0.01 to about 20 mg / kg (where kg is the body weight of the subject), or optionally about 0.01 to about 10 mg / kg (where kg is the body weight of the subject), or optionally about 0.01 to about 5.0 mg / kg (where kg is the body weight of the subject). In some embodiments, the compounds of the present invention are administered via the gastrointestinal route at an effective dose of about 0.001 to 1 mg / kg, preferably about 0.01 to 0.5 mg / kg body weight. 【0122】 Typical administration regimens for drugs intended for oral administration include three times a week, twice a week, once a week, three times a day, twice a day, or once a day. In some embodiments, the compounds of the present invention are administered as active ingredients in a total amount of about 0.001 to about 50 mg / kg body weight per 24 hours, preferably about 0.001 to about 10 mg / kg body weight, and may optionally be administered in the form of multiple single doses for the purpose of obtaining the desired results. A single dose may preferably contain an amount of about 0.001 to about 30 mg / kg body weight of the compounds of the present invention, particularly 0.001 to 3 mg / kg body weight. 【0123】 The effective amount or therapeutically effective amount or dose of a drug (e.g., the compound of the present invention) means the amount of the drug or compound that causes improvement in the symptoms or extension of the survival period of an individual. The toxicity and therapeutic effect of the molecule can be determined by standard pharmaceutical procedures, for example, by determining the LD50 (the dose that causes lethality in 50% of the population) and ED50 (the dose that is therapeutically effective in 50% of the population) in cell cultures or experimental animals. The dose ratio of the toxic effect to the therapeutic effect is the therapeutic index, which can be expressed as LD50 / ED50. Drugs exhibiting a high therapeutic index are preferred. 【0124】 An effective dose or therapeutically effective dose is the amount of a compound or pharmaceutical composition that elicits a biological or medical response in the tissue, system, animal, or human being being investigated by the researcher, veterinarian, physician, or other clinician. The dose is preferably within the range of circulating concentrations containing the ED50, which is minimal or no toxicity. The dose may vary within this range depending on the dosage form and / or route of administration used. The appropriate dosage form, route of administration, dose, and administration interval should be selected according to methods known in the art, taking into account the specific characteristics of the individual pathological condition. 【0125】 The dosage and administration interval can be individually adjusted to obtain a plasma concentration of the active portion sufficient to achieve the desired effect, i.e., the minimum effective concentration (MEC). MEC varies depending on the compound, but can be estimated, for example, from in vitro data or animal experiments. The dosage required to obtain the MEC varies depending on the individual's characteristics and the route of administration. In the case of local administration or selective uptake, the effective local concentration of the drug may not depend on the plasma concentration. 【0126】 The amount of drug or composition administered may depend on various factors, including the individual being treated's sex, age, and weight, the severity of the disease, the mode of administration, and the prescribing physician's judgment. 【0127】 If necessary, the compositions of the present invention may be provided in a package or dispensing device containing one or more unit dosage forms (containing the active ingredient). For example, the package or device may consist of metal or plastic foil (e.g., polystyrene foam packaging) or glass and a rubber stopper. Instructions for administration may be attached to the package or dispensing device. It is also possible to prepare compositions consisting of the compounds of the present invention formulated in a suitable pharmaceutical carrier, place them in appropriate containers, and label them for the treatment of a specified condition. 【0128】 The compounds of the present invention have good safety. Here, the maximum tolerated dose for repeated administration over 14 days in mice shows that compound 62 has high safety. In particular, the maximum tolerated dose for repeated administration over 14 days of compound 36 is shown to be more than 2.7 times that of compound 62. Moreover, its safety window is more than 230 times the equivalent dose, providing high safety. 【0129】 Furthermore, because compound 36 of the present invention has less CYP3A4 inhibitory activity, the contraindications of finelenone are reduced, and it also has a lower cardiac / renal AUC (tissue distribution) ratio than finelenone, which greatly contributes to reducing the side effects of finelenone. 【0130】 The compounds of the present invention are suitable for the prevention and / or treatment of a wide range of pathological conditions and disease-related conditions, particularly those characterized by elevated plasma aldosterone concentrations or changes in plasma aldosterone concentration relative to plasma renin concentrations, or conditions associated with these changes. Examples that can be cited include, in particular, spontaneous primary aldosterone excess, aldosterone excess associated with adrenal hyperplasia, adrenal adenoma and / or adrenal carcinoma, aldosterone excess associated with liver cirrhosis, aldosterone excess associated with heart failure, and (relative) aldosterone excess associated with essential hypertension. 【0131】 Due to its mechanism of action, the compounds of the present invention are also suitable for preventing sudden cardiac death in patients at increased risk of death due to sudden cardiac death. These patients are particularly those suffering from any of the following conditions: primary and secondary hypertension, hypertensive heart disease with or without congestive heart failure, refractory hypertension, acute and chronic heart failure, coronary artery disease, stable and unstable angina, myocardial ischemia, myocardial infarction, dilated cardiomyopathy, congenital primary cardiomyopathy (e.g., Bmgada syndrome), cardiomyopathy due to Chagas disease, shock, atherosclerosis, atrial and ventricular arrhythmias, transient and ischemic episodes, stroke, inflammatory cardiovascular disease, peripheral and cardiovascular disease, peripheral blood flow disorders, obstructive arterial disease such as intermittent claudication, asymptomatic left ventricular dysfunction, myocarditis, cardiac hypertrophic changes, pulmonary arterial hypertension, coronary and peripheral artery spasms, thrombosis, thromboembolic disease, vasculitis, etc. 【0132】 The compounds of the present invention can further be used to prevent and / or treat edema formation such as pulmonary edema, renal edema, or pulmonary edema associated with heart failure, as well as to prevent and / or treat restenosis after, for example, thrombolytic therapy, percutaneous transluminal angioplasty (PTA) and coronary angioplasty (PTCA), heart transplantation, and bypass surgery. 【0133】 The compounds of the present invention are also suitable for use as potassium-sparing diuretics and for the treatment of electrolyte disorders such as hypercalcemia, hypernatremia, or hypokalemia. 【0134】 The compounds of the present invention are also suitable for the treatment of kidney diseases such as acute and chronic renal failure, hypertensive nephropathy, atherosclerotic nephritis (chronic and interstitial), nephrosclerosis, chronic renal failure, and cystic nephropathy, as well as for the prevention of renal injury (e.g., renal injury induced by immunosuppressants associated with organ transplantation (e.g., cyclosporine A)) and for use in renal cancer. 【0135】 The compounds of the present invention can further be used for the prevention and / or treatment of diabetes and its sequelae, such as neuropathy and nephropathy. 【0136】 The compounds of the present invention can also be used, for example, to prevent and / or treat microalbuminuria and proteinuria caused by diabetes or hypertension. 【0137】 The compounds of the present invention are also suitable for the prevention and / or treatment of conditions associated with elevated plasma glucocorticoid concentrations or localized elevated glucocorticoid concentrations in tissues (e.g., the heart). Examples include adrenal insufficiency (Cushing's syndrome) leading to glucocorticoid overproduction, adrenocortical tumors leading to glucocorticoid overproduction, and pituitary tumors that autonomously produce ACTH (adrenocorticotropic hormone), thereby leading to adrenal hyperplasia and Cushing's disease. 【0138】 The compounds of the present invention can further be used for the prevention and / or treatment of obesity, metabolic syndrome, and obstructive sleep apnea syndrome. 【0139】 The compounds of the present invention can further be used to prevent and / or treat inflammatory conditions caused by, for example, viruses, spirochetes, fungi, bacteria or mycobacteria, and inflammatory conditions of unknown cause such as polyarthritis, lupus erythematosus, periarthritis or polyarteritis, dermatomyositis, scleroderma, and nodular diseases. 【0140】 The compounds of the present invention can further be used to treat depression, anxiety, chronic pain, central nervous system disorders such as migraines in particular, and neurodegenerative diseases such as Alzheimer's disease and Parkinson's syndrome. 【0141】 The compounds of the present invention are also suitable, for example, for the prevention and / or treatment of vascular injury following percutaneous transcatheter coronary angioplasty (PTCA), stent implantation, coronary angiography, bypass surgery, and endothelial dysfunction, Raynaud's disease, thromboembolic vasculitis (Buerger's syndrome), and tinnitus syndrome. 【0142】 The compounds of the present invention can be used alone or, optionally, in combination with other active ingredients. The present invention further relates to a pharmaceutical (particularly for the treatment and / or prevention of the aforementioned diseases) comprising at least one compound of the present invention and one or more other active ingredients, and in particular to a combination of a pharmaceutical for the treatment and / or prevention of the diseases described in the present invention. Suitable active ingredients for concomitant use include: active ingredients for lowering blood pressure, for example, preferably calcium channel blockers, angiotensin II receptor blockers, ACE inhibitors, endothelin antagonists, renin inhibitors, α-blockers, β-blockers and Rho kinase inhibitors; diuretics, especially tabula diuretics and thiazide diuretics; antithrombotic agents, for example, preferably platelet aggregation inhibitors, anticoagulants or fibrinolytic agents; active ingredients for altering lipid metabolism, for example, preferably thyroid receptor agonists; cholesterol synthesis inhibitors, for example, preferably HMG-coenzyme A reductase inhibitors or squalene synthesis inhibitors, ACAT inhibitors, CETP inhibitors, bile acid reabsorption inhibitors and lipoprotein (a) antagonists; organic nitrates and NO donors such as organic nitroprusside sodium, nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, morphine or SIN-1, inhaled NO; cardiac glycosides (digoxin); isoproterenol; epinephrine. Compounds with positive cardiotonic effects such as norepinephrine, dopamine, and dopabutylamine; compounds that inhibit the degradation of cyclic guanosine phosphate (cGMP) and / or cyclic adenosine phosphate (cAMP), such as phosphodiesterase (PDE) 1, 2, 3, 4 and / or 5 inhibitors (e.g., sildenafil, vardenafil, tadalafil, amrinone and milrinone); diuretic natriuretic peptides, such as atrial natriuretic peptide, type B natriuretic peptide, etc. Thorium diuretic peptide or brain natriuretic peptide, type C natriuretic peptide (CNP) and dilating hormones, calcium sensitizers, for example, preferably levocimendan, NO-independent but hematoxylin-dependent guanylate cyclase stimulants, particularly compounds described in WO00 / 06568, WO00 / 06569, WO02 / 42301 and WO03 / 095451 (e.g., Riociguat), NO- and heme-independent guanylate cyclase activators.This includes, but is not limited to, the compounds described in WO 01 / 19355, WO 01 / 19776, WO 01 / 19778, WO 02 / 070462 and WO 02 / 070510, human neutrophil elastase (HNE) inhibitors such as sevirastaton or DX-890 (Reltran), compounds that inhibit signaling cascades, such as tyrosine kinase inhibitors, particularly sorafenib, imatinib, gefitinib, erlotinib, and / or compounds that affect cardiac energy metabolism, such as emoxetine, dichloroacetate, lanolazine, trimetazidine, etc. 【0143】 The compounds of the present invention can also be administered in combination with active ingredients other than those mentioned above. For example, in a preferred embodiment of the present invention, the compounds of the present invention are administered in combination with diuretics such as abscisic acid, bumetanide, torsemide, bendroflumethiazide, ketanserin, dihydrochlorothiazide, hydrofluoromethylthiazide, meclothiazide, porphyrin, triclothiazide, chlorthalidone, indapamide, metrazone, kinestrol, acetazolamide, diclobenzenesulfonamide, vinpocetine, glycerin, isosorbide, mannitol, amiloride, or aminopyralide. [Effects of the Invention] 【0144】 The present invention has the following beneficial effects. 【0145】 This invention provides a novel compound that acts as a mineralocorticoid receptor inhibitor, exhibits good semi-inhibitory concentrations, and is used to effectively treat and prevent conditions related to diabetic nephropathy, hypertension, heart failure, other cardiovascular diseases, and other aldosteronisms. [Brief explanation of the drawing] 【0146】 The advantages of the above and / or other embodiments of the present invention will become more apparent as the present invention is described more specifically below in relation to the attached drawings and specific embodiments. 【0147】 [Figure 1] The asymmetric unit diagram of the crystal structure of compound 36 is shown. [Figure 2] A single-cell diagram of the crystal structure of compound 36 is shown. [Figure 3] The packing diagram of the crystal structure of compound 36 is shown. [Figure 4] This shows a comparison of calculated and experimental crystalline XRPD diagrams for compound 36. [Figure 5] The asymmetric unit diagram of the crystal structure of compound 62 is shown. [Figure 6] A single-cell diagram of the crystal structure of compound 62 is shown. [Figure 7] The crystal structure packing diagram of compound 62 is shown. [Figure 8] This shows a comparison of calculated and experimental crystalline XRPD diagrams for compound 62. [Figure 9] A single-crystal microscope image of compound 36 is shown. [Figure 10] A single-crystal microscope image of compound 62 is shown. [Modes for carrying out the invention] 【0148】 In this specification, if there is a difference between the chemical name and the chemical structure, the structure shall prevail. 【0149】 In general, the compounds of the present invention can be prepared by the methods of the present invention unless otherwise indicated, where substituents are defined as shown in formula (I). The following reaction schemes and examples are used to further illustrate the present invention. 【0150】 Those skilled in the art will recognize that the chemical reactions described in the present invention can be used to suitably prepare other compounds of the present invention, and other methods for preparing the compounds of the present invention are considered to be within the scope of the present invention. For example, the synthesis of those not exemplified by the present invention can be successfully achieved by those skilled in the art by modification methods such as appropriate protection of interfering groups, by using other known reagents in addition to those described in the present invention, or by making some conventional modifications to the reaction conditions. Furthermore, it will be recognized that the reactions disclosed in the present invention or known reaction conditions are applicable to the preparation of other compounds of the present invention. 【0151】 In the examples described below, all temperatures are set in Celsius unless otherwise specified. Unless otherwise specified, reagents were purchased from commercially available suppliers such as Aldrich Chemical Company, Arco Chemical Company, and Alfa Chemical Company and used without further purification. Typical reagents were purchased from Shantou Xilonghua Plant, Guangdong Guanghua Chemical Reagent Plant, Guangzhou Chemical Reagent Plant, Tianjin Haoyuyu Chemical Co., Ltd., Qingdao Tenglong Chemical Reagent Co., Ltd., and Qingdao Marine Chemical Plant. 【0152】 Anhydrous tetrahydrofuran, dioxane, toluene, and ether were obtained by reflux drying over metallic sodium. Anhydrous dichloromethane and chloroform were obtained by reflux drying over calcium hydride. Ethyl acetate, petroleum ether, hexane, N,N-dimethylacetamide, and N,N-dimethylformamide were dried beforehand over anhydrous sodium sulfate before use. 【0153】 The following reactions are generally carried out under positive pressure under nitrogen or argon, or over anhydrous solvent in a dry tube (unless otherwise specified), the reaction flask is corked with a suitable rubber stopper, and the substrate is introduced by syringe. Glassware should be dry. 【0154】 Silica gel columns were used for chromatography. Silica gel (300-400 mesh) was purchased from the Qingdao Marine Chemical Plant. Nuclear magnetic resonance (MFC) spectroscopy data were measured using a Bruker Avance 400 or Bruker Avance III HD 600 spectrometer, with CDCl3, DMSO-d6, CD3OD, or Acetone-d6 as solvents (in ppm), and TMS (0 ppm) or chloroform (7.25 ppm) as the reference standard. When multiple peaks were present, the following abbreviations were used. s (singlet, single peak), d (doublet, double peak), t (triplet, triple peak), m (multiplet, multi-peak), q (quartet, quartet peak), br (broadened, broad peak), dd (doublet of doublets), dt (doublet of triplets), dq (doublet of quartets), ddd (doublet of doublets), ddt (doublet of doublets), dddd (doublet of doublets). The coupling constant is expressed in Hertz (Hz). 【0155】 Low-resolution mass spectrometry (MS) data were measured using an Agilent 6320 series LC-MS spectrometer equipped with a G1312A binary pump and a G1316A TCC (column temperature maintained at 30°C), with a G1329A autosampler and G1315B DAD detector applied to the analysis, and an ESI source applied to the LC-MS spectrometer. 【0156】 Low-resolution mass spectrometry (MS) data were measured using an Agilent 6120 series LC-MS spectrometer equipped with a G1311A quat pump and a G1316A TCC (column temperature maintained at 30°C), with a G1329A autosampler and G1315D DAD detector applied to the analysis, and an ESI source applied to the LC-MS spectrometer. 【0157】 Both of the above spectrometers are equipped with Agilent Zorbax SB-C18 columns with specifications of 2.1 × 30 mm and 5 μm. The injection volume is determined according to the sample concentration, the flow rate is 0.6 mL / min, and the HPLC peaks are recorded and read at UV-Vis wavelengths of 210 nm and 254 nm. The mobile phases are a 0.1% acetonitrile formate solution (phase A) and a 0.1% ultrapure aqueous solution of formate (phase B). The gradient elution conditions are shown in Table 1. 【0158】 Table 1 (Gradient elution conditions for mobile phases for low-resolution mass spectrometry) [Table 1] 【0159】 The following abbreviations are used in this invention. 【0160】 DMSO-d6 Deuterated Dimethyl Sulfoxide, g (grams), mg (milligrams), mol (moles), mmol (millimoles), mL (milliliters), μL (microliters). 【0161】 The following reaction schemes describe the steps in the preparation of the compounds disclosed in the present invention. Herein, unless otherwise specified, R1, R2, R3, R4, R6, R7, R8, and R9 all have the meanings described in the present invention. Unless otherwise specified, each reaction step in each reaction scheme described in the present invention is carried out in a solvent inert to the reaction, and the solvent inert to the reaction includes, but is not limited to, the solvents involved in the examples of the present invention or their substitutes. 【0162】 The method for preparing 4-(4-cyano-2-methoxylphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid, as described in the following examples, is as follows. [ka] 【0163】 (Example 1) 4-(5-ethoxy-2,8-dimethyl-3-oxazol-2-yl)-1,4-dihydro-1,6-naphthyridine-4-yl)-3-methoxybenzonitrile [ka] 【0164】 Step 1) 4-(4-cyano-2-methoxylphenyl)-N-(2,2-dimethoxylethyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide 4-(4-cyano-2-methoxylphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid (150 mg, 0.395 mmol), 2-(7-azobenzotriazolyl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (180 mg, 0.474 mmol), N,N-diisopropylethylamine (102 mg, 0.790 mmol), and N,N-dimethylcarboxamide (1.5 ml) were added to an 8 ml vial at room temperature. The mixture was allowed to react at room temperature for 2 hours. Aminoacetaldehyde dimethyl acetal (83 mg, 0.790 mmol) was added. The mixture was allowed to react overnight at room temperature. Water (15 ml) was added to quench the mixture. Extraction was performed with ethyl acetate (10 ml x 3 times), the organic phase was combined, washed with saturated saline solution (10 ml), and dried over anhydrous sodium sulfate. The solution was filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol (v / v) = 10 / 1) to obtain a pale yellow solid (86 mg, yield 47.0%). MS (ESI) M / Z:467.6 [M+H] + 【0165】 Step 2) 4-(4-cyano-2-methoxylphenyl)-5-ethoxy-2,8-dimethyl-N-(2-oxoethyl)-1,4-dihydro-1,6-naphthyridine-3-carboxamide 65 mg (0.139 mmol) of 4-(4-cyano-2-methoxylphenyl)-N-(2,2-dimethoxylethyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyrizine-3-carboxamide, 6 ml of acetone, and 42 ml of 12.0 M 36% concentrated hydrochloric acid solution were added to a 25 ml single-neck bottle at room temperature. The mixture was reacted at room temperature for 1 hour. Under an ice bath, saturated sodium bicarbonate aqueous solution was added to adjust the pH to 7. Ethyl acetate was added (10 ml x 3 times) for extraction, the organic phases were combined, washed with saturated saline solution (10 ml), and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol (v / v) = 10 / 1) to obtain a pale yellow solid (25 mg, yield 42.7%). MS(ESI) M / Z:421.5 [M+H] + 【0166】 Step 3) 4-(5-ethoxy-2,8-dimethyl-3-oxazol-2-yl)-1,4-dihydro-1,6-naphthyridine-4-yl)-3-methoxybenzonitrile 4-(4-cyano-2-methoxylphenyl)-5-ethoxy-2,8-dimethyl-N-(2-oxoethyl)-1,4-dihydro-1,6-naphthyridine-3-carboxamide (20 mg, 48.0 μmol), toluene (0.5 ml), and trichlormethrin (40.0 ml) were added to an 8 ml vial at room temperature. The mixture was heated to 120 °C and reacted for 1 hour. After cooling to room temperature, water (2 ml) was added, and ethyl acetate was added (2 ml x 3 times) for extraction. The organic phases were combined, washed with saturated saline solution (2 ml), and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated under reduced pressure. The obtained residue was purified by preparative high-performance liquid chromatography (purification conditions were as follows: chromatography column: XBridge Prep C18 OBD 30mm*150mm, 5μm; mobile phase: water (containing 0.1% formic acid) and acetonitrile; flow rate: 60 ml / min; gradient: 7 minutes, acetonitrile increased from 37% to 52%; detection wavelength: 254 / 220 nm), yielding a white solid (1.7 mg, yield 8.8%). MS(ESI) M / Z:403.50 [M+H] + 1 H NMR(400 MHz, Chloroform-d) δ 7.72(s, 1H), 7.50(s, 1H), 7.42(d, J =7.8 Hz, 1H), 7.21(d, J =7.8, 1H), 7.05(s, 1H), 6.99(s, 1H), 5.80(s, 1H), 5.70(s, 1H), 4.23-4.09(m, 2H), 3.78(s, 3H), 2.46(s, 3H), 2.17(s, 3H), 1.28-1.18(m, 3H). 【0167】 (Example 2) 4-(5-ethoxy-2,8-dimethyl-3-(1,3,4-oxadiazole-2-yl)-1,4-dihydro-1,6-naphthyridine-4-yl)-3-methoxybenzonitrile [ka] 【0168】 Step 1) 4-(4-cyano-2-methoxylphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carbohydrazide 4-(4-cyano-2-methoxylphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid (28 mg, 0.0740 mmol), dichloromethane (0.2 ml), and N,N-dimethylcarboxamide (0.05 ml) were added to an 8 ml vial at room temperature. After purging with nitrogen, oxalyl chloride (0.1 ml) was added dropwise under an ice water bath. The mixture was allowed to react at room temperature for 30 minutes. At room temperature, a solution of hydrazine hydrate (2 ml) and N,N-diisopropylethylamine (0.1 ml) in dichloromethane (0.5 ml) was added to the reaction mixture and stirred for 1 hour. Water (10 ml) was added to the reaction mixture, extracted with ethyl acetate (10 ml x 2), the organic phases were combined, washed with saturated brine (10 ml), and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated under reduced pressure to obtain a dark yellow oily substance (50 mg, crude product), which was used directly in the next step of the reaction. 