Pharmaceutical composition for preventing or treating cerebral aneurysm

Abstract

The present invention relates to a pharmaceutical composition for preventing or treating cerebral aneurysms, the pharmaceutical composition containing, as an active ingredient, a compound having a P2X4 receptor antagonistic activity or a pharmaceutically acceptable salt thereof.

Description

Pharmaceutical composition for preventing or treating cerebral aneurysms

[0001] The present invention relates to a pharmaceutical composition containing, as an active ingredient, a compound having P2X4 receptor antagonistic activity or a pharmaceutically acceptable salt thereof, for example, a pharmaceutical composition for preventing or treating cerebral aneurysms. This application claims priority based on Japanese Patent Application No. 2024-049250, filed on March 26, 2024, the contents of which are incorporated herein by reference.

[0002] Despite recent advances in medical technology, subarachnoid hemorrhage due to ruptured cerebral aneurysms still has a poor prognosis. It has been reported that 19.4% of patients treated at a hospital died, and 26.3% required assistance with daily activities (Japan Stroke Data Bank Report 2021). Furthermore, many patients experience sudden death and do not reach the hospital, resulting in these statistics being omitted. It is estimated that approximately one-quarter of subarachnoid hemorrhage cases in Japan result in sudden death. Furthermore, subarachnoid hemorrhage frequently occurs among people of working age, resulting in labor force loss. Therefore, subarachnoid hemorrhage due to ruptured cerebral aneurysms represents an "unmet medical need" disease, with a poor prognosis even with current medical standards. The prevalence of cerebral aneurysms is high, at several percent of the population. Therefore, with recent advances in diagnostic imaging, the widespread availability of diagnostic imaging equipment, and widespread brain checkups, cerebral aneurysms are increasingly being discovered before rupture, with an estimated tens of thousands of cases occurring annually in Japan alone. For these unruptured cerebral aneurysms, there is an opportunity to intervene to prevent the onset of subarachnoid hemorrhage. Therefore, it is socially important to intervene appropriately as a form of "preemptive medicine" to prevent rupture.

[0003] Currently, treatment of cerebral aneurysms, whether unruptured or ruptured, involves craniotomy for clipping and endovascular procedures such as coil embolization and flow diverter placement. Endovascular procedures, which are less invasive and leave smaller incisions than craniotomy, are becoming increasingly popular for treating both unruptured and ruptured aneurysms. However, endovascular procedures have a more uncertain long-term prognosis than clipping, as aneurysm recurrence and rerupture often require retreatment. Furthermore, flow diverter placement can sometimes result in early rupture, resulting in disastrous outcomes. Therefore, minimally invasive surgical interventions for cerebral aneurysms remain inadequate. It has been suggested that the placement of embolization coils or flow diverters during endovascular treatment of cerebral aneurysms places unphysiological hemodynamic stress on the vessel wall, which may contribute to aneurysm recurrence and rupture. Therefore, in order to obtain a safer and more reliable therapeutic effect, some kind of additional treatment is required to suppress the occurrence or growth of cerebral aneurysms in parallel with current endovascular treatment, and ultimately to prevent the recurrence of cerebral aneurysms.

[0004] According to Non-Patent Documents 1 and 2, vascular endothelial cells (ECs) sense shear stress caused by the applied blood flow, and ECs rapidly release endogenous ATP, which activates P2X4 and P2Y2 receptors and releases extracellular Ca. 2+ influx and intracellular Ca 2+ Ca from storage 2+ It has been reported that this causes the release of cytosolic Ca. 2+It has also been reported that increased concentrations of paroxetine increase nitric oxide production, which plays an important role in blood pressure regulation, flow-dependent vasodilation, and tissue vascular remodeling. However, no further reports have been published on the involvement of P2X4 and P2Y2 receptors, and no suggestion has been made regarding their involvement in the suppression of the development or growth of cerebral aneurysms after endovascular treatment or in treatment to prevent recurrence. According to Patent Document 1 and Non-Patent Document 3, administration of paroxetine to rats after aneurysm induction surgery starting two weeks after surgery inhibited the expansion of formed aneurysms, suggesting the possibility of attenuating aneurysm growth. Patent Document 1 and Non-Patent Document 3 also report that paroxetine is known as a P2X4 receptor inhibitor. However, since paroxetine is known as an antidepressant of the SSRI (selective serotonin reuptake inhibitor) type and no experimental results have been reported in which drugs (compounds) other than paroxetine were administered, it is unclear whether P2X4 receptor inhibitory activity exerts the above-mentioned effects.

[0005] Patent Document 2 describes inhibitors of P2X4 receptor channels (hereinafter referred to as P2X4 receptor antagonists). However, the compounds described in the examples of Patent Document 2 are selective serotonin reuptake inhibitors such as Paroxetine and Fluoxetine, which have a completely different structure from the compound of the present application, which is a benzodiazepine derivative compound. Furthermore, only experimental results using a neuropathic pain pathology model in which nerve injury (L5 spinal nerve injury model) was performed are shown, and it has not been found that P2X4 receptor antagonists have a preventive or therapeutic effect on cerebral aneurysms.

[0006] Patent Document 3 also describes a compound that exhibits P2X4 receptor antagonistic activity, but similar to Patent Document 2, it only demonstrates its effect in a neuropathic pain model, and it is unclear whether it has any preventive or therapeutic effect on cerebral aneurysms.

[0007] The applicant of the present application has also filed patent applications relating to P2X4 receptor antagonists as shown in Patent Documents 4 to 11, but none of these applications disclose that they have an effect in preventing or treating cerebral aneurysms.

[0008] JP 2021-070638 A International Publication No. 2008 / 020651 International Publication No. 2010 / 093061 International Publication No. 2008 / 023847 International Publication No. 2012 / 008478 International Publication No. 2012 / 014910 International Publication No. 2012 / 017876 International Publication No. 2013 / 105608 International Publication No. 2015 / 005468 International Publication No. 2015 / 005467 International Publication No. 2021 / 049628

[0009] Yamamoto K. Am. J. Physiol. Heart Circ. Physiol. 315(5):1477-1485, 2018Am. J. Physiol. Heart Circ. Physiol. 293(3):1646-1653, 2007Fukuda M et al. Journal of Neurosurgery 134:102-114, 2021

[0010] An object of the present invention is to provide a pharmaceutical composition useful for preventing or treating cerebral aneurysms.A further object of the present invention is to provide a pharmaceutical composition useful for preventing the rupture of cerebral aneurysms.A particular object of the present invention is to provide a pharmaceutical composition useful for inhibiting the growth or occurrence of cerebral aneurysms.A more particular object of the present invention is to provide a pharmaceutical composition useful for inhibiting the occurrence of cerebral aneurysms after surgical treatment.An even more particular object of the present invention is to provide a pharmaceutical composition useful for preventing the recurrence of cerebral aneurysms.An even more particular object of the present invention is to provide a pharmaceutical composition useful for inhibiting the occurrence of cerebral aneurysms after endovascular treatment.

[0011] Therefore, the present inventors have conducted intensive research to solve the above-mentioned problems, and as a result, have found that compounds represented by general formula (A) to (BII) or pharmaceutically acceptable salts thereof, which have P2X4 receptor antagonist activity, are useful for the prevention or treatment of cerebral aneurysms, and further, that they are useful for preventing the rupture of cerebral aneurysms, and particularly, that they are useful for inhibiting the growth or occurrence of cerebral aneurysms, and more particularly, that they are useful for inhibiting the occurrence of cerebral aneurysms after surgical treatment, and even more particularly, that they are useful for preventing the recurrence of cerebral aneurysms, and even more particularly, that they are useful for inhibiting the occurrence of cerebral aneurysms after endovascular treatment, and have completed the present invention.

[0012] That is, the present invention provides a pharmaceutical composition useful for preventing or treating cerebral aneurysms, which comprises as an active ingredient a compound having P2X4 receptor antagonistic activity or a pharmaceutically acceptable salt thereof. Furthermore, the present invention provides a pharmaceutical composition useful for preventing rupture of cerebral aneurysms, which comprises as an active ingredient a compound having P2X4 receptor antagonistic activity or a pharmaceutically acceptable salt thereof. In particular, the present invention provides a pharmaceutical composition useful for inhibiting the growth or occurrence of cerebral aneurysms, which comprises as an active ingredient a compound having P2X4 receptor antagonistic activity or a pharmaceutically acceptable salt thereof. More particularly, the present invention provides a pharmaceutical composition useful for inhibiting the occurrence of cerebral aneurysms after surgical treatment, which comprises as an active ingredient a compound having P2X4 receptor antagonistic activity or a pharmaceutically acceptable salt thereof. Still more particularly, the present invention provides a pharmaceutical composition useful for preventing the recurrence of cerebral aneurysms, which comprises as an active ingredient a compound having P2X4 receptor antagonistic activity or a pharmaceutically acceptable salt thereof. More particularly, the present invention provides a pharmaceutical composition useful for suppressing the occurrence of cerebral aneurysms after endovascular treatment, which comprises, as an active ingredient, a compound having P2X4 receptor antagonistic activity or a pharmaceutically acceptable salt thereof.

[0013] As a compound having a P2X4 receptor antagonistic activity, for example, a compound represented by the following general formula (A) to (BII) can be used. More preferably, as a compound having a P2X4 receptor antagonistic activity, a compound represented by the following general formula (BI) or (BII) can be used. Furthermore, a pharmaceutically acceptable salt of the compound can be used.

[0014] The pharmaceutical composition of the present invention can be used, for example, for the prevention or treatment of cerebral aneurysms. Furthermore, the pharmaceutical composition of the present invention can be used to prevent the rupture of cerebral aneurysms. In particular, the pharmaceutical composition of the present invention can be used to inhibit the growth or occurrence of cerebral aneurysms. More particularly, the pharmaceutical composition of the present invention can be used to inhibit the occurrence of cerebral aneurysms after surgical treatment. Even more particularly, the pharmaceutical composition of the present invention can be used to prevent the recurrence of cerebral aneurysms. Still more particularly, the pharmaceutical composition of the present invention can be used to inhibit the occurrence of cerebral aneurysms after endovascular treatment.

[0015] From another aspect, the present invention provides use of a compound having P2X4 receptor antagonistic activity or a pharmaceutically acceptable salt thereof for producing the above-mentioned pharmaceutical composition. The present invention also provides a method for preventing or treating cerebral aneurysms, comprising the step of administering to a mammal, including a human, an effective amount for prevention or treatment of a compound having P2X4 receptor antagonistic activity or a pharmaceutically acceptable salt thereof. Furthermore, the present invention provides a method for preventing the rupture of a cerebral aneurysm, comprising the step of administering to a mammal, including a human, an effective amount for prevention of rupture of a compound having P2X4 receptor antagonistic activity or a pharmaceutically acceptable salt thereof. In particular, the present invention provides a method for inhibiting the growth or occurrence of cerebral aneurysms, comprising the step of administering to a mammal, including a human, an effective amount for inhibition of rupture of a compound having P2X4 receptor antagonistic activity or a pharmaceutically acceptable salt thereof. More particularly, the present invention provides a method for suppressing the occurrence of cerebral aneurysms after surgical treatment, which comprises administering an effective amount of a compound having P2X4 receptor antagonistic activity or a pharmaceutically acceptable salt thereof to a mammal, including a human. Still more particularly, the present invention provides a method for preventing the recurrence of cerebral aneurysms, which comprises administering an effective amount of a compound having P2X4 receptor antagonistic activity or a pharmaceutically acceptable salt thereof to a mammal, including a human. Still more particularly, the present invention provides a method for suppressing the occurrence of cerebral aneurysms after endovascular treatment, which comprises administering an effective amount of a compound having P2X4 receptor antagonistic activity or a pharmaceutically acceptable salt thereof to a mammal, including a human.

[0016] The pharmaceutical composition of the present invention is useful as a pharmaceutical composition useful for preventing or treating cerebral aneurysms. Furthermore, the pharmaceutical composition of the present invention is useful as a pharmaceutical composition useful for preventing the rupture of cerebral aneurysms. In particular, the pharmaceutical composition of the present invention is useful as a pharmaceutical composition useful for inhibiting the growth or occurrence of cerebral aneurysms. Even more particularly, the pharmaceutical composition of the present invention is useful as a pharmaceutical composition useful for inhibiting the occurrence of cerebral aneurysms after surgical treatment. Even more particularly, the pharmaceutical composition of the present invention is useful as a pharmaceutical composition useful for preventing the recurrence of cerebral aneurysms. Still more particularly, the pharmaceutical composition of the present invention is useful as a pharmaceutical composition useful for inhibiting the occurrence of cerebral aneurysms after endovascular treatment. Each of the pharmaceutical compositions of the present invention is expected to be highly effective.

[0017] Figure showing the results of staining endothelial cells and cell nuclei with P2X4 receptor and CD31 in human cerebral aneurysm lesions, and the merged results. Wild-type and P2X4 receptor-deficient animals obtained by crossbreeding P2X4 receptor heterozygous animals were divided into a placebo group (vehicle group) and a compound A group, respectively, and the results of cerebral aneurysm induction rate and blood pressure after cerebral aneurysm induction surgery were shown in this figure.

[0018] The pharmaceutical composition of the present invention can be used as a pharmaceutical composition useful for preventing or treating cerebral aneurysms, but can also be used as a pharmaceutical composition for the following applications. The pharmaceutical composition of the present invention can be used as a pharmaceutical composition useful for preventing rupture of cerebral aneurysms. The pharmaceutical composition of the present invention can be used as a pharmaceutical composition useful for inhibiting the growth of cerebral aneurysms. The pharmaceutical composition of the present invention can be used as a pharmaceutical composition useful for inhibiting the occurrence ... after surgical treatment. The pharmaceutical composition of the present invention can be used as a pharmaceutical composition useful for preventing the recurrence of cerebral aneurysms. The pharmaceutical composition of the present invention can be used as a pharmaceutical composition useful for inhibiting the occurrence of cerebral aneurysms after endovascular treatment.

[0019] As used herein, "cerebral aneurysm" refers to a lump-like or spindle-shaped swelling that develops in a cerebral artery, and refers to a recognizable lump or spindle shape. Specifically, it refers to a size ranging from, for example, a small one of about 1 mm to 25 mm or larger. As used herein, "development" refers to a state in which a recognizable lump or spindle shape develops in a cerebral artery from a state in which there was no recognizable lump or spindle shape, and "inhibition of development" refers to an action or means for inhibiting the development of a recognizable lump or spindle shape from a state in which there was no recognizable lump or spindle shape in a cerebral artery. As used herein, "growth" refers to the increase in size of a cerebral aneurysm, and "inhibition of growth" refers to an action or means for inhibiting the growth of a cerebral aneurysm. As used herein, "prevention" refers to the prevention of the onset of "pathological" or "abnormal" symptoms, conditions, or diseases, and includes actions or means for achieving this. As used herein, "treatment" refers to the elimination, cure, or remission of a "pathological" or "abnormal" symptom, condition, or disease, and includes actions or means to achieve such an end, as well as the suppression of the worsening of a "pathological" or "abnormal" symptom, condition, or disease, and includes actions or means to achieve such an end, and is a concept that also includes improvement. Here, "improvement" refers to the bringing of a "pathological" or "abnormal" symptom, condition, or disease closer to a "healthy" or "normal" state, or includes actions or means to achieve such an end, and also includes the bringing of a "pathological" or "abnormal" symptom, condition, or disease closer to a "healthy" or "normal" state, or includes actions or means to achieve such an end. Thus, in one embodiment, "improvement" refers to the reduction or increase of a numerical value that is an indicator of a "pathological" or "abnormal" symptom or condition, in accordance with the "improvement," approaching a normal value or becoming a normal value. Furthermore, "suppression" refers to the stopping or slowing of the worsening or progression of a symptom, condition, or disease, and includes actions or means to achieve such an end, and is a concept that also includes the improvement of the symptom, condition, or disease, or includes actions or means to achieve such an end. Here, "improvement" has the above meaning.The "worsening or progression of a symptom, condition, or disease" includes the worsening or progression of a "pathological" or "abnormal" symptom, condition, or disease, and the worsening or progression from a "healthy" or "normal" state to a "pathological" or "abnormal" symptom, condition, or disease. In one embodiment, "suppression" refers to stopping or slowing the worsening or progression of a symptom, condition, or disease, or an action or means therefor. In another embodiment, "suppression" refers to stopping or slowing the worsening or progression of a symptom, condition, or disease. In one embodiment, "treatment" refers to eliminating, curing, curing, or ameliorating a "pathological" or "abnormal" symptom, condition, or disease, or an action or means therefor. In another embodiment, "treatment" refers to eliminating, curing, curing, or ameliorating a "pathological" or "abnormal" symptom, condition, or disease. As used herein, "recurrence" refers to the occurrence of a "pathological" or "abnormal" symptom, condition, or disease after it has been treated, cured, or ameliorated, but the occurrence of the same or a similar "pathological" or "abnormal" symptom, condition, or disease in the same or a nearby area, and "prevention of recurrence" refers to an action or measure to prevent the occurrence of the same or a similar "pathological" or "abnormal" symptom, condition, or disease in the same or a nearby area. As used herein, the symptom, condition, or disease, or a numerical value that serves as an indicator thereof, or a condition or function, can be evaluated by comparing the results before and after administration of the pharmaceutical provided by the present invention, or by comparing a group administered with a pharmaceutical provided by the present invention and a group administered with a placebo or a control that does not contain the pharmaceutical provided by the present invention.