【0169】 Step 2) 4-[5-ethoxy-2,8-dimethyl-3-(1,3,4-oxadiazole-2-yl)-1,4-dihydro-1,6-naphthyridine-4-yl]-3-methoxybenzonitrile 4-(4-cyano-2-methoxylphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyrizine-3-carbohydrazide (35 mg, 0.0890 mmol), triethyl orthoformate (2 ml), and p-toluenesulfonic acid (40 mg, 0.232 mmol) were sequentially added to an 8 ml vial at room temperature. After purging with nitrogen, the mixture was stirred at 120°C for 1 hour. The mixture was cooled to room temperature and concentrated under reduced pressure. The residue was purified in a dispensing dish (petroleum ether / ethyl acetate (v / v) = 2 / 1) to obtain a white solid (2.5 mg, 6.92%). MS(ESI) M / Z:403.95 [M+H] + 1H NMR(400 MHz, Chloroform-d) δ 8.24(s, 1H), 7.71(s, 1H), 7.42(d, J =7.8 Hz, 1H), 7.13(d, J =7.8 Hz, 1H), 7.01(s, 1H), 6.07(s, 1H), 5.64(s, 1H), 4.28-4.12(m, 2H), 3.77(s, 3H), 2.51(s, 3H), 2.19(s, 3H), 1.23(t, J =6.8 Hz, 3H). 【0170】 (Example 3) 4-(5-ethoxy-2,8-dimethyl-3-(5-methyl-1,3,4-oxadiazole-2-yl)-1,4-dihydro-1,6-naphthyridine-4-yl)-3-methoxybenzonitrile [ka] 4-(4-cyano-2-methoxylphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyrizine-3-carbohydrazide (20 mg, 0.0510 mmol), triethyl orthoacetate (2 ml), and p-toluenesulfonic acid (30 mg, 0.174 mmol) were sequentially added to an 8 ml vial at room temperature. After purging with nitrogen, the mixture was stirred at 120°C for 1 hour. The mixture was cooled to room temperature and concentrated under reduced pressure. The resulting residue was purified in a dispensing dish (petroleum ether / ethyl acetate (v / v) = 2:1) to obtain a white solid (1.9 mg, 8.93%). MS(ESI) M / Z:418.45 [M+H] + 1H NMR(300 MHz, Chloroform-d) δ7.71(s, 1H), 7.39(d, J =7.5 Hz, 1H), 7.12(dd, J1=7.8 Hz, J2=1.5 Hz, 1H), 7.00(d, J =1.5 Hz, 1H), 6.05(s, 1H), 5.62(s, 1H), 4.28 - 4.16(m, 2H), 3.79(s, 3H), 2.47(s, 3H), 2.45(s, 3H), 2.18(s, 3H), 1.22(t, J =9.6 Hz, 3H). 【0171】 (Example 4) 4-(4-cyano-2-methoxylphenyl)-5-ethoxy-2-methyl-4,7,8,9-tetrahydrocyclopentane-1H-cyclopentanamide [ka] 【0172】 Step 1) N-(2-cyanocyclopentan-1-en-1-yl)acetamide 1-amino-2-cyano-1-cyclopentene (5.00 g, 46.2 mmol) and acetic anhydride (32 ml) were added to a 100 ml single-neck bottle at room temperature. The mixture was reacted overnight at room temperature. The mixture was concentrated under reduced pressure, the residue was pulped with petroleum ether (10 ml x 3), and filtered to obtain white needle-shaped crystals (4.80 g, yield 69.1%). MS(ESI) M / Z:151.10 [M+H] + 【0173】 Step 2) 4-amino-1,5,6,7-tetrahydro-2H-cyclopentylpyridine-2-one N-(2-cyanocyclopentan-1-en-1-yl)acetamide (2.40 g, 14.4 mmol) and tetrahydrofuran (50 ml) were added to a 250 ml three-neck bottle at room temperature. After purging with nitrogen, lithium diisopropylammonium (12 ml, 88.6 mmol) was slowly added dropwise at -78°C. The mixture was reacted at -78°C for 30 minutes, then heated to 80°C and reacted overnight. After cooling to room temperature, saturated ammonium chloride aqueous solution (30 ml) was added to quench the reaction. Extraction was performed with ethyl acetate (30 ml x 3), the organic phases were combined, washed with saturated brine (30 ml), and dried over anhydrous sodium sulfate. The mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane / methanol (v / v) = 5 / 1) to obtain a pale yellow solid (1.25 g, yield 52.1%). MS(ESI) M / Z:151.10 [M+H] + 【0174】 Step 3) 2-Cyanoethyl 4-(4-cyano-2-methoxylphenyl)-5-hydroxy-2-methyl-1H,4H,7H,8H,9H-cyclopenta[h]1,6-naphthyridine-3-carboxylate 4-amino-1,5,6,7-tetrahydro-2H-cyclopentylpyridine-2-one (1.00 g, 6.66 mmol), 2-cyanoethyl-2-[(4-cyano-2-methoxylphenyl)methylidene]-3-oxobutyrate (2.18 g, 7.33 mmol), isopropanol (20 ml), and acetic acid (19 ml) were added to a 50 ml single-neck bottle at room temperature. After purging with nitrogen, the mixture was reacted overnight at 90°C. The mixture was cooled to room temperature and filtered. The resulting solid was pulped with methyl tert-butyl ether (5 ml x 3) and filtered to obtain a yellow solid (1.70 g, 60.4%). 【0175】 Step 4) 2-Cyanoethyl 4-(4-cyano-2-methoxylphenyl)-5-ethoxy-2-methyl-1H,4H,7H,8H,9H-cyclopenta[h]1,6-naphthyridine-3-carboxylate 2-Cyanoethyl 4-(4-cyano-2-methoxylphenyl)-5-hydroxy-2-methyl-1H,4H,7H,8H,9H-cyclopenta[h]1,6-naphthyridine-3-carboxylate (1.70 g, 4.02 mmol), methyl iodide (940 mg, 6.03 mmol), silver carbonate (1.11 g, 4.02 mmol), and 1,4-dioxane (15 ml) were added to a 50 ml single-neck bottle at room temperature. After purging with nitrogen, the mixture was reacted at 80°C for 1 hour. The mixture was cooled to room temperature and quenched with water (50 ml). Extraction was performed with ethyl acetate (50 ml x 3 times), the organic phases were combined, washed with saturated brine (50 ml), and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated under reduced pressure. The resulting residue was purified by preparative high-performance liquid chromatography. The purification conditions were as follows: chromatography column: C18 silica gel column, mobile phase A: water (containing 0.1% formic acid) and mobile phase B: acetonitrile, flow rate: 60 ml / min, gradient: 15 minutes, acetonitrile increased from 30% to 50%, detection wavelength: 254 nm. A yellow solid was obtained (460 mg, yield 25.0%). 【0176】 Step 5) 4-(4-cyano-2-methoxylphenyl)-5-ethoxy-2-methyl-4,7,8,9-tetrahydrocyclopentane[h][1,6]naphthyridine-3-carboxylic acid At room temperature, 440 mg (0.960 mmol) of 2-cyanoethyl 4-(4-cyano-2-methoxylphenyl)-5-ethoxy-2-methyl-1H,4H,7H,8H,9H-cyclopenta[h]1,6-naphthyrizine-3-carboxylate, 4.5 ml of ethylene glycol dimethyl ether, and 1.5 ml of an aqueous solution of sodium hydroxide (77 mg, 1.92 mmol) were added to a 50 ml single-neck bottle. The mixture was reacted at room temperature for 1 hour. The mixture was quenched with hydrochloric acid solution (1.0 mol / l) under an ice bath to adjust the pH to 5. The mixture was extracted with ethyl acetate (15 ml x 3 times), the organic phases were combined, washed with saturated brine (15 ml x 3 times), and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated under reduced pressure. The resulting residue was purified by preparative high-performance liquid chromatography. The purification conditions were as follows: chromatography column: C18 silica gel column, mobile phase A: water (containing 0.04% aqueous ammonia) and mobile phase B: acetonitrile, flow rate: 60 ml / min, gradient: 20 minutes, acetonitrile increased from 15% to 40%, detection wavelength: 254 nm. The product was collected and lyophilized under reduced pressure. 【0177】 A pale yellow solid was obtained (40 mg, yield 10.3%). 【0178】 Step 6) 4-(4-cyano-2-methoxylphenyl)-5-hydroxy-2-methyl-1H,4H,7H,8H,9H-cyclopenta-1,6-naphthyridine-3-carbonitrile 4-(4-cyano-2-methoxylphenyl)-5-ethoxy-2-methyl-4,7,8,9-tetrahydrocyclopentane[h][1,6]naphthyrizine-3-carboxylic acid (40 mg, 0.100 mmol), N,N-diisopropylethylamine (38 mg, 0.297 mmol), N,N-dimethylcarboxamide (1.5 ml), and 2-(7-azobenzotriazolyl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (19 mg, 0.119 mmol) were added to an 8 ml vial at room temperature. The mixture was allowed to react at room temperature for 1 hour. At room temperature, a solution of 1,4-dioxane ammonia (1.0 M, 0.5 ml) was added to the reaction mixture. The mixture was allowed to react at 60°C for 3 hours. The mixture was cooled to room temperature and quenched with water (15 ml). Extraction was performed with ethyl acetate (15 ml x 3 times), the organic phase was combined, washed with saturated brine (15 ml x 3 times), and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated under reduced pressure. The resulting residue was purified by preparative high-performance liquid chromatography. The purification conditions were as follows: chromatography column: Sunfire prep C18, mobile phase A: water (containing 0.1% formic acid) and mobile phase B: acetonitrile, flow rate: 60 ml / min, gradient: 7 minutes, acetonitrile increased from 20% to 42%, detection wavelength: 254 nm. The product was collected, lyophilized under reduced pressure, and a white solid was obtained (9.0 mg, yield 22.6%). MS(ESI) M / Z:405.45 [M+H] + 1 H NMR(400 MHz,DMSO-d6) δ8.05(s,1H),7.36(s,1H),7.28(d,J=7.6 Hz,1H),7.15(d,J=7.6 Hz,1H),6.65(s,1H),5.33(s,1H),4.03 - 3.97(m,2H),3.83(s,3H),2.76(t,J=7.2 Hz,1H),2.68(t,J=7.2 Hz,1H),2.17(s,3H),2.08 - 1.90(m,2H),1.04(t,J=7.2 Hz,3H). 【0179】 (Example 5) 4-(4-cyano-2-methoxylphenyl)-2-methyl-4,7,8,9-tetrahydrocyclopentane-3-carbonitrile [ka] 【0180】 At room temperature, a solution of 2,3-dihydro-4-indenamine (12 mg, 0.0890 mmol), 4-cyano-2-methoxybenzaldehyde (24 mg, 0.150 mmol), sodium 1-cyanopropene-2-pentanoate (16 mg, 0.150 mmol), and glacial acetic acid (9 ml) in isopropanol (0.5 ml) was added to an 8 ml vial. After purging with nitrogen, the mixture was heated to 90°C and reacted overnight. It was cooled to room temperature. The mixture was concentrated under reduced pressure, and the resulting residue was purified by C18 reversed-phase column chromatography under the following conditions: (C18 BIOTAGE 40 g reversed-phase column, mobile phase A (0.1% formic acid aqueous solution) and mobile phase B (acetonitrile), from 15% B to 50% B over 15 minutes, monitoring wavelength 254 nm), yielding a pale yellow solid (2.3 mg, yield 4.5%). MS(ESI) M / Z: 340.25 [MH] - 1 H NMR(400 MHz,Chloroform-d) δ7.18 - 7.16(m,1H),7.14 - 7.09(m,2H),6.78(s,3H),5.90(s,1H),5.49(s,1H),3.93(s,3H),2.90 - 2.75(m,4H),2.24(s,3H),2.19 - 2.12(m,2H). 【0181】 (Example 6) 4-(5-cyanochrome-8-yl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide [ka] [ka] 【0182】 Step 1) Methyl 2-allyloxy-4-bromobenzoate 5.00 g, 21.6 mmol methyl 4-bromo-2-hydroxybenzoate, 5.98 g, 43.3 mmol potassium carbonate, 50 ml N,N-dimethylcarboxamide, and 3.75 g, 43.3 mmol 3-bromopropene were added to a 250 ml single-neck bottle at room temperature. The mixture was heated to 80°C and reacted for 2 hours. It was cooled to room temperature. Water (300 ml) was added to quench the mixture. The mixture was extracted with ethyl acetate (500 ml x 3), the organic phases were combined, washed with saturated brine (500 ml), and dried over anhydrous sodium sulfate. The mixture was filtered, concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 5:1) to obtain a yellow solid (4.32 g, yield 69.9%). LCMS(ESI,m / z): 271.0 [M+H] + 【0183】 Step 2) Methyl 3-allyl-4-bromo-2-hydroxybenzoate 4.19 g, 15.5 mmol of methyl 2-allyloxy-4-bromobenzoate and 30 ml of N-methylpyrrolidone were added to a 250 ml single-neck bottle at room temperature. The mixture was heated to 200 °C and reacted for 4 hours. It was cooled to room temperature. Water (300 ml) was added to quench the mixture. The mixture was extracted with ethyl acetate (500 ml x 3), the organic phases were combined, washed with saturated brine (500 ml), and dried over anhydrous sodium sulfate. The mixture was filtered, concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 4:1) to obtain a colorless oily substance (2.66 g, yield 63.4%). LCMS(ESI,m / z): 271.1 [M+H] + 【0184】 Step 3) 4-Bromo-2-hydroxy-3-(3-hydroxypropyl)methyl benzoate 4.19 g, 15.5 mmol of methyl 3-allyl-4-bromo-2-hydroxybenzoate and 30 ml of N-methylpyrrolidone were added to a 250 ml single-neck bottle at room temperature. The mixture was heated to 200 °C and reacted for 4 hours. It was cooled to room temperature. Water (300 ml) was added to quench the mixture. The mixture was extracted with ethyl acetate (500 ml x 3), the organic phases were combined, washed with saturated brine (500 ml), and dried over anhydrous sodium sulfate. The mixture was filtered, concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 4:1) to obtain a colorless oily substance (2.31 g, yield 83.3%). LCMS(ESI,m / z): 289.1 [M+H] + 【0185】 Step 4) 5-bromochrome-8-carboxylate methyl 4-bromo-2-hydroxy-3-(3-hydroxypropyl)methyl benzoate (2.31 g, 7.99 mmol), triphenylphosphine (5.03 g, 19.2 mmol), and tetrahydrofuran (40 ml) were added to a 100 ml single-neck bottle at room temperature. After nitrogen purging, diethyl azodicarboxylate (3.34 g, 19.2 mmol) was slowly added dropwise under ice bath. The mixture was allowed to react overnight at room temperature. It was cooled to room temperature. Water (100 ml) was added to quench the reaction. The mixture was extracted with ethyl acetate (100 ml x 3), the organic phases were combined, washed with saturated brine (100 ml), and dried over anhydrous sodium sulfate. The mixture was filtered, concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 5:1) to obtain a yellow oily substance (1.67 g, yield 77.1%). LCMS(ESI,m / z): 271.1 [M+H] + 【0186】 Step 5) 5-cyanochrome-8-carboxylate methyl At room temperature, 5-bromochrome-8-carboxylate methyl (1.62 g, 5.96 mmol), zinc cyanide (3.51 g, 29.9 mmol), tris(dibenzylideneacetone)dipalladium (1.09 g, 1.20 mmol), 1,1'-bis(diphenylphosphino)ferrocene (1.32 g, 2.40 mmol), and N-methylpyrrolidone (30 ml) were added to a 50 ml single-neck bottle. After purging with nitrogen, the mixture was heated to 120 °C and reacted for 2 hours. It was cooled to room temperature. An aqueous solution (100 ml) was added to quench the mixture. Extraction was performed with ethyl acetate (100 ml x 3), the organic phases were combined, washed with saturated brine (100 ml), and dried over anhydrous sodium sulfate. The mixture was filtered, concentrated under reduced pressure, and the residue was purified by column chromatography (petroleum ether / ethyl acetate (v / v) = 4:1) to obtain a white solid (952 mg, yield 73.3%). LCMS(ESI,m / z): 218.1 [M+H] + 【0187】 Step 6) 8-hydroxymethyl-5-cromonitrile 5-Cyanochrome-8-carboxylate methyl (860 mg, 3.96 mmol), tetrahydrofuran (10 ml), and a solution of lithium borohydride in tetrahydrofuran (3.96 ml, 2.0 mol / l, 7.92 mmol) were added to a 50 ml single-neck bottle at room temperature. After purging with nitrogen, the mixture was heated to 60°C and reacted for 15 minutes. It was cooled to room temperature. Water (30 ml) was added to quench the mixture. The mixture was extracted with ethyl acetate (30 ml x 3), the organic phases were combined, washed with saturated brine (30 ml), and dried over anhydrous sodium sulfate. The mixture was filtered, concentrated under reduced pressure, and the residue was purified by column chromatography (petroleum ether / ethyl acetate (v / v) = 3:1) to obtain a yellow oily substance (450 mg, yield 60.1%). LCMS(ESI,m / z): 190.1 [M+H] + 【0188】 Step 7) 8-Formil Roman-5-Carbonitrile 8-hydroxymethyl-5-cromonitrile (385 mg, 1.75 mmol), dichloromethane (5 ml), and Dess Martin's reagent (890 mg, 2.10 mmol) were added to a 25 ml single-neck bottle at room temperature. The mixture was reacted at room temperature for 2 hours. The mixture was concentrated under reduced pressure, and the residue was purified by column chromatography (petroleum ether / ethyl acetate (v / v) = 6:1) to obtain a yellow solid (280 mg, yield 72.9%). LCMS(ESI,m / z): 188.1 [M+H] + 【0189】 Step 8) 2-Cyanoethyl 4-(5-Cyano-8-Hydroxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylate) 8-Formil-chroman-5-carbonitrile (200 mg, 1.07 mmol), 4-amino-5-methylpyridine-2-ol (200 mg, 1.61 mmol), 3-oxobutanoate 2-cyanoethyl (200 mg, 1.29 mmol), isopropanol (5 ml), and acetic acid (90 ml) were added to an 8 ml vial at room temperature. After purging with nitrogen, the mixture was reacted overnight at 90°C. After cooling to room temperature and concentrating under reduced pressure, the resulting residue was purified by C18 reversed-phase column chromatography under the following conditions (C18 BIOTAGE 120 g reversed-phase column, mobile phase A (0.1% formic acid aqueous solution) and mobile phase B (acetonitrile), from 20%B to 50%B over 15 minutes, monitoring wavelength 254 nm), yielding a yellow solid (175 mg, yield 36.7%). LCMS(ESI,m / z): 431.2 [M+H] + 【0190】 Step 9) 2-Cyanoethyl 4-(5-cyano-8-cyano)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylate 2-Cyanoethyl 4-(5-cyano-8-hydroxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylate) (175 mg, 0.407 mmol), silver carbonate (112 mg, 0.407 mmol), ethyl iodide (95 mg, 0.610 mmol), and 1,4-dioxane (2 ml) were added to an 8 ml vial at room temperature. After purging with nitrogen, the mixture was reacted at 90°C for 2 hours. The mixture was cooled to room temperature, filtered, and the filter cake was washed with ethyl acetate (50 ml). The filtrate was collected and concentrated under reduced pressure. The resulting residue was purified by C18 reversed-phase column chromatography under the following conditions: C18 BIOTAGE 120g reversed-phase chromatography column, mobile phase A: (0.1% aqueous ammonium bicarbonate solution) and mobile phase B: (acetonitrile), gradient from 15%B to 60%B for 10 minutes, and a pale yellow oily substance was obtained using a 254nm ultraviolet detector (134 mg, yield 71.9%). LCMS(ESI,m / z):459.2 [M+H] + 【0191】 Step 10) 4-(5-cyanochrome-8-yl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid At room temperature, 134 mg (0.292 mmol) of 2-cyanoethyl 4-(5-cyano-8-cyano)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylate, 1 ml of ethylene glycol dimethyl ether, and 0.5 ml of an aqueous solution of sodium hydroxide (24 mg, 0.600 mmol) were added to an 8 ml single-neck bottle. The mixture was reacted at room temperature for 1 hour. The mixture was quenched with hydrochloric acid solution (1.0 mol / l) under an ice bath to adjust the pH to 5. The mixture was extracted with ethyl acetate (20 ml x 3 times), the organic phases were combined, washed with saturated brine (20 ml), and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated under reduced pressure to obtain a pale yellow solid (83 mg, 70.1%), which was used directly in the next step without further purification. LCMS(ESI,m / z): 406.2 [M+H] + 【0192】 Step 11) 4-(5-cyanochrome-8-yl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide 4-(5-cyanochrome-8-yl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid (80 mg, 0.197 mmol), N,N-diisopropylethylamine (77 mg, 0.591 mmol), N,N-dimethylcarboxamide (2 ml), and 2-(7-azobenzotriazolyl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (225 mg, 0.591 mmol) were added to an 8 ml vial at room temperature. The mixture was allowed to react at room temperature for 1 hour. A solution of aqueous ammonia (1.0 M, 0.7 ml) was added to the reaction mixture at room temperature. The mixture was allowed to react at room temperature for 2 hours. The mixture was filtered, and the resulting filtrate was purified by preparative high-performance liquid chromatography. The purification conditions were as follows: chromatography column: YMC-Actus Triart C18, mobile phase A: water (containing 0.1% ammonium bicarbonate) and mobile phase B: acetonitrile, flow rate: 60 ml / min, gradient: 7 minutes, acetonitrile increased from 25% to 45%, detection wavelength: 254 / 220 nm. The product was collected, lyophilized under reduced pressure, and a yellow solid was obtained (59.0 mg, yield 73.9%). LCMS(ESI,m / z): 405.25 [M+H] + 1 H NMR(400 MHz,DMSO-d6) δ 7.70(s,1H),7.56(s,1H),7.18(d,J=8.0 Hz,1H),6.94(d,J=8.0 Hz,1H),6.68(s,2H),5.32(s,1H),4.28 - 4.20(m,2H),4.05(q,J=7.2 Hz,1H),2.87(t,J=6.4 Hz,2H),2.21(s,3H),2.12(s,3H),2.03 - 1.94(m,2H),1.10(t,J=7.2 Hz,3H). 【0193】 (Example 7) 10-(4-cyano-2-methoxylphenyl)-6,8-dimethyl-7H,10H-pyrazolo[3,2-f]1,6-naphthyridine-9-carbonitrile [ka] 【0194】 Step 1) N-(2-bromo-5-methylpyridine-4-yl)aminoformate tert-butyl 2-bromo-5-methylpyridine-4-amine (1.00 g, 5.35 mmol), N,N-dimethylpyridine-4-amine (66 ml, 0.540 mmol), di-tert-butyl dicarbonate (1.4 g, 6.42 mmol), and acetonitrile (12 ml) were added to a 50 ml single-neck bottle at room temperature. The mixture was reacted at room temperature for 3 hours. It was cooled to room temperature. Water (30 ml) was added to quench the mixture. The mixture was extracted with ethyl acetate (30 ml x 3), the organic phases were combined, washed with saturated brine (30 ml), and dried over anhydrous sodium sulfate. The mixture was filtered, concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate (v / v) = 3 / 1) to obtain a yellow solid (1.05 g, yield 28.3%). MS(ESI) M / Z:288 [MH] - 【0195】 Step 2) N-{5-methyl-2-[2-(trimethylsilyl)ethynyl]pyridine-4-yl}aminoformate tert-butyl In a 100 ml single-neck bottle at room temperature, tert-butyl N-(2-bromo-5-methylpyridine-4-yl)aminoformate (1.0 g, 3.48 mmol), bis(triphenylphosphine)palladium dichloride (733 mg, 1.05 mmol), cuprous iodide (3.99 g, 2.10 mmol), trimethylsilylacetylsilane (4.51 ml, 34.8 mmol), and tetrahydrofuran (30 ml) were added. After purging with nitrogen, the mixture was heated to 110 °C and reacted for 2 hours. The mixture was cooled to room temperature. The mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate (v / v) = 5 / 1) to obtain a gray solid (640 mg, yield 56.1%). MS(ESI) M / Z:303.20 [MH] - 【0196】 Step 3) 1-amino-4-[tert-butoxycarbonylamino]-5-methyl-2-[2-(trimethylsilyl)ethynyl]pyridine-1-salt At room temperature, tert-butyl N-{5-methyl-2-[2-(trimethylsilyl)ethynyl]pyridine-4-yl}aminoformate (130 mg, 0.427 mmol), dichloromethane (2.5 ml), and amino 2,4,6-trimethylbenzene sulfonate (276 mg, 1.28 mmol) were added to an 8 ml vial. After purging with nitrogen, the mixture was reacted at room temperature for 2 hours. The mixture was cooled to room temperature. The mixture was concentrated under reduced pressure, and the residue was obtained as methyl tert-butyl ether (5 ml x 3), a gray solid (120 mg, yield 87.7%). MS(ESI) M / Z:319.90 [MH] - 【0197】 Step 4) N-{6-methylpyrazolo[1,5-a]pyridin-5-yl}aminoformate tert-butyl 1-amino-4-[tert-butoxycarbonylamino]-5-methyl-2-[2-(trimethylsilyl)ethynyl]pyridine-1-salt (400 mg, 1.25 mmol), potassium carbonate (345 mg, 2.45 mmol), and N,N-dimethylcarboxamide (4 ml) were added to an 8 ml vial at room temperature. After purging with nitrogen, the mixture was heated to 80°C and reacted for 5 hours. The mixture was cooled to room temperature. The filtrate was filtered and purified by C18 reversed-phase column chromatography under the following conditions (C18 BIOTAGE 40 g reversed-phase column, mobile phase A (0.1% formic acid aqueous solution) and mobile phase B (acetonitrile), 15 minutes from 40%B to 90%B, monitoring wavelength 254 nm), yielding a gray solid (100 mg, yield 28.2%). MS(ESI) M / Z:248.25 [M+H] + 【0198】 Step 5) 6-Methylpyrazolo[1,5-a]pyridine-5-amine 200 mg, 0.81 mmol, tert-butyl N-{6-methylpyrazolo[1,5-a]pyridin-5-yl}aminoformate, 4 ml dichloromethane, and 1 ml trifluoroacetic acid were added to a 25 ml single-neck bottle at room temperature. The mixture was reacted at room temperature for 2 hours. The mixture was concentrated under reduced pressure, the residue was dissolved in ethyl acetate (10 ml), washed sequentially with saturated sodium bicarbonate aqueous solution (10 ml) and saturated saline solution (10 ml), and dried over anhydrous sodium sulfate. The mixture was concentrated under reduced pressure to obtain a gray solid (100 mg, yield 84.1%). 【0199】 Step 6) 10-(4-cyano-2-methoxylphenyl)-6,8-dimethyl-7H,10H-pyrazolo[3,2-f]1,6-naphthyridine-9-carbonitrile 6-methylpyrazolo[1,5-a]pyridine-5-amine (85 mg, 0.578 mmol), 4-(2-cyano-3-oxobut-1-en-1-yl)-3-methoxybenzonitrile (145 mg, 0.639 mmol), and a solution of glacial acetic acid (36 ml) in isopropanol (2 ml) were added to an 8 ml vial at room temperature. After purging with nitrogen, the mixture was heated to 90°C and reacted overnight. It was cooled to room temperature. The mixture was concentrated under reduced pressure, and the resulting residue was purified by C18 reversed-phase column chromatography under the following conditions: (C18 BIOTAGE 40 g reversed-phase column, mobile phase A (0.1% formic acid aqueous solution) and mobile phase B (acetonitrile), 15 minutes from 15%B to 45%B, monitoring wavelength 254 nm), yielding a white solid (7 mg, yield 3.4%). LCMS(ESI,m / z): 356.15 [M+H] + 1 H NMR(400 MHz,DMSO-d6) δ 8.70(s,1H), 8.41(s,1H), 7.68(s,1H), 7.52(s,1H), 7.33(d,J=8.0 Hz,1H), 7.26(d,J=8.0 Hz,1H), 5.92(s,1H), 5.46(s,1H), 3.95(s,3H), 2.30(s,3H), 2.20(s,3H). 【0200】 (Example 8) 4-(4-cyano-2-methoxylphenyl)-2-methyl-1,4-dihydrobenzo[4,5]thieno[2,3-b]pyridine-3-carbonitrile [ka] 【0201】 Step 1) 1-Cyanopropene-2-Enoate Sodium 5.00 g, 60.0 mmol of sodium methanol and 30 ml of anhydrous methanol were added to a 100 ml single-neck bottle at room temperature. 3.25 g, 60.0 mmol of 5-methylisoxazole was added dropwise in an ice bath. The mixture was allowed to react overnight at room temperature. A precipitate formed. The mixture was filtered, and the resulting solid was pulped with 15 ml of methanol and filtered to obtain a yellow solid (3.10 g, yield 84.7%). 