[0020] The active ingredient of the pharmaceutical composition of the present invention may be a compound represented by the following general formula (A) to (BII) or a pharmaceutically acceptable salt thereof. The abbreviations used in the tables below are as follows: Me: methyl group, Et: ethyl group, Pr: n-propyl group, iPr: isopropyl group, tBu: tert-butyl group, Ac: acetyl group, Ph: phenyl group. In the tables below, a substituent may be indicated together with the position number of its substitution position. In addition, in a chemical formula, a prime "'" may be added to one of the position numbers for convenience in order to distinguish between seemingly identical position numbers. However, in a compound name, the position number may be written without the prime as long as the structure can be uniquely identified.

[0021] (A-1) The following general formula (A): (In the formula, R １Ａ represents a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, or an alkyl group having 1 to 3 carbon atoms substituted with a phenyl group; R ２Ａ and R ３Ａ may be the same or different and represent a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an acylamino group having 2 to 8 carbon atoms, an acylamino group having 2 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkylsulfonylamino group having 1 to 8 carbon atoms, a carboxyl group, an acyl group having 2 to 8 carbon atoms, an alkoxycarbonyl group (the number of carbon atoms in the alkoxy moiety is 1 to 8), a carbamoyl group, an alkylthio group having 1 to 8 carbon atoms, an alkylsulfinyl group having 1 to 8 carbon atoms, an alkylsulfonyl group having 1 to 8 carbon atoms, or a sulfamoyl group; R ４Ａ and R ５Ａmay be the same or different and represent a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, or an alkyl group having 1 to 3 carbon atoms substituted with a phenyl group, and W Ａ represents a 5- or 6-membered heterocyclic ring containing 1 to 4 nitrogen atoms as ring constituent elements which may have a substituent, or a pharmaceutically acceptable salt thereof.

[0022] In general formula (A), R １Ａ , R ２Ａ , R ３Ａ , R ４Ａ and R ５Ａ Examples of the alkyl group having 1 to 8 carbon atoms include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an i-butyl group, a t-butyl group, a pentyl group, and a hexyl group. １Ａ Examples of the alkenyl group having 2 to 8 carbon atoms include an allyl group. １Ａ , R ２Ａ , R ３Ａ , R ４Ａ and R ５Ａ or R １１Ａ , R １２Ａ , R １３Ａ , R １４Ａ and R １５Ａ Examples of the alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, or a t-butyl group substituted with 1 to 3 halogen atoms such as a fluorine atom, a chlorine atom, or a bromine atom, and preferred examples include a trifluoromethyl group, a chloromethyl group, a 2-chloroethyl group, a 2-bromoethyl group, or a 2-fluoroethyl group. １Ａ , R ４Ａ and R ５Ａ Examples of the alkyl group having 1 to 3 carbon atoms substituted with a phenyl group include a benzyl group. ２Ａ and R ３Ａ Examples of the alkoxy group having 1 to 8 carbon atoms include a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, an i-butoxy group, a t-butoxy group, a pentyloxy group, and a hexyloxy group.

[0023] R２Ａ and R ３Ａ Examples of the alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, or a t-butyl group substituted with 1 to 3 halogen atoms such as a fluorine atom, a chlorine atom, or a bromine atom, and preferred examples include a trifluoromethoxy group, a 2-chloroethoxy group, a 2-bromoethoxy group, or a 2-fluoroethoxy group. ２Ａ and R ３Ａ Examples of the halogen atom in R include a fluorine atom, a chlorine atom, and a bromine atom. ２Ａ and R ３Ａ Examples of the alkylamino group having 1 to 8 carbon atoms include a methylamino group and an ethylamino group. ２Ａ and R ３Ａ Examples of the dialkylamino group having 1 to 8 carbon atoms include a dimethylamino group and a diethylamino group. ２Ａ and R ３Ａ Examples of the acylamino group having 2 to 8 carbon atoms include an acetylamino group. ２Ａ and R ３Ａ Examples of the acylamino group having 2 to 8 carbon atoms and substituted with 1 to 3 halogen atoms include a trifluoromethylcarbonylamino group.

[0024] R ２Ａ and R ３Ａ Examples of the alkylsulfonylamino group having 1 to 8 carbon atoms include a methylsulfonylamino group. ２Ａ and R ３Ａ Examples of the acyl group having 2 to 8 carbon atoms include an acetyl group. ２Ａ and R ３Ａ Examples of the alkoxycarbonyl group (the alkoxy moiety has 1 to 8 carbon atoms) include a methoxycarbonyl group and an ethoxycarbonyl group. ２Ａ and R ３Ａ Examples of the alkylthio group having 1 to 8 carbon atoms include a methylthio group. ２Ａ and R ３Ａ Examples of the alkylsulfinyl group having 1 to 8 carbon atoms include a methylsulfinyl group.２Ａ and R ３Ａ Examples of the alkylsulfonyl group having 1 to 8 carbon atoms include a methylsulfonyl group.

[0025] W Ａ Examples of the 5- or 6-membered heterocyclic ring containing 1 to 4 nitrogen atoms as ring constituent elements which may have a substituent include tetrazole, 1,2,4-triazole, 1,2,3-triazole, 1,2,4-oxadiazole, pyrazole, imidazole, oxazole, isoxazole, pyrrole, thiazole, pyridine, and pyrrolidine. Ａ Examples of the substituent that may be possessed by the 5- or 6-membered heterocyclic ring containing 1 to 4 nitrogen atoms as a ring-constituting element that may have a substituent include an alkyl group having 1 to 8 carbon atoms such as a methyl group or an ethyl group, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms such as a trifluoromethyl group, a halogen atom such as a fluorine atom, a cyano group, an oxo group, or a thioxo group. ２Ａ and R ３Ａ is R ２Ａ , and R ３Ａ The benzene ring substituted with may have 1 to 3 identical or different groups.

[0026] The compound of formula (A) is preferably the compound shown below: (A-2) W Ａ is tetrazole, 1,2,4-triazole, 1,2,3-triazole, 1,2,4-oxadiazole, pyrazole or imidazole, which may have as a substituent a group selected from an alkyl group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a cyano group, an oxo group or a thioxo group. Ａ is a tetrazole, 1,2,4-triazole or 1,2,3-triazole which may have as a substituent a group selected from an alkyl group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom or a cyano group. Ａ(A-5) The compound according to any one of (A-1) to (A-3), wherein W is 5-oxo-1,2,4-oxadiazole or 5-thioxo-1,2,4-oxadiazole. Ａ The compound according to any one of (A-1) to (A-4), wherein

[0027] (A-6)R １Ａ (A-7) The compound according to any one of (A-1) to (A-5), wherein R is a hydrogen atom or an alkyl group having 1 to 8 carbon atoms. １Ａ (A-8) The compound according to any one of (A-1) to (A-6), wherein R is a hydrogen atom. ４Ａ is a hydrogen atom, and R ５Ａ (A-9) The compound according to any one of (A-1) to (A-7), wherein R is a hydrogen atom or an alkyl group having 1 to 8 carbon atoms. ４Ａ and R ５Ａ (A-10) The compound according to any one of (A-1) to (A-8), wherein R ２Ａ (A-11) The compound according to any one of (A-1) to (A-9), wherein R is a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, a carboxyl group, an acyl group having 2 to 8 carbon atoms, or an alkoxycarbonyl group (the alkoxy moiety has 1 to 8 carbon atoms). ２Ａ (A-12) The compound according to any one of (A-1) to (A-10), wherein R is a hydrogen atom. ３Ａ (A-13) The compound according to any one of (A-1) to (A-11), wherein R is a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, a carboxyl group, an acyl group having 2 to 8 carbon atoms, or an alkoxycarbonyl group (the alkoxy moiety has 1 to 8 carbon atoms). ３ＡThe compound according to any one of (A-1) to (A-12), wherein R is a hydrogen atom. Examples of pharmaceutically acceptable salts of the compound represented by general formula (A) include the compound represented by general formula (A), ２Ａ , or R ３Ａ When R is an amino group or the like, examples of the salt include hydrochloride. ２Ａ , or R ３Ａ When is a carboxyl group, examples of the salt include alkali metal salts such as sodium, potassium, and lithium.

[0028] Representative compounds encompassed by general formula (A) are shown below. <Representative Compound A-100> (In the formula, R １Ａ , R ４Ａ , R ５Ａ and W Ａ and W Ａ The substitution positions of are as shown in Tables 1 to 3. Ａ The substitution positions in the table indicate the substitution positions on the benzene ring. That is, the 2-, 3-, and 4-positions in the table correspond to the 2'-, 3'-, and 4'-positions in the formula of Representative Compound A-100, respectively.

[0029]

[0030]

[0031]

[0032] <Representative compound A-200> (In the formula, R １Ａ , R ２Ａ , R ４Ａ , R ５Ａ and W Ａ and W Ａ The substitution positions of are as shown in Tables 4 and 5. Ａ The substitution positions in the table indicate the substitution positions on the benzene ring. That is, the 2-, 3-, and 4-positions in the table correspond to the 2'-, 3'-, and 4'-positions in the formula of Representative Compound A-200, respectively.

[0033]

[0034] ​​​​

[0035] <Representative compound A-300> (In the formula, R １Ａ , R ２Ａ , R ３Ａ , R ４Ａ , R ５Ａ and W Ａ and W Ａ The substitution positions of are as shown in Tables 6 and 7. Ａ The substitution positions in the table indicate the substitution positions on the benzene ring. That is, the 3rd and 4th positions in the table correspond to the 3'- and 4'-positions in the formula of Representative Compound A-300, respectively.

[0036]

[0037]

[0038] (B-1) The following general formula (BI): (In the formula, R １Ｂ and R ２Ｂ may be the same or different and represent a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an acylamino group having 2 to 8 carbon atoms, a carboxyl group, an acyl group having 2 to 8 carbon atoms, an alkoxycarbonyl group (the alkoxy moiety has 1 to 8 carbon atoms), a phenyl group which may have a substituent, a pyridyl group which may have a substituent, or an aralkyl group (the aryl moiety has 6 to 10 carbon atoms and the alkylene moiety has 1 to 8 carbon atoms), or R １Ｂ and R ２Ｂ may be taken together with the benzene ring to which they are attached to form a fused ring selected from a naphthalene ring, a quinoline ring, an isoquinoline ring, a tetrahydronaphthalene ring, an indane ring, a tetrahydroquinoline ring, or a tetrahydroisoquinoline ring, and R １Ｂ and R ２Ｂ Together, R １Ｂ and R２Ｂ are bonded to a ring consisting of carbon atoms, and may be substituted with 1 to 4 substituents, which may be the same or different, selected from an alkyl group having 1 to 8 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an acylamino group having 2 to 8 carbon atoms, a carboxyl group, an acyl group having 2 to 8 carbon atoms, an alkoxycarbonyl group (the alkoxy moiety has 1 to 8 carbon atoms), or an aralkyl group (the aryl moiety has 6 to 10 carbon atoms, and the alkylene moiety has 1 to 8 carbon atoms); ３Ｂ and R ４Ｂ may be the same or different and represent a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an acylamino group having 2 to 8 carbon atoms, a carboxyl group, an acyl group having 2 to 8 carbon atoms, an alkoxycarbonyl group (the alkoxy moiety has 1 to 8 carbon atoms), or an aralkyl group (the aryl moiety has 6 to 10 carbon atoms and the alkylene moiety has 1 to 8 carbon atoms); R ５Ｂ represents a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkyl group having 1 to 8 carbon atoms substituted with a hydroxyl group, or an aralkyl group (the aryl portion has 6 to 10 carbon atoms, and the alkylene portion has 1 to 8 carbon atoms); R ６Ｂ and R ７Ｂmay be the same or different and represent a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, or an amino group; X Ｂ represents C, CH or N; Y Ｂ represents N, NH or C(=O), provided that X Ｂ When N, Y Ｂ is not N or NH, and X Ｂ When is C or CH, Y Ｂ is not C(=O), a double line consisting of a solid line and a dashed line represents a single bond or a double bond, Z Ｂ represents an oxygen atom or a sulfur atom; Ｂ represents a benzene ring, pyridine ring, thiophene ring, pyrimidine ring, naphthalene ring, quinoline ring or indole ring which may have 1 to 4 substituents, which may be the same or different, selected from an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an aralkyl group (the aryl portion has 6 to 10 carbon atoms and the alkylene portion has 1 to 8 carbon atoms), a phenyl group or a pyridyl group, or represents a bond; B Ｂ is N(R ８Ｂ )C(=O),NHCONH,CON(R ９Ｂ ), NHC(=S)NH,N(R １０Ｂ ) SO ２ , S.O. ２ N (R １１Ｂ ) or OSO ２ where R ８Ｂ , R ９Ｂ , R １０Ｂ and R １１Ｂrepresents a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkyl group having 1 to 8 carbon atoms substituted with a hydroxyl group, or an aralkyl group (the aryl portion has 6 to 10 carbon atoms, and the alkylene portion has 1 to 8 carbon atoms); D Ｂ represents an alkylene chain having 1 to 6 carbon atoms which may have 1 to 4 substituents, which may be the same or different, selected from an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkyl group having 1 to 8 carbon atoms substituted with a hydroxyl group, or an aralkyl group (the aryl portion has 6 to 10 carbon atoms, and the alkylene portion has 1 to 8 carbon atoms), and which may further have a double bond, or a bond; Ｂ is O, S, NR １２Ｂ , or a bond, where R １２Ｂ represents a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkyl group having 1 to 8 carbon atoms substituted with a hydroxyl group, or an aralkyl group (the aryl portion has 6 to 10 carbon atoms and the alkylene portion has 1 to 8 carbon atoms), Ｂis substituted with an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an acyl group having 2 to 8 carbon atoms, a methylenedioxy group, a carboxyl group, an alkylsulfinyl group having 1 to 6 carbon atoms, an alkylthio group having 1 to 6 carbon atoms, an alkylsulfonyl group having 1 to 6 carbon atoms, an aralkyl group (wherein the carbon atom of the aryl moiety is m represents piperazine, piperidine, morpholine, cyclohexane, benzene, naphthalene, quinoline, quinoxaline, benzimidazole, thiophene, imidazole, thiazole, oxazole, indole, benzofuran, pyrrole, pyridine or pyrimidine, each of which may have 1 to 4 identical or different substituents selected from an optionally substituted phenyl group, an optionally substituted pyridyl group, an optionally substituted imidazolyl group, an optionally substituted oxazolyl group, or an optionally substituted thiazolyl group; and Ｂ represents an integer of 0 to 5. １Ｂ and R ２Ｂ do not form a ring together, and X Ｂ is C, Y Ｂ is N, the double line consisting of a solid line and a dashed line is a double bond, and Z Ｂ is an oxygen atom, and A Ｂ is a benzene ring, and m Ｂ is 0, B Ｂ is C(=O)NH, and E Ｂ is a bond and G Ｂ is a phenyl group.) or a pharmaceutically acceptable salt thereof.

[0039] (B-2) The following general formula (BII): (In the formula, represents a naphthalene ring, quinoline ring, isoquinoline ring, tetrahydronaphthalene ring, indane ring, tetrahydroquinoline ring or tetrahydroisoquinoline ring, and these rings may be substituted with 1 to 4 substituents, which may be the same or different, selected from an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an acylamino group having 2 to 8 carbon atoms, a carboxyl group, an acyl group having 2 to 8 carbon atoms, an alkoxycarbonyl group (the alkoxy moiety has 1 to 8 carbon atoms), or an aralkyl group (the aryl moiety has 6 to 10 carbon atoms and the alkylene moiety has 1 to 8 carbon atoms); R ３Ｂａ and R ４Ｂａ may be the same or different and represent a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an acylamino group having 2 to 8 carbon atoms, a carboxyl group, an acyl group having 2 to 8 carbon atoms, an alkoxycarbonyl group (the alkoxy moiety has 1 to 8 carbon atoms), or an aralkyl group (the aryl moiety has 6 to 10 carbon atoms and the alkylene moiety has 1 to 8 carbon atoms); R ５Ｂａ represents a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkyl group having 1 to 8 carbon atoms substituted with a hydroxyl group, or an aralkyl group (the aryl portion has 6 to 10 carbon atoms, and the alkylene portion has 1 to 8 carbon atoms); R ６Ｂａ and R ７Ｂａmay be the same or different and represent a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, or an amino group; represents a benzene ring, pyridine ring, thiophene ring, pyrimidine ring, naphthalene ring, quinoline ring, or indole ring which may have, as substituents, 1 to 4 substituents which may be the same or different and which are selected from an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an aralkyl group (the aryl moiety has 6 to 10 carbon atoms and the alkylene moiety has 1 to 8 carbon atoms), a phenyl group, or a pyridyl group; B Ｂａ is N(R ８Ｂａ )C(=O),NHCONH,CON(R ９Ｂａ ), NHC(=S)NH,N(R １０Ｂａ ) SO ２ , S.O. ２ N (R １１Ｂａ ), or OSO ２ where R ８Ｂａ , R ９Ｂａ , R １０Ｂａ and R １１Ｂａ represents a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkyl group having 1 to 8 carbon atoms substituted with a hydroxyl group, or an aralkyl group (the aryl portion has 6 to 10 carbon atoms and the alkylene portion has 1 to 8 carbon atoms), Ｂａ is O, S, NR １２Ｂａ or a bond, where R １２Ｂａrepresents a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkyl group having 1 to 8 carbon atoms substituted with a hydroxyl group, or an aralkyl group (the aryl portion has 6 to 10 carbon atoms, and the alkylene portion has 1 to 8 carbon atoms); G Ｂａ is substituted with an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an acyl group having 2 to 8 carbon atoms, a methylenedioxy group, a carboxyl group, an alkylsulfinyl group having 1 to 6 carbon atoms, an alkylthio group having 1 to 6 carbon atoms, an alkylsulfonyl group having 1 to 6 carbon atoms, an aralkyl group (wherein the carbon atom of the aryl moiety is the number of carbon atoms in the alkylene moiety is 1 to 8), piperazine, piperidine, morpholine, cyclohexane, benzene, naphthalene, quinoline, quinoxaline, benzimidazole, thiophene, imidazole, thiazole, oxazole, indole, benzofuran, pyrrole, pyridine or pyrimidine which may have 1 to 4 identical or different substituents selected from an optionally substituted phenyl group, an optionally substituted pyridyl group, an optionally substituted imidazolyl group, an optionally substituted oxazolyl group, or an optionally substituted thiazolyl group, and Ｂ represents an integer of 0 to 5, or a pharmaceutically acceptable salt thereof.

[0040] Next, the substituents in general formulae (BI) and (BII) in this specification will be explained. Examples of alkyl groups having 1 to 8 carbon atoms include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an i-butyl group, a t-butyl group, a pentyl group, and a hexyl group. Examples of cycloalkyl groups having 3 to 8 carbon atoms include a cyclopropyl group and a cyclohexyl group. Examples of alkenyl groups having 2 to 8 carbon atoms include an allyl group. Examples of alkoxy groups having 1 to 8 carbon atoms include a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, an i-butoxy group, a t-butoxy group, a pentyloxy group, and a hexyloxy group.

[0041] Examples of alkyl groups having 1 to 8 carbon atoms and substituted with 1 to 3 halogen atoms include methyl, ethyl, propyl, isopropyl, butyl, and t-butyl groups substituted with 1 to 3 halogen atoms such as fluorine, chlorine, or bromine, and preferred examples include trifluoromethyl, chloromethyl, 2-chloroethyl, 2-bromoethyl, and 2-fluoroethyl groups. Examples of alkoxy groups having 1 to 8 carbon atoms and substituted with 1 to 3 halogen atoms include methoxy, ethoxy, propoxy, isopropoxy, butoxy, and t-butoxy groups substituted with 1 to 3 halogen atoms such as fluorine, chlorine, or bromine, and preferred examples include trifluoromethoxy, chloromethoxy, 2-chloroethoxy, 2-bromoethoxy, and 2-fluoroethoxy groups. Examples of halogen atoms include fluorine, chlorine, and bromine atoms.

[0042] Examples of alkylamino groups having 1 to 8 carbon atoms include a methylamino group and an ethylamino group. Examples of dialkylamino groups having 2 to 8 carbon atoms include a dimethylamino group and a diethylamino group. Examples of acylamino groups having 2 to 8 carbon atoms include an acetylamino group. Examples of acyl groups having 2 to 8 carbon atoms include an acetyl group.

[0043] Examples of alkoxycarbonyl groups (the alkoxy moiety has 1 to 8 carbon atoms) include a methoxycarbonyl group. Examples of aralkyl groups (the aryl moiety has 6 to 10 carbon atoms, and the alkylene moiety has 1 to 8 carbon atoms) include a benzyl group. Examples of alkyl groups having 1 to 8 carbon atoms substituted with a hydroxyl group include a 2-hydroxyethyl group.

[0044] Examples of alkylsulfinyl groups having 1 to 6 carbon atoms include methanesulfinyl groups, etc. Examples of alkylthio groups having 1 to 6 carbon atoms include methylthio groups, etc. Examples of alkylsulfonyl groups having 1 to 6 carbon atoms include methanesulfonyl groups, etc.

[0045] Examples of the substituent that the optionally substituted phenyl group, optionally substituted pyridyl group, optionally substituted imidazolyl group, optionally substituted oxazolyl group, and optionally substituted thiazolyl group may have include a halogen atom, an alkyl group having 1 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, and an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms.

[0046] As the compound of the above general formula (BI), the following compound is preferred: (B-1-1) R １Ｂ and R ２Ｂ may be the same or different and are a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, a phenyl group which may have a substituent, a pyridyl group which may have a substituent, or an aralkyl group (the aryl portion has 6 to 10 carbon atoms, and the alkylene portion has 1 to 8 carbon atoms).

[0047] (B-1-2) R １Ｂ and R ２Ｂtogether with the benzene ring to which they are attached form a naphthalene ring or a tetrahydronaphthalene ring, and R １Ｂ and R ２Ｂ Together, R １Ｂ and R ２Ｂ and R are bonded to a benzene ring or a cyclohexene ring, each of which may be substituted with 1 to 4 identical or different substituents selected from an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an acylamino group having 2 to 8 carbon atoms, a carboxyl group, an acyl group having 2 to 8 carbon atoms, an alkoxycarbonyl group (the alkoxy portion has 1 to 8 carbon atoms), or an aralkyl group (the aryl portion has 6 to 10 carbon atoms, and the alkylene portion has 1 to 8 carbon atoms). (B-1-3) The compound according to (B-1) or (B-1-1) above, １Ｂ and R ２Ｂ together form a naphthalene ring together with the benzene ring to which they are attached, and R １Ｂ and R ２Ｂ Together, R １Ｂ and R ２Ｂ and (B-1-4) are compounds according to (B-1) or (B-1-1) above, wherein the benzene ring formed from the carbon atoms to which R are bonded is optionally substituted with 1 to 4 substituents, which may be the same or different, selected from an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, or an amino group. １Ｂ and R ２Ｂ and (B-1) or (B-1-1) above, in which, together with the benzene ring to which they are attached, form a naphthalene ring or a tetrahydronaphthalene ring.

[0048] (B-1-5) R ３Ｂ and R ４Ｂ (B-1-6) The compound according to any one of (B-1) or (B-1-1) to (B-1-4) above, wherein R may be the same or different and are a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, or an aralkyl group (the aryl portion has 6 to 10 carbon atoms, and the alkylene portion has 1 to 8 carbon atoms). ５Ｂ (B-1-7) The compound according to any one of (B-1) or (B-1-1) to (B-1-5), wherein R is a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, or an aralkyl group (the aryl portion has 6 to 10 carbon atoms, and the alkylene portion has 1 to 8 carbon atoms). ５Ｂ (B-1-8) The compound according to any one of (B-1) or (B-1-1) to (B-1-6) above, wherein R ６Ｂ and R ７Ｂ (B-1-9) The compound or pharmaceutically acceptable salt thereof according to any one of (B-1) or (B-1-1) to (B-1-7), wherein R may be the same or different and is a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, or an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms. ６Ｂ and R ７Ｂ The compound according to any one of (B-1) or (B-1-1) to (B-1-8) above, wherein both are hydrogen atoms.

[0049] (B-1-10) R ３Ｂ , R ４Ｂ , R ５Ｂ , R ６Ｂ and R ７Ｂ The compound according to any one of (B-1) or (B-1-1) to (B-1-9) above, wherein

[0050] (B-1-11) X Ｂ is N and Y Ｂ(B-1-12) The compound according to any one of (B-1) or (B-1-1) to (B-1-10) above, wherein X is C(═O) and the double line consisting of a solid line and a dashed line is a single bond. Ｂ is C and Y Ｂ (B-1-13) The compound according to any one of (B-1) or (B-1-1) to (B-1-11) above, wherein Z is N and the double line consisting of a solid line and a dashed line is a double bond. Ｂ The compound according to any one of (B-1) or (B-1-1) to (B-1-12) above, wherein

[0051] (B-1-14) A Ｂ is a phenyl group or a pyridyl group, which may have 1 to 4 substituents, which may be the same or different, selected from an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an aralkyl group (the aryl portion has 6 to 10 carbon atoms and the alkylene portion has 1 to 8 carbon atoms), a phenyl group, or a pyridyl group. (B-1-15) A Ｂ is a phenyl group optionally having 1 to 4 substituents, which may be the same or different, selected from an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, or an amino group.

[0052] (B-1-16) A Ｂ (B-1-17) The compound according to any one of (B-1) or (B-1-1) to (B-1-15), wherein A is a phenyl group or a pyridyl group. ＢThe compound according to any one of (B-1) or (B-1-1) to (B-1-16) above, wherein

[0053] (B-1-18) B Ｂ is NHC(=O),NHCONH,CONH,NHC(=S)NH,NHSO ２ , SO ２ NH or OSO ２ The compound according to any one of (B-1) or (B-1-1) to (B-1-17) above, wherein Ｂ is NHC(=O), NHCONH or NHSO ２ The compound according to any one of (B-1) or (B-1-1) to (B-1-18) above, wherein

[0054] (B-1-20) B Ｂ is NHC(=O) or NHSO ２ (B-1-21) The compound according to any one of (B-1) or (B-1-1) to (B-1-19) above, Ｂ The compound according to any one of the above (B-1) or (B-1-1) to (B-1-20), wherein is NHC(=O). (B-1-22) D Ｂ is an alkylene chain having 1 to 6 carbon atoms and optionally having a double bond, and which may have 1 to 4 substituents, which may be the same or different, selected from an alkyl group having 1 to 8 carbon atoms or an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms. (B-1-23) D Ｂ The compound according to any one of (B-1) or (B-1-1) to (B-1-22) above, wherein

[0055] (B-1-24) D Ｂ The compound according to any one of (B-1) or (B-1-1) to (B-1-23) above, wherein the compound has 1 to 4 substituents, which may be the same or different, selected from alkyl groups having 1 to 8 carbon atoms and alkenyl groups having 2 to 8 carbon atoms. (B-1-25) D ＢThe compound according to any one of (B-1) or (B-1-1) to (B-1-24) above, wherein the compound has 1 to 4 substituents, which may be the same or different, selected from alkyl groups having 1 to 3 carbon atoms and alkenyl groups having 2 to 3 carbon atoms. Ｂ The compound according to any one of (B-1) or (B-1-1) to (B-1-25) above, wherein

[0056] (B-1-27) G Ｂ and the substituents include an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an acyl group having 2 to 8 carbon atoms, a methylenedioxy group, a carboxyl group, an alkylsulfinyl group having 1 to 6 carbon atoms, a carbon ... carboxyl group, a hydroxyl group, a nitro group, a cyano group, an amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an acyl group having 2 to 8 carbon atoms, a methylenedioxy group, a carboxyl group, an alkylsulfinyl group having 1 to 6 carbon atoms, a hydroxyl group, a hydroxyl group, a nitro group, a cyano group, an amino group, an alkylamino group having 1 to 8 carbon The compound according to any one of (B-1) or (B-1-1) to (B-1-26) above, which is piperazine, piperidine, morpholine, cyclohexane, benzene, naphthalene, quinoline, quinoxaline, benzimidazole, thiophene, imidazole, thiazole, oxazole, indole, benzofuran, pyrrole, pyridine, or pyrimidine, each optionally having 1 to 4 identical or different substituents selected from alkylthio groups having 1 to 6 carbon atoms or alkylsulfonyl groups having 1 to 6 carbon atoms. (B-1-28) G ＢThe compound according to any one of (B-1) and (B-1-1) to (B-1-27), wherein the alkyl group is benzene optionally having 1 to 4 of the same or different substituents selected from an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an acyl group having 2 to 8 carbon atoms, a methylenedioxy group, a carboxyl group, an alkylsulfinyl group having 1 to 6 carbon atoms, an alkylthio group having 1 to 6 carbon atoms, or an alkylsulfonyl group having 1 to 6 carbon atoms.

[0057] (B-1-29) G Ｂ is benzene or pyridine which may have, as substituents, 1 to 4 of the same or different substituents selected from an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, an amino group, a dialkylamino group having 2 to 8 carbon atoms, a carboxyl group, an alkylsulfinyl group having 1 to 6 carbon atoms, an alkylthio group having 1 to 6 carbon atoms, or an alkylsulfonyl group having 1 to 6 carbon atoms.

[0058] (B-1-30) G Ｂ is benzene which may have 1 to 4 identical or different substituents selected from an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, or a hydroxyl group as substituents.

[0059] (B-1-31) m Ｂ The compound according to any one of the above (B-1) or (B-1-1) to (B-1-30), wherein is 0.

[0060] (B-1-32) A Ｂ is a benzene ring, and m Ｂis 0, and B Ｂ is NHC(=O) or NHSO ２ and D Ｂ is an alkyl group having 1 to 3 carbon atoms or a bond, and E Ｂ is a bond, and G Ｂ is benzene which may have, as substituents, 1 to 4 of the same or different substituents selected from an alkyl group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, or a hydroxyl group.

[0061] (B-1-33) A Ｂ is a benzene ring, and m Ｂ is 0, and B Ｂ is NHC(=O), and D Ｂ is a bond, and E Ｂ is a bond, and G Ｂ (B-1-34) The compound according to any one of (B-1) or (B-1-1) to (B-1-32), wherein R is benzene which may have 1 to 4 identical or different substituents selected from an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, or a hydroxyl group as substituents. １Ｂ and R ２Ｂ together with the benzene ring to which they are attached to form a naphthalene ring, and R ３Ｂ , R ４Ｂ , R ５Ｂ , R ６Ｂ and R ７Ｂ represents a hydrogen atom, and X Ｂ is N and Y Ｂ is C(=O), the double line consisting of a solid line and a dashed line represents a single bond, and Z Ｂ represents an oxygen atom, and A Ｂ represents a benzene ring, m Ｂ represents 0, B Ｂ is NHC(=O) or NHSO ２ represents D Ｂ represents an alkyl group having 1 to 3 carbon atoms or a bond, E Ｂ represents a bond, and G Ｂ(B-1-35) The compound according to any one of the above (B-1) or (B-1-1) to (B-1-33), wherein R is benzene optionally having 1 to 4 identical or different substituents selected from an alkyl group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, or a hydroxyl group as substituents. １Ｂ and R ２Ｂ together with the benzene ring to which they are attached to form a naphthalene ring, and R ３Ｂ , R ４Ｂ , R ５Ｂ , R ６Ｂ and R ７Ｂ represents a hydrogen atom, and X Ｂ is N and Y Ｂ is C(=O), the double line consisting of a solid line and a dashed line represents a single bond, and Z Ｂ represents an oxygen atom, and A Ｂ represents a benzene ring, m Ｂ represents 0, B Ｂ represents NHC(=O), and D Ｂ represents a bond, and E Ｂ represents a bond, and G Ｂ is a benzene which may have, as substituents, 1 to 4 of the same or different substituents selected from an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, or a hydroxyl group.

[0062] As the compound of the above general formula (BII), the following compound is preferred: (B-2-1) is a naphthalene ring or tetrahydronaphthalene ring optionally substituted with 1 to 4 identical or different substituents selected from an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an acylamino group having 2 to 8 carbon atoms, a carboxyl group, an acyl group having 2 to 8 carbon atoms, an alkoxycarbonyl group (the alkoxy portion has 1 to 8 carbon atoms), or an aralkyl group (the aryl portion has 6 to 10 carbon atoms, and the alkylene portion has 1 to 8 carbon atoms). (B-2-2) is a naphthalene ring optionally substituted with 1 to 4 substituents, which may be the same or different, selected from an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, or an amino group.

[0063] (B-2-3) R ３Ｂａ and R ４Ｂａ (B-2-4) The compound according to any one of (B-2) or (B-2-1) or (B-2-2) above, wherein R may be the same or different and is a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, or an aralkyl group (the aryl portion has 6 to 10 carbon atoms, and the alkylene portion has 1 to 8 carbon atoms). ５Ｂａ(B-2-5) The compound according to any one of (B-2) or (B-2-1) to (B-2-3), wherein R is a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, or an aralkyl group (the aryl portion has 6 to 10 carbon atoms, and the alkylene portion has 1 to 8 carbon atoms). ５Ｂａ (B-2-6) The compound according to any one of (B-2) or (B-2-1) to (B-2-4) above, wherein R ６Ｂａ and R ７Ｂａ (B-2-7) The compound according to any one of (B-2) or (B-2-1) to (B-2-5), wherein R may be the same or different and is a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, or an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms. ６Ｂａ and R ７Ｂａ The compound according to any one of (B-2) or (B-2-1) to (B-2-6) above, wherein both are hydrogen atoms.