【0202】 Step 2) 4-(2-cyano-3-oxobuto-1-en-1-yl)-3-methoxybenzonitrile 1-Cyanopropene-2-enoate sodium (3.00 g, 28.6 mmol), 4-formyl-3-methoxybenzonitrile (4.59 g, 28.6 mmol), dichloromethane (50 ml), piperidine (240 mg, 2.85 mmol), and glacial acetic acid (2.28 g, 57.1 mmol) were added to a 100 ml single-neck bottle at room temperature. After purging with nitrogen, the mixture was heated to 60°C and reacted overnight. It was then cooled to room temperature. The mixture was concentrated under reduced pressure, the residue was pulped with ethyl acetate (10 ml x 5), and filtered to obtain a yellow solid (2.50 g, yield 38.8%). MS(ESI) M / Z:227.95 [M+H] + 【0203】 Step 3) 4-(4-cyano-2-methoxylphenyl)-2-methyl-1,4-dihydrobenzo[4,5]thieno[2,3-b]pyridine-3-carbonitrile At room temperature, a solution of 1-benzothiophene-2-amine (50 mg, 0.335 mmol), 4-(2-cyano-3-oxobuto-1-en-1-yl)-3-methoxybenzonitrile (76 mg, 0.335 mmol), and glacial acetic acid (9 ml) in isopropanol (0.5 ml) was added to an 8 ml vial. After purging with nitrogen, the mixture was heated to 80°C and reacted for 1 hour. The mixture was then cooled to room temperature. The solution was concentrated under reduced pressure, and the resulting residue was purified by preparative high-performance liquid chromatography (column model: Sunfire prep C18 silica gel column, 30*150 mm, 5 μm, mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile, flow rate: 60 ml / min, gradient: 48%B to 68%B over 8 minutes, 68%B, wavelength: 254 / 220 nm, peak time (min): 6.90), yielding a white solid (22.3 mg, yield 18.1%). MS(ESI) M / Z:356.05 [MH] - 1 H NMR(400 MHz,DMSO-d6) δ 10.25(s,1H), 7.81 - 7.75(m,1H), 7.50(S,1H) 7.38 - 7.22(m,2H), 7.20 - 7.10(m,2H), 7.08 - 7.02(m,1H), 5.60(s,1H), 3.97(s,3H), 2.13(s,3H). 【0204】 (Example 9) 4-(4-cyano-2-methoxylphenyl)-3-ethoxy-1,6-dimethyl-4,7-dihydropyrazolo[3,4-b]pyridine-5-carbonitrile [ka] 【0205】 Step 1) N-(2-cyanocyclopentan-1-en-1-yl)acetamide 3-hydroxy-1-methylpyrazole-5-carboxylate methyl (2.30 g, 14.7 mmol), ethyl iodide (3.40 g, 22.1 mmol), potassium carbonate (2.00 g, 14.7 mmol), and N,N-dimethylcarboxamide (25 ml) were added to a 100 ml single-neck bottle at room temperature. After purging with nitrogen, the mixture was heated to 60°C and reacted for 5 hours. It was cooled to room temperature. Water (30 ml) was added to quench the mixture. The mixture was extracted with ethyl acetate (30 ml x 3), the organic phases were combined, washed with saturated brine (30 ml), and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated under reduced pressure to obtain a pale yellow oily substance (2.30 g, yield 84.7%). LCMS(ESI,m / z):185.10 [M+H] + 【0206】 Step 2) 3-ethoxy-1-methylpyrazole-5-carboxylic acid N-(2-cyanocyclopentan-1-en-1-yl)acetamide (2.30 g, 12.5 mmol), tetrahydrofuran (15 ml), and saturated aqueous solution of lithium hydroxide (15 ml) were added to a 100 ml single-neck bottle at room temperature. The mixture was reacted at room temperature for 3 hours. The solution was quenched with dilute hydrochloric acid solution (1.0 mol / l) to adjust the pH to 5. The mixture was extracted with ethyl acetate (30 ml x 3 times), the organic phases were combined, washed with saturated saline solution (30 ml), and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated under reduced pressure to obtain a white solid (2.00 g, yield 94.1%). LCMS(ESI,m / z):171.10 [M+H] + 【0207】 Step 3) tert-butyl(3-ethoxy-1-methylpyrazole-5-yl)carbamate 3-ethoxy-1-methylpyrazole-5-carboxylic acid (2.00 g, 11.7 mmol), triethylamine (3.57 g, 35.3 mmol), and tert-butyl alcohol (15 ml) were added to a 100 ml single-neck bottle at room temperature. After nitrogen purging, diphenyl phosphoryl azide (4.85 g, 17.6 mmol) was slowly added dropwise. The mixture was heated to 80°C and allowed to react overnight. It was cooled to room temperature. Water (20 ml) was added to quench the reaction. The mixture was extracted with ethyl acetate (30 ml x 3 times), the organic phases were combined, washed with saturated saline solution (30 ml), and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated under reduced pressure. The obtained residue was purified by C18 reversed-phase column chromatography under the following conditions (C18 BIOTAGE 40g reversed-phase column, mobile phase A (0.1% formic acid aqueous solution) and mobile phase B (acetonitrile), 10 minutes from 30%B to 50%B, monitoring wavelength 254nm), yielding a white solid (1.60g, yield 56.4%). LCMS(ESI,m / z):242.20 [M+H] + 【0208】 Step 4) 3-ethoxy-1-methylpyrazole-5-amine 800 mg (3.32 mmol) of tert-butyl (3-ethoxy-1-methylpyrazole-5-yl) carbamate and 5 ml (4.0 M, 5 ml) of 1,4-dioxane solution of hydrogen chloride were added to a 25 ml single-neck bottle at room temperature. The mixture was stirred overnight at room temperature. Saturated sodium bicarbonate aqueous solution was added to quench the mixture and adjust the pH to 7. The mixture was extracted with ethyl acetate (50 ml x 3 times), the organic phases were combined, washed with saturated saline solution (30 ml), and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated under reduced pressure to obtain a yellow solid (405 mg, yield 86.5%). LCMS(ESI,m / z):142.10 [M+H] + 【0209】 Step 5) 4-(4-cyano-2-methoxylphenyl)-3-ethoxy-1,6-dimethyl-4,7-dihydropyrazolo[3,4-b]pyridine-5-carbonitrile At room temperature, a solution of 3-ethoxy-1-methylpyrazole-5-amine (50 mg, 0.344 mmol), 4-(2-cyano-3-oxobut-1-en-1-yl)-3-methoxybenzonitrile (78 mg, 0.344 mmol), and glacial acetic acid (18 ml) in isopropanol (1 ml) was added to an 8 ml vial. Under nitrogen protection, the mixture was heated to 80°C and reacted for 2 hours. After cooling to room temperature, water (5 ml) was added to quench the reaction. Extraction was performed with ethyl acetate (10 ml x 3 times), the organic phases were combined, washed with saturated saline solution (10 ml), and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated under reduced pressure. The obtained residue was purified by C18 reversed-phase column chromatography under the following conditions (C18 BIOTAGE 40g reversed-phase column, mobile phase A (10 mmol / l ammonium bicarbonate aqueous solution) and mobile phase B (acetonitrile), 10 minutes from 30%B to 50%B, monitoring wavelength 254 nm), yielding a white solid (8.5 mg, yield 7.73%). MS(ESI)M / Z:350.20 [M+H] + . 1 H NMR(300 MHz,DMSO-d6)δ 9.74(s,1H), 7.47(s,1H), 7.38(d,J=7.9 Hz,1H), 7.17(d,J=7.9 Hz,1H), 5.16(s,1H), 3.99 - 3.78(m,5H), 3.80(s,3H), 2.13(s,3H), 1.03(t,J=7.0 Hz,3H). 【0210】 (Example 10) 9-(4-cyano-2-methoxylphenyl)-5,7-dimethyl-6,9-dihydro[1,2,4]tricleoxazolo[4,3-a][1,5]naphthyridine-8-carbonitrile [ka] 【0211】 Step 1) 1-Cyanopropene-2-Enoate Sodium Sodium methanol (5.00 g, 60.0 mmol) and anhydrous methanol (30 ml) were added to a 100 ml single-neck bottle at room temperature. 5-methylisoxazole (3.25 g, 60.0 mmol) was added dropwise under an ice bath. The mixture was reacted overnight at room temperature. A precipitate formed. The mixture was filtered, and the resulting solid was pulped with methanol (15 ml), filtered, and a yellow solid was obtained (3.10 g, yield 84.7%). 【0212】 Step 2) 4-(2-cyano-3-oxobuto-1-en-1-yl)-3-methoxybenzonitrile 1-Cyanopropene-2-enoate sodium (3.00 g, 28.6 mmol), 4-formyl-3-methoxybenzonitrile (4.59 g, 28.6 mmol), dichloromethane (50 ml), piperidine (240 mg, 2.85 mmol), and glacial acetic acid (2.28 g, 57.1 mmol) were added to a 100 ml single-neck bottle at room temperature. After purging with nitrogen, the mixture was heated to 60°C and reacted overnight. The mixture was cooled to room temperature. The mixture was concentrated under reduced pressure, the residue was pulped with ethyl acetate (10 ml x 5), and filtered to obtain a yellow solid (2.50 g, yield 38.8%). 【0213】 Step 3) 2-Hydrazino-4-methyl-5-nitropyridine 6-chloro-2-methyl-3-nitropyridine (1.73 g, 10.0 mmol) and 1,4-dioxane (15 ml) were added to a 100 ml single-neck bottle at room temperature. Hydrazine hydrate (2.00 g, 40 mmol) was added under ice water bath conditions. The mixture was reacted overnight at room temperature. The mixture was concentrated under reduced pressure. The residue was pulped with water (5 ml) and filtered to obtain a pale yellow solid (1.30 g, crude product). This was used directly in the next step without further purification. 【0214】 Step 4) 7-methyl-6-nitro[1,2,4]tricleoxazolo[4,3-a]pyridine 2-Hydrazino-4-methyl-5-nitropyridine (1.00 g, 5.95 mmol), triethyl orthoformate (2.52 g, 23.8 mmol), and dichloromethane (50 ml) were added to a 100 ml single-neck bottle at room temperature. Trifluoroacetic acid (140 mg, 1.19 mmol) was added under an ice bath. The mixture was reacted overnight at room temperature. The mixture was concentrated under reduced pressure to obtain a pale yellow solid (900 mg, crude product). 【0215】 Step 5) 7-methyl-[1,2,4]tricleoxazolo[4,3-a]pyridine-6-amine 7-methyl-6-nitro[1,2,4]tricleoxazolo[4,3-a]pyridine (900 mg, 5.01 mmol), iron powder (1.13 g, 20.2 mmol), ammonium chloride (1.07 g, 20.2 mmol), and tetrahydrofuran (50 ml) were added to a 100 ml single-neck bottle at room temperature. The mixture was heated to 50°C and reacted overnight. After cooling to room temperature, the mixture was filtered through diatomaceous earth, concentrated under reduced pressure, and the residue was purified by column chromatography (petroleum ether / ethyl acetate (v / v) = 2 / 1) to obtain a pale yellow solid (400 mg, yield 53.5%). 【0216】 Step 6) 9-(4-cyano-2-methoxylphenyl)-5,7-dimethyl-6,9-dihydro[1,2,4]tricleoxazolo[4,3-a][1,5]naphthyridine-8-carbonitrile 7-methyl-[1,2,4]tricleoxazolo[4,3-a]pyridine-6-amine (50 mg, 0.337 mmol), 4-(2-cyano-3-oxobut-1-en-1-yl)-3-methoxybenzonitrile (76 mg, 0.337 mmol), and a solution of glacial acetic acid (54 ml) in isopropanol (3 ml) were added to an 8 ml vial at room temperature. After purging with nitrogen, the mixture was heated to 80°C and reacted overnight. The mixture was cooled to room temperature. The mixture was concentrated under reduced pressure, and the resulting residue was purified by C18 reversed-phase column chromatography under the following conditions (C18 BIOTAGE 40 g reversed-phase column, mobile phase A (0.1% formic acid aqueous solution) and mobile phase B (acetonitrile), 10 minutes from 30%B to 50%B, monitoring wavelength 254 nm), yielding a white solid (20.0 mg, yield 16.7%). MS(ESI)M / Z:357.15[M+H] + 1 H NMR (400 MHz,DMSO-d6)δ 8.80(s,1H), 8.18(s,1H), 7.82-7.52(m,2H), 7.28(s,1H), 7.04(s,1H), 5.89(s,1H), 3.88(s,3H), 2.19(s,3H). 【0217】 (Example 11) 4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide [ka] 【0218】 Step 1) 4-amino-5-chloro-2,3-dihydro-1-benzofuran-7-carboxylate methyl 4-amino-5-chloro-2,3-dihydro-1-benzofuran-7-carboxylic acid (10.0 g, 46.9 mmol) and methanol (200 ml) were added to a 500 ml single-neck bottle at room temperature. Dichlorosulfoxide (8.35 g, 61.9 mmol) was slowly added dropwise under an ice bath. The mixture was heated to 70°C and reacted for 1.5 hours. It was cooled to room temperature. Saturated sodium bicarbonate aqueous solution (300 ml) was added to quench the mixture. The mixture was extracted with ethyl acetate (500 ml x 3), the organic phases were combined, washed with saturated brine (500 ml), and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated under reduced pressure to obtain a yellow solid (10.5 g, yield 98.5%). LCMS(ESI,m / z):228.6 [M+H] + 【0219】 Step 2) 4-amino-2,3-dihydro-1-benzofuran-7-carboxylate methyl 4-amino-5-chloro-2,3-dihydro-1-benzofuran-7-carboxylate methyl (10.5 g, 46.2 mmol), 10% palladium carbon (5.35 g, 4.99 mmol), sodium hydroxide (3.15 g, 78.8 mmol), and methanol (200 ml) were added to a 500 ml sealed tube liner at room temperature. The mixture was heated to 30°C under a hydrogen pressure of 3 atmospheres and allowed to react overnight. It was cooled to room temperature. The mixture was filtered through diatomaceous earth, and the filter cake was washed with ethyl acetate (500 ml). The filtrates were combined, washed with saturated brine (500 ml), and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated under reduced pressure to obtain a yellow solid (4.80 g, yield 53.6%). LCMS(ESI,m / z):194.2 [M+H] + 【0220】 Step 3) 4-bromo-2,3-dihydro-1-benzofuran-7-carboxylate methyl At room temperature, methyl 4-amino-2,3-dihydro-1-benzofuran-7-carboxylate (4.20 g, 21.8 mmol), tert-butyl nitrite (3.15 g, 30.7 mmol), cuprous bromide (4.20 g, 29.4 mmol), and acetonitrile (20 ml) were added to a 50 ml single-neck bottle. After purging with nitrogen, the mixture was heated to 70°C and reacted for 30 minutes. The mixture was cooled to room temperature. The mixture was concentrated under reduced pressure, and the residue was purified by column chromatography (petroleum ether / ethyl acetate (v / v) = 5:1) to obtain a yellow solid (3.50 g, yield 62.8%). 【0221】 Step 4) 4-Cyano-2,3-Dihydro-1-Benzofuran-7-Carboxylate Methyl At room temperature, methyl 4-bromo-2,3-dihydro-1-benzofuran-7-carboxylate (3.20 g, 12.5 mmol), zinc cyanide (9.54 g, 81.6 mmol), tris(dibenzylideneacetone)dipalladium (1.13 g, 1.25 mmol), 1,1'-bis(diphenylphosphino)ferrocene (1.37 g, 2.50 mmol), and N-methylpyrrolidone (20 ml) were added to a 50 ml single-neck bottle. After purging with nitrogen, the mixture was heated to 120 °C and reacted for 2 hours. It was cooled to room temperature. An aqueous solution (100 ml) was added to quench the mixture. The mixture was extracted with ethyl acetate (100 ml x 3), the organic phases were combined, washed with saturated brine (100 ml), and dried over anhydrous sodium sulfate. The solution was filtered, concentrated under reduced pressure, and the residue was purified by column chromatography (petroleum ether / ethyl acetate (v / v) = 6:1) to obtain a white solid (2.20 g, yield 86.6%). 【0222】 Step 5) 7-Hydroxymethyl-2,3-dihydro-1-benzofuran-4-carbonitrile At room temperature, methyl 4-cyano-2,3-dihydro-1-benzofuran-7-carboxylate (1.80 g, 8.86 mmol), tetrahydrofuran (20 ml), and a solution of lithium borohydride in tetrahydrofuran (6.54 ml, 2.0 mol / l, 13.3 mmol) were added to a 50 ml single-neck bottle. After purging with nitrogen, the mixture was heated to 60°C and reacted for 20 minutes. It was cooled to room temperature. Water (50 ml) was added to quench the mixture. The mixture was extracted with ethyl acetate (50 ml x 3), the organic phases were combined, washed with saturated brine (50 ml), and dried over anhydrous sodium sulfate. The mixture was filtered, concentrated under reduced pressure, and the residue was purified by column chromatography (petroleum ether / ethyl acetate (v / v) = 3:1) to obtain a white solid (960 mg, yield 61.9%). 【0223】 Step 6) 7-Formyl-2,3-dihydro-1-benzofuran-4-carbonitri 7-hydroxymethyl-2,3-dihydro-1-benzofuran-4-carbonitride (920 mg, 6.58 mmol), dichloromethane (10 ml), and Dessmartin's reagent (3.24 g, 7.04 mmol) were added to a 25 ml single-neck bottle at room temperature. After purging with nitrogen, the mixture was reacted at room temperature for 2 hours. The mixture was concentrated under reduced pressure, and the residue was purified by column chromatography (petroleum ether / ethyl acetate (v / v) = 6:1) to obtain a yellow solid (800 mg, yield 70.2%). 【0224】 Step 7) 2-Cyanoethyl-4-(4-Cyano-2,3-dihydro-1-benzofuran-7-yl)-5-hydroxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylate 7-formyl-2,3-dihydro-1-benzofuran-4-carbonitrile (100 mg, 0.577 mmol), 4-amino-5-methylpyridine-2-ol (100 mg, 0.806 mmol), 3-oxobutanoate 2-cyanoethyl (100 mg, 0.645 mmol), isopropanol (2.5 ml), and acetic acid (45 ml) were added to an 8 ml vial at room temperature. After purging with nitrogen, the mixture was reacted overnight at 90°C. The mixture was cooled to room temperature, concentrated under reduced pressure, and the resulting residue was purified by C18 reversed-phase column chromatography under the following conditions (C18 BIOTAGE 40 g reversed-phase column, mobile phase A (10 mmol / l aqueous ammonium bicarbonate solution) and mobile phase B (acetonitrile), 15 minutes from 30%B to 50%B, monitoring wavelength 254 nm), yielding a yellow solid (110 mg, yield 45.7%). LCMS(ESI,m / z):417.4 [M+H] + 【0225】 Step 8) 2-Cyanoethyl 4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylate 2-Cyanoethyl-4-(4-Cyano-2,3-dihydro-1-benzofuran-7-yl)-5-hydroxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylate (100 mg, 0.240 mmol), silver carbonate (73 mg, 0.264 mmol), ethyl iodide (75 mg, 0.480 mmol), and 1,4-dioxane (3 ml) were added to an 8 ml vial at room temperature. After purging with nitrogen, the mixture was reacted at 90°C for 1 hour. The mixture was cooled to room temperature, filtered, and the filter cake was washed with ethyl acetate (50 ml). The filtrate was collected, concentrated under reduced pressure, and a yellow solid was obtained (110 mg, yield 45.7%), which was used directly in the next step without further purification. LCMS(ESI,m / z):445.20 [M+H] + 【0226】 Step 9) 4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid At room temperature, 100 mg (0.225 mmol) of 2-cyanoethyl 4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylate, 0.6 ml of ethylene glycol dimethyl ether, and 0.3 ml of an aqueous solution of sodium hydroxide (18 mg, 0.450 mmol) were added to an 8 ml single-neck bottle. The mixture was reacted at room temperature for 1 hour. Under an ice bath, hydrochloric acid solution (1.0 mol / l) was added to quench the mixture and adjust the pH to 5. The mixture was extracted with ethyl acetate (20 ml x 3 times), the organic phases were combined, washed with saturated brine (20 ml), and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated under reduced pressure to obtain a pale yellow solid (80 mg, 90.7%), which was used directly in the next step without further purification. LCMS(ESI,m / z):392.4 [M+H]+ 【0227】 Step 10) 4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide 4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid (80 mg, 0.204 mmol), N,N-diisopropylethylamine (91 mg, 0.712 mmol), N,N-dimethylcarboxamide (1 ml), and 2-(7-azobenzotriazolyl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (39 mg, 0.245 mmol) were added to an 8 ml vial at room temperature. The mixture was allowed to react at room temperature for 1 hour. An aqueous solution of ammonia (1.0 M, 0.5 ml) was added to the reaction mixture at room temperature. The mixture was allowed to react at room temperature for 1 hour. The mixture was filtered, and the resulting filtrate was purified by preparative high-performance liquid chromatography. The purification conditions were as follows: chromatography column: YMC-Actus Triart C18, mobile phase A: water (containing 0.1% formic acid) and mobile phase B: acetonitrile, flow rate: 60 ml / min, gradient: 7 minutes, acetonitrile increased from 20% to 40%, detection wavelength: 254 / 220 nm. The product was collected, lyophilized under reduced pressure, and a yellow solid was obtained (45.0 mg, yield 56.1%). LCMS(ESI,m / z):391.10 [M+H] + 1 H NMR(400 MHz,DMSO-d6)δ 7.70(s,1H), 7.55(s,1H), 7.11(d,J=8.0 Hz,1H), 6.98(d,J=8.0 Hz,1H), 6.71(s,2H), 5.18(s,1H), 4.63(t,J=8.8 Hz,2H), 4.04(q,J=6.8 Hz,2H), 3.40(t,J=8.8 Hz,2H), 2.11(s,3H), 2.07(s,3H), 1.10(t,J=6.8 Hz,3H). 【0228】 (Example 12) 4-(4-cyano-2-methoxylphenyl)-5-ethoxy-2-methyl-1H,4H-benzo[h]1,6-naphthyridine-3-carbonitrile [ka] 【0229】 Step 1) 2-Ethoxyquinoline-4-amine 2-chloroquinoline-4-amine (200 mg, 1.12 mmol), sodium ethanol (305 mg, 4.48 mmol), and ethanol (2.5 ml) were added to a 10 ml microwave tube at room temperature. The mixture was heated to 140°C by microwave and reacted for 1 hour. It was cooled to room temperature. The mixture was concentrated under reduced pressure, the resulting residue was dissolved in ethyl acetate (100 ml), washed with saturated saline solution (100 ml), and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated under reduced pressure. The resulting residue was purified by C18 reversed-phase column chromatography under the following conditions (C18 BIOTAGE 40 g reversed-phase column, mobile phase A (0.1% aqueous ammonia) and mobile phase B (acetonitrile), 10 minutes from 25%B to 35%B, monitoring wavelength 254 nm), yielding a white solid (75 mg, yield 35.6%). MS(ESI)M / Z:189 [M+H] + 【0230】 Step 2) 4-(4-cyano-2-methoxylphenyl)-5-ethoxy-2-methyl-1H,4H-benzo[h]1,6-naphthyridine-3-carbonitrile At room temperature, a solution of 2-ethoxyquinoline-4-amine (75 mg, 0.398 mmol), 4-(2-cyano-3-oxobut-1-en-1-yl)-3-methoxybenzonitrile (90 mg, 0.398 mmol), and glacial acetic acid (36 ml) in isopropanol (2 ml) was added to an 8 ml vial. After purging with nitrogen, the mixture was heated to 80°C and reacted overnight. The mixture was then cooled to room temperature. The solution was concentrated under reduced pressure, and the resulting residue was purified using a high-performance liquid chromatography column: column model YMC-Actus Triart C18, 30*150 mm, 5 μm, mobile phase A: water (0.1% formic acid), mobile phase B: acetonitrile, flow rate: 60 ml / min, gradient: 55% B to 85% B over 7 minutes, wavelength: 254 / 220 nm, peak time (min): 6.15. The fraction was collected, lyophilized under reduced pressure, and a white solid was obtained (48.8 mg, yield 30.7%). MS(ESI)M / Z:397.15 [M+H] + 1 H NMR(400 MHz,DMSO-d6)δ 9.60(s,1H), 8.36(d,J=8.4 Hz,1H), 7.63(d,J=3.9 Hz,2H), 7.52 - 7.41(m,2H), 7.29 -7.33(m,1H), 7.12(d,J=7.9 Hz,1H), 5.37(s,1H), 4.23-4.13(m,2H), 3.87(s,3H), 2.23(m,3H), 1.04(t,J=7.0 Hz,3H). 【0231】 (Example 13) 6-(4-cyano-2-methoxylphenyl)-5-ethoxy-8-methyl-6,9-dihydrothieno[3,2-h][1,6]naphthyridine-7-carboxamide [ka] 【0232】 Step 1) N-(2-cyanothiophen-3-yl)acetamide 3-amino-2-cyanothiophene (1.00 g, 8.05 mmol) and acetic anhydride (10 ml) were added to a 50 ml single-neck bottle at room temperature. The mixture was reacted overnight at room temperature. The mixture was concentrated under reduced pressure, the residue was pulped with petroleum ether (30 ml), and filtered to obtain a white solid (1.20 g, yield 89.6%). LCMS(ESI,m / z):167.0 [M+H] + 【0233】 Step 2) 7-aminothieno[3,2-b]pyridine-5-ol N-(2-cyanothiophen-3-yl)acetamide (1.20 g, 7.22 mmol) and tetrahydrofuran (24 ml) were added to a 100 ml three-neck bottle at room temperature. After nitrogen purging, lithium diisopropylammonium (6 ml, 44.3 mmol) was slowly added dropwise at -78°C. The mixture was reacted at -78°C for 30 minutes, then heated to 80°C and reacted for 1 hour. After cooling to room temperature, saturated ammonium chloride aqueous solution (10 ml) was added to quench the reaction. Extraction was performed with ethyl acetate (15 ml x 3), the organic phases were combined, washed with saturated brine (15 ml), and dried over anhydrous sodium sulfate. The mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane / methanol (v / v) = 5 / 1) to obtain a pale yellow solid (650 mg, yield 54.2%). LCMS(ESI,m / z):167.0 [M+H] + 【0234】 Step 3) 2-Cyanoethyl 6-(4-Cyano-2-methoxylphenyl)-5-Hydroxy-8-methyl-6,9-Dihydrothieno[3,2-h][1,6]naphthyridine-7-carboxylate 7-aminothieno[3,2-b]pyridine-5-ol (907 mg, 5.42 mmol), 2-cyanoethyl-2-(4-cyano-2-methoxybenzylidene)-3-oxobutanoic acid (359 mg, 1.20 mmol), isopropanol (25 ml), and acetic acid (450 ml) were added to a 50 ml single-neck bottle at room temperature. After purging with nitrogen, the mixture was reacted overnight at 90°C. The mixture was cooled to room temperature and filtered. The resulting solid was pulped with ethyl acetate (15 ml x 3), filtered, and the crude product was purified by C18 reversed-phase column chromatography under the following conditions: C18 BIOTAGE 330 g chromatography column, mobile phase A (0.1% FA aqueous solution) and mobile phase B (acetonitrile), gradient from 15% B to 50% B for 15 minutes, monitoring wavelength 254 nm, yielding a pale yellow solid (1.09 g, yield 45.4%). LCMS(ESI,m / z):447.1 [M+H] + 【0235】 Step 4) 2-Cyanoethyl 6-(4-Cyano-2-Methoxylphenyl)-5-Ethoxy-8-methyl-6,9-Dihydrothieno[3,2-h][1,6]Naphthyridine-7-Carboxylate 2-Cyanoethyl 6-(4-cyano-2-methoxylphenyl)-5-hydroxy-8-methyl-6,9-dihydrothieno[3,2-h][1,6]naphthirizine-7-carboxylate (195 mg, 0.437 mmol), methyl iodide (102 mg, 0.655 mmol), silver carbonate (120 mg, 0.437 mmol), and 1,4-dioxane (2 ml) were added to a 50 ml single-neck bottle at room temperature. After purging with nitrogen, the mixture was reacted at 90°C for 2 hours. After cooling to room temperature, saturated ammonium chloride aqueous solution (5 ml) was added to quench the mixture. Extraction was performed with ethyl acetate (10 ml x 3 times), the organic phases were combined, washed with saturated brine (10 ml), and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated under reduced pressure. The resulting residue was purified by C18 reverse-phase column chromatography. The purification conditions were as follows: chromatography column: BIOTAGE C18 reversed-phase column 120 g, mobile phase A: water (containing 0.1% aqueous ammonium bicarbonate solution) and mobile phase B: acetonitrile, flow rate: 60 ml / min, gradient: 15 minutes, acetonitrile increased from 20% to 60%, detection wavelength: 254 nm. A white solid was obtained (120 mg, yield 57.9%). LCMS(ESI,m / z):475.1 [M+H] + 【0236】 Step 5) 6-(4-cyano-2-methoxylphenyl)-5-ethoxy-8-methyl-6,9-dihydrothieno[3,2-h][1,6]naphthyridine-7-carboxylic acid 155 mg, 0.327 mmol of 2-cyanoethyl 6-(4-cyano-2-methoxylphenyl)-5-ethoxy-8-methyl-6,9-dihydrothieno[3,2-h][1,6]naphthyridine-7-carboxylate, 1.5 ml of ethylene glycol dimethyl ether, and 0.5 ml of an aqueous solution of sodium hydroxide (26 mg, 0.655 mmol) were added to a 50 ml single-neck bottle at room temperature. The mixture was allowed to react at room temperature for 1 hour. The mixture was quenched with hydrochloric acid solution (1.0 mol / l) under an ice bath to adjust the pH to 5. The mixture was extracted with ethyl acetate (5 ml x 3 times), the organic phases were combined, washed with saturated brine (15 ml x 3 times), and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated under reduced pressure. The resulting residue was purified by preparative high-performance liquid chromatography. The purification conditions were as follows: chromatography column: C18 silica gel column, mobile phase A: water (containing 0.1% formic acid) and mobile phase B: acetonitrile, flow rate: 60 ml / min, gradient: 10 minutes, acetonitrile increased from 10% to 40%, detection wavelength: 254 nm. The product was collected, lyophilized under reduced pressure, and a white solid was obtained (111 mg, yield 80.6%). LCMS(ESI,m / z):422.1 [M+H] + 【0237】 Step 6) 6-(4-cyano-2-methoxylphenyl)-5-ethoxy-8-methyl-6,9-dihydrothieno[3,2-h][1,6]naphthyridine-7-carboxamide 6-(4-cyano-2-methoxylphenyl)-5-ethoxy-8-methyl-6,9-dihydrothieno[3,2-h][1,6]naphthyridine-7-carboxylic acid (105 mg, 0.249 mmol), N,N-diisopropylethylamine (97 mg, 0.747 mmol), N,N-dimethylcarboxamide (2 ml), and 2-(7-azobenzotriazolyl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (284 mg, 0.747 mmol) were added to an 8 ml vial at room temperature. The mixture was allowed to react for 30 minutes at room temperature. 