[0064] (B-2-8) is a phenyl group or a pyridyl group, which may have 1 to 4 substituents, which may be the same or different, selected from an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an aralkyl group (the aryl portion has 6 to 10 carbon atoms and the alkylene portion has 1 to 8 carbon atoms), a phenyl group, or a pyridyl group. (B-2-9) is a phenyl group optionally having 1 to 4 substituents, which may be the same or different, selected from an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, or an amino group. (B-2-10) The compound according to any one of (B-2) or (B-2-1) to (B-2-9) above, wherein

[0065] (B-2-11) B Ｂａ is NHC(=O),NHCONH,CONH,NHC(=S)NH,NHSO ２ , SO ２ NH or OSO ２ (B-2-12) The compound according to any one of (B-2) or (B-2-1) to (B-2-10), Ｂａ is NHC(=O), NHCONH or NHSO ２ (B-2-13) The compound according to any one of (B-2) or (B-2-1) to (B-2-11), wherein E Ｂａ The compound according to any one of (B-2) or (B-2-1) to (B-2-12) above, wherein

[0066] (B-2-14) G Ｂａand the substituents include an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an acyl group having 2 to 8 carbon atoms, a methylenedioxy group, a carboxyl group, an alkylsulfinyl group having 1 to 6 carbon atoms, The compound according to any one of (B-2) or (B-2-1) to (B-2-13) above, which is piperazine, piperidine, morpholine, cyclohexane, benzene, naphthalene, quinoline, quinoxaline, benzimidazole, thiophene, imidazole, thiazole, oxazole, indole, benzofuran, pyrrole, pyridine, or pyrimidine, each optionally having 1 to 4 identical or different substituents selected from alkylthio groups having 1 to 6 carbon atoms or alkylsulfonyl groups having 1 to 6 carbon atoms. (B-2-15) G Ｂａ The compound according to any one of (B-2) and (B-2-1) to (B-2-14), wherein the benzene ring is a benzene ring optionally having 1 to 4 of the same or different substituents selected from an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an acyl group having 2 to 8 carbon atoms, a methylenedioxy group, a carboxyl group, an alkylsulfinyl group having 1 to 6 carbon atoms, an alkylthio group having 1 to 6 carbon atoms, or an alkylsulfonyl group having 1 to 6 carbon atoms.

[0067] (B-2-16) n Ｂ The compound according to any one of (B-2) or (B-2-1) to (B-2-15) above, wherein is 0.

[0068] In the above general formula (BI), R Ｂ１ and R Ｂ２are preferably taken together with the benzene ring to which they are attached to form a fused ring selected from a naphthalene ring or a tetrahydronaphthalene ring, and particularly preferably form a naphthalene ring.

[0069] In the above general formula (BI), R Ｂ３ , R Ｂ４ , R Ｂ５ , R Ｂ６ and R Ｂ７ preferably represents a hydrogen atom.

[0070] In the above general formula (BI), X Ｂ is N and Y Ｂ is preferably C(=O), and the double line consisting of a solid line and a dashed line is preferably a single bond.

[0071] In the above general formula (BI), Z Ｂ is preferably an oxygen atom.

[0072] In the above general formula (BI), A Ｂ preferably represents a benzene ring or a pyridine ring, and particularly preferably represents a benzene ring.

[0073] In the above general formula (BI), m Ｂ Preferably, represents 0 to 4, and particularly preferably represents 0.

[0074] In the above general formula (BI), B Ｂ is N(R ８Ｂ ) C(=O) or N(R １０Ｂ ) SO ２ Preferably, R represents ８Ｂ and R １０Ｂ More preferably, B represents a hydrogen atom. Ｂ It is particularly preferred that represents NHC(=O).

[0075] In the above general formula (BI), D Ｂpreferably represents an alkylene chain or bond having 1 to 6 carbon atoms having 1 to 4 substituents, which may be the same or different, selected from alkyl groups having 1 to 8 carbon atoms or alkenyl groups having 2 to 8 carbon atoms as substituents, more preferably represents an alkylene chain or bond having 1 to 6 carbon atoms having 1 to 4 substituents, which may be the same or different, selected from alkyl groups having 1 to 3 carbon atoms or alkenyl groups having 2 to 3 carbon atoms, and particularly preferably represents a bond.

[0076] In the above general formula (BI), E Ｂ preferably represents O or a bond, and particularly preferably represents a bond.

[0077] In the above general formula (BI), G Ｂ preferably represents benzene or pyridine, which may have, as substituents, 1 to 4 identical or different substituents selected from an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, an amino group, a dialkylamino group having 2 to 8 carbon atoms, a carboxyl group, an alkylsulfinyl group having 1 to 6 carbon atoms, an alkylthio group having 1 to 6 carbon atoms, or an alkylsulfonyl group having 1 to 6 carbon atoms; Ｂ It is particularly preferable that represents benzene which may have, as substituents, 1 to 4 identical or different substituents selected from an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, or a hydroxyl group.

[0078] In the above general formula (BI), A Ｂ represents a benzene ring, m Ｂ represents 0, B Ｂ is NHC(=O) or NHSO ２ represents D Ｂ represents an alkyl group having 1 to 3 carbon atoms or a bond, E Ｂ represents a bond, and G ＢIt is particularly preferable that represents benzene optionally having, as substituents, 1 to 4 identical or different substituents selected from an alkyl group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, or a hydroxyl group.

[0079] In the above general formula (BI), A Ｂ represents a benzene ring, m Ｂ represents 0, B Ｂ represents NHC(=O), and D Ｂ represents a bond, and E Ｂ represents a bond, and G Ｂ It is particularly preferable that represents benzene which may have, as substituents, 1 to 4 identical or different substituents selected from an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, or a hydroxyl group.

[0080] In the above general formula (BI), R Ｂ１ and R Ｂ２ together with the benzene ring to which they are attached to form a naphthalene ring, and R Ｂ３ , R Ｂ４ , R Ｂ５ , R Ｂ６ and R Ｂ７ represents a hydrogen atom, and X Ｂ is N and Y Ｂ is C(=O), the double line consisting of a solid line and a dashed line represents a single bond, and Z Ｂ represents an oxygen atom, and A Ｂ represents a benzene ring, m Ｂ represents 0, B Ｂ is NHC(=O) or NHSO ２ represents D Ｂ represents an alkyl group having 1 to 3 carbon atoms or a bond, E Ｂ represents a bond, and G Ｂ It is more preferable that represents benzene optionally having 1 to 4 identical or different substituents selected from an alkyl group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, or a hydroxyl group as substituents.

[0081] In the above general formula (BI), R Ｂ１and R Ｂ２ together with the benzene ring to which they are attached to form a naphthalene ring, and R Ｂ３ , R Ｂ４ , R Ｂ５ , R Ｂ６ and R Ｂ７ represents a hydrogen atom, and X Ｂ is N and Y Ｂ is C(=O), the double line consisting of a solid line and a dashed line represents a single bond, and Z Ｂ represents an oxygen atom, and A Ｂ represents a benzene ring, m Ｂ represents 0, B Ｂ represents NHC(=O), and D Ｂ represents a bond, and E Ｂ represents a bond, and G Ｂ It is particularly preferable that represents benzene which may have, as substituents, 1 to 4 identical or different substituents selected from an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, or a hydroxyl group.

[0082] Representative compounds encompassed by general formula (BI) and / or (BII) are shown below.

[0083] <Representative compound example B-100>

[0084]

[0085] (In the formula, B Ｂａ (replacement position), n Ｂ , E Ｂａ and G Ｂａ as shown in Tables 8 to 17)

[0086]

[0087]

[0088]

[0089]

[0090]

[0091]

[0092] ​

[0093]

[0094]

[0095]

[0096] <Representative compound example B-200>

[0097]

[0098] (In the formula, B Ｂａ (replacement position), n Ｂ , E Ｂａ and G Ｂａ as shown in Tables 18 and 19)

[0099]

[0100]

[0101] <Representative compound example B-300>

[0102]

[0103] (In the formula, R １Ｂ , B Ｂａ (replacement position), n Ｂ , E Ｂａ and G Ｂａ as shown in Table 20)

[0104]

[0105] <Representative compound example B-400>

[0106]

[0107] (In the formula, B Ｂa (replacement position), n Ｂ , E Ｂa and G Ｂa as shown in Table 21)

[0108]

[0109] <Representative compound example B-500>

[0110]

[0111] (In the formula, B Ｂa(replacement position), n Ｂ , E Ｂa and G Ｂa as shown in Table 22)

[0112]

[0113] <Representative compound example B-600>

[0114]

[0115] (In the formula, B Ｂ (substitution position), D Ｂ , E Ｂ and G Ｂ as shown in Table 23)

[0116]

[0117] <Representative compound example B-700>

[0118]

[0119] (In the formula, m Ｂ (replacement position), B Ｂ , D Ｂ , E Ｂ and G Ｂ as shown in Table 24)

[0120]

[0121] <Representative compound example B-800>

[0122]

[0123] (In the formula, X Ｂａ , Y Ｂａ , B Ｂａ (replacement position), n Ｂ , E Ｂａ and G Ｂａ as shown in Table 25)

[0124]

[0125] <Representative compound example B-900>

[0126]

[0127] (In the formula, I=II-III=IV, B Ｂａ (replacement position), n Ｂ, E Ｂａ and G Ｂａ as shown in Table 26)

[0128]

[0129] <Representative compound example B-1000>

[0130]

[0131] (In the formula, I-II-III-IV, B Ｂa (replacement position), n Ｂ , E Ｂa and G Ｂa (See Table 27)

[0132]

[0133] <Representative compound example B-1100>

[0134]

[0135] (In the formula, R ５Ｂａ , B Ｂa (replacement position), n Ｂ , E Ｂa and G Ｂa as shown in Table 28)

[0136]

[0137] The compounds represented by the general formula (A) are disclosed in International Publication No. 2010 / 093061, and any of these compounds can be easily obtained by referring to these international publications. The disclosures of these international publications are incorporated herein by reference in their entirety.

[0138] The compounds represented by the general formulas (BI) and (BII) are disclosed in International Publication No. WO 2013 / 105608, and therefore, any of these compounds can be easily obtained by referring to these international publications. The disclosures of these international publications are incorporated herein by reference in their entirety.

[0139] Furthermore, the above-mentioned International Publication Nos. 2010 / 093061 and 2013 / 105608 describe that the compounds represented by the above-mentioned general formulae (A) to (BII) have a P2X4 receptor antagonistic activity.

[0140] Specific examples of suitable compounds included in the compounds represented by the above general formulas (A) to (BII) or pharmaceutically acceptable salts thereof are shown below, but the compounds usable as active ingredients in the pharmaceutical composition of the present invention or pharmaceutically acceptable salts thereof are not limited to these. (Compound A1) 5-[3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound A2) 5-[3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione sodium salt; (Compound A3) 5-[3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione potassium salt; (Compound A4) 5-[4-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound A5) 5-[4-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione sodium salt; (Compound A6) 1-methyl-5-[3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound A7) 1,3-dimethyl-5-[3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound A8) 5-[2-chloro-5-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound A9) 5-[2-chloro-5-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione sodium salt; (Compound A10) 5-[2-methyl-5-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione;

[0141] (Compound A11) 5-[2-methyl-5-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione sodium salt; (Compound A12) 5-[2-bromo-5-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound A13) 5-[3-(2-methyl-2H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound A14) 5-[3-(1-methyl-1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound A15) 5-[3-(5-oxo-4H-[1,2,4]oxadiazol-3-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound A16) 5-[3-(5-thioxo-4H-[1,2,4]oxadiazol-3-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound A17) 5-[3-(5-Thioxo-4H-[1,2,4]oxadiazol-3-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione sodium salt; (Compound A18) 5-[3-(oxazol-2-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound A19) 5-[3-(1H-pyrazol-4-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound A20) 5-[4-fluoro-3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound A21) 5-[4-fluoro-3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione sodium salt;

[0142] (Compound B1) 5-(4-benzoylaminophenyl)-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B2) 5-[4-[2-(trifluoromethyl)benzoyl]aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B3) 5-[4-(3-bromobenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B4) 5-[4-[4-(trifluoromethyl)benzoyl]aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B5) 5-[4-(2-methylbenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B6) 5-[4-(2,6-dimethylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B7) 5-[4-(2,6-dichlorobenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B8) 5-[4-(3-chlorobenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B9) 5-[4-(2-phenylacetylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B10) 1-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-3-phenylthiourea;

[0143] (Compound B11) 5-[4-(2,3-dimethoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B12) 5-[4-(2-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B13) 5-[4-[(2-chlorophenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B14) (Compound B16) 5-[4-(5-bromo-2-chlorobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B17) 5-[4-(2,4-dichlorobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B18) 5-[4-(2-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B19) 5-[4-(2,3-dihydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B20) 1-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-3-phenylurea;

[0144] (Compound B21) 5-[4-[(2,6-dichlorophenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B22) 5-[4-[(2-methoxyphenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B23) 5-[4-[(2-hydroxyphenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B24) 1-(2-chlorophenyl)-3-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]thiourea; (Compound B25) 5-[4-[3-(trifluoromethyl)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B26) 5-[4-[2-[2-(trifluoromethyl)phenyl]acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B27) 1-(2-chlorophenyl)-3-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]urea; (Compound B28) 5-[4-[(2-phenylpropionyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B29) 5-[4-(2-chloro-3-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B30) 5-[4-(3-phenylpropionylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione;

[0145] (Compound B31) 5-[4-[(1H-indole-3-carbonyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B32) 5-[4-(2-chloro-3-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B33) 5-[4-[(2-methyl-2-phenylpropionyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B34) 5-[4-(2-phenoxyacetylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B35) 5-[4-[2-(2-chloro-4-methoxyphenyl)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B36) 5-[4-[(1-methyl-1H-imidazole-2-carbonyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B37) 5-[4-[2-(2,4-dichlorophenyl)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B38) 5-[4-[2-(2-chloro-4-hydroxyphenyl)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B39) 5-[4-(3-phenylpropenylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B40) 5-[4-[(3-pyridylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione hydrochloride;

[0146] (Compound B41) 5-[4-(1H-benzimidazole-2-carbonylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B42) 1-[4-(2,3-dimethylbenzoylamino)phenyl]-7-methoxy-1H-1,5-benzodiazepine-2,4(3H,5H)-dione; (Compound B43) 5-[4-[(benzoylamino)methyl]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B44) 5-[4-[(2-chlorobenzoylamino)methyl]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B45) 1-[4-(2,3-dimethylbenzoylamino)phenyl]-7-hydroxy-1H-1,5-benzodiazepine-2,4(3H,5H)-dione; (Compound B46) 5-[4-(2-chlorobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B47) 5-[4-(2-bromobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B48) 5-[4-(2-iodobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B49) 5-[4-(2,3-dimethylbenzoylamino)-3-fluorophenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B50) 5-[4-[2-(2-methylphenyl)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione;

[0147] (Compound B51) 5-[4-[(quinoxalin-2yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B52) 5-[4-[(5-methylthiophen-2yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B53) 5-[3-[(2-chlorophenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B54) 5-[4-[(2,4,6-trimethylbenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B55) 5-[4-(cyclohexylcarbonylamino)phenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B56) 1-[4-(2,3-dimethylbenzoyl)aminophenyl]-6-methyl-1H-1,5-benzodiazepine-2,4(3H,5H)-dione; (Compound B57) 5-[4-[(2-ethylbenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B58) 5-[4-[(6-methylpyridin-2-yl)carbonylamino]phenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B59) 5-[4-[(2-methylpyridin-3-yl)carbonylamino]phenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B60) 1-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-3-(2-methylphenyl)thiourea;

[0148] (Compound B61) 5-[4-(2-methoxy-3-methylbenzoyl)aminophenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B62) 5-[4-(2,3-dichlorobenzoyl)aminophenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B63) 5-[4-(2,3-dimethylbenzoylamino)-3-hydroxyphenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B64) 5-[4-(2-chloro-3-methoxybenzoylamino)phenyl]-1,3-dihydronaphtho[1,2-e]-1,4-diazepin-2-one; (Compound B65) 5-[4-[(4-dimethylaminobenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B66) 5-[4-[2-(2,4-dichlorophenoxy)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B67) (Compound B68) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)butyl]-2-chloro-3-methoxybenzamide; (Compound B69) 5-[4-(2-chloro-3-hydroxybenzoylamino)phenyl]-1,3-dihydronaphtho[1,2-e]-1,4-diazepin-2-one; (Compound B70) 5-[4-(2-acetylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione;

[0149] (Compound B71) 5-[4-(2-tert-butylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B72) 5-[2-(2-iodobenzoyl)aminoethyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B73) 5-[3-[(2-iodobenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B74) 6,7-dimethyl-1-[4-(2-iodobenzoyl)aminophenyl]-1H-1,5-benzodiazepine-2,4(3H,5H)-dione; (Compound B75) 5-[4-[(1-methylpiperidin-4-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione hydrochloride; (Compound B76) 5-[4-[(benzofuran-2-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B77) 5-[4-[(1-methyl-1H-indol-3-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B78) 5-[4-(2-propenylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B79) 5-[4-(2-propylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B80) 5-[3-fluoro-4-(2-iodobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione;

[0150] (Compound B81) 5-[4-(2-hydroxy-3-methylbenzoyl)aminophenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B82) 5-[4-[(2-isopropoxybenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B83) 5-[4-[(3-methylthiophen-2-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B84) 5-[4-(2-phenoxypropionylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B85) 5-[4-[2-(4-chloro-2-methylphenoxy)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B86) 5-[4-[(4-fluoro-2-trifluoromethyl)benzoyl]aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B87) 5-[4-(4-Fluoro-2-methoxybenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B88) 5-[4-(4-Fluoro-2-hydroxybenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B89) 5-[3-[(2-iodophenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B90) 5-[4-(2-methyl-2-phenoxypropionylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione;

[0151] (Compound B91) 5-[4-(2-tert-butylbenzoylamino)phenyl]-1,3-dihydronaphtho[1,2-e]-1,4-diazepin-2-one; (Compound B92) 5-[4-[(3-dimethylaminobenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B93) 5-[4-(4-iodo-2-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B94) 5-[4-(6-Fluoro-2-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B95) 5-[4-(2-hydroxy-4-iodobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B96) 5-[4-(6-Fluoro-2-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B97) 5-[4-(2-Fluorobenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B98) 5-[4-[(2-dimethylaminobenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B99) 5-[4-(2-methoxy-6-methylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B100) 5-[4-(2-hydroxy-6-methylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione;

[0152] (Compound B101) 5-[4-[3-(2-methylphenyl)propionylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B102) 5-(4-phenylcarbamoylphenyl)-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B103) 5-(4-benzylcarbamoylphenyl)-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B104) 5-[4-[3-(2-methylphenyl)propenoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B105) 5-[4-[3-(2-chlorophenyl)propionylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B106) 5-[4-(2-iodobenzoyl)aminophenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B107) 5-[4-[(1-methyl-1H-pyrrol-2-ylacetyl)amino]phenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B108) 5-[4-(2-chlorobenzyl)carbamoylphenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B109) 5-[4-[3-(2-chlorophenyl)propenoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B110) 5-[4-(2-chlorophenyl)carbamoylphenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione;

[0153] (Compound B111) 5-[4-(6-bromo-2,3-methylenedioxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B112) 5-[4-(6-bromo-2-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B113) 5-[4-[(2-tert-butylbenzoyl)amino]phenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B114) 5-[2-(2-Iodobenzoyl)aminopyridin-5-yl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B115) 5-[4-(6-bromo-2-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B116) 5-[4-(6-chloro-2-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B117) 5-[4-(2-iodobenzoylamino)phenyl]-1H-[1,4]diazepino[2,3-h]quinoline-2,4(3H,5H)-dione; (Compound B118) 5-[4-(6-chloro-2-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B119) 5-[4-(2-hydroxy-6-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B120) 5-[4-[2-methoxy-6-(trifluoromethyl)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione;

[0154] (Compound B121) 5-[4-[2-hydroxy-6-(trifluoromethyl)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B122) 5-[4-[(2-isopropenylbenzoyl)amino]phenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B123) 5-[4-[(2-isopropylbenzoyl)amino]phenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B124) 5-[4-[2-chloro-5-(methylthio)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B125) 5-[4-[2-(methylthio)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B126) 5-[4-[3-(methylthio)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B127) (Compound B128) 5-[4-(3-methanesulfonylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B129) 6-ethyl-1-[4-(2-iodobenzoyl)aminophenyl]-1H-1,5-benzodiazepine-2,4(3H,5H)-dione; (Compound B130) 5-[4-[2-ethyl-6-hydroxybenzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione;

[0155] (Compound B131) 5-[4-(3-methanesulfinylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B132) 5-[4-(2-chloro-5-methanesulfinylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B133) 5-[4-(2-methanesulfinylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B134) 5-[4-[[2-(4-morpholinyl)acetyl]amino]phenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione hydrochloride; (Compound B135) 5-[4-(2-chloro-6-methoxybenzoylamino)phenyl]-1,3-dihydronaphtho[1,2-e]-1,4-diazepin-2-one; (Compound B136) 5-[4-[[(3-chloropyridin-2-yl)carbonyl]amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B137) 5-[4-(2-chloro-6-hydroxybenzoylamino)phenyl]-1,3-dihydronaphtho[1,2-e]-1,4-diazepin-2-one; (Compound B138) 5-[4-(3-chloro-2-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B139) 5-[4-[(3-methylpyridin-2-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B140) 5-[4-[[(3-chloropyridin-2-yl)carbonyl]amino]phenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione;

[0156] (Compound B141) 5-[4-(3-chloro-2-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B142) 5-[4-[[(3-hydroxypyridin-2-yl)carbonyl]amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B143) 5-[4-[(3-vinylpyridin-2-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B144) 5-[4-[(3-ethylpyridin-2-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B145) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho-[1,2-b][1,4]-diazepin-5-yl)phenyl]-2-nitrobenzenesulfonamide; (Compound B146) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]benzenesulfonamide; (Compound B147) 3-Bromo-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]benzenesulfonamide; (Compound B148) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-3-methoxybenzenesulfonamide; (Compound B149) N-[3-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepin-5-yl)phenyl]benzenesulfonamide; (Compound B150) N-[3-(2,4-dioxo-1,2,3,4-tetrahydronaphtho-[1,2-b][1,4]-diazepin-5-yl)phenyl]-2-nitrobenzenesulfonamide;

[0157] (Compound B151) N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydro-naphtho[1,2-b][1,4]-diazepin-5-yl)phenyl]-2-nitro-benzenesulfonamide; (Compound B152) N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydro-naphtho[1,2-b][1,4]-diazepin-5-yl)phenyl]-N-methyl-2-nitrobenzenesulfonamide; (Compound B153) N-[3-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]-diazepin-5-yl)phenyl]-N-methyl-2-nitrobenzenesulfonamide; (Compound B154) 4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-5-yl)-N-phenylbenzenesulfonamide; (Compound B155) N-[3-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b]-[1,4]diazepin-5-yl)phenyl]-2-naphthalenesulfonamide; (Compound B156) N-[3-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b]-[1,4]diazepin-5-yl)phenyl]-1-naphthalenesulfonamide; (Compound B157) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5yl)phenyl]cyclohexanesulfonamide; (Compound B158) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5yl)phenyl]-3-pyridinesulfonamide hydrochloride; (Compound B159) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-4-isopropylbenzenesulfonamide; (Compound B160) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]phenylmethanesulfonamide;

[0158] (Compound B161) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5yl)phenyl]-2-thiophenesulfonamide; (Compound B162) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5yl)phenyl]-2-naphthalenesulfonamide; (Compound B163) 4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl 3-bromobenzenesulfonate; (Compound B164) N-benzyl-N-[4-(1-benzyl-2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5yl)phenyl]-2-nitrobenzenesulfonamide; (Compound B165) N-benzyl-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5yl)phenyl]-2-nitrobenzenesulfonamide; (Compound B166) 3-bromo-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-N-methylbenzenesulfonamide; (Compound B167) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho-[1,2-b][1,4]-diazepin-5-yl)phenyl]-N-methyl-2-nitrobenzenesulfonamide; (Compound B168) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho-[1,2-b][1,4]-diazepin-5-yl)phenyl]-N-(2-hydroxyethyl)-2-nitrobenzenesulfonamide; (Compound B169) N-[4-(7-chloro-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-1-yl)phenyl]benzenesulfonamide; (Compound B170) N-[4-(7-bromo-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-1-yl)phenyl]benzenesulfonamide;

[0159] (Compound B171) N-[4-[(2,4-dioxo-7-(trifluoromethyl)-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-1-yl)]phenyl]benzenesulfonamide; (Compound B172) N-[4-(2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-1-yl)phenyl]benzenesulfonamide; (Compound B173) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]methanesulfonamide; (Compound B174) 1-(3-bromophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]methanesulfonamide; (Compound B175) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho-[1,2-b][1,4]-diazepin-5-yl)phenyl]-2-trifluoromethylbenzenesulfonamide; (Compound B176) N-[4-(7-bromo-6-methyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-1-yl)phenyl]benzenesulfonamide; (Compound B177) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]methanesulfonamide; (Compound B178) 3-bromo-N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]benzenesulfonamide; (Compound B179) N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-3-methoxybenzenesulfonamide; (Compound B180) 1-(2-bromophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]methanesulfonamide;

[0160] (Compound B181) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-1-(2-methylphenyl)methanesulfonamide; (Compound B182) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-1-(2-nitrophenyl)methanesulfonamide; (Compound B183) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-2-phenylethanesulfonamide; (Compound B184) 1-(2,3-Dichlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]methanesulfonamide; (Compound B185) 1-(2-Chlorophenyl)-N-[4-(2,4-dioxo-7-methoxy-1H-benzo[1,2-b][1,4]diazepin-1-yl)phenyl]methanesulfonamide; (Compound B186) 1-(2-Chlorophenyl)-N-[4-(2,4-dioxo-7-hydroxy-1H-benzo[1,2-b][1,4]diazepin-1-yl)phenyl]methanesulfonamide; (Compound B187) 1-(4-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]methanesulfonamide; (Compound B188) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)benzyl]methanesulfonamide; (Compound B189) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)-2-methoxyphenyl]methanesulfonamide; (Compound B190) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)-2-hydroxyphenyl]methanesulfonamide;

[0161] (Compound B191) 1-(2,6-dichlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]methanesulfonamide; (Compound B192) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-6-methyl-1H-benzo[1,2-b][1,4]diazepin-1-yl)phenyl]methanesulfonamide; (Compound B193) 1-(2-chlorophenyl)-N-[3-(2,4-dioxy-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)propyl]methanesulfonamide; (Compound B194) 1-(2-chlorophenyl)-N-[2-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)ethyl]methanesulfonamide; (Compound B195) N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-1-(2-iodophenyl)methanesulfonamide; (Compound B196) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-N-methylmethanesulfonamide; (Compound B197) (Compound B198) 1-[2-(trifluoromethyl)phenyl]-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]phenyl-N-methylmethanesulfonamide; (Compound B199) 1-(2-ethylphenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]phenyl-N-methylmethanesulfonamide;(Compound B200) 1-(2,3-dimethylphenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]phenyl-N-methylmethanesulfonamide;

[0162] (Compound B201) 2-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]phenyl-N-methylethanesulfonamide; (Compound B202) 1-(2-nitrophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]phenyl-N-methylmethanesulfonamide; (Compound B203) 1-(2-aminophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]phenyl-N-methylmethanesulfonamide; (Compound B204) 1-(2-dimethylaminophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]phenyl-N-methylmethanesulfonamide; (Compound B205) 5-[4-[(pyridin-4-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione hydrochloride; (Compound B206) 5-[4-[2-[(pyridin-3-yl)oxy]acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione hydrochloride; (Compound B207) 5-[4-[(pyridin-3-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione hydrochloride; (Compound B208) 5-[4-[(2-methylpyridin-3-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione hydrochloride; (Compound B209) 5-[4-[(2-chloropyridin-3-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B210) 5-[4-[2-[(pyridin-2-yl)oxy]acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione;

[0163] (Compound B211) 5-[4-[[4-(trifluoromethyl)pyridin-3-yl]carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (Compound B212) 5-[4-[(2-chloropyridin-3-yl)carbonylamino]phenyl]-1H-[1,4]diazepino[2,3-f]isoquinoline-2,4(3H,5H)-dione; (Compound B213) 5-[4-[(2-chloropyridin-3-yl)carbonylamino]phenyl]-8,9,10,11-tetrahydro-1H-[1,4]diazepino[2,3-f]isoquinoline-2,4(3H,5H)-dione; and (Compound B214) 5-[4-[(2-isopropylbenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione.

[0164] Compounds or pharmaceutically acceptable salts thereof that are more suitable as active ingredients of the pharmaceutical composition of the present invention are encompassed by the compounds represented by general formulas (A) to (BII) or pharmaceutically acceptable salts thereof. More specifically, 5-[3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; 5-[3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione sodium salt; 5-[3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione. Potassium salt; 5-[3-(5-thioxo-4H-[1,2,4]oxadiazol-3-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; 5-[3-(5-thioxo-4H-[1,2,4]oxadiazol-3-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione Sodium salt; 5-[4-fluoro-3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; 5-[4-fluoro-3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione Sodium salt; 5-[4-[2-(trifluoromethyl)benzoyl]aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; 5-[4-[(2-chlorophenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; 1-[4-(2,4-dioxo-1,2,3,4-tetrafluoroethylene) Hydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-3-phenylurea; 5-[4-(2-iodobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; 5-[4-[(2-ethylbenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione;5-[4-(2-tert-butylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; 5-[4-(2-iodobenzoyl)aminophenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; 5-[4-(6-chloro-2-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; N-[4-(2,4-dioxo-1, 2,3,4-Tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]benzenesulfonamide; 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]methanesulfonamide; 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]methanesulfonamide; 1-(2-bromophenyl)-N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]methanesulfonamide; )-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]methanesulfonamide; N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-1-(2-methylphenyl)methanesulfonamide; N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-2-phenylethanesulfonamide; 1-(2-chlorophenoxy)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-2-phenylethanesulfonamide; 1-(2-chlorophenyl)-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepin-5-yl)phenyl]methanesulfonamide; 5-[4-[(2-methylpyridin-3-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione hydrochloride;Examples include 5-[4-[(2-chloropyridin-3-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; 5-[4-[2-[(pyridin-2-yl)oxy]acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; and 5-[4-[(2-isopropylbenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione. However, the active ingredient of the pharmaceutical composition of the present invention is not limited to the above-mentioned specific compounds or pharmaceutically acceptable salts thereof.

[0165] Compounds or pharmaceutically acceptable salts thereof further suitable as an active ingredient of the pharmaceutical composition of the present invention are encompassed by the compounds represented by general formulas (A) to (BII) or pharmaceutically acceptable salts thereof. More specifically, 5-[3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; 5-[3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione. Sodium salt; 5-[3-(5-thioxo-4H-[1,2,4]oxadiazol-3-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; 5-[3-(5-thioxo-4H-[1,2,4]oxadiazol-3-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione sodium salt; 5-[4-[2-(trifluoromethyl)benzoyl]aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; 5-[4-(2-iodobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione, and 5-[4-(6-chloro-2-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione. However, the active ingredient of the pharmaceutical composition of the present invention is not limited to the above-mentioned specific compounds or pharmaceutically acceptable salts thereof.

[0166] The compounds represented by the above general formulas (A) to (BII) may exist as stereoisomers such as cis-trans isomers, optically active compounds, and racemates, and all of these are included in the present invention.

[0167] The compounds represented by the above general formulas (A) to (BII) may have tautomers, but these tautomers exhibit activity equivalent to that of the compounds and are included in the present invention.

[0168] Furthermore, the compounds represented by the above general formulas (A) to (BII) may have one or more asymmetric carbon atoms depending on the type of substituent, and any optical isomer based on these asymmetric carbon atoms, any mixture of optical isomers, racemates, diastereoisomers based on two or more asymmetric carbon atoms, or any mixture of diastereoisomers may be used as the active ingredient of the pharmaceutical composition of the present invention. When the compounds represented by the above general formulas (AI) to (BII) contain a double bond or a cyclic structure, geometric isomers may exist, and in addition to pure geometric isomers, mixtures of these isomers in any ratio may be used as the active ingredient of the pharmaceutical composition of the present invention.

[0169] In addition to the compounds represented by the above general formulas (A) to (BII), any solvates of the free or salt forms of the compounds may be used as the active ingredient of the pharmaceutical composition of the present invention. The solvates include hydrates.

[0170] In this specification, unless otherwise specified, the compounds represented by the above general formulas (A) to (BII) may include cis-trans isomers, optically active compounds, stereoisomers such as racemates, tautomers, any optical isomers based on an asymmetric carbon, racemates, diastereoisomers based on two or more asymmetric carbons, and mixtures thereof of the compounds.

[0171] In addition to the compounds represented by the above general formulas (A) to (BII), acid addition salts or base addition salts of these compounds may also be used as active ingredients in the pharmaceutical composition of the present invention. Examples of acid addition salts that can be used include, but are not limited to, mineral acid salts such as hydrochloride, sulfate, or nitrate, and organic acid salts such as methanesulfonate, p-toluenesulfonate, oxalate, or malate. Examples of base addition salts that can be used include, but are not limited to, metal salts such as lithium salt, sodium salt, potassium salt, magnesium salt, or calcium salt, ammonium salt, or organic amine salts such as triethylamine salt or ethanolamine salt. Of these salts, it is preferable to use a pharmaceutically acceptable salt as the active ingredient in the pharmaceutical composition of the present invention.

[0172] The pharmaceutical composition of the present invention can be used for the prevention or treatment of cerebral aneurysms. It can also be used to prevent rupture of cerebral aneurysms. Preferably, it can be used to inhibit the growth or occurrence of cerebral aneurysms. More preferably, it can be used to inhibit the occurrence of cerebral aneurysms after surgical treatment, and further, it can be used to prevent the recurrence of cerebral aneurysms, and further, it can be used to inhibit the occurrence of cerebral aneurysms after endovascular treatment.

[0173] The pharmaceutical composition of the present invention can be administered orally or parenterally. The pharmaceutical composition of the present invention can be prepared in an appropriate dosage form such as tablets, granules, powders, capsules, suspensions, inhalants, inhalation powders, inhalation solutions, inhalation aerosols, ointments, gels, creams, compresses, patches, liniments, tapes, poultices, injections, or suppositories, according to a conventional method in the technical field of formulation. In one embodiment, the "pharmaceutical composition" comprises the active ingredient and a pharmaceutically acceptable excipient.

[0174] These preparations can be manufactured using common techniques, and for example, in the case of tablets, pharmaceutically acceptable additives such as ordinary excipients, disintegrants, binders, lubricants, or pigments can be used. Examples of excipients include lactose, D-mannitol, crystalline cellulose, and glucose; examples of disintegrants include starch and carboxymethylcellulose calcium (CMC-Ca); examples of lubricants include magnesium stearate and talc; and examples of binders include hydroxypropyl cellulose (HPC), gelatin, and polyvinylpyrrolidone (PVP).