0.8 ml of aqueous ammonia solution was added to the reaction mixture at room temperature. The mixture was allowed to react for 3 hours at room temperature. 10 ml of water was added to quench the reaction. The organic phases were extracted with ethyl acetate (10 ml x 3 times), washed with saturated brine (10 ml), and dried over anhydrous sodium sulfate. The solution was filtered and concentrated under reduced pressure. The resulting residue was purified by preparative high-performance liquid chromatography. The purification conditions were as follows: chromatography column: Sunfire prep C18, mobile phase A: water (containing 0.1% aqueous ammonium bicarbonate solution) and mobile phase B: acetonitrile, flow rate: 60 ml / min, gradient: 7 minutes, acetonitrile increased from 18% to 50%, detection wavelength: 254 nm. The product was collected, lyophilized under reduced pressure, and a white solid was obtained (47.0 mg, yield 44.9%). LCMS(ESI,m / z):421.0 [M+H] + 1 H NMR(400 MHz,DMSO-d6)δ 8.83(s,1H), 7.88(d,J=5.4 Hz,1H), 7.38(d,J=1.5 Hz,1H), 7.29 -7.22(m,2H), 7.18(d,J=7.9 Hz,1H), 6.88 -6.73(m,2H), 5.48(s,1H), 4.18 -4.04(m,2H), 3.82(s,3H), 2.19(s,3H), 1.10(t,J=7.0 Hz,3H). 【0238】 (Example 14) 4-(7-cyanobenzo[d][1,3]dioxol-4-yl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide [ka] 【0239】 Step 1) Diethyl 2,3-dihydroxyterephthalate 2,3-dihydroxyterephthalic acid (260 g, 1.31 mol) and ethanol (2.60 liters) were added to a 10-liter four-neck bottle at room temperature. Dichlorosulfoxide (908 g, 7.63 mol) was slowly added dropwise at 0°C, and the mixture was reacted overnight at 70°C. After cooling to room temperature, the reaction mixture was slowly quenched by adding it dropwise to a saturated sodium bicarbonate aqueous solution (5.20 liters). The mixture was extracted with ethyl acetate (5.00 liters x 3), the organic phases were combined, washed with saturated brine (3.00 liters), and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated under reduced pressure to obtain an off-white solid (312 g, yield 93.5%). MS(ESI)M / Z:255.1 [M+H] + 【0240】 Step 2) Benzo[d][1,3]dioxol-4,7-dicarboxylate diethyl 312 g, 1.23 mol, diethyl 2,3-dihydroxyterephthalate, 175 g, 1.35 mol, potassium carbonate, 340 g, 2.46 mol, and 1.90 liter of DMSO were added to a 10-liter four-neck bottle at room temperature. After purging with nitrogen, the mixture was reacted overnight at 90°C. The mixture was cooled to room temperature and quenched with saturated brine (19.0 liters). Extraction was performed with ethyl acetate (12.0 liters x 3), the organic phases were combined, washed with saturated brine (12.0 liters), and dried over anhydrous sodium sulfate. The mixture was filtered, and the filtrate was concentrated under reduced pressure to obtain an off-white solid (289 g, yield 88.4%). MS(ESI)M / Z:267.1 [M+H] + 【0241】 Step 3) 7-Hydroxymethylbenzo[d][1,3]dioxol-4-carboxylate ethyl 289 g, 1.09 mol, 2.90 liters, and a solution of lithium borohydride in tetrahydrofuran (545 ml, 2.0 mol / l, 1.09 mol) were added to a 10-liter four-neck bottle at room temperature. After purging with nitrogen, the mixture was reacted at 60°C for 2 hours. The mixture was cooled to 0°C, and the reaction was slowly added to a saturated aqueous solution of ammonium chloride (6.00 liters) to quench the reaction. The mixture was extracted with ethyl acetate (4.50 liters x 3), the organic phases were combined, washed with saturated brine (4.50 liters), and dried over anhydrous sodium sulfate. The mixture was filtered, the filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography (petroleum ether / ethyl acetate (v / v) = 7:3) to obtain a white solid (168 g, yield 69.0%). MS(ESI)M / Z:225.0 [M+H] + 【0242】 Step 4) 7-Formylbenzo[d][1,3]dioxol-4-carboxylate ethyl ester 7-hydroxymethylbenzo[d][1,3]dioxol-4-carboxylate ethyl (168 g, 750 mmol), dichloromethane (1.70 L), and Dess Martin's reagent (397 g, 937 mmol) were added to a 3-liter three-neck bottle at room temperature. After purging with nitrogen, the mixture was reacted overnight at room temperature. The mixture was concentrated under reduced pressure, and the residue was purified by column chromatography (petroleum ether / ethyl acetate (v / v) = 1:1) to obtain a yellow solid (165 g, 99.1% yield). MS(ESI)M / Z:223.1 [M+H] + 【0243】 Step 5) 7-Cyanobenzo[d][1,3]dioxol-4-carboxylate ethyl ester 7-Formylbenzo[d][1,3]dioxol-4-carboxylate ethyl (165 g, 757 mmol), hydroxylamine hydrochloride (158 g, 2.27 mol), and DMSO (1.00 liter) were added to a 3-liter three-neck bottle at room temperature. After purging with nitrogen, the mixture was heated to 90°C and reacted for 1 hour. After cooling to room temperature, saturated brine (10.0 liters) was added to quench the mixture. Extraction was performed with ethyl acetate (6.00 liters x 3), the organic phases were combined, washed with saturated brine (6.00 liters), and dried over anhydrous sodium sulfate. The mixture was filtered, the filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography (petroleum ether / ethyl acetate (v / v) = 4:1) to obtain a yellow solid (120 g, yield 73.7%). 【0244】 Step 6) 7-Hydroxymethylbenzo[d][1,3]dioxol-4-Carbonitrile 7-Cyanobenzo[d][1,3]dioxol-4-carboxylate ethyl (120 g, 548 mmol), tetrahydrofuran (1.20 L), and a solution of lithium borohydride in tetrahydrofuran (411 ml, 2.0 mol / L, 822 mmol) were added to a 3-liter three-neck bottle at room temperature. After purging with nitrogen, the mixture was reacted at 60°C for 2 hours. After cooling to 0°C, the reaction mixture was slowly added to saturated ammonium chloride aqueous solution (3.20 L) to quench. Extraction was performed with ethyl acetate (2.50 L x 3), the organic phases were combined, washed with saturated brine (2.50 L), and dried over anhydrous sodium sulfate. The mixture was filtered, the filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography (petroleum ether / ethyl acetate (v / v) = 5:1) to obtain a white solid (75.0 g, yield 77.3%). 【0245】 Step 7) 7-Formylbenzo[1,3]dioxol-4-carbonil 7-hydroxymethylbenzo[d][1,3]dioxol-4-carbonitrile (75.0 g, 424 mmol), dichloromethane (1.50 L), and Dess Martin's reagent (270 g, 636 mmol) were added to a 3-liter three-neck bottle at room temperature. After purging with nitrogen, the mixture was reacted overnight at room temperature. The mixture was concentrated under reduced pressure, and the residue was purified by column chromatography (petroleum ether / ethyl acetate (v / v) = 3:1) to obtain a yellow solid (67.0 g, yield 90.4%). 【0246】 Step 8) 2-Cyanoethyl 4-(7-Cyanobenzo[d][1,3]dioxol-4-yl)-5-hydroxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylate 7-formylbenzo[1,3]dioxol-4-carbonitrilate (65.0 g, 371 mmol), 2-cyanoethyl-3-oxobutyrate (63.3 g, 408 mmol), 4-amino-5-methylpyridine-2-ol (50.7 g, 408 mmol), isopropanol (1.30 L), and acetic acid (23.4 ml) were added to a 3-liter three-neck bottle at room temperature. After purging with nitrogen, the mixture was reacted overnight at 90°C. The mixture was cooled to room temperature and filtered. The resulting solid was pulped with methyl tert-butyl ether (500 ml x 3) and filtered to obtain a pale yellow solid (88.0 g, 56.7%). MS(ESI)M / Z:419.2 [M+H] + 【0247】 Step 9) 2-Cyanoethyl 4-(7-Cyanobenzo[d][1,3]dioxol-4-yl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylate 2-Cyanoethyl 4-(7-cyanobenzo[d][1,3]dioxol-4-yl)-5-hydroxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylate (88.0 g, 210 mmol), ethyl iodide (49.3 g, 316 mmol), silver carbonate (58.1 g, 210 mmol), and 1,4-dioxane (880 ml) were added to a 2-liter three-neck bottle at room temperature. After purging with nitrogen, the mixture was reacted at 90°C for 2 hours. The mixture was cooled to room temperature, filtered, and the filtrate was concentrated under reduced pressure to obtain a yellow solid (86.5 g, 92.1%). MS(ESI)M / Z:447.1 [M+H] + 【0248】 Step 10) 4-(7-cyanobenzo[d][1,3]dioxol-4-yl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid 85.0 g, 190 mmol of 2-cyanoethyl 4-(7-cyanobenzo[d][1,3]dioxol-4-yl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylate, 1275 ml of ethylene glycol dimethyl ether, 425 ml of water, and 380 ml of aqueous sodium hydroxide solution were added to a 3-liter three-neck bottle at room temperature. The mixture was allowed to react at room temperature for 1 hour. The mixture was diluted with 1.50 liters of water, extracted with ethyl acetate (1.00 liter x 1 time), and the aqueous phase was retained. The mixture was quenched with hydrochloric acid solution (1.00 mol / l) under an ice bath to adjust the pH to 5. The mixture was extracted with ethyl acetate (1.00 liter x 3 times), the organic phases were combined, washed with saturated brine (500 ml x 1 time), and dried over anhydrous sodium sulfate. The mixture was filtered, and the filtrate was concentrated under reduced pressure to obtain a pale yellow solid (70.0 g, 91.8%), which was used directly in the next step of the reaction. MS(ESI)M / Z:394.2 [M+H] + 【0249】 Step 11) 4-(7-cyanobenzo[d][1,3]dioxol-4-yl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide 4-(7-cyanobenzo[d][1,3]dioxol-4-yl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid (57.0 g, 145 mmol), N,N-diisopropylethylamine (37.4 g, 290 mmol), N,N-dimethylcarboxamide (570 ml), and 2-(7-azobenzotriazolyl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (92.4 g, 218 mmol) were added to a 2-liter three-neck bottle at room temperature. 120 ml of 25% aqueous ammonia solution was added to the reaction mixture at room temperature. The reaction was allowed to proceed at room temperature for 1.5 hours. The reaction mixture was purified by preparative high-performance liquid chromatography. The purification conditions were as follows: chromatography column: DAC prep C18, mobile phase A: water (containing 0.1% ammonium bicarbonate) and mobile phase B: acetonitrile, flow rate: 1 liter / min, gradient: 30 minutes, acetonitrile increased from 20% to 42%, detection wavelength: 254 nm. The product was collected, lyophilized under reduced pressure, and a white solid was obtained (38.0 g, 66.8%). MS(ESI)M / Z:393.3 [M+H] + 1 H NMR(400 MHz,Chloroform-d)δ 7.68(s,1H), 6.91(d,J=8.4 Hz,1H), 6.78(d,J=8.4 Hz,1H), 6.14 -6.12(m,2H), 5.79(s,1H), 5.43(s,2H), 5.16(s,1H), 4.26 -4.16(m,2H), 2.44(s,3H), 2.14(s,3H), 1.26(t,J=7.0 Hz,3H). 【0250】 (Example 15) 4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-cyclopentyloxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide [ka] 【0251】 Step 1) 2-Cyanoethyl-4-(4-Cyano-2,3-dihydro-1-benzofuran-7-yl)-5-cyclopentyloxy)-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylate At room temperature, 2-cyanoethyl-4-(4-cyano-2,3-dihydro-1-benzofuran-7-yl)-5-hydroxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylate (100 mg, 0.240 mmol), iodine cyclopenta (71 mg, 0.360 mmol), silver carbonate (66 mg, 0.240 mmol), and 1,4-dioxane (3 ml) were added to an 8 ml single-neck bottle. After purging with nitrogen, the mixture was reacted at 90°C for 2 hours. After cooling to room temperature, the reaction mixture was filtered, the filtrate was collected, washed with ethyl acetate (3 × 10 ml), and the cake was filtered. The filtrate was concentrated under reduced pressure to obtain a yellow solid (110.0 mg, yield 94.5%). MS(ESI)M / Z:485.5 [M+H] + 【0252】 Step 2) 4-(4-cyano-2,3-dihydro-1-benzofuran-7-yl)-5-cyclopentyloxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid At room temperature, 110 mg (0.227 mmol) of 2-cyanoethyl-4-(4-cyano-2,3-dihydro-1-benzofuran-7-yl)-5-cyclopentyloxy)-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylate, 3 ml of ethylene glycol dimethyl ether, and 1 ml of an aqueous solution of sodium hydroxide (18 mg, 0.454 mmol) were added to an 8 ml single-neck bottle. The mixture was reacted at room temperature for 1 hour. Under an ice bath, hydrochloric acid solution (1.0 mol / l) was added to quench the mixture and adjust the pH to 5. The mixture was extracted with ethyl acetate (5 ml x 3 times), the organic phases were combined, washed with saturated brine (5 ml x 3 times), and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated under reduced pressure to obtain a pale yellow solid (100 mg, yield 93.6%), which was used directly in the next step of the reaction. MS(ESI)M / Z:432.5 [M+H] + 【0253】 Step 3) 4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-cyclopentyloxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide 4-(4-cyano-2,3-dihydro-1-benzofuran-7-yl)-5-cyclopentyloxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid (90 mg, 0.209 mmol), N,N-diisopropylethylamine (54 mg, 0.418 mmol), N,N-dimethylcarboxamide (1.5 ml), and 2-(7-azobenzotriazolyl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (127 mg, 0.334 mmol) were added to an 8 ml vial at room temperature. The mixture was allowed to react for 30 minutes at room temperature. An aqueous solution of ammonia (25% content) (1.5 ml) was added to the reaction mixture at room temperature. The mixture was allowed to react for 30 minutes at room temperature. The mixture was filtered, and the filtrate was purified by preparative high-performance liquid chromatography. The purification conditions were as follows: chromatography column: YMC-Actus Triart C18, 30*150 mm, 5 μm; mobile phase A: water (containing 0.1% formic acid) and mobile phase B: acetonitrile; flow rate: 60 ml / min; gradient: 7 minutes, increasing acetonitrile from 38% to 55%; detection wavelength: 254 / 220 nm. The product was collected, lyophilized under reduced pressure, and a white solid was obtained (50.0 mg, yield 55.7%). LCMS(ESI,m / z):431.1 [M+H] + 1 H NMR(400 MHz,DMSO-d6)δ 7.67(s,1H), 7.56(s,1H), 7.12(d,J=8.0 Hz,1H), 6.95(d,J=8.0 Hz,1H), 6.72(s,2H), 5.17(s,1H), 5.12(s,1H), 4.62-4.52(m,2H), 3.50-3.36(m,2H), 2.17(s,3H), 2.11(s,3H), 1.80-1.18(m,8H). 【0254】 (Example 16) 4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-(3,3-difluorocyclobutyl)methoxyl)-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide [ka] 【0255】 Step 1) 4-(4-cyano-2,3-dihydro-1-benzofuran-7-yl)-5-hydroxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide 7-formyl-2,3-dihydro-1-benzofuran-4-carbonitrile (300 mg, 1.73 mmol), benzyl acetate (333 mg, 1.73 mmol), 4-amino-5-methylpyridine-2-ol (215 mg, 1.73 mmol), isopropanol (8.5 ml), and acetic acid (0.15 ml) were added to an 8 ml single-neck bottle at room temperature. After purging with nitrogen, the mixture was reacted overnight at 90°C. The mixture was cooled to room temperature and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (100% ethyl acetate) to obtain a white solid (185 mg, yield 23.6%). MS(ESI)M / Z:454.5 [M+H] + 【0256】 Step 2) 4-(4-cyano-2,3-dihydro-1-benzofuran-7-yl)-5-[(3,3-difluorocyclobutyl)methoxy]-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide At room temperature, 4-(4-cyano-2,3-dihydro-1-benzofuran-7-yl)-5-hydroxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide (110 mg, 0.240 mmol), 3-bromomethyl-1,1-difluorocyclobutane (67 mg, 0.360 mmol), cesium carbonate (158 mg, 0.490 mmol), and N,N-dimethylcarboxamide (1 ml) were added to an 8 ml single-neck bottle. The mixture was reacted at 60°C for 2 hours. After cooling to room temperature, water (10 ml) was added to quench the mixture. Extraction was performed with ethyl acetate (10 ml x 3 times), the organic phases were combined, washed with saturated saline solution (10 ml), and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated under reduced pressure. The obtained residue was purified by pre-TLC (petroleum ether / ethyl acetate = 5 / 1). A white solid was obtained (40 mg, yield 29.6%). MS(ESI)M / Z:558.6 [M+H] + 【0257】 Step 3) 4-(4-cyano-2,3-dihydro-1-benzofuran-7-yl)-5-[(3,3-difluorocyclobutyl)methoxy]-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid 4-(4-cyano-2,3-dihydro-1-benzofuran-7-yl)-5-[(3,3-difluorocyclobutyl)methoxy]-2,8-dimethyl-1,4-dihydro-1,6-naphthyrizine-3-carboxamide (100 mg, 0.180 mmol), palladium carbon (10% content, 100 mg), and tetrahydrofuran (2 ml) were added to a 30 ml autoclave liner at room temperature. After purging with nitrogen, hydrogen at 3 standard atmospheric pressure was introduced, and the mixture was reacted overnight at room temperature. The filtrate was filtered and concentrated under reduced pressure to obtain a pale yellow solid (30 mg, yield 35.8%), which was used directly in the next step of the reaction. MS(ESI)M / Z:468.5 [M+H] + 【0258】 Step 4) 4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-(3,3-difluorocyclobutyl)methoxyl)-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide 4-(4-cyano-2,3-dihydro-1-benzofuran-7-yl)-5-[(3,3-difluorocyclobutyl)methoxy]-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid (30 mg, 0.064 mmol), N,N-diisopropylethylamine (17 mg, 0.130 mmol), N,N-dimethylcarboxamide (0.5 ml), and 2-(7-azobenzotriazolyl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (37 mg, 0.096 mmol) were added to an 8 ml vial at room temperature. The mixture was allowed to react for 30 minutes at room temperature. 0.2 ml of 25% aqueous ammonia solution was added to the reaction mixture at room temperature. The mixture was allowed to react for 1 hour at room temperature. The mixture was filtered, and the resulting filtrate was purified by preparative high-performance liquid chromatography. The purification conditions were as follows: column model XBridge Shield RP18 OBD Column, 30*150 mm, 5 μm; mobile phase A: water (containing 0.1% aqueous ammonia); mobile phase B: acetonitrile; flow rate: 60 ml / min; gradient: increased from 25%B to 60%B; rinse for 7 minutes; 60%B; wavelength: 254 / 220 nm; peak time (min): 6.58; fractions were collected, lyophilized under reduced pressure, and a white solid was obtained (17.0 mg, yield 56.8%). LCMS(ESI,m / z):467.5 [M+H] + 1 H NMR(400 MHz,CDCl3)δ 7.73(s,1H), 7.56(s,1H), 7.12(d,J=8.0 Hz,1H), 6.96(d,J=8.0 Hz,1H), 5.17(s,1H), 4.66 - 4.50(m,2H), 4.17 - 4.04(m,2H), 2.47 - 2.12(m,13H). 19 F NMR (376 MHz, CDCl3)δ -83.5, -94.4. 【0259】 (Example 17) 4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-(difluoromethoxy)-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide [ka] 【0260】 Step 1) 4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-(difluoromethoxy)-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide At room temperature, 4-(4-cyano-2,3-dihydro-1-benzofuran-7-yl)-5-hydroxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide (100 mg, 0.221 mmol), 2-bromo-2,2-difluoroethyl acetate (67 mg, 0.332 mmol), cesium carbonate (144 mg, 0.442 mmol), and N,N-dimethylcarboxamide (2 ml) were added to an 8 ml single-neck bottle. The mixture was reacted at 60°C for 2 hours. After cooling to room temperature, water (20 ml) was added to quench the mixture. Extraction was performed with ethyl acetate (20 ml x 3 times), the organic phases were combined, washed with saturated saline solution (20 ml), and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated under reduced pressure. The resulting residue was purified by pre-TLC (petroleum ether / ethyl acetate = 5 / 1). A yellow solid was obtained (60 mg, yield 54.6%). MS(ESI)M / Z:504.6 [M+H] + 【0261】 Step 2) 4-Cyano-2,3-dihydrobenzofuran-7-yl-5-(difluoromethoxy)-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid 4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-(difluoromethoxy)-2,8-dimethyl-1,4-dihydro-1,6-naphthyrizine-3-carboxamide (60 mg, 0.119 mmol), palladium carbon (10% content, 60 mg), and tetrahydrofuran (2 ml) were added to a 30 ml autoclave liner at room temperature. After purging with nitrogen, hydrogen at 3 standard atmospheric pressure was introduced, and the mixture was reacted overnight at 70°C. After cooling to room temperature, the reaction mixture was filtered to obtain a filtrate, which was concentrated under reduced pressure to obtain a pale yellow solid (30 mg, yield 60.9%), which was used directly in the next step of the reaction. MS(ESI)M / Z:414.4 [M+H] + 【0262】 Step 3) 4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-(difluoromethoxy)-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide 4-Cyano-2,3-dihydrobenzofuran-7-yl-5-(difluoromethoxy)-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid (20 mg, 0.048 mmol), N,N-diisopropylethylamine (13 mg, 0.096 mmol), N,N-dimethylcarboxamide (0.3 ml), and 2-(7-azobenzotriazolyl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (28 mg, 0.072 mmol) were added to an 8 ml vial at room temperature. The mixture was allowed to react for 30 minutes at room temperature. 0.2 ml of 25% aqueous ammonia was added to the reaction mixture at room temperature. The mixture was allowed to react for 1 hour at room temperature. The mixture was filtered, and the resulting filtrate was purified by preparative high-performance liquid chromatography. The purification conditions were as follows: column model XBridge Shield RP18 OBD Column, 30*150 mm, 5 μm; mobile phase A: water (containing 0.1% aqueous ammonia); mobile phase B: acetonitrile; flow rate: 60 ml / min; gradient: increasing from 30%B to 60%B; rinse for 7 minutes; wavelength: 254 / 220 nm; fractions were collected, lyophilized under reduced pressure, and a white solid was obtained (1.1 mg, yield 5.51%). LCMS(ESI,m / z):413.05 [M+H] + 1 H NMR(300 MHz,CDCl3)δ 7.68(s,1H), 7.05 - 6.99(m,2H), 5.87(s,1H), 5.23(s,1H), 4.75(t,J=8.7 Hz,2H), 3.43(t,J=8.7 Hz,2H), 2.51(s,3H), 2.19(s,3H). 19 F NMR(282 MHz,CDCl3)δ -87.2,-90.2. 【0263】 (Example 18) 4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-cyclopropoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide [ka] 【0264】 Step 1) (Z)-2-(4-cyano-2,3-dihydro-1-benzofuran-7-yl)methylidene)-3-hydroxybutyrate benzyl 7-Formyl-2,3-dihydro-1-benzofuran-4-carbonitrile (566 mg, 3.27 mmol), piperidine (28 mg, 0.327 mmol), acetic acid (0.22 ml), benzyl acetacetate (628 mg, 3.27 mmol), and dichloromethane (12.0 ml) were added to a 40 ml single-neck bottle at room temperature. After purging with nitrogen, the mixture was reacted overnight at 40°C. The mixture was cooled to room temperature and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 3:1) to obtain a yellow oily substance (600 mg, yield 52.9%). LCMS(ESI,m / z):348.10 [M+H] + 【0265】 Step 2) 4-(4-cyano-2,3-dihydro-1-benzofuran-7-yl)-5-hydroxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide (Z)-2-(4-cyano-2,3-dihydro-1-benzofuran-7-yl)methylidene)-3-hydroxybutyrate benzyl (100 mg, 0.288 mmol), 4-amino-5-methylpyridine-2-ol (35.7 mg, 0.288 mmol), acetic acid (0.02 ml), and dichloromethane (2.0 ml) were added to a 40 ml single-neck bottle at room temperature. After purging with nitrogen, the mixture was reacted overnight at 90°C. The mixture was cooled to room temperature and filtered. The resulting solid was pulped with isopropanol (2.0 ml x 3) and filtered to obtain a pale yellow solid (105 mg, yield 80.8%). LCMS(ESI,m / z):454.25 [M+H] + 【0266】 Step 3) 4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-cyclopropoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide 4-(4-cyano-2,3-dihydro-1-benzofuran-7-yl)-5-hydroxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyrizine-3-carboxamide (200 mg, 0.441 mmol), cyclopropyl bromide (534 mg, 4.41 mmol), cesium carbonate (719 mg, 2.21 mmol), and N,N-dimethylcarboxamide (2 ml) were added to an 8 ml single-neck bottle at room temperature. The mixture was reacted at 130 °C under nitrogen protection and stirred overnight. After cooling to room temperature, the mixture was filtered, and the resulting filtrate was purified using a carbon-18 column (mobile phase A: 0.1% aqueous formic acid solution, mobile phase B: acetonitrile, flow rate: 60 ml / min, increasing from 10% to 50% over 10 minutes, detection wavelength: 254 nm). The fraction was collected, lyophilized under reduced pressure, and a yellow solid was obtained (35 mg, yield 16.1%). MS(ESI)M / Z:494.2 [M+H] + 【0267】 Step 4) 4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-cyclopropoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid 4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-cyclopropoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyrizine-3-carboxamide (35 mg, 0.071 mmol), palladium carbon (10% content, 35 mg), and tetrahydrofuran (2 ml) were added to a 30 ml autoclave liner at room temperature. After purging with nitrogen, hydrogen at 3 standard atmospheric pressure was introduced, and the reaction was carried out at 50°C for 3 hours. After cooling to room temperature, the reaction mixture was filtered to obtain a filtrate, which was concentrated under reduced pressure to obtain a pale yellow solid (28 mg, yield 97.8%), which was used directly in the next step of the reaction. MS(ESI)M / Z:404.2 [M+H] + 【0268】 Step 5) 4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-cyclopropoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide 4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-cyclopropoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid (28 mg, 0.069 mmol), N,N-diisopropylethylamine (27 mg, 0.207 mmol), N,N-dimethylcarboxamide (0.5 ml), and 2-(7-azobenzotriazolyl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (42 mg, 0.110 mmol) were added to an 8 ml vial at room temperature. The mixture was allowed to react at room temperature for 30 minutes. At room temperature, 0.5 ml of 25% aqueous ammonia was added to the reaction mixture. The mixture was allowed to react at room temperature for 1 hour. The reaction mixture was filtered, and the resulting filtrate was purified using a carbon 18 column (mobile phase A: aqueous solution containing 0.1% ammonium bicarbonate, mobile phase B: acetonitrile, flow rate: 60 ml / min, increasing from 20% to 50% over 10 minutes, detection wavelength: 254 nm). The fraction was collected, lyophilized under reduced pressure, and a white solid was obtained (20.2 mg, yield 72.3%). LCMS(ESI,m / z):403.05 [M+H] + 1 H NMR(400 MHz,Chloroform-d)δ7.74(s,1H), 7.02 - 6.98(m,2H), 5.82(s,1H), 5.08(s,1H), 4.79 - 4.65(m,2H), 4.42 - 4.18(m,2H), 3.43(t,J=8.4 Hz,2H), 2.47(s,3H), 2.16(s,3H), 0.74 - 0.54(m,3H), 0.20 - 0.15(m,1H). 