[0175] Pharmaceutically acceptable additives such as solvents, stabilizers, solubilizers, suspending agents, emulsifiers, soothing agents, buffers, or preservatives are used in the preparation of injections. These pharmaceutically acceptable additives and preparation methods for formulations can be appropriately selected by those skilled in the art. That is, the pharmaceutical composition of the present invention can be provided as a pharmaceutical composition containing the active ingredient and pharmaceutically acceptable additives.

[0176] Inhalants for parenteral administration include aerosols, powders for inhalation, liquids for inhalation (e.g., solutions for inhalation, suspensions for inhalation, etc.), and capsule-shaped inhalants, and the liquids for inhalation may be in a form that is dissolved or suspended in water or other suitable medium before use. These inhalants can be administered using an appropriate inhalation container; for example, a sprayer (atomizer, nebulizer) or the like can be used when administering liquids for inhalation, and a powder inhaler or the like can be used when administering powders for inhalation.

[0177] These inhalants are produced according to known methods. For example, a compound represented by general formula (A) to (BII) is powdered or liquid, blended with an inhalation propellant or carrier, and filled into an appropriate inhalation container. When powdering a compound represented by general formula (A) to (BII), it is powdered according to conventional methods. For example, it is finely powdered with lactose, starch, magnesium stearate, or the like, and then homogeneously mixed or granulated to prepare a powder. When liquefying a compound represented by general formula (A) to (BII), for example, the compound may be dissolved in a liquid carrier such as water, physiological saline, or an organic solvent. Examples of propellants that can be used include conventional propellants, such as alternatives to chlorofluorocarbons, liquefied gas propellants (e.g., fluorocarbons, liquefied petroleum, diethyl ether, dimethyl ether, etc.), compressed gases (e.g., soluble gases (e.g., carbon dioxide, nitrous oxide, etc.), or insoluble gases (e.g., nitrogen gas, etc.)).

[0178] The inhalant may further contain, as necessary, pharmaceutically acceptable additives. The additives may be any commonly used additives, for example, solid excipients (e.g., sucrose, lactose, glucose, mannitol, sorbitol, maltose, cellulose, etc.), liquid excipients (e.g., propylene glycol, etc.), binders (starch, dextrin, methylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, polyethylene glycol, sucrose, etc.), lubricants (e.g., magnesium stearate, light anhydrous silicic acid, talc, sodium lauryl sulfate, etc.), flavoring agents (e.g., citric acid, menthol, ammonium glycyrrhizinate, glycine, orange powder, etc.), preservatives (e.g., sodium benzoate, sodium bisulfite, etc.), and the like. In the case of inhalation solutions, additives such as sodium thorium, methylparaben, or propylparaben, stabilizers (e.g., citric acid or sodium citrate, etc.), suspending agents or emulsifiers (e.g., methylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, lecithin, or sorbitan trioleate, etc.), dispersants (e.g., surfactants, etc.), solvents (e.g., water, etc.), isotonicity agents (e.g., sodium chloride or concentrated glycerin, etc.), pH adjusters (e.g., hydrochloric acid or sulfuric acid, etc.), solubilizers (e.g., ethanol, etc.), preservatives (benzalkonium chloride or parabens, etc.), colorants, buffers (sodium phosphate or sodium acetate, etc.), thickeners (carboxyvinyl polymers, etc.), or absorption enhancers may be used. For example, in the case of inhalation solutions, preservatives, colorants, buffers, isotonicity agents, thickeners, or absorption enhancers may be appropriately selected and prepared as needed. In the case of powders for inhalation, lubricants, binders, excipients, colorants, preservatives, absorption enhancers (bile salts, chitosan, etc.), etc. may be appropriately selected as needed to prepare the powders.

[0179] Furthermore, inhalants may contain a biodegradable polymer to sustain the release of the compound represented by general formula (A) to (BII). Examples of biodegradable polymers include fatty acid ester polymers or copolymers thereof, polyacrylic acid esters, polyhydroxybutyric acids, polyalkylene oxalates, polyorthoesters, polycarbonates, and polyamino acids, and these may be used alone or in combination. Phospholipids such as egg yolk lecithin, chitosan, etc. may also be used. Examples of fatty acid ester polymers or copolymers thereof include polylactic acid, polyglycolic acid, polycitric acid, polymalic acid, and lactic acid-glycolic acid copolymers, and these may be used alone or in combination. Other examples include poly-α-cyanoacrylic acid esters, poly-β-hydroxybutyric acid, polytrimethylene oxide, polyorthoesters, polyorthocarbonates, polyethylene carbonates, poly-γ-benzyl-L-glutamic acid, and poly-L-alanine, and these may be used alone or in combination. Preferably, polylactic acid, polyglycolic acid, or lactic acid-glycolic acid copolymer is used, and more preferably, lactic acid-glycolic acid copolymer. Furthermore, microspheres or nanospheres encapsulating a drug may be prepared using biodegradable polymers such as lactic acid-glycolic acid copolymer.

[0180] Ointments are prepared by known or commonly used methods. For example, they are prepared by triturating or dissolving one or more active substances in a base. The ointment base is selected from known or commonly used bases. For example, higher fatty acids or higher fatty acid esters (adipic acid, myristic acid, palmitic acid, stearic acid, oleic acid, adipate esters, myristate esters, palmitate esters, stearate esters, oleate esters, etc.), waxes (beeswax, spermaceti, ceresin, etc.), surfactants (polyoxyethylene alkyl ether phosphate esters, etc.), higher alcohols (cetanol, stearyl alcohol, cetostearyl alcohol, etc.), silicone oils (dimethylpolysiloxane, etc.), hydrocarbons (hydrophilic petrolatum, white petrolatum, purified lanolin, liquid paraffin, etc.), glycols (ethylene glycol, diethylene glycol, propylene glycol, polyethylene glycol, macrogol, etc.), vegetable oils (castor oil, olive oil, sesame oil, turpentine oil, etc.), animal oils (mink oil, egg yolk oil, squalane, squalene, etc.), water, absorption enhancers, and anti-rash agents may be used alone or in combination of two or more. Furthermore, the composition may contain a moisturizing agent, a preservative, a stabilizer, an antioxidant, a flavoring agent, or the like.

[0181] Gels are prepared by known or commonly used methods. For example, they are prepared by dissolving one or more active substances in a base. The gel base can be selected from known or commonly used materials. For example, a single or a mixture of two or more of the following can be used: lower alcohols (e.g., ethanol or isopropyl alcohol), gelling agents (e.g., carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, or ethylcellulose), neutralizing agents (e.g., triethanolamine or diisopropanolamine), surfactants (e.g., polyethylene glycol monostearate), gums, water, absorption enhancers, or anti-rash agents. Furthermore, the gel may contain preservatives, antioxidants, flavoring agents, etc.

[0182] Creams are manufactured using known or commonly used formulations. For example, they are manufactured or prepared by dissolving or emulsifying one or more active substances in a base. The cream base is selected from known or commonly used bases. For example, a single or a mixture of two or more of the following may be used: higher fatty acid esters, lower alcohols, hydrocarbons, polyhydric alcohols (propylene glycol, 1,3-butylene glycol, etc.), higher alcohols (2-hexyldecanol, cetanol, etc.), emulsifiers (polyoxyethylene alkyl ethers, fatty acid esters, etc.), water, absorption enhancers, or anti-rash agents. Furthermore, the cream may contain preservatives, antioxidants, flavoring agents, etc.

[0183] Poultices are prepared using known or commonly used formulations. For example, they are prepared by dissolving one or more active substances in a base, kneading the mixture, and spreading it on a support. The poultice base can be selected from known or commonly used bases. For example, thickeners (polyacrylic acid, polyvinylpyrrolidone, gum arabic, starch, gelatin, methylcellulose, etc.), humectants (urea, glycerin, propylene glycol, etc.), fillers (kaolin, zinc oxide, talc, calcium, magnesium, etc.), water, solubilizers, tackifiers, and anti-rash agents can be used alone or in combination of two or more. They may also contain preservatives, antioxidants, flavoring agents, etc.

[0184] Patches are manufactured using known or commonly used formulations. For example, they are manufactured by dissolving one or more active substances in a base and spreading the resulting mixture on a support. The base for the patch is selected from known or commonly used bases. For example, a polymer base, oil or fat, higher fatty acid, tackifier, or anti-rash agent may be used alone or in combination of two or more. Furthermore, the patch may contain a preservative, antioxidant, flavoring agent, etc.

[0185] Liniments are manufactured using known or commonly used formulations. For example, they are manufactured or prepared by dissolving, suspending, or emulsifying one or more active ingredients in one or more of water, alcohol (ethanol, polyethylene glycol, etc.), higher fatty acids, glycerin, soap, emulsifiers, suspending agents, etc. They may further contain preservatives, antioxidants, flavoring agents, etc.

[0186] The dosage of the pharmaceutical composition of the present invention is not particularly limited, but generally, for an adult, the active ingredient can be administered in an amount of about 0.01 μg to 100 mg, preferably 0.3 μg to 10 mg, per day for inhalants, inhalable powders, inhalable liquids, or inhalable aerosols; about 0.01 mg to 1000 mg per day for ointments, gels, creams, compresses, patches, liniments, tapes, or poultices; about 0.01 mg to 100 mg per day for injections; and about 0.01 mg to 2000 mg per day for oral administration. However, the dosage is not limited to the above amounts and is determined appropriately depending on the administration method, the age, weight, sex, symptoms, or drug sensitivity of the subject, etc., and the dosage may be adjusted depending on the state of symptom improvement, and can be increased or decreased depending on the age, symptoms, etc.

[0187] The pharmaceutical composition of the present invention can be used in combination with other drugs. The individual components of such a combination can be administered separately or simultaneously in separate or single preparations during the treatment or prevention period. Therefore, the present invention should be interpreted as including all simultaneous or different administrations, and the administration in the present invention should be interpreted accordingly. The scope of the combination of the pharmaceutical composition of the present invention with other drugs essentially includes any combination with any pharmaceutical preparation useful for the treatment or prevention of cerebral aneurysms as described above.

[0188] Each formulation in the combination preparation of the present invention can be selected from various forms and can be prepared in the same manner as the above-mentioned preparations. Furthermore, a combination preparation containing the pharmaceutical composition of the present invention and other drugs can also be easily prepared by those skilled in the art using conventional methods or techniques. The above combinations include not only a combination of the pharmaceutical composition of the present invention with one other active substance, but also two or more other active substances. There are many examples of combinations of the pharmaceutical composition of the present invention with one, two, or more active substances selected from other drugs.

[0189] Drugs that can be combined with the pharmaceutical composition of the present invention include, for example, antiplatelet drugs, antihypertensive drugs, vasodilators, etc. The pharmaceutical composition of the present invention can also be combined with herbal medicines.

[0190] Examples of the antiplatelet agent include aspirin, clopidogrel, cilostazol, ethyl icosapentate, beraprost, limaprost, sarpogrelate hydrochloride, dipyridamole, prasugrel, and ticagrelor.

[0191] Examples of the antihypertensive drugs include calcium channel blockers, angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin II receptor blockers (ARBs), diuretics, α-blockers, β-blockers, and central sympathetic nervous system inhibitors (central α2 agonists), etc. Examples of the vasodilators include calcium channel blockers, nitrate vasodilators, renin inhibitors, angiotensin-converting enzyme inhibitors (ACE inhibitors), and angiotensin II receptor blockers (ARBs), etc. Examples of the calcium antagonists include amlodipine, felodipine, isradipine, nicardipine, nifedipine, nimodipine, nisoldipine, nitrendipine, lacidipine, nilvadipine, manidipine, barnidipine, lercanidipine, cilnidipine, benidipine, clevidipine, levamlodipine malate, azelnidipine, aranidipine, efonidipine, remildipine, vatanidipine hydrochloride, dalodipine, flordipine, terdipine hydrochloride, and kirenidipine hydrochloride (all dihydropyridine-based), verapamil (phenylalkylamine-based), and diltiazem (benzothiazepine-based). Examples of the angiotensin-converting enzyme inhibitor include captopril, enalapril, lisinopril, perindopril, ramipril, quinapril, benazepril, cilazapril, fosinopril, trandolapril, spirapril, delapril, moexipril, temocapril, zofenopril, imidapril, alacepril, benazeprilat, ceronapril, indolapril hydrochloride, libenzapril, pentopril, pivopril, enalaprilat, fosinoprilat, quinaprilat, spiraprilat, zofenoprilat arginine, and teprotide. Examples of the angiotensin II receptor antagonists include losartan, eprosartan, valsartan, irbesartan, tasosartan, candesartan, telmisartan, olmesartan, azilsartan, fimasartan, pratosartan, saralasin acetate, forasartan, and saprisartan potassium. Examples of the diuretics include bendroflumethiazide, hydroflumethiazide, hydrochlorothiazide, chlorothiazide, polythiazide, trichlormethiazide, cyclopenthiazide, methyclothiazide, cyclothiazide, mebutizide, benzthiazide,Penflutizide, benzylhydrochlorothiazide, ethiazide, flumethiazide, althiazide, buthiazide, epithiazide and methalthiazide (all thiazide diuretics), indapamide, tripamide and mefruside (all thiazide-like (non-thiazide) diuretics), furosemide, torasemide and azosemide (all loop diuretics), spironolactone, canrenoate potassium, canrenone, eplerenone, finerenone, amiloride, triamterene, prorenoate potassium and spiroxasone (all , potassium-sparing diuretics), spironolactone, canrenoate potassium, canrenone, eplerenone, finerenone, drospirenone, esaxerenone, disirenone, mexrenoate potassium, prorenoate potassium and spiroxasone (all aldosterone antagonists), urapidil, terazosin, prazosin, doxazosin and bunazosin (all alpha-blockers), alprenolol, oxprenolol, pindolol, propranolol, timolol, sotalol, nadolol, mepindolol, carteolol tertatolol, bopindolol, bupranolol, penbutolol, cloranolol, levobunolol, metipranolol, befunolol, bufetolol hydrochloride, medroxalol, tilisolol, indenolol, bucumolol hydrochloride, primidrol, adaprolol maleate, alprenoxime hydrochloride, bunolol hydrochloride, dexpropranolol hydrochloride, diacetolol hydrochloride, flestolol sulfate, pamatolol sulfate and beradilol monoethyl maleate (all beta-blockers), practic lol, metoprolol, atenolol, acebutolol, betaxolol, bisoprolol, celiprolol, esmolol, epanolol, esatenolol, nebivolol, talinolol, landiolol, cetamolol hydrochloride, cycloprolol hydrochloride and levobetaxolol hydrochloride (all of which are β1 selective blockers), rauwolfia alkaloids, methyldopa, clonidine, guanfacine, tolonidine, moxonidine, rilmenidine and guanabenz (all of which are central sympathetic nervous system depressants), etc. Examples of the nitrate vasodilators include nitroglycerin, pentaerythritol tetranitrate, propatyl nitrate, isosorbide dinitrate, tetrol nitrate phosphate, erythrityl tetranitrate,Examples of the renin inhibitor include remikiren, aliskiren, enalkiren, ditekiren, terlakiren, and zankiren hydrochloride.

[0192] Examples of the intravascular treatment according to the present invention include coil embolization, stent-assisted coil embolization, and flow diverter placement.

[0193] The present invention has the following aspects. <1a> A method for preventing or treating cerebral aneurysm, comprising administering to a subject in need thereof (e.g., a mammal including a human) an effective amount for prevention, suppression, or treatment of a compound having P2X4 receptor antagonistic activity (e.g., a compound represented by general formula (A) to (BII)) or a pharmaceutically acceptable salt thereof; <2a> The method according to <1a>, wherein the prevention or treatment of cerebral aneurysm is prevention of rupture of cerebral aneurysm; <3a> The method according to <1a> or <2a>, wherein the prevention or treatment of cerebral aneurysm is inhibition of growth of cerebral aneurysm; <4a> The method according to any one of <1a> to <2a>, wherein the prevention or treatment of cerebral aneurysm is inhibition of occurrence of cerebral aneurysm; <5a> The method according to any one of <1a> to <4a>, wherein the prevention or treatment of cerebral aneurysm is inhibition of occurrence after surgical treatment of cerebral aneurysm; <6a> The method according to any one of <1a> to <5a>, wherein the inhibition of occurrence after surgical treatment is prevention of recurrence; or <7a> The method according to any one of <1a> to <6a>, wherein the surgical treatment is an intravascular treatment.

[0194] The present invention has the following other aspects. <1b> A compound having P2X4 receptor antagonistic activity (e.g., a compound represented by general formula (A) to (BII)) or a pharmaceutically acceptable salt thereof for use in the prevention or treatment of cerebral aneurysm; <2b> A compound or a pharmaceutically acceptable salt thereof for use according to <1b>, wherein the prevention or treatment of cerebral aneurysm is prevention of rupture of cerebral aneurysm; <3b> A compound or a pharmaceutically acceptable salt thereof for use according to <1b> or <2b>, wherein the prevention or treatment of cerebral aneurysm is inhibition of growth of cerebral aneurysm; <4b> A compound or a pharmaceutically acceptable salt thereof for use according to any one of <1b> to <2b>, wherein the prevention or treatment of cerebral aneurysm is inhibition of occurrence of cerebral aneurysm; <5b> A compound or a pharmaceutically acceptable salt thereof for use according to any one of <1b> to <4b>, wherein the prevention or treatment of cerebral aneurysm is inhibition of occurrence after surgical treatment of cerebral aneurysm; <6b> A compound or a pharmaceutically acceptable salt thereof for use according to any one of <1b> to <5b>, wherein the suppression of occurrence after the surgical treatment is prevention of recurrence; or <7b> A compound or a pharmaceutically acceptable salt thereof for use according to any one of <1b> to <6b>, wherein the surgical treatment is intravascular treatment.