【0269】 (Example 19) 4-Cyano-2,3-dihydrobenzofuran-7-yl-5-cyclopropylmethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide [ka] 【0270】 Step 1) 2-Cyanoethyl 4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-cyclopropylmethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylate 2-Cyanoethyl-4-(4-cyano-2,3-dihydro-1-benzofuran-7-yl)-5-hydroxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylate (40 mg, 0.096 mmol), (iodomethyl)cyclopropane (71 mg, 0.360 mmol), silver carbonate (27 mg, 0.096 mmol), and 1,4-dioxane (1 ml) were added to an 8 ml single-neck bottle at room temperature. After purging with nitrogen, the mixture was reacted at 90°C for 2 hours. The mixture was cooled to room temperature, concentrated under reduced pressure, and the residue was purified using a carbon 18 column (mobile phase A: 0.1% aqueous formic acid solution, mobile phase B: acetonitrile, flow rate: 60 ml / min, increasing from 10%B to 50%B over 10 minutes, detection wavelength: 254 nm). The fraction was collected, lyophilized under reduced pressure, and a yellow solid was obtained (22.5 mg, yield 49.8%). MS(ESI)M / Z:471.2 [M+H] + 【0271】 Step 2) 4-Cyano-2,3-dihydrobenzofuran-7-yl-5-cyclopropylmethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid 2-Cyanoethyl 4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-cyclopropylmethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylate (20 mg, 0.042 mmol), ethylene glycol dimethyl ether (0.6 ml), and an aqueous solution of sodium hydroxide (4 mg, 0.084 mmol) (0.2 ml) were added to an 8 ml single-neck bottle at room temperature. The mixture was reacted at room temperature for 1 hour. Under an ice bath, hydrochloric acid solution (1.0 mol / l) was added to quench the mixture and adjust the pH to 5. The mixture was extracted with ethyl acetate (5 ml x 3 times), the organic phases were combined, washed with saturated brine (5 ml x 3 times), and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated under reduced pressure to obtain a pale yellow solid (17 mg, yield 96.9%), which was used directly in the next step of the reaction. MS(ESI)M / Z:418.5 [M+H] + 【0272】 Step 3) 4-Cyano-2,3-dihydrobenzofuran-7-yl-5-cyclopropylmethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide 4-Cyano-2,3-dihydrobenzofuran-7-yl-5-cyclopropylmethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid (16 mg, 0.038 mmol), N,N-diisopropylethylamine (15 mg, 0.115 mmol), N,N-dimethylcarboxamide (0.3 ml), and 2-(7-azobenzotriazolyl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (23 mg, 0.062 mmol) were added to an 8 ml vial at room temperature. The mixture was allowed to react for 30 minutes at room temperature. An aqueous solution of ammonia (25% content) (0.1 ml) was added to the reaction mixture at room temperature. The mixture was allowed to react for 30 minutes at room temperature. The reaction mixture was filtered, and the filtrate was purified using a carbon 18 column (mobile phase A: 0.1% aqueous ammonium bicarbonate solution, mobile phase B: acetonitrile, flow rate: 60 ml / min, increasing from 20%B to 50%B over 10 minutes, detection wavelength: 254 nm). The fractions were collected, lyophilized under reduced pressure, and the product was recovered and lyophilized under reduced pressure to obtain a white solid (2.2 mg, yield 12.9%). LCMS(ESI,m / z):417.0 [M+H] + 1 H NMR(400 MHz,CDCl3)δ 7.85(s,1H), 7.06 - 7.00(m,2H), 6.69(s,2H), 6.23(s,1H), 5.20(s,1H), 4.73(t,J=8.8 Hz,2H), 4.42 - 4.03(m,2H), 3.45(t,J=8.8 Hz,2H), 2.50(s,3H), 1.13 - 1.08(m,1H), 0.61 - 0.50(m,2H), 0.31 - 0.15(m,2H). 【0273】 (Example 20) 4-(4-cyano-2,3-dihydro-1-benzofuran-7-yl)-5-isopropoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide [ka] 【0274】 Step 1) 2-Cyanoethyl 4-(4-cyano-2,3-dihydro-1-benzofuran-7-yl)-5-isopropoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylate 2-cyanoethyl-4-(4-cyano-2,3-dihydro-1-benzofuran-7-yl)-5-hydroxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylate (50 mg, 0.120 mmol), 2-iodopropane (33 mg, 0.192 mmol), silver carbonate (33 mg, 0.120 mmol), and 1,4-dioxane (1 ml) were added to an 8 ml single-neck bottle at room temperature. After purging with nitrogen, the mixture was reacted at 90°C for 2 hours. After cooling to room temperature, the reaction mixture was filtered, and the filter cake was washed with ethyl acetate (3 × 5 ml). The filtrate was collected and concentrated to dryness under reduced pressure to obtain a white solid (40 mg, yield 72.7%). MS(ESI)M / Z:459.2 [MH] - 【0275】 Step 2) 4-Cyano-2,3-dihydrobenzofuran-7-yl-5-isopropoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid 40 mg (0.087 mmol) of 2-cyanoethyl 4-(4-cyano-2,3-dihydro-1-benzofuran-7-yl)-5-isopropoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylate, 0.9 ml of ethylene glycol dimethyl ether, and 0.3 ml of an aqueous solution of sodium hydroxide (7 mg, 0.174 mmol) were added to an 8 ml single-neck bottle at room temperature. The mixture was allowed to react at room temperature for 1 hour. Under an ice bath, hydrochloric acid solution (1.0 mol / l) was added to quench the mixture and adjust the pH to 5. The mixture was extracted with ethyl acetate (3 ml x 3 times), the organic phases were combined, washed with saturated brine (3 ml x 3 times), and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated under reduced pressure to obtain a pale yellow solid (30 mg, yield 84.6%), which was used directly in the next step of the reaction. MS(ESI)M / Z:406.3 [M+H] + 【0276】 Step 3) 4-(4-cyano-2,3-dihydro-1-benzofuran-7-yl)-5-isopropoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide 4-Cyano-2,3-dihydrobenzofuran-7-yl-5-isopropoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid (30 mg, 0.074 mmol), N,N-diisopropylethylamine (0.05 ml), N,N-dimethylcarboxamide (0.5 ml), and 2-(7-azobenzotriazolyl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (42 mg, 0.111 mmol) were added to an 8 ml vial at room temperature. The mixture was allowed to react at room temperature for 30 minutes. An aqueous solution of ammonia (25% content) (0.2 ml) was added to the reaction mixture at room temperature. The mixture was allowed to react at room temperature for 30 minutes. The reaction mixture was filtered, and the filtrate was purified using a carbon 18 column (mobile phase A: aqueous solution containing 0.05% aqueous ammonia, mobile phase B: acetonitrile, flow rate: 60 ml / min, increasing from 15%B to 40%B over 15 minutes, detection wavelength: 254 nm). The product was collected, lyophilized under reduced pressure, and a white solid was obtained (14.4 mg, yield 48.1%). LCMS(ESI,m / z):404.10 [M+H] + 1 H NMR(400 MHz,CDCl3)δ 7.68(s,1H), 7.13-6.83(m,2H), 6.20(s,1H), 5.78(s,1H), 5.33-5.03(m,3H), 4.92-4.53(m,2H), 3.43(t,J=9.2 Hz,2H), 2.49(s,3H), 2.15(s,3H), 1.25(d,J=6.1 Hz,3H), 0.94(d,J=6.1 Hz,3H). 【0277】 (Example 21) 4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-cyclobutoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide [ka] 【0278】 Step 1) 4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-cyclobutoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide 4-(4-cyano-2,3-dihydro-1-benzofuran-7-yl)-5-hydroxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide (50 mg, 0.110 mmol), iodocyclobutane (60 mg, 0.331 mmol), cesium carbonate (72 mg, 0.221 mmol), and N,N-dimethylcarboxamide (1 ml) were added to an 8 ml single-neck bottle at room temperature. The reaction was carried out at 60°C under nitrogen protection and stirred overnight. The reaction mixture was cooled to room temperature, diluted with water (10 ml), and extracted with ethyl acetate (3 × 10 ml). The organic phases were combined, washed with saturated brine (3 × 10 ml), dried over anhydrous sodium sulfate, filtered to obtain the filtrate, and concentrated to dryness under reduced pressure. The obtained residue was purified using a pre-TLC (petroleum ether / ethyl acetate = 4 / 1) pre-chromatographic plate to obtain a white solid (40 mg, yield 71.4%). MS(ESI)M / Z:508.2 [M+H] + 【0279】 Step 2) 4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-cyclobutoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid 4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-cyclobutoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyrizine-3-carboxamide (40 mg, 0.085 mmol), palladium carbon (10% content, 40 mg), and tetrahydrofuran (2 ml) were added to a 30 ml autoclave liner at room temperature. After purging with nitrogen, hydrogen at 3 standard atmospheric pressure was introduced, and the mixture was reacted at 50°C for 2 hours. After cooling to room temperature, the reaction mixture was filtered to obtain the filtrate, which was concentrated under reduced pressure to obtain a white solid (30 mg, yield 91.3%), which was used directly in the next step of the reaction. MS(ESI)M / Z:418.2 [M+H] + 【0280】 Step 3) 4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-cyclobutoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide 4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-cyclobutoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid (30 mg, 0.072 mmol), N,N-diisopropylethylamine (19 mg, 0.145 mmol), N,N-dimethylcarboxamide (1 ml), and 2-(7-azobenzotriazolyl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (41 mg, 0.109 mmol) were added to an 8 ml vial at room temperature. The mixture was allowed to react at room temperature for 30 minutes. 0.5 ml of 25% aqueous ammonia solution was added to the reaction mixture at room temperature. The mixture was allowed to react at room temperature for 1 hour. The reaction mixture was filtered, and the resulting filtrate was purified by preparative high-performance liquid chromatography. The purification conditions were as follows: chromatography column: Xselect CSH C18 OBD, mobile phase A: water (containing 5 mmol / l ammonium bicarbonate), mobile phase B: acetonitrile, flow rate: 50 ml / min, gradient: 7 minutes, acetonitrile increased from 40% to 50%, detection wavelength: 254 / 220 nm. The product was collected, lyophilized under reduced pressure, and a white solid was obtained (15.0 mg, yield 49.8%). LCMS(ESI,m / z):417.2 [M+H] + 1 H NMR(400 MHz,Chloroform-d)δ 7.66(s,1H), 7.10-6.96(m,2H), 6.28(s,1H), 5.77(s,1H), 5.20(s,1H), 5.12-5.00 (m,1H), 4.83-4.66(m,2H), 3.52-3.36(m,2H), 2.49(s,3H), 2.46-2.38(m,1H), 2.28 -2.18(m,1H), 2.14(s,3H), 2.06~1.95(m,1H), 1.76 -1.64(m,3H). 【0281】 (Example 22) 4-Cyano-2,3-dihydrobenzofuran-7-yl-5-cyclobutyl-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide [ka] 【0282】 Step 1) 4-Cyano-2,3-dihydrobenzofuran-7-yl-5-cyclobutyl-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide 4-(4-cyano-2,3-dihydro-1-benzofuran-7-yl)-5-hydroxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide (300 mg, 0.663 mmol), (iodomethyl)cyclobutane (194 mg, 0.996 mmol), cesium carbonate (431 mg, 1.27 mmol), and N,N-dimethylcarboxamide (3 ml) were added to an 8 ml single-neck bottle at room temperature. The reaction was carried out at 60°C under nitrogen protection and stirred for 2 hours. The reaction mixture was cooled to room temperature, filtered, and the filtrate was purified by carbon-18 reverse column (under the following conditions: mobile phase A: water (containing 0.1% formic acid), mobile phase B: acetonitrile, flow rate: 60 ml / min, gradient: increasing from 30%B to 60%B, rinse for 15 minutes, detection wavelength 254 nm). The product was collected at a reference wavelength of 220 nm, concentrated under reduced pressure, and a white solid was obtained (47 mg, yield 13.7%). MS(ESI)M / Z:522.2 [M+H] + 【0283】 Step 2) 4-Cyano-2,3-dihydrobenzofuran-7-yl-5-cyclobutyl-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid 4-cyano-2,3-dihydrobenzofuran-7-yl-5-cyclobutyl-2,8-dimethyl-1,4-dihydro-1,6-naphthyrizine-3-carboxamide (47 mg, 0.090 mmol), palladium carbon (10% content, 47 mg), and tetrahydrofuran (2 ml) were added to a 30 ml autoclave liner at room temperature. After purging with nitrogen, hydrogen at 3 standard atmospheric pressure was introduced, and the mixture was reacted at 50°C for 2 hours. After cooling to room temperature, the reaction mixture was filtered to obtain the filtrate, which was concentrated under reduced pressure to obtain a pale yellow solid (30 mg, yield 77.2%), which was used directly in the next step of the reaction. MS(ESI)M / Z:432.2 [M+H] + 【0284】 Step 3) 4-Cyano-2,3-dihydrobenzofuran-7-yl-5-cyclobutyl-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide 4-Cyano-2,3-dihydrobenzofuran-7-yl-5-cyclobutyl-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid (30 mg, 0.070 mmol), N,N-diisopropylethylamine (19 mg, 0.145 mmol), N,N-dimethylcarboxamide (0.5 ml), and 2-(7-azobenzotriazolyl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (42 mg, 0.110 mmol) were added to an 8 ml vial at room temperature. The mixture was allowed to react for 30 minutes at room temperature. 0.2 ml of 25% aqueous ammonia solution was added to the reaction mixture at room temperature. The mixture was allowed to react for 1 hour at room temperature. The reaction mixture was filtered, and the resulting filtrate was purified by preparative high-performance liquid chromatography. The purification conditions were as follows: chromatography column: Xselect CSH C18 OBD, mobile phase A: water (containing 5 mmol / l ammonium bicarbonate), mobile phase B: acetonitrile, flow rate: 50 ml / min, gradient: 7 minutes, acetonitrile increased from 35% to 50%, detection wavelength: 254 / 220 nm. The product was collected, lyophilized under reduced pressure, and a white solid was obtained (17.9 mg, yield 59.8%). LCMS(ESI,m / z):431.2 [M+H] + 1 H NMR(400 MHz,Chloroform-d3)δ 7.68(s,1H), 7.01(d,J=8.1 Hz,2H), 6.68(s,2H), 5.82(s,1H), 5.17(s,1H), 4.72(t,J=8.6 Hz,2H), 4.17-4.08(m,2H), 3.42(t,J=8.6 Hz,2H), 2.62-2.52(m,1H), 2.48(s,3H), 2.16(s,3H), 2.06~1.61(m,6H). 【0285】 (Example 23) 4-Cyano-2,3-dihydrobenzofuran-7-yl-2,8-dimethyl-5-trifluoromethoxy-1,4-dihydro-1,6-naphthyridine-3-carboxamide [ka] 【0286】 Step 1) 4-Cyano-2,3-dihydrobenzofuran-7-yl-2,8-dimethyl-5-trifluoromethoxy-1,4-dihydro-1,6-naphthyridine-3-carboxamide 4-(4-cyano-2,3-dihydro-1-benzofuran-7-yl)-5-hydroxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide (100 mg, 0.220 mmol), 3,3-dimethyl-1-(trifluoromethyl)-1,2-benziodioxolane (218 mg, 0.663 mmol), and nitromethane (4 ml) were added to an 8 ml single-neck bottle at room temperature. The reaction was carried out at 100 °C under nitrogen protection and stirred for 5 hours. The reaction mixture was cooled to room temperature, diluted with water (10 ml), and extracted with ethyl acetate (3 × 10 ml). The organic phases were combined, washed with saturated brine (3 × 10 ml), dried over anhydrous sodium sulfate, filtered to obtain the filtrate, and concentrated to dryness under reduced pressure. The obtained residue was purified using pre-TLC (petroleum ether / ethyl acetate = 1 / 1) to obtain a yellow solid (40 mg, yield 34.8%). MS(ESI)M / Z:522.2 [M+H] + 【0287】 Step 2) 4-Cyano-2,3-dihydrobenzofuran-7-yl-2,8-dimethyl-5-trifluoromethoxy-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid 4-cyano-2,3-dihydrobenzofuran-7-yl-2,8-dimethyl-5-trifluoromethoxy-1,4-dihydro-1,6-naphthyrizine-3-carboxamide (20 mg, 0.038 mmol), palladium carbon (10% content, 20 mg), and methanol (2 ml) were added to a 30 ml autoclave liner at room temperature. After nitrogen purging, hydrogen at 3 standard atmospheric pressure was introduced, and the reaction was carried out at 70°C for 4 hours. After cooling to room temperature, the reaction mixture was filtered to obtain the filtrate, which was purified by preparative high-performance liquid chromatography. The purification conditions were as follows: chromatography column: carbon-18 reverse column, mobile phase: water (containing 0.1% formic acid) and acetonitrile, flow rate: 40 ml / min, gradient: rise from 30%B to 50%B over 15 minutes, detection wavelength: 254 nm. The product was collected, subjected to reduced pressure, freeze-dried, and concentrated under reduced pressure to obtain a white solid (12 mg, 72.5% yield), which was used directly in the next step of the reaction. MS(ESI)M / Z:432.2 [M+H] + 【0288】 Step 3) 4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-cyclobutoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide 4-Cyano-2,3-dihydrobenzofuran-7-yl-2,8-dimethyl-5-trifluoromethoxy-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid (12 mg, 0.028 mmol), N,N-diisopropylethylamine (7 mg, 0.054 mmol), N,N-dimethylcarboxamide (0.3 ml), and 2-(7-azobenzotriazolyl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (16 mg, 0.042 mmol) were added to an 8 ml vial at room temperature. The mixture was allowed to react for 30 minutes at room temperature. 0.1 ml of 25% aqueous ammonia solution was added to the reaction mixture at room temperature. The mixture was allowed to react for 1 hour at room temperature. The reaction mixture was filtered, and the resulting filtrate was purified by preparative high-performance liquid chromatography. The purification conditions were as follows: chromatography column: Xselect CSH C18 OBD, mobile phase A: water (containing 0.1% trifluorocarboxylic acid), mobile phase B: acetonitrile, flow rate: 50 ml / min, gradient: 7 minutes, acetonitrile increased from 20% to 50%, detection wavelength: 254 / 220 nm. The product was collected, lyophilized under reduced pressure, and a white solid was obtained (2.9 mg, yield 24.2%). LCMS(ESI,m / z):431.2 [M+H] + 1 H NMR(400 MHz,CDCl3)δ 7.82(s,1H), 7.06-6.98(m,2H), 5.97(s,1H), 5.22(s,1H), 4.78(t,J=8.7 Hz,2H), 3.47(t,J=8.7 Hz,2H), 2.55(s,3H), 2.26(s,3H). 19 F NMR (377 MHz, CDCl3) δ -56.0. 【0289】 (Example 24) 4-Cyano-2,3-dihydrobenzofuran-7-yl-2,8-dimethyl-5-(2,2,2-trifluoroethoxy)-1,4-dihydro-1,6-naphthyridine-3-carboxamide [ka] 【0290】 Step 1) 4-Cyano-2,3-dihydrobenzofuran-7-yl-2,8-dimethyl-5-(2,2,2-trifluoroethoxy)-1,4-dihydro-1,6-naphthyridine-3-carboxamide 4-(4-cyano-2,3-dihydro-1-benzofuran-7-yl)-5-hydroxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide (100 mg, 0.221 mmol), 2,2,2-trifluoroethyltrifluoromethanesulfonate (92 mg, 0.354 mmol), cesium carbonate (144 mg, 0.442 mmol), and N,N-dimethylcarboxamide (2 ml) were added to an 8 ml single-neck bottle at room temperature. The mixture was reacted at room temperature and stirred for 2 hours. The mixture was diluted with water (20 ml) and extracted with ethyl acetate (3 × 20 ml). The organic phases were combined, washed with saturated brine (20 ml), dried over anhydrous sodium sulfate, filtered to obtain the filtrate, and concentrated to dryness under reduced pressure. The obtained residue was purified using pre-TLC (petroleum ether / ethyl acetate = 2 / 1) to obtain a yellow solid (36 mg, yield 36.1%). MS(ESI)M / Z:536.2 [M+H] + 【0291】 Step 2) 4-Cyano-2,3-dihydrobenzofuran-7-yl-2,8-dimethyl-5-(2,2,2-trifluoroethoxy)-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid 4-cyano-2,3-dihydrobenzofuran-7-yl-2,8-dimethyl-5-(2,2,2-trifluoroethoxy)-1,4-dihydro-1,6-naphthyrizine-3-carboxamide (36.0 mg, 0.067 mmol), palladium carbon (10% content, 36 mg), and tetrahydrofuran (2 ml) were added to a 30 ml autoclave liner at room temperature. After purging with nitrogen, hydrogen at 3 standard atmospheric pressure was introduced, and the reaction was carried out at 70°C for 3 hours. After cooling to room temperature, the reaction mixture was filtered to obtain the filtrate, which was concentrated under reduced pressure to obtain a white solid (24 mg, yield 80.1%), which was used directly in the next step of the reaction. MS(ESI)M / Z:446.2 [M+H] + 【0292】 Step 3) 4-Cyano-2,3-dihydrobenzofuran-7-yl-2,8-dimethyl-5-(2,2,2-trifluoroethoxy)-1,4-dihydro-1,6-naphthyridine-3-carboxamide 4-Cyano-2,3-dihydrobenzofuran-7-yl-2,8-dimethyl-5-(2,2,2-trifluoroethoxy)-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid (24 mg, 0.054 mmol), N,N-diisopropylethylamine (19 mg, 0.145 mmol), N,N-dimethylcarboxamide (0.5 ml), and 2-(7-azobenzotriazolyl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (30 mg, 0.081 mmol) were added to an 8 ml vial at room temperature. The mixture was allowed to react for 30 minutes at room temperature. 0.2 ml of 25% aqueous ammonia solution was added to the reaction mixture at room temperature. The mixture was allowed to react for 1 hour at room temperature. The reaction mixture was filtered, and the resulting filtrate was purified by preparative high-performance liquid chromatography. The purification conditions were as follows: chromatography column: Xselect CSH C18 OBD, mobile phase A: water (containing 5 mmol / l ammonium bicarbonate), mobile phase B: acetonitrile, flow rate: 50 ml / min, gradient: 7 minutes, acetonitrile increased from 40% to 50%, detection wavelength: 254 / 220 nm. The product was collected, lyophilized under reduced pressure, and a white solid was obtained (6.3 mg, yield 26.3%). MS(ESI)M / Z:445.15 [M+H] + 1 H NMR(400 MHz,CDCl3)δ 7.66(s,1H), 7.05-6.92(m,2H), 5.83(s,1H), 5.22(s,1H), 4.80-4.40(m,4H), 3.42(t,J=8.7 Hz,2H), 2.52(s,3H), 2.23(s,3H). 19 F NMR (282 MHz, CDCl3) δ -74.1. 【0293】 (Example 25) 4-(8-cyano-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide [ka] 【0294】 Step 1) 8-amino-2,3-dihydro-1,4-benzodioxazine-5-carboxamide 8-amino-2,3-dihydro-1,4-benzodioxazine-5-carboxylic acid (1.00 g, 5.12 mmol), N,N-dimethylcarboxamide (25 ml), N,N-diisopropylethylamine (1.32 g, 10.2 mmol), and 2-(7-azobenzotriazolyl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (2.92 g, 7.69 mmol) were added to a 100 ml single-neck bottle at room temperature. The mixture was allowed to react for 0.5 hours at room temperature. 6 ml of 1.0 M aqueous ammonia solution was added to the reaction mixture at room temperature. The mixture was allowed to react for 1 hour at room temperature. The mixture was diluted with water (250 ml). The organic phases were extracted with ethyl acetate (250 ml x 3), washed with saturated brine (250 ml), and dried over anhydrous sodium sulfate. The mixture was filtered, concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: pure ethyl acetate) to obtain an orange oily substance (800 mg, yield 80.4%). LCMS(ESI,m / z):195.1 [M+H] + 【0295】 Step 2) 8-amino-2,3-dihydro-1,4-benzodioxazine-5-carbonitrine 766 mg (3.95 mmol) of 8-amino-2,3-dihydro-1,4-benzodioxazine-5-carboxamide and 15 ml of trichlormethrin were added to a 50 ml single-neck bottle at room temperature. The mixture was heated to 80°C and reacted for 1 hour. It was cooled to room temperature. Sodium hydroxide solution (1.0 mol / l) was added to quench the mixture and adjust the pH to approximately 8. The mixture was extracted with ethyl acetate (50 ml x 3), the organic phases were combined, washed with saturated brine (50 ml), and dried over anhydrous sodium sulfate. The mixture was filtered, concentrated under reduced pressure, and the residue was purified by column chromatography (dichloromethane / methanol (v / v) = 20 / 1) to obtain a white solid (310 mg, yield 44.6%). LCMS(ESI,m / z):177.1 [M+H] + 【0296】 Step 3) 8-Bromo-2,3-dihydro-1,4-benzodioxazine-5-carbonitri At room temperature, 8-amino-2,3-dihydro-1,4-benzodioxazine-5-carbonitrile (310 mg, 1.76 mmol), tert-butyl nitrite (181 mg, 1.76 mmol), cuprous bromide (366 mg, 2.55 mmol), and acetonitrile (8 ml) were added to a 40 ml sample bottle. The mixture was reacted at 70°C for 1.5 hours. The reaction mixture was cooled to room temperature, filtered, and rinsed three times with ethyl acetate (8 ml). The filtrate was obtained, concentrated under reduced pressure, and the residue was purified in a dispensing dish (petroleum ether / ethyl acetate (v / v) = 5 / 1) to obtain a white solid (110 mg, yield 26.0%). 【0297】 Step 4) 8-Formyl-2,3-dihydro-1,4-benzodioxazine-5-carbonitri 8-bromo-2,3-dihydro-1,4-benzodioxazine-5-carbonitride (110 mg, 0.458 mmol) and tetrahydrofuran (0.5 ml) were added to an 8 ml sample bottle at room temperature. After purging with nitrogen, the reaction mixture was cooled to -78°C. A solution of n-butyllithium (0.2 ml, 2.5 mmol / ml, 0.50 mmol) in n-hexane was slowly added dropwise. The reaction was allowed to proceed at -78°C for 30 minutes. N,N-dimethylcarboxamide (0.5 ml) was added, and the reaction was allowed to proceed at -78°C for 30 minutes. Saturated ammonium chloride aqueous solution (5 ml) was added to quench the reaction. The mixture was extracted with dichloromethane (5 ml x 3), the organic phases were combined, washed with saturated brine (5 ml), and dried over anhydrous sodium sulfate. The filtrate was obtained by filtration and concentrated under reduced pressure. The residue was purified in a dispensing dish (petroleum ether / ethyl acetate (v / v) = 5 / 1) to obtain a white solid (40 mg, yield 46.2%). 【0298】 Step 5) 2-Cyanoethyl 4-(8-Cyano-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-5-hydroxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylate 8-formyl-2,3-dihydro-1,4-benzodioxazine-5-carbonitrile (35 mg, 0.185 mmol), 2-cyanoethyl-3-oxobutyrate (29 mg, 0.185 mmol), 4-amino-5-methylpyridine-2-ol (23 mg, 0.185 mmol), isopropanol (0.6 ml), and acetic acid (12 ml) were added to an 8 ml single-neck bottle at room temperature. After purging with nitrogen, the mixture was reacted at 90°C for 4 hours. The mixture was cooled to room temperature, concentrated under reduced pressure, and the resulting residue was purified by C18 reversed-phase column chromatography under the following conditions (C18 BIOTAGE 40 g reversed-phase column, mobile phase A (0.1% aqueous ammonium bicarbonate solution) and mobile phase B (acetonitrile), gradient from 25% B to 30% B for 15 minutes, monitoring wavelength 254 nm), yielding a pale yellow solid (15 mg, yield 18.8%). MS(ESI)M / Z:433.2 [M+H] + 【0299】 Step 6) 2-Cyanoethyl 4-(8-Cyano-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylate 2-cyanoethyl 4-(8-cyano-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-5-hydroxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyrizine-3-carboxylate (15 mg, 0.035 mmol), ethyl iodide (8 mg, 0.053 mmol), silver carbonate (10 mg, 0.035 mmol), and 1,4-dioxane (0.3 ml) were added to an 8 ml single-neck bottle at room temperature. After purging with nitrogen, the mixture was reacted at 90°C for 1 hour. The mixture was cooled to room temperature. The mixture was filtered, rinsed with acetonitrile (3 ml), and the filtrate was obtained. The filtrate was concentrated under reduced pressure to obtain a yellow solid (15 mg, crude product), which was used directly in the next step without further purification. MS(ESI)M / Z:461.3 [M+H] + 【0300】 Step 7) 4-(8-cyano-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid At room temperature, 15 mg (0.033 mmol) of 2-cyanoethyl 4-(8-cyano-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyrizine-3-carboxylate, 0.45 ml of ethylene glycol dimethyl ether, and 0.15 ml of an aqueous solution of sodium hydroxide (3 mg, 0.066 mmol) were added to an 8 ml single-neck bottle. The mixture was reacted at room temperature for 1 hour. Under an ice bath, the mixture was quenched with hydrochloric acid solution (1.0 mol / l) to adjust the pH to 5. The mixture was extracted with ethyl acetate (5 ml x 3 times), the organic phases were combined, washed with saturated brine (5 ml x 3 times), and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated under reduced pressure to obtain a pale yellow solid (10 mg, crude product), which was used directly in the next step without further purification. LCMS(ESI,m / z):408.1 [M+H] + 【0301】 Step 8) 4-(8-cyano-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide 4-(8-cyano-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid (10 mg, 0.025 mmol), N,N-diisopropylethylamine (6 mg, 0.049 mmol), N,N-dimethylcarboxamide (0.3 ml), and 2-(7-azobenzotriazolyl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (14 mg, 0.038 mmol) were added to an 8 ml vial at room temperature. The mixture was allowed to react for 30 minutes at room temperature. 0.1 ml of 25% aqueous ammonia was added to the reaction mixture at room temperature. The mixture was allowed to react for 1 hour at room temperature. The reaction mixture was purified by preparative high-performance liquid chromatography. The purification conditions were as follows: chromatography column: YMC-Actus Triart C18, mobile phase A: water (containing 0.1% formic acid) and mobile phase B: acetonitrile, flow rate: 50 ml / min, gradient: 10 minutes, acetonitrile increased from 25% to 30%, detection wavelength: 254 / 220 nm. The product was collected, lyophilized under reduced pressure, and a white solid was obtained (1.1 mg, yield 11.0%). MS(ESI)M / Z:407.30 [M+H] + 1 H NMR(300 MHz,DMSO-d6)δ 7.69(s,1H), 7.57(d,J=8.1 Hz,1H), 7.12(d,J=8.1 Hz,1H), 6.76 -6.62(m,3H), 5.34(s,1H), 4.44 -4.25(m,4H), 4.06(d,J=7.0 Hz,2H), 2.18(s,3H), 2.12(s,3H), 1.11(t,J=7.0 Hz,3H). 【0302】 (Preparation of chiral compounds:) (Examples 32 and 33) (S)-4-(5-cyanochrome-8-yl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide 32 and (R)-4-(5-cyanochrome-8-yl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide 33 [ka] 4-(5-cyanochrome-8-yl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide (56 mg, 0.138 mmol) (Compound 6) was subjected to chiral resolution, with the following resolution conditions: (Chiral column: CHIRALPAK IG, 2*25cm, 5μm, mobile phase A: n-hexane (methanol solution in 10 mmol / l ammonia), mobile phase B: ethanol, flow rate: 20 ml / min, gradient: 40% B for 15 minutes, wavelength: 208 / 258 nm, 33 peak time: 8.80 min, 32 peak time: 12.0 min, sample solution: ethanol, injection volume: 0.8 ml, number of injection needles: 5. Two enantiomer isomers were obtained: elemental 33: white solid (20.3 mg, yield 36.2%) and elemental 32: white solid (16.9 mg, yield 30.1%). 32 LCMS(ESI,m / z):405.25 [M+H] + 32 1 H NMR(400 MHz,DMSO-d6)δ 7.70(s,1H), 7.56(s,1H), 7.18(d,J=8.0 Hz,1H), 6.94(d,J=8.0 Hz,1H), 6.68(s,2H), 5.32(s,1H), 4.28 -4.20(m,2H), 4.08 -4.00(m,2H), 2.89(d,J=7.0 Hz,2H), 2.12(s,3H), 2.07(s,3H), 2.03 -1.94(m,2H), 1.10(t,J=7.0 Hz,3H). 33 LCMS(ESI,m / z):405.25 [M+H] + 33 1H NMR(400 MHz,DMSO-d6)δ 7.70(s,1H), 7.56(s,1H), 7.18(d,J=8.0 Hz,1H), 6.94(d,J=8.0 Hz,1H), 6.68(s,2H), 5.32(s,1H), 4.28 -4.20(m,2H), 4.08 -4.00(m,2H), 2.89(d,J=7.0 Hz,2H), 2.12(s,3H), 2.07(s,3H), 2.03 -1.94(m,2H), 1.10(t,J=7.0 Hz,3H). 【0303】 (Examples 36 and 37) (S)-4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide 36 (R)-4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide 37 [ka] Chiral resolution was performed on 4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide (40 mg, 0.102 mmol) (Compound 11). Resolution conditions: (Chiral column: CHIRAL ART Cellulose-SB, 2*25 cm, 5 μm; Mobile phase A: n-hexane (methanol solution in 10 mmol / l ammonia); Mobile phase B: ethanol; Flow rate: 20 ml / min; Gradient: 20% B to 20% B) The injection was performed for 15 minutes, with wavelengths of 218 / 270 nm, peak times for 36 at 9.47 minutes and 37 at 11.2 minutes. The sample solution was ethanol, with an injection volume of 0.5 ml and 9 injection needles. Two enantiomer isomers were obtained: elemental 37: white solid (7.5 mg, yield 18.8%) and elemental 36: white solid (9.3 mg, yield 23.3%). 36 LCMS(ESI,m / z):391.10 [M+H] + 36 1H NMR(400 MHz,DMSO-d6)δ 7.70(s,1H), 7.55(s,1H), 7.11(d,J=8.0 Hz,1H), 6.98(d,J=8.0 Hz,1H), 6.71(s,2H), 5.18(s,1H), 4.63(t,J=8.8 Hz,2H), 4.04(q,J=6.8 Hz,2H), 3.40(t,J=8.8 Hz,2H), 2.11(s,3H), 2.07(s,3H), 1.10(t,J=6.8 Hz,3H). 37 LCMS(ESI,m / z):391.10 [M+H] + 37 1 H NMR(400 MHz,DMSO-d6)δ 7.70(s,1H), 7.55(s,1H), 7.11(d,J=8.0 Hz,1H), 6.98(d,J=8.0 Hz,1H), 6.71(s,2H), 5.18(s,1H), 4.63(t,J=8.8 Hz,2H), 4.04(q,J=6.8 Hz,2H), 3.40(t,J=8.8 Hz,2H), 2.11(s,3H), 2.07(s,3H), 1.10(t,J=6.8 Hz,3H). 【0304】 (Examples 38 and 39) (S)-6-(4-cyano-2-methoxylphenyl)-5-ethoxy-8-methyl-6,9-dihydrothieno[3,2-h][1,6]naphthyridine-7-carboxamide 38 (R)-6-(4-cyano-2-methoxylphenyl)-5-ethoxy-8-methyl-6,9-dihydrothieno[3,2-h][1,6]naphthyridine-7-carboxamide 39 [ka] 6-(4-cyano-2-methoxylphenyl)-5-ethoxy-8-methyl-6,9-dihydrothieno[3,2-h][1,6]naphthyridine-7-carboxamide (60 mg, 0.148 mmol) was chiral-cleared using the following conditions: chiral column: CHIRALPAK. IG, 2*25cm, 5μm, mobile phase A: n-hexane (methanol solution in 10 mmol / l ammonia), mobile phase B: ethanol, flow rate: 20 ml / min, gradient: 10% B for 34.5 minutes, wavelength: 210 / 220 nm, (39 peak time): 20.68 min, (38 peak time): 28.59 min, sample solution: methanol:dichloromethane = 1:1, injection volume: 0.35 ml, number of injection needles: 12. Two enantiomer isomers were obtained: elemental 0A: white solid (13.8 mg, yield 33.6%) and elemental 0B: white solid (14.0 mg, white solid, yield 34.1%). 38 MS(ESI)M / Z:421.00 [M+H] + 38 1 H NMR(400 MHz,DMSO-d6)δ 8.83(s,1H), 7.88(d,J=5.6 Hz,1H), 7.37(d,J=1.6 Hz,1H), 7.29 - 7.22(m,2H), 7.18(d,J=7.6 Hz,1H), 6.88 - 6.73(m,2H), 5.48(s,1H), 4.18 - 4.04(m,2H), 3.82(s,3H), 2.19(s,3H), 1.10(t,J=7.2 Hz,3H). 39 MS(ESI)M / Z:421.05 [M+H] + 39 1 H NMR(400 MHz,DMSO-d6)δ 8.83(s,1H), 7.88(d,J=5.6 Hz,1H), 7.37(d,J=1.6 Hz,1H), 7.29 - 7.22(m,2H), 7.18(d,J=7.6 Hz,1H), 6.88 - 6.73(m,2H), 5.48(s,1H), 4.18 - 4.04(m,2H), 3.82(s,3H), 2.19(s,3H), 1.10(t,J=7.2 Hz,3H). 【0305】 (Examples 40 and 41) (R)-4-(8-cyano-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide 41 (S)-4-(8-cyano-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide 40 [ka] 4-(8-cyano-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide (32.0 mg, 0.079 mmol) (Compound 25) was chiral-resolved (the resolution conditions were as follows: chiral column: CHIRALPAK IG, 2*25 cm, 5 μm, mobile phase A: n-hexane (methanol solution in 10 mmol ammonia), mobile phase B: ethanol, flow rate: 20 ml / min, gradient: 15% B to Enantiomer 41 (10.8 mg, white solid, yield 33.7%) and enantiomer 40 (9.8 mg, white solid, yield 30.6%) were obtained. (15% B, 20 minutes, wavelength: 218 / 260 nm, peak time for 41: 10.22 min, peak time for 40: 16.14 min, sample solution: ethanol:dichloromethane = 1:1, injection volume: 0.5 ml, number of injection needles: 3) 40:MS(ESI)M / Z:407.30 [M+H] + 1 H NMR(300 MHz,DMSO-d6)δ 7.69(s,1H), 7.57(d,J=8.1 Hz,1H), 7.12(d,J=8.1 Hz,1H), 6.76 -6.62(m,3H), 5.34(s,1H), 4.44 -4.25(m,4H), 4.06(d,J=7.0 Hz,2H), 2.18(s,3H), 2.12(s,3H), 1.11(t,J=7.0 Hz,3H). 41:MS(ESI)M / Z:407.30 [M+H] + 1 H NMR(300 MHz,DMSO-d6)δ 7.69(s,1H), 7.57(d,J=8.1 Hz,1H), 7.12(d,J=8.1 Hz,1H), 6.76 -6.62(m,3H), 5.34(s,1H), 4.44 -4.25(m,4H), 4.06(d,J=7.0 Hz,2H), 2.18(s,3H), 2.12(s,3H), 1.11(t,J=7.0 Hz,3H). 【0306】 (Examples 46 and 47) (S)-4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-(difluoromethoxy)-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide 46 (R)-4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-(difluoromethoxy)-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide 47 [ka] 4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-(difluoromethoxy)-2,8-dimethyl-1,4-dihydro-1,6-naphthyrizine-3-carboxamide (32.0 mg, 0.057 mmol) was chiral-resolved (the resolving conditions were as follows: chiral column: CHIRAL ART Cellulose-SZ, 3*25 cm, 5 μm; mobile phase A: n-hexane (methanol solution in 2 mmol ammonia); mobile phase B: ethanol; flow rate: 40 ml / min; gradient: 20% B) From 20% B, for 23 minutes, wavelength: 207 / 236 nm, (47) peak time: 11.6 min, (46 peak time): 20.3 min, sample solution: methanol:dichloromethane = 1:1, injection volume: 0.2 ml, number of injection needles: 3), two enantiomer isomers, elemental 0A (8.50 mg, white solid, yield 26.6%) and 0B (10.5 mg, white solid, yield 32.8%), were obtained. 46:MS(ESI)M / Z:413.05 [M+H] + 46 1H NMR(300 MHz,CDCl3)δ 7.68(s,1H), 7.05 - 6.99(m,2H), 5.87(s,1H), 5.23(s,1H), 4.75(t,J=8.7 Hz,2H), 3.43(t,J=8.7 Hz,2H), 2.51(s,3H), 2.19(s,3H). 19F NMR(282 MHz,CDCl3)δ -87.2,-90.2. 47:MS(ESI)M / Z:413.05 [M+H] + 47 1 H NMR(300 MHz,CDCl3)δ 7.68(s,1H), 7.05 - 6.99(m,2H), 5.87(s,1H), 5.23(s,1H), 4.75(t,J=8.7 Hz,2H), 3.43(t,J=8.7 Hz,2H), 2.51(s,3H), 2.19(s,3H). 19F NMR(282 MHz,CDCl3)δ -87.2,-90.2. 【0307】 (Examples 48 and 49) (S)4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-cyclopropoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide 48 (R)4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-cyclopropoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide 49 [ka] 4-(4-cyano-2,3-dihydrobenzofuran-7-yl)-5-cyclopropoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide (20.2 mg, 0.050 mmol) was chiral-resolved (the resolving conditions were as follows: chiral column: CHIRAL ART Cellulose-SZ, 3*25 cm, 5 μm; mobile phase A: n-hexane (methanol solution in 10 mmol ammonia); mobile phase B: ethanol; flow rate: 20 ml / min; gradient: 30% B to Under 30% B, for 22 minutes, wavelength: 200 / 220 nm, (49) peak time: 13.4 min, (48 peak time): 19.8 min, methanol:dichloromethane = 1:1, injection volume: 2 ml, number of injection needles: 3), two enantiomer isomers were obtained: elemental 49 (6.20 mg, white solid, yield 22.2%) and 48 (5.40 mg, white solid, yield 19.3%). 48:LCMS(ESI)M / Z:403.20 [M+H] + 48 1 H NMR(400 MHz,Chloroform-d)δ7.74(s,1H), 7.02 - 6.98(m,2H), 5.82(s,1H), 5.08(s,1H), 4.79 - 4.65(m,2H), 4.42 - 4.18(m,2H), 3.43(t,J=8.4 Hz,2H), 2.47(s,3H), 2.16(s,3H), 0.74 - 0.54(m,3H), 0.20 - 0.15(m,1H). 49:LCMS(ESI)M / Z:403.20 [M+H] + 49 1 H NMR(400 MHz,Chloroform-d)δ7.74(s,1H), 7.02 - 6.98(m,2H), 5.82(s,1H), 5.08(s,1H), 4.79 - 4.65(m,2H), 4.42 - 4.18(m,2H), 3.43(t,J=8.4 Hz,2H), 2.47(s,3H), 2.16(s,3H), 0.74 - 0.54(m,3H), 0.20 - 0.15(m,1H). 【0308】 (Examples 62 and 63) (R)-4-(7-cyanobenzo[d][1,3]dioxol-4-yl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide 63 (S)-4-(7-cyanobenzo[d][1,3]dioxol-4-yl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide 62 [ka] 4-(7-cyanobenzo[d][1,3]dioxol-4-yl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide (20 mg, 0.148 mmol) (compound 14) was chiral-resolved (the resolution conditions were as follows: chiral column CHIRAL ART Amylose-C NEO, 2*25 cm, 5 μm; mobile phase A: n-hexane (methanol solution in 10 mmol ammonia); mobile phase B: ethanol; flow rate: 20 ml / min; gradient: 10% B to (10% B, 28 minutes, wavelength: 214 / 254 nm, (63) peak time: 10.7 min, (62 peak time): 15.6 min, n-hexane:ethanol = 85:15, injection volume: 0.4 ml, number of injection needles: 2) Two enantiomer isomers were obtained: elemental 63 (5.7 mg, white solid, yield 28.5%) and 62 (3.7 mg, white solid, yield 18.5%). 62:LCMS(ESI)M / Z:393.1 [M+H] + 62 1 H NMR(400 MHz,Chloroform-d)δ δ 7.70(s,1H), 6.91(d,J=8.4 Hz,1H), 6.77(d,J=8.4 Hz,1H), 6.14(s,2H), 5.78(s,1H), 5.47(s,2H), 5.14(s,1H), 4.20(q,J=7.0 Hz,2H), 2.46(s,3H), 2.15(s,3H), 1.26(t,J=7.0 Hz,3H). 63:LCMS(ESI)M / Z:393.1 [M+H] + 63 1H NMR(400 MHz,Chloroform-d)δ δ 7.70(s,1H), 6.91(d,J=8.4 Hz,1H), 6.77(d,J=8.4 Hz,1H), 6.14(s,2H), 5.78(s,1H), 5.47(s,2H), 5.14(s,1H), 4.20(q,J=7.0 Hz,2H), 2.46(s,3H), 2.15(s,3H), 1.26(t,J=7.0 Hz,3H). 【0309】 Other examples of racemic mixtures in this application were divided in a similar manner. 【0310】 (Single-crystal X-ray diffraction analysis) (Compound 36 single-crystal X-ray diffraction analysis) Approximately 5 mg of compound 36 was dissolved in 0.6 mL of acetone at room temperature, and then 1.4 mL of water was gradually added. The filtrate was filtered into a clean vial, covered with a pinhole membrane, and slowly evaporated under room temperature conditions. After 1 day, a bulk single crystal was formed, and single-crystal X-ray diffraction was performed using the obtained single crystal, which is shown in Figure 9. 【0311】 36 crystallizes in the C2 space group as a monoclinic crystal, and its chemical formula is C 22 H 22 The molecule is N4O3. There are 36 molecules, one in each asymmetric unit, and each cell contains four asymmetric units. As shown in Figure 1, the chiral carbon of C10 is determined to be an "S" configuration. The position of the terminal ethyl group is irregular. 【0312】 The refined single-crystal structure is shown in Figures 2 and 3 (for clarity, the main three-dimensional structure and hydrogen atoms are omitted). The crystal structure data is summarized in Table 2, and detailed information on atomic coordinates, anisotropic displacement parameters, bond length and angle, hydrogen bonds, torsion angle, and atomic occupancy is shown in Tables 3 to 10. The XRPD pattern calculated from the single-crystal structure (top) was consistent with the experimental pattern (bottom) (Figure 4). 【0313】 Table 2 (Crystal data and refined structural diagrams of compound 36) [Table 2] 【0314】 Table 3 (Fractional atomic coordinates of compound 36 (×10) 4 ) and equivalent isotropic displacement parameter (Ų × 10⁻¹⁰ 3 )) [Table 3] 【0315】 U(eq) is defined as one-third of the orthogonalized Uij tensor locus. 【0316】 Table 4 (Anisotropic displacement parameters (Å) of compound 36 2 ×10 3 )) [Table 4-1] [Table 4-2] 【0317】 The anisotropic displacement factor index is -2π 2 [h 2 a* 2 U 11 +2hka*b*U 12 +...] is the case. 【0318】 Table 5 (Bond length of compound 36) [Table 5] 【0319】 Table 6 (Bond angles of compound 36) [Table 6] 【0320】 Table 7 (Hydrogen Bonding in Compound 36) [Table 7] 【0321】 1 1-x, 1+y, -z, 2 3 / 2-x, -1 / 2+y, -z 【0322】 Table 8 (Twist angle of compound 36) [Table 8-1] [Table 8-2] 【0323】 Table 9 (Hydrogen atom coordinates of compound 36 (Å × 10) 4 ) and isotropic displacement parameter (Ų × 10⁻¹⁰ 3 )) [Table 9] 【0324】 Table 10 (Atomic occupancy of 36 compounds) [Table 10] 【0325】 (Compound 62 single-crystal X-ray diffraction analysis) Approximately 5 mg of compound 62 was dissolved in 0.1 mL of ethanol at room temperature, and then 0.35 mL of n-heptane was slowly added. The solution was filtered into a clean sample bottle, the filtrate was covered with a pinhole membrane, and gradually evaporated under ambient conditions. After one day, a bulk single crystal was formed, and single-crystal X-ray diffraction was performed using the obtained single crystal, which is shown in Figure 10. 【0326】 62 crystallizes in the C2 space group in a monoclinic form, and its chemical formula is C 21 H 20 It is N4O4. There are 62 molecules in each asymmetric unit, and each cell contains 4 asymmetric units. As shown in Figure 5, the chiral carbon of C9 (C30) is determined to be an "S" configuration. 【0327】 The refined single-crystal structures are shown in Figures 6 and 7 (hydrogen atoms are omitted for clarity). The crystal structure data is summarized in Table 11, and detailed information on atomic coordinates, anisotropic displacement parameters, bond lengths and angles, hydrogen bonds, and torsion angles is shown in Tables 12 to 18. The XRPD pattern calculated from the single-crystal structure was consistent with the experimental pattern (Figure 8). 【0328】 Table 11 (Crystal data and structural optimization of 62 compounds) [Table 11] 【0329】 Table 12 (Fractional atomic coordinates of compound 62 (×10) 4 ) and equivalent isotropic displacement parameter (Ų × 10⁻¹⁰ 3 )) [Table 12-1] [Table 12-2] 【0330】 U(eq) is defined as one-third of the orthogonalized Uij tensor locus. 【0331】 Table 13 (Anisotropic displacement parameters of compound 62 (Ų × 10) 3 )) [Table 13-1] [Table 13-2] [Table 13-3] 【0332】 The exponent of the anisotropic displacement coefficient is in the following form: -2π 2 [h 2 a* 2 U 11 +2hka*b*U12 +...]. 【0333】 Table 14 (Bond length of compound 62) [Table 14] 【0334】 Table 15 (Bond angles of compound 62) [Table 15-1] [Table 15-2] 【0335】 Table 16 (Hydrogen Bonding in Compound 62) [Table 16] 【0336】 1 1-x, -1+y, -z, 2 3 / 2-x, -1 / 2+y, -z, 3 2-x, -1+y, 1-z 【0337】 Table 17 (Twist angle of compound 62) [Table 17-1] [Table 17-2] [Table 17-3] 【0338】 Table 18 (Hydrogen atom coordinates of compound 62 (Å × 10) 4 ) and isotropic displacement parameter (Ų × 10⁻¹⁰ 3 )) [Table 18] 【0339】 (Examples) (In vitro activity test) 1. Experimental principle: Using the chemiluminescence reaction that luciferase undergoes when binding to a substrate, a plasmid in which the ligand-binding domain (LBD) of the mineralocorticoid receptor (MR) was fused to the Gal4 DNA-binding domain (DBD), and a plasmid of a firefly luciferase reporter gene regulated by Gal4UAS (upstream activation sequence) were transfected into human embryonic kidney cells (HEK293). Changes in mineralocorticoid receptor activity before and after stimulation, or the effects of different stimuli on mineralocorticoid receptor activity, were determined at the level of firefly luciferase activity. 【0340】 2. Experimental method: 1. Preparation and processing of the compound 1.1 Preparation of DMSO storage solution All compounds were dissolved in DMSO to prepare a 25 mM storage solution, which was then stored in a refrigerator at -20°C. 1.2 Preparation of the working solution 1) The test compound was gradient-diluted threefold with DMSO to create 10 concentration gradients, with the starting concentration being 10 mM. 2) The positive compound (Finelenone) was gradient diluted threefold with DMSO to create 10 concentration gradients, with the starting concentration being 1 mM. 3) A 1000× positive control (1 mM, Finelenone) and a 1000× negative control (100% DMSO) were prepared. 4) The compound plate was sealed and shaken for 5 minutes. 【0341】 2. Preparation of cell suspension 1) All cells were cultured according to ATCC standard procedures, and HEK293T was tested during the exponential growth phase. 2) Gently discard the culture medium supernatant. Wash the cells twice with PBS. 3) The cells were digested with trypsin digestant, digestion was completed in complete culture medium, and the cells were collected and counted. 4) 6 x 10⁶ HEK293T cells were inoculated into 100 mm cell culture dishes. 5) The culture dishes inoculated with cells were incubated overnight (16 hours) in a 37°C, 5% CO2 incubator. 【0342】 3. Cell transfection 1) Lipofectamine® 3000&P3000 transfection reagent was left at room temperature. 2) Lipofectamine® 3000 reagent was added to Opti-MEM® medium, and at the same time, P3000, plasmid, and Opti-MEM® medium were added to another tube, taking care not to touch the tube walls. 3) Mix uniformly using a pipette gun and let stand at room temperature for 5 minutes. 4) The plasmid was added to the diluted transfection reagent, mixed uniformly with a pipette gun, and allowed to stand at room temperature for 20 minutes. 5) The transfection reagent mixed with the plasmid was added to a 60 mm cell culture dish. 6) The culture dishes were incubated in a 37°C, 5% CO2 incubator for 5-6 hours. 【0343】 4. Compound treatment 1) 25 nL of the compound diluted with Echo655 was transferred to a cell culture plate. 2) Cells (see Step 1.3) were inoculated into 384 cell culture plates, with 17,000 cells per well, and 25 μL of phenol-red-free DMEM medium containing 5% CFBS and 0.8 nM Aldosterone. 3) The cell culture plates were incubated overnight in a 37°C, 5% CO2 incubator for 18-20 hours. 【0344】 5. Detection of Compounds 1) The Britlite plus detection reagent was left at room temperature. 2) The 384-cell plate was left at room temperature. 3) 25 μL of Britlite plus detection reagent was added to each well of the cell culture plate. 4) The light emission value was detected using Envision. 【0345】 6. Result processing: 1) By reading the luminescence, the firefly luciferase signal is determined and the inhibition rate is calculated. 2) % inhibition rate = 100 - [(RLU compound - avgRLU positive control) / (RLU negative control - avgRLU positive control) × 100%, where avgRLU positive control is the average value of all positive control pore luminescence across the entire plate, avgRLU negative control is the average value of all negative control pore luminescence across the entire plate, and RLU compound is the luminescence value of the test compound at different concentrations. 3) Calculate the IC50 of the compound using Graphpad 8.0 graphing software. 【0346】 7. Experimental results: Table 19 (In vitro activity data of the compounds of the present invention) [Table 19] 【0347】 Conclusion: As can be seen from the experimental results in Table 19, the compounds described in the present invention have good mineralocorticoid receptor (MR) antagonistic activity and can be used as effective mineralocorticoid receptor antagonists. 【0348】 (Examples) (Drug metabolism kinetics study in test rats) The purpose of this experiment is to evaluate the pharmacokinetic behavior of the compounds in the examples after intravenous injection or oral administration into rats. Intravenous injection: The test compound was formulated as a 0.2 mg / ml clarified solution, and the solvent was 10% ethanol, 40% polyethylene glycol 400, and 50% water. Plasma was collected at 0.083h, 0.25h, 0.5h, 1h, 2h, 4h, 8h, and 24h after administration. Oral administration: The test compound was formulated as a 1 mg / ml clarified solution, and the solvent was 10% ethanol / 40% polyethylene glycol 400 / 50% water. Plasma was collected at 0.25h, 0.5h, 1h, 2h, 4h, 8h, and 24h after administration. 【0349】 The concentrations of the test compounds in plasma were measured by high-performance liquid chromatography-tandem mass spectrometry (LC-MS / MS). Retention times for the compounds and internal standards, chromatogram acquisition, and chromatogram integration were processed using the software Analyst (Applied Biosystems), and data statistics were also processed using the software Analyst (Applied Biosystems). 【0350】 Plasma concentrations were processed using a non-atrial model of the WinNonlin™ Version 6.1 (Pharsight, Mountain View, CA) pharmacokinetic software, and pharmacokinetic parameters were calculated using the linear logarithmic trapezoidal method. 