[0195] The present invention has the following further aspects. <1c> Use of a compound having P2X4 receptor antagonistic activity (e.g., a compound represented by general formula (A) to (BII)) or a pharmaceutically acceptable salt thereof for producing a pharmaceutical composition for preventing or treating cerebral aneurysms; <2c> The use according to <1c>, wherein the prevention or treatment of cerebral aneurysms is prevention of rupture of cerebral aneurysms; <3c> The use according to <1c> or <2c>, wherein the prevention or treatment of cerebral aneurysms is inhibition of growth of cerebral aneurysms; <4c> The use according to any one of <1c> to <2c>, wherein the prevention or treatment of cerebral aneurysms is inhibition of occurrence of cerebral aneurysms; <5c> The use according to any one of <1c> to <4c>, wherein the prevention or treatment of cerebral aneurysms is inhibition of occurrence after surgical treatment of cerebral aneurysms; <6c> The use according to any one of <1c> to <5c>, wherein the inhibition of occurrence after surgical treatment is prevention of recurrence; or <7c> The use described in any one of <1c> to <6c>, wherein the surgical treatment is an endovascular treatment.

[0196] The present invention will be described in more detail below with reference to examples, but the scope of the present invention is not limited to the following examples. In the following examples, 5-[4-(2-iodobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione (the compound of Example 48 in WO2013 / 105608, hereinafter referred to as "Compound A") and other compounds shown below were used as P2X4 receptor antagonists: 5-[3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione Sodium salt; 5-[4-[2-(trifluoromethyl)benzoyl]aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; 5-[4-[(2-chlorophenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; 1-[4-(2,4-dioxo-1,2 ,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-3-phenylurea; 5-[4-[(2-ethylbenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; 5-[4-(2-tert-butylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4] Diazepine-2,4(3H,5H)-dione; 5-[4-(2-iodobenzoyl)aminophenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; 5-[4-(6-chloro-2-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4 (3H,5H)-dione; N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]benzenesulfonamide; 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]methanesulfonamide;1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]methanesulfonamide; 1-(2-bromophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]methanesulfonamide; N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-1-(2-methylphenyl)methanesulfonamide; N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1, 2-b][1,4]diazepin-5-yl)phenyl]-2-phenylethanesulfonamide; 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-N-methylmethanesulfonamide; 1-(2-chlorophenyl)-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepin-5-yl)phenyl]methanesulfonamide; 5-[4-[(2-methylpyridin-3-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione Hydrochloride salt; 5-[4-[(2-chloropyridin-3-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; 5-[4-[2-[(pyridin-2-yl)oxy]acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione and 5-[4-[(2-isopropylbenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione.

[0197] Example 1 Measurement of P2X4 receptor antagonistic activity of the compound of the present invention (Test method) The P2X4 receptor antagonistic activity of the compound of the present invention was measured. ATP receptor (human P2X4) was introduced into 1321N1 cells and used as a stable P2X4 receptor expression system. P2X4 receptor-expressing cells were seeded on a 96-well plate and incubated at 37°C, 5% CO ２ The cells were cultured under these conditions for 24 hours and then used for calcium measurement. The calcium fluorescent indicator Fura-2 AM was dissolved in extracellular solution for calcium imaging, and the seeded cells were treated with this solution. The cells were then allowed to stand at room temperature for 45 minutes to allow Fura-2 AM to enter the cells. Measurements were performed using an EnVision microplate reader (PerkinElmer). Light emitted from a xenon lamp was passed through 340 nm and 380 nm filters, respectively, and the 510 nm fluorescence F340 and F380 values ​​emitted upon irradiation were observed. Changes in the ratio F340 / F380 were used as an index of changes in intracellular calcium. ATP was added to each well to a final concentration of 1 μM, and the ATP-induced intracellular calcium response was observed over time. The inhibitory activity of the test substance was measured by pretreating the test substance with ATP for 15 minutes and calculated by comparing the activity with that in the absence of the test substance. The results are shown in Table 29 below.

[0198] (Test results)

[0199] Example 2: Confirmation of P2X4 Receptor Expression in Vascular Endothelial Cells Using Human Cerebral Aneurysm Specimens (Objective of the Study) Human cerebral aneurysm specimens were used to confirm the expression of P2X4 receptors in endothelial cells of cerebral blood vessels with aneurysms. (Test Method) Human cerebral aneurysm specimens were obtained by resecting a portion of the aneurysm wall after craniotomy and clipping surgery to treat cerebral aneurysms. The specimens were then fixed in 10% neutral buffered formalin, paraffin-embedded, and sliced ​​to a thickness of 4 micrometers for the following study. After deparaffinization and blocking with 10% donkey serum, the specimens were reacted with anti-CD31 antibody (#ab182981, Abcam) and anti-P2X4 antibody (#APR-002, Alomone Labs), followed by exposure to a secondary antibody conjugated with a fluorescent dye. Images were then taken using a confocal microscope system (Olympus, FV-3000). (Test results) As shown in Figure 1, when the stained areas treated with anti-CD31 antibody and those treated with anti-P2X4 antibody were merged, it was observed that roughly the same areas were stained, confirming that P2X4 receptors are expressed in the endothelial cells of cerebral blood vessels where aneurysms have developed.

[0200] Example 3: Inhibitory effect on the occurrence of cerebral aneurysms (Preparation of a P2X4 receptor-deficient model) The P2X4 receptor-deficient model was established by deleting 171 base pairs from the promoter region to exon 1 of the P2rx4 gene using the CRISPR / Cas9 system. This rat strain is available from the National BioResource Project Rat established at Kyoto University (SD-P2rx4 em18Taoki (Registered as No. 0961). Wild-type and P2X4 receptor-deficient animals obtained by crossbreeding P2X4 receptor heterozygous deficient animals were used in the experiment.

[0201] (Preparation of Reagents) Solid Dispersion: Production by Spray Drying Method 1) Preparation of Spray Solution 50 g of Compound A was dissolved in 17.98 kg of THF (Kanto Chemical, containing stabilizers). 200 g of HPMC (Shin-Etsu Chemical Co., Ltd.) and 50 g of SLS (Kokusan Kagaku Co., Ltd.) were added sequentially to a mixed solvent of 7.89 kg of ethanol (Kanto Chemical Co., Ltd.) and 2.5 kg of ion-exchanged water under stirring, and the mixture was then sieved (using 300 and 500 mesh sieves). The two solutions were mixed and stirred to prepare a spray solution with a weight ratio of Compound A / HPMC / SLS of 1:4:1. 2) Spray drying and secondary drying The prepared spray solution was pumped into a spray dryer (CL-8i, Okawahara Kakoki) via a peristaltic pump, and spray drying was carried out under the following conditions: a raw solution throughput of 4 kg / h, a two-fluid nozzle spray gas pressure of 0.2 MPa, an inlet temperature of 120°C, and an outlet temperature of 70°C. The obtained primary dried product (270.18 g) was further subjected to secondary drying (40°C / 60 hours) in a vacuum dryer, yielding 237.4 g of a solid dispersion as a white powder (recovery rate 79.1%).

[0202] (Test Method) Starting the day before cerebral aneurysm induction surgery, 7-week-old male SD rats (Slc:SD) were fed ad libitum with a special diet (0% or 0.15% solid dispersion of Compound A, 8% sodium chloride, and 0.12% 3-aminopropionitrile (Tokyo Kasei)). (Each group consisted of 5-6 rats, with two independent experiments conducted, resulting in n=10-12 rats per group. A small number of rats died during the experiment or could not be evaluated due to technical problems with specimen preparation, and their data were deleted, resulting in n=9-12 rats.) Cerebral aneurysm induction surgery was performed under general anesthesia with isoflurane (induction 5.0%, maintenance 1.5-2.0%, #IYESC-0001, Pfizer Inc.) by ligating the left common carotid artery and left renal artery. Postoperative pain was managed with a subcutaneous injection of 1 mg / kg of Metacam (Boehringer Ingelheim) as needed. After surgery, the mice were maintained with free access to water and food for 5 days. Blood pressure was measured without anesthesia using the tail-cuff method to obtain systolic, mean, and diastolic blood pressure values ​​(using a CODA® non-invasive sphygmomanometer for mice and rats, Kent Scientific). The brains were then removed along with their cerebral vessels and post-fixed in 4% paraformaldehyde overnight and then substituted with 30% sucrose solution for at least 1 day. The right anterior cerebral artery branch, where cerebral aneurysms would develop, was then dissected and frozen into thin sections. Elastica van Gieson staining was performed on the thin sections to visualize the internal elastic lamina. Cerebral aneurysm development was assessed using internal elastic lamina rupture as a histological indicator. Cerebral aneurysm development was defined as rupture of the internal elastic lamina under light microscopy.

[0203] (Test Results) As shown in Figure 2, P2X4 was increased by cerebral aneurysm induction surgery. ＋／＋ Cerebral aneurysms were induced in rats (Vehicle group), but P2X4 －／－ In rats (Vehicle group), the induction rate of cerebral aneurysms was approximately 40%. On the other hand, in rats in which compound A-containing samples were administered from the day before the cerebral aneurysm induction surgery, the P2X4 ＋／＋In rats (Compound A group), the incidence of cerebral aneurysms was suppressed to about 40%. －／－ In rats (Compound A group), the induction rate of cerebral aneurysms was significantly higher than that of P2X4. －／－ The results were comparable to those of rats (vehicle group). ＋／＋ In rats, the Compound A group showed an increase in blood pressure compared to the vehicle group, while the P2X4 －／－ In rats, no changes in blood pressure were observed between the vehicle group and the Compound A group. ＋／＋ In rats, blood pressure increases and P2X4 －／－ The disappearance of the effect in rats is presumed to be due to the inhibitory effect of P2X4 receptors expressed in vascular endothelial cells. This result supports the idea that Compound A exerts an inhibitory effect on cerebral aneurysms via P2X4 receptor antagonism. In Figure 2, SBP, MBP, and DBP refer to systolic blood pressure, mean blood pressure, and diastolic blood pressure, respectively.

[0204] The pharmaceutical composition of the present invention is useful as a pharmaceutical composition useful for preventing or treating cerebral aneurysms, particularly as a pharmaceutical composition useful for preventing the rupture of cerebral aneurysms, more particularly as a pharmaceutical composition useful for inhibiting the growth of cerebral aneurysms or inhibiting the occurrence of cerebral aneurysms, and even more particularly as a pharmaceutical composition useful for inhibiting the occurrence of cerebral aneurysms after surgical treatment, useful for preventing the recurrence of cerebral aneurysms, or useful for inhibiting the occurrence of cerebral aneurysms after endovascular treatment, and is expected to be highly effective in each case.

Claims

1. A pharmaceutical composition for preventing or treating cerebral aneurysms, comprising as an active ingredient a compound having P2X4 receptor antagonistic activity or a pharmaceutically acceptable salt thereof.

2. The compound has the following general formula (A): (In the formula, R １Ａ represents a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, or an alkyl group having 1 to 3 carbon atoms substituted with a phenyl group; R ２Ａ and R ３Ａ may be the same or different and represent a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an acylamino group having 2 to 8 carbon atoms, an acylamino group having 2 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkylsulfonylamino group having 1 to 8 carbon atoms, a carboxyl group, an acyl group having 2 to 8 carbon atoms, an alkoxycarbonyl group (the number of carbon atoms in the alkoxy moiety is 1 to 8), a carbamoyl group, an alkylthio group having 1 to 8 carbon atoms, an alkylsulfinyl group having 1 to 8 carbon atoms, an alkylsulfonyl group having 1 to 8 carbon atoms, or a sulfamoyl group; R ４Ａ and R ５Ａ may be the same or different and represent a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, or an alkyl group having 1 to 3 carbon atoms substituted with a phenyl group, and W Ａ The pharmaceutical composition according to claim 1, wherein the compound is represented by the formula (I) wherein R represents a 5- or 6-membered heterocyclic ring containing 1 to 4 nitrogen atoms as ring constituent elements which may have a substituent.

3. The compound has the following general formula (BI): (In the formula, R １Ｂ and R ２Ｂ may be the same or different and represent a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an acylamino group having 2 to 8 carbon atoms, a carboxyl group, an acyl group having 2 to 8 carbon atoms, an alkoxycarbonyl group (the alkoxy moiety has 1 to 8 carbon atoms), a phenyl group which may have a substituent, a pyridyl group which may have a substituent, or an aralkyl group (the aryl moiety has 6 to 10 carbon atoms and the alkylene moiety has 1 to 8 carbon atoms), or R １Ｂ and R ２Ｂ may be taken together with the benzene ring to which they are attached to form a fused ring selected from a naphthalene ring, a quinoline ring, an isoquinoline ring, a tetrahydronaphthalene ring, an indane ring, a tetrahydroquinoline ring, or a tetrahydroisoquinoline ring, and R １Ｂ and R ２Ｂ Together, R １Ｂ and R ２Ｂ are bonded to a ring consisting of carbon atoms, and may be substituted with 1 to 4 substituents, which may be the same or different, selected from an alkyl group having 1 to 8 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an acylamino group having 2 to 8 carbon atoms, a carboxyl group, an acyl group having 2 to 8 carbon atoms, an alkoxycarbonyl group (the alkoxy moiety has 1 to 8 carbon atoms), or an aralkyl group (the aryl moiety has 6 to 10 carbon atoms, and the alkylene moiety has 1 to 8 carbon atoms); ３Ｂ and R ４Ｂ may be the same or different and represent a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an acylamino group having 2 to 8 carbon atoms, a carboxyl group, an acyl group having 2 to 8 carbon atoms, an alkoxycarbonyl group (the alkoxy moiety has 1 to 8 carbon atoms), or an aralkyl group (the aryl moiety has 6 to 10 carbon atoms and the alkylene moiety has 1 to 8 carbon atoms); R ５Ｂ represents a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkyl group having 1 to 8 carbon atoms substituted with a hydroxyl group, or an aralkyl group (the aryl portion has 6 to 10 carbon atoms, and the alkylene portion has 1 to 8 carbon atoms); R ６Ｂ and R ７Ｂ may be the same or different and represent a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, or an amino group; X Ｂ represents C, CH or N; Y Ｂ represents N, NH or C(=O), provided that X Ｂ When N, Y Ｂ is not N or NH, and X Ｂ When is C or CH, Y Ｂ is not C(=O), a double line consisting of a solid line and a dashed line represents a single bond or a double bond, Z Ｂ represents an oxygen atom or a sulfur atom; Ｂ represents a benzene ring, pyridine ring, thiophene ring, pyrimidine ring, naphthalene ring, quinoline ring or indole ring which may have 1 to 4 substituents, which may be the same or different, selected from an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an aralkyl group (the aryl portion has 6 to 10 carbon atoms and the alkylene portion has 1 to 8 carbon atoms), a phenyl group or a pyridyl group, or represents a bond; B Ｂ is N(R ８Ｂ )C(=O),NHCONH,CON(R ９Ｂ ), NHC(=S)NH,N(R １０Ｂ ) SO ２ , S.O. ２ N (R １１Ｂ ) or OSO ２ where R ８Ｂ , R ９Ｂ , R １０Ｂ and R １１Ｂ represents a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkyl group having 1 to 8 carbon atoms substituted with a hydroxyl group, or an aralkyl group (the aryl portion has 6 to 10 carbon atoms, and the alkylene portion has 1 to 8 carbon atoms), Ｂ represents an alkylene chain having 1 to 6 carbon atoms which may have 1 to 4 substituents, which may be the same or different, selected from an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkyl group having 1 to 8 carbon atoms substituted with a hydroxyl group, or an aralkyl group (the aryl portion has 6 to 10 carbon atoms, and the alkylene portion has 1 to 8 carbon atoms), and which may further have a double bond, or a bond; Ｂ is O, S, NR １２Ｂ , or a bond, where R １２Ｂ represents a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkyl group having 1 to 8 carbon atoms substituted with a hydroxyl group, or an aralkyl group (the aryl portion has 6 to 10 carbon atoms and the alkylene portion has 1 to 8 carbon atoms), Ｂ is substituted with an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an acyl group having 2 to 8 carbon atoms, a methylenedioxy group, a carboxyl group, an alkylsulfinyl group having 1 to 6 carbon atoms, an alkylthio group having 1 to 6 carbon atoms, an alkylsulfonyl group having 1 to 6 carbon atoms, an aralkyl group (wherein the carbon atom of the aryl moiety is m represents piperazine, piperidine, morpholine, cyclohexane, benzene, naphthalene, quinoline, quinoxaline, benzimidazole, thiophene, imidazole, thiazole, oxazole, indole, benzofuran, pyrrole, pyridine or pyrimidine, each of which may have 1 to 4 identical or different substituents selected from an optionally substituted phenyl group, an optionally substituted pyridyl group, an optionally substituted imidazolyl group, an optionally substituted oxazolyl group, or an optionally substituted thiazolyl group; and Ｂ represents an integer of 0 to 5. １Ｂ and R ２Ｂ do not form a ring together, and X Ｂ is C, Y Ｂ is N, the double line consisting of a solid line and a dashed line is a double bond, and Z Ｂ is an oxygen atom, and A Ｂ is a benzene ring, and m Ｂ is 0, B Ｂ is C(=O)NH, and E Ｂ is a bond and G Ｂ The pharmaceutical composition according to claim 1, wherein the compound is represented by the formula (I) (excluding the case where R is a phenyl group).