【0351】 The parameters for the pharmacokinetics of rats after intravenous administration of the compound at a dose of 1 mg / kg and oral administration at a dose of 5 mg / kg are shown in Table 20 below. 【0352】 Table 20 (SD rat drug metabolism kinetics (PK) data) [Table 20] 【0353】 As can be seen from the experimental results in Table 20, the compounds described in the present invention have good in vivo drug metabolism kinetics. 【0354】 (Examples) (Drug metabolism kinetics study in test mice) The purpose of this experiment was to evaluate the pharmacokinetic behavior of compounds after intravenous injection or oral administration to mice. Intravenous injection: The test compound was formulated as a 0.2 mg / ml clarified solution, and the solvent was 10% ethanol / 40% polyethylene glycol 400 / 50% ultrapure water. Plasma was collected at 0.083, 0.25, 0.5, 1, 2, 4, 8, 24, and 48 hours after administration. 【0355】 The concentrations of the test compounds in plasma were measured by high-performance liquid chromatography-tandem mass spectrometry (LC-MS / MS). Retention times for the compounds and internal standards, chromatogram acquisition, and chromatogram integration were processed using the software Analyst (Applied Biosystems), and data statistics were also processed using the software Analyst (Applied Biosystems). 【0356】 Plasma concentrations were processed using a non-atrial model of the WinNonlin™ Version 6.1 (Pharsight, Mountain View, CA) pharmacokinetic software, and pharmacokinetic parameters were calculated using the linear logarithmic trapezoidal method. 【0357】 The parameters related to the drug metabolism kinetics of mice when the compound is administered intravenously at a dose of 1 mg / kg are shown in Table 21 below. 【0358】 Table 21 (CD1 mouse drug metabolism kinetics (PK) data) [Table 21] 【0359】 (Example 70) (Pharmacodynamic effects of compounds 36 and 62 on a mouse model of diabetic nephropathy) 1. Research purpose The pharmacodynamic effects of compounds 36 and 62 on a mouse model of diabetic nephropathy will be evaluated. 【0360】 2. Preparation of drugs The solvent and positive agent must be prepared on the same day, and the preparation method is shown in Table 70-1. 【0361】 Table 70-1 (Preparation of drugs) [Table 70-1] 【0362】 3. Laboratory animals and their care 3.1 Laboratory animals Family lineage: C57BL / 6 mouse, KK-Ay mouse Age in weeks: The animals reach 6-8 weeks of age, and the experiment begins at 7-9 weeks. Gender: Male Weight: C57BL / 6 mice 21-23g, KK-Ay mice 25-30g Number of experimental animals: 72 【0363】 3.2 Animal Husbandry 3.2.1 Quarantine The quarantine and adaptation period will total 7 days, routine health checks will be performed by a veterinarian, and animals exhibiting abnormal behavior will be excluded before the experiment. 3.2.2 Animal Rearing Conditions The experimental animals were housed in single cages within an SPF-class constant temperature and humidity laminar flow cleanroom at the animal center (AAALAC-certified unit) of Kanglong Chemical (Beijing) New Drug Technology Co., Ltd. The rearing temperature was 22-25°C, the humidity 40-80%, and irradiation was alternated every 12 hours. The cages were made of polycarbonate. Clean, autoclaved, soft corn cob bedding was used and replaced twice a week. Drinking water was autoclaved, and the feed was irradiated with cobalt-60. The animals had free access to sterile food and water. 3.2.3 Animal Number Each cage was labeled with a cage label indicating the number of animals, sex, lineage, check-in time, group number, and experiment start time. Each animal was also marked with an individual identification number on its tail. 【0364】 4. Sorting of experimental animals and administration of drugs On the day of administration, the animals were randomly divided into nine groups according to their body weight: a model group (KK-Ay + solvent), a finelenone group (KK-Ay + finelenone: 3 mg / kg), a low-dose compound 62 group (KK-Ay + compound 62: 1 mg / kg), a medium-dose compound 62 group (KK-Ay + compound 62: 3 mg / kg), a high-dose compound 62 group (KK-Ay + compound 62: 10 mg / kg), a low-dose compound 36 group (KK-Ay + compound 36: 1 mg / kg), a medium-dose compound 36 group (KK-Ay + compound 36: 3 mg / kg), and a high-dose compound 36 group (KK-Ay + compound 36: 10 mg / kg). The specific group assignments and administration methods are shown in Table 70-2. 【0365】 Table 70-2 (Assortment of experimental animals and drug administration) [Table 70-2] 【0366】 7. Experimental methods and detection indicators 7.1 Urine collection Before modeling and at weeks 2, 4, 6, and 8 after modeling, mouse urine was collected over 24 hours using a metabolic cage. The urinary microalbumin (MALB) and creatinine (CREA) content was detected using a Canon TBA-120FR automated blood biochemistry detector. The (MALB / CREA) ratio was calculated. 【0367】 7.2 Detection of insulin content and serum ions After the experiment, the mice were euthanized, blood was collected by cardiac puncture, placed in an EP tube without anticoagulants, left to stand at room temperature for 0.5 hours, then centrifuged at 4°C and 6000g for 15 minutes to collect serum, transferred to a new EP tube, stored in a refrigerator at -80°C, and the insulin content and serum ion assay in the serum were detected by ELISA. 【0368】 7.3 Tissue collection After the experiment, the kidneys of all animals were dissected and collected, fixed in formalin, embedded, and sectioned. PAS staining, Masson staining, and quantitative analysis were then performed. 【0369】 8. Statistics The experimental results were expressed as "mean ± standard deviation". The data were statistically analyzed using GraphPad 8.0 software, and p < 0.05 was considered statistically significant. 【0370】 9.Results Both compound 62 and compound 36 significantly promoted urinary sodium excretion and significantly reduced the urinary protein / creatinine ratio, demonstrating beneficial effects on diabetic nephropathy and hypertension. 【0371】 (Example 71) (Study on in vitro CPY enzyme inhibition) According to the research results, the IC50 (μM) data for the main drug-metabolizing enzyme CYP3A4 in humans are as follows: CYP3A4-5M and CYP3A4-5T are finelenone (9.98, 8.02), compound 36 (22.86, 15.78), and compound 62 (13.66, 5.35), respectively. 【0372】 Therefore, compounds 36 and 62 are safer than finelenone. Compound 36 has a higher half-life inhibitory concentration than finelenone for CYP3A4-5M / CYP3A4-5T, two isoforms of the major human metabolic enzyme CYP3A4 (this enzyme metabolizes approximately 50% of drugs). 【0373】 In this specification, reference terms such as “one embodiment,” “several embodiments,” “examples,” “specific examples,” or “several examples” mean that the specific features, structures, materials, or properties described with reference to such embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not need to refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or properties described can be combined in an appropriate manner in any one or more embodiments or examples. Moreover, a person skilled in the art can combine and combine different embodiments or examples and features of different embodiments or examples described herein, provided that they do not conflict with each other. 【0374】 Although embodiments of the present invention have been shown and described above, these embodiments are merely illustrative and should not be understood as limiting the present invention. Those skilled in the art should understand that changes, modifications, substitutions, and variations can be made to the above embodiments within the scope of the present invention. 【0375】 (Note) (Note 1) The compound represented by formula (I) and its stereoisomers, geometric isomers, reverse isomers, nitrogen oxides, hydrates, solvates, metabolites, esters, pharmaceutically acceptable salts, or prodrugs, [ka] (I) Here, [ka] teeth, [ka] And, R1, R2, R3, and R4 are independently hydrogen, deuterium, amino, hydroxyl, mercapto, cyano, nitro, and C. 1~6 Alkyl, C 1~6 Alkoxy, C 1~6 Haloalkyl, C 1~6Haloalkoxy, C 1~6 Alkylamino, carboxyl, C 1~6 Alkanoyl, C 1~6 Alkyl sulfonyl, aminoacyl, aminosulfonyl, C 3~8 Cycloalkyl, C 6~10 These are aryls, heterocyclines consisting of 3 to 8 atoms, or heteroaryls consisting of 5 to 10 atoms. R5 is [ka] And, R6 is hydrogen, deuterium, C 1~6 Alkyl, C 1~6 Alkoxy, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, C 1~6 Alkylamino, C 3~8 Cycloalkyl, C 6~10 These are aryls, heterocyclines consisting of 3 to 8 atoms, or heteroaryls consisting of 5 to 10 atoms. [ka] teeth, [ka] And, X is either C or N, Y is either O or S, R7 is C 1~6 Alkyl, C 3~8 Cycloalkyl, heterocyclyl consisting of 3-8 atoms, heteroaryl consisting of 5-6 atoms, C 3~8 Cycloalkyl C 1~6 Alkyl, (heterocyclyl consisting of 3 to 8 atoms) C 1~6 Alkyl, (heteroaryl, consisting of 5-6 atoms) C 1~6 Alkyl, phenyl, or phenyl C 1~6 It is an alkyl group, and R7 is either unsubstituted or substituted with 1, 2, 3, or 4 Rz. Each Rz independently corresponds to O, deuterium, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, NH2, and C. 1~6 Alkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 1~6 Haloalkyl, C 1~6 Alkylamino, C 1~6 Alkyl sulfonyl, C 1~6 Alkylacyl, C 3~8 Cycloalkyl, heterocyclyl consisting of 3 to 8 atoms, heteroaryl or C consisting of 5 to 6 atoms 6~10 Aaryl, where each Rz is independently unsubstituted or substituted by 1, 2, 3, or 4 Rw, Each Rw is independently O, deuterium, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, amino, C 1~6 Alkyl, C 1~6 Alkoxy, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, C 1~6 Alkylamino, C 1~6 Alkyl sulfonyl, C 1~6 Alkylacyl, C 3~8 Cycloalkyl, heterocyclyl consisting of 3 to 8 atoms, heteroaryl or C consisting of 5 to 6 atoms 6~10 It is Ariel, [ka] teeth, [ka] And, R8 and R9 are hydrogen, deuterium, and C 1~6 Alkyl, C 1~6 Alkoxy, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, C 1~6 Alkylamino, C 3~8 Cycloalkyl, C 6~10 A compound characterized by being an aryl, a heterocyclyl consisting of 3 to 8 atoms, or a heteroaryl consisting of 5 to 10 atoms. 【0376】 (Note 2) The compound represented by formula (I) and its stereoisomers, geometric isomers, reverse isomers, nitrogen oxides, hydrates, solvates, metabolites, esters, pharmaceutically acceptable salts, or prodrugs, [ka] (I) Here, [ka] teeth, [ka] or [ka] And, R1, R2, R3, and R4 are independently hydrogen, deuterium, amino, hydroxyl, mercapto, cyano, nitro, and C. 1~6 Alkyl, C 1~6 Alkoxy, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, C 1~6 Alkylamino, carboxyl, C 1~6 Alkanoyl, C 1~6 Alkyl sulfonyl, aminoacyl, aminosulfonyl, C 3~8 Cycloalkyl, C 6~10 These are aryls, heterocyclines consisting of 3 to 8 atoms, or heteroaryls consisting of 5 to 10 atoms. R5 is [ka] And, R6 is hydrogen, deuterium, C 1~6 Alkyl, C 1~6 Alkoxy, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, C 1~6 Alkylamino, C 3~8 Cycloalkyl, C 6~10These are aryls, heterocyclines consisting of 3 to 8 atoms, or heteroaryls consisting of 5 to 10 atoms. [ka] teeth, [ka] And, X is either C or N, Y is either O or S, R7 is C 1~6 Alkyl, C 3~8 Cycloalkyl, heterocyclyl consisting of 3-8 atoms, heteroaryl consisting of 5-6 atoms, C 3~8 Cycloalkyl C 1~6 Alkyl, (heterocyclyl consisting of 3 to 8 atoms) C 1~6 Alkyl, (heteroaryl, consisting of 5-6 atoms) C 1~6 Alkyl, phenyl, or phenyl C 1~6 Alkyl, R7 is unsubstituted or substituted with 1, 2, 3 or 4 Rz. Each Rz independently corresponds to O, deuterium, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, NH2, and C. 1~6 Alkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 1~6 Haloalkyl, C 1~6 Alkylamino, C 1~6 Alkyl sulfonyl, C 1~6 Alkylacyl, C 3~8 Cycloalkyl, heterocyclyl consisting of 3 to 8 atoms, heteroaryl or C consisting of 5 to 6 atoms 6~10 It is an aryl, where each Rz is independently unsubstituted or substituted with 1, 2, 3, or 4 Rws. Each Rw is independently O, deuterium, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, amino, C 1~6 Alkyl, C 1~6 Alkoxy, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, C 1~6Alkylamino, C 1~6 Alkyl sulfonyl, C 1~6 Alkylacyl, C 3~8 Cycloalkyl, heterocyclyl consisting of 3 to 8 atoms, heteroaryl or C consisting of 5 to 6 atoms 6~10 It is Ariel, [ka] teeth, [ka] And, R8 and R9 are hydrogen, deuterium, and C 1~6 Alkyl, C 1~6 Alkoxy, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, C 1~6 Alkylamino, C 3~8 Cycloalkyl, C 6~10 These are aryls, heterocyclines consisting of 3 to 8 atoms, or heteroaryls consisting of 5 to 10 atoms. R 10 and R 11 Each is independently selected from -CH2- or O, and at least one is O. R 12 is -CH2- or -CH2-CH2-, R 12 If R is -CH2-, 10 and R 11 Each is independently selected from -CH2- or O, with at least one being O, and R 12 If R is -CH2-CH2-, 10 and R 11 It is O at the same time, or R 10 is -CH2-, and R 11 A compound characterized by being O. 【0377】 (Note 3) The compound according to Appendix 1, characterized in that it is selected from compounds represented by formula (Ia) or formula (Ib), and more preferably the compound represented by formula (Ia). [ka] (Ia) [ka] (Ib) 【0378】 (Note 4) Each of R1, R2, R3, and R4 is independently hydrogen, deuterium, amino, hydroxyl, mercapto, cyano, nitro, and C. 1~4 Alkyl, C 1~4 Alkoxy, C 1~4 Haloalkyl, C 1~4 Haloalkoxy, C 1~4 Alkylamino, carboxyl, C 1~4 Alkanoyl, C 1~4 Alkyl sulfonyl, aminoacyl, aminosulfonyl, C 3~6 Cycloalkyl, C 6~10 These are aryls, heterocyclines consisting of 3 to 6 atoms, or heteroaryls consisting of 5 to 6 atoms. R6 is hydrogen, deuterium, C 1~4 Alkyl, C 1~4 Alkoxy, C 1~4 Haloalkyl, C 1~4 Haloalkoxy, C 1~4 Alkylamino, C 3~6 Cycloalkyl, C 6~10 These are aryls, heterocyclines consisting of 3 to 6 atoms, or heteroaryls consisting of 5 to 6 atoms. Each of R8 and R9 is independently hydrogen, deuterium, halogen, cyano, and C. 1~4 Alkoxyacyl, carboxyl, C 1~4 Alkyl, C 1~4 Alkoxy, C 1~4 Haloalkyl, C 1~4 Haloalkoxy, C 1~4 Alkylamino, C 1~4 Alkanoyl, C 1~4 A compound according to any one of the appendices 1 to 3, characterized in that it is an alkylsulfonyl, aminoacyl, or aminosulfonyl. 【0379】 (Note 5) Each R1, R2, R3, and R4 is independently hydrogen, deuterium, amino, hydroxyl, mercapto, cyano, nitro, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, butoxy, trifluoromethyl, difluoromethyl, monofluoromethyl, 2,2-difluoroethyl, 1,2-difluoroethyl, trifluoroethyl, trifluoromethoxy, difluoromethoxy, monofluoromethoxy, methylamino, dimethylamino, carboxyl, methylacyl, ethylacyl, methylsulfonyl, aminoacyl, or aminosulfonyl. R6 is hydrogen, deuterium, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, butoxy, trifluoromethyl, difluoromethyl, monofluoromethyl, 2,2-difluoroethyl, 1,2-difluoroethyl, trifluoroethyl, trifluoromethoxy, difluoromethoxy, monofluoromethoxy, methylamino, dimethylamino, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthalenyl, cyclohexylethyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholino, pyridinyl, pyrrolidinyl, thiazole, pyrazole, or pyrimidinyl. The compound described in any one of the appendices 1 to 3, characterized in that R8 is hydrogen, deuterium, cyano, methylacyl, ethylacyl, propylacyl, methoxyacyl, ethoxyacyl, propoxyacyl, carboxyl, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, butoxy, trifluoromethyl, difluoromethyl, monofluoromethyl, 2,2-difluoroethyl, 1,2-difluoroethyl, trifluoroethyl, trifluoromethoxy, difluoromethoxy, monofluoromethoxy, methylamino, or dimethylamino. 【0380】 (Note 6) A compound according to any one of the appendices 1 to 3, characterized in that it is selected from the compounds represented by formula (II). [ka] (II) 【0381】 (Note 7) A compound according to any one of the appendices 1 to 3, characterized in that it is a compound represented by formula (IIa) or formula (IIb). [ka] (IIa) [ka] (IIb) 【0382】 (Note 8) R7 is C 3~6 Cycloalkyl, heterocyclyl consisting of 3-6 atoms, heteroaryl consisting of 5-6 atoms, C 3~6 Cycloalkyl C 1~4 Alkyl, (heterocyclyl consisting of 3-6 atoms) C 1~4 Alkyl or (heteroaryl) C (consisting of 5-6 atoms) 1~4 The compound according to any one of the appendices 1 to 7, characterized in that it is an alkyl group, where R7 is either unsubstituted or substituted with 1, 2, 3, or 4 Rz groups. 【0383】 (Note 9) R7 is C 1~3 The compound according to any one of the appendices 1 to 7, characterized in that it is an alkyl group, where R7 is unsubstituted or substituted with 1, 2, 3 or 4 Rz values, preferably R7 is methyl, ethyl, or isopropyl, where R7 is unsubstituted or substituted with 1, 2, 3 or 4 Rz values. 【0384】 (Note 10) R7 contains cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ethylene oxide, azetidinyl, oxetidinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, thiazolidinyl, pyrazolidinyl, oxazolidinyl, imidazolidinyl, isoxazolidinyl, piperidinyl, piperazinyl, morpholino, pyrrolidinyl, furanyl, thiophene, thiazole, pyrazole, pyridinyl, pyrimidinyl, cyclopropylmethyl, cyclopropylethyl, cyclopropylmethyl, cyclopropylethyl, cyclopentylmethyl, cyclopentylethyl, cyclohexylmethyl, cyclohexylethyl, azetidinylmethyl, azetidinylethyl, oxetidinylmethyl, oxetidinylethyl, pyrrolidinylmethyl, pyrrolidinylethyl, tetrahydrofuranylmethyl The compound is one of the compounds described in any one of the appendices 1 to 7, characterized in that R7 is either unsubstituted or substituted with 1, 2, 3, or 4 Rz values. 【0385】 (Note 11) Each Rz independently corresponds to O, deuterium, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, NH2, and C. 1~4 Alkyl, C 1~4 Alkoxy, C 1~4 Haloalkoxy, C 1~4 Haloalkyl, C 1~4 Alkylamino, C 1~4 Alkyl sulfonyl, C 1~4 Alkylacyl, C 3~6Cycloalkyl, heterocyclyl consisting of 3-6 atoms, heteroaryl or C consisting of 5-6 atoms 6~10 It is an aryl compound, where each Rz is independently unsubstituted or substituted with 1, 2, 3, or 4 Rws, each Rw independently being O, deuterium, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, NH2, or C 1~4 Alkyl, C 1~4 Alkoxy, C 1~4 Haloalkyl, C 1~4 Haloalkoxy, C 1~4 Alkylamino, C 1~4 Alkyl sulfonyl, C 1~4 Alkylacyl, C 3~6 Cycloalkyl, heterocyclyl consisting of 3-6 atoms, heteroaryl or C consisting of 5-6 atoms 6~10 A compound according to any one of the appendices 1 to 8, characterized by being an aryl compound. 【0386】 (Note 12) Each Rz independently corresponds to O, deuterium, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, NH2, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, trifluoromethoxy, monofluoromethoxy, difluoromethoxy, trifluoromethyl, difluoromethyl, monofluoromethyl, methylamino, ethylamino, dimethylamino, methylethylamino, diethylamino, methylsulfonyl, ethylsulfonyl, methylacyl, ethylacyl, cyclopropyl, cyclobutyl cyclopentyl, cyclohexyl, ethylene oxide, azetidinyl, oxetidinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, thiazolidinyl, pyrazolidinyl, oxazolidinyl, imidazolidinyl, isoxazolidinyl, piperidinyl, piperazinyl, morpholino, pyrrolidinyl, furanyl, thiophene, thiazole, pyrazole, pyridinyl, pyrimidinyl, or phenyl, where each Rz is independently unsubstituted or has 1, 2, 3, or 4 R Substituted with w, each Rw independently is O, deuterium, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, NH2, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, trifluoromethoxy, monofluoromethoxy, difluoromethoxy, trifluoromethyl, difluoromethyl, monofluoromethyl, methylamino, ethylamino, dimethylamino, methylethylamino, diethylamino, methylsulfonyl, ethylsulfonyl, methylacyl, ethylacyl, cyclopropyl A compound according to any one of the appendices 1 to 8, characterized in that it is cyclobutyl, cyclopentyl, cyclohexyl, ethylene oxide, azetidinyl, oxetidinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, thiazolidinyl, pyrazolidinyl, oxazolidinyl, imidazolidinyl, isoxazolidinyl, piperidinyl, piperazinyl, morpholino, pyrrolidinyl, furanyl, thiophene, thiazole, pyrazole, pyridinyl, pyrimidinyl, or phenyl. 【0387】 (Note 13) Selected from the compounds shown in formula (III), [ka] (III) Here, R5 [ka] The compound according to Appendix 1, characterized by being selected from the above. 【0388】 (Note 14) R1, R2, R3, and R4 are independently hydrogen, deuterium, and C 1~6 It is an alkoxy, R5 is [ka] And, R6 is hydrogen, deuterium, C 1~6 The compound according to Appendix 13, characterized in that it is selected from alkyl groups. 【0389】 (Note 15) R1, R2, R3, and R4 are independently hydrogen, deuterium, and C 1~3 It is an alkoxy, R5 is [ka] And, R6 is hydrogen, deuterium, C 1~3 The compound according to Appendix 13, characterized in that it is selected from alkyl groups. 【0390】 (Note 16) R1, R2, R3, and R4 are independently hydrogen, deuterium, and methoxyl. R5 is [ka] And, The compound according to Appendix 14, characterized in that R6 is selected from hydrogen, deuterium, and methyl. 【0391】 (Note 17) Selected from the compounds shown in formula (IV), [ka] (IV) Here, [ka] teeth [ka] And, R1, R2, R3, and R4 are independently hydrogen, deuterium, and C 1~6 It is an alkoxy, R5 is [ka] Selected from, R6 is C 1~6 It is alkyl, R7 is C 1~6 It is alkyl, R8 and R9 are hydrogen, deuterium, and C 1~6 It is alkyl, Y is selected from O, The compound according to Appendix 1, characterized in that X is selected from C. 【0392】 (Note 18) R1, R2, R3, and R4 are independently hydrogen, deuterium, and C 1~3 It is an alkoxy, R6 is C 1~3 It is alkyl, R7 is C 1~3 It is alkyl, R8 and R9 are hydrogen, deuterium, and C 1~3 The compound described in Appendix 17, characterized by being alkyl. 【0393】 (Note 19) Selected from the compounds represented by formula (V), [ka] (V) Here, [ka] teeth [ka] And, R3 and R4 are independently hydrogen and deuterium. R5 is [ka] Selected from, R6 is C 1~6 It is alkyl, R7 is C 1~6 Alkyl, C 3~8 Cycloalkyl, C 3~8 Cycloalkyl C 1~6 It is an alkyl group, where R7 is either unsubstituted or substituted with 1, 2, 3, or 4 Rz atoms, each Rz atom independently being a halogen. R8 and R9 are hydrogen, deuterium, and C 1~6 It is alkyl, X is selected from C, The compound according to Appendix 1, characterized in that Y is selected from O. 【0394】 (Note 20) R6 is C 1~3 It is alkyl, R7 is C 1~3 Alkyl, C 3~5 Cycloalkyl, C 3-4 Cycloalkyl C 1~3 It is an alkyl group, where R7 is either unsubstituted or substituted with 1, 2, 3, or 4 Rz atoms, each Rz atom independently being fluorine, chlorine, bromine, or iodine. R8 and R9 are hydrogen, deuterium, and C 1~3 The compound described in Appendix 19, characterized by being alkyl. 【0395】 (Note 21) R6 is C 1~3 It is alkyl, R7 is C1~3 Alkyl, C 3~5 Cycloalkyl, C 3-4 Cycloalkyl C 1~3 It is an alkyl group, where R7 is either unsubstituted or substituted with 1, 2, 3, or 4 Rz atoms, each Rz atom independently being fluorine. The compound described in Appendix 19, characterized in that R8 and R9 are hydrogen and methyl, respectively. 【0396】 (Note 22) Selected from the compounds represented by formula (V), [ka] (V) Here, [ka] teeth [ka] And, R3 and R4 are independently hydrogen and deuterium. R5 is [ka] Selected from, R6 is C 1~6 It is alkyl, R7 is C 1~6 Alkyl, C 3~8 Cycloalkyl, C 3~8 Cycloalkyl C 1~6 It is an alkyl group, where R7 is either unsubstituted or substituted with 1, 2, 3, or 4 Rz, each Rz independently of a halogen, C 1~6 It is alkyl, R8 and R9 are hydrogen, deuterium, and C 1~6 It is alkyl, X is selected from C, The compound according to any one of the appendices 1 to 3, characterized in that Y is selected from O. 【0397】 (Note 23) A compound is selected from those represented by formula (Va) or formula (Vb), [ka] (Va) (Vb) Here, [ka] teeth [ka] And, R3 and R4 are independently hydrogen and deuterium. R5 is [ka] Selected from, R6 is C 1~6 It is alkyl, R7 is C 1~6 Alkyl, C 3~8 Cycloalkyl, C 3~8 Cycloalkyl C 1~6 It is an alkyl group, where R7 is either unsubstituted or substituted with 1, 2, 3, or 4 Rz, each Rz independently of a halogen, C 1~6 It is alkyl, R8 and R9 are hydrogen, deuterium, and C 1~6 It is alkyl, X is selected from C, The compound according to Appendix 22, characterized in that Y is selected from O. 【0398】 (Note 24) R6 is C 1~3 It is alkyl, R7 is C 1~3 Alkyl, C 3~5 Cycloalkyl, C 3-4 Cycloalkyl C 1~3 It is an alkyl group, where R7 is either unsubstituted or substituted with 1, 2, 3, or 4 Rz atoms, each Rz atom independently of fluorine, chlorine, bromine, iodine, or C. 1~4It is alkyl, R8 and R9 are hydrogen, deuterium, and C 1~3 A compound according to any one of appendices 22 to 23, characterized by being alkyl. 【0399】 (Note 25) R6 is C 1~3 It is alkyl, R7 is C 1~3 Alkyl, C 3~5 Cycloalkyl, C 3-4 Cycloalkyl C 1~3 It is an alkyl group, where R7 is either unsubstituted or substituted with 1, 2, 3, or 4 Rz atoms, each Rz atom independently being fluorine or methyl. The compound described in any one of the appendices 22 to 23, characterized in that R8 and R9 are hydrogen and methyl, respectively. 【0400】 (Note 26) A compound is selected from those represented by formula (VI), formula (VIa), or formula (VIb), [ka] (VI) [ka] (VIa) [ka] (VIb) R 10 and R 11 Each is independently selected from -CH2- or O, and at least one is O. R 12 is -CH2- or -CH2-CH2-, and R 12 is -CH2-, and R 10 and R 11 Each is independently selected from -CH2- or O, with at least one being O, and R 12 is -CH2-CH2-, and R 10 and R 11 It is O at the same time, or R10 is -CH2-, and R 11 is O, R7 is C 1~3 Alkyl, C 3~6 Cycloalkyl, heterocyclyl consisting of 3-6 atoms, heteroaryl consisting of 5-6 atoms, C 3~6 Cycloalkyl C 1~4 Alkyl, (heterocyclyl consisting of 3-6 atoms) C 1~4 Alkyl or (heteroaryl) C (consisting of 5-6 atoms) 1~4 It is an alkyl group, where R7 is either unsubstituted or substituted with 1, 2, 3, or 4 Rz atoms. Preferably, R7 is methyl, ethyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ethylene oxide, azetidinyl, oxetidinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, thiazolidinyl, pyrazolidinyl, oxazolidinyl, imidazolidinyl, isoxazolidinyl, piperidinyl, piperazinyl, morpholino, pyrrolidinyl, furanyl, thiophene, thiazole, pyrazole, pyridinyl, pyrimidinyl, cyclopropylmethyl, cyclopropylethyl, cyclopropylmethyl, cyclopropylethyl, cyclopentylmethyl, cyclopentylethyl, cyclohexylmethyl, cyclohexylethyl, azetidinylmethyl, azetidinylethyl, oxetidinylmethyl, oxetidinylethyl, pyrrolidinylmethyl , pyrrolidinyl ethyl, tetrahydrofuranylmethyl, tetrahydrofuranyl ethyl, tetrahydrothienylmethyl, tetrahydrothienyl ethyl, piperidinyl methyl, piperidinyl ethyl, piperadinyl methyl, piperadinyl ethyl, morpholinomethyl, morpholinoethyl, pyrrolidinyl methyl, pyrrolidinyl ethyl, furanyl methyl, furanyl ethyl, thiophene methyl, thiophene ethyl, thiazole methyl, thiazole ethyl, pyrazole methyl, pyrazole ethyl, imidazolyl methyl, imidazolyl ethyl, triazolyl methyl, triazolyl ethyl, tetrazolyl methyl, tetrazolyl ethyl, pyridinyl methyl, pyridinyl ethyl, pyrimidinyl methyl or pyrimidinyl ethyl, where R7 is unsubstituted or substituted with 1, 2, 3 or 4 Rz values. Preferably, each Rz is independently O, deuterium, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, NH2, C 1~4 Alkyl, C 1~4 Alkoxy, C 1~4 Haloalkoxy, C 1~4 Haloalkyl, C 1~4 Alkylamino, C 1~4 Alkyl sulfonyl, C 1~4 Alkylacyl, C 3~6 Cycloalkyl, heterocyclyl consisting of 3-6 atoms, heteroaryl or C consisting of 5-6 atoms 6~10It is an aryl compound, where each Rz is independently unsubstituted or substituted with 1, 2, 3, or 4 Rws, each Rw independently being O, deuterium, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, NH2, or C 1~4 Alkyl, C 1~4 Alkoxy, C 1~4 Haloalkyl, C 1~4 Haloalkoxy, C 1~4 Alkylamino, C 1~4 Alkyl sulfonyl, C 1~4 Alkylacyl, C 3~6 Cycloalkyl, heterocyclyl consisting of 3-6 atoms, heteroaryl or C consisting of 5-6 atoms 6~10 It is Ariel, Preferably, each Rz is independently O, deuterium, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, NH2, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, trifluoromethoxy, monofluoromethoxy, difluoromethoxy, trifluoromethyl, difluoromethyl, monofluoromethyl, methylamino, ethylamino, dimethylamino, methylethylamino, diethylamino, methylsulfonyl, ethylsulfonyl, methylacyl, ethylacyl, cyclopropyl, cy Crobutyl, cyclopentyl, cyclohexyl, ethylene oxide, azetidinyl, oxetidinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, thiazolidinyl, pyrazolidinyl, oxazolidinyl, imidazolidinyl, isoxazolidinyl, piperidinyl, piperazinyl, morpholino, pyrrolidinyl, furanyl, thiophene, thiazole, pyrazole, pyridinyl, pyrimidinyl, or phenyl, where each Rz is independently unsubstituted or 1, 2, 3, or 4 Substituted with Rw, each Rw independently of O, deuterium, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, NH2, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, trifluoromethoxy, monofluoromethoxy, difluoromethoxy, trifluoromethyl, difluoromethyl, monofluoromethyl, methylamino, ethylamino, dimethylamino, methylethylamino, diethylamino, methylsulfonyl, ethylsulfonyl, methylacyl, ethylacyl, cyclopropyl A compound according to any one of the following appendices 1 to 3, characterized in that it is pyr, cyclobutyl, cyclopentyl, cyclohexyl, ethylene oxide, azetidinyl, oxetidinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, thiazolidinyl, pyrazolidinyl, oxazolidinyl, imidazolidinyl, isoxazolidinyl, piperidinyl, piperazinyl, morpholino, pyrrolidinyl, furanyl, thiophene, thiazole, pyrazole, pyridinyl, pyrimidinyl, or phenyl. 【0401】 (Note 27) A compound according to any one of the following appendices 1 to 26, characterized by being selected from the following. [ka] [ka] [ka] [ka] 【0402】 (Note 28) Uses of the compounds described in any one of Appendix 1 to 27 in the preparation of drugs, preferably drugs for treating, preventing or alleviating diseases in patients such as diabetic nephropathy, aldosterone excess, hypertension, heart failure, sequelae of myocardial infarction, cirrhosis of the liver, renal failure, or stroke, or in the preparation of drugs for treating or preventing diseases or conditions related to mineralocorticoids. 【0403】 (Note 29) Uses of any one of the compounds described in Appendix 1 to 27 in the preparation of drugs used as mineralocorticoid receptor antagonists.

Claims

[Claim 1] The compound represented by formula (I) and its stereoisomers, geometric isomers, hydrates, solvates, or pharmaceutically acceptable salts, 【Chemistry 1】 (I) Here, 【Chemistry 2】 teeth, 【Transformation 3】 And, R3 and R ４ are independently hydrogen, deuterium, amino, hydroxyl, mercapto, cyano, nitro, C １～６ alkyl, C １～６ alkoxy, C １～６ haloalkyl, C １～６ haloalkoxy, C １～６ alkylamino, carboxyl, C １～６ alkanoyl, C １～６ alkylsulfonyl, aminoacyl, aminosulfonyl, C ３～８ cycloalkyl, C ６～１０ aryl, heterocyclyl consisting of 3 to 8 atoms or heteroaryl consisting of 5 - 10 atoms, R ５ teeth, 【Chemistry 4】 And, R ６ is hydrogen, deuterium, C １～６ Alkyl, C １～６ Alkoxy, C １～６ Haloalkyl, C １～６ Haloalkoxy, C １～６ Alkylamino, C ３～８ Cycloalkyl, C ６～１０ These are aryls, heterocyclines consisting of 3 to 8 atoms, or heteroaryls consisting of 5 to 10 atoms. 【Transformation 5】 teeth, 【Transformation 6】 And, X is either C or N, Y is either O or S, R ７ C １～６ Alkyl, C ３～８ Cycloalkyl, heterocyclyl consisting of 3 to 8 atoms, heteroaryl consisting of 5 to 6 atoms, C ３～８ Cycloalkyl C １～６ Alkyl, heterocyclyl C containing a heterocyclyl group consisting of 3 to 8 atoms １～６ Alkyl, heteroaryl C containing a heteroaryl group consisting of 5-6 atoms １～６ Alkyl, phenyl, or phenyl C １～６ It is alkyl, R ７ It is either unsubstituted or substituted with 1, 2, 3, or 4 Rz. Each Rz independently corresponds to O, deuterium, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, and NH. ２ , C １～６ Alkyl, C １～６ Alkoxy, C １～６ Haloalkoxy, C １～６ Haloalkyl, C １～６ Alkylamino, C １～６ Alkyl sulfonyl, C １～６ Alkylacyl, C ３～８ Cycloalkyl, heterocyclyl consisting of 3 to 8 atoms, heteroaryl or C consisting of 5 to 6 atoms ６～１０ Aryl, where each Rz is independently unsubstituted or substituted with 1, 2, 3, or 4 Rw, Each Rw independently consists of O, deuterium, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, amino, and C. １～６ Alkyl, C １～６ Alkoxy, C １～６ Haloalkyl, C １～６ Haloalkoxy, C １～６ Alkylamino, C １～６ Alkyl sulfonyl, C １～６ Alkylacyl, C ３～８ Cycloalkyl, heterocyclyl consisting of 3 to 8 atoms, heteroaryl or C consisting of 5 to 6 atoms ６～１０ It is Ariel, 【Transformation 7】 teeth, 【Transformation 8】 And, R ８ , R ９ is hydrogen, deuterium, C １～６ Alkyl, C １～６ Alkoxy, C １～６ Haloalkyl, C １～６ Haloalkoxy, C １～６ Alkylamino, C ３～８ Cycloalkyl, C ６～１０ A compound characterized by being an aryl, a heterocyclyl consisting of 3 to 8 atoms, or a heteroaryl consisting of 5 to 10 atoms. [Claim 2] The compound according to claim 1, characterized in that it is selected from compounds represented by formula (Ia) or formula (Ib). 【Chemistry 9】 (Ia) 【Chemistry 10】 (Ib) [Claim 3] Each R3 and R ４ These are independently hydrogen, deuterium, amino, hydroxyl, mercapto, cyano, nitro, and C. １～４ Alkyl, C １～４ Alkoxy, C １～４ Haloalkyl, C １～４ Haloalkoxy, C １～４ Alkylamino, carboxyl, C １～４ Alkanoyl, C １～４ Alkyl sulfonyl, aminoacyl, aminosulfonyl, C ３～６ Cycloalkyl, C ６～１０ These are aryls, heterocyclines consisting of 3 to 6 atoms, or heteroaryls consisting of 5 to 6 atoms. R ６ is hydrogen, deuterium, C １～４ Alkyl, C １～４ Alkoxy, C １～４ Haloalkyl, C １～４ Haloalkoxy, C １～４ Alkylamino, C ３～６ Cycloalkyl, C ６～１０ These are aryls, heterocyclines consisting of 3 to 6 atoms, or heteroaryls consisting of 5 to 6 atoms. Each R ８ and R ９ These are independently hydrogen, deuterium, halogen, cyano, and C １～４ Alkoxyacyl, carboxyl, C １～４ Alkyl, C １～４ Alkoxy, C １～４ Haloalkyl, C １～４ Haloalkoxy, C １～４ Alkylamino, C １～４ Alkanoyl, C １～４ The compound according to claim 1, characterized in that it is an alkylsulfonyl, aminoacyl, or aminosulfonyl. [Claim 4] Each R3 and R ４ These are independently hydrogen, deuterium, amino, hydroxyl, mercapto, cyano, nitro, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, butoxy, trifluoromethyl, difluoromethyl, monofluoromethyl, 2,2-difluoroethyl, 1,2-difluoroethyl, trifluoroethyl, trifluoromethoxy, difluoromethoxy, monofluoromethoxy, methylamino, dimethylamino, carboxyl, methylacyl, ethylacyl, methylsulfonyl, aminoacyl, or aminosulfonyl. R ６ These are hydrogen, deuterium, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, butoxy, trifluoromethyl, difluoromethyl, monofluoromethyl, 2,2-difluoroethyl, 1,2-difluoroethyl, trifluoroethyl, trifluoromethoxy, difluoromethoxy, monofluoromethoxy, methylamino, dimethylamino, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthalenyl, cyclohexylethyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholino, pyridinyl, pyrrolidinyl, thiazole, pyrazole, or pyrimidinyl. R ８ The compound according to claim 3, characterized in that is hydrogen, deuterium, cyano, methylacyl, ethylacyl, propylacyl, methoxyacyl, ethoxyacyl, propoxyacyl, carboxyl, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, butoxy, trifluoromethyl, difluoromethyl, monofluoromethyl, 2,2-difluoroethyl, 1,2-difluoroethyl, trifluoroethyl, trifluoromethoxy, difluoromethoxy, monofluoromethoxy, methylamino, or dimethylamino. [Claim 5] The compound according to claim 1, characterized in that it is selected from the compounds represented by formula (II), formula (IIa), and formula (IIb). 【Chemistry 11】 [Claim 6] R ７ is C ３～６ cycloalkyl, heterocyclyl consisting of 3 to 6 atoms, heteroaryl consisting of 5 to 6 atoms, C ３～６ cycloalkyl C １～４ alkyl, heterocyclyl C containing a heterocyclyl group consisting of 3 to 6 atoms １～４ alkyl or heteroaryl C containing a heteroaryl group consisting of 5 to 6 atoms １～４ alkyl, wherein R ７ is unsubstituted or substituted with 1, 2, 3 or 4 Rz, the compound according to claim 1, characterized in that. [Claim 7] R ７ is C １～３ alkyl, and R ７ is unsubstituted or substituted with 1, 2, 3 or 4 Rz, the compound according to claim 1, characterized in that. [Claim 8] The compound according to claim 1, characterized in that R7 is methyl, ethyl, or isopropyl, and R7 is either unsubstituted or substituted with 1, 2, 3, or 4 Rz values. [Claim 9] R ７ This includes cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ethylene oxide, azetidinyl, oxetidinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, thiazolidinyl, pyrazolidinyl, oxazolidinyl, imidazolidinyl, isoxazolidinyl, piperidinyl, piperazinyl, morpholino, pyrrolidinyl, furanyl, thiophene, thiazole, pyrazole, pyridinyl, pyrimidinyl, cyclopropylmethyl, cyclopropylethyl, cyclopropylmethyl, cyclopropylethyl, cyclopentylmethyl, cyclopentylethyl, cyclohexylmethyl, cyclohexylethyl, azetidinylmethyl, azetidinylethyl, oxetidinylmethyl, oxetidinylethyl, pyrrolidinyl Nylmethyl, pyrrolidinylethyl, tetrahydrofuranylmethyl, tetrahydrofuranylethyl, tetrahydrothienylmethyl, tetrahydrothienylethyl, piperidinylmethyl, piperidinylethyl, piperadinylmethyl, piperadinylethyl, morpholinomethyl, morpholinoethyl, pyrrolidinylmethyl, pyrrolidinylethyl, furanylmethyl, furanylethyl, thiophenemethyl, thiopheneethyl, thiazolemethyl, thiazoleethyl, pyrazolemethyl, pyrazoleethyl, imidazolylmethyl, imidazolylethyl, triazolylmethyl, triazolylethyl, tetrazolylmethyl, tetrazolylethyl, pyridinylmethyl, pyridinylethyl, pyrimidinylmethyl or pyrimidinylethyl, where R ７ The compound according to claim 6, characterized in that is unsubstituted or substituted with 1, 2, 3, or 4 Rz. [Claim 10] Each Rz independently corresponds to O, deuterium, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, and NH. ２ , C １～４ Alkyl, C １～４ Alkoxy, C １～４ Haloalkoxy, C １～４ Haloalkyl, C １～４ Alkylamino, C １～４ Alkyl sulfonyl, C １～４ Alkylacyl, C ３～６ Cycloalkyl, heterocyclyl consisting of 3 to 6 atoms, heteroaryl or C consisting of 5 to 6 atoms ６～１０ It is an aryl compound, where each Rz is independently unsubstituted or substituted with 1, 2, 3, or 4 Rw, and each Rw is independently O, deuterium, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, or NH ２ , C １～４ Alkyl, C １～４ Alkoxy, C １～４ Haloalkyl, C １～４ Haloalkoxy, C １～４ Alkylamino, C １～４ Alkyl sulfonyl, C １～４ Alkylacyl, C ３～６ Cycloalkyl, heterocyclyl consisting of 3 to 6 atoms, heteroaryl or C consisting of 5 to 6 atoms ６～１０ The compound according to claim 1, characterized in that it is an aryl compound. [Claim 11] Each Rz independently corresponds to O, deuterium, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, and NH. ２ Methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, trifluoromethoxy, monofluoromethoxy, difluoromethoxy, trifluoromethyl, difluoromethyl, monofluoromethyl, methylamino, ethylamino, dimethylamino, methylethylamino, diethylamino, methylsulfonyl, ethylsulfonyl, methylacyl, ethylacyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ethylene oxide, azetidinyl, oxetidinyl, pyrrolidine The compounds are nyl, tetrahydrofuranyl, tetrahydrothienyl, thiazolidinyl, pyrazolidinyl, oxazolidinyl, imidazolidinyl, isoxazolidinyl, piperidinyl, piperazinyl, morpholino, pyrrolidinyl, furanyl, thiophene, thiazole, pyrazole, pyridinyl, pyrimidinyl, or phenyl, where each Rz is independently unsubstituted or substituted with 1, 2, 3, or 4 Rw, each Rw independently being O, deuterium, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, or NH ２ The compound according to claim 10, characterized in that it is methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, trifluoromethoxy, monofluoromethoxy, difluoromethoxy, trifluoromethyl, difluoromethyl, monofluoromethyl, methylamino, ethylamino, dimethylamino, methylethylamino, diethylamino, methylsulfonyl, ethylsulfonyl, methylacyl, ethylacyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ethylene oxide, azetidinyl, oxetidinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, thiazolidinyl, pyrazolidinyl, oxazolidinyl, imidazolidinyl, isoxazolidinyl, piperidinyl, piperazinyl, morpholino, pyrrolidinyl, furanyl, thiophene, thiazole, pyrazole, pyridinyl, pyrimidinyl, or phenyl. [Claim 12] The compound represented by formula (III) and its stereoisomers, geometric isomers, hydrates, solvates, or pharmaceutically acceptable salts, 【Chemistry 12】 (III) Here, each R1, R2, R3 and R4 is independently hydrogen, deuterium, amino, hydroxyl, mercapto, cyano, nitro, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, butoxy, trifluoromethyl, difluoromethyl, monofluoromethyl, 2,2-difluoroethyl, 1,2-difluoroethyl, trifluoroethyl, trifluoromethoxy, difluoromethoxy, monofluoromethoxy, methylamino, dimethylamino, carboxyl, methylacyl, ethylacyl, methylsulfonyl, aminoacyl, or aminosulfonyl. R ５ teeth 【Chemistry 13】 Selected from, A compound characterized in that R6 is hydrogen, deuterium, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, butoxy, trifluoromethyl, difluoromethyl, monofluoromethyl, 2,2-difluoroethyl, 1,2-difluoroethyl, trifluoroethyl, trifluoromethoxy, difluoromethoxy, monofluoromethoxy, methylamino, dimethylamino, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthalenyl, cyclohexylethyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholino, pyridinyl, pyrrolidinyl, thiazole, pyrazole, or pyrimidinyl. [Claim 13] R １ , R ２ , R ３ , R ４ They are independently hydrogen, deuterium, and C １～６ It is an alkoxy, R ５ teeth 【Chemistry 14】 And, R ６ is hydrogen, deuterium, C １～６ The compound according to claim 12, characterized by being selected from alkyl groups. [Claim 14] R １ , R ２ , R ３ , R ４ They are independently hydrogen, deuterium, and C １～３ It is an alkoxy, R ５ teeth 【Chemistry 15】 And, R ６ is hydrogen, deuterium, C １～３ The compound according to claim 13, characterized by being selected from alkyl groups. [Claim 15] R １ , R ２ , R ３ , R ４ These are independently hydrogen, deuterium, and methoxyl, R ５ teeth 【Chemistry 16】 And, R ６ The compound according to claim 14, characterized in that is selected from hydrogen, deuterium, and methyl. 【Request Item 16】 【Chemistry 17】 The compound according to claim 12, characterized by being selected from the above. [Claim 17] The compound represented by formula (IV) and its stereoisomers, geometric isomers, hydrates, solvates, or pharmaceutically acceptable salts, [Chemistry 18] (IV) Here, 【Chemistry 19】 teeth 【Chemistry 20】 And, R １ , R ２ , R ３ and R ４ They are independently hydrogen, deuterium, and C １～６ It is an alkoxy, R ５ teeth 【Chemistry 21】 Selected from, R ６ C １～６ It is alkyl, R ７ C １～６ It is alkyl, R ８ , R ９ is hydrogen, deuterium, C １～６ It is alkyl, Y is selected from O, A compound characterized in that X is selected from C. [Claim 18] R １ , R ２ , R ３ and R ４ They are independently hydrogen, deuterium, and C １～３ It is an alkoxy, R ６ C １～３ It is alkyl, R ７ C １～３ It is alkyl, R ８ , R ９ is hydrogen, deuterium, C １～３ The compound according to claim 17, characterized in that it is alkyl. 【Request Item 19】 【Chemistry 22】 The compound according to claim 17, characterized by being selected from the above. [Claim 20] Selected from the compounds represented by formula (V), 【Chemistry 23】 (V) Here, 【Chemistry 24】 teeth 【Chemistry 25】 And, R ３ and R ４ These are hydrogen and deuterium, independently of each other. R ５ teeth 【Chemistry 26】 Selected from, R ６ C １～６ It is alkyl, R ７ C １～６ Alkyl, C ３～８ Cycloalkyl, C ３～８ Cycloalkyl C １～６ It is alkyl, and here, R ７ It is either unsubstituted or substituted with 1, 2, 3, or 4 Rz atoms, each Rz atom being an independent halogen. R ８ , R ９ is hydrogen, deuterium, C １～６ It is alkyl, X is selected from C, The compound according to claim 1, characterized in that Y is selected from O. [Claim 21] R ６ C １～３ It is alkyl, R ７ C １～３ Alkyl, C ３～５ Cycloalkyl, C ３－４ Cycloalkyl C １～３ It is alkyl, and here, R ７ It is either unsubstituted or substituted with 1, 2, 3, or 4 Rz atoms, each Rz atom independently being fluorine, chlorine, bromine, or iodine. R ８ , R ９ is hydrogen, deuterium, C １～３ The compound according to claim 20, characterized in that it is alkyl. [Claim 22] R ６ C １～３ It is alkyl, R ７ C １～３ Alkyl, C ３～５ Cycloalkyl, C ３－４ Cycloalkyl C １～３ It is alkyl, and here, R ７ It is either unsubstituted or substituted with 1, 2, 3, or 4 Rz atoms, where each Rz atom is independently fluorine. R ８ , R ９ The compound according to claim 21, characterized in that it is hydrogen and methyl. [Claim 23] A compound is selected from those represented by formulas (V), (Va), and (Vb). 【Chemistry 27】 Here, 【Chemistry 28】 teeth 【Chemistry 29】 And, R ３ and R ４ These are hydrogen and deuterium, independently of each other. R ５ teeth 【Transformation 30】 Selected from, R ６ C １～６ It is alkyl, R ７ C １～６ Alkyl, C ３～８ Cycloalkyl, C ３～８ Cycloalkyl C １～６ It is alkyl, and here, R ７ It is either unsubstituted or substituted with 1, 2, 3, or 4 Rz, each Rz independently of a halogen, C １～６ It is alkyl, R ８ , R ９ is hydrogen, deuterium, C １～６ It is alkyl, X is selected from C, The compound according to claim 1, characterized in that Y is selected from O. [Claim 24] R ６ C １～３ It is alkyl, R ７ C １～３ Alkyl, C ３～５ Cycloalkyl, C ３－４ Cycloalkyl C １～３ It is alkyl, and here, R ７ It is either unsubstituted or substituted with 1, 2, 3, or 4 Rz, each Rz independently being fluorine, chlorine, bromine, iodine, or C １～４ It is alkyl, R ８ , R ９ is hydrogen, deuterium, C １～３ The compound according to claim 23, characterized in that it is alkyl. [Claim 25] R ６ C １～３ It is alkyl, R ７ C １～３ Alkyl, C ３～５ Cycloalkyl, C ３－４ Cycloalkyl C １～３ It is alkyl, and here, R ７ It is either unsubstituted or substituted with 1, 2, 3, or 4 Rz, where each Rz is independently fluorine or methyl. R ８ , R ９ The compound according to claim 24, characterized in that it is hydrogen and methyl. [Claim 26] A compound is selected from those represented by formula (VI), formula (VIa), or formula (VIb), 【Chemistry 31】 R 12 is -CH ２ - or -CH ２ -CH ２ - and R １２ ga-CH ２ - If R １０ and R １１ Each is independently -CH ２ - or selected from O, with at least one being O, R １２ ga-CH ２ -CH ２ - If R １０ and R １１ It is either O or R at the same time. １０ ha-CH ２ - and R １１ is O, R ７ C １～３ Alkyl, C ３～６ Cycloalkyl, heterocyclyl consisting of 3 to 6 atoms, heteroaryl consisting of 5 to 6 atoms, C ３～６ Cycloalkyl C １～４ Alkyl, heterocyclyl C containing a heterocyclyl group consisting of 3 to 6 atoms １～４ Heteroaryl C containing an alkyl or heteroaryl group consisting of 5-6 atoms １～４ It is alkyl, and here, R ７ It is either unsubstituted or substituted with 1, 2, 3, or 4 Rz. Each Rz independently corresponds to O, deuterium, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, and NH. ２ , C １～４ Alkyl, C １～４ Alkoxy, C １～４ Haloalkoxy, C １～４ Haloalkyl, C １～４ Alkylamino, C １～４ Alkyl sulfonyl, C １～４ Alkylacyl, C ３～６ Cycloalkyl, heterocyclyl consisting of 3 to 6 atoms, heteroaryl or C consisting of 5 to 6 atoms ６～１０ It is an aryl compound, where each Rz is independently unsubstituted or substituted with 1, 2, 3, or 4 Rw, and each Rw is independently O, deuterium, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, or NH ２ , C １～４ Alkyl, C １～４ Alkoxy, C １～４ Haloalkyl, C １～４ Haloalkoxy, C １～４ Alkylamino, C １～４ Alkyl sulfonyl, C １～４ Alkylacyl, C ３～６ Cycloalkyl, heterocyclyl consisting of 3 to 6 atoms, heteroaryl or C consisting of 5 to 6 atoms ６～１０ The compound according to claim 1, characterized in that it is an aryl compound. [Claim 27] R ７ Methyl, ethyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ethylene oxide, azetidinyl, oxetidinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, thiazolidinyl, pyrazolidinyl, oxazolidinyl, imidazolidinyl, isoxazolidinyl, piperidinyl, piperazinyl, morpholino, pyrrolidinyl, furanyl, thiophene, thiazole, pyrazole, pyridinyl, pyrimidinyl, cyclopropylmethyl, cyclopropylethyl, cyclopropylmethyl, cyclopropylethyl, cyclopentylmethyl, cyclopentylethyl, cyclohexylmethyl, cyclohexylethyl, azetidinylmethyl, azetidinylethyl, oxetidinylmethyl, oxetidinyl The following are Cyl, pyrrolidinylmethyl, pyrrolidinylethyl, tetrahydrofuranylmethyl, tetrahydrofuranylethyl, tetrahydrothienylmethyl, tetrahydrothienylethyl, piperidinylmethyl, piperidinylethyl, piperadinylmethyl, piperadinylethyl, morpholinomethyl, morpholinoethyl, pyrrolidinylmethyl, pyrrolidinylethyl, furanylmethyl, furanylethyl, thiophenemethyl, thiopheneethyl, thiazolemethyl, thiazoleethyl, pyrazolemethyl, pyrazoleethyl, imidazolylmethyl, imidazolylethyl, triazolylmethyl, triazolylethyl, tetrazolylmethyl, tetrazolylethyl, pyridinylmethyl, pyridinylethyl, pyrimidinylmethyl or pyrimidinylethyl, where R ７ It is either unsubstituted or substituted with 1, 2, 3, or 4 Rz. Each Rz independently corresponds to O, deuterium, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, and NH. ２ Methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, trifluoromethoxy, monofluoromethoxy, difluoromethoxy, trifluoromethyl, difluoromethyl, monofluoromethyl, methylamino, ethylamino, dimethylamino, methylethylamino, diethylamino, methylsulfonyl, ethylsulfonyl, methylacyl, ethylacyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ethylene oxide, azetidinyl, oxetidinyl, pyrrolidine The compounds are nyl, tetrahydrofuranyl, tetrahydrothienyl, thiazolidinyl, pyrazolidinyl, oxazolidinyl, imidazolidinyl, isoxazolidinyl, piperidinyl, piperazinyl, morpholino, pyrrolidinyl, furanyl, thiophene, thiazole, pyrazole, pyridinyl, pyrimidinyl, or phenyl, where each Rz is independently unsubstituted or substituted with 1, 2, 3, or 4 Rw, each Rw independently being O, deuterium, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, or NH ２ The compound according to claim 1, characterized in that it is methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, trifluoromethoxy, monofluoromethoxy, difluoromethoxy, trifluoromethyl, difluoromethyl, monofluoromethyl, methylamino, ethylamino, dimethylamino, methylethylamino, diethylamino, methylsulfonyl, ethylsulfonyl, methylacyl, ethylacyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ethylene oxide, azetidinyl, oxetidinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, thiazolidinyl, pyrazolidinyl, oxazolidinyl, imidazolidinyl, isoxazolidinyl, piperidinyl, piperazinyl, morpholino, pyrrolidinyl, furanyl, thiophene, thiazole, pyrazole, pyridinyl, pyrimidinyl, or phenyl. [Claim 28] The compound according to claim 1, selected from the following: 【Chemistry 32】 【Transformation 33】 【Transformation 34】 【Chemistry 35】 [Claim 29] Use of the compound according to claim 1 in the preparation of a drug, or in the preparation of a drug for treating or preventing a disease or condition related to mineralocorticoids. [Claim 30] The use of the compound according to claim 29, characterized in that the drug treats, prevents or alleviates diseases in patients such as diabetic nephropathy, aldosterone excess, hypertension, heart failure, sequelae of myocardial infarction, cirrhosis of the liver, renal failure, or stroke. [Claim 31] Use of the compound according to claim 1 in the preparation of a drug used as a mineralocorticoid receptor antagonist.

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