4. The pharmaceutical composition according to claim 1, wherein the compound or a pharmaceutically acceptable salt thereof is a compound or a pharmaceutically acceptable salt thereof selected from the group consisting of the following (A1) to (A21) and (B1) to (B214): (A1) 5-[3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (A2) 5-[3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione sodium salt; (A3) 5-[3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione (A4) 5-[4-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (A5) 5-[4-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione sodium salt; (A6) 1-methyl-5-[3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (A7) 1,3-dimethyl-5-[3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (A8) 5-[2-chloro-5-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (A9) 5-[2-chloro-5-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione sodium salt; (A10) 5-[2-methyl-5-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (A11) 5-[2-methyl-5-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione sodium salt;(A12) 5-[2-bromo-5-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (A13) 5-[3-(2-methyl-2H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (A14) 5-[3-(1-methyl-1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (A15) (A16) 5-[3-(5-oxo-4H-[1,2,4]oxadiazol-3-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (A17) 5-[3-(5-thioxo-4H-[1,2,4]oxadiazol-3-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione sodium salt; (A18) 5-[3-(oxazol-2-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; and (A19) 5-[3-(1H-pyrazol-4-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (A20) 5-[4-fluoro-3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (A21) 5-[4-fluoro-3-(1H-tetrazol-5-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione sodium salt; (B1) 5-(4-benzoylaminophenyl)-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B2) 5-[4-[2-(trifluoromethyl)benzoyl]aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione;(B3) 5-[4-(3-bromobenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B4) 5-[4-[4-(trifluoromethyl)benzoyl]aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B5) 5-[4-(2-methylbenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B6) 5-[4-(2,6-dimethylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B7) (B10) 1-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-3-phenylthiourea; (B11) 5-[4-(2,6-dichlorobenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B8) 5-[4-(3-chlorobenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B9) 5[4-(2-phenylacetylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B10) 1-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-3-phenylthiourea; (B11) (B11) 5-[4-(2,3-dimethoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B12) 5-[4-(2-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B13) 5-[4-[(2-chlorophenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B14) 5-[4-(2,3-dimethylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B15) 5-[4-(2,5-dimethylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione;(B16) 5-[4-(5-bromo-2-chlorobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B17) 5-[4-(2,4-dichlorobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B18) 5-[4-(2-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B19) (B20) 1-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-3-phenylurea; (B21) 5-[4-[(2,6-dichlorophenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B22) 5-[4-[(2-methoxyphenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B23) 5-[4-[(2-hydroxyphenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B24) 1-(2-chlorophenyl)-3-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]thiourea; (B25) 5-[4-[3-(trifluoromethyl)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B26) (B27) 1-(2-chlorophenyl)-3-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]urea;(B28) 5-[4-[(2-phenylpropionyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B29) 5-[4-(2-chloro-3-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B30) 5-[4-(3-phenylpropionylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B31) (B31) 5-[4-[(1H-indole-3-carbonyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B32) 5-[4-(2-chloro-3-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B33) 5-[4-[(2-methyl-2-phenylpropionyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B34) (B35) 5-[4-[2-(2-chloro-4-methoxyphenyl)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B36) 5-[4-[(1-methyl-1H-imidazole-2-carbonyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B37) (B38) 5-[4-[2-(2-chloro-4-hydroxyphenyl)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B39) 5-[4-(3-phenylpropenylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione;(B40) 5-[4-[(3-pyridylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione hydrochloride; (B41) 5-[4-(1H-benzimidazole-2-carbonylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B42) 1-[4-(2,3-dimethylbenzoylamino)phenyl]-7-methoxy-1H-1,5-benzodiazepine-2,4(3H,5H)-dione; (B43) (B44) 5-[4-[(2-chlorobenzoylamino)methyl]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B45) 1-[4-(2,3-dimethylbenzoylamino)phenyl]-7-hydroxy-1H-1,5-benzodiazepine-2,4(3H,5H)-dione; (B46) 5-[4-(2-chlorobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B47) (B48) 5-[4-(2-Iodobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B49) 5-[4-(2,3-dimethylbenzoylamino)-3-fluorophenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B50) 5-[4-[2-(2-methylphenyl)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B51) 5-[4-[(quinoxalin-2yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione;(B52) 5-[4-[(5-methylthiophen-2yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B53) 5-[3-[(2-chlorophenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B54) 5-[4-[(2,4,6-trimethylbenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B55) (B56) 1-[4-(2,3-dimethylbenzoyl)aminophenyl]-6-methyl-1H-1,5-benzodiazepine-2,4(3H,5H)-dione; (B57) 5-[4-[(2-ethylbenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B58) (B61) 5-[4-[(6-methylpyridin-2-yl)carbonylamino]phenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B59) 5-[4-[(2-methylpyridin-3-yl)carbonylamino]phenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B60) 1-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-3-(2-methylphenyl)thiourea; (B61) (B62) 5-[4-(2,3-dichlorobenzoyl)aminophenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B63) 5-[4-(2,3-dichlorobenzoyl)aminophenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione;(B63) 5-[4-(2,3-dimethylbenzoylamino)-3-hydroxyphenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B64) 5-[4-(2-chloro-3-methoxybenzoylamino)phenyl]-1,3-dihydronaphtho[1,2-e]-1,4-diazepin-2-one; (B65) 5-[4-[(4-dimethylaminobenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B66) (B67) 5-[4-[2-(2-methylphenoxy)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B68) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)butyl]-2-chloro-3-methoxybenzamide; (B69) (B70) 5-[4-(2-acetylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B71) 5-[4-(2-tert-butylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B72) 5-[2-(2-iodobenzoyl)aminoethyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B73) 5-[3-[(2-iodobenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B74) 6,7-dimethyl-1-[4-(2-iodobenzoyl)aminophenyl]-1H-1,5-benzodiazepine-2,4(3H,5H)-dione;(B75) 5-[4-[(1-methylpiperidin-4-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione hydrochloride; (B76) 5[4-[(benzofuran-2-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B77) 5-[4-[(1-methyl-1H-indol-3-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B78) (B79) 5-[4-(2-propylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B80) 5-[3-fluoro-4-(2-iodobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B81) (B81) 5-[4-(2-hydroxy-3-methylbenzoyl)aminophenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B82) 5-[4-[(2-isopropoxybenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B83) 5-[4-[(3-methylthiophen-2-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B84) 5-[4-(2-phenoxypropionylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B85) 5-[4-[2-(4-chloro-2-methylphenoxy)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione;(B86) 5-[4-[(4-fluoro-2-trifluoromethyl)benzoyl]aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B87) 5-[4-(4-fluoro-2-methoxybenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B88) 5-[4-(4-fluoro-2-hydroxybenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B89) (B91) 5-[4-(2-tert-butylbenzoylamino)phenyl]-1,3-dihydronaphtho[1,2-e]-1,4-diazepine-2-one; (B92) 5-[4-[(3-dimethylaminobenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B93) 5-[4-[(3-dimethylaminobenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B94) 5-[4-[(3-dimethylaminobenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B93) 5-[4-(4-iodo-2-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B94) 5-[4-(6-fluoro-2-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B95) 5-[4-(2-hydroxy-4-iodobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B96) 5-[4-(6-fluoro-2-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B97) 5-[4-(2-fluorobenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione;(B98) 5-[4-[(2-dimethylaminobenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B99) 5-[4-(2-methoxy-6-methylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B100) 5-[4-(2-hydroxy-6-methylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B101) (B102) 5-(4-phenylcarbamoylphenyl)-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B103) 5-(4-benzylcarbamoylphenyl)-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B104) 5-[4-[3-(2-methylphenyl)propenoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B105) 5-[4-[3-(2-chlorophenyl)propionylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B106) 5-[4-(2-iodobenzoyl)aminophenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B107) 5-[4-[(1-methyl-1H-pyrrol-2-ylacetyl)amino]phenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B108) 5-[4-(2-chlorobenzyl)carbamoylphenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B109) 5-[4-[3-(2-chlorophenyl)propenoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione;(B110) 5-[4-(2-chlorophenyl)carbamoylphenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B111) 5-[4-(6-bromo-2,3-methylenedioxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B112) 5-[4-(6-bromo-2-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B113) (B114) 5-[2-(2-iodobenzoyl)aminopyridin-5-yl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B115) 5-[4-(6-bromo-2-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B116) (B117) 5-[4-(2-iodobenzoylamino)phenyl]-1H-[1,4]diazepino[2,3-h]quinoline-2,4(3H,5H)-dione; (B118) 5-[4-(6-chloro-2-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B119) (B120) 5-[4-[2-methoxy-6-(trifluoromethyl)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B121) 5-[4-[2-methoxy-6-(trifluoromethyl)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione;(B121) 5-[4-[2-hydroxy-6-(trifluoromethyl)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B122) 5-[4-[(2-isopropenylbenzoyl)amino]phenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B123) 5-[4-[(2-isopropylbenzoyl)amino]phenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B124) (B126) 5-[4-[3-(methylthio)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B127) 5-[4-[2-(methylthio)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B128) 5-[4-[2-(methylthio)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B129) (B128) 5-[4-(3-methanesulfonylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B129) 6-ethyl-1-[4-(2-iodobenzoyl)aminophenyl]-1H-1,5-benzodiazepine-2,4(3H,5H)-dione; (B130) 5-[4-[2-ethyl-6-hydroxybenzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B131) 5-[4-(3-methanesulfinylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione;(B132) 5-[4-(2-chloro-5-methanesulfinylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B133) 5-[4-(2-methanesulfinylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B134) 5-[4-[[2-(4-morpholinyl)acetyl]amino]phenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione hydrochloride; (B135) (B136) 5-[4-[[(3-chloropyridin-2-yl)carbonyl]amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B137) 5-[4-(2-chloro-6-hydroxybenzoylamino)phenyl]-1,3-dihydronaphtho[1,2-e]-1,4-diazepine-2-one; (B138) 5-[4-(3-chloro-2-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B139) 5-[4-[(3-methylpyridin-2-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B140) 5-[4-[[(3-chloropyridin-2-yl)carbonyl]amino]phenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B141) 5-[4-(3-chloro-2-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B142) 5-[4-[[(3-hydroxypyridin-2-yl)carbonyl]amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione;(B143) 5-[4-[(3-vinylpyridin-2-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B144) 5-[4-[(3-ethylpyridin-2-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B145) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho-[1,2-b][1,4]-diazepin-5-yl)phenyl]-2-nitrobenzenesulfonamide; (B146) (B147) 3-bromo-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]benzenesulfonamide; (B148) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-3-methoxybenzenesulfonamide; (B149) (B151) N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydro-naphtho[1,2-b][1,4]-diazepin-5-yl)phenyl]-2-nitro-benzenesulfonamide; (B152) N-[3-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepin-5-yl)phenyl]benzenesulfonamide; (B153) N-[3-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]-diazepin-5-yl)phenyl]-2-nitro-benzenesulfonamide; (B154) (B153) N-[3-(2,4-dioxo-1,2,3,4-tetrahydronaphtho-[1,2-b][1,4]-diazepin-5-yl)phenyl]-N-methyl-2-nitrobenzenesulfonamide; (B154) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho-[1,2-b][1,4]-diazepin-5-yl)phenyl]-N-methyl-2-nitrobenzenesulfonamide; (B155) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho-[1,2-b][1,4]-diazepin-5-yl)phenyl]-N-methyl-2-nitrobenzenesulfonamide;(B154) 4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-5-yl)-N-phenylbenzenesulfonamide; (B155) N-[3-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b]-[1,4]diazepin-5-yl)phenyl]-2-naphthalenesulfonamide; (B156) N-[3-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b]-[1,4]diazepin-5-yl)phenyl]-1-naphthalenesulfonamide; (B157) (B160) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]cyclohexanesulfonamide; (B158) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-3-pyridinesulfonamide hydrochloride; (B159) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-4-isopropylbenzenesulfonamide; (B160) (B161) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]phenylmethanesulfonamide; (B162) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5yl)phenyl]-2-thiophene-sulfonamide; (B163) 4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho-[1,2-b][1,4]diazepin-5-yl)phenyl 3-bromobenzene-sulfonate; (B164) N-benzyl-N-[4-(1-benzyl-2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5yl)phenyl]-2-nitrobenzenesulfonamide;(B165) N-benzyl-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-2-nitrobenzenesulfonamide; (B166) 3-bromo-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-N-methylbenzenesulfonamide; (B167) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]-diazepin-5-yl)phenyl]-N-methyl-2-nitrobenzenesulfonamide; (B168) (B169) N-[4-(7-chloro-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-1-yl)phenyl]benzenesulfonamide; (B170) N-[4-(7-bromo-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-1-yl)phenyl]benzenesulfonamide; (B171) (B172) N-[4-(2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-1-yl)phenyl]benzenesulfonamide; (B173) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]methanesulfonamide; (B174) 1-(3-bromophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]methanesulfonamide;(B175) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho-[1,2-b][1,4]-diazepin-5-yl)phenyl]-2-trifluoromethylbenzenesulfonamide; (B176) N-[4-(7-bromo-6-methyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-1-yl)phenyl]benzenesulfonamide; (B177) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]methanesulfonamide; (B178) (B179) N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-3-methoxybenzenesulfonamide; (B180) 1-(2-bromophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]methanesulfonamide; (B181) (B182) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-1-(2-methylphenyl)methanesulfonamide; (B183) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-2-phenylethanesulfonamide; (B184) 1-(2,3-dichlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]methanesulfonamide;(B185) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-7-methoxy-1H-benzo[1,2-b][1,4]diazepin-1-yl)phenyl]methanesulfonamide; (B186) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-7-hydroxy-1H-benzo[1,2-b][1,4]diazepin-1-yl)phenyl]methanesulfonamide; (B187) 1-(4-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]methanesulfonamide; (B188) (B189) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)benzyl]methanesulfonamide; (B189) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)-2-methoxyphenyl]methanesulfonamide; (B190) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)-2-hydroxyphenyl]methanesulfonamide; (B191) (B192) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-6-methyl-1H-benzo[1,2-b][1,4]diazepin-1-yl)phenyl]methanesulfonamide; (B193) 1-(2-chlorophenyl)-N-[3-(2,4-dioxy-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)propyl]methanesulfonamide; (B194) 1-(2-chlorophenyl)-N-[2-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)ethyl]methanesulfonamide;(B195) N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-1-(2-iodophenyl)methanesulfonamide; (B196) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-N-methylmethanesulfonamide; (B197) 1-(2-chlorophenyl)-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepin-5-yl)phenyl]methanesulfonamide; (B198) 1-[2-(trifluoromethyl)phenyl]-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]phenyl-N-methylmethanesulfonamide; (B199) 1-(2-ethylphenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]phenyl-N-methylmethanesulfonamide; (B200) 1-(2,3-dimethylphenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]phenyl-N-methylmethanesulfonamide; (B201) (B201) 2-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]phenyl-N-methylethanesulfonamide; (B202) 1-(2-nitrophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]phenyl-N-methylmethanesulfonamide; (B203) 1-(2-aminophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]phenyl-N-methylmethanesulfonamide;(B204) 1-(2-dimethylaminophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepin-5-yl)phenyl]phenyl-N-methylmethanesulfonamide; (B205) 5-[4-[(pyridin-4-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione hydrochloride; (B206) 5-[4-[2-[(pyridin-3-yl)oxy]acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione hydrochloride; (B207) (B209) 5-[4-[(2-chloropyridin-3-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B210) (B211) 5-[4-[[4-(trifluoromethyl)pyridin-3-yl]carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione; (B212) 5-[4-[(2-chloropyridin-3-yl)carbonylamino]phenyl]-1H-[1,4]diazepino[2,3-f]isoquinoline-2,4(3H,5H)-dione; (B213) 5-[4-[(2-chloropyridin-3-yl)carbonylamino]phenyl]-8,9,10,11-tetrahydro-1H-[1,4]diazepino[2,3-f]isoquinoline-2,4(3H,5H)-dione; and (B214) 5-[4-[(2-isopropylbenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione.

5. A pharmaceutical composition according to any one of claims 1 to 4, wherein the prevention or treatment of cerebral aneurysms is prevention of rupture of cerebral aneurysms.

6. A pharmaceutical composition according to any one of claims 1 to 5, wherein the prevention or treatment of cerebral aneurysms is inhibition of the growth of cerebral aneurysms.

7. A pharmaceutical composition according to any one of claims 1 to 5, wherein the prevention or treatment of cerebral aneurysms is suppression of the occurrence of cerebral aneurysms.

8. A pharmaceutical composition according to any one of claims 1 to 7, wherein the prevention or treatment of cerebral aneurysms is suppression of the occurrence of cerebral aneurysms after surgical treatment.

9. The pharmaceutical composition according to claim 8, wherein the suppression of occurrence after surgical treatment is the prevention of recurrence.

10. The pharmaceutical composition according to any one of claims 1 to 9, wherein the surgical treatment is an intravascular treatment.

11. The pharmaceutical composition according to any one of claims 1 to 10, wherein the intravascular treatment is coil embolization, stent-assisted coil embolization, or flow diverter